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  “Vibrations refer to the oscillating and vibrating movement of atoms and particles caused by energy. Even solid objects like tables are actually made up of microscopic vibrating atoms that receive, store, and emit energy. Pretty neat, huh? Because of this, all humans and objects have an energy field that has its own vibrational frequency.”  [Balance Your Body: Vibrations and Frequencies, Purely Simple Organic Living Aug 23, 2020 Christina Sessums, Autoimmune Disease Specialist]

“Vibrations are periodic back-and-forth motions of atoms, molecules and other particles of all physical systems by their energy. Vibrations fall into 2 harmonic motion categories: 

• 1. Natural Occurring Oscillations: Every physical, material, mass system in our Universe inherently, unrecognizably and microscopically oscillate freely. Most are hidden and inconspicuous. Ohers are obvious and visible.  
• 2. Secondary, Forced Oscillations : Systems are secondarily oscillated by external forces that alter their vibration dynamics and develop unrecognizable and microscopic oscillations or develop recognizable and macroscopic oscillations.
• 3. Damping, in physics, is restraining the vibratory motion of systems, such as mechanical oscillations, noise, and electric currents, when systems’ energy has been dissipated.

“When pushing a playground swing, the swing’s motion subsides because of 'damping'. Automobile Shock absorbers and carpet pads are examples of damping devices.” [Physics Editors of Encyclopedia Britannica]

Years ago (1948) scientists discovered that “Viruses were mechanically disintegrated with intense vibrations.” [The Relative Sensitivities of Bacterial Viruses (Bacteriophage) to Intense Sonic Vibration, by Thomas F. Anderson, Shiela Boggs and Betty C. Winters, Science  02 Jul 1948: Vol. 108, Issue 2792, pp. 18, AAAS, DOI: 10.1126/science.108.2792.18, https://science.sciencemag.org/content/108/2792/18 ] “For PDF Purchase digital access to this article” go to the following address"  

 {{{Sidebar: The free flow of Scientific Information, whose research has been sponsored directly or indirectly, by U.S. citizens’ tax money, by U.S. government agencies, or private companies’ pharmaceutical research monies from citizens purchases, is essential for meta-research. The purchase of Journal Research Papers and other similar publications are incomprehensible , regressive and despicable.  This reporter has seldom, maybe never,  purchased research publications. }}}

“Scientists may one day be able to destroy viruses in the same way that opera singers presumably shatter wine glasses. New research mathematically determined the frequencies at which simple viruses could be shaken to death.”  [New Way to Kill Viruses: Shake Them to Death, experiments led by K. T. Tsen and physicist Otto Sankey from Arizona State University, February 05, 2008. Jan. 14 issue of Physical Review Letters, reported by Michael Schirber LiveScience]

“Recent frontiers in technology are exploring the possibility of using external excitations to vibrate a virus to its death. ” Protective protein shell (Capsid) of viruses is influenced by mechanical excitations in the form of inaudible, extremely high frequency focused Ultrasonic Sound Waves. 

Focused Ultrasonic Sound Waves (FUSW)  tuned to the natural vibration frequency of virus shell result in resonance. At resonance, the FUSW energy’s mechanical stress will compress and rarefy the protective Virus Capsid shell severe enough to shatter the shell just like an operettic will shatter a wine glass and inactivate the virus. FUSW applied properly should deactivate Coronavirus. [Virus and Vibrations, by Saikat Chaterjee, March 30, 2020, Adamas University]

"Viruses are known to resonate in the confined-acoustic dipolar mode with microwave of the same frequency. Research revealed that resonant energy transfer, from reasonable microwave power and safe for the open public, to influenza viruses, can be sufficient to inactivate airborne virus. Inactivation was primarily from physically fracturing the virus structure, which was confirmed by real-time reverse transcription polymerase chain reaction. These results provide a pathway toward establishing a new epidemic prevention strategy in open public for airborne virus." [Ijaz Durrani, PhD 28th Mar, 2020 discussion with Jay Srivastava PhD, Indian Institute of Technology (ISM) Dhanbad]

This referenced research demonstrated important implications for the interaction between microwaves and biological tissues. With an observed inactivation threshold with a microwave power density within the IEEE safety standard, the demonstrated Efficient Structure Resonance Energy Transfer (SRET) mechanism provides a pathway for prevention for airborne viruses in open public. [Yang, S., Lin, H., Liu, T. et al. Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses. Sci Rep 5, 18030 (2016). https://doi.org/10.1038/srep18030]

THERAPEUTIC VIBRATIONS MIGHT CONFUSE HUMAN-TISSUE-COVID-19-TROPISM   

• A. Scientists better understand the mediators of Tissue Tropism, But cannot account for all the factors involved. 
• Scientists better understand the tissue targets but cannot account, for all paths used by specific Pathogens to reach tissue targets locations.
• There Are 3 important facts about Pathogenic Tropism: Location, Location, Location
• [Location, Location, Location: Five Facts about Tissue Tropism and Pathogenesis. McCall L-I, Siqueira-Neto JL, McKerrow JH (2016) PLoS Pathog 12(5): e1005519. https://doi.org/10.1371/journal.ppat.1005519]

• B. : In response to Tropism Stimuli from Human and other Zoonotic Host Tissue to be infected, Tissue Tropism ‘GPS-like’ Receptive Entrained Vibration Signals guide the directions of COVID-19 Pathogenic Entrained Vibration Signals to the specific Tissue Location. 
• THERAPEUTIC VIBRATIONS MIGHT CONFUSE HUMAN-TISSUE-COVID-19-TROPISM  [mbmsrmd]  

 ABSTRACT:  MELATONIN, THE "HORMONE OF DARKNESS" AND COVID-19 VIRULENCE

Both sunlight and darkness have a dramatic effects on COVID-19 morbidity and mortality. Sunlight, vitamin D, zinc and others have been discussed, but not the “hormone of darkness", Melatonin. 

The onset of Melatonin hormone is triggered at dusk and initiates activity in nocturnal (night-active) animals like Bats and initiates sleep in diurnal Humans and other diurnal animals animals.

“There were 85 coronavirus infections linked to a single college town bar. News last week revealed at least 14 people had contracted the COVID-19 after visiting Harper’s Restaurant & Brew Pub in East Lansing, home to Michigan Sate University, between June 12 and 20. All who tested positive were said to be between the ages of 18 and 23.  Now, the Ingham County Health Department says that number is up to 85.” [Lexington Herald Leader, by Dawson White. June 28, 2020]

Nocturnal Bar Patrons and night owls, who hoot till dawn, socializing, after a day at the beach or other recreational areas, appear to be major problems, when identified, tracked and traced.

Therefore, in addition to social distancing and masks, rather than all day Bar and business closings, Bar and businesses are suggested to close at dusk following  CURFEW REGULATIONS, when nightlife activities for the both night-active-Humans’ socializing and nocturnal-viruses infestations intensely begin.

To answer the question posed by a publication:  NO administered Melatonin medication cannot reduce the severity of a COVID-19 pandemic [mbmsrmd’s Conclusion], because of the explanations listed in publication D. below. (Can Melatonin reduce the severity of COVID-19 pandemic? By Shneider A, Kudriavtsev A, Vakhrusheva A. [published online ahead of print, 2020 Apr 29]. Int Rev Immunol. 2020;1-10. doi:10.1080/08830185.2020.1756284)

SEE PUBLICATION D. BELOW OR DETAILS

1.    Picture 1. “The Sun, Earth and Moon (SEM) paths around the Black Hole at the center of our Milky Way Galaxy (MWG): The planar inclinations of the SEM paths are shown. Our SEM and Solar System rotate around the MWG center in a sinusoidal path. Our Sun and Earth rotate counterclockwise on their own axes. The Earth, other planets, their satellites and asteroids rotates in a counterclockwise direction around the Sun. But the Sun and its satellites revolve clockwise around the Milky Way.” [‘Motion of Sun, Earth and Moon around the Milky Way’ picture attribution Jim slater307 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) https://commons.wikimedia.org/wiki/File:Motion_of_Sun,_Earth_and_Moon_around_the_Milky_Way.jpg]
2. Picture 2.  "Band of Milky Way Galaxy. seen with several Atacama (Credit: ESO/B. Tafreshi(Credit: ESO/B. Tafreshi"
3. Picture 3. Molecular Evolution Virus Root time scale MCMCTREE analysis  >64–65 Ma. 95% confidence blue band 

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) are 2 highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century.

