IL-6/STAT3 axis is hijacked by GCRV to facilitate viral replication via suppressing type â IFN signaling.

Grass carp reovirus (GCRV) infections and hemorrhagic disease (GCHD) outbreaks are typically seasonally periodic and temperature-dependent, yet the molecular mechanism remains unclear. Herein, we depicted that temperature-dependent IL-6/STAT3 axis was exploited by GCRV to facilitate viral replication via suppressing type Ⅰ IFN signaling. Combined multi-omics analysis and qPCR identified IL-6, STAT3, and IRF3 as potential effector molecules mediating GCRV infection. Deploying GCRV challenge at 18 °C and 28 °C as models of resistant and permissive infections and switched to the corresponding temperatures as temperature stress models, we illustrated that IL-6 and STAT3 expression, genome level of GCRV, and phosphorylation of STAT3 were temperature dependent and regulated by temperature stress. Further research revealed that activating IL-6/STAT3 axis enhanced GCRV replication and suppressed the expression of IFNs, whereas blocking the axis impaired viral replication. Mechanistically, grass carp STAT3 inhibited IRF3 nuclear translocation via interacting with it, thus down-regulating IFNs expression, restraining transcriptional activation of the IFN promoter, and facilitating GCRV replication. Overall, our work sheds light on an immune evasion mechanism whereby GCRV facilitates viral replication by hijacking IL-6/STAT3 axis to down-regulate IFNs expression, thus providing a valuable reference for targeted prevention and therapy of GCRV.

Autophagy mediated degradation of MITA/TBK1/IRF3 by a hnRNP family member attenuates interferon production in fish.

HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted Spring viremia of carp virus (SVCV) and Cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA. Our study provides novel insights into the functions of hnRNP A/B in regulating host antiviral response.

[Effect of Zuogui Jiangtang Qinggan Formula on lipid metabolism in db/db mouse model of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease].

This study aims to explore the effect of Zuogui Jiangtang Qinggan Formula(ZGJTQGF) on the lipid metabolism in the db/db mouse model of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD) via the insulin receptor(INSR)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/sterol-regulatory element-binding protein 2(SREBP-2) signaling pathway. Twenty-four db/db mice were randomized into positive drug(metformin, 0.067 g·kg~(-1)) and low-(7.5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) ZGJTQGF groups. Six C57 mice were used as the blank group and administrated with an equal volume of distilled water. The mice in other groups except the blank group were administrated with corresponding drugs by gavage for 6 consecutive weeks. At the end of drug administration, fasting blood glucose(FBG) and blood lipid levels were measured, and oral glucose tolerance test was performed. Compared with the blank group, the mice treated with ZGJTQGF showed decreased body mass and liver weight coefficient, lowered levels of FBG, total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL), and weakened liver function. The pathological changes and lipid accumulation in the liver tissue were examined. Western blot was employed to measure the protein levels of INSR, AMPK, p-AMPK, and SREBP-2. Compared with the blank group, the model group showed down-regulated protein levels of INSR and p-AMPK/AMPK and up-regulated protein level of SREBP-2. Compared with the model group, high-dose ZGJTQGF up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2. Low-dose ZGJTQGF slightly up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2, without significant differences. The results suggested that ZGJTQGF may alleviate insulin resistance and improve lipid metabolism in db/db mice by activating the INSR/AMPK/SREBP-2 signaling pathway.

Crosstalk between m6A modification and autophagy in cancer.

Autophagy is a cellular self-degradation process that plays a crucial role in maintaining metabolic functions in cells and organisms. Dysfunctional autophagy has been linked to various diseases, including cancer. In cancer, dysregulated autophagy is closely associated with the development of cancer and drug resistance, and it can have both oncogenic and oncostatic effects. Research evidence supports the connection between m6A modification and human diseases, particularly cancer. Abnormalities in m6A modification are involved in the initiation and progression of cancer by regulating the expression of oncogenes and oncostatic genes. There is an interaction between m6A modification and autophagy, both of which play significant roles in cancer. However, the molecular mechanisms underlying this relationship are still unclear. m6A modification can either directly inhibit autophagy or promote its initiation, but the complex relationship between m6A modification, autophagy, and cancer remains poorly understood. Therefore, this paper aims to review the dual role of m6A and autophagy in cancer, explore the impact of m6A modification on autophagy regulation, and discuss the crucial role of the m6A modification-autophagy axis in cancer progression and treatment resistance.

