The increasing life expectancy of humans has led to a growing numbers of patients with chronic diseases and end-stage organ failure. Transplantation is an effective approach for the treatment of ...end-stage organ failure; however, the imbalance between organ supply and the demand for human organs is a bottleneck for clinical transplantation. Therefore, xenotransplantation might be a promising alternative approach to bridge the gap between the supply and demand of organs, tissues, and cells; however, immunological barriers are limiting factors in clinical xenotransplantation. Thanks to advances in gene-editing tools and immunosuppressive therapy as well as the prolonged xenograft survival time in pig-to-non-human primate models, clinical xenotransplantation has become more viable. In this review, we focus on the evolution and current status of xenotransplantation research, including our current understanding of the immunological mechanisms involved in xenograft rejection, genetically modified pigs used for xenotransplantation, and progress that has been made in developing pig-to-pig-to-non-human primate models. Three main types of rejection can occur after xenotransplantation, which we discuss in detail: (1) hyperacute xenograft rejection, (2) acute humoral xenograft rejection, and (3) acute cellular rejection. Furthermore, in studies on immunological rejection, genetically modified pigs have been generated to bridge cross-species molecular incompatibilities; in the last decade, most advances made in the field of xenotransplantation have resulted from the production of genetically engineered pigs; accordingly, we summarize the genetically modified pigs that are currently available for xenotransplantation. Next, we summarize the longest survival time of solid organs in preclinical models in recent years, including heart, liver, kidney, and lung xenotransplantation. Overall, we conclude that recent achievements and the accumulation of experience in xenotransplantation mean that the first-in-human clinical trial could be possible in the near future. Furthermore, we hope that xenotransplantation and various approaches will be able to collectively solve the problem of human organ shortage.
According to the traditional Chinese zodiac, 2023 is the Year of the Rabbit, which holds the meaning of life and hope due to the rabbit's vigorous reproductive ability. In line with its remit of ...combining animal models and experimental medicine, AMEM publishes original articles, reviews, research highlights, reviews and other different types of articles on laboratory animals and animal experimental research to meet the needs of readers. Animal models are an important part of laboratory animal science, and are widely used in experimental medicine for simulating human diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus ...therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
AMEM is jointly published by the Chinese Society of Experimental Animals and the Institute of Medical Laboratory Animals of the Chinese Academy of Medical Sciences & Peking Union Medical College, in ...collaboration with Wiley, a renowned international publishing group. Since its inception in 2018, AMEM has received 333 manuscripts from 45 countries and regions, including Mainland China, the United States, India, Nigeria, Brazil, Bangladesh, Australia, Japan, Spain, and Israel. With a high degree of academic acumen and a sense of national mission, the editorial team of AMEM took the lead in publishing the research results of the new coronary pneumonia model of the rhesus monkey in the first issue in March 2020. At present, this article has been cited 134 times, setting the highest citation rate since AMEM was published, significantly improving AMEM's international dissemination power and also reflecting the social responsibility of the journal's expert team and manuscript authors in public health emergencies.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute ...respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Elastic metal–organic materials (MOMs) capable of multiple stimuli‐responsiveness based on dual‐stress and thermally responsive triple‐helix coordination polymers are presented. The strong ...metal‐coordination linkage and the flexibility of organic linkers in these MOMs, rather than the 4 Å stacking interactions observed in organic crystals, causes the helical chain to act like a molecular spring and thus accounts for their macroscopic elasticity. The thermosalient effect of elastic MOMs is reported for the first time. Crystal structure analyses at different temperatures reveal that this thermoresponsiveness is achieved by adaptive regulation of the triple‐helix chains by fine‐tuning the opening angle of flexible V‐shaped organic linkers and rotation of its lateral conjugated groups to resist possible expansion, thus demonstrating the vital role of adaptive reorganization of triple‐helix metal–organic chains as a molecular spring‐like motif in crystal jumping.
Dual‐stress and thermally responsive crystalline metal–organic materials (MOMs) based on molecular spring‐like triple‐helix coordination polymers are presented. As the first example of thermosalient effect in elastic MOMs, these compounds undergo elastic flexure upon external stress as well as cracking and jumping after thermal treatment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
AMEM is jointly founded by Chinese Association for Laboratory Animal Sciences (CALAS), Asian Federation of Laboratory Animal Science Associations (AFLAS), the International Council for Laboratory ...Animal Science (ICLAS) and Institute of Laboratory Animal Sciences (ILAS), Chinese Academy of Medical Sciences & Peking Union Medical College. Since its first publication in 2018, it has now entered into its fourth year. Together with experts and authors, AMEM has published a series of animal models and experimental medicine studies on COVID‐19 under the precondition of strict review and rapid processing. 1,2 In 2021, we will continue to welcome submissions of animal studies on COVID‐19 to deepen the understanding and communication. At present, AMEM has 7 Editor‐in‐Chief and executive Editor‐in‐Chief, 14 associate editors, and more than 40 experts in editorial board from China, the United States, Brazil, Israel, France, Australia, India, Thailand, and other countries, specialized in basic and clinical research studies in animal models and experimental medicine.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty ...of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.
Gut microbiota, comprising a vast number of microorganism species with complex metagenome, are known to be associated with Alzheimer's disease (AD) and amyloid deposition. However, studies related to ...gut microbiota have been mostly restricted to comparisons of amyloid deposits, while investigations on neurobehavioral changes and the pathogenesis of AD are limited. Therefore, we aimed to identify the relationship between changes in the intestinal microbiome and the pathogenesis of AD. APPswe/PS1ΔE9 (PAP) transgenic mice and wild‐type (WT) mice of different age groups were used. The composition of intestinal bacterial communities in the mice was determined by 16S ribosomal RNA sequencing (16S rRNA Seq), and the Y maze was used to measure cognitive function. Transcriptome sequencing (RNA Seq) and Gene Expression Omnibus (GEO) database (GSE 36980) were used to filter differentially expressed genes (DEGs) between specific pathogen‐free (SPF) and germ‐free (GF) mice. Quantitative reverse‐transcriptase PCR (qRT‐PCR) and western blot (WB) were used to verify the results. We found that the intestinal microbiota was significantly different between 5‐month‐old PAP and WT mice and the cognition of SPF PAP mice was diminished compared to GF PAP and SPF WT mice. DEGs in 5‐month‐old SPF and GF mice were enriched in the MAPK signalling pathway, and expression of amyloid precursor protein and amyloid deposition increased in 5‐month‐old SPF PAP mice. Results from this study showed that changes in intestinal microbiota were correlated with impairment of cognitive function and might promote amyloid deposition by stimulating the MAPK signalling pathway in the brain.
This study showed that signals from gut microbes were required for the neuroinflammatory responses and cognitive deficits in a mouse model of Alzheimer's disease. A clear association was established between changes in intestinal microbiota in APPswe/PS1ΔE9 transgenic mice and amyloid deposition via the activation of the MAPK signalling pathway, confirmed by 16S rRNA sequencing and transcriptome analysis. We believe that these findings will have direct implications in the development of methods that can exploit gut microbiota to control amyloid deposition, and thus alleviate neuroinflammation and provide clinical benefits in patients with Alzheimer's disease.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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