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Abstract Background The risk of liver fibrosis in HBeAg-positive chronic hepatitis B (CHB) patients with indeterminate phase is not well characterized. We aimed to compare the presence of liver fibrosis in HBeAg-positive CHB patients between indeterminate phase and immune-tolerant phase. Methods This multi-center, retrospective cohort study included 719 treatment-naïve HBeAg-positive CHB patients with normal alanine aminotransferase (ALT). Patients with HBV DNA > 106 IU/mL were categorized into immune-tolerant phase, whereas those with HBV DNA ≤ 106 IU/mL were classified into indeterminate phase. Significant liver fibrosis and cirrhosis were determined by APRI, FIB-4, transient elastography, or liver biopsy. Results The median age of patients was 33.0 years and 59.8% of patients were male. 81.5% and 18.5% of patients were in the immune-tolerant phase and indeterminate phase, respectively. The APRI (0.33 vs. 0.27, P

Abstract Background Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. Methods A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). Results In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P

Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg

Abstract Background Triple-negative breast cancer (TNBC) is characterized by its high metastatic potential, which results in poor patient survival. Cancer-associated fibroblasts (CAFs) are crucial in facilitating TNBC metastasis via induction of mitochondrial biogenesis. However, how to inhibit CAF-conferred mitochondrial biogenesis is still needed to explore. Methods We investigated metastasis using wound healing and cell invasion assays, 3D-culture, anoikis detection, and NOD/SCID mice. Mitochondrial biogenesis was detected by MitoTracker green FM staining, quantification of mitochondrial DNA levels, and blue-native polyacrylamide gel electrophoresis. The expression, transcription, and phosphorylation of peroxisome-proliferator activated receptor coactivator 1α (PGC-1α) were detected by western blotting, chromatin immunoprecipitation, dual-luciferase reporter assay, quantitative polymerase chain reaction, immunoprecipitation, and liquid chromatography-tandem mass spectrometry. The prognostic role of PGC-1α in TNBC was evaluated using the Kaplan–Meier plotter database and clinical breast cancer tissue samples. Results We demonstrated that PGC-1α indicated lymph node metastasis, tumor thrombus formation, and poor survival in TNBC patients, and it was induced by CAFs, which functioned as an inducer of mitochondrial biogenesis and metastasis in TNBC. Shikonin impeded the CAF-induced PGC-1α expression, nuclear localization, and interaction with estrogen-related receptor alpha (ERRα), thereby inhibiting PGC-1α/ERRα-targeted mitochondrial genes. Mechanistically, the downregulation of PGC-1α was mediated by synthase kinase 3β-induced phosphorylation of PGC-1α at Thr295, which associated with neural precursor cell expressed developmentally downregulated 4e1 recognition and subsequent degradation by ubiquitin proteolysis. Mutation of PGC-1α at Thr295 negated the suppressive effects of shikonin on CAF-stimulated TNBC mitochondrial biogenesis and metastasis in vitro and in vivo. Conclusions Our findings indicate that PGC-1α is a viable target for blocking TNBC metastasis by disrupting mitochondrial biogenesis, and that shikonin merits potential for treatment of TNBC metastasis as an inhibitor of mitochondrial biogenesis through targeting PGC-1α.

Numerous studies reported risk assessment of human exposure to plasticizers in toys through dermal pathways, however, dermal bioaccessibility and percutaneous penetration of plasticizers under effects of lead had been seldom studied. In the present study, dermal bioaccessibility of plasticizers including phthalate esters and alternative plasticizers in toys were examined in artificial sweat and SSSM (synthetic sweat and sebum mixture), and percutaneous penetration of plasticizers were investigated by skin cells under individual plasticizers exposure or combined exposure conditions (plasticizers + lead). The present results indicated that dermal bioaccessibility of plasticizers in SSSM were higher than that in artificial sweat. DEHP (Di-2-ethylhexyl Phthalate) showed highest bioaccessibility among all the plasticizers, DEHT (Di (2-ethylhexyl) terephthalate) showed highest bioaccessibility among all the alternative plasticizers. DEHP and DEHT were selected to perform the cell absorption assay. Skin cell absorption assay demonstrated that MEHP (Mono-(2-ethylhexyl) phthalate) was the major metabolite of DEHP and the absorption percentage of DEHP was higher than that of DEHT. Compared to individual exposure of plasticizers, the absorption percentage of DEHP and DEHT in skin cells under the combined exposure condition were increased by 12.40 %–14.63 % and 8.35 %–9.84 %, respectively. Risk assessment indicated that the plasticizers in toy would not result in unacceptable risk for children, but the health risk of plasticizers in toys to children under combined exposure condition would be 1.5–2 times higher than that under individual exposure condition.

Background: The clinical significance of gastrointestinal (GI) symptoms in patients with severe fever and thrombocytopenia syndrome (SFTS) is poorly characterized. This study aimed to determine the prevalence and effect of GI symptoms on the prognosis of patients with SFTS. Methods: This was a retrospective multi-center cohort study that included hospitalized patients with SFTS from three institutions between October 2010 and August 2022. The risk factors for mortality and intensive care unit (ICU) admission were identified by Cox and logistic regression analyses, respectively. Kaplan-Meier curves were used to analyze the cumulative mortality risk. Results: Among 304 patients, the median age was 62.0 years and 51.0 % of the patients were male. A total of 202 patients (66.4 %) had at least one GI symptom on admission. Diarrhea (69.8 %) and nausea (57.4 %) were the most common symptoms. Patients with GI symptoms had lower male proportion (46.0 % vs. 60.8 %, P = 0.015), higher aspartate aminotransferase (177.5 U/L vs. 118.0 U/L, P = 0.010) and lactic dehydrogenase (771.0 U/L vs. 666.5 U/L, P = 0.017) levels than that of patients without GI symptoms. However, there was no significant difference in mortality rates (23.8 % vs. 21.6 %, P = 0.668) and ICU admission (14.4 % vs. 12.7 %, P = 0.701) between SFTS patients with and without GI symptoms. Multivariate analysis suggested that GI symptoms at admission were not associated with mortality and ICU admission. Conclusions: GI symptoms are common in patients with SFTS. However, the presence of GI symptoms was not an independent risk factor for poor prognosis.