Efficacy and Safety of Covered Stents Versus Bare-Metal Stents for Aortoiliac Occlusive Disease: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to assess the efficacy and safety outcome of covered stents (CSs), as compared with bare-metal stents (BMSs), for the treatment of patients with aortoiliac occlusive disease (AIOD). MATERIALS AND METHODS: A systematic literature search was conducted in PubMed, Embase, and Cochrane Library up to August 2023 to identify all studies comparing efficacy and safety outcomes of CSs versus BMSs for treating AIOD. Our outcome was primary patency, secondary patency, technical success, ankle-brachial index (ABI) variation, target lesion revascularization (TLR), limb salvage, complications, and long-term survival. Dichotomous outcomes were pooled as relative risks (RR) or hazard ratio with the 95% confidence interval (CI). Continuous outcomes were pooled as weighted mean differences and 95% CI. Model selection was based on the heterogeneity of the included studies. RESULTS: There were 10 studies (2 randomized controlled trials, 8 retrospective cohort studies), comprising 1676 sample size. Compared with BMSs, CSs use was associated with better primary patency of patients with a Trans-Atlantic Inter-Society Consensus II (TASC) D lesion (RR, 1.15, 95% CI, 1.04 to 1.27, p=0.007), TLR (RR, 0.39, 95% CI, 0.27 to 0.56, p<0.001), technical success (RR, 1.01, 95% CI, 1.00 to 1.02, p=0.010), and long-term survival (RR, 1.06, 95% CI, 1.01 to 1.11, p=0.020). There is no difference between CSs and BMSs regarding primary patency of all patients, secondary patency, variation in ABI, limb salvage, and complications. CONCLUSIONS: Compared with BMSs, CSs used in AIOD was associated with more favorable primary patency in patients with TASC D lesions, TLR, technical success rates, and patient long-term survival. These results provide evidence of the advantages of using CSs for AIOD treatment. Future studies focusing on long-term variations in ABI, primary patency of different degrees of calcification, vascular segments, and TASC classification are warranted. CLINICAL IMPACT: Although several studies evaluated the clinical efficacy of CS in the context of AIOD treatment, the significance and consistency of these findings were not determined to date. We found that CS was used in AIOD associated with better technical success rate, long-term patient survival, lower target lesion revascularization, and higher primary patency of patients with a Trans-Atlantic Inter-Society Consensus II D lesion when compared with BMSs. Our study provides evidence supporting the superiority of CSs over BMSs in the treatment of AIOD, and furnishing clinicians with guidance for treatment decisions.

On the approximation of bi-Lipschitz maps by invertible neural networks.

Invertible neural networks (INNs) represent an important class of deep neural network architectures that have been widely used in applications. The universal approximation properties of INNs have been established recently. However, the approximation rate of INNs is largely missing. In this work, we provide an analysis of the capacity of a class of coupling-based INNs to approximate bi-Lipschitz continuous mappings on a compact domain, and the result shows that it can well approximate both forward and inverse maps simultaneously. Furthermore, we develop an approach for approximating bi-Lipschitz maps on infinite-dimensional spaces that simultaneously approximate the forward and inverse maps, by combining model reduction with principal component analysis and INNs for approximating the reduced map, and we analyze the overall approximation error of the approach. Preliminary numerical results show the feasibility of the approach for approximating the solution operator for parameterized second-order elliptic problems.

Study on Thermomechanical Properties and Morphology of an Epoxy Resin Thermally Conductive Adhesive under Different Curing Conditions.

