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Abstract Background/objectives The hemoglobin glycation index (HGI) has been demonstrated to serve as a substitute for the individual bias in glycosylated hemoglobin A1c (HbA1c). Our objective was to assess the correlation between HGI and cardiovascular (CV) outcomes in patients with diabetes and coronary artery disease (CAD). Subjects/methods We sequentially recruited 11921 patients with diabetes and CAD at Fuwai Hospital. The patients were categorized into five groups based on their HGI quintiles, ranging from Q1 to Q5. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), which included CV death and nonfatal myocardial infarction. Results During the median 3-year follow-up, 327 (2.7%) MACEs were observed. A U-shaped relationship between HGI and 3-year MACEs was demonstrated by restricted cubic spline (RCS) after multivariable adjustment (nonlinear P = 0.014). The Kaplan-Meier curves demonstrated that the Q2 group had the lowest risk of MACE (P = 0.006). When comparing the HGI Q2 group, multivariable Cox regression models showed that both low (Q1) and high (Q4 or Q5) HGI were linked to a higher risk of MACEs (all P

Abstract Background Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear. Methods 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)–2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI). Results During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58–2.52, P

Dual antiplatelet therapy (DAPT), comprising both aspirin and the P2Y12 receptor inhibitor, is crucial in managing patients with coronary artery disease following percutaneous coronary intervention (PCI). The optimal duration for DAPT in patients with angiography-detected moderate-to-severe calcified coronary (MSCC) lesions who underwent PCI with drug-eluting stents (DES) implantation remains uncertain. We recruited patients with angiography-detected MSCC lesions who received DES implantation from the prospective Fuwai Percutaneous Coronary Intervention Registry. Patients were classified into two groups according to the duration of DAPT: those with a DAPT duration of one year or less, and those with a DAPT duration of more than one year. The primary endpoint was the major adverse cardiovascular and cerebrovascular event, which was defined as composed of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. The key-safety endpoint was bleeding type 2, 3, or 5 according to the Bleeding Academic Research Consortium criteria. There were 1730 patients included in the study, and 470 (27.17 %) continued DAPT for more than one year after undergoing MSCC-PCI with DES implantation. The median follow-up time was 2.5 years. DAPT>1-year versus ≤1-year DAPT was significantly associated with a reduced risk of the primary outcome (1.59 % versus 3.19 %; adjusted hazard ratio=0.44; 95 % CI: 0.22–0.88). Similar trends were observed for all-cause death (0.16 % versus 1.91 %; P

This study evaluated the effects of replacing dietary fish meal (FM) with defatted black soldier fly (Hermetia illucens) larvae meal (DBSFLM) on growth, non-specific immunity, antioxidative capacity, intestinal histology and microbiota of juvenile Chinese mitten crab (Eriocheir sinensis). A control diet was designed to contain 200 g/kg FM (Con), then 25 %, 50 %, 75 %, and 100 % of dietary FM was replaced by DBSFLM, referring to DBSFLM25, DBSFLM50, DBSFLM75 and DBSFLM100, respectively. The five isoproteic and isolipidic diets were fed to crab (7.15 ± 0.10 g) for 8 weeks. The results indicated that the final weight, weight gain, feed conversion ratio and survival of DBSFLM25 and DBSFLM50 groups all reached the same level as Con (P > 0.05). The proper DBSFLM replacement on WG and FCR from broken line model were 49.70 % and 52.90 %, respectively. For immune enzyme activity, ACP, ALP, and LZM activities showed a trend of first increasing and then decreasing, the DBSFLM50 group had the highest activity, and the DBSFLM100 group was significantly lower than the DBSFLM50 group (P < 0.05). In terms of antioxidant capacity, the T-AOC, T-SOD, GSH-Px activities and MDA content of DBSFLM25 DBSFLM50 and DBSFLM75 groups all shows no significant difference with Con (P > 0.05), the DBSFLM100 group has the lowest antioxidant enzyme activities and highest MDA content. The intestinal number of folds and folds height in DBSFLM25 and DBSFLM50 groups reached the same level as Con (P > 0.05). The abundance of intestinal harmful bacteria Vibrio was enhanced with the increase of dietary DBSFLM level (P < 0.05). In conclusion, the recommended level of replacing FM with DBSFLM was at 50 % (100 g/kg) without negative effect on growth, non-specific immunity, antioxidative capacity, intestinal histology and microbiota of Chinese mitten crab.

The hybrid grouper (Epinephelus lanceolatus♂ × E. fuscoguttatus♀) is a novel and commercially important fish for mariculture in China. Recent years, the outbreak of viral and bacterial diseases have caused huge losses of hybrid grouper culture. However, the immune response of hybrid grouper against viral and bacterial infection remains unexplored. In this study, a total of 9 splenic transcriptomic libraries of hybrid grouper including untreated control, Red-spotted grouper nervous necrosis virus (RGNNV)-challenged, Vibrio alginolyticus-challenged were constructed. A sum of 6024 differentially expressed genes (DEGs) with significant differences were identified, of which the overlapped DEGs between RGNNV and V. alginolyticus challenged were significantly enriched in multiple immune-related pathway including interleukin-17 NOD-like receptor, C-type lectin receptor, chemokine signaling pathway and natural killer cell mediated cytotoxicity, indicating their important roles in immune defense of hybrid grouper against (both) viral and bacterial infection. To the best of our knowledge, this is the first report that investigated the immune response of hybrid grouper following viral and bacterial pathogen stimuli using transcriptomic analysis. These results provide comprehensive understandings of the innate immunity of hybrid grouper and valuable references to develop disease control strategy in grouper aquaculture.

The ultimate enrichment level and quantity of gas hydrate resources are influenced by the dynamic process of accumulation and preservation. High-resolution 3-D seismic data, logging while drilling (LWD), pressured coring, and in situ testing were used to characterize the dynamic accumulation and preservation of the trial production high-grade gas hydrate reservoir (HGGHR) in the Shenhu area. Through seismic variance analysis and ant-tracking, we found that newly identified mud diapir-associated faults with three development stages controlled the migration and accumulation of gas hydrate and shifted the base of the gas hydrate stability zone (BGHSZ), resulting in dynamic accumulation and dissociation of gas hydrates. The recognized double bottom simulating reflectors (BSRs) were concluded to have been formed due to the shift of the BGHSZ caused by the variational equilibrium conditions. The interval between the double BSRs was inferred to be a disequilibrium zone where gas recycling occurred, contributing to the coexistence of gas hydrates and free gas and the dynamic formation of the HGGHR. Multiple gliding faults formed within the GHSZ in the late period have altered the HGGHR and control the present thickness and distribution of the gas hydrates and free gas in the hanging wall and footwall. Under the influence of geothermal fluids and the fault system associated with the mud diapir, the HGGHR experienced dynamic accumulation with three stages, including early accumulation, medium-term adjustment, and late alteration and preservation. We conclude that four factors affected the formation, distribution, and occurrence of the HGGHR: the geothermal fluids accompanying the deep mud diapir below the reservoir, the dual supply of thermogenic gas and biogenic gas, the recycling of hydrate gas beneath the BGHSZ, and the post-gas hydrate faults developed within the GHSZ. A geological model illustrating the dynamic formation of the trial production HGGHR was proposed, providing a reference for future exploration of HGGHRs with a great production potential in deepwater settings.

Abstract Background Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI. Methods This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke. Results During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13–1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96–1.45) or METS-IR (HR, 1.00; 95%CI 0.98–1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P 0.05) to the original model. Conclusions The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.

