Zoonotic origins of human coronavirus 2019(HCoV-19/SARS-CoV-2):why is this work important?

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.

Prevalence and Seroprevalence of Non-SARS Human Coronaviruses 229E and OC43 in East Tyrol/Austria

The recent SARS-CoV-2 pandemic renewed interest in other previously discovered human coronaviruses—the non-severe acute respiratory syndrome human coronavirus (non-SARS hCoVs) and this study is a starting point for a closer investigation of those. With the pandemic behind us we believe it to be important to also examine the current and past respiratory pathogen landscape in the patient population in our care. Therefore, 954 nasopharyngeal swabs of patients with respiratory diseases collected between October 2018 and March 2020 were tested against the pathogens Mycoplasma pneumoniae, Bordetella pertussis, Influenza A and virus, Human metapneumovirus, respiratory syncytial virus, Parainfluenza virus, human Adenovirus and Polyoma virus BK/JC. Swabs negative against these pathogens were further tested for OC43 and 229E by RT-qPCR. Human coronaviruses 229E and OC43 were proven as the causative agents in a considerable number of cases, confirmed by PCR. Overall, our results show that those two non-SARS hCoVs were responsible for 13.9% (11 of 79) of infections with flu-like symptoms of unknown etiology in the study area. In the subsequent seroprevalence study, it was shown that the seroprevalence rate of IgG antibodies against 229E and OC43 was over 50%, indicating that a big part of the population in our study area has been in contact with these non-SARS-CoVs and has built the specific humoral immune response accordingly.

Stability of SARS Coronavirus in Human Specimens and Environment and Its Sensitivity to Heating and UV Irradiation

Objective The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied. Methods Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistances to temperature and UV irradiation were analyzed. A total of 106 TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infectionn. Results The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4℃, at room temperature (20℃) and at 37℃ for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56℃, at 67℃ and at 75℃, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level. Conclusion The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.

A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry

It is unknown whether pangolins,the most trafficked mammals,play a role in the zoonotic transmission of bat coronaviruses.We report the circulation of a novel MERS-like coronavirus in Malayan pangolins,named Manis javanica HKU4-related coronavirus(MjHKU4r-CoV).Among 86 animals,four tested positive by pan-CoV PCR,and seven tested seropositive(11 and 12.8%).

SARS Patients-derived Human Recombinant Antibodies to S and M Proteins Efficiently Neutralize SARS-Coronavirus Infectivity

Objective To develop a specific SARS virus-targeted antibody preparation for emergent prophylaxis and treatment of SARS virus infection. Methods By using phage display technology, we constructed a naive antibody library from convalescent SARS patient lymphocytes. To obtain the neutralizing antibody to SARS virus surface proteins, the library panning procedure was performed on purified SARS virions and the specific Fab antibody clones were enriched by four rounds of repeated panning procedure and screened by highthroughput selection. The selected Fab antibodies expressed in the periplasma of E. coli were soluble and further purified and tested for their binding properties and antiviral function to SARS virus. The functional Fab antibodies were converted to full human IgG antibodies with recombinant baculovirus/insect cell systems and their neutralizing activities were further determined. Results After four rounds of the panning, a number of SARS-CoV virus-targeted human recombinant Fab antibodies were isolated from the SARS patient antibody library. Most of these were identified to recognize both natural and recombinant SARS spike （S） proteins, two Fab antibodies were specific for the virus membrane （M） protein, only one bound to SARS-CoV nucleocapsid protein. The SARS-CoV S and M protein-targeted Fab or IgG antibodies showed significant neutralizing activities in cytopathic effect （CPE） inhibition neutralization test, these antibodies were able to completely neutralize the SARS virus and protect the Vero cells from CPE after virus infection. However, the N protein-targeted Fab or IgG antibodies failed to neutralize the virus. In addition, the SARS N protein-targeted human Fab antibody reacted with the denatured N proteins, whereas none of the S and M protein specific neutralizing antibodies did. These results suggested that the S and M protein-specific neutralizing antibodies could recognize conformational epitopes which might be involved in the binding of virions to cellular receptors and the fusion activity of the virus Conclusion The SARS-CoV spike protein and membrane proteins are able to elicite efficient neutralizing antibodies in SARS patients. The neutralizing antibodies we generated in this study may be more promising candidates for prophylaxis and treatment of SARS infection.