“Bats are mammals of the order Chiroptera and are the 2nd largest order of mammals after rodents. Bats comprise about 20% of all classified mammal species worldwide, with over 1,200 species.[Asteroid Impact That Killed the Dinosaurs: New Evidence By Charles Q. Choi February 07, 2013, LiveScience]

66 million years ago (mya).[3] Mass Extinction of 75% of Earth’s plant and animal species, selective larger mammalian and Dinosaurs resultedand the earth-shaking catastrophe was called Cretaceous–Paleogene (K–Pg) Dinosaur Extinction Event,[a] aka Cretaceous–Tertiary (KT) extinction.[b] 

The Sun, Earth and Solar System (SESS) during normal rotations cross the Galactic Plane. SESS pass through the plane every 35 to 40 million years, [Cardiff Centre of Astrobiology]

Scientists concluded a lethal asteroid(s) in the Galactic Plane halo of dark dense matter were accelerated and crashed into Earth. [‘Motion of Sun, Earth and Moon around the Milky Way’ picture attribution Jim slater307 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) (https://commons.wikimedia.org/wiki/File:Motion_of_Sun,_Earth_and_Moon_around_the_Milky_Way.jpg)]

66 million years ago (mya),[3] following Asteroid Collision(s), explosions equivalent to 100 trillion tons of TNT (more than a billion times greater than the atom bombs that destroyed Hiroshima and Nagasaki) Earth was colossally shaken and portions were totally destroyed and decimated . [Asteroid Impact That Killed the Dinosaurs: New Evidence By Charles Q. Choi February 07, 2013, LiveScience]

Mass Extinction of 75% of Earth’s plant and animal species, selective larger mammalian and Dinosaurs resulted. This was called Cretaceous–Paleogene (K–Pg) Dinosaur Extinction Event,[a] aka Cretaceous–Tertiary (KT) extinction,[b] 

Birds and Bats survived the explosions. There might have been multiple fallout explosions, for possibly years afterwards, following the initial earth-shaking cataclysm. Scientists postulated that DNA and RNA covalent, chemical and quantum entangled and coherent bonds likewise were exploded, earth-shaken and disassociated, disentangled, separated, fragmented and scattered. 

Covalent, chemical bonds and quantum entangled and coherent bonds hold DNA strands and DNA double helixes together and RNA strands and RNA and RNA proteins together. 

Without these bonds, DNA and RNA and other bonded compounds and molecules disassociate, disentangle, fall apart and RNA virus-like-pieces can form and scatter.

Massive, forceful explosions, as in the catastrophic K-Pg Dinosaur Extinction Period, will cause massive bond disassociations and disentanglements.

References

• [Yuki Kobayashi, Kristina F. Chang, Tao Zeng, Daniel M. Neumark, Stephen R. Leone. Direct mapping of curve-crossing dynamics in IBr by attosecond transient absorption spectroscopy. Science, 2019; 365 (6448): 79 DOI: 10.1126/science.aax0076]
• [Mihelic FM. Model of biological quantum logic in DNA. Life (Basel). 2013;3(3):474–481. Published 2013 Aug 2. doi:10.3390/life3030474] 
• [Biology, www.mvla.net/download.cfm id=20525]
• [What are the Ingredients of Life? By Natalie Wolchover,  Feb 2, 2011, LiveScence] [Life's Little Mysteries consulted Matthew Pasek, a biogeochemist at the University of South Florida]
• [Being the skunk at an atheist convention, La Jolla, Salk Institute, November 5-7, 2006 by Stuart Hameroff (Session 4), Post Conference Remarks - S. Hameroff]
• [Timeless Quantum Universe is in Dynamic Equilibrium by Amrit S. Sorli sorli.bistra@gmail.com, Scientific Research CentreBistra, Ptuj, Sloveni]
• [‘Einstein's Unfinished Dream: Marrying Relativity to Quantum World’ by Don Lincoln Nov 18, 2015 Science & Astronomy, Space.com]
• [Hameroff and Chopra Describe God, on Youtube] Please review: [DR. HAMEROFF DESCRIBES GOD https://myscientistgod.us/dr-hameroff-describes-go]
• [Scientist: Quantum physics can prove there's an afterlife, Chris Matyszczyk, November 16, 2013 cInet]

The visible disk of Milky Way Galaxy (Galactic Plane) is thought to be embedded in a much larger, roughly spherical halo of dark matter. The dark matter density drops off with distance from the galactic center. It is now believed that about 95% of the galaxy is composed of dark matter.

During our Solar System’s rotation around the black hole in the center of our Milky Way Galaxy, 1.) our Solar System crossed the Galactic Plane and lethal asteroids were accelerated out from the plane and crashed into our Earth and caused the Dinosaur Extinction Period. aka Cretaceous Paleocene Period (K-Pg). 

The 2.) Asteroid Impact Killed the Dinosaurs. The only survivors among the dinosaurs were the birds, including the bats [Asteroid Impact That Killed the Dinosaurs: New Evidence By Charles Q. Choi February 07, 2013, LiveScience]

This hypothesis proposes that at the same time, selective larger mammalian, like dinosaurs, 3.) DNA and RNA Quantum Entanglements were shaken, separated and fragmented. The strands of DNA and RNA formed were disseminated and spread worldwide. [mbmsrmd hypothesis]

Dating the original Relic Bats requires sophisticated calculations: “The Molecular Time Scale resulting from MCMCTREE analysis in PAM: Phylogenetic Analysis by Maximum Likelihoodusing the BEAST topology revealed the Rhinolophid and Hipposiderid bats fossil calibrations and Molecular time scale date to ~ 64–65 million years ago. 

Rhinolophid and Hipposiderid bats became the hosts for the RNA Coronavirus and other respiratory viruses were postulated. [How and why overcome the impediments to resolution: lessons from rhinolophid and hipposiderid bats. Mol Biol Evol. 2015;32(2):313–333. doi:10.1093/molbev/msu329]

The Cretaceous–Paleogene (K–Pg) extinction event,[a] also known as the Cretaceous–Tertiary (K–T) extinction,[b] was a sudden mass extinction of 3/4 of the plant and animal species on Earth and formation of Relic Coronavirus Ancestors and other Respiratory viruses that dates to approximately 66 million years ago.  [[Renne, Paul R.; et al, ‘ (PDF). Science. 339 (6120): 684–687. Jan (7 February 2013). Bibcode: 2013 Sci. 339.. 684R. doi: 10.1126/science. 1230492. PMID 23393261. Archived (PDF) from the original on 7 February 2017]

The Cretaceous–Paleogene (K–Pg) extinction event,[a] also known as the Cretaceous–Tertiary (K–T) extinction,[b] was a sudden mass extinction of three-quarters of the plant and animal species on Earth [2][3][4] approximately,

“Bayesian inference provides a powerful framework for integrating different sources of information (in particular, molecules and fossils) to derive estimates of species divergence times. Indeed, it is currently the only framework that can adequately account for uncertainties in fossil calibrations. 2 Bayesian Markov chain Monte Carlo programs, MULTIDIVTIME and MCMCTREE, were used to analyze 3 empirical datasets to estimate divergence times in amphibians, actinopterygians, and felids. 

“Scientists evaluated the impact of various factors, including the priors on rates and times, fossil calibrations, substitution model, the violation of the molecular clock and the rate-drift model, and the exact and approximate likelihood calculation. Scientists assumed the molecular clock caused seriously biased time estimates when the clock was violated. Therefore, 2 different rate-drift models produced similar estimates.

“The prior times, which incorporates fossil-calibration information, had the greatest impact on posterior time estimation. In particular, the strategies used by the 2 programs to incorporate minimum- and maximum-age bounds led to vastly different time priors and were responsible for large differences in posterior time estimates in a previous study. The results highlight the critical importance of fossil calibrations to molecular dating and the need for probabilistic modeling of fossil depositions, preservations, and sampling to provide statistical summaries of information in the fossil record concerning species divergence times.[Jun Inoue, Philip C. J. Donoghue, Ziheng Yang, The Impact of the Representation of Fossil Calibrations on Bayesian Estimation of Species Divergence Times, Systematic Biology, Volume 59, Issue 1, January 2010, Pages 74–89, https://doi.org/10.1093/sysbio/syp078]

“With the exception of some ectothermic species such as the leatherback sea turtle and crocodiles, no tetrapods weighing more than 25 kilograms (55 pounds) survived.[5] It marked the end of the Cretaceous period, and with it the end of the entire Mesozoic Era, opening the Cenozoic Era that continues today.

“The geologic record, the K–Pg event is marked by a thin layer of sediment called the K–Pg boundary, which can be found throughout the world in marine and terrestrial rocks. The boundary clay shows high levels of the metal iridium, which is rare in the Earth's crust, but abundant in asteroids.[6]

“As originally proposed in 1980 by a team of scientists led by Luis Alvarez and his son Walter, it is now generally thought that the K–Pg extinction was caused by the impact of a massive comet or asteroid 10 to 15 km (6 to 9 mi) wide,[7][8] 66 million years ago,[3] which devastated the global environment, mainly through a lingering impact winter which halted photosynthesis in plants and plankton.[9][10] 

“The impact hypothesis, also known as the ‘Alvarez Hypothesis’ was bolstered by the discovery of the 180 km (112 mi) Chicxulub crater in the Gulf of Mexico's Yucatán Peninsula in the early 1990s,[11] which provided conclusive evidence that the K–Pg boundary clay represented debris from an asteroid impact.[12]

“The fact that the extinctions occurred simultaneously provides strong evidence that they were caused by the asteroid.[12] A 2016 drilling project into the Chicxulub peak ring confirmed that the peak ring comprised granite ejected within minutes from deep in the earth, but contained hardly any gypsum, the usual sulfate-containing sea floor rock in the region: The gypsum would have vaporized and dispersed as an aerosol into the atmosphere, causing longer-term effects on the climate and food chain. In October 2019, researchers reported that the event rapidly acidified the oceans producing ecological collapse and, in this way as well, produced long-lasting effects on the climate, and accordingly was a key reason for the end-Cretaceous mass extinction.[13][14] In January 2020, scientists reported new evidence that the extinction event was mostly a result of the meteorite impact and not volcanism.[15][16]

“Other causal or contributing factors to the extinction may have been the Deccan Traps and other volcanic eruptions,[17][18] climate change, and sea level change.

