Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Virus diversity, wildlife-domestic animal circulation and potential zoonotic viruses of small mammals, pangolins and zoo animals.

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.

Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

Advances in Study on Role of Vagus Nerve in Gut-brain Interaction Disorder in Irritable Bowel Syndrome / 胃肠病学

The vagus nerve serves as an important part of the gut-brain axis, which regulates intestinal movement and secretion, emotional and immune response, and is involved in gut-brain interaction disorder in patients with irritable bowel syndrome (IBS). This article provides an overview of the vagus nerve function, the relationship between vagus nerve dysfunction in gut-brain axis and pathogenesis of IBS, and the application of vagus nerve in IBS treatment, with the aim for helping clinicians to better understand the correlation between vagus nerve and gut - brain interaction disorder, and shedding light on potential treatment in IBS.

Primary Breast Small Cell Carcinoma With Merkel Cell Features: A Case Report and Literature Review / 한국유방암학회지

Neuroendocrine carcinoma of the breast is a rare malignant tumor which, with the features of Merkel cells is even rarer. Herein, we report a case of small cell carcinoma with Merkel cell features in a 52-year-old female. Microscopically, the tumor was characterized by diffuse and consistent small round cells that were de-adherent. The tumor cells had round or oval nuclei with delicate chromatin and small nucleoli, the cytoplasm was sparse and eosinophilic. Additionally, the tumor was accompanied by high-grade ductal carcinoma in situ. Immunohistochemical staining showed that infiltrating tumor cells were positive for neuroendocrine markers, and punctately positive for CK20. The patient underwent modified radical mastectomy, axillary lymph node dissection, and postoperative adjuvant chemotherapy. No recurrence or metastasis was observed during follow-up period. Primary breast small cell carcinoma with Merkel cell features is rare and easily misdiagnosed as Merkel cell carcinoma. Early diagnosis and treatment may improve patient prognosis.

Mechanism of Zhibai Dihuang decotion in treating postmenopausal osteoporosis / 药学学报

In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg-1·day-1) and high dose (64 g·kg-1·day-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.

Secondary coronary artery ostial lesions: Three case reports.

BACKGROUND: Atherosclerosis is one of the main causes of coronary artery ostial lesions seen clinically. Secondary coronary artery ostial lesions are rare, and cases reported previously were associated with syphilitic vasculitis and aortic dissection. Here, we report three rare cases of secondary coronary ostial lesions. Due to their rareness, these lesions can easily be neglected, which may lead to misdiagnosis and missed diagnosis. CASE SUMMARY: We present three patients with acute myocardial infarction and unstable angina caused by secondary coronary artery ostial lesions. In Case 1, coronary angiography (CAG) revealed 90% stenosis of the left main coronary ostium. Chest contrast computed tomography (CT) suggested thymic carcinoma invading the left main coronary ostium. Coronary artery bypass grafting and tumor resection were performed. In Case 2, echocardiography revealed a sinus of Valsalva aneurysm (SVA)-like dilatation. CAG showed a right coronary sinus giant aneurysm and complete obstruction of the right coronary artery (RCA) ostium. Aortic contrast CT confirmed these findings. The Bentall procedure was performed. In Case 3, CT CAG identified an anomalous origin of the right coronary artery (AORCA) from the left sinus of Valsalva coursing between the aorta and pulmonary trunk, causing severe RCA ostium stenosis by compression. Surgical correction of the AORCA was performed. CONCLUSION: The cases reported here suggest that we should consider other causes of coronary ostial lesions other than atherosclerosis.

Twelve natural estrogens in urines of six threatened or endangered mammalian species in Zoo Park: implications and their potential risk.

This work was the first to report twelve natural estrogens (NEs) in the urines of six threatened or endangered mammalians in a Zoo Park of Guangzhou (i.e., panda, gorilla, elephant, African lion, jaguar, and leopard). Ten out of twelve NEs were detected at least in one urine sample of the six mammalians studied, including the four major NEs (i.e., estrone (E1), 17ß-estradiol (E2), 17α-estradiol (αE2), estriol (E3)), and six other NEs (i.e., 4-hydroxyestrone (4OHE1), 2-hydroxyestradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 16α-hydroxyestrone (16α-OHE1), 16ketoestradiol (16ketoE2), and 17epiestriol (17epiE3)). The six studied mammalians, ranked in the order of high to low urinary concentration of total NEs, were jaguar, African lion, gorilla, elephant, panda, and leopard, with respective urinary concentrations of 110.4, 86.4, 71.4, 66.0, 55.9, and 52.8 ng/mL. According to the average urinary concentration of NE in the six mammalians ranked from high to low, the top five NEs detected were 16α-OHE1, 4OHE1, E1, E3, and 17epiE3, respectively. These clearly indicated the occurrence of NEs other than the four major types in urines of animals in a Zoo Park. Moreover, the daily excretion rates of the five detected NEs by one elephant ranged from 1162-2254 µg/d with a total daily excretion rate of 8260 µg/d, suggesting that the total urinary excretion of NEs by one adult elephant was equivalent to that by 170 premenopausal women or 506 adult men. Consequently, it appears from this study that NEs in the urines of zoo animals should be considered an emerging source of NEs.

