Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.

Objective:To systematically evaluate the prevalence of norovirus causing sporadic acute gastroenteritis in China.Methods:Relevant articles on acute gastroenteritis caused by norovirus in China published between January 2010 and October 2023 were retrieved from Wanfang, CNKI and PubMed database. The articles met inclusion and exclusion criteria were enrolled in this study. Excel software and SPSS20.0 software were used for statistical analysis. The epidemiological features of sporadic cases of acute gastroenteritis caused by norovirus in China were summarized using descriptive statistical analysis.Results:A total of 500 articles were included in this study, involving 784 486 cases of acute gastroenteritis and 670 292 samples in 32 provinces and regions. Norovirus GⅡ was the predominant genogroup causing acute gastroenteritis in China in recent years, but there were significant differences in the distribution of genotypes and epidemic strains at different times. GⅡ.4 was the predominant genotype in each year, and GⅡ.4/2006b and GⅡ.4 /Sydney_2012 were the main epidemic strains. Norovirus-related diarrhea occurred throughout the year, especially between the months of October and December. The incidence of norovirus infection was high in children under five years old and varied in different regions.Conclusions:Norovirus GⅡ was the predominant genogroup causing norovirus-related sporadic acute gastroenteritis in China, but there was an obvious genetic evolutionary trend in the epidemic strains. Factors such as epidemic strains, season and geographical region should be considered when making strategies for the prevention and control of norovirus-related diarrhea and developing vaccines.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

Sex reversal, representing extraordinary sexual plasticity during the life cycle, not only triggers reproduction in animals but also affects reproductive and endocrine system-related diseases and cancers in humans. Sex reversal has been broadly reported in animals; however, an integrated resource hub of sex reversal information is still lacking. Here, we constructed a comprehensive database named ASER (Animal Sex Reversal) by integrating sex reversal-related data of 18 species from teleostei to mammalia. We systematically collected 40,018 published papers and mined the sex reversal-associated genes (SRGs), including their regulatory networks, from 1611 core papers. We annotated homologous genes and computed conservation scores for whole genomes across the 18 species. Furthermore, we collected available RNA-seq datasets and investigated the expression dynamics of SRGs during sex reversal or sex determination processes. In addition, we manually annotated 550 in situ hybridization (ISH), fluorescence in situ hybridization (FISH), and im-munohistochemistry (IHC) images of SRGs from the literature and described their spatial expression in the gonads. Collectively, ASER provides a unique and integrated resource for researchers to query and reuse organized data to explore the mechanisms and applications of SRGs in animal breeding and human health. The ASER database is publicly available at http://aser.ihb.ac.cn/.

Objective:To investigate the early clinical characteristics and radiographic changes in confirmed novel coronavirus pneumonia (COVID-19) and COVID-19 excluded patients.Methods:Twenty-four patients with suspected COVID-19 admitted to Shanghai Jiaotong University Affiliated Sixth People’s Hospital and Jinshan Branch Hospital between January and February, 2020 were enrolled in this research. Early clinical features and radiographic changes were analyzed in 10 confirmed COVID-19 patients and 14 COVID-19 excluded patients.Results:In the early stage, all 24 suspected patients had minor symptoms, and had normal blood gas analysis results. Of 10 confirmed COVID-19 patients, 5 patients were male. All the 10 patients had fever and fatigue, with body temperature between 37.5 and 38.5 °C. Only 1 patient had hacking cough. Two patients had no clear epidemiological exposure history, the other 8 had clear epidemiological exposure history, with a possible incubation period of 1-10 days. From CT imaging, lesions were characterized as ground glass shadow ( n=9), which could be unilateral ( n=1) or bilateral ( n=9), and were mainly close to the pleura ( n=9), with nodule shadow ( n=1) and without focal necrosis, and could combined with pleural effusion ( n=1). Among the COVID-19 excluded patients, all 14 patients had clear history of epidemic exposure, with an onset time of 1 to 13 days. Twelve patients had fever, including 4 patients with body temperature > 38.5 °C, 8 patients with body temperature bwteen 37.3-38.5 °C, and 2 patients without fever. All patients had fatigue, 7 patients had hacking cough and 2 patients had chest pain. From CT imaging, ground glass shadow appeared in 4 patients, lesions were unilateral in 10 patients and bilateral in 4 patients, and the lesions were relatively sporadic, without necrosis or pleural effusion. Conclusions:Not all patients with COVID-19 have a direct epidemiology exposure history, some patients may be infected unknowingly. According to CT imaging, COVID-19 seems to have no special manifestations being different from other viral pneumonia. COVID-19 is more common among middle-aged people.