Abstract Background The role of triglyceride-glucose (TyG) index, an insulin resistance indicator, in glycemic management for diabetic patients with coronary artery disease (CAD) was still unknown. Therefore, we aimed to explore the association between glycemic control and cardiovascular (CV) outcomes in patients with diabetes and CAD according to different TyG index levels. Methods A total of 9996 diabetic patients with angiograph-proven CAD were consecutively recruited from 2017 to 2018 at Fuwai Hospital. Patients were assigned into 3 groups according to TyG index tertiles (T) (T1:

Abstract Background Liver stiffness (LS) is regarded as an indicator of the stages of liver fibrosis and liver cirrhosis. Numerous studies have investigated the relationship between body mass index (BMI) and LS; however, the conclusions remain controversial. In the current study, we utilized transient elastography (TE) technique, which could measure LS in a non-painful and noninvasive way, to explore the relationship between BMI and the risk of elevated LS in common community residents. Methods 5791 participants were included in the present study. To calculate BMI value, height and weight of the participants were carefully measured. Liver stiffness measurement (LSM) > 9.1 kPa was considered as a cutoff suggesting elevated LS. The relationship of BMI and risk of elevated LS was derived using generalized linear regression models, and the threshold effect was then analyzed by smooth curve fitting and segmented regression model. Results Elevated LS was detected in 230 participants (3.97%) using the TE technique. After potential confounders were adjusted according to the individual’s demographic variables, underlying comorbidities and blood biochemical test results, we observed a J-shaped relationship between BMI and the risk of elevated LS, with the inflection point at 23.05 kg/m2. The effect size (and confidence interval) was 0.84 (0.71, 0.98) on the left side of the inflection point, and 1.32 (1.24, 1.41) on the right side of it. Conclusions Our study found a novel J-shaped relationship between BMI and the risk of elevated LS assessed by TE technique. Abnormal BMI, either higher or lower, was associated with an increased risk of elevated LS.

Traditional drug development is a long and expensive process with high rates of failure. This has prompted the pharmaceutical industry to seek more efficient drug development frameworks, driving the emergence of organ-on-a-chip (OOC) based on microfluidic technologies. Unlike traditional animal experiments, OOC systems provide a more accurate simulation of human organ microenvironments and physiological responses, therefore offering a cost-effective and efficient platform for biomedical research, particularly in the development of new medicines. Additionally, OOC systems enable quick and real-time analysis, high-throughput experimentation, and automation. These advantages have shown significant promise in enhancing the drug development process. The success of an OOC system hinges on the integration of specific designs, manufacturing techniques, and biosensors to meet the need for integrated multiparameter datasets. This review focuses on the manufacturing, design, sensing systems, and applications of OOC systems, highlighting their design and sensing capabilities, as well as the technical challenges they currently face.

Abstract Background Coronary bifurcation lesion, as a complex coronary lesion, is associated with higher risk of long-term poor prognosis than non-bifurcation lesions. The triglyceride-glucose (TyG) index has been shown to predict cardiovascular (CV) events in patients with coronary artery disease (CAD). However, the prognostic value of the TyG index in patients with bifurcation lesions who are at high risk of CV events remains undetermined. Therefore, this study aimed to investigate the association between the TyG index and CV events in patients with bifurcation lesions. Methods A total of 4530 consecutive patients with angiography-proven CAD and bifurcation lesions were included in this study from January 2017 to December 2018. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Patients were assigned into 3 groups according to TyG tertiles (T) (T1:

Glyptothorax pallozonus Lin, 1934 is a small benthic fish belonging to the Sisoridae family that is distributed in the Dongjiang and Rongjiang Rivers of China. In the present study, we sequenced and characterized the complete mitochondrial genome of G. pallozonus for the first time. The complete mitogenome of G. pallozonus is 16,542 bp in length and includes 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNA (rRNAs), and a control region (CR). The mitogenome architecture was identical to that of other teleosts. Maximum likelihood (ML) phylogenetic analysis strongly supported the monophyly of Glyptothorax, which contains two clades. These results advance our understanding of the molecular phylogeny of the genus Glyptothorax.

ABSTRACT: Avian influenza virus (AIV) poses a significant threat to the poultry industry and public health. Among the diverse AIV subtypes, H3, H4, and H5 are frequently detected in waterfowl and live poultry markets (LPM). The expeditious and precise identification of these subtypes is imperative in impeding the dissemination of the disease. In this study, we have developed a triplex real-time PCR assay endowed with the capacity to simultaneously discriminate AIV subtypes H3, H4, and H5. This method showcases remarkable specificity, selectively amplifying H3, H4, and H5 AIV subtypes sans any cross-reactivity with other subtypes or common avian pathogens. Furthermore, this method exhibits high sensitivity, with a detection threshold of 2.1 × 102 copies/μL for H3, H4, and H5 AIV subtypes. Additionally, the assay demonstrates reproducibility, as evidenced by intra- and interassay variability, with a coefficient of variation below 1.5%. A total of 338 cloacal swabs were collected from LPM to evaluate the performance of our assay. The obtained results evinced a high level of concordance with the sequencing data. In summary, our study has developed a triplex real-time PCR method that can be employed in laboratory-based testing and surveillance of AIV. This assay holds promise in augmenting our ability to detect and monitor AIV subtypes, thereby facilitating timely interventions and safeguarding both the poultry industry and public health.

ABSTRACT: Since 2021, a novel strain of goose reovirus (GRV) has emerged within the goose farming industry in Guangdong province, China. This particular viral variant is distinguished by the presence of white necrotic foci primarily localized in the liver and spleen, leading to substantial economic losses for the poultry industry. However, the etiology, prevalence and genomic characteristics of the causative agent have not been thoroughly investigated. In this study, we conducted an epidemiological inquiry employing suspected GRV samples collected from May 2021 to September 2022. The macroscopic pathological and histopathological lesions associated with GRV-infected clinical specimens were examined. Moreover, we successfully isolated the GRV strain and elucidated the complete genome sequence of the isolate GD21/88. Through phylogenetic and recombination analysis, we unveiled that the GRV strains represent a novel variant resulting from multiple reassortment events. Specifically, the μNS, λC, and σNS genes of GRV were found to have originated from chicken reovirus, while the σA gene of GRV exhibited a higher degree of similarity with a novel duck reovirus. The remaining genes of GRV were traced back to Muscovy duck reovirus. Collectively, our findings underscore the significance of GRV as a pathogenic agent impacting the goose farming industry. The insights gleaned from this study contribute to a more comprehensive understanding of the epidemiology of GRV in Southern China and shed light on the genetic reassortment events exhibited by the virus.

A network model based on the self-attention mechanism is proposed to address the difficulties in extracting features from ghost imaging targets, low recognition efficiency, and potential errors. First, a ghost imaging detection system is constructed using a laser, spatial light modulator, bucket detector, etc. The object is illuminated with speckles generated by the spatial light modulator. The detected data are then input into the self-attention mechanism network model for training. Experimental results show that for the handwritten digits in the experimental dataset, the highest accuracy and average accuracy of the self-attention mechanism network are 99.13% and 96.41%, respectively. This experiment demonstrates the potential of using the self-attention mechanism network for target recognition in ghost imaging, improving the speed of target recognition and significantly enhancing the accuracy of recognition.