Deletion of Dcf1 Reduces Amyloid-ß Aggregation and Mitigates Memory Deficits.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease. One of the pathologies of AD is the accumulation of amyloid-ß (Aß) to form senile plaques, leading to a decline in cognitive ability and a lack of learning and memory. However, the cause leading to Aß aggregation is not well understood. Dendritic cell factor 1 (Dcf1) shows a high expression in the entorhinal cortex neurons and neurofibrillary tangles in AD patients. OBJECTIVE: Our goal is to investigate the effect of Dcf1 on Aß aggregation and memory deficits in AD development. METHODS: The mouse and Drosophila AD model were used to test the expression and aggregation of Aß, senile plaque formation, and pathological changes in cognitive behavior during dcf1 knockout and expression. We finally explored possible drug target effects through intracerebroventricular delivery of Dcf1 antibodies. RESULTS: Deletion of Dcf1 resulted in decreased Aß42 level and deposition, and rescued AMPA Receptor (GluA2) levels in the hippocampus of APP-PS1-AD mice. In Aß42 AD Drosophila, the expression of Dcf1 in Aß42 AD flies aggravated the formation and accumulation of senile plaques, significantly reduced its climbing ability and learning-memory. Data analysis from all 20 donors with and without AD patients aged between 80 and 90 indicated a high-level expression of Dcf1 in the temporal neocortex. Dcf1 contributed to Aß aggregation by UV spectroscopy assay. Intracerebroventricular delivery of Dcf1 antibodies in the hippocampus reduced the area of senile plaques and reversed learning and memory deficits in APP-PS1-AD mice. CONCLUSION: Dcf1 causes Aß-plaque accumulation, inhibiting dcf1 expression could potentially offer therapeutic avenues.

LncRNA H19 Inhibits the Progression of Sepsis-Induced Myocardial Injury via Regulation of the miR-93-5p/SORBS2 Axis.

Sepsis is an infectious disease that seriously endangers human health. It usually leads to myocardial injury which seriously endangers to the health of human beings. H19 has been confirmed to play key roles in various diseases, including sepsis. However, its function in the progression of sepsis-induced myocardial injury remains largely unknown. H9C2 cells were treated with lipopolysaccharide (LPS) to mimic sepsis-induced myocardial injury in vitro. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry, respectively. In addition, gene and protein expression levels in H9C2 cells were measured by quantitative real-time PCR (qRT-PCR) and Western blotting. The levels of inflammatory cytokines in H9C2 cell supernatants were tested by ELISA. JC-1 staining was performed to observe the mitochondrial membrane potential level in H9C2 cells. H19 and SORBS2 were downregulated in H9C2 cells following LPS treatment, while miR-93-5p was upregulated. Moreover, LPS-induced cell growth inhibition and mitochondrial damage were significantly reversed by overexpression of H19. In addition, H19 upregulation notably suppressed LPS-induced inflammatory responses in H9C2 cells. Moreover, H19 sponged miR-93-5p to promote SORBS2 expression. Overall, H19 suppressed sepsis-induced myocardial injury via regulation of the miR-93-5p/SORBS2 axis. H19 attenuated the development of sepsis-induced myocardial injury in vitro via modulation of the miR-93-5p/SORBS2 axis. Thus, H19 could serve as a potential target for the treatment of sepsis-induced myocardial injury.

Therapeutic effect of ginsenoside metabolite compound K on mouse psoriasis induced by imiquimod / 中国药理学通报

Aim To investigate the mechanism of therapeutic effect of ginsenoside metabolite compound K (GCK) on imiquimod-induced psoriasis mice. Methods Model mice induced by imiquimod (IMQ) were randomly divided into the following groups; model group, GCK (14, 28, 56, 112 mg • kg-

Construction and implementation of graded training model of clinical nutrition nursing in general hospital / 中国实用护理杂志

Objective:To establish and evaluate the effect of graded training mode of clinical nutrition nursing in general hospital.Methods:A clinical nutrition nursing group was established, including core management group, quality control group, education and training group and liaison nurse group. Hierarchical training and practice of clinical nutrition nursing was conducted throughout the hospital, and effect of training was evaluated.Results:The nurses' nutrition knowledge increased from (66.60±9.72) to (85.06±7.85) points, nutrition attitude increased from (72.38±5.55) to (92.50±5.10) points, nutrition behavior increased from (66.87 ± 6.83) to (88.76 ± 7.60) points, and the differences were statistically significant ( t values were -15.520, -11.128, -12.238, P<0.01). The nutritional risk screening rate and nutritional intervention rate of patients were improved to 100%, and the academic level of nurses in nutritional nursing was further improved. Conclusion:The application of graded training mode of clinical nutrition nursing can improve nurses' nutritional knowledge and skills, improve nurses' professional and academic level, and improve patient clinical outcomes.