An epoxy resin thermally conductive adhesive is a type of thermosetting polymer encapsulation material that exhibits comprehensive performance, and the thermomechanical properties of this adhesive vary significantly under different curing conditions. In this paper, spherical alumina was used as a filler for thermal conductivity to prepare an epoxy resin thermal conductivity adhesive using a multistage freezing mixing method. The effects of various curing conditions on the thermal-mechanical properties and fracture morphology of the epoxy resin thermal conductivity adhesive were studied. The results showed that the curing condition of 150 °C/2.5 h significantly improved the performance of the epoxy resin thermally conductive adhesive. Through the shear test of the composite material, the influence of the curing agent on the adhesion of the thermally conductive adhesive under fixed conditions was explored. It was found that the curing agent with a superbranched structure exhibited latent properties and greatly enhanced the toughness of the cured epoxy resin product. Altering the curing conditions increases the shear strength by up to 307%. With the increase in curing temperature and the extension of curing temperature, the glass transition temperature gradually increased from 103.9 to 159.8 °C. The initial decomposition temperature TIDT gradually increased from 295.4 to 310.1 °C, and the temperature at which the fastest decomposition rate occurs (Tmax) gradually increased from 312.48 to 330.33 °C. The thermal stability of the substance increased with both temperature and time. The curing time and curing temperature were increased, and the morphology of the fracture of the epoxy resin thermally conductive adhesive cured sample gradually showed a ductile fracture from a typical brittle fracture. The research results reveal the influence of curing conditions on the thermal conductivity and thermal stability of the epoxy resin thermally conductive adhesive, which has a specific reference value for improving the performance of the epoxy resin thermally conductive adhesive, optimizing its usage conditions, and improving production efficiency.

[Tillage Depth Regulation and the Effect of Straw Return on Soil Respiration in Farmland].

Straw return and tillage depth treatments are one of the most important agricultural management measures that affect farmland soil respiration, but the mechanism of their interaction affecting farmland soil respiration remains unclear. Therefore, 116 published research articles were used through Meta-analysis technology for dryland farmland ecosystems in China to explore the effects of straw return and tillage depth treatments and their interaction on farmland soil respiration and its regulatory factors, which will provide important data support and a theoretical basis for achieving "carbon neutrality" in farmland ecosystems. The results showed that no tillage reduced soil respiration by 8.3%, and the effects of shallow and deep tillage treatments on soil respiration were not significant, but the increase in soil respiration still showed a trend of deep tillage>shallow tillage>no tillage. However, both shallow and deep tillage had relatively small effects on soil respiration and soil organic carbon (SOC), whereas no tillage reduced soil respiration by 8.3% and increased SOC by 7.05%. Therefore, implementing no tillage measures is of great significance for soil carbon sequestration and emission reduction in farmland ecosystems. In addition, tillage depth significantly regulated the impact of straw return on soil respiration, and the increase in soil respiration showed a trend of deep tillage straw return>shallow tillage straw return>no tillage straw return, with an overall average increase of 14.51%. The increase in soil respiration under different tillage depth treatments after straw return was closely related to the change in soil bulk density, crop yield, SOC, soil temperature, and moisture, and the contribution to the increase in soil respiration showed a trend of soil bulk density>crop yield>soil organic carbon>soil moisture>soil temperature. However, SOC increased by 29.32%, 10.12%, and 23.94%, respectively, in the deep tillage straw return, shallow tillage straw return, and no tillage straw return treatments, whereas soil respiration increased by 29.32% and 18.92%, respectively, in the deep tillage straw return and shallow tillage straw return treatments, and it only increased by 1.2% in the no tillage straw return treatment. Therefore, no tillage straw return was also beneficial to soil carbon sequestration and emission reduction in farmland ecosystems. Thus, in the dryland farmland ecosystem of China, tillage depth treatments regulated the impact of straw return on soil respiration, which was mainly related to soil physical and chemical properties, especially being closely related to soil bulk density. Moreover, no tillage and no tillage straw return are important agricultural management measures that are conducive to soil carbon sequestration and emission reduction.

Functional genomics of Brassica napus: Progresses, challenges, and perspectives.

Brassica napus, commonly known as rapeseed or canola, is a major oil crop contributing over 13% to the stable supply of edible vegetable oil worldwide. Identification and understanding the gene functions in the B. napus genome is crucial for genomic breeding. A group of genes controlling agronomic traits have been successfully cloned through functional genomics studies in B. napus. In this review, we present an overview of the progress made in the functional genomics of B. napus, including the availability of germplasm resources, omics databases and cloned functional genes. Based on the current progress, we also highlight the main challenges and perspectives in this field. The advances in the functional genomics of B. napus contribute to a better understanding of the genetic basis underlying the complex agronomic traits in B. napus and will expedite the breeding of high quality, high resistance and high yield in B. napus varieties.

Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China.

INTRODUCTION: Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS. METHODS AND ANALYSIS: We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient's efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples. ETHICS AND DISSEMINATION: The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/). TRIAL REGISTRATION NUMBER: ISRCTN62094626.

High-frequency surface-micromachined optical ultrasound transducer array for 3D micro photoacoustic computed tomography.

This Letter reports a new, to the best of our knowledge, high-frequency surface-micromachined optical ultrasound transducer (HF-SMOUT) array for micro photoacoustic computed tomography (µPACT). An 11 × 11 mm2 2D array of 220 × 220 elements (35 µm in diameter) is designed, fabricated, and characterized. The optical resonance wavelength (ORW) of ≥90% of the elements falls within a 6-nm range. The acoustic center frequency and bandwidth of the elements are ∼14 MHz and ∼18 MHz (129%), respectively. The noise equivalent pressure (NEP) is 161 Pa (or 18 m P a/H z) within a measurement bandwidth of 5-75 MHz. The standard deviation of the ORW drift is 0.45 nm and 0.93 nm within 25°C-55°C, respectively, and during a seven-day continuous water immersion. PACT experiments are conducted to evaluate the imaging performances of the HF-SMOUT array. The spatial resolution is estimated as 90 µm (axial) and 250-750 µm (lateral) within a 10 × 10 mm2 field of view (FoV) and the imaging depth of 16 mm. A 3D PA image of a knotted black hair target is also successfully acquired. These results demonstrate the feasibility of using the HF-SMOUT array for µPACT applications.

Precore mutation enhances viral replication to facilitate persistent infection especially in HBeAg-negative patients.

Naturally occurred precore (PC, G1896A) and/or basal core promoter (BCP, A1762T/G1764A) mutations are prevalent in chronic HBV-infected patients, especially those under HBeAg-negative status. However, the replicative capacity of HBV with PC/BCP mutations remains ambiguous. Herein, meta-analysis showed that, only under HBeAg-negative status, the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the mutation. Both PC mutation alone and BCP â€‹+ â€‹PC mutations promoted HBV replication in cell and hydrodynamic injection mouse models. In human hepatocyte chimeric mouse model, BCP â€‹+ â€‹PC mutations led to elevated replicative capacity and intrahepatic core protein accumulation. Mechanistically, preC RNA harboring PC mutation could serve as mRNA to express core and P proteins, and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative status. Additionally, BCP â€‹+ â€‹PC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric mice. This study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease in the world. Immunity is the major contributing factor in NAFLD; however, the interaction of immune cells and hepatocytes in disease progression has not been fully elucidated. As a popular species for studying NAFLD, zebrafish, whose liver is a complex immune system mediated by immune cells and non-immune cells in maintaining immune tolerance and homeostasis. Understanding the cellular composition and immune environment of zebrafish liver is of great significance for its application in NAFLD. Here, we established a liver atlas that consists of 10 cell types using single-cell RNA sequencing (scRNA-seq). By examining the heterogeneity of hepatocytes and analyzing the expression of NAFLD-associated genes in the specific cluster, we provide a potential target cell model to study NAFLD. Additionally, our analysis identified two subtypes of distinct resident macrophages with inflammatory and non-inflammatory functions and characterized the successive stepwise development of T cell subclusters in the liver. Importantly, we uncovered the possible regulation of macrophages and T cells on target cells of fatty liver by analyzing the cellular interaction between hepatocytes and immune cells. Our data provide valuable information for an in-depth study of immune cells targeting hepatocytes to regulate the immune balance in NAFLD.

Anoikis and SPP1 in idiopathic pulmonary fibrosis: integrating bioinformatics, cell, and animal studies to explore prognostic biomarkers and PI3K/AKT signaling regulation.

