新冠疫情对上海某三甲医院老年科认知障碍患者及照料者的影响与远程医疗模式的初步探索

目的:2022年3月,新冠疫情在上海暴发,为了解此次新冠疫情对老年认知障碍患者及照料者的影响,并进一步明确远程医疗(电话访谈形式)在疫情下对认知障碍老人可能的帮助作用,展开此项研究。方法:纳入2021年1月~12月在上海市精神卫生中心老年科住院的69例认知障碍患者,在2022年4月通过自制问卷以电话访谈形式收集患者疫情期间的相关情况,采用NPI问卷明确认知障碍老人精神行为症状情况、Zarit负担量表了解家属负担情况,并给予个体化远程指导和心理支持。一月后再次进行电话随访。结果:最终有49名患者及照料者顺利完成评估,结果提示:认知障碍老人的精神行为症状在疫情期间以情感淡漠(67.3%),幻觉(61.2%),睡眠夜间行为(61.2%),妄想(53.1%)、易激惹(51%)为主要症状。家属负担量表显示:认知障碍的照料者中有一半以上(59.2%)的家属有较重的负担,77.6%的家属认为疫情期间最大的困难就是购买药物,其他困难还包括看病(57.1%)、担心患者被感染隔离(36.7%),以及担心患者病情反复(44.9%)等。电话随访证实85.7%的患者家属认可远程电话医疗方式,有77.6%的患者家属认为这样的方式能很有效的帮助患者,同时也能缓解在疫情期间的焦虑情绪。结论:此次上海新冠疫情对老年认知障碍患者及照料者身体和心理负担造成了一定的影响。而远程电话医疗方式能被多数家属所接受,可能为以后更好地帮助有认知障碍的患者及照料者发挥更大的作用。

Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus

Following the outbreak of coronavirus disease 2019(COVID-19),several severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-related coronaviruses have been discovered.Previous research has identified a novel lineage of SARS-CoV-2-related CoVs in bats,including RsYN04,which recognizes human angiotensin-converting enzyme 2(ACE2)and thus poses a potential threat to humans.Here,we screened the binding of the RsYN04receptor-binding domain(RBD)to ACE2 orthologs from 52animal species and found that the virus showed a narrower ACE2-binding spectrum than SARS-CoV-2.However,the presence of the T484W mutation in the RsYN04 RBD broadened its range.We also evaluated 44 SARS-CoV-2antibodies targeting seven epitope communities in the SARS-CoV-2 RBD,together with serum obtained from COVID-19 convalescents and vaccinees,to determine their cross-reaction against RsYN04.Results showed that no antibodies,except for the RBD-6 and RBD-7 classes,bound to the RsYN04 RBD,indicating substantial immune differences from SARS-CoV-2.Furthermore,the structure of the RsYN04 RBD in complex with cross-reactive antibody S43 in RBD-7 revealed a potently broad epitope for the development of therapeutics and vaccines.Our findings suggest RsYN04 and other viruses belonging to the same clade have the potential to infect several species,including humans,highlighting the necessity for viral surveillance and development of broad anticoronavirus countermeasures.

The trajectories of physical growth in 4 months postnatal corrected age among preterm infants discharged from neonatal intensive care units and associated factors: A prospective study

Objectives Growth retardation is a risk for premature infants.In addition to demographic and perinatal factors,preterm infants’physical growth may be affected by neonatal intensive care unit(NICU)stress,maternal postpartum depression,and mother-infant interaction.This study aimed to investigate the trajectories of physical growth in 4 months corrected age among preterm infants discharged from the NICU and the impactors on these trajectories.Methods A prospective study was conducted among 318 preterm infants from September 2019 to April 2021 in Shanghai,China.Latent growth modeling was applied to identify the weight,length,and head circumference growth trajectories in 4 months corrected age and explore the effects of demographic and medical characteristics,infant stress during NICU stay,maternal postpartum depression,and mother-infant interaction on each trajectory.Results Unconditional latent growth models showed curve trajectories with increasingly slower growth in weight,length,and head circumference until 4 months of corrected age.Conditional latent growth models showed that a longer length of stay in the NICU and more skin punctures were negatively associated with weight at 40 weeks corrected gestational age(β=−0.43 and−0.19,respectively,P<0.05).The maternal postpartum depression between 40 weeks corrected gestational age and 1 month corrected postnatal age was associated with a lower growth rate of length(β=−0.17,P=0.040),while between 2 and 3 months corrected postnatal age,there were lower growth rates of weight and head circumference(β=−0.15 and−0.19,respectively,P<0.05).The mother-infant interaction scores between 40 weeks corrected gestational age and 1 month corrected postnatal age negatively predicted the growth rate of weight(β=−0.19,P=0.020).Conclusion The physical growth trajectories of preterm infants discharged from the NICU were influenced by infant stress during the NICU stay,maternal postpartum depression and mother-infant interaction.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its sub-variants.This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies.Here,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its sub-variants.Cryo-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S protein.The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex.Furthermore,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus particles.Compared to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro.The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Efficient inhibition of SARS-CoV-2 emerging EG.5,EG.5.1 and BA.2.86 variants by fusion inhibitor HY3000 peptide