ObjectivesSevere fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS.MethodsA total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks.Results60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 μmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome.ConclusionsLiver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

Introduction and Objectives: Seroclearance of hepatitis B e antigen (HBeAg) is an important treatment goal for patients with chronic hepatitis B (CHB). This study developed a nomogram for predicting HBeAg seroclearance in CHB patients treated with nucleos(t)ide analogues (NAs). Patients and Methods: Five hundred and sixty-nine CHB patients treated with NAs from two institutions between July 2016 to November 2021 were retrospectively included. One institution served as the training set (n = 374) and the other as the external validation set (n = 195). A predictive nomogram was established based on cox regression analysis. Results: The overall HBeAg seroclearance rates were 27.3 and 21.5 % after the median follow-up of 100.2 weeks and 65.1 weeks in the training set and validation set, respectively. In the training set, baseline aspartate aminotransferase, gamma-glutamyl transpeptidase, HBeAg, and hepatitis B core antibody levels were independently associated with HBeAg seroclearance and were used to establish the HBEAg SeroClearance (ESC)-nomogram. The calibration curve revealed that the ESC-nomogram had a good agreement with actual observation. The ESC-nomogram showed relatively high accuracy for predicting 48 weeks, 96 weeks, and 144 weeks of HBeAg seroclearance in the training set (AUCs: 0.782, 0.734 and 0.671) and validation set (AUCs: 0.699, 0.718 and 0.689). The patients with high ESC-nomogram scores (≥ 79.51) had significantly higher cumulative incidence of HBeAg seroclearance and seroconversion than patients with low scores (

ABSTRACTThe presence of significant liver inflammation is an important indication for antiviral treatment in patients with chronic hepatitis B (CHB) in the indeterminate phase. We aimed to establish a non-invasive nomogram to predict significant liver inflammation in these patients. A total of 195 CHB patients in the indeterminate phase were randomly split into training and validation sets. The least absolute shrinkage and selection operator and logistic regression were applied to identify risk factors and establish a predictive model. A calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve were applied to assess the performance of the nomogram. The median age was 42.0 y and 59.5% of the patients were male. Alkaline phosphatase, γ-glutamyl transpeptidase, and prothrombin time were independent predictors for significant liver inflammation and selected to establish the AGP-nomogram. The calibration plot demonstrated that the predicted results matched the actual values. The DCA showed a high net benefit when the threshold probability was 25-83% in the training set and 31-100% in the validation set. The areas under ROC curves of AGP-nomogram in predicting significant inflammation were significantly higher than ALT in the training set (0.744 vs. 0.642, P = 0.049) and validation set (0.766 vs. 0.660, P = 0.047). The ability of AGP-nomogram in predicting advanced inflammation was also superior to ALT. The AGP-nomogram can accurately identify significant inflammation in CHB patients in the indeterminate phase, and its application may reduce the need for liver biopsy and help identify candidates for antiviral treatment.Abbreviations: AASLD: American Association for the Study of Liver Diseases; ALB: albumin; ALP: alkaline phosphatase; ALT: alanine aminotransferase; APRI: aspartate aminotransferase-to-platelet ratio index; AST: aspartate aminotransferase; AUROC: area under the receiver operating characteristic curve; CHB: chronic hepatitis B; CI: confidence interval; DCA: decision curve analysis; FIB-4: fibrosis index based on the four factors; GLB: globulin; GGT: γ-glutamyl transpeptidase; HBcAb: hepatitis B core antibody; HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HIV: human immunodeficiency virus; INR: international-normalized ratio; IQR: interquartile range; LASSO: least absolute shrinkage and selection operator; LB: liver biopsy; LR: Likelihood ratio; NAFLD: non-alcoholic fatty liver disease; NPV: negative predictive value; PLT: platelets; PPV: positive predictive value; PT: prothrombin time; ROC: receiver operating characteristic; TB: total bilirubin; TE: transient elastography; ULN: upper limit of normal.

Background: Patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome have a worse prognosis compared to AIH or PBC alone and accurately predicting the severity and dynamically monitoring the progression of disease are therefore essential. We aimed to develop a nomogram-based model to predict advanced liver fibrosis in patients with AIH-PBC overlap syndrome. Methods: A total of 121 patients with AIH-PBC overlap syndrome were retrospectively included and randomly assigned to a development set and a validation set. Backward stepwise regression's best model with the lowest AIC was employed to create a nomogram. Diagnose accuracy was evaluated using the area under the receiver operator characteristic curve (AUROC), calibration analysis, and decision curve analysis (DCA) and was compared with aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors-4 (FIB-4) score. Results: The median age of patients was 53.0 years (IQR: 46.0–63.0), and female patients accounted for 95.0 %. Platelets, globulin, total bilirubin, and prothrombin time were associated with advanced fibrosis (≥S3) and used to construct an AIH-PBC overlap syndrome fibrosis (APOSF)-nomogram (available online at https://ndth-zzy.shinyapps.io/APOSF-nomogram/). The AUROCs of APOSF-nomogram were 0.845 (95 % CI: 0.754–0.936) and 0.843 (95 % CI: 0.705–0.982) in development set and validation set respectively, which was significantly better than APRI and FIB-4. Calibration revealed that the estimated risk fits well with biopsy-proven observation. DCA outperformed APRI and FIB4 in terms of net benefit, demonstrating clinical utility. Conclusion: This novel non-invasive web-based online APOSF-nomogram provided a convenient tool for identifying advanced fibrosis in patients with AIH-PBC overlap syndrome. Further prospective, multicenter studies with large sample size are necessary to validate the applicability of APOSF-nomogram.