OBJECTIVE: This study aims to explore the relevance of anoikis in idiopathic pulmonary fibrosis (IPF) and identify associated biomarkers and signaling pathways. METHOD: Unsupervised consensus cluster analysis was employed to categorize IPF patients into subtypes. We utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and Protein-Protein Interaction network construction to identify anoikis-related modules and key genes. A prognostic signature was developed using Lasso and multivariate Cox regression analysis. Single-cell sequencing assessed hub gene expression in various cell types, and both cell and animal experiments confirmed IPF-related pathways. RESULTS: We identified two distinct anoikis-associated subtypes with differing prognoses. WGCNA revealed essential hub genes, with SPP1 being prominent in the anoikis-related signature. The anoikis-related signature is effective in determining the prognosis of patients with IPF. Single-cell sequencing highlighted significant differences in SPP1 expression, notably elevated in fibroblasts derived from IPF patients. In vivo and in vitro experiments demonstrated that SPP1 enhances fibrosis in mouse lung fibroblasts by regulating p27 through the PI3K/Akt pathway. CONCLUSION: Our research demonstrates a robust prognostic signature associated with anoikis and highlights SPP1 as a pivotal regulator of the PI3K/AKT signaling pathway in pulmonary fibrosis.

[Effect of Personality and Physical Activity on Bone Mineral Density in College Students: A Cross-sectional Survey]. / å¤§å­¦ç”Ÿäººæ ¼å’Œä½“åŠ›æ´»åŠ¨å¯¹éª¨å¯†åº¦çš„å½±å“ï¼šä¸€é¡¹æ¨ªæ–­é¢è°ƒæŸ¥.

Objective: To explore the correlation between 5 dimensions of personality, physical activity (PA), and bone mineral density (BMD) among college students. Methods: A total of 705 undergraduates (329 males and 376 females) from a sports university were recruited. Based on their sports training experience, the participants were divided into 6 major sports groups, including ball sports, skilled sports, competitive sports, track and field, leisure sports, and no sports. Students with professional sports training (ie, athletes) were categorized into ballgame, skilled, competitive, and track and field groups, while the rest (non-athletes) were placed in leisure and no sports groups. Ten-Item Personality Inventory in China (TIPI-C), or the 5-factor model of personality, was used to measure the 5 personality dimensions of openness, conscientiousness, extraversion, agreeableness, and neuroticism of the participants. Their daily level was measured with GT3X+ triaxial accelerometers over 7 continuous days. Then, parameter thresholds were established and the participants' PA was categorized as light (LPA), moderate (MPA), and vigorous (VPA). The bone mineral density (BMD) of arms, legs, and the total body was measured using dual-energy X-ray absorptiometry. The mediation effect of PA and that of the 5-factor model of personality were tested using PROCESS and Sobel tests. The correlation between the 5 personality dimensions, PA, and BMD was explored, with PA and the 5 personality dimensions as mediator variables. A comparison of PA and BMD was conducted across the 6 major sports groups. The correlation between PA of different intensities and BMD was also analyzed using Spearman's correlation. Results: Although there were 90 potential relationships between PA, the 5 personality dimensions, and BMD, only 3 were significant. When conscientiousness was used as an independent variable and MPA, as a mediating variable, statistically significant differences in PROCESS results were reported (P<0.01), with MPA mediating 17.3% of arm BMD, 19.4% of leg BMD, and 19.1% of total body BMD. Among male students, there was no significant difference in LPA among the 6 groups, but significant differences in MPA and VPA (P<0.05). Among female students, significant differences in LPA, MPA, and VPA were observed in all 6 groups and the differences between MPA and VPA were especially prominent (P<0.05). For both males and females, the differences in arm, leg, and total body BMD across the 6 groups were statistically significant (P<0.05), with these differences being more pronounced in females. There was no correlation between LPA and BMD in either sex. MPA and VPA were positively correlated with BMD, with MPA correlating with arm, leg, and total body BMD (males, Spearman's correlation [rs]: 0.11-0.14, P<0.05; females, rs: 0.20-0.23, P<0.01). VPA correlated with arm, leg, and total body BMD (males, rs: 0.11-0.23, P<0.05; females, rs: 0.26-0.30, P<0.01). Conclusion: MPA is associated with BMD in college students scoring high in the conscientiousness dimension of personality. In addition, there is a weak positive correlation between both MPA and VPA and BMD levels, with these associations being more pronounced in females.

Redefining left bundle branch block from high-density electroanatomical mapping.