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to pose a significant threat to the world,as it continually evolves and gives rise to multiple variants and sub-variants.Recently,the Omicron EG.5 linage,which was first detected in Indonesia on 17 February 2023,has raised concerns due to its increased prevalence and extended immune escape properties,according to the risk analysis by the World Health Organization(WHO)[1].As of 3 October 2023,EG.5 and its sub-linages have been reported in 83 countries with shared 49,008 genome sequences in GISAID database(https://gisaid.org/hcov19-variants/).EG.5 has become the dominant strain in the United States according to Centers for Disease Control and Prevention(CDC),accounting for 29.4%of SARS-CoV-2 infections(https://covid.cdc.gov/covid-data-tracker/#variant-proportions).

A pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery

Coronaviruses(Co Vs)have brought serious threats to humans,particularly severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which continually evolves into multiple variants.These variants,especially Omicron,reportedly escape therapeutic antibodies and vaccines,indicating an urgent need for new antivirals with pan-SARS-Co V-2 inhibitory activity.We previously reported that a peptide fusion inhibitor,P3,targeting heptad repeated-1(HR1)of SARS-Co V-2 spike(S)protein,could inhibit viral infections.Here,we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative,the P315V3,showed the most efficient antiviral activity against SARS-Co V-2 variants and several other sarbecoviruses,as well as other human-Co Vs(HCo Vs).P315V3 also exhibited effective prophylactic efficacy against the SARS-Co V-2 Delta and Omicron variants in mice via intranasal administration.These results suggest that P315V3,which is in PhaseⅡclinical trial,is promising for further development as a nasal pan-SARS-Co V-2 or pan-Co Vs inhibitor to prevent or treat CoV diseases.

Infection of SARS-CoV-2 causes severe pathological changes in mouse testis

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has affected more than 600 million people worldwide.Several organs including lung,intestine,and brain are infected by SARS-CoV-2.It has been reported that SARS-CoV-2 receptor angiotensin-converting enzyme-2(ACE2)is expressed in human testis.However,whether testis is also affected by SARS-CoV-2 is still unclear.In this study,we generate a human ACE2(hACE2)transgenic mouse model in which the expression of hACE2 gene is regulated by hACE2 promoter.Sertoli and Leydig cells from hACE2 transgenic mice can be infected by SARS-CoV-2 pseudovirus in vitro,and severe pathological changes are observed after injecting the SARS-CoV-2 pseudovirus into the seminiferous tubules.Further studies reveal that Sertoli and Leydig cells from hACE2 transgenic mice are also infected by authentic SARS-CoV-2 virus in vitro.After testis interstitium injection,authentic SARS-CoV-2 viruses are first disseminated to the interstitial cells,and then detected inside the seminiferous tubules which in turn cause germ cell loss and disruption of seminiferous tubules.Our study demonstrates that testis is most likely a target of SARS-CoV-2 virus.Attention should be paid to the reproductive function in SARS-CoV-2 patients.

Dentin-desensitizing biomaterials

Dentin hypersensitivity(DH)associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration.Medication,filling repair,laser irradiation,crown therapy,and desensitizing toothpaste are standard clinical treatment strategies,but unsatisfactory treatment modalities are marked by long-term administration,poor dentinal tubule closure,microleakage,and the development of secondary caries.To improve the treatment efficiency of DH,numerous organic or inorganic biomaterials have been developed to relieve toothache and reverse the instability of desensitization.Biomaterials are expected to participate in dental remineralization to achieve desensitization.This review discusses various biomaterials for DH therapy based on different desensitization mechanisms,including dentinal tubule closure and dental nerve blockade,and presents a perspective on the underlying future of dentin regeneration medicine for DH therapy.