Introduction and Objectives: Assessment of liver inflammation plays a vital role in the management of patients with autoimmune hepatitis (AIH). We aimed to establish and validate a nomogram to predict severe liver inflammation in AIH patients. Patients and Methods: AIH patients who underwent liver biopsy were included and randomly divided into a training set and a validation set. Independent predictors of severe liver inflammation were selected by the least absolute shrinkage and selection operator regression from the training set and used to conduct a nomogram. Receiver characteristic curves (ROC), calibration curves, and decision curve analysis (DCA) were adopted to evaluate the performance of nomogram. Results: Of the 213 patients, female patients accounted for 83.1% and the median age was 53.0 years. The albumin, gamma-glutamyl transpeptidase, total bilirubin, red cell distribution width, prothrombin time, and platelets were independent predictors of severe inflammation. An online AIHI-nomogram was established and was available at https://ndth-zzy.shinyapps.io/AIHI-nomogram/. The calibration curve revealed that the AIHI-nomogram had a good agreement with actual observation in the training and validation sets. The area under the ROCs of AIHI-nomogram were 0.795 in the training set and 0.759 in the validation set, showing significantly better performance than alanine aminotransferase and immunoglobulin G in the training and validation sets, as well in AIH patients with normal ALT in the training set. DCA indicated that the AIHI-nomogram was clinically useful. Conclusions: This novel AIHI-nomogram provided an excellent prediction of severe liver inflammation in AIH patients and could be used for the better management of AIH.

Feathers are important economic products. Anser cygnoide (AC) is superior in reproduction, growth and feather quality, while Anser anser (AA) has an advantage in feather yield. Understanding the development of feather follicles facilitates deliberate crossbreeding. Here, we compared feather follicles morphogenesis between AC and AA. Feathers and dorsal skin were sampled at multiple embryonic days to investigate feather phenotypes, feather follicle morphology and the expression of hub molecules (FZD4, β-catenin, LEF1, TCF4 and c-Myc) in the Wnt signalling pathway. We found a marked difference in plumage colour between the two breeds. Feather colour in AA has undergone a ‘black dorsum’ stage and cavity formation in AC was earlier. Furthermore, different trends in molecular hub expression helped explain the phenotypical and morphological differences: the upregulated Wnt signals in AC at E12 and/or E15, as well as in AA at E18, were associated with early epidermal placode formation and cavity formation in AC, also, related to the development of the secondary feather follicles and ‘black dorsum’ in AA. Summarily, breed-specific expression patterns of Wnt signalling pathway between AC and AA might participate in the shaping of breed-specific feather follicles morphogenesis and feather phenotypes. This work provides references for feather follicles development in geese.

Hong Kong oysters (Crassostrea hongkongensis) are an important marine bivalve with nutritional and commercial value. The expanded off-bottom farming scale in recent years makes the oysters more susceptible to exposure to abiotic stresses, such as salinity stress, an important environmental factor that has been proven to have significant effects on oyster growth and development. However, the molecular mechanism is still unclear. Cyclin E is an important protein in the process of cell cycle regulation that is indispensable for propelling G1/S phase transition in a dose-dependent manner. In order to investigate whether the salinity stress affects cyclin E expression in oysters, the cDNA sequence of C. hongkongensis cyclin E (Ch-CCNE) was isolated from a gill cDNA library, and the 2.8 kbp length cDNA fragment contained a complete open reading frame (ORF) encoding 440 amino acid residues. Ch-CCNE mRNA was highly expressed in the gonad and low in the adductor mussel, mantle, gill, labial palp, and digestive gland. The recombinant CCNE protein was expressed and purified in a pET32a(+)-CCNE/Escherichia coli BL21(DE3) system via IPTG induction and was used for generating mice anti-Ch-CCNE antiserums. Western blot analysis showed that the CCNE protein in the gill was maintained at low expression levels under either hypo- (5 ppt) or hyper- (35 ppt) salinity, and could be produced at high levels under appropriate salinity during a 10-day exposure period. The immuno-localization indicated that the Ch-CCNE protein was distributed in the nucleus. These results suggested that either hypo- or hyper-salinity stress could inhibit the CCNE expression of Hong Kong oysters and their negative impact on cell division and proliferation.

BackgroundThe evaluation of liver fibrosis is essential in the management of patients with autoimmune hepatitis (AIH). We aimed to establish and validate an easy-to-use nomogram to identify AIH patients with advanced liver fibrosis.MethodsAIH patients who underwent liver biopsies were included and randomly divided into a training set and a validation set. The least absolute shrinkage and selection operator (LASSO) regression was used to select independent predictors of advanced liver fibrosis from the training set, which were utilized to establish a nomogram. The performance of the nomogram was evaluated using the receiver characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsThe median age of 235 patients with AIH was 54 years old, with 83.0% of them being female. Six independent factors associated with advanced fibrosis, including sex, age, red cell distribution width, platelets, alkaline phosphatase, and prothrombin time, were combined to construct a predictive AIH fibrosis (AIHF)-nomogram. The AIHF-nomogram showed good agreement with real observations in the training and validation sets, according to the calibration curve. The AIHF-nomogram performed significantly better than the fibrosis-4 and aminotransferase-to-platelet ratio scores in the training and validation sets, with an area under the ROCs for predicting advanced fibrosis of 0.804 in the training set and 0.781 in the validation set. DCA indicated that the AIHFI-nomogram was clinically useful. The nomogram will be available at http://ndth-zzy.shinyapps.io/AIHF-nomogram/as a web-based calculator.ConclusionsThe novel, easy-to-use web-based AIHF-nomogram model provides an insightful and applicable tool to identify AIH patients with advanced liver fibrosis.