“A wide range of species perished in the K–Pg extinction, the best-known being the non-avian dinosaurs. It also destroyed a myriad of other terrestrial organisms, including some mammals, pterosaurs, birds,[19] lizards,[20] insects,[21][22] and plants.[23] In the oceans, the K–Pg extinction killed off plesiosaurs and mosasaurs and devastated teleost fish,[24] sharks, mollusks (especially ammonites, which became extinct), and many species of plankton. 

“It is estimated that 75% or more of all species on Earth vanished.[25] Yet the extinction also provided evolutionary opportunities: In its wake, many groups underwent remarkable adaptive radiation — sudden and prolific divergence into new forms and species within the disrupted and emptied ecological niches. Mammals in particular diversified in the Paleogene,[26] evolving new forms such as horses, whales, bats, and primates. Birds,[27] fish,[28] and perhaps lizards[20] also radiated.

With the addition of COVID-19, there are now 7 Human Coronaviruses. [CDC] Both viruses likely originated in bats. Genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV have been discovered in bats worldwide.

This Research reference summarized the current knowledge on the origin and evolution of these 2 pathogenic coronaviruses and implicated the extrapolation to COVID-19. This Research reference discussed the viruses receptor usage.

This research reference report also highlighted the diversity and potential spillover of bat-borne coronaviruses, as evidenced by the recent coronavirus (SADS-CoV) spillover causing ‘swine acute diarrhea syndrome’ (in pigs).

Scientists collected data on genetic evolution, receptor binding and pathogenesis demonstrated that SARS-CoV most likely originated in bats through sequential recombination of bat SARSr-CoVs.

A similar scenario might have happened for MERS-CoV. Since its outbreak in 2012, MERSr-CoVs and related viruses (HKU4 and HKU5) have been found in different bat species in five continents 17,21,106,110,111,116,126,127,132.

Given the massive number of coronaviruses carried by different bat species, the high plasticity in receptor usage and other features such as adaptive mutation, reassortment and recombination, frequent interspecies transmission from bats to animals and humans is expected.

Furthermore, little is known about the replication and pathogenesis of these bat viruses.

“It is widely accepted that many viruses have existed in their natural reservoirs for a very long time. The constant spillover of viruses from natural hosts to humans and other animals is largely due to human activities, including modern and industrial agricultural practices, poor animal slaughter practices and ‘waste feeding’ practices, wild game animal capture for food sources and urbanization.

“Therefore, the most effective way to prevent viral zoonosis is to maintain the barriers between natural reservoirs and human society. [Origin and evolution of pathogenic coronaviruses, Jie Cui,1 Fang Li,2 and Zheng-Li Shi, 1 Nat Rev Microbiol. 2019; 17(3): 181–192. 2018 Dec 10. PMCID: PMC7097006, PMID: 30531947doi: 10.1038/s41579-018-0118-9]

From reputable, peer reviewed research journal surveys, this clinician, scientist and reporter summarized and concluded the following  3 events occurred within the same time-frame. 

•  Relic Bat Survival during Bolide Chicxulub Dinosaur Extinction Event together with Extinction of selective larger mammalian, like dinosaurs  
•  plus, the shaken, separated and fragmented, formerly living cellular, DNA and RNA pieces, formed strands of DNA and RNA Relic Coronavirus Ancestors and other DNA, RNA and virus segments which were disseminated and spread worldwide. 
•  1. Relic Bat Survival was the Origin for Adaptation and Evolution of the Relic Bats 
•  2. and the explosive shaken, separated and fragmented Dinosaur and other Mammal cells’ DNA and RNA into pieces, possibly as small as single strands, which before were living cells which contained CHNOPS, the elements for 98% of life, 
• 2. = were the 
•  The Origin of the Pathogenic Coronaviruses Summarized and Hypothesized: resulted from: 
• 1. Relic Bat Survival 
• 2. + explosive fragmented pieces of formerly living cellular Dinosaur and other mammal DNA and RNA secoOrigin for Adaptation and Evolution of their Relic Parasite Coronavirus Ancestors that parasitized 1. the surviving Relic Bats ndary to earth-shaking catastrophe called Mass Extinction approximately 66 Million Years Ago 
• 3. which was called Bolide Dinosaur Extinction Event, the Cretaceous–Paleogene (K–Pg) Dinosaur Extinction Event, the Cretaceous–Tertiary (KT) extinction.   

Dr. Jim Wellehan, D.V.M, Ph.D. published in 2018 his results and conclusions, which were similar to this Clinician, Analyst and Reporter’s summarized conclusions from other scientists’ real-time research, excluding the research of Dr. Wellehan.

Dr. Jim Wellehan’s Abstract: “Dr. Jim Wellehan, D.V.M, Ph.D.an associate professor of zoological medicine at UF’s College of Veterinary Medicine and a member of the UF Emerging Pathogens Institute, suggests the protection offered through the integration of bornaviruses into the genomes of Cretaceous-era mammals may have given them an advantage after the dinosaur extinction event that occurred 66 million years ago.

Working in collaboration with an international cohort of veterinary scientists, Wellehan helped identify new species of bornaviruses — a family of viruses that cause neurologic disease in a variety of species — that were impacting Australian carpet pythons.

When comparing these new viruses to available genetic data, the researchers found the viruses varied significantly from previously known bornaviruses; in fact, the most closely related sequences of these python bornaviruses were bornavirus genes that had integrated into mammal genomes.

These bornavirus genes, called “endogenous bornaviral-like elements,” or EBLs, have been found in other species. According to a 2014 study published in “Proceedings of the National Academy of Sciences,” an EBL in thirteen-lined ground squirrels protects them against infection from related bornaviruses. Several studies have demonstrated that endogenous viral elements protect their hosts from related viruses.

“While studying the genetic history of these EBLs and their locations in the genomes of various species, we concluded that they likely integrated into mammal DNA  approximately 70 million years ago,” Wellehan said.

Sixty-six million years ago, the end-Cretaceous extinction led to the disappearance of all dinosaurs and non-avian dinosaurs.

Bornaviruses are in the same order of viruses as Ebola, measles and rabies, all of which are capable of causing significant population-level effects. 

During the end-Cretaceous extinction, EBLs within mammal genomes may have protected mammals from bornaviruses that affected birds and reptiles, allowing them to step into the ecological niche left by extinct dinosaur species.

“Before the end-Cretaceous extinction, mammals had a poor track record for adapting to extreme climate shifts,” Wellehan said. “During times of environmental stress, infectious diseases can have greater impacts on populations. 

Mammals living during the end of the Cretaceous era, therefore, had a level of protection against bornaviruses that was lacking in birds and reptiles.”

The end-Permian extinction, which preceded the end-Cretaceous extinction by nearly 200 million years, occurred due to major climate warming from volcanic carbon dioxide release. The fossil record suggests that climate changes occurring during this time resulted in the extinction of nearly all species.

Before the end-Permian extinction, the dominant species were part of the mammal lineage. The avian/reptile lineage has renal and respiratory physiological advantages over the mammal lineage, however. In the hot, dry conditions of the time, reduced water loss gave reptiles the advantage, setting the stage for the age of dinosaurs.

[Ancient virus may have given mammals the edge during dinosaur extinction era

Published: Jul 3, 2018 By: Evan BartonCategory: University of Florida, UF Health, College of Veterinary Medicine, Emerging Pathogens Institute]

….[Dr. Wellehan collaborated with colleagues Timothy Hyndman, Ph.D., a veterinary medicine professor at Murdoch University in Australia, Mark Stenglein, Ph.D., a veterinary microbiologist at Colorado State University, Catherine Shilton, Ph.D., Berrimah Veterinary Laboratories in Australia, Wellehan was responsible for the phylogenetics, forming the connection between the strain found in the carpet pythons and the EBLs that have existed in mammal DNA for millions of years.]

  " The 1st illustration shows the Sun, Earth and Solar Systems's Path Around the central Black Hole of the Milky Way Galaxy. The inclinations of the Ecliptic Plane and Celestial Equator are shown with respect to the Galactic North Pole and Galactic Plane. The inclination of the moon's orbit is shown relative to the Ecliptic Plane. The Solar System traces out a sinusoidal path in its orbit around the galactic center and black hole. Using Galactic North as the initial frame of reference, the Earth and Sun rotate counterclockwise, and the Earth revolves in a counterclockwise direction around the Sun. However, the Sun and its satellites revolve CLOCKWISE around the Milky Way." [Picture credit Jim Slater 307, July 13, 2017]

2nd image of the night sky: "The band of the Milky Way Galaxy can be seen at night in areas with dark skies. Here it is seen with several Atacama Large Millimeter/submillimeter Arra (ALMA) antenna. (Credit: ESO/B. Tafreshi." [NaSA] 

For multiple complex reasons, U.S infection controls for all Coronaviruses including COVID-19 are drastically insufficient.