Rapid evaluation of heterologous chimeric RBD-dimer mRNA vaccine for currently-epidemic Omicron sub-variants as booster shot after inactivated vaccine

With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines.

导致狐狸重症腹泻疫情的新型犬冠状病毒的发现与鉴定

2019年末,中国东北地区狐狸群中暴发大规模疫情,发病狐狸表现出急性腹泻症状,并出现大量狐狸死亡.通过对该疫源地发病狐狸肛拭子、血液与发病组织的检测分析,获得了多条全长新型犬冠状病毒(CCoV)基因组序列,研究团队将该病毒命名为VuCCoV,并确认VuCCoV是引起该疫情的病原.进一步分析表明,VuCCoV基因组的4个结构基因(S,E,M,N)中的3个(E,M,N)与犬冠状病毒(CCoV)对应基因具有超过90%的核苷酸同一性,但S基因核苷酸序列表现出较大的差异.VuCCoV的RNA依赖的RNA聚合酶与蝙蝠冠状病毒PB025的对应蛋白仅存在2~3个氨基酸差异,系统进化分析提示VuCCoV很可能来源于蝙蝠.表面等离子体共振分析实验表明,VuCCoV刺突蛋白受体结合区(RBD)可与犬和狐狸的氨肽酶N(APN)结合,但不与人APN结合,假病毒感染及病毒分离培养实验进一步证实该VuCCoV不易感染人源细胞.蝙蝠等野生动物宿主的病毒跨物种传播对人类和家畜健康构成了显著威胁,VuCCoV的发现和溯源证实蝙蝠作为疫情出现的潜在驱动因素的重要性.积极监控蝙蝠及其他犬科动物中的病毒感染,发现、鉴定对人兽健康构成潜在威胁的新型冠状病毒并研究其进化变异特征与感染特性,对于防控新发人兽共患传染病、建设国家生物安q全体系具有重要意义.

Back to Science in Searching for SARS-CoV-2 Origins

In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)became the first-known pandemic hastening CoV with tremendous wrecking to the world(2).The origin tracing of these emerging pathogens is of great significance in infectious disease prevention and control(3–4).The origin of SARS-CoV-2 remains elusive after the more than 3-year pandemic,though scientists around the world are making great efforts.From the experience of studying many other infectious pathogens,origin tracing is systematic and time-consuming work.The supposed origins of many infectious pathogens are still in debate,including SARS-CoV and human immunodeficiency virus,etc(5).

A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites IV and V of the viral fusion glycoprotein

Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.

Mouse model for pangolin-origin coronavirus GX/P2V/2017 infection and cross-protection from COVID-19 ZF2001 subunit vaccine

Many severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)–related coronaviruses have been discovered,constituting potential threats to human health.However,it remains unclear whether the currently available vaccines are effective against these coronaviruses.Here,we constructed a wild-type mouse model to evaluate pathogenicity of the SARS-CoV-2-related pangolin coronavirus GX/P2V/2017 and neutralization efficacy of the approved tandemrepeat SARS-CoV-2 spike receptor-binding domain(RBD)vaccine ZF2001.We found that ZF2001-induced cross-reactive and cross-neutralizing antibodies against GX/P2V/2017,and the vaccination alleviated the pathological lung damage caused by GX/P2V/2017 in mice.These results indicate that RBD may work as a promising candidate for pan-coronavirus vaccine development.