BACKGROUND: The existing ECG criteria for diagnosing left bundle branch block (LBBB) are insufficient to distinguish between true and false blocks accurately. METHODS: We hypothesized that the notch width of the QRS complex in the lateral leads (I, avL, V5, V6) on the LBBB-like ECG could further confirm the diagnosis of true complete left bundle branch block (t-LBBB). We conducted high-density, three-dimensional electroanatomical mapping in the cardiac chambers of 37 patients scheduled to undergo CRT. These patients' preoperative electrocardiograms met the ACC/AHA/HRS guidelines for the diagnosis of complete LBBB. If the left bundle branch potential could be mapped from the base of the heart to the apex on the left ventricular septum, it was defined as a false complete left bundle branch block (f-LBBB). Otherwise, it was categorized as a t-LBBB. We conducted a comparative analysis between the two groups, considering the clinical characteristics, real-time correspondence between the spread of ventricular electrical excitation and the QRS wave, QRS notch width of the lateral leads (I, avL, V5, V6), and the notch width/left ventricular end-diastolic diameter (Nw/LVd) ratio. We performed the ROC correlation analysis of Nw/LVd and t-LBBB to determine the sensitivity and specificity for diagnostic authenticity. RESULTS: Twenty-five patients were included in the t-LBBB group, while 12 patients were assigned to the f-LBBB group. Within the t-LBBB group, the first peak of the QRS notch correlated with the depolarization of the right ventricle and septum, the trough corresponded to the depolarization of the left ventricle across the left ventricle, and the second peak aligned with the depolarization of the left ventricular free wall. In contrast, within the f-LBBB group, the first peak coincided with the depolarization of the right ventricle and a majority of the left ventricle, the second peak occurred due to the depolarization of the latest, locally-activated myocardium in the left ventricle, and the trough was a result of delayed activation of the left ventricle that did not align with the usual peak timing. The QRS notch width (45.2 ± 12.3 ms vs. 52.5 ± 9.2 ms, P < 0.05) and the Nw/LVd ratio (0.65 ± 0.19 ms/mm vs. 0.81 ± 0.17 ms/mm, P < 0.05) were compared between the two groups. After conducting the ROC correlation analysis, a sensitivity of 56% and a specificity of 91.7% for diagnosing t-LBBB using Nw/LVd were obtained. CONCLUSION: By utilizing the current diagnostic criteria for LBBB, an increased Nw/LVd value can enhance the effectiveness of diagnosing LBBB.

Cytonuclear Interactions and Subgenome Dominance Shape the Evolution of Organelle-Targeted Genes in the Brassica Triangle of U.

The interaction and coevolution between nuclear and cytoplasmic genomes are one of the fundamental hallmarks of eukaryotic genome evolution and, 2 billion yr later, are still major contributors to the formation of new species. Although many studies have investigated the role of cytonuclear interactions following allopolyploidization, the relative magnitude of the effect of subgenome dominance versus cytonuclear interaction on genome evolution remains unclear. The Brassica triangle of U features 3 diploid species that together have formed 3 separate allotetraploid species on similar evolutionary timescales, providing an ideal system for understanding the contribution of the cytoplasmic donor to hybrid polyploid. Here, we investigated the evolutionary pattern of organelle-targeted genes in Brassica carinata (BBCC) and 2 varieties of Brassica juncea (AABB) at the whole-genome level, with particular focus on cytonuclear enzyme complexes. We found partial evidence that plastid-targeted genes experience selection to match plastid genomes, but no obvious corresponding signal in mitochondria-targeted genes from these 2 separately formed allopolyploids. Interestingly, selection acting on plastid genomes always reduced the retention rate of plastid-targeted genes encoded by the B subgenome, regardless of whether the Brassica nigra (BB) subgenome was contributed by the paternal or maternal progenitor. More broadly, this study illustrates the distinct selective pressures experienced by plastid- and mitochondria-targeted genes, despite a shared pattern of inheritance and natural history. Our study also highlights an important role for subgenome dominance in allopolyploid genome evolution, even in genes whose function depends on separately inherited molecules.

Determination of [Glu1]-fibrinopeptide B purity by gas chromatography - isotope dilution mass spectrometry.