An In-depth Interpretation of the Universal Declaration of Human Rights With the Common Values of Humanity As the Research Paradigm

Interpreting the Universal Declaration of Human Rights from political,juridical and philosophical perspectives is es-sential for promoting the guiding principles of the Declaration,build-ing consensus on human rights,and advancing human rights practice in the new historical context.To conduct an academic,systematic in-terpretation of the Declaration that conforms to the trends of the times and answers the fundamental questions of the world,it is necessary to find a new research paradigm.The common values of humanity,namely peace,development,equity,justice,democracy and freedom,put forward by Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,provide the most explanatory and penetrating scientific paradigm for reaching the issue.This paper an-alyzes and reflects on the views,value foundation and principled(con-tractual)consensus of human rights in the Declaration,and narrates and foresees the far-reaching significance of the three global initia-tives(namely,the Global Development Initiative,the Global Security Initiative,and the Global Civilization Initiative)with the common val-ues of humanity as the soul in advancing the modernization of global human rights governance and building a new form of human rights civilization.

Role of viruses in periodontitis:An extensive review of herpesviruses,human immunodeficiency virus,coronavirus-19,papillomavirus and hepatitis viruses

Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,biochemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

The Historical Position and Value Dimensions of Human Rights Civilization

Human beings are the mainstay and the ultimate goal of civilization.The history of human civilization is a continuous struggle to realize the respect,liberation,protection,and development of humanity.Human rights are an achievement of humanity and a symbol of progress,and the human rights civilization is an important component of human civilization.Understanding and interpreting human rights from the perspective of human rights civilization means that human rights are not only a concept or an idea but also a grand historical and long-term social practice.Up to now,the development of human rights civilization has roughly experienced four awakening eras:initialization,revolution,popularization,and globalization.In terms of its value dimensions,it has the characteristics of progressiveness,diversity,commonality,inclusiveness,indivisibility,openness,and so on.The historical position of human rights civilization and the development of its value dimensions have shown to the world that human rights are the common wealth of humanity,and human rights belong to all mankind;human rights are historical,concrete,and developmental;the concept of human rights is constantly evolving,and its connotations and categories are constantly expanding;achieving the free and well-rounded development of every person is the highest value realm of human rights civilization.The Chinese modernization endows Chinese civilization with modern strength and opens up new horizons for human rights civilization.The new pattern of human rights civilization to be created by Chinese modernization not only possesses the common characteristics of human rights civilization but also enjoys Chinese characteristics based on its own national conditions,enriching and developing the diversity of human rights civilization for all mankind.

Human Rights and Development:China's Contributions Based on a Larger Concept of Human Rights

The Western liberal view of global governance can no longer effectively address the challenges facing the world today or respond to the demands of developing countries in the fields of human rights and development.Meanwhile,the United Nations human rights and development agenda also has its limitations.Against such a backdrop,China's path of human rights development has avoided the trap of human rights confrontation and the clash of civilizations.It has set an example of complementarity and positive interaction between human rights and development by unifying collective human rights with individual human rights and integrating the universality and particularity of human rights.Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,delivered a speech at the 37th group study session of the Political Bureau of the CPC Central Committee on China's Path of Human Rights Development.This elevated China's human rights development to a new historical height.Practice has proved that China's concept and path of human rights in the new era have not only effectively promoted the development of its human rights cause,but also contributed Chinese wisdom to the global cause of human rights and development with a larger concept of human rights.Under the framework of the concept of building a community with a shared future for mankind,the Belt and Road Initiative,and the Global Development Initiative,China has contributed to enhancing the discourse power of developing countries in human rights and building a fairer,more just,more reasonable and more inclusive system for global human rights governance.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Pioneering a New Realm of Human Rights Civilization in the Chinese Path to Modernization——An Overview of the Symposium on“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”

On October 14,2023,a symposium themed“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”was held in Changchun,Jilin Province,China.More than fifty experts,scholars,and researchers from national institutions and universities engaged in discussions and exchanges on human rights on the Chinese path to modernization,including the path,practice,knowledge systems,and civilization forms of human rights.This symposium played a significant role in advancing the construction of the disciplinary system,academic system,and discourse system of human rights in China.