Liver biopsies are recommended to exclude significant liver inflammation in patients with chronic hepatitis B (CHB) with elevated HBV DNA but without other indications for antiviral treatment. We aimed to investigate the proportions and determinants of significant inflammation in Asian patients with CHB with detectable HBV DNA. We conducted a cross‐sectional study that retrospectively included 581 patients with CHB with detectable HBV DNA who had undergone liver biopsy. Liver inflammation and fibrosis were staged by Scheuer’s classification. Significant inflammation and significant fibrosis were defined as G ≥ 2 and S ≥ 2, respectively. There were 179 (30.8%) patients with alanine aminotransferase (ALT) 2 × ULN. A total of 397 (68.3%) patients had significant inflammation, and 340 (58.5%) patients had significant fibrosis. Significant inflammation was found in 85% of patients with significant fibrosis and in 44.8% of patients without significant fibrosis. Furthermore, 28.7% of patients with CHB with detectable HBV DNA and normal ALT in the absence of significant fibrosis had significant inflammation. Moderate HBV DNA (5‐7 log10 IU/mL) was a risk factor for significant inflammation (odds ratio [OR] 6.929, 95% confidence interval [CI] 2.830‐16.966, P

Abstract The E3 ubiquitin ligase HECTD3 is homologous with the E6 related protein carboxyl terminus, which plays a vital role in biological modification, including immunoreactivity, drug resistance and apoptosis. Current research indicates that HECTD3 promotes the malignant proliferation of multiple tumors and increases drug tolerance. Our study primarily explored the important function and effects of HECTD3 in gastric cancer. Here, we discovered that HECTD3 is abnormally activated in gastric cancer, and the clinical prognosis database suggested that HECTD3 was strongly expressed in gastric cancer. Depletion of HECTD3 restrained the proliferative and clone abilities of cells and induced the apoptosis of gastric cancer cells. Mechanistically, our findings revealed that interaction between HECTD3 and c-MYC, and that the DOC domain of HECTD3 interacted with the CP and bHLHZ domains of c-MYC. Furthermore, we discovered that HECTD3 mediates K29-linked polyubiquitination of c-MYC. Then, our research indicated that cysteine mutation at amino acid 823 (ubiquitinase active site) of HECTD3 reduces the polyubiquitination of c-MYC. Our experimental results reveal that HECTD3 facilitates the malignant proliferation of gastric cancer by mediating K29 site-linked polyubiquitination of c-MYC. HECTD3 might become a curative marker.

Abstract Background Alternative splicing (AS) is an important mechanism of posttranscriptional modification and dynamically regulates multiple physiological processes in plants, including fruit ripening. However, little is known about alternative splicing during fruit development in fleshy fruits. Results We studied the alternative splicing at the immature and ripe stages during fruit development in cucumber, melon, papaya and peach. We found that 14.96–17.48% of multiexon genes exhibited alternative splicing. Intron retention was not always the most frequent event, indicating that the alternative splicing pattern during different developmental process differs. Alternative splicing was significantly more prevalent at the ripe stage than at the immature stage in cucumber and melon, while the opposite trend was shown in papaya and peach, implying that developmental stages adopt different alternative splicing strategies for their specific functions. Some genes involved in fruit ripening underwent stage-specific alternative splicing, indicating that alternative splicing regulates fruits ripening. Conserved alternative splicing events did not appear to be stage-specific. Clustering fruit developmental stages across the four species based on alternative splicing profiles resulted in species-specific clustering, suggesting that diversification of alternative splicing contributes to lineage-specific evolution in fleshy fruits. Conclusions We obtained high quality transcriptomes and alternative splicing events during fruit development across the four species. Dynamics and nonconserved alternative splicing were discovered. The candidate stage-specific AS genes involved in fruit ripening will provide valuable insight into the roles of alternative splicing during the developmental processes of fleshy fruits.

ABSTRACT Widespread in public databases, foreign contaminant sequences pose a substantial obstacle in genomic analyses. Such contamination in viral genome databases is also notorious but more complicated and often causes questionable results in various applications, particularly in virome-based virus detection. Here, we conducted comprehensive screening and identification of the foreign sequences hidden in the largest eukaryotic viral genome collections of GenBank and UniProt using a scrutiny pipeline, which enables us to rigorously detect those problematic viral sequences (PVSs) with origins in hosts, vectors, and laboratory components. As a result, a total of 766 nucleotide PVSs and 276 amino acid PVSs with lengths up to 6,605 bp were determined, which were widely distributed in 39 families with many involving highly public health-concerning viruses, such as hepatitis C virus, Crimean-Congo hemorrhagic fever virus, and filovirus. The majority of these PVSs are genomic fragments of hosts including humans and bacteria. However, they cannot simply be regarded as foreign contaminants, since parts of them are results of natural occurrence or artificial engineering of viruses. Nevertheless, they severely disturb such sequence-based analyses as genome annotation, taxonomic assignment, and virome profiling. Therefore, we provide a clean version of the eukaryotic viral reference data set by the removal of these PVSs, which allows more accurate virome analysis with less time consumed than with other comprehensive databases. IMPORTANCE High-throughput sequencing-based viromics highly depends on reference databases, but foreign contamination is widespread in public databases and often leads to confusing and even wrong conclusions in genomic analysis and viromic profiling. To address this issue, we systematically detected and identified the contamination in the largest viral sequence collections of GenBank and UniProt based on a stringent scrutiny pipeline. We found hundreds of PVSs that are related to hosts, vectors, and laboratory components. By the removal of them, the resulting data set greatly improves the accuracy and efficiency of eukaryotic virome profiling. These results refresh our knowledge of the type and origin of PVSs and also have warning implications for viromic analysis. Viromic practitioners should be aware of these problems caused by PVSs and need to realize that a careful review of bioinformatic results is necessary for a reliable conclusion.