“Human Coronavirus Types"[CDC Website, U.S.Department of Health & Human Services,USA.gov]

Coronaviruses are named for the crown-like spikes on their surface. There are four main sub-groupings of coronaviruses, known as alpha, beta, gamma, and delta.

Human Coronaviruses were 1st identified in the mid-1960s.  Now there are 7 Human Coronaviruses. The 7 Coronaviruses that can infect Humans  are 4 Common Human Coronaviruses and 3 Other More Recent Human Coronaviruses: 

• Common Human coronaviruses: 

1. (alpha coronavirus)
2. NL63 (alpha coronavirus)
3. OC43 (beta coronavirus)
4. HKU1 (beta coronavirus)

• Other More Recent Human Coronaviruses
• 5. MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS)
• 6. SARS-CoV (the beta coronavirus that causes severe acute respiratory syndrome, or SARS)
• 7. SARS-CoV-2 (novel coronavirus that causes coronavirus disease 2019, or COVID-19)

Around the world, the common infection with human coronaviruses are 229E, NL63, OC43, HKU1.

Sometimes Coronaviruses that infect animals can adapt and evolve and make people sick and become a new Human Coronavirus. 3 recent examples of this are 2019-nCoV, SARS-CoV, and MERS-CoV.” [CDC Website, U.S. Department of Health & Human Services, USA.gov]

Science knows 66 million years ago (mya/Ma) the Dinosaurs other animals and plants died. The Period was called Cretaceous–Paleogene (K–Pg) Dinosaur Extinction Event, [a] aka Cretaceous–Tertiary (KT) extinction, [b] The animals and plants that survived, flourished and are seen in the clues of sedentary rock. 

Science knows from Molecular time Clock and Biogeographical Analysis Methods that fossil calibrations place the fossil root-age of viruses at 64–65 million years. As best determined, viruses began 64–65 million years ago (Ma). Viruses with Bat hosts are aka Bat-phage and 64–65 million years ago (Ma) is the root-age of the 1st Zoonoses. Bats became the natural parasitic hosts of viruses. 

• CHNOPS are the chemical symbols of the 6 most common elements (Carbon, Hydrogen, Nitrogen, Oxygen, Phosphorus, Sulfur) discovered and  known to comprise 98% of Earthly Life within living cells.
• CHNOPS nuclearsynthesis dispels an extraterrestrial asteroidal system that delivered  viral DNA and RNA virus strands to Earth
• because our Solar System, with the exception of Earth, is otherwise lifeless. 
• Understood to this date CHNOPS nuclearsynthesis known to comprise 98% of Earthly Life, within living cells, has only happened 1 time in the history of our Universe 
• and  supports (9.) a  Bolide Dinosaur Extinction Causative Impact Event.

The novel hypothesis posits that 66 million years ago the Bolide Impact defragmented DNA and RNA strands of living animals that are now extinct and their DNA and RNA strands were not disintegrated. Their DNA and RNA strands remained and were availed as CHNOPS Morowitz Cybernetic virus codes and, fortuitously precise, interconnected with Bat-host-mammals for parasite-host virus replication and co-evolution. 

As a suggested alternative by other postulaters, a Systematic interplanetary DNA and RNA insertable Bat-phage code, in our otherwise lifeless Solar System and Universe, rocketing as a passenger to earth on an asteroid, appears improbable. The Intelligent Design Creation of our Homo sapien-sapiens species is earthly specific.

Simplified, at ~ 66 million years ago (mya/Ma), when our Solar System crossed the Milky Way Galactic Plane, the "Bolide" (fireball) Asteroid hit earth and ferociously exploded: 

the Asteroid Impact Explosions that Killed the Dinosaurs. were equivalent to 100 trillion tons of TNT, which was more than a billion x times greater than the atom bombs that destroyed Hiroshima and Nagasaki. [Asteroid Impact That Killed the Dinosaurs: New Evidence By Charles Q. Choi February 07, 2013, LiveScience]

Dinosaurs and 75% of the other animals and plants were extinguished Bats survived. 

The "Bolide" (fireball) Asteroid Explosion extinguished species and also fragmented living mammal chemical and quantum entangled DNA and RNA bonds Massive, forceful explosions, as in the catastrophic K-Pg Dinosaur Extinction Period, will cause massive Chemical and Quantum bond disassociations and disentanglements.,,,

[Repeated blast exposures cause brain DNA fragmentation in mice. Wang Y, Arun P, Wei Y, et al. J Neurotrauma. 2014;31(5):498–504.  doi:10.1089/neu.2013.3074]....and formed deceased mammal DNA and RNA segmental strands or codes aka viruses or parasites and ~64-65 mya the Bats that survived and flourished as determined by Molecular time scale resulting from MCMCTREE analysis [Fig. 4. Tables and Comments from Reference: Nicole M. Foley, et al How and Why Overcome the Impediments to Resolution: Lessons from rhinolophid and hipposiderid Bats, Molecular Biology and Evolution, Volume 32, Issue 2, February 2015, Pages 313–333, https://doi.org/10.1093/molbev/msu329 ]

Viruses are found wherever there is life and have probably existed since living cells first evolved.[44] [Iyer LM, Balaji S, Koonin EV, Aravind L (April 2006). "Evolutionary genomics of nucleo-cytoplasmic large DNA viruses". Virus Research. 117 (1): 156–84. doi:10.1016/j.virusres.2006.01.009. PMID 16494962]

the viruses parasitized surviving mammal Bats forming parasite-hosts for virus replications and parasite-hosts co-evolution. Molecular techniques are used to investigate viruses origin.[45] 

[Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R (October 2010). "Viral mutation rates". Journal of Virology. 84 (19): 9733–48. doi:10.1128/JVI.00694-10. PMC 2937809. PMID 20660197.]

Including the 7th Coronavirus the novel coronavirus that causes coronavirus disease 2019, or COVID-19 aka SARS-CoV-2. Now there are 7 Human coronaviruses.

Viruses are found wherever there is life and have probably existed since living cells first evolved.[44] [Iyer LM, Balaji S, Koonin EV, Aravind L (April 2006). "Evolutionary genomics of nucleo-cytoplasmic large DNA viruses". Virus Research. 117 (1): 156–84. doi:10.1016/j.virusres.2006.01.009. PMID 16494962]

The origin of viruses is unclear because they do not form fossils, so molecular techniques are used to investigate their origin.[45] [ Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R (October 2010). "Viral mutation rates". Journal of Virology. 84 (19): 9733–48. doi:10.1128/JVI.00694-10. PMC 2937809. PMID 20660197.] [Wikipedia]