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.

Expression rates of p16,p53 in head and neck cutaneous squamous cell carcinoma based on human-papillomavirus positivity

BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.

Revisiting the Spirit of the UDHR and Discussing Human Rights Development——Summary of Views from the Seminar Commemorating the 75th Anniversary of the Universal Declaration of Human Rights

On December 4,2023,the China Society for Human Rights Studies hosted a seminar in Beijing commemorating the 75^(th) Anniversary of the Universal Declaration of Human Rights.Participants discussed topics such as the significance of the Universal Declaration of Human Rights,China’s theories and practices in respecting and safeguarding human rights,the three global initiatives and global human rights governance,human rights protection in the digital age,and telling Chinese stories of human rights in the new era.The discussions led to a broad consensus and achieved positive results.

Insights into gastrointestinal manifestation of human immunodeficiency virus:A narrative review

Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.

Addressing Japan’s disposal of nuclear-contaminated water from the perspective of international human rights law

The discharge of nuclear-contaminated water containing radionuclides into the ocean by Japan will lead to its integration into the entire ecosystem through processes of circulation and biomagnification,eventually entering the human body via the food chain.This poses a substantial risk of irreversible damage to both the ecosystem and human health,a situation that will worsen with the ongoing discharge of such water.The respect and protection of human rights represent an international consensus,and safeguarding fundamental human rights is a substantial obligation that states must undertake in accordance with both international and domestic law.Since the Fukushima nuclear disaster,Japan has continuously violated its international legal obligations to protect human rights in several areas,including the resettlement of disaster victims,the reduction of nuclear radiation levels,and the handling of contaminated water.Such actions have compromised and will continue to compromise the basic human rights of not only its citizens but also those of people worldwide,including environmental rights,the right to life,development rights,and food rights.In the aftermath of the Fukushima meltdown,the public and workers involved in handling nuclear contaminants have been continually exposed to high radiation levels,endangering their rights to life,development,and health.Japan’s inadequate efforts in victim resettlement and environmental restoration have jeopardized the environmental and food rights of its citizens to live healthily and access food in an environment unaffected by nuclear radiation.The release of nuclear-contaminated water poses a risk of Japan’s nuclear pollution to the people of neighboring countries and the global population at large.The principle of human rights underpins the theory of a community with a shared future for humanity,and human rights are a crucial area of China’s active participation in United Nations affairs and global governance.By voicing concerns over Japan’s potential human rights violations globally,China demonstrates its role as a responsible major country.In response to Japan’s breach of legal obligations and human rights violations,China can adopt a reasoned and beneficial approach,including calling on the international community to hold Japan criminally accountable for crimes against humanity under the Rome Statute and advancing scholarly discussions on ecocide and crimes against the marine environment.Furthermore,China should persist in seeking advisory opinions from the International Court of Justice and strive for substantive accountability,utilizing the mechanisms of international human rights organizations to make its voice heard.

On the Theoretical System Development of Contemporary Chinese Outlook on Human Rights

Centering on the systematic construction of human rights theories,Xi Jinping’s discourses on respecting and protecting human rights creatively put forward a series of original theoretical viewpoints and academic propositions,profoundly revealing the basic connotation of a contemporary Chinese outlook on human rights and realizing all-around and deep-level innovation in the construction of a contemporary human rights theoretical system.In ontology,the four-in-one view of human rights of the political party,the govern-ment,society,and the people goes beyond the dichotomy between the political state and civil society.In element theory,the substantive view of human rights surpasses the formalist view of human rights.In category theory,the view of human rights focusing on the right to sub-sistence and the right to development transcends the view of human rights based on the individual’s right to freedom.In operation theory,the“development-based human rights path”goes beyond the“hu-man rights-based development path.”In practice,the positive view of human rights based on the rule of law surpasses the negative view of human rights based on the rule of law.