In recent years, with the frequent occurrence of severe drought events, climate change in arid regions has become one of the research hotspots. However, previous studies mainly focused on a specific arid region, and the correlations and differences of drought among various arid regions have not been clearly understood. In this study, based on the latest monthly gridded dataset of the CRU, we compare the characteristics of climate change and its relationship with large-scale oceanic oscillation indexes in the three typical arid regions of Pan-Central-Asia (PCA), North America (NAm) and North Africa (NAf) in multiple perspectives. The results show that the precipitation in the PCA and NAm has increased obviously over the past 80 years, while the NAf precipitation has decreased. After the 1980s, the climate in the PCA and NAm show warm-wet types. This type of the former continues to the present, but the latter’s has changed to a warm-dry type since the 21st century. The NAf climate remains the warm-dry type since the 1990s. Nonetheless, the arid and semi-arid climate patterns in the three typical arid regions remain unchanged. The NAm precipitation has an anti-phase variability pattern compared with the NAf precipitation on both interdecadal and multi-decadal time scales. The Pacific Decadal Oscillation (PDO) has a great influence on the precipitation of the PCA and NAm. The temperature of three arid regions is significantly related to the variations in the Arctic oscillation (AO). In the inland arid region, the contribution of strong warming effect during cold season to the whole year is much greater than that during warm season, while the contribution of the coastal arid regions in warm season is greater. The precipitation in the mid-latitude arid regions is dominated by cold-season precipitation regardless of whether these regions are near the sea or not. The precipitation in the low-latitude arid regions has little difference between cold and warm seasons.

Abstract Background The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. Methods A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. Results The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0–21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454–0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050–1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. Conclusions Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

ABSTRACT Viral metagenomics is the most powerful tool to profile viromic composition for a given sample. Different viromic methods, including amplification-free ones, have been developed, but choosing them for different purposes requires comprehensive benchmarks. Here, we assessed the performance of four routinely used methods, i.e., multiple displacement amplification (MDA), direct metagenomic sequencing (MTG), sequence-independent single-primer amplification (SIA), and metatranscriptomic sequencing (MTT), using marmot rectal samples as the templates spiked with five known viruses of different genome types. The obtained clean data were differently contaminated by host and bacterial genomes, resulting in MDA having the most, with ~72.1%, but MTT had only ~7.5% data, useful for follow-up viromic analysis. MDA showed a broader spectrum with higher efficiency to profile the DNA virome, and MTT captured almost all RNA viruses with extraordinary sensitivity; hence, they are advisable in richness-based viromic studies. MTG was weak in capturing single-stranded DNA viruses, and SIA could detect both RNA and DNA viruses but with high randomness. Due to biases to certain types of viruses, the four methods caused different alterations to species abundance compared to the initial virus composition. SIA and MDA introduced greater stochastic errors to relative abundances of species, genus, and family taxa, whereas the two amplification-free methods were more tolerant toward such errors and thus are recommendable in abundance-based analyses. In addition, genus taxon is a compromising analytic level that ensures technically supported and biologically and/or ecologically meaningful viromic conclusions. IMPORTANCE Viral metagenomics can be roughly divided into species richness-based studies and species abundance-based analyses. Viromic methods with different principles have been developed, but rational selection of these techniques according to different purposes requires comprehensive understanding of their properties. By assessing the four most widely used methods using template samples, we found that multiple displacement amplification (MDA) and metatranscriptomic sequencing (MTT) are advisable for species richness-based viromic studies, as they show excellent efficiency to detect DNA and RNA viruses. Meanwhile, metagenomic sequencing (MTG) and MTT are more compatible with stochastic errors of methods introduced into relative abundance of viromic taxa and hence are rational choices in species abundance-based analyses. This study also highlights that MTG needs to tackle host genome contamination and ameliorate the capacity to detect single-stranded DNA viruses in the future, and the MTT method requires an improvement in bacterial rRNA depletion prior to library preparation.

Liver diseases seriously challenge the health of chickens raised on scaled farms and cause tremendous economic losses to farm owners. The causative agents for liver diseases are still elusive, even though various pathogens, such as the hepatitis E virus, have been reported. In the winter of 2021, a liver disease was observed on a chicken farm in Dalian, China, which increased chicken mortality by up to 18%. We conducted panvirome profiling of the livers, spleens, kidneys, and recta of 20 diseased chickens. The viromic results revealed coinfection of multiple viruses, including pathogenic ones, in these organs. The viruses were highly identical to those detected in other provinces, and the vaccine and field strains of avian encephalomyelitis virus (AEV) and chicken infectious anemia virus (CIAV) cocirculated on the farm. In particular, the liver showed higher abundance of AEV and multiple fowl adenoviruses than other organs. Furthermore, the liver also contracted avian leukemia virus and CIAV. Experimental animals with infected liver samples developed minor to medium lesions of the liver and showed a virus abundance profile for AEV across internal organs similar to that in the original samples. These results suggest that coinfection with multiple pathogenic viruses influences the occurrence and development of infectious liver disease. The results also highlight that strong farm management standards with strict biosafety measures are needed to minimize the risk of pathogenic virus introduction to the farm.

Cashmere goat from Inner Mongolia is an excellent local breed in China, and the related cashmere product is a kind of precious textile raw material with high price. Cashmere is generated from secondary hair follicles, which has obvious annual periodicity and includes three different stages: anagen, catagen, and telogen. Therefore, we investigated skin transcriptome data for 12 months using weighted gene co-expression network analysis (WGCNA) to explore essential modules, pathways, and genes responsible for the periodic growth and development of secondary hair follicles. A total of 17 co-expression modules were discovered by WGCNA, and there is a strong correlation between steelblue module and month (0.65, p = 3E−09), anagen (0.52, p = 1E−05), telogen (−0.6, p = 8E−08). Gene expression was generally high during late anagen to catagen (June to December), while expression was downregulated from telogen to early anagen (January–May), which is similar to the growth rule of hair follicle cycle. KEGG pathway enrichment analyses of the genes of steelblue module indicated that genes are mainly enriched in Cell cycle, Wnt signaling pathway, p53 signaling pathway and other important signal pathways. These genes were also significantly enriched in GO functional annotation of the cell cycle, microtubule movement, microtubule binding, tubulin binding, and so on. Ten genes (WIF1, WNT11, BAMBI, FZD10, NKD1, LEF1, CCND3, E2F3, CDC6, and CDC25A) were selected from these modules, and further identified as candidate biomarkers to regulate periodic development of hair follicles using qRT-PCR. The Wnt signaling pathway and Cell cycle play an important role in the periodic development of hair follicles. Ten genes were identified as essential functional molecules related to periodic development of hair follicle. These findings laid a foundation for understanding molecular mechanisms in biological functions such as hair follicle development and hair growth in cashmere goats.