Abstract Background Dietary management plays an important role in diabetes care, while the trends in dietary patterns over the last decade in US adults with diagnosed and undiagnosed diabetes remain unknown. This study aims to estimate the dietary patterns over the last decade by baseline diabetes diagnoses and explore their association with long-term prognosis. Methods Participants’ data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2007–2018, which were divided into three groups according to the diabetes diagnosis: without diabetes, undiagnosed diabetes, and diagnosed diabetes. Healthy eating index (HEI) and dietary inflammatory index (DII) were used to evaluate dietary patterns. Survival analyses were adopted to estimate the association between HEI/DII scores and long-term all-cause mortality and cause-specific mortality. Results The prevalence of diabetes was increasing among US adults over the last decade. HEI scores of all three groups presented a downward trend in recent years. Participants with undiagnosed diabetes (weighted mean: 50.58, 95% CI: 49.79, 51.36) got significantly lower HEI score in comparison to participants with diagnosed diabetes (weighted mean: 51.59, 95% CI: 50.93, 52.25). Compared with participants without diabetes, participants in the undiagnosed or diagnosed diabetes group had higher DII scores, indicating a higher dietary inflammatory potential. Survival analysis found a significant association between HEI scores and all-cause mortality and death of heart diseases. Similar correlation was observed in DII scores. Conclusions Along with the growth in diabetes prevalence in the US, dietary management of people with diabetes is decreasing. The management of US adults’ diets needs special attention, and dietary inflammatory potential may be considered in the dietary intervention.

Abstract Background Prediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions. Methods A total of 1532 patients attending Fuwai hospital (Beijing, China), with intermediate angiographic coronary lesions, not undergoing revascularization, were followed-up from 2013 to 2021. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting plasma glucose (FPG). The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk. Results The proportion of patients defined as prediabetes ranged from 3.92% to 47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c

Introduction: Mantle cell lymphoma (MCL) can be stratified into blastoid and classical subtypes based on morphological features, with the former subtype having a poorer prognosis. Despite recent advances in targeted approaches, including multiple bruton tyrosine kinase inhibitors which yield impressive clinical responses and improve prognoses, MCL remains an incurable disease with frequent relapses. Additional therapeutic interventions are therefore unmet medical needs for the management of patients with MCL. Methods: Cell viability and apoptosis assays were employed to analyze the therapeutic interaction of venetoclax combined with selinexor in MCL cells. Western blot was used to investigate the potential mechanism of action for the synergy of venetoclax in combination with selinexor in MCL cells. Results: In this study, we revealed that both blastoid and classical MCL cells were vulnerable to the cytotoxic effects of selinexor, a well-established XPO1 inhibitor, manifested by loss of cell viability and induction of cell apoptosis. Moreover, our data indicated that the addition of venetoclax to selinexor showed synergistically decreased cell viabilities and increased cell deaths in blastoid and classical MCL cells compared to each single drug treatment. Either selinexor or venetoclax treatment alone decreased MCL1 expressions and increased BAX levels in MCL cells, and these effects were further enhanced by their combined regimen. Mechanistically, our findings demonstrated that induction of DNA damage and inactivation of DNA damage response were involved in the synergistic interaction of the drug combination regimen. Conclusion: Collectively, this study might provide a potential attractive therapy option for the treatment of MCL. However, the conclusion needs additional experimental validation in in vivo models and clinical evaluations are mandatory.

The paper develops a two-type behavioral heterogeneous agent model including fundamentalists and chartists. It examines whether investors’ behavioral heterogeneity is related to the excessive volatility of RMB exchange rate. We use the deviation of the real exchange rate from the fundamental exchange rate as a measure of excessive exchange rate volatility. The fundamental value is calculated by the revised RMB fundamental exchange rate model with cointegration technology. After estimating the behavioral heterogeneous agent model using the monthly RMB exchange rate data from October 2006 to November 2020, we find that the heterogeneity of traders in price and trading strategies can significantly explain excess volatility of the RMB exchange rate. Our analysis of two significant fluctuations in 2015-2016 and 2018-2019 further corroborates our key finding that investors’ behavioral heterogeneity plays an important role in explaining excess volatility of RMB exchange rate.

Abstract Background Inflammation plays a crucial role in the pathogenesis and progression of coronary artery disease (CAD). The neutrophil to lymphocyte ratio (NLR) is a novel inflammatory biomarker and its association with clinical outcomes in CAD patients with different glycemic metabolism after percutaneous coronary intervention (PCI) remains undetermined. Therefore, this study aimed to investigate the effect of NLR on the prognosis of patients undergoing PCI with or without type 2 diabetes mellitus (T2DM). Methods We consecutively enrolled 8,835 patients with CAD hospitalized for PCI at Fuwai hospital. NLR was calculated using the following formula: neutrophil (*109/L)/lymphocyte (*109/L). According to optimal cut-off value, study patients were categorized as higher level of NLR (NLR-H) and lower level of NLR (NLR-L) and were further stratified as NLR-H with T2DM and non-T2DM, and NLR-L with T2DM and non-T2DM. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as all-cause mortality, myocardial infarction (MI), stroke and target vessel revascularization. Results A total of 674 (7.6%) MACCEs were recorded during a median follow-up of 2.4 years. The optimal cut-off value of NLR was 2.85 determined by the surv_cutpoint function. Compared to those in the NLR-H/T2DM groups, patients in the NLR-L/non-T2DM, NLR-H/non-T2DM and NLR-L/T2DM groups were at significantly lower risk of 2-year MACCEs [adjusted hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.52 to 0.87, P = 0.003; adjusted HR: 0.62, 95%CI: 0.45 to 0.85, P = 0.003; adjusted HR: 0.77, 95%CI: 0.61 to 0.97, P = 0.025; respectively]. Remarkably, patients in the NLR-L/non-T2DM group also had significantly lower risk of a composite of all-cause mortality and MI than those in the NLR-H/T2DM group (adjusted HR: 0.57, 95%CI: 0.35 to 0.93, P = 0.024). Multivariable Cox proportional hazards model also indicated the highest risk of MACCEs in diabetic patients with higher level of NLR than others (P for trend = 0.009). Additionally, subgroup analysis indicated consistent impact of NLR on MACCEs across different subgroups. Conclusions Presence of T2DM with elevated NLR is associated with worse clinical outcomes in CAD patients undergoing PCI. Categorization of patients with elevated NLR and T2DM could provide valuable information for risk stratification of CAD patients.

ABSTRACT: Mycoplasma synoviae (MS) infection is a serious threat to poultry industry in China, thus it is essential to study the pharmacokinetics (PK) in the target site of MS-infected chickens, but there are no relevant reports at present. The aim of this study was to compare the PK of tilmicosin in plasma and joint dialysate in MS-infected chickens. The MS infection model was established by evaluating the influence factors of the susceptibility of chicken species, day age of chicken, infection routes, infection cycle, infection dose, and stress response. The clinical symptoms, pathogen isolation, PCR identification, and ELISA antibody were detected to determine whether the MS infection model has been successfully established. Eight-week-old Mahuang chickens were challenged with MS by joint combined with footpad, 2 mL each time, twice a day for 5 d, then the MS infection model was successfully established. The infection group was orally administrated a single dose of 15 mg/kgbody weight (b. w.) tilmicosin. The joint dialysate was collected by the microdialysis technique, then the concentration of tilmicosin in plasma samples and joint dialysate were determined by triple quadrupole high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). There was no significant difference in elimination half-life (t1/2) and the mean residence time (MRT) of dialysate and plasma. In contrast, the time of the area under the concentration-time curve (AUC) and the (maximum concentration of tilmicosin in plasma) Cmax of tilmicosin in plasma was 2.1 and 1.4 times higher than in dialysate. The distribution coefficient of tilmicosin in joint and plasma (AUCdialysate/AUCplasma) was 0.51. In conclusion, tilmicosin concentration in joints of MS-infected chicken was much lower than that of plasma, which may result in the poor clinical effect and drug resistance. The study could provide a reference for the clinical use of tilmicosin against MS.