• · Science knows: 66 million years ago (mya) [3] during our Solar System, Sun and Earth (SSSE) normal cyclic rotation around the black hole in the center of our Milky Way Galaxy, a.) 
• · And our Solar System, Sun and Earth (SSSE) crossed the Galactic Plane (GP) and lethal asteroids were accelerated and crashed into our Earth and caused the Dinosaur Extinction Period. aka Cretaceous Paleocene Period (K-Pg). 
• · And during that period 66 million years ago (mya) [3] mass Extinction of 75% of Earth’s plant and animal species, selective larger mammals and Dinosaurs resulted
• · The Era was called Cretaceous–Paleogene (K–Pg) Dinosaur Extinction Event,[a] aka Cretaceous–Tertiary (KT) Extinction Period,[b]
• · Lethal Asteroids in the Galactic Plane halo of dark dense matter were accelerated and crashed into Earth during the K–Pg. [‘Motion of Sun, Earth and Moon around the Milky Way’ picture attribution Jim slater307 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) https://commons.wikimedia.org/wiki/File:Motion_of_Sun,_Earth_and_Moon_around_the_Milky_Way
• · SSSE pass through the GP every 35 to 40 million years. [Cardiff Centre of Astrobiology] 
• · The Asteroid Impact Explosions that Killed the Dinosaurs. were equivalent to 100 trillion tons of TNT (more than a billion times greater than the atom bombs that destroyed Hiroshima and Nagasaki}. [Asteroid Impact That Killed the Dinosaurs: New Evidence By Charles Q. Choi February 07, 2013, LiveScience]
• · Only survivors among the dinosaur mammals were Bats 
• · “Bats are mammals of the order Chiroptera and are the 2nd largest order of mammals after rodents. Bats comprise about 20% of all classified mammal species worldwide, with over 1,200 species.
• · Also surviving were Birds, a group of warm-blooded vertebrates in the class Aves, [Asteroid Impact That Killed the Dinosaurs: New Evidence By Charles Q. Choi February 07, 2013, LiveScience]
• · Science knows which animals and plants survived and flourished, because clues are in sedentary rock
• · Molecular techniques are used to investigate viruses origin.[45]The Molecular time scale age, MCMCTREE analysis in PAM: Phylogenetic Analysis, Maximum Likelihood using BEAST topology revealed age of Bat-phage, that are natural hosts of viruses
• · The Molecular time scale age, MCMCTREE analysis in PAM: Phylogenetic Analysis, Maximum Likelihood using BEAST topology revealed age of viruses, the 1st Zoonoses, by extrapolation 
• · Asteroid Bolide are thunderous, earth-shaking, fireball explosions due to rocky celestial bodies, especially originating between planetary orbits, that crash into planets
• · Chemical bonds and Quantum Entanglement bonds hold DNA strands and DNA double helixes together and RNA strands and RNA and RNA proteins together. 
• · Without Chemical and QE bonds, DNA and RNA disassociate, disentangle, fall apart and RNA virus-like-pieces scatter. 
• · “Are viruses alive? Appears any such virus definition is bound to be arbitrary and does not lead to any constructive developments. In contrast, the status of viruses in the realm of biology is naturally defined within the framework of the replicator paradigm.” 
• · No replication / replicator system can evolve without the emergence of parasites, and parasitic replicators drive the evolution of complexity at more than one level. The entire history of life is a story of parasite-host coevolution that includes various forms of cooperation. 
• · Virus ‘evolution’ itself is an epiphenomenon of replication: selection, drift and parasite formation necessarily ensue as soon as replication with sufficient fidelity is established (Eigen 1971; Koonin 2011; Takeuchi and Hogeweg 2012).
• · The virus replicator paradigm is truly central to biology as both a conceptual framework and a research program. Among other major issues, it settles the status of viruses in the biological world.
• · The (partial) replicative autonomy is the key feature that makes each replicator a distinct unit of evolution which employs a specific evolutionary strategy and evolves along a unique trajectory. Certainly, the autonomy of replicators is never complete, and no replicator can survive in isolation. 
• · The degree of a replicator’s autonomy can be readily measured by the repertoire of the components of the replication machinery (enzymes and other proteins required for replication) that are encoded in the replicator genome, and by the presence of dedicated replication and/or transposition signals.Replicators form a continuum along the autonomy axis although with some degree of arbitrariness, distinct classes ranked by the level of autonomy can be envisaged. (Figure 1 and Table 1). 
• · The replicators are sharply divided into 2 major categories with respect to resource production: 
• i) producers that make all the resources required for replication or make some of the resources and actively import others in an energy-dependent manner, i.e. cellular life forms, 
• ii) and ii) non-producers that lack most of the biosynthetic and active transport capabilities, i.e. viruses and other parasitic replicators. The distinction between producers and non-producers reflects another type of autonomy that can be denoted “resource autonomy”. There is a sharp distinction between autonomous cellular life forms and non-autonomous selfish replicators. Yet, as almost always is the case in biology, borderline situations exist.
• iii) While most of the producers (cellular life forms) make all of the energy they use and most if not all building blocks, some intracellular bacteria are energy parasites that obtain most if not all of their ATP from the host (Moran 2002; Tamas et al 2001). 
• Conversely, some of the non-producers, such as large viruses, encode some metabolic enzymes, e.g. nucleotide kinases, that modify the production of building blocks in infected cells. The largest known viruses, in particular mimiviruses, encode many such enzymes including multiple components of the translation system such that multiple synthetic pathways in the infected cell are modified (Claverie, Abergel, & Ogata, 2009; Yutin, Wolf, Raoult, & Koonin, 2009). Among other processes, non-producers can contribute to energy conversion as is the case with cyanophages many of which encode cyanobacterial photosystems (Clokie and Mann 2006; Thompson et al 2011).
•  Furthermore, even small non-producing replicators, such as RNA viruses, affect modifications of the host cell metabolism and the formation of structures, such as virus factories, that channel substrates into viral genome replication (Harak and Lohmann 2015; Romero-Brey and Bartenschlager 2014). All the prowess of viruses in the modulation of the host metabolism notwithstanding, producers and non-producers are clearly distinct: to the best of our current knowledge, non-producers never direct the formation of energizable membranes, extremely rarely encode complete metabolic pathways and never a complete translation system (Koonin and Dolja 2013; Raoult and Forterre 2008).” [Koonin EV, Starokadomskyy P. Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question. Stud Hist Philos Biol Biomed Sci. 2016;59:125–134. doi:10.1016/j.shpsc.2016.02.016]
• · Hypothesis Science hypothesizes key facts that have facilitated the origin of viruses and viral Pandemics and social distancing
• · CHNOPS nuclearsynthesis dispels an extraterrestrial delivery system of viral DNA and RNA and supports 9. Bolide Impact
• · One Systematic universe interplanetary DNA and RNA insertable Batphage code in our otherwise lifeless Solar System is improbable
• · During the K–Pg animal species, selective larger mammals and Dinosaurs DNA and RNA Chemical bonds and Quantum Entanglement bonds likewise exploded, were shaken, disassociated, disentangled, separated, fragmented and scattered, which were the cause of their death
• · Massive, forceful explosions, as in the catastrophic K-Pg Dinosaur Extinction Period, will cause massive Chemical and Quantum bond disassociations and disentanglements.
• · [Repeated blast exposures cause brain DNA fragmentation in mice. Wang Y, Arun P, Wei Y, et al. J Neurotrauma. 2014;31(5):498–504. doi:10.1089/neu.2013.3074]
• · “Molecular time scale MCMCTREE analysis in PAM: Phylogenetic Analysis, Maximum Likelihood using BEAST topology revealed the Birds and Bats survived the explosions and Rhinolophid and Hipposiderid bat fossil calibrations and Molecular time scale date them to have Emerged 64 to 65 mya
• Fig. 4. Molecular time scale resulting from MCMCTREE analysis in PAML using the BEAST topology shown in figure 2, four fossil calibrations (as described in Materials and Methods using stratigraphic bounding), and a root prior of 64–65 Ma. Numbers at nodes are divergence time estimates in millions of years and the 95% confidence interval for each estimate is denoted by a blue shaded bar. Biogeographic reconstructions resulting from ML analysis in Lagrange under the same topology are shown as letters at each node. Areas are coded as follows: A—Europe, B—South America, C—South East Asia, D—India, E—Middle East, F—East Asia, G—Australia, and H—Africa. 
• "Comments on Molecular Clock and Biogeographical Analysis Methods: Bats have a poor and limited fossil record (Teeling et al. 2005; Eiting and Gunnell 2009). Although the oldest fossil attributable to a lineage can provide a minimum age in a soft bound analysis, choosing a maximum bound is more difficult, here we use the stratigraphic bounding method of Meredith et al. (2011) to standardize the way in which maximum boundaries are chosen across the tree. With the inclusion of fossil record of the Hipposideridae to biogeographic analysis to overcome the limitations inherent in the bat fossil record, research used only the distribution of extant taxa in our analysis. This phylogeny comprises representatives from all Hipposideridae, Rhinolophidae, and Rhinonycteridae genera. A recent study of Emballonura bats has shown that the basal clade of a group can drastically impact its biogeographical reconstruction (Ruedi et al. 2012). Although the basal clade of the Rhinolophidae remains unresolved, our reconstruction is the first to include all previously recovered basal candidates for this group as a strategy to minimize the impacts of partial taxonomic sampling of this group." [Fig. 4. Tables and Comments from Reference: Nicole M. Foley, Vu Dinh Thong, Pipat Soisook, Steven M. Goodman, Kyle N. Armstrong, David S. Jacobs, Sébastien J. Puechmaille, Emma C. Teeling, How and Why Overcome the Impediments to Resolution: Lessons from rhinolophid and hipposiderid Bats, Molecular Biology and Evolution, Volume 32, Issue 2, February 2015, Pages 313–333, https://doi.org/10.1093/molbev/msu329 ]
• 66 million years ago: Mass Extinction of 75% of Earth’s plant and animal species, selective larger mammalian and Dinosaurs resulted
• · and was called Cretaceous–Paleogene (K–Pg) Dinosaur Extinction Event,[a] aka Cretaceous–Tertiary (KT) extinction,[b] 
• · Birds and Bats survived the explosions
• · DNA and RNA Quantum Entanglements likewise exploded, were shaken, disassociated, disentangled, separated, fragmented and scattered 
• · Chemical bonds and Quantum Entanglement bonds hold DNA strands and DNA double helixes together and RNA strands and RNA and RNA proteins together. 
• · Without Chemical and QE bonds, DNA and RNA disassociate, disentangle, fall apart and RNA virus-like-pieces scatter.
• · Massive, forceful explosions, as in the catastrophic K-Pg Dinosaur Extinction Period, will cause massive Chemical and Quantum bond disassociations and disentanglements.
• · [Yuki Kobayashi, Kristina F. Chang, Tao Zeng, Daniel M. Neumark, Stephen R. Leone. Direct mapping of curve-crossing dynamics in IBr by attosecond transient absorption spectroscopy. Science, 2019; 365 (6448): 79 DOI: 10.1126/science.aax0076]
• · [Mihelic FM. Model of biological quantum logic in DNA. Life (Basel). 2013;3(3):474–481. Published 2013 Aug 2. doi:10.3390/life3030474] 
• · [Biology, www.mvla.net/download.cfm id=20525]
• · [What are the Ingredients of Life? By Natalie Wolchover, Feb 2, 2011, LiveScence] [Life's Little Mysteries consulted Matthew Pasek, a biogeochemist at the University of South Florida]
• · [Being the skunk at an atheist convention, La Jolla, Salk Institute, November 5-7, 2006 by Stuart Hameroff (Session 4), Post Conference Remarks - S. Hameroff]
• · [Timeless Quantum Universe is in Dynamic Equilibrium by Amrit S. Sorli sorli.bistra@gmail.com, Scientific Research CentreBistra, Ptuj, Sloveni]
• · [‘Einstein's Unfinished Dream: Marrying Relativity to Quantum World’ by Don Lincoln Nov 18, 2015 Science & Astronomy, Space.com]
• · [Hameroff and Chopra Describe God, on Youtube] Please review: [DR. HAMEROFF DESCRIBES GOD https://myscientistgod.us/dr-hameroff-describes-go]
• · [Scientist: Quantum physics can prove there's an afterlife, Chris Matyszczyk, November 16, 2013 cInet]
• · “Molecular time scale MCMCTREE analysis in PAM: Phylogenetic Analysis, Maximum Likelihood using BEAST topology revealed the Rhinolophid and Hipposiderid bats fossil calibrations and Molecular time scale date them to 64–65 mya. 
• · The exploded strands of DNA and RNA formed Relic Coronavirus  Ancestors and other RNA Relic Respiratory Virus segments and then disseminated worldwide. [novel hypothesis mbmsrmd]
• · Similar to Dinosaur Extinction time period 66 million years ago and Rhinolophid and Hipposiderid bats fossil date to 64–65 mya. [[Renne, Paul R.; et al, ‘ (PDF). Science. 339 (6120): 684–687. Jan (7 February 2013). Bibcode: 2013 Sci. 339.. 684R. doi: 10.1126/science. 1230492. PMID 23393261. Archived (PDF) from the original on 7 February 2017]
• · *Novel hypothesis the formation of RNA Relic Coronavirus Ancestors and other Relic Respiratory Viruses Ancestors date to 64–65 mya [novel hypothesis mbmsrmd]
• · *Seeking sustainability, viruses sought transmission and replication, therefore requiring host infestation and ‘reverse genetics’, “a recombination occurs between a murine coronavirus in which the ectodomain of the spike has been replaced with that of the feline coronavirus FIPV spike (called fMHV) and a synthetic RNA carrying the 3′ portion of the MHV genome from the HE gene through the 3′ end. [Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev. 2005;69(4):635–664. doi:10.1128/MMBR.69.4.635-664.2005]
• · Then shedding, for survival 
• · *Rhinolophid and Hipposiderid bats became the hosts for the RNA Coronavirus and other respiratory viruses. [How and why overcome the impediments to resolution: lessons from rhinolophid and hipposiderid bats. Mol Biol Evol. 2015;32(2):313–333. doi:10.1093/molbev/msu329]
• · Respiratory Viruses and Zoonoses are millions years old. 
• · Relic  Coronaviruse Ancestors and other Relic Respiratory Viruse Ancestors infested the Bats and the 1st Zoonoses formed. [novel hypothesis mbmsrmd]
• Files coming soon.
• PICTURE CREDIT JIM SLATER 307, JULY 13, 2017 THE PATH OF SUN, SOLAR SYSTEM, EARTH AROUND CENTRAL BLACK HOLE IN OUR MILKY WAY GALAXY