ABSTRACT: The Wingless-types/beta-catenin (Wnt/β-catenin) signaling pathway plays an important role in embryonic development and affects the physiological development processes of feather follicles. To investigate the role of Wnt/β-catenin pathway in regulating feather follicles morphogenesis, in ovo injection of CHIR-99021, an activator of the Wnt/β-catenin signaling pathway, was conducted in chick embryo model. Initially, a total of 40 embryos were used to assess feather follicles morphogenesis and the expression of β-catenin (E9–E17). The histological results showed that feather follicle morphogenesis was mainly completed from E9 to E17. β-catenin was involved in the processing of the appearance of dermal cell condensation (E9) and the completion of the feather follicles morphogenesis (E17). Next, a total of 160 fertilized eggs were randomly divided into 8 groups for in ovo injection at E9, including a Normal Saline injected group (CON) and the 500, 1,000, 2,000, 5,000, 10,000, 50,000, and 100,000 ng CHIR-99021 groups. Dorsal skin tissue samples were collected at E17 for investigating feather follicles morphology and expressions of β-catenin and lymphoid enhancerbinding factor-1 (LEF1) at gene and protein levels. The results showed that feather follicle diameter in the injected groups were significantly (P < 0.05) increased with limit dose-independence compared to the CON group. CHIR-99021 significantly (P < 0.05) influenced the mRNA expressions of catenin beta-1 (CTNNB1) and downstream target LEF1. In ovo injection of CHIR-99021 caused that β-catenin and LEF1 were significantly (P < 0.05) increased followed the increased doses as determined by western blotting. The immunochemical results showed that β-catenin was detected in the dermal papilla of feather follicles. Given these results, this study suggests to developmental biology that in ovo injection of CHIR-99021 promoted feather follicles morphogenesis and development via activating Wnt/β-catenin signaling pathway and upregulating downstream target LEF1 during embryonic period in chick embryo model. Moreover, CHIR-99021 may be a strong candidate to promote the animal feather/hair industry, especially as a reference for bird feather production.

Feather performs important physiological functions in birds, and it is also one of the economic productions in goose farming. Understanding and modulating feather follicle development during embryogenesis are essential for bird biology and the poultry industry. CHIR-99021 is a potent Wnt/β-catenin signaling pathway activator associated with feather follicle development. In this study, goose embryos (Anser cygnoides) received an in ovo injection of CHIR-9902, which was conducted at the beginning of feather follicle development (E9). The results showed that feather growth and feather follicle development were promoted. The Wnt signaling pathway was activated by the inhibition of GSK-3β. Transcriptomic analyses showed that the transcription changes were related to translation, metabolism, energy transport, and stress in dorsal tissue of embryos that received CHIR-99021, which might be to adapt and coordinate the promoting effects of CHIR-99021 on feather follicle development. This study suggests that in ovo injection of CHIR-99021 is a potential strategy to improve feather follicle development and feather-related traits for goose farming and provides profiling of the Wnt signaling pathway and transcriptome in dorsal tissue of goose embryos for further understanding of feather follicle development.

Abstract Introduction As an emerging infectious disease, coronavirus disease 2019 (COVID‐19) has rapidly spread throughout worldwide. Health care workers (HCWs) on frontline directly participated in the diagnosis, treatment, and care of COVID‐19 patients are at high risk of getting infected with the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the novel coronavirus that causes COVID‐19. In Nanjing Drum Tower Hospital, a total of 222 medical staff went to Wuhan city for support. In this study, we aimed to determine any nosocomial infection among our cohort of HCWs who worked in Wuhan. Methods Throat swab samples were obtained for RNA testing on day 1 and 14 of their quarantine upon their return to Nanjing. Radiological assessments were performed by chest computed tomography (CT) on day 14 of their quarantine. The blood was collected from 191 HCWs between May 12 and May 15. Anti‐SARS‐CoV‐2 immunoglobulin M (IgM) and IgG antibody responses were determined by a chemiluminescence immunoassay. Results All the throat swab specimens were found negative for SARS‐CoV‐2. The radiological analysis revealed that there was no typical chest CT scan of COVID‐19 among 222 HCWs. Consistently, anti‐SARS‐CoV‐2 IgM or IgG was also found to be negative among 191 HCWs. Conclusions There was no nosocomial infection of SARS‐CoV‐2 among our cohort of the frontline HCWs, suggesting that zero occupational infection is an achievable goal with appropriate training, strict compliance, and psychological support for the frontline HCWs.

Background: Bloodstream infection (BSI) caused by Klebsiella pneumoniae (KP), especially carbapenem-resistant KP (CRKP), results in high morbidity and mortality. Aims: We aim to identify risk factors that associated with the mortality of patients with KP BSI, as well as predictors of developing CRKP BSI. Results: In this retrospective cohort study, we examined 285 inpatients with BSI caused by KP in a tertiary hospital in China between 2014 and 2018, and 46 patients were infected with CRKP. We identified that hematological tumor (odds ratio (OR): 8.359, [95% CI: 2.162–33.721], P = 0.002), CRKP isolation (OR: 7.766, [95% CI: 2.796–21.576], P = 0.001), chronic lung disease (OR: 5.020, [95% CI: 1.275–19.768], P = 0.020), and septic shock (OR: 4.591, [95% CI: 1.686–12.496], P = 0.003) were independent risk factors for the death of KP BSI. A 28-day mortality of KP BSI score ranging from 0 to 22 was developed based on the above 4 independent variables. Our scoring system revealed that the 28-day mortality were 9.14%, 35.29%, 38.10 %, 75% and 100% for carriers with a score of 0, 5, 6–10, 11–13 and ≥14, respectively. Additionally, CRKP infection were independently associated with intensive care unit stay (OR: 5.506, [95% CI: 2.258–13.424], P = 0.001), exposure to antifungals (OR: 4.679, [95% CI: 2.065–10.063], P = 0.001), exposure to fluoroquinolones (OR: 2.892, [95% CI: 1.151–7.267], P = 0.020), and the number of isolated bacterial species from the patient ≥ 3 (OR: 2.414, [95% CI: 1.306–4.463], P = 0.005). Conclusion: Our study may be useful for the reduction of the mortality of patients with KP BSI and the prevention of developing CRKP BSI in hospitals. Keywords: Bloodstream infections, Carbapenem resistance, Klebsiella pneumoniae, Risk factors, Mortality