ObjectivesWe aimed to determine a method to identify normal cerebrospinal fluid (CSF) glucose levels by examining the correlation between blood and CSF glucose levels in patients with normal and abnormal glucose metabolism.MethodsOne hundred ninety-five patients were divided into two groups according to their glucose metabolism. The glucose levels were obtained from CSF and fingertip blood at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. SPSS 22.0 software was used for the statistical analysis.ResultsIn both the normal and abnormal glucose metabolism groups, CSF glucose levels increased with blood glucose levels at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. In the normal glucose metabolism group, the CSF/blood glucose ratio range was 0.35–0.95 at 0–6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.43–0.74. In the abnormal glucose metabolism group, the CSF/blood glucose ratio range was 0.25–1.2 at 0–6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.33–0.78.ConclusionThe CSF glucose level is influenced by the blood glucose level 6 h before lumbar puncture. In patients with normal glucose metabolism, direct measurement of the CSF glucose level can be used to determine whether the CSF level is normal. However, in patients with abnormal or unclear glucose metabolism, the CSF/average blood glucose ratio should be used to determine whether the CSF glucose level is normal.

BackgroundInflammatory processes crucially modulate the development, progression, and outcomes of coronary artery disease (CAD). Since hyperglycemia could alter inflammatory responses, this study aimed to investigate the effect of ANC, a novel and rapidly available inflammatory biomarker, on the prognosis of patients undergoing PCI with or without type 2 diabetes (T2D).MethodsA total of 7,826 patients with CAD hospitalized for PCI at Fuwai Hospital were consecutively recruited. According to the median ANC value, patients were stratified as having high ANC (ANC-H) or low ANC (ANC-L) and were further classified into four groups by T2D. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause mortality, myocardial infarction, stroke, and target vessel revascularization.ResultsDuring a median follow-up of 2.4 years, 509 (6.5%) MACCEs were documented. Diabetic patients with increased ANC were at significantly higher risk of MACCEs (aHR, 1.55; 95% CI, 1.21–1.99; P = 0.001) compared to those in the ANC-L/non-T2D group (P for interaction between T2D and ANC categories = 0.044). Meanwhile, multivariable regression analysis demonstrated the highest MACCE risk in diabetic patients with a higher level of ANC than others (P for trend

The novel duck reovirus (NDRV) emerged in southeast China in 2005. The virus causes severe liver and spleen hemorrhage and necrosis in various duck species, bringing serious harm to waterfowl farming. In this study, three strains of NDRV designated as NDRV-ZSS-FJ20, NDRV-LRS-GD20, and NDRV-FJ19 were isolated from diseased Muscovy ducks in Guangdong and Fujian provinces. Pairwise sequence comparisons revealed that the three strains were closely related to NDRV, with nucleotide sequence identities for 10 genomic fragments ranging between 84.8 and 99.8%. In contrast, the nucleotide sequences of the three strains were only 38.9–80.9% similar to the chicken-origin reovirus and only 37.6–98.9% similar to the classical waterfowl-origin reovirus. Similarly, phylogenetic analysis revealed that the three strains clustered together with NDRV and were significantly different from classical waterfowl-origin reovirus and chicken-origin reovirus. In addition, the analyses showed that the L1 segment of the NDRV-FJ19 strain was a recombinant of 03G and J18 strains. Experimental reproduction of the disease showed that the NDRV-FJ19 strain was pathogenic to both ducks and chickens and could lead to symptoms of hemorrhage and necrosis in the liver and spleen. This was somewhat different from previous reports that NDRV is less pathogenic to chickens. In conclusion, we speculated that the NDRV-FJ19 causing duck liver and spleen necrosis is a new variant of a duck orthoreovirus that is significantly different in pathogenicity from any previously reported waterfowl-origin orthoreovirus.

Bovine hepacivirus (BovHepV) is a member of the genus Hepacivirus of the family Flaviviridae, which can cause acute or persistent infections in cattle. Currently, BovHepV strains identified in cattle populations worldwide can be classified into two genotypes with eight subtypes in genotype 1. BovHepV has been identified in a wide geographic area in China. Interestingly, the viral RNA of BovHepV has also been detected in ticks in Guangdong province, China. In this study, Rhipicephalus microplus tick samples were collected in Heilongjiang province, northeastern China, and BovHepV was screened with an overall positive rate of 10.9%. Sequence comparison and phylogenetic analysis showed that the BovHepV strains detected in this study belong to the subtype G. This is the first report about the detection of BovHepV in ticks in Heilongjiang province, China, which expands our knowledge that ticks may be a transmission vector of BovHepV.

To explore the action time and molecular mechanism underlying the effect of acetaminophen (APAP) on liver injury. APAP was used to establish drug-induced liver injury (DILI) model in mice. Mice in the model group were intraperitoneally injected 300 mg/kg APAP for 6, 12, and 24 h respectively, and control group mice were given the same volume of normal saline. The mice were anesthetized through intravenous injection of sodium pentobarbital at 6, 12, and 24 h after APAP poisoning. Analysis of ALT, AST and ALP in serum, liver histopathological observation, oxidative damage and western blot were performed. The livers in APAP exposed mice were pale, smaller, with a rough texture, and poorly arranged cells. Lesions, large areas of hyperemia, inflammation, swelling, poorly cell arrangement, necrosis, and apoptosis of liver cells were obvious in the liver tissue sections. Serum ALT, AST and ALP levels were significantly enhanced at 12 h of APAP adminstration mice than that of in control group mice (P＜0.05). The histopathological alterations and proinflammatory cytokines (IL-1β, TNF-α and IL-6) levels were most severe at 12 h of APAP-induced hepatotoxicity. APAP treatment induced oxidative stress by decreasing hepatic activities of superoxide dismutase (SOD) and glutathione (GSH) (P＜0.05), and enhancing malondialdehyde (MDA) content (P＜0.05). Moreover, APAP inhibited erythroid 2-related factor 2 (Nrf2) antioxidative pathway with decreased of Nrf2 and HO-1 proteins levels. Furthermore, APAP aggravated the activation of NLRP3 inflammasome by increasing of NLRP3, caspase-1, ASC, IL-1β and IL-18 proteins levels. Finally, APAP further significantly activated the toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. This study demonstrated that APAP-induced hepatotoxicity by inhibiting of Nrf2 antioxidative pathway and promoting TLR4-NF-κB-MAPK inflammatory response and NLRP3 inflammasome activation.

Breast cancer is one of the most common female diseases, posing a great threat to women’s health, and breast ultrasound imaging is a common method for breast cancer diagnosis. In recent years, U-Net and its variants have dominated the medical image segmentation field with their excellent performance. However, the existing U-type segmentation networks have the following problems: (1) the design of the feature extractor is complicated, and the calculation difficulty is increased; (2) the skip connection operation simply combines the features of the encoder and the decoder, without considering both spatial and channel dimensions; (3) during the downsampling phase, the pooling operation results in the loss of feature information. To address the above deficiencies, this paper proposes a breast tumor segmentation network, RMAU-Net, that combines residual depthwise separable convolution and a multi-scale channel attention gate. Specifically, we designed the RDw block, which has a simple structure and a larger sensory field, to overcome the localization problem of convolutional operations. Meanwhile, the MCAG module is designed to correct the low-level features in both spatial and channel dimensions and assist the high-level features to recover the up-sampling and pinpoint non-regular breast tumor features. In addition, this paper used the Patch Merging operation instead of the pooling method to prevent the loss of breast ultrasound image information. Experiments were conducted on two breast ultrasound datasets, Dataset B and BUSI, and the results show that the method in this paper has superior segmentation performance and better generalization.