MELATONIN AND COVID-19 VIRULENCE  == mbmsrmd ABSTRACT 

IN THIS REPORTER'S OPINION MELATONIN IS NOT AN ADJUVANT TREATMENT FOR 

COVID-19,  BUT THE FOLLOWING PUBLICATION IS AN EXCELLENT DISCUSSION OF MELATONIN HORMONE NEUROPHYSIOLOGY

Are Your Flu Symptoms getting worse at night ? https://www.avogel.co.uk/health/immune-system/flu/are-your-flu-symptoms-getting-worse-at-night/ 

Why Do Humans Always Feel Sicker with viruses at Night?.... It’s simple, because Humans are actually Sicker From Viruses at Night. https://time.com/5521313/why-you-feel-sicker-at-night/ 

Does Melatonin, “The Hormone of Darkness” Increase Nocturnal COVID-19 Virulence?

“Melatonin's main job in the Human body is to regulate night and day cycles or sleep-wake cycles.

“Darkness causes the Human body to produce more Melatonin, which signals the body to prepare for sleep. 

“Daylight decreases Melatonin production and signals the Human body to prepare for being awake. [WebMD ] 

“Humans are Diurnal; typically, awake during day and asleep at night.“Bats are nocturnal; awake during night and asleep during day.Because Bats were the original hosts and have hosted Viruses for the past 64 to 66 million years and during that time have depended on Bats for energy, liveliness, reproduction and transmission resources, Acute Respiratory Viruses and COVID-19, like other viruses, are probably, preferably nocturnal, also.

Additionally, Bats, most viruses, Acute Respiratory Viruses and COVID-19 are potentially more virulent nocturnally, because melatonin in Hosts Bats at dusk promotes activity in nocturnal (night-active) animals, when awake during night, unlike their cousin vertebrate Humans, who sleep.

For vertebrates, melatonin is produced in darkness, thus usually at night, by the pineal gland, a small endocrine gland[91] located in the center of the brain but outside the blood–brain barrier. 

Light/dark information reaches the suprachiasmatic nuclei from retinal photosensitive ganglion cells of the eyes[92][93] and triggers the pineal gland, which is the melatonin secreation signal (as was once postulated). 

Known as "the hormone of darkness", the onset of melatonin at dusk promotes activity in nocturnal (night-active) animals like Bats and sleep in diurnal animals including humans

There are more viruses than stars in the universe. Why do only some infect us https://www.nationalgeographic.com/science/2020/04/factors-allow-viruses-infect-humans-coronavirus/

All viruses are not pathogens. But after the pathogenic viruses have cunningly hawked certain vulnerable Humans, Animals, Plants and Bacteria, some viruses contaminate their targets with fatal virulent contagion.

• Research suggests that Human body’s circadian rhythms, as well as some other factors, can exacerbate Human symptoms after sundown. 
• Along with regulating Human sleep, Human bodies’ ‘circadian clocks’ help manage your immune system. [Michael Smolensky, biological rhythm researcher and adjunct professor of biomedical engineering at the University of Texas.] 
• “When the immune system is activated” when Humans are sick with the common cold, “its infection-fighting cells release a variety of chemicals, some of which induce inflammation in the infected tissues,” 
• “Humans tend to experience symptoms as most severe when “their immune system kicks into highest gear, which is normally at night during sleep,” Smolensky, explains. https://time.com/5521313/why-you-feel-sicker-at-night/ 
•  “The body clock is said to have an effect on the body's cells. 
•  And because viruses make use of our cell activity to replicate, proliferate and scatter, the researchers feel viruses may use this to their advantage.
•  “Nocturnal animals and viruses evening body clock ‘winds-up’ (and research revealed viruses have greater replication), when the Humans body clock ‘winds-down’. 
•  “In the event of a future Flu Pandemic, nocturnal (night-time) Human and worker activities should be regarded as especially vulnerable to the effects of an infection.”
•  “Circadian rhythms are biological cycles in the body related to the time of day. They are sometimes referred to as the body clock, or as the body's individual biological timing.
•  “The body's receptors and cells have their own clocks, which interact with each other and are controlled by this master 24-hour clock in the brain. 
•  It is this effect on the cells that the researchers feel is responsible for the differences in viral spread.
•  Conclusion: “Viruses exploit their-own-clockwork for their own gain (virulence) and the Human body clock plays a part in controlling the spread of a virus. [University of Cambridge. Wellcome Trust, the European Research Council, the European Molecular Biology Organization Young Investigators Programme, the Lister Institute of Preventative Medicine, and the Medical Research Council. University of Cambridge, peer-reviewed Proceedings of the National Academy of Sciences (PNAS) journal. The study was published in the peer-reviewed Proceedings of the National Academy of Sciences (PNAS) journal] [ https://www.nhs.uk/news/medical-practice/does-time-of-day-influence-our-susceptibility-to-infection]
•  [Pévet P.]“The physiological roles of the hormone directly relate to the temporal information it conveys. 
•  In fact, nocturnal melatonin secretion is a hormonal output signal of the circadian clock able to convey photoperiodic as well as circadian signals to multiple structures and organs possessing melatonin receptors, within the brain or at the periphery. This explains why melatonin appears to act in so many different ways in so many different systems.
•  [Pévet P.]“The physiological roles of the hormone directly relate to the temporal information it conveys. 
•  In fact, nocturnal melatonin secretion is a hormonal output signal of the circadian clock able to convey photoperiodic as well as circadian signals to multiple structures and organs possessing melatonin receptors, within the brain or at the periphery. This explains why melatonin appears to act in so many different ways in so many different systems. [Pévet P. Melatonin in animal models. Dialogues Clin Neurosci. 2003;5(4):343-352.]
•  Therefore, in addition to social distancing or masks, if social distancing is not Humanly possible, curfews beginning at dusk, during height of activitiesnocturnal night-active-animals and viruses. 
•  NO in mbmsrmd’s Conclusion, because of the above exaltations, Melatonin cannot reduce the severity of COVID-19 pandemic? By Shneider A, Kudriavtsev A, Vakhrusheva A. [published online ahead of print, 2020 Apr 29]. Int Rev Immunol. 2020;1-10. doi:10.1080/08830185.2020.1756284
• == End MBMSRMD ABSTRACT 