Genomic selection in plants and animals has become a standard tool for breeding because of the advantages of high accuracy and short generation intervals. Implementation of this technology is hindered by the high cost of genotyping and other factors. The aim of this study was to determine an optional marker density panel and reference population size for using genomic selection of goats, with speculation on the number of QTLs that affect the important economic traits of goats. In addition, the effect of buck population size in the reference population on the accuracy of genomic estimated breeding value (GEBV) was discussed. Based on the previous genetic evaluation results of Inner Mongolia White Cashmere Goats, live body weight (LBW, h2 = 0.11) and fiber diameter (FD, h2 = 0.34) were chosen to perform genomic selection in this study. Reasonable genome parameters and generation transmission processes were set, and phenotypic and genotype data of the two traits were simulated. Then, different sizes of the reference population and validation population were selected from progeny. The GEBVs were obtained by six methods, including GBLUP (Genomic Best Linear Unbiased Prediction), ssGBLUP (Single Step Genomic Best Linear Unbiased Prediction), BayesA, BayesB, Bayesian ridge regression, and Bayesian LASSO. The correlation coefficient between the predicted and realized phenotypes from simulation was calculated and used as a measure of the accuracy of GEBV in each trait. The results showed that the medium marker density Panel (45 K) could be used for genomic selection in goats, which can ensure the accuracy of the GEBV. The reference population size of 1,500 can achieve greater genetic progress in genomic selection for fiber diameter and live body weight in goats by comparing with the population size below this level. The accuracy of the GEBV for live body weight and fiber diameter was better when the number of QTLs was 100 and 50, respectively. Additionally, the accuracy of GEBV was discovered to be good when the buck population size was up to 200. Meanwhile, the accuracy of the GEBV for medium heritability traits (FDs) was found to be higher than the accuracy of the GEBV for low heritability traits (LBWs). These findings will provide theoretical guidance for genomic selection in goats by using real data.

Mammalian orthoreoviruses (MRVs) are increasingly reported to cause various diseases in humans and other animals, with many possibly originating from bats, highlighting the urgent need to investigate the diversity of bat-borne MRVs (BtMRVs). Here, we report the detection and characterization of a reassortant MRV that was isolated from a bat colony in Xinjiang, China. The BtMRV showed a wide host and organ tropism and can efficiently propagate the cell lines of different animals. It caused mild damage in the lungs of the experimentally inoculated suckling mice and was able to replicate in multiple organs for up to three weeks post-inoculation. Complete genome analyses showed that the virus was closely related to MRVs in a wide range of animals. An intricate reassortment network was revealed between the BtMRV and MRVs of human, deer, cattle, civet and other bat species. Specifically, we found a bat-specific clade of segment M1 that provides a gene source for the reassortment of human MRVs. These data provide important insights to understand the diversity of MRVs and their natural circulation between bats, humans, and other animals. Further investigation and surveillance of MRV in bats and other animals are needed to control and prevent potential MRV-related diseases.

Pigs are deeply involved in human lives; hence, their viruses are associated with public health. Here, we established the most comprehensive virome of healthy piglets to date, which provides a viromic baseline of weaned pigs for disease prevention and control, highlighting that longitudinal viromic monitoring is needed to better understand the dynamics of the virome in pig development and disease occurrence.

An anode-supported tubular protonic ceramic fuel cell with BaCe0.7Zr0.1Y0.2O3-δ electrolyte is fabricated using dip-coating technique. Electrochemical performances of the cell are tested at temperatures from 600 to 200 °C, utilizing humidified H2 (3 vol% H2O) as fuel and ambient air as oxidant. With an effective area of 2.3 cm2, the cell yields a peak power density of 465 mW cm−2 at 600 °C and 118 mW cm−2 at 450 °C. Even when the temperature is as low as 200 °C, there is still an output power of 3 mW. Stability of the cell under 600 °C is tested by operating the cell at a constant voltage of 0.7 V. The test lasts for 30 h during which the operating power density decreases rapidly in the first 10 h, then tend to be stable at 300 mW cm−2.

The Inner Mongolia cashmere goat is an excellent local breed in China. According to the characteristics of wool quilts, the Inner Mongolia cashmere goat can be divided into three types: a long-hair type (hair length of >22 cm), a short-hair type (hair length of ≤13 cm), and an intermediate type (hair length of >13 cm and ≤22 cm). It is found that hair length has a certain reference value for the indirect selection of other important economic traits of cashmere. In order to explore the molecular mechanisms and related regulatory genes of the different hair types, a weighted gene coexpression network analysis (WGCNA) was carried out on the gene expression data and phenotypic data of 12-month-old Inner Mongolia cashmere goats with a long-hair type (LHG) and a short-hair type (SHG) to explore the coexpression modules related to different coat types and nine candidate genes, and detect the relative expression of key candidate genes. The results showed that the WGCNA divided these genes into 19 coexpression modules and found that there was a strong correlation between one module and different hair types. The expression trends of this module’s genes were different in the two hair types, with high expression in the LHG and low expression in the SHG. GO functions are mainly concentrated in cellular components, including intermediate filaments (GO:0005882), intermediate filament cytoskeletons (GO:0045111), and cytoskeletal parts (GO:0044430). The KEGG pathway is mainly enriched in arginine as well as proline metabolism (chx00330) and the MAPK signaling pathway (chx04010). The candidate genes of the different hair types, including the KRT39, KRT74, LOC100861184, LOC102177231, LOC102178767, LOC102179881, LOC106503203, LOC108638293, and LOC108638298 genes, were screened. Through qRT-PCR, it was found that there were significant differences in these candidate genes between the two hair types, and most of them had a significant positive correlation with hair length. It was preliminarily inferred that these candidate genes could regulate the different hair types of cashmere goats and provide molecular markers for hair growth.