Abstract Background Coronary artery ectasia (CAE) is a rare finding in coronary angiography and associated with poor clinical outcomes. Unlike atherosclerosis, diabetes mellitus (DM) is not commonly associated with CAE. This study aims to investigate the effect of type 2 diabetes mellitus (DM2) on coronary artery ectasia, especially the differences in angiographic characteristics and clinical outcomes. Methods Patients with angiographically confirmed CAE from 2009 to 2015 were included. Quantitative coronary angiography (QCA) was performed to measure the diameter and length of the dilated lesion. The primary endpoint was the maximum diameter and maximum length of the dilated lesion at baseline coronary angiography. The secondary endpoint was 5-year major adverse cardiovascular events (MACE), which was a component of cardiovascular death and nonfatal myocardial infarction (MI). Propensity score weighting (PSW) and propensity score matching (PSM) were used to balance covariates. Kaplan–Meier method and Cox regression were performed to assess the clinical outcomes. Results A total of 1128 patients were included and 258 were combined with DM2. In the DM2 group, the maximum diameter of dilated lesion was significantly lower (5.26 mm vs. 5.47 mm, P = 0.004) and the maximum length of the dilated lesion was significantly shorter (25.20 mm vs. 31.34 mm, P = 0.002). This reduction in dilated lesion diameter (5.26 mm vs. 5.41 mm, P = 0.050 in PSW; 5.26 mm vs. 5.46 mm, P = 0.007 in PSM, respectively) and length (25.17 mm vs. 30.17 mm, P = 0.010 in PSW; 25.20 mm vs. 30.81 mm, P = 0.012 in PSM, respectively) was consistently observed in the propensity score analysis. A total of 27 cardiovascular deaths and 41 myocardial infarctions occurred at 5-year follow-up. Compared with non-DM group, there were similar risks of MACE (6.02% vs. 6.27%; HR 0.96, 95% CI 0.54–1.71, P = 0.894), cardiovascular death (2.05% vs. 2.61%; HR 0.78, 95% CI 0.29–2.05, P = 0.605) and MI (4.07% vs. 3.72%; HR 1.11, 95% CI 0.54–2.26, P = 0.782) in patients with DM2. Consistent result was observed in multivariable regression. Conclusions Compared to non-DM patients, patients with CAE and type 2 diabetes were associated with a smaller diameter and shorter length of dilated vessels, suggesting the important effect of DM2 on the pathophysiological process of CAE. Similar risks of MACE were found during 5-year follow up among diabetic and non-DM patients.

Avian infectious bronchitis virus (IBV) is a prevalent RNA virus that causes respiratory distress, nephritis, salpingitis, and egg production decline in chickens, resulting in significant economic loss. IBV is composed of complex genotypes and serotypes, which poses a great challenge for disease control. The current study reports 2 IBV outbreaks which were characterized by respiratory symptoms in IBV vaccinated commercial broilers and layers in Guangdong, China, in 2021. Two IBV strains, ZH01 and HH09, were identified via a RT-PCR assay through targeting the N gene and further characterization through full-length spike (S) gene sequence analysis. Phylogenetic analysis of S1 gene revealed that both ZH01 and HH09 belonged to the GI-19 lineage but contained a certain genetic distance from the GI-19 strain. Of note, the ZH01 and HH09 strains share a low homology of 70 and 86%, respectively, with common vaccine strains (H120), resulting in low vaccine protection. Further recombination analysis based on the S1 sequence suggested the newly identified IBV strains emerged through an intragroup recombination events between CK/CH/SCDY2003-2 and I0305/19 from G1-19 lineage. In addition, a number of novel mutations such as T273I, T292A, and S331K were found in the emerging IBV strains. Taken together, this study reports the genetic characteristics of 2 recent IBV outbreaks in southern China and emphasizes the urgent need for enhanced surveillance and development of novel vaccines for the control of IBV.

ABSTRACT: Duck circovirus (DuCV) is the smallest known virus in waterfowl that infects both domestic and wild duck. Infected ducks often show stunted growth and immunosuppression, which increases the rate of secondary infection with other pathogens. In this study, 270 liver tissue samples were collected to screen the presence of DuCV in Guangdong province, China, and the complete genome sequences were recovered and systematically analyzed. Genetic analyses revealed that sequences determined in this study shared 81.6% to 100.0% genome-wide pairwise identity with previously identified DuCV genomes. Phylogenetic analyses showed that 2 DuCV genotypes with a high infection rate were co-circulating in duck population in Guangdong province, and extensive recombination events have occurred during the evolution of DuCV. Our results expand upon the knowledge regarding the genetic diversity and evolution of DuCV, and also indicate that extensive genetically divergent DuCV are co-circulating in the duck populations in Guangdong, southern China.

Mycoplasma gallisepticum (M. gallisepticum) is a primary respiratory pathogen of poultry and causes significant economic losses to the poultry industry. There were no reported articles concerning the Pharmacokinetics/Pharmacodynamics (PK/PD) interactions of tilmicosin against M. gallisepticum in vivo. In the current study, we established an in vivo M. gallisepticum infection model and tilmicosin was administered orally to the M. gallisepticum-infected chickens by different dosage regimens. The concentration of tilmicosin in lung tissue was determined by high-pressure liquid chromatography/tandem mass spectrometry (HPLC–MS/MS), besides the counting of the viable colony of M. gallisepticum in lung tissue was also monitored dynamically to appraise the PK/PD interactions of tilmicosin against M. gallisepticum. We found that anti-mycoplasmal activity was concentration-dependent and mycoplasmacidal activity was observed at tilmicosin dosage >7.5 mg/kg. The PK/PD parameter of AUC/MIC (The area under the concentration–time curve divided by the minimal inhibitory concentration) correlated well with anti-mycoplasmal efficacy (R2 = 0.92). The ratios of AUC/MIC for 1 log10 and 3 log10 colony-forming units [CFU]/lung reductions were 300.02 and 6,950.15 h, respectively. These findings indicated that tilmicosin may be therapeutically effective in chickens to treat M. gallisepticum lung infections if administered at a dose of 9.12 mg/kg.

Anomaly detection of liquid levels in molds is an important task in continuous casting. Data that consists of a series of liquid levels in mold during a continuous casting process can be viewed as a time series, on which Time Series Anomaly Detection (TSAD) methods can be applied. However, the abnormal and normal data in the liquid data in the mold sequence share similar features. And due to manual control limitations, the anomaly sequence in liquid level in mold data lasts longer. Therefore, using existing TSAD methods based on AutoEncoders (AEs) often results in high false positive rates. In this paper, a novel framework is proposed for anomaly detection of liquid level in mold by using unsupervised deep-learning-based TSAD. The framework decomposes a time series into normal and error sequences. A forecasting network reconstructs the normal sequence to solve the first issue, which allows the proposed method to consider the context. An error extraction network generates errors from the original sequence to solve the second issue. It removes anomalies from the original sequence during training to prevent anomaly pollution and allows the forecasting network’s training to be free from anomaly pollution. A new dynamic threshold method is proposed to identify anomalies. The proposed method is evaluated on the actual casting dataset by comparing it with baseline methods. The experiment results indicate that the proposed framework outperforms some of the best anomaly detection methods in terms of accuracy, precision, and F1 score.