Animals use the variation in duration of melatonin production each day as a seasonal clock.[94] In animals including humans,[95] the profile of melatonin synthesis and secretion is affected by the variable duration of night in summer as compared to winter. The change in duration of secretion thus serves as a biological signal for the organization of daylength-dependent (photoperiodic) seasonal functions such as reproduction, behavior, coat growth, and camouflage coloring in seasonal animals.[95] 

Can melatonin reduce the severity of COVID-19 pandemic? By Shneider A, Kudriavtsev A, Vakhrusheva A. [published online ahead of print, 2020 Apr 29]. Int Rev Immunol. 2020;1-10. doi:10.1080/08830185.2020.1756284

• 89. Arendt J (August 2005). "Melatonin: characteristics, concerns, and prospects". Journal of Biological Rhythms. 20 (4): 291–303. doi:10.1177/0748730405277492. PMID 16077149. There is very little evidence in the short term for toxicity or undesirable effects in humans. The extensive promotion of the miraculous powers of melatonin in the recent past did a disservice to acceptance of its genuine benefits.
• 90. Arendt J (October 2000). "Melatonin, circadian rhythms, and sleep". The New England Journal of Medicine. 343 (15): 1114–6. doi:10.1056/NEJM200010123431510. PMID 11027748.
• 91. Reiter RJ (May 1991). "Pineal melatonin: cell biology of its synthesis and of its physiological interactions". Endocrine Reviews. 12 (2): 151–80. doi:10.1210/edrv-12-2-151. PMID 1649044.
• 92. Richardson GS (2005). "The human circadian system in normal and disordered sleep". The Journal of Clinical Psychiatry. 66 Suppl 9: 3–9, quiz 42–3. PMID 16336035.Perreau-Lenz S, Pévet P, Buijs RM, Kalsbeek A (January 2004). "The biological clock: the bodyguard of temporal homeostasis". Chronobiology International. 21 (1): 1–25. doi:10.1081/CBI-120027984. PMID 15129821.
• 93. Lincoln GA, Andersson H, Loudon A (October 2003). "Clock genes in calendar cells as the basis of annual timekeeping in mammals—a unifying hypothesis". The Journal of Endocrinology. 179 (1): 1–13. doi:10.1677/joe.0.1790001. PMID 14529560.
• 94. Arendt J, Skene DJ (February 2005). "Melatonin as a chronobiotic". Sleep Medicine Reviews. 9 (1): 25–39. doi:10.1016/j.smrv.2004.05.002. PMID 15649736. Exogenous melatonin has acute sleepiness-inducing and temperature-lowering effects during 'biological daytime', and when suitably timed (it is most effective around dusk and dawn), it will shift the phase of the human circadian clock (sleep, endogenous melatonin, core body temperature, cortisol) to earlier (advance phase shift) or later (delay phase shift) times.
• 95. Chaturvedi CM (1984). "Effect of Melatonin on the Adrenl and Gonad of the Common Mynah Acridtheres tristis". Australian Journal of Zoology. 32 (6): 803–09. doi:10.1071/ZO9840803.
• 96. Chen HJ (July 1981). "Spontaneous and melatonin-induced testicular regression in male golden hamsters: augmented sensitivity of the old male to melatonin inhibition". Neuroendocrinology. 33 (1): 43–6. doi:10.1159/000123198. PMID 7254478.
• {Wikipedia]

===========================================================

FROM THIS REPORTER'S RESEARCH, MELATONIN IS NOT AN ADJUVANT TREATMENT FOR COVID-19, BUT THE FOLLOWING PUBLICATION IS AN EXCELLENT DISCUSSION OF MELATONIN HORMONE NEUROPHYSIOLOGY

COVID-19: Melatonin as a potential adjuvant treatment [Zhang R, Wang X, Ni L, et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020;250:117583. doi:10.1016/j.lfs.2020.117583] 

Abstract: This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death. Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation

• 1.  Introduction: Coronaviruses (CoVs) are RNA viruses infecting both human and animals; this infection involves the respiratory, gastrointestinal and central nervous system [1]. Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are infectious and lethal, and have caused thousands of deaths in the past two decades. The recent outbreak was discovered in Wuhan, China; this highly contagious disease has spread throughout China and other countries [2]. Although antiviral therapy, corticosteroid therapy and mechanical respiratory support have been applied, there is lack of a specific treatment for COVID-19 [2].
• Melatonin (N-acetyl-5-methoxytryptamine) is a bioactive molecule with an array of health-promoting properties; melatonin has been successfully used to treat sleep disorders, delirium, atherosclerosis, respiratory disease and viral infections [3]. Previous research has documented the positive effects of melatonin in alleviating acute respiratory stress induced by virus, bacteria, radiation, etc. [[4], [5], [6]]. Herein, we review the evidence indicating that melatonin will have supportive adjuvant utility in treating COVID-19 induced pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
• 2. Pathogenesis of COVID-19 and the rationale for melatonin use Patients with COVID-19 (who were infected by SARS-CoV-2) are reported to present with fever, dry cough, myalgia, fatigue, and diarrhea, etc. with symptoms varying somewhat with the patients' age. In some cases, the severe progression of the disease results in ALI/ARDS, respiratory failure, heart failure, sepsis, and sudden cardiac arrest within a few days [2,7]. The pathogenic examination of lung specimens from mild COVID-19 patients (who were retrospectively found to have COVID-19 at the time of lung cancer surgery) showed edema, proteinaceous exudate with globules, patchy inflammatory cellular infiltration and moderate formation of hyaline membranes [8]. In a postmortem assessment of a COVID-19 patient with severe ARDS, specimens of infected lungs demonstrated bilateral diffuse alveolar damage with edema, pneumocyte desquamation and hyaline membrane formation [9].
• Though these pathological reports were reported in only a small number of cases, the findings do resemble the pathological features found in SARS- and MERS-induced pneumonia [10]. SARS-CoVs, MERS-CoVs and SARS-CoV-2 are classified in beta-coronavirus family members [11]. Recent published research suggests that SARS-CoV-2 shares 79.0% nucleotide identity to SARS-CoV and 51.8% identity to MERS-CoV [12], indicating a high genetic homology among SARS-CoV-2, MERS-CoV and SARS-CoV. In SARS-CoV and MERS-CoV infected animal model, marked inflammatory and immune responsesmay activate a “cytokine storm”, and apoptosis of epithelial cells and endothelial cells; subsequently, vascular leakage, abnormal T cell and macrophages responses ensue and induce ALI/ARDS or even death [13].
• Based on genetic homology and pathologic features of the infected lung, we predicted that a cytokine storm also prevails in patients with COVID-19. In the blood of patients with COVID-19, there was a marked increase in interleukin 1β (IL-1β), interferon γ (IFN-γ), interferon-inducible protein 10 (IP-10), and monocyte chemoattractant protein 1 (MCP-1), as well as IL-4 and IL-10 when compared to that of SARS patients. This suggests some potential difference from SARS and MERS in the pathogenesis of coronavirus [2]. There is also a potential repressed immune function in COVID-19 patients with the hypo-albuminemia, lymphopenia, neutropenia, and decreased percentage of CD8+ T cell [2,7]. Recent reports suggest that in some COVID-19 patients, although being negative for the viral nucleic acid test, still sometimes present with a high level of inflammation. A clinical trial using certolizumab pegol (a TNF blocker) along with other anti-virus therapies may have beneficial effects in COVID-19 patients. Collectively, the finding indicates that inflammation is a major feature in COVID-19 patients. Thus, we hypothesize that excessive inflammation, depressed immune system, and an activate cytokine storm substantially contribute to the pathogenesis of COVID-19.
• In the early stages of coronaviruses infection, dendritic cells and epithelial cells are activated and express a cluster of pro-inflammatory cytokines and chemokines including IL-1β, IL-2, IL-6, IL-8, both IFN-α/β, tumor necrosis factor (TNF), C—C motif chemokine 3 (CCL3), CCL5, CCL2, and IP-10, etc. These are under the control of immune system. Thus, the overproduction of these cytokines and chemokines contributes to the development in disease [[14], [15], [16]].
• IL-10, produced by T-helper-2 (Th2), is antiviral, with an infection of coronaviruses leading to a marked decrease in this agent [17,18]. Interestingly, COVID-19 patients sometimes have a significantly elevated level of IL-10 [2]. Whether this is a feature of the COVID-19 infection or the result of medical treatment is unknown. The amplification of the inflammatory response would promote cellular apoptosis or necrosis of the affected cells, which would further fuel inflammation, followed by increasing permeability of blood vessels and the aberrant accumulation of inflammatory monocytes, macrophages and neutrophils in the lung alveoli [19]. This vicious circle would intensify the situation as the regulation of immune response is lost and cytokine storm is further activated, resulting in dire consequences.
• This known “cytokine storm” pathology associated with coronaviruses is also supported by experimental SARS-CoV models, one of which showed that the severity of Acute Lung Injury (ALI) was accompanied by an elevated expression of inflammation-relatd genes rather than increased viral titers. 
• In another case, the ablation of IFN-α/β receptor or the depletion of inflammatory monocytes/macrophages caused a marked rise in the survival rate of coronaviruses host without a change in viral load [19,20]. Both situations suggest a potential amplifying mechanism involved in CoV-induced ALI/ARDS regardless of the viral load. If a similar pathology also exists in COVID-19, the attenuation of the cytokine storm by targeting several key steps in the process could bring about improved outcomes.
• Melatonin is not viricidal….but it has indirect anti-viral actions [3] due to its 1. anti-inflammation, 2. anti-oxidation and 3. immune enhancing features [[21], [22], [23], [24]].There are situations in which melatonin suppresses the features of viral infections. In mice whose central nervous system is infected by virus (e.g., encephalitis), the use of melatonin caused less viremia, reduced paralysis and death, and decreased virus load [25]. In previous respiratory syncytial virus models, melatonin caused 1. down-regulation of acute lung oxidative injury, 2. pro-inflammatory cytokine release 3. and inflammatory cell recruitment. 4. These findings, along with those recently summarized by Reiter et al. [3], support a rationale for melatonin use in viral diseases. Also, melatonin's anti-inflammation, anti-oxidation, immune enhancing actions supports its potential attenuation of COVID-19 infection (Fig. 1 
• Pathogenesis of COVID-19 and potential adjuvant use of melatonin. We postulated that lungs infected by SARS-CoV-2, and a suppressed immune response, elevated inflammation and excessive oxidation stress proceed unabated, this results in the activation of the cytokine storm. ALI/ARDS may ensue, accompanied by a series of complications, the outcomes of which vary according to the severity of the disease. Melatonin may play a role of adjuvant medication in the regulation of immune system, inflammation and oxidation stress, and provide support for patients with ALI/ARDS and related complications. ALI: Acute lung injury; ARDS: Acute respiratory distress syndrome.
• 3. Melatonin & anti-inflammation: Melatonin exerts anti-inflammatory effects through various pathways. Sirtuin-1 (SIRT1) may mediate the anti-inflammatory actions of melatonin by inhibiting high mobility group boxechromosomal protein 1 (HMGB1), and thus down-regulating the polarization of macrophages towards the pro-inflammatory type [26]. In sepsis-induced ALI, the proper regulation of SIRT1 attenuates lung injury and inflammation, in which the application of melatonin might be beneficial [27]. Nuclear factor kappa-B (NF-κB) is closely associated with pro-inflammatory and pro-oxidative responses while being an inflammatory mediator in ALI. The anti-inflammatory effect of melatonin involves the suppression of NF-κB activation in ARDS [28,29]. Melatonin reportedly down-regulate NF-κB activation in T cells and lung tissue [30,31]. The stimulation of NF-E2-related factor 2 (Nrf2) is crucial in protecting lung from injury. In related studies, melatonin induces the up-regulation of Nrf2 with therapeutic effects in hepatoprotection, cardioprotection, etc. [32]. Whether Nrf2 is involved in the CoV-induced ALI remains unknown, but the close interaction of SIRT1, NF-κB and Nrf2 suggests their participation in the CoV-induced ALI/ARDS. As such, the data support the potential anti-inflammatory action of melatonin. Inflammation is commonly associated with an elevated production of cytokines and chemokines, while melatonin causes a reduction in the pro-inflammatory cytokines. TNF-α, IL-1β, IL-6, and IL-8, and an elevation in the level of anti-inflammatory cytokine IL-10 [33,34]. There may be, however, some concerns about the potential pro-inflammatory actions of melatonin when used in very high doses or under suppressed immune conditions where it may induce an increase production of pro-inflammatory cytokines, IL-1β, IL-2, IL-6, IL-12, TNF-α, and IFN-γ [35]. Conversely, in ALI infection models, melatonin presents with anti-inflammatory and protective action [6].
• 4. Melatonin & anti-oxidation: The anti-oxidative effect of melatonin cooperates with its anti-inflammatory actions by up-regulating anti-oxidative enzymes (e.g. superoxide dismutase), down-regulating pro-oxidative enzymes (e.g. nitric oxide synthase), and it may also interact directly with free radicals, functioning as free radical scavenger [3,4]. Viral infections and their replication constantly generate oxidized products. In a SARS-induced ALI model, the production of oxidized low density lipoprotein activates innate immune response by the overproduction of IL-6 alveolar macrophages via Toll-like receptor 4 (TLR4)/NF-kB signaling, thereby leading to ALI [36]. TLR4 is a receptor for the innate immune system, and it is also a therapeutic target for melatonin. In brain ischemia, gastritis and periodontitis disease models, melatonin has documented anti-inflammation actions via TLR4 signaling [[37], [38], [39]]. The anti-oxidative effect of melatonin has also been confirmed in ALI caused by radiation, sepsis and ischemia-reperfusion [4,40,41]. In ALI/ARDS patients, especially when the disease is advanced and in patients treated in intense care units (ICUs), severe inflammation, hypoxemia and mechanical ventilation with high oxygen concentrations inevitably increases oxidant generation locally and systematically [42,43]. Accordingly, we speculate that excessive oxidation also is likely involved in COVID-19. The extensive studies of Gitto et al. [44,45], who used melatonin to treat newborn infants with respiratory distress, has documented the anti-oxidant and anti-inflammatory actions of melatonin in the lung. Thus, it is likely that the application of melatonin would be beneficial in controlling the inflammation and oxidation in coronavirus infected subjects.
• 5. Melatonin & immunomodulation: When virus is inhaled and infects respiratory epithelial cells, dendritic cells phagocytose the virus and present antigens to T cells. Effector T cell function by killing the infected epithelial cells, and cytotoxic CD8+ T cells produce and release pro-inflammatory cytokines which induce cell apoptosis [46]. Both the pathogen (CoV) and cell apoptosis trigger and amplify the immune response. The exacerbation of cytokine production, excessive recruitment of immune cells and the uncontrollable epithelial damage generates a vicious circle for infection related ALI/ARDS [47]. The clinical characteristics of COVID-19 suggest that a reduced level of neutrophils, lymphocytes and CD8+ T cells in peripheral blood [7,48]. Melatonin exerts regulatory actions on the immune system and directly enhances the immune response by improving proliferation and maturation of natural killing cells, T and B lymphocytes, granulocytes and monocytes in both bone marrow and other tissues [49]. In macrophages, antigen presentation is also augmented after the application of melatonin, where the up-regulation of complement receptor 3, MHC class I and class II, and CD4 antigens were detected [50].
• NOD-like receptor 3 (NLRP3) inflammasome is part of the innate immune response during lung infection. The pathogen, including a virus (CoVs has not yet been tested), triggers NLRP3 activation to amplify the inflammation. There is probably a balance of the protective and damaging actions of NLRP3 in the lung. Thus, in a mouse experiment, inhibition of NLRP3 in the early phase of infection increased mortality, whereas suppression of NLRP3 at the peak of infection allowed for a protective effect [51]. This supports the use of melatonin in ALI/ARDS when inflammation is most severe. Inflammasome NLRP3 is correlated to lung diseases caused by infection, including influenza A virus, syncytial virus, and bacteria [[51], [52], [53]]. The efficacy of melatonin in regulating NLRP3 has been proven in radiation-induced lung injury, allergic airway inflammation and oxygen-induced ALI and LPS-induced ALI models, in which melatonin reduced the infiltration of macrophages and neutrophils into the lung in ALI due to the inhibition of NLRP3 inflammasome [4,28,54,55].
• 6. Melatonin effects in cytokine levels in human. Although there is obviously no report related to the use of melatonin in COVID-19 patients, in subjects with other diseases and an increased level of inflammation, the application of melatonin showed promising results regarding the attenuation of circulating cytokines levels. In a randomized controlled trial, 8-week oral intake of 6 mg/d melatonin caused a significant decrease in serum levels of IL-6, TNF-α and hs-C-reactive protein (hs-CRP) in patients with diabetes mellitus and periodontitis [56]. In another trial of patients suffering with severe multiple sclerosis, orally 25 mg/d of melatonin for 6 months also promoted a significant reduction in serum concentrations of TNF-α, IL-6, IL-1β and lipoperoxides [57]. In the acute phase of inflammation, including during surgical stress [58], brain reperfusion [59], and coronary artery reperfusion [60], melatonin intake of 10 mg/d, 6 mg/d and 5 mg/d of melatonin for less than 5 days induced a reduced level of pro-inflammatory cytokines. A recent meta-analysis of a total of 22 randomized controlled trials suggested that a supplementary use of melatonin is associated with a significant reduction of TNF-α and IL-6 level [61]. This clinical evidence suggests that the use of melatonin as a supplement may effectively reduce the levels of circulating cytokines, and may potentially also lower pro-inflammatory cytokine levels in COVID-19 patients.
• 9. Conclusion: Possible beneficial effects of melatonin as adjuvant use in COVID-19: 
• in anti-inflammation · anti-oxidation · immune response regulation has been repeatedly demonstrated in respiratory disorder models induced by infections and associated complications. 
• Melatonin has a high safety profile. Although the direct evidence of melatonin application in COVID-19 is unclear, both its use in experimental animal models and in studies on humans has continuously documented its efficacy and safety and its use by COVID-19 patients predictably would be highly beneficial.  [Rui Zhang:Resources, Writing - original draft.Xuebin Wang:Writing - original draft.Leng Ni:Writing - review & editing, Supervision.Xiao Di:Visualization.Baitao Ma:Writing - review & editing.Shuai Niu:Resources.Changwei Liu:Conceptualization, Supervision.Russel J. Reiter:Writing - review & editing.]
• See References