The present work assessed the purity of [Glu1]-fibrinopeptide B (GFB) as a model peptide using gas chromatography - isotope dilution mass spectrometry. GFB and various isotope-labeled amino acids were hydrolyzed in HCl and then derivatized using optimized procedures. The primary impurity in GFB was also identified and used to correct the final result. A method repeatability of 0.5% was achieved and linear calibrations were obtained for five amino acids. The LOD and LOQ were 0.041 to 0.096 µg g-1, and 0.16 to 0.56 µg g-1, respectively. The purity of GFB was found to be (0.715 ± 0.012) g g-1. This technique exhibited comparable accuracy to that obtainable from liquid chromatography - isotope dilution mass spectrometry but at lower cost. This method could be employed as a reference technique or in fields such as clinical diagnostics or bio-pharmaceutical peptide purity analysis.

Clinical heterogeneity and five phenotypes identified in pediatric Behçet's syndrome: a cohort study from Shanghai Behçet's syndrome database.

OBJECTIVES: Behçet's syndrome (BS) is a rare disease of unknown etiology, with limited reports especially in pediatric BS. The clinical characteristics and phenotypes of pediatric BS as a highly heterogeneous variable vessel vasculitis were investigated in this study. METHODS: A cross-sectional study was conducted to compare clinical variables and descriptive characteristics of BS by age of onset and gender. Cluster analysis was then performed to identify the phenotypes of pediatric BS. RESULTS: A total of 2082 BS patients were included in this study, 1834 adults and 248 children. Compared with adult-onset BS, pediatric BS had a higher incidence of folliculitis [relative risks (RR) and 95% confidence interval (CI) 1.3 (1.0-1.5)], uveitis of the left eye [RR and 95% CI 2.3 (1.0-5.0)], intestinal ulcer complications [RR and 95% CI 2.1 (1.1-4.2)], pericarditis [RR and 95% CI 2.5 (1.0-6.2)], and psychiatric disorders [RR and 95% CI 2.8(1.0-7.9)], while the incidence of thrombocytopenia was lower [RR 0.2 (0.1-1.0)]. Among pediatric BS, females had more genital ulcers, while males were more likely to have skin lesions, panuveitis, vascular involvement, venous lesions, cardiac involvement, and aortic aneurysms. Cluster analysis classified pediatric BS into five clusters (C1-C5): C1 (n = 61, 24.6%) showed gastrointestinal (GI) involvement; C2 (n = 44, 17.7%) was the central nervous system (CNS) type where 23 cases overlapped joint involvement; in C3 (n = 35, 14.1%), all patients presented with arthritis or arthralgia; all patients in C4 (n = 29, 11.7%) manifested ocular involvement, with a few patients overlapping with GI involvement or joint damage; C5 (n = 79, 31.9%) was the mucocutaneous type, presenting both oral ulcers, genital ulcers, and skin lesions. CONCLUSIONS: The clinical features of pediatric and adult BS differ significantly. Male and female pediatric BS also have a distinct demography. Five phenotypes including GI, CNS, joint, ocular, and mucocutaneous types were identified for pediatric BS.

A case of chronic wounds caused by Sporothrix schenckii infection was rapidly detected by metagenomic next generation sequencing.

The dimorphic fungus Sporothrix schenckii is widely distributed in soil, vegetation, and decaying organic matter, and can cause sporotrichosis when the patient's skin trauma was exposed to contaminated material with Sporothrix spp. The cases of Sporothrix schenckii infection in chronic wounds are rarely reported. Here we reported a 53-year-old male construction worker who was admitted to our hospital on July 9, 2022, without underlying disease presented with a painless subcutaneous hard nodule on his right calf, which later ulcerated and oozed, with an enlarged wound and no fever during the course of the disease. His procalcitonin, C-reactive protein, erythrocyte sedimentation rate increased, and necrotic histopathology suggested chronic granulomatous inflammation. Then his necrotic tissue and pus were sent for metagenomic next generation sequencing(mNGS), the result reported Sporothrix schenckii after 43 hours, which was consistent with the result of culture after 18 days. mNGS might be more useful and valuable in diseases such as sporotrichosis where it is difficult to see the yeast cells in the tissues.