BackgroundThe optimal treatment strategy for patients with coronary intermediate lesions, defined as diameter stenosis of 50–70%, remains a great challenge for cardiologists. Identification of potential biomarkers predictive of major adverse cardiovascular events (MACEs) risk may assist in risk stratification and clinical decision.MethodsA total of 1,187 patients with intermediate coronary lesions and available N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were enrolled in the current study. A baseline NT-proBNP level was obtained. The primary endpoint was defined as MACEs, the composite endpoint of all-cause death and non-fatal myocardial infarction. A multivariate Cox regression model was used to explore the association between NT-proBNP level and MACE risk.ResultsThe mean age of the study cohort was 59.2 years. A total of 68 patients experienced MACE during a median follow-up of 6.1 years. Restricted cubic spline analysis delineated a linear relationship between the baseline NT-proBNP level and MACE risk. Both univariate and multivariate analyses demonstrated that an increased NT-proBNP level was associated with an increased risk of MACE [adjusted hazard ratio (HR) per doubling: 1.412, 95% confidence interval (CI): 1.022–1.952, p = 0.0365]. This association remains consistent in clinical meaningful subgroups according to age, sex, body mass index (BMI), and diabetes.ConclusionAn increased NT-proBNP level is associated with an increased risk of MACE in patients with intermediate coronary lesions and may serve as the potential biomarker for risk stratification and treatment decision guidance.

PurposeThe specific mechanisms and biomarkersunderlying the progression of stable coronary artery disease (CAD) to acute myocardial infarction (AMI) remain unclear. The current study aims to explore novel gene biomarkers associated with CAD progression by analyzing the transcriptomic sequencing data of peripheral blood monocytes in different stages of CAD.Material and MethodsA total of 24 age- and sex- matched patients at different CAD stages who received coronary angiography were enrolled, which included 8 patients with normal coronary angiography, 8 patients with angiographic intermediate lesion, and 8 patients with AMI. The RNA from peripheral blood monocytes was extracted and transcriptome sequenced to analyze the gene expression and the differentially expressed genes (DEG). A Gene Oncology (GO) enrichment analysis was performed to analyze the biological function of genes. Weighted gene correlation network analysis (WGCNA) was performed to classify genes into several gene modules with similar expression profiles, and correlation analysis was carried out to explore the association of each gene module with a clinical trait. The dynamic network biomarker (DNB) algorithm was used to calculate the key genes that promote disease progression. Finally, the overlapping genes between different analytic methods were explored.ResultsWGCNA analysis identified a total of nine gene modules, of which two modules have the highest positive association with CAD stages. GO enrichment analysis indicated that the biological function of genes in these two gene modules was closely related to inflammatory response, which included T-cell activation, cell response to inflammatory stimuli, lymphocyte activation, cytokine production, and the apoptotic signaling pathway. DNB analysis identified a total of 103 genes that may play key roles in the progression of atherosclerosis plaque. The overlapping genes between DEG/WGCAN and DNB analysis identified the following 13 genes that may play key roles in the progression of atherosclerosis disease: SGPP2, DAZAP2, INSIG1, CD82, OLR1, ARL6IP1, LIMS1, CCL5, CDK7, HBP1, PLAU, SELENOS, and DNAJB6.ConclusionsThe current study identified a total of 13 genes that may play key roles in the progression of atherosclerotic plaque and provides new insights for early warning biomarkers and underlying mechanisms underlying the progression of CAD.

Background Coronary diffuse disease associates with poor outcomes, but little is known about its role after percutaneous coronary intervention (PCI). We aimed to investigate the prognostic implication of pre‐PCI focal or diffuse disease patterns combined with post‐PCI quantitative flow ratio (QFR). Methods and Results Pre‐PCI QFR derived pullback pressure gradient (PPG) (QFR‐PPG) was measured to assess physiological disease patterns for 1685 included vessels; the vessels were classified according to dichotomous pre‐PCI QFR‐PPG and post‐PCI QFR. Vessel‐oriented composite outcome, a composite of vessel‐related ischemia‐driven revascularization, vessel‐related myocardial infarction, or cardiac death at 2 years was compared among these groups. Vessels with low pre‐PCI PPG (3.9% versus 2.0%, hazard ratio [HR], 1.93; 95% CI, 1.08–3.44; P=0.02) or low post‐PCI QFR (9.8% versus 2.7%, HR, 3.78; 95% CI, 1.61–8.87; P=0.001) demonstrated higher vessel‐oriented composite outcome risk after stent implantation. Of note, despite high post‐PCI QFR achieved, vessels with low pre‐PCI QFR‐PPG presented higher risk of vessel‐oriented composite outcome than those with high pre‐PCI QFR‐PPG (3.7% versus 1.8%, HR, 2.03; 95% CI, 1.09–3.76; P=0.03) and pre‐PCI QFR‐PPG demonstrated direct prognostic effect not mediated by post‐PCI QFR. Integration of groups classified by pre‐PCI QFR‐PPG and post‐PCI QFR showed significantly higher discriminant and reclassification abilities than clinical factors (C‐index 0.77 versus 0.72, P=0.03; integrated discrimination improvement 0.93%, P=0.04; net reclassification index 0.33, P=0.02). Conclusions Prognostic value of pre‐PCI focal or diffuse disease patterns assessed by QFR‐PPG index was retained even after successful PCI, which is mostly explained by its direct effect that was not mediated by post‐PCI QFR. Integration of both pre‐PCI and post‐PCI physiological information can provide better risk stratification in vessels with stent implantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05104580.

Abstract Background Highly pathogenic avian influenza viruses (HPAIVs) of H5 subtype pose a great threat to the poultry industry and human health. In recent years, H5N6 subtype has rapidly replaced H5N1 as the most predominate HPAIV subtype circulating in domestic poultry in China. In this study, we describe the genetic and phylogenetic characteristics of a prevalent H5N6 strain in Guangdong, China. Results Nucleotide sequencing identified a H5N6 subtype HPAIV, designated as A/chicken/Dongguan/1101/2019 (DG/19), with a multibasic cleavage site in the hemagglutinin (HA). Phylogenetic analysis revealed DG/19 was a reassortant of H5N1, H5N2, H5N8, and H6N6 subtypes of avian influenza viruses. A number of mammalian adaptive markers such as D36N in the HA were identified. Conclusions Our results showed that HPAIV H5N6 strains still emerge in well-managed groups of chicken farms. Considering the increasing prevalence of H5N6 HPAIV, and the fact that H5N6 HPAIVs are well adapted to migratory birds, an enhanced surveillance for the East Asian-Australasian flyway should be undertaken to prevent potential threats to the poultry industry and human health.

Continuous casting production is an important stage in smelting high-quality steel, and automatic casting control based on artificial intelligence is a key technology to improve the continuous casting process and the product quality. By controlling the opening degree of the stopper rod reasonably, the mold can be filled with liquid steel stably in the specified time window, and automatic casting can be realized. In this paper, an automatic casting control method of continuous casting based on an improved Soft Actor–Critic (SAC) algorithm is proposed. Firstly, a relational model of the stopper rod opening degree and the liquid steel outflow velocity is established according to historical casting data. Then the Markov Decision Process (MDP) model of the automatic casting problem and the reinforcement learning framework based on the SAC algorithm are established. Finally, a Heterogeneous Experience Pool (HEP) is introduced to improve the SAC algorithm. According to the simulation results, the proposed algorithm can predict the stopper rod opening degree sequence under the constraint of the target liquid level curve. Under different billet specifications and interference conditions, an accuracy of 80% of liquid level in the mold and a stopper rod opening degree stability rate of 75% can be achieved, which is 4.29% and 3.17% higher than those for the baseline algorithms, respectively.