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P

In recent years, the warming–wetting trend in the arid region of Northwest China has attracted widespread attention. To reveal whether this phenomenon exists in the whole Pan-Central-Asia arid region, this paper adopts the latest monthly gridded dataset of the Climate Research Unit Time Series version 4.05 (CRU TS v4.05) and the multi-model ensemble data of the Coupled Model Intercomparison Project Phase 6 (CIMP6) for discussion from multiple perspectives. The results show that the Pan-Central-Asia arid region has been getting warmer and wetter in the last 80 years. Since the turn of the 21st century, there has been an apparent slowdown in the regional wetting trend despite the acceleration of precipitation increase, mainly caused by the growth in evapotranspiration potential. The interannual scale dominates the precipitation change, including significant quasi-three-year and quasi-six-year cycles. The interannual variability in precipitation is mainly affected by the change in the phases of Pacific decadal oscillation (PDO), while long-term variation dominates the temperature change, which is significantly related to the variations in the Arctic oscillation (AO). Thus, future research and predictions of regional precipitation should focus on the PDO variations, followed by the Southern Oscillation Index (SOI), whereas for research on, and predictions of, temperature, the effect of AO variations should be emphasized. Except for a few regions in Central-Eastern Mongolia and Central Kazakhstan, precipitation levels in most parts of the Pan-Central-Asia region have been increasing. The regional temperature exhibits a distribution pattern which decreases from northwest to southeast. The increase in precipitation in the Pan-Central-Asia arid region alleviates the drought in most regions, including most of Northwest China. However, the arid and semi-arid climate patterns in this region have not changed. The warming–wetting trend will significantly accelerate in medium-emissions scenarios in the next 80 years. Although the increase in precipitation may be a positive aspect of this trend, the rise in potential evapotranspiration caused by sharp warming may cause greater challenges to the regional climate and ecological environment.

Abstract The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease caused by the SFTS bunyavirus (SFTSV) with an estimated high case-fatality rate of 12.7% to 32.6%. Currently, the disease has been reported in mainland China, Japan, Korea, and the United States. At present, there is no specific antiviral therapy for SFTSV infection. Considering the higher mortality rate and rapid clinical progress of SFTS, supporting the appropriate treatment in time to SFTS patients is critical. Therefore, it is very important for clinicians to predict these SFTS cases who are more likely to have a poor prognosis or even more likely to decease. In the present study, we established a simple and feasible model for assessing the severity and predicting the prognosis of SFTS patients with high sensitivity and specificity. This model may aid the physicians to immediately initiate prompt treatment to block the rapid development of the illness and reduce the fatality of SFTS patients.

Leflunomide as an immunosuppressive drug is generally used in the treatment of rheumatoid arthritis. It inhibits DHODH (dihydroorotate dehydrogenase ), which is one of the essential enzymes in the de novo pyrimidine biosynthetic pathway. Here we showed that leflunomide significantly reduced cell proliferation and self-renewal activity. Annexin V-FITC/PI staining assay revealed that leflunomide induced S-phase cell cycle arrest, and promoted cell apoptosis. In vivo xenograft study in SCID mice showed that leflunomide inhibited tumor growth and development. We also observed that DHODH was commonly expressed in neuroblastoma. When treated with leflunomide, the neuroblastoma cell lines BE(2)-C, SK-N-DZ, and SK-N-F1 showed dramatic inhibition of DHODH at mRNA and protein levels. Considering the favorable toxicity profile and the successful clinical experience with leflunomide in rheumatoid arthritis, this drug represents a potential new candidate for targeted therapy in neuroblastoma.

The article discusses the rapid diagnosis of a fox's death case using nanopore sequencing, revealing an infection with an Arctic-like rabies virus. The study highlights the importance of early diagnosis of emerging infectious diseases (EIDs) in wildlife conservation. Nanopore sequencing proved to be a portable and affordable technique for rapid diagnosis of viral EIDs, showcasing its potential in wildlife conservation efforts. The study also emphasizes the need for active surveillance of rabies in the fox population in northeastern China due to the complex circulation of rabies viruses in the region. [Extracted from the article]

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region. [ABSTRACT FROM AUTHOR]

Abstract Background Ancient Chang’an in the Tang Dynasty (618–907 AD) was one of the world’s largest and most populated cities and acted as the eastern end of the world-famous Silk Road. However, little is known about the genetics of Chang’an people and whether the Western Regions-related gene flows have been prevalent in this cosmopolitan city. Results Here, we present seven genomes from Xingfulindai (XFLD) sites dating to the Tang Dynasty in Chang’an. We observed that four of seven XFLD individuals (XFLD_1) were genetically homogenous with the Late Neolithic Wadian, Pingliangtai, and Haojiatai populations from the middle reaches of the Yellow River Basin (YR_LN), with no genetic influence from the Western Eurasian or other non-Yellow River-related lineages. The remaining three XFLD individuals were a mixture of YR_LN-related ancestry and ~ 3–15% Western Eurasian-related ancestry. Mixtures of XFLD_1 and Western Eurasian-related ancestry drove the main gradient of genetic variation in northern and central Shaanxi Province today. Conclusions Our study underlined the widespread distribution of the YR_LN-related ancestry alongside the Silk Road within the territory of China during the historical era and provided direct evidence of trans-Eurasian communication in Chang’an from a genetic perspective.