Biosafety and immunology:An interdisciplinary field for health priority

Biosafety hazards can trigger a host immune response after infection,invasion,or contact with the host.Whether infection with a microorganism results in disease or biosafety concerns depends to a large extent on the immune status of the population.Therefore,it is essential to investigate the immunological character-istics of the host and the mechanisms of biological threats and agents to protect the host more effectively.Emerging and re-emerging infectious diseases,such as the current coronavirus disease 2019(COVID-19)pan-demic,have raised concerns regarding both biosafety and immunology worldwide.Interdisciplinary studies involved in biosafety and immunology are relevant in many fields,including the development of vaccines and other immune interventions such as monoclonal antibodies and T-cells,herd immunity(or population-level barrier immunity),immunopathology,and multispecies immunity,i.e.,animals and even plants.Meanwhile,advances in immunological science and technology are occurring rapidly,resulting in important research achievements that may contribute to the recognition of emerging biosafety hazards,as well as early warning,prevention,and defense systems.This review provides an overview of the interdisciplinary field of biosafety and immunology.Close collaboration and innovative application of immunology in the field of bio-safety is becoming essential for human health.

平急一体化传染病防控平台在新冠肺炎疫情中的应用

以新冠肺炎为代表的传染病对人类健康和经济发展造成重大威胁。疫情暴发时的应急科研攻关是开发抗击疫情有力武器的关键,而有机结合了平时研究和应急攻关为一体的传染病防控平台是抗击疫情的基础。新冠肺炎疫情暴发以来,高福院士团队基于长期的研究积累,利用平急一体传染病防控平台,在新冠病毒的基础研究和应用研究两方面取得了重要成果,鉴定出新冠病毒的受体,揭示了新冠病毒以及变异株的入侵机制,跨种传播能力,基于入侵机制的理论基础开发出国际上第一个获批临床使用的新冠病毒重组亚单位疫苗以及在美国等十余国紧急使用的新冠肺炎治疗性抗体药物,迅速开发靶向3CL蛋白酶药物以及靶向入侵的多肽抑制剂,为中国以及世界新冠肺炎疫情的防控做出了重大贡献。

A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture

While human induced pluripotent stem cells(hiPSCs)have promising applications in regenerative medicine,most of the hiPSC lines available today are not suitable for clinical applications due to contamination with nonhuman materials,such as sialic acid,and potential pathogens from animal-product-containing cell culture systems.Although several xeno-free cell culture systems have been established recently,their use of human fibroblasts as feeders reduces the clinical potential of hiPSCs due to batch-to-batch variation in the feeders and time-consuming preparation processes.In this study,we have developed a xeno-free and feeder-cell-free human embryonic stem cell(hESC)/hiPSC culture system using human plasma and human placenta extracts.The system maintains the self-renewing capacity and pluripotency of hESCs for more than 40 passages.Human iPSCs were also derived from human dermal fibroblasts using this culture system by overexpressing three transcription factors—Oct4,Sox2 and Nanog.The culture system developed here is inexpensive and suitable for large scale production.

On the origin of SARS-CoV-2——The blind watchmaker argument

In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.

Genomic Perspectives on the Emerging SARS-CoV-2 Omicron Variant

A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,2021.This study analyzed the viral genome sequencing data of 108 samples collected from patients infected with Omicron.First,we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to.Second,the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time(median:62 vs.45),especially in the Spike gene.Mutations in the Spike gene confer alterations in 32 amino acid residues,more than those observed in other SARS-CoV-2 variants.Moreover,a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein,which could potentially affect the replication,infectivity,and antigenicity of SARS-CoV-2.Third,there are 53 mutations between the Omicron variant and its closest sequences available in public databases.Many of these mutations were rarely observed in public databases and had a low mutation rate.In addition,the linkage disequilibrium between these mutations was low,with a limited number of mutations concurrently observed in the same genome,suggesting that the Omicron variant would be in a different evolutionary branch from the currently prevalent variants.To improve our ability to detect and track the source of new variants rapidly,it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.

The mysterious origins of the Omicron variant of SARS-CoV-2

The coronavirus disease 2019(COVID-19)pandemic has ravaged theworld for nearly 2 years,with continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Omicron,the latest Variant of Concern(VOC),has spread to all six continents,leading to a rapid increase in confirmed COVID-19 cases and surpassing Delta as the dominant variant in many countries.

Both structure and function of human monoclonal antibodies contribute to enhancement of Zika virus infectivity in vitro

Dear Editor,Antibody-dependent enhancement（ADE）has long been recognized for dengue virus（DENV）in vitro and in vivo.It is now clear that antibodies to DENV can also enhance Zika virus（ZIKV）infection in vitro,and vice versa（Dejnirattisai et al.,2016;Stettler et al.,2016）.The characteristics of enhancing antibodies,however,remain elusive.