A endo-1,4-β-mannanase (CcMan5C) gene was cloned from Coprinopsis cinerea and heterologously expressed in Pichia pastoris, and the recombinant enzyme was purified by Ni-affinity chromatography and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). CcMan5C hydrolyzed only locust bean gum galactomannan (LBG) but not α-mannan from S. cerevisiae or Avicel cellulose, oat spelt xylan, or laminarin from Laminaria digitata. CcMan5C exhibited distinctive catalytic features that were different from previously reported β-mannanases. (1) CcMan5C is the first reported fungal β-mannase with an optimal alkalic pH of 8.0–9.0 for hydrolytic activity under assay conditions. (2) CcMan5C is the first reported alkalic fungal β-mannase with an optimal temperature of 70 °C for hydrolytic activity under assay conditions. (3) The organic solvents methanol, ethanol, isopropanol, and acetone at concentrations of 10% or 20% did not inhibit CcMan5C activity, while 10% or 20% isopropanol and acetone even enhanced CcMan5C activity by 9.20–34.98%. Furthermore, CcMan5C tolerated detergents such as Tween 20 and Triton X-100, and its activity was even enhanced to 26.2–45.6% by 1% or 10% Tween 20 and Triton X-100. (4) CcMan5C solution or lyophilized CcMan5C exhibited unchanged activity and even increasing activity after being stored at −20 °C or −80 °C for 12 months and retained above 50% activity after being stored at 4 °C for 12 months. These features make CcMan5C a suitable candidate for the detergent industry and paper and pulp industry.

ABSTRACT: Circoviruses represent a group of small viruses with circular single-strand DNA genome that infect a wide range of both domesticated and wild animals. Domesticated geese infected with circovirus have been confirmed in many parts of the world, and is considered to cause immunosuppression and facilitate the secondary infections caused by other pathogens. In the present study, extensive genetically diversified goose circoviruses (GoCVs) were identified in the liver samples of domesticated geese from Guangdong province, southern China. Genetic analysis revealed that the sequences generated in this study shared 81.5 to 99.7% genome-wide pairwise identity with previously identified GoCV genomes. More importantly, nine recombination events were identified among all known complete genomome sequences of GoCV including those obtained herein, and the majority was determined associate with the sequences identified from Guangdong province, suggesting that recombination is the primary driver for the diversification of GoCVs. Additionally, purifying selection was the dominant evolutionary pressure acting on the genomes of GoCVs, and the ORF C1 gene of GoCV showed a higher genetic variation than ORF V1 gene. These results expand the knowledge about the genetic diversity and evolution of GoCV, and also indicate extensive genetically divergent GoCV strains were co-circulating in goose population in partial areas of Guangdong province, southern China.

ABSTRACT Coprinopsis cinerea has seven homologs of the Aspergillus nidulans transcription factor NsdD. Of these, CcNsdD1 and CcNsdD2 from C. cinerea show the best identities of 62 and 50% to A. nidulans NsdD, respectively. After 4 days of constant darkness cultivation, CcnsdD2, but not CcnsdD1, was upregulated on the first day of light/dark cultivation to induce fruiting bodies, and overexpression of CcnsdD2, but not CcnsdD1, produced more fruiting bodies under a light/dark rhythm. Although single knockdown of CcnsdD2 did not affect fruiting body production due to upregulation of its homolog CcnsdD1, the double-knockdown CcNsdD1/NsdD2-RNAi transformant showed defects in fruiting body formation under a light/dark rhythm. Knockdown of CcnsdD1/nsdD2 led to the differentiation of primary hyphal knots into sclerotia rather than secondary hyphal knots under a light/dark rhythm, similar to the differentiation of primary hyphal knots into sclerotia of the wild-type strain under darkness. The CcNsdD2-overexpressing transformant produced more primary hyphal knots, secondary hyphal knots, and fruiting bodies under a light/dark rhythm but only more primary hyphal knots and sclerotia under darkness. RNA-seq revealed that some genes reported previously to be involved in formation of hyphal knots and primordia, cyclopropane-fatty-acyl-phospholipid synthases cfs1-3, galectins cgl1-3, and hydrophobins hyd1-3 were downregulated in the CcNsdD1/NsdD2-RNAi transformant compared to the mock transformant. ChIP-seq and electrophoretic mobility shift assay demonstrated that CcNsdD2 bound to promoter regulatory sequences containing a GATC motif in cfs1, cfs2, cgl1, and hyd1. A molecular mechanism by which CcNsdD2 regulates the developmental fate of C. cinerea under dark or light conditions is proposed. IMPORTANCE The model mushroom Coprinopsis cinerea exhibits remarkable photomorphogenesis during fruiting body development. This study reports that the C. cinerea transcription factor CcNsdD2 promotes primary hyphal knot formation by upregulating cfs1, cfs2, cgl1, and hyd1. Although the induction of CcnsdD2 is not under direct control of light and photoreceptors, the CcNsdD2-mediated developmental fates of the primary hyphal knots depend on the following light/dark rhythm cultivation or dark cultivation after full growth of mycelia in the constant dark cultivation. This study provides new insight into the molecular mechanism by which CcNsdD2 regulates the developmental fate of C. cinerea under dark or light conditions. In addition, the result that overexpression of CcnsdD2 induced more secondary hyphal knots, primordia, and fruiting bodies under light/dark rhythm cultivation conditions has potential applied value in the edible mushroom industry.

Background: The relative benefit of immediate complete revascularization, staged complete revascularization, and culprit-only percutaneous coronary intervention (PCI) remains unclear in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The aim of this study was to compare the clinical outcomes of the 3 PCI strategies in this population.Methods: We followed a pre-specified protocol (PROSPERO number: CRD42020183801). A comprehensive search of the electronic databases including PubMed, EMBASE and Cochrane Library from inception through February 21, 2020 was conducted. Randomized trials evaluating the comparative efficacy and safety of at least 2 of the 3 PCI strategies were identified. The primary endpoint was the composite of cardiovascular mortality or myocardial infarction (MI) during the longest follow-up. Pairwise and network meta-analyses were performed with random-effects model.Results: Eleven trials including 6,942 patients were analyzed. Pairwise meta-analysis noted that immediate complete revascularization and staged complete revascularization were respectively associated with a 52 and 27% reduction in the risk of cardiovascular death or MI (relative risk [RR] 0.48, 95% confidence interval [CI] 0.32–0.73, I2 = 0%; and RR 0.73, 95% CI 0.61–0.88, I2 = 0%, respectively), compared with culprit-only PCI. The risk of cardiovascular death or MI was not statistically different in staged and immediate complete revascularization groups (RR 0.88, 95% CI 0.45–1.72, I2 = 0%). Network meta-analysis obtained almost similar results compared with pairwise meta-analysis, and immediate complete revascularization had a 77% probability of being the best strategy for reducing cardiovascular death or MI among the 3 PCI strategies.Conclusion: The current evidence suggests that both immediate and staged complete revascularization were associated with a reduction of cardiovascular death or MI compared with culprit-only PCI. Further trials are warranted to directly compare immediate vs. staged complete revascularization in this population.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42020183801].

Background. There is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. Methods. This study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. Results. DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients’ noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236–3.399]; IPTW-adjusted HR: 1.843 [1.250–2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128–2.216]; PS matching-HR: 1.639 [1.075–2.499]; IPTW-adjusted HR: 1.554 [1.110–2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. Conclusions. In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.

Duck plague (DP) is a highly contagious viral disease in ducks caused by the duck plague virus (DPV). The DPV, a member of Herpesviridae, poses a severe threat to the waterfowl farming industry worldwide. In this study, we reported a recent outbreak of DPV in domestic laying ducks at 310 days of age from southern China in December 2021. The gross lesion, histopathologic examination, molecular detection, and genetic characterization studies of DPV are described here. As a result, gross lesions such as an enlarged congestive spleen and liver were observed. Liver with vacuolar degeneration and small vacuoles and spleen with hemosiderosis were remarkable microscopic findings. Our results suggested that the liver had the highest viral load, followed by the trachea, pancreas, kidney, brain, spleen, and heart. In addition, DPV was successfully isolated in chicken embryo fibroblast cell culture and designated as DP-GD-305-21. The UL2, UL12, UL41, UL47, and LORF11 genes of DP-GD-305-21 shared a high nucleotide homology with the Chinese virulent (CHv) strain and the Chinese variant (CV) strain. In conclusion, this study reports the isolation and molecular characterization of DPV from a recent outbreak in southern China. Our results contributed to the understanding of the pathological and molecular characterization of currently circulating DPV in China.

