Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses

The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health risk.Yet,the evolutionary principles of MPXV remain largely unknown.Here,we examined the evolutionary patterns of protein sequences and codon usage in MPXV.We first demonstrated the signal of positive selection in OPG027,specifically in the CladeⅠlineage of MPXV.Subsequently,we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak.Furthermore,we showed strong epistasis between amino acid substitutions located in different genes.The codon adaptation index(CAI)analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes,and the CAI decreased over time and diverged between clades,with CladeⅠ>Ⅱa andⅡb-A>Ⅱb-B.While the decrease in fatality rate among the three groups aligned with the CAI pattern,it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates.This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.

Insights into varicella-zoster virus assembly from the B-and C-capsid at near-atomic resolution structures

Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.

Immunogenicity and Safety of Homologous Booster Doses of CoronaVac COVID-19 Vaccine in Elderly Individuals Aged 60 Years and Older:A Dosing Interval Study—Yunnan Province,China,2021–2022

Summary What is already known about this topic?Neutralization levels induced by inactivated vaccines rapidly wane after primary immunization,and a homologous booster can recall specific immune memory,resulting in a remarkable increase in antibody concentration.The optimal interval between primary and booster doses has yet to be determined.

Safety and Effectiveness of SA58 Nasal Spray Against COVID-19 Infection in Medical Personnel:An Open-Label,Blank-Controlled Study—Hohhot City,Inner Mongolia Autonomous Region,China,2022

Summary What is already known about this topic?The active ingredient of the SA58 Nasal Spray is a broad-spectrum neutralizing antibody with a high neutralizing capacity against different Omicron subvariants in vitro studies.What is added by this report?This study demonstrated the safety and effectiveness of SA58 Nasal Spray against coronavirus disease 2019(COVID-19)infection in medical personnel for the first time.What are the implications for public health practice?This study provides an effective approach for the public to reduce their risk of COVID-19 infection.The findings of this research have the potential to significantly reduce the risk of infection and limit human-to-human transmission in the event of a COVID-19 outbreak.

Sense to Tune: Engaging Microglia with Dynamic Neuronal Activity

Microglia,the primary resident immune cells in the central nervous system(CNS),continuously survey the microenvironment via their ramified and motile processes to maintain brain homeostasis[1].As immune sentinels,microglia detect exogenous pathogens,elicit inflammation,promote tissue repair,and engage in the onset and progression of brain diseases[1].

MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

MicroRNAs （miRNAs） that exert function by posttran- scriptional suppression have recently brought insight in our understanding of the role of non.protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer （CRC） and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues （NCTs）, and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phe- nocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potentialtumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.

Norepinephrine from the Locus Coeruleus Regulates Microglia Dynamics During Wakefulness

Microglia,the brain’s"busy bees",continuously survey the microenvironment by extending and retracting their ramified processes to maintain brain homeostasis[1,2].Upon disease or injury,microglia quickly transform their morphology and extend their processes towards the disease/injury sites to clear damage[2].The mechanisms underlying the high motility of microglial processes and the rapid morphological transformation of microglia have been extensively investigated.

Factors Associated with SARS-CoV-2 Repeat Positivity—Beijing,China,June–September 2020

Introduction:Repeat positive severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)following COVID-19 initial viral clearance(repositivity)poses a public health management challenge.The objective was to determine factors associated with neutralizing antibody(Nab)level and re-positivity among patients infected with a single strain SARS-CoV-2.Methods:During a single strain SARS-CoV-2 cluster in Beijing,China,longitudinal individual clinical,virological,and immunological data were collected from 368 infections from June 13 to September 22,2020.Factors associated with Nab level and re-positivity were analyzed using generalized estimating equations.Results:A total of 353(96%)SARS-CoV-2 infections had demographic,clinical,and laboratory data available.Among the 353 infections,55(15.5%)were re-positive,and blood draws were taken from 346 individuals(98.0%)during hospitalization and/or during the follow-up period.Symptoms were milder for the second-time admission for the re-positives,although 36.4%of re-positives presented with radiographic appearance of pneumonia manifestation.Compared to non-re-positive patients,NAb titers were lower among re-positives;NAb was positively associated with clinical severity.Samples from the lower respiratory tract manifested higher viral load than that from the upper respiratory tract.Multivariable analysis showed re-positivity was positively associated with being female[odd ratio(OR)=1.7,95%confidence interval(CI)1.1–2.8]and being aged<18 years(OR=5.2,95%CI 1.5–18.1);having initially asymptomatic infection(OR=13.7,95%CI 1.6–116.3);and negatively associated with a higher NAb level(OR=0.9,95%CI 0.5–1.7).Conclusions:NAb may be important for sustained viral clearance.Lower respiratory tract infection was associated with higher viral load among all infections when compared to upper respiratory tract infection.Continuous lower respiratory and intermittent upper respiratory viral shedding among COVID-19 infections may occur.

Vital Surveillances: Factors Associated with SARS-CoV-2 Repeat Positivity-Beijing, China, June-September 2020

全球各地陆续出现新冠患者康复后再次核酸阳性的情况,引发了行业内的关注。先前有关复阳的研究均来自于不同的传播链,感染者感染的毒株不尽相同。为减少不同毒株而引发的复阳的选择偏倚,有必要对感染同一毒株的新冠患者的复阳情况进行研究。中和抗体水平被认为在清除新冠病毒中发挥重要作用,被用于治疗新冠患者。本研究纳入人口学、临床、实验室数据及重复测量中和抗体和病毒载量,分析了影响新冠患者复阳的因素。结果显示,353个病例中,约15%患者康复后复阳,这一结果与大部分有关复阳的研究结果相符。使用多因素广义估计模型对复阳进行分析发现,复阳和患者中和抗体水平成负相关,即抗体水平低,复阳的可能性更大。提示可能因抗体水平低,不足以完全清除病毒而导致复阳。

Brain Macrophages:Close or Distant Relatives?

The concept of a mononuclear phagocyte system in which tissue-resident macrophages arise from the circulating monocytes has been dogma in immunology for more than half a century[1].While monocytes do give rise to macrophages under certain conditions,recent studies clearly dem on strate that monocytes do not primarily contribute to most adult tissue-resident macrophage pools under the steady state[2].Instead,the majority of adult tissue-resident macrophages are derived from erythromyeloid progenitors(EMPs)in the yolk sac that seed tissue before birth[2].

An Immunocompetent Patient with High Neutralizing Antibody Titers Who Shed COVID-19 Virus for 169 days——China,2020

Few reports are available about prolonged shedding of coronavirus disease(COVID-19)virus,also known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),by immunocompetent patients.We report a case of an infected,immunocompetent person with 169 days of COVID-19 virus shedding during which time he had two brief periods when he tested negative for COVID-19 followed by again testing positive.We describe relevant clinical,immunological,and genomic features.We found that continuous and prolonged viral replication and infectivity existed in an immunocompetent COVID-19 patient,despite having high neutralizing antibody titers.