Objective To investigate the early clinical characteristics and radiographic changes in confirmed Novel coronavirus pneumonia (NCP) and excluded NCP patients. Methods Twenty-four patients with suspected NCP admitted to Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and Jinshan Branch Hospital between January and February, 2020 were chosen as our research subjects. Early clinical features and radiographic changes were analyzed in 10 patients of confirmed NCP and 14 patients of excluded NCP. Results In the early stage, all 24 suspected patients were mild, and had normal blood gas analysis. Of 10 diagnosed patients, 50% were male. All the 10 patients had fever and fatigue, with body temperature between 37.5℃ and 38.5℃. Only 1 patient had dry cough. 2 patients had no clear epidemiological exposure history, the other 8 had a clear epidemiological exposure, with a possible incubation period of 1-10 days. From CT imaging, lesions were characterized as ground glass shadow ( n =9), which could be unilateral ( n =1) or bilateral ( n =9), and were mainly close to the pleura ( n =9), with nodule shadow ( n =1) and without focal necrosis, and could combined with pleural effusion ( n =1. Among patients excluded NCP, all 14 patients had a clear history of epidemic exposure, with an onset time of 1 to 13 days. 12 patients had fever , including 4 with temperature > 38.5°C, 8 with temperature 37.3-38.5°C, and 2 without fever. All patients had fatigue , 7 patients had dry cough and 2 patients had chest pain. From CT imaging, ground glass shadow appeared in 4 patients , lesions were unilateral in 10 patients and bilateral in 4 patients , and the lesions were relatively sporadic, without necrosis or pleural effusion. Conclusion 1．Not all patients with NCP have a direct history of epidemiology exposure, some patients may be infected unknowingly. 2. According to CT imaging, NCP seems to have no special manifestations different from other viral pneumonia. 3. NCP is more common among middle-aged people.

BACKGROUND/OBJECTIVES: The aim of this study was to analyze the factors related to sarcopenic obesity among the elderly in South Korea. SUBJECTS/METHODS: A total of 3,367 elderly (≥ 65 years) from the Korea National Health and Nutrition Examination Survey (2008–2011) were included in this analysis. The subjects were assessed to determine their sarcopenia and obesity status. Sarcopenia was assessed by determining their appendicular skeletal muscle mass (ASM). Obesity was defined by the waist circumference. An association of sarcopenic obesity and the related factors was analyzed using multiple logistic regression models. RESULTS: The risk of sarcopenic obesity of the subjects was decreased by active physical activity. After adjusting for age, smoking, and alcohol consumption, the risk of sarcopenic obesity in men of the highest level group (Q4) decreased by 45% (OR = 0.550, 95% CI = 0.334–0.905, P trend 0.018) compared to that in the reference group (Q1). Among the women, the risk of sarcopenic obesity in the Q3 and Q4 groups decreased by 29.0% (OR = 0.710, 95% CI = 0.512–0,984) and 56.7% (OR = 0.433, 95% CI = 0.281–0.668), respectively, compared to that in the Q1 group (P trend < 0.001). The mean daily energy intake was higher in the non-sarcopenia group than in the sarcopenia group. The risk of sarcopenic obesity in subjects not meeting the recommended intakes of energy, riboflavin, and vitamin C increased significantly by 25.4%, and 36.6%, and 32.6%, respectively, compared to that in the subjects meeting the recommended nutrient intake. CONCLUSION: Active physical activity as well as an adequate intake of energy and some vitamins might be negatively associated with the development of sarcopenia and sarcopenic obesity in the elderly.
Aged ; Alcohol Drinking ; Ascorbic Acid ; Energy Intake ; Female ; Humans ; Korea ; Logistic Models ; Male ; Motor Activity ; Muscle, Skeletal ; Nutrition Surveys ; Obesity ; Riboflavin ; Sarcopenia ; Smoke ; Smoking ; Vitamins ; Waist Circumference

Objective To evaluate the immune effects of virus-like particles ( VLPs) assembled from the capsid protein VP1 of a recombinant norovirus ( NoV) GⅡ. 17 genotype. Methods The recombi-nant NoV GⅡ. 17 VP1 VLPs were purified, and then tested by SDS-PAGE and Western blot to analyze the purity. The size, morphology and diameter distribution of the recombinant VLPs were detected by transmis-sion electron microscopy ( TEM) and dynamic light scattering ( DLS) analyzer. The recombinant VP1 VLPs adsorbed by aluminium adjuvant were used to immunize BALB/c mice. Serum samples were collected after immunization. Specific antibody level and neutralizing antibody activity were evaluated with enzyme linked immunosorbent assay ( ELISA) and histo-blood group antigen ( HBGA)-VLP blocking test. Cross-reactivity of serum samples with GⅠ. 1 and GⅡ. 4 VP1 VLPs were detected. Moreover, cross-protection against GⅠ. 1 and GⅡ. 4 VP1 VLPs was analyzed. Results The purity of the recombinant NoV GⅡ. 17 VP1 VLP was greater than 90％ and specific bands were detected by Western blot. TEM images and DLS experiments showed that VLPs were 30-50 nm in size with good morphology and uniformity, indicating that the recombi-nant VLPs were similar to the wildtype virus. High titers of specific antibodies were detected in serum sam-ples of the immunized mice. A certain degree of cross-reactions between serum samples and VP1 VLPs of NoV GⅠ. 1 and GⅡ. 4 were observed, but no cross-protection was detected. Conclusion The recombinant GⅡ. 17 VP1 VLPs in combination with aluminum adjuvant can induce higher titers of HBGA blocking anti-bodies in mice, suggesting that it could be used as a candidate target antigen for norovirus vaccine.