Background: Coronary artery ectasia (CAE) is found in about 1% of coronary angiography and is associated with poor clinical outcomes. The prognostic value of plasma big Endothelin-1 (ET-1) in CAE remains unknown.Methods: Patients with angiographically confirmed CAE from 2009 to 2015, who had big ET-1 data available were included. The primary outcome was 5-year major adverse cardiovascular events (MACE), defined as a component of cardiovascular death and non-fatal myocardial infarction (MI). Patients were divided into high or low big ET-1 groups using a cut-off value of 0.58 pmol/L, according to the receiver operating characteristic curve. Kaplan-Meier method, propensity score method, and Cox regression were used to assess the clinical outcomes in the 2 groups.Results: A total of 992 patients were included, with 260 in the high big ET-1 group and 732 in the low big ET-1 group. At 5-year follow-up, 57 MACEs were observed. Kaplan-Meier analysis and univariable Cox regression showed that patients with high big ET-1 levels were at increased risk of MACE (9.87 vs. 4.50%; HR 2.23, 95% CI 1.32–3.78, P = 0.003), cardiovascular death (4.01 vs. 1.69%; HR 2.37, 95% CI 1.02–5.48, P = 0.044), and non-fatal MI (6.09 vs. 2.84%; HR 2.17, 95% CI 1.11–4.24, P = 0.023). A higher risk of MACE in the high big ET-1 group was consistent in the propensity score matched cohort and propensity score weighted analysis. In multivariable analysis, a high plasma big ET-1 level was still an independent predictor of MACE (HR 1.82, 95% CI 1.02–3.25, P = 0.043). A combination of high plasma big ET-1 concentrate and diffuse dilation, when used to predict 5-year MACE risk, yielded a C-statistic of 0.67 (95% CI 0.59–0.74).Conclusion: Among patients with CAE, high plasma big ET-1 level was associated with increased risk of MACE, a finding that could improve risk stratification.

Previous studies have suggested that reading stories of role models can improve the growth mindsets of students. The current study aimed to investigate the types of stories that can increase the growth mindsets of high school students, undergraduates, and graduates and how many specific stories undergraduates with low and high perseverance need to read to improve their growth mindsets. In study 1, high school students, undergraduates, and graduates were assigned to read either five struggle stories or five achievement stories of role models. Their mindsets were measured before and after reading the stories. The results showed that reading struggle stories rather than achievement stories of role models increased the growth mindsets of undergraduates and graduates. In study 2, undergraduates with high and low perseverance were assigned to read five struggle stories or five achievement stories of role models. Their mindsets were measured before reading stories and after reading each story. The results showed that the growth mindsets of undergraduates with low perseverance increased after reading two struggle stories of role models, and increased further after reading five struggle stories of role models. More importantly, the level of growth mindsets of undergraduates with low perseverance was equal to that of undergraduates with high perseverance after reading five struggle stories of role models. These findings reveal that reading struggle stories of role models can improve the growth mindsets of undergraduates and graduates. The personality of students affects the effectiveness of story-based mindset intervention.

In this work, we propose a novel dual optical frequency comb (DOFC) generation scheme based on dual cascaded difference frequency generation (DCDFG). Feasible designs are introduced that enable the two sets of cascaded optical waves, initially generated by DCDFG in an aperiodically periodically poled lithium niobate (APPLN) crystal with a pump wave and two signal waves, then transferred to high-order Stokes waves by oscillations of cascaded Stokes waves and the optimization of phase mismatching of each-order DCDFG; finally, a DOFC was constructed. We demonstrate a high-performance DOFC with characteristics of high repetition frequency difference, tunable repetition frequency difference, high flatness, and a tunable spectral distribution range by providing a theoretical framework. We argue that the scheme proposed in this work is promising for achieving a high-quality DOFC.

Abstract Background Novel Muscovy duck reovirus (N-MDRV), emerged in southeast China in 2002, which can infect a wide range of waterfowl and induces clinical signs and cytopathic effects that are distinct from those of classical MDRV, and continues to cause high morbidity and 5–50% mortality in ducklings. The present study aimed to investigate the characteristics of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China. Results Two novel MDRV strains, designated as MDRV-SH12 and MDRV-DH13, were isolated from two diseased Muscovy ducklings in Guangdong province, China in June 2012 and September 2013, respectively. Sequencing of the complete genomes of these two viruses showed that they consisted of 23,418 bp and were divided into 10 segments, ranging from 1191 bp (S4) to 3959 bp (L1) in length, and all segments contained conserved sequences in the 5′ non-coding region (GCUUUU) and 3′ non-coding region (UCAUC). Pairwise sequence comparisons demonstrated that MDRV-SH12 and MDRV-DH13 showed the highest similarity with novel MDRVs. Phylogenetic analyses of the nucleotide sequences of all 10 segments revealed that MDRV-SH12 and MDRV-DH13 were clustered together with other novel waterfowl-origin reoviruses and were distinct from classical waterfowl-origin and chicken-origin reoviruses. The analyses also showed possible genetic re-assortment events in segment M2 between waterfowl-origin and chicken-origin reoviruses and the segments encoding λA, μA, μNS, σA, and σNS between classical and novel waterfowl-origin reoviruses. Potential recombination events detection in segment S2 suggests that MDRV-SH12 and MDRV-DH13 may be recombinants of classical and novel WRVs. Conclusions The results presented in this study, the full genomic data for two novel MDRV strains, will improve our understanding of the evolutionary relationships among the waterfowl-origin reoviruses circulating in China, and may aid in the development of more effective vaccines against various waterfowl-origin reoviruses.

Abstract Background Hepatitis E virus (HEV) is one of most important zoonotic viruses, and it can infect a wide range of host species. Avian HEV has been identified as the aetiological agent of big liver and spleen disease or hepatitis-splenomegaly syndrome in chickens. HEV infection is common among chicken flocks in China, and there are currently no practical measures for preventing the spread of the disease. The predominant avian HEV genotype circulating in China have been identified as genotype 3 strains, although some novel genotypes have also been identified from chicken flocks in China. Results In this study, we used a meta-transcriptomics approach to identify a new subtype of genotype 3 avian HEV in broiler chickens at a poultry farm located in Shenzhen, Guangdong Province, China. The complete genome sequence of the avian HEV, designated CaHEV-GDSZ01, is 6655-nt long, including a 5′ UTR of 24 nt and a 3′ UTR of 125 nt (excluding the poly(A) tail), and contains three open reading frames (ORFs). Sequence analysis indicated that the complete ORF1 (4599 nt/1532 aa), ORF2 (1821 nt/606 aa) and ORF3 (264 nt/87 aa) of CaHEV-GDSZ01 share the highest nucleotide sequence identity (85.8, 86.7 and 95.8%, respectively) with the corresponding ORFs of genotype 3 avian HEV. Phylogenetic analyses further demonstrated that the avian HEV identified in this study is a new subtype of genotype 3 avian HEV. Conclusions Our results demonstrate that a new subtype of genotype 3 avian HEV is endemic in Guangdong, China, and could cause high mortality in infected chickens. This study also provides full genomic data for better understanding the evolutionary relationships of avian HEV circulating in China. Altogether, the results presented in this study suggest that more attention should be paid to avian HEV and its potential disease manifestation.