Association between dietary patterns and central precocious puberty in girls / 中国学校卫生

Objective@#To explore the relationship between dietary patterns and central precocious puberty in children, and to provide a scientific basis for dietary prevention of precocious puberty.@*Methods@#A case-control study was conducted, among 35 newly diagnosed central precocious puberty girls from May to December 2019 as the case group, and 70 healthy girls with normal development as the control group. Physical development examination, parent questionnaire survey and child interview were carried out. Dietary information was assessed using a simplified food frequency questionnaire(FFQ). Principal component analysis was used to identify children s dietary patterns, and multiple Logistic regression was used to assess the association between dietary patterns and precocious puberty.@*Results@#Three different dietary patterns have been established, namely "snack and processed food type", "animal protein type" and "nutritional tonic type" dietary patterns, respectively. After adjusting for covariates such as age and BMI, Logistic regression analysis showed that the "snack and processed food type" dietary pattern was positively correlated with precocious puberty(OR=10.81, 95%CI=2.59-45.15, P<0.01). There was a negative correlation between "animal protein type" and precocious puberty(OR=0.24, 95%CI=0.06-0.91, P=0.04), while the association between "nutritive tonic" and precocious puberty was not statistically significant(OR=0.28, 95%CI=0.07-1.05, P=0.06).@*Conclusion@#Children s dietary patterns were related to precocious puberty." Snack and processed food "dietary pattern with a high intake of fried foods, puffed foods, foods containing preservatives or pigments, western fast foods, chocolate and products, was closely related to central precocious puberty.

Value of Combination of Heart, Lung, and Diaphragm Ultrasound in Predicting Weaning Outcome of Mechanical Ventilation.

BACKGROUND Postextubation distress is detrimental to the prognosis of critically ill patients with successful spontaneous breathing trial. The known risk factors of failed weaning are associated with the heart, lungs, and diaphragm. The aim of this study was to explore the role of a combined model including indicators of heart, lung, and diaphragm ultrasound in predicting the weaning outcome. MATERIAL AND METHODS Patients' clinical data and ultrasonic features of heart, lungs, and diaphragm were recorded. Patients were included in either the failed weaning group (n=24) or the successful weaning group (n=81). The association of potential variables with the risk of weaning failure was determined using multivariate logistic regression analysis. The accuracy of potential indicators for predicting the weaning outcome were evaluated and a multiindicator combined model was established to improve the predictive accuracy. RESULTS Brain natriuretic peptide (odds ratio [OR]=1.120, P=0.004), left-atrial pressure (LAP) (OR=1.333, P=0.005), lung ultrasound score (LUS) (OR=1.736, P=0.001), and hemidiaphragm dysfunction (OR=3.942, P=0.014) were associated with an increased risk of weaning failure. However, all of these indicators could not accurately predict the weaning outcome independently (all areas under the curve [AUCs] <0.9). The combination of LAP, LUS, and hemidiaphragm dysfunction showed the highest AUC (AUC=0.919). CONCLUSIONS The combined model including LAP, LUS, and hemidiaphragm dysfunction were the most accurate method for the prediction.

Author Correction: 863 genomes reveal the origin and domestication of chicken.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

863 genomes reveal the origin and domestication of chicken.

Despite the substantial role that chickens have played in human societies across the world, both the geographic and temporal origins of their domestication remain controversial. To address this issue, we analyzed 863 genomes from a worldwide sampling of chickens and representatives of all four species of wild jungle fowl and each of the five subspecies of red jungle fowl (RJF). Our study suggests that domestic chickens were initially derived from the RJF subspecies Gallus gallus spadiceus whose present-day distribution is predominantly in southwestern China, northern Thailand and Myanmar. Following their domestication, chickens were translocated across Southeast and South Asia where they interbred locally with both RJF subspecies and other jungle fowl species. In addition, our results show that the White Leghorn chicken breed possesses a mosaic of divergent ancestries inherited from other subspecies of RJF. Despite the strong episodic gene flow from geographically divergent lineages of jungle fowls, our analyses show that domestic chickens undergo genetic adaptations that underlie their unique behavioral, morphological and reproductive traits. Our study provides novel insights into the evolutionary history of domestic chickens and a valuable resource to facilitate ongoing genetic and functional investigations of the world's most numerous domestic animal.

Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins.

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.

Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins

The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world1. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus2. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.

Progress of Intestinal Secretagogue in Treating Chronic Constipation / 胃肠病学

Chronic idiopathic constipation (CIC) is one of the most common digestive motility disorders in outpatient with long course, high recurrence and low therapy satisfaction. It can be classified as 3 subtypes, of which, normal and slow transit constipation depend on laxatives for relieving symptoms. Intestinal secretagogue is a novel kind of laxatives with high efficacy and safety, and is recommended to be used in patients with CIC and irritable bowel syndrome with constipation (IBS-C). Linaclotide is approved for marketing in China now. In this article, the clinical value and progression of intestinal secretagogue in treating chronic constipation were reviewed.