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IntroductionCopper metabolism encompasses all cellular metabolic processes involving copper ions and plays a significant role in the pathogenesis of diseases, including cancer. Furthermore, copper is intricately involved in various processes related to nucleotide metabolism. However, a comprehensive analysis of copper metabolism in gliomas remains lacking despite its importance.MethodsTo address this gap, glioma patients were stratified based on the expression levels of copper metabolism-related genes. By utilizing machine learning techniques, a novel copper metabolism-associated biomarker was developed. The potential of this biomarker in prognosis, mutation analysis, and predicting immunotherapy response efficiency in gliomas was systematically investigated.ResultsNotably, IGFBP2, identified as a glioma tumor promoter, was found to promote disease progression and influence immunotherapy response. Additionally, glioma-derived IGFBP2 was observed to enhance microglial migration. High IGFBP2 expression in GBM cells facilitated macrophage interactions through the EGFR, CD63, ITGB1, and CD44 signaling pathways. Discussion: Overall, the copper metabolism-associated biomarker shows promising potential to enhance the clinical management of gliomas, offering valuable insights into disease prognosis and treatment strategies.

Abstract Introduction This study aimed to investigate the treatment effect of G protein‐coupled receptor 30 (GPR30) agonist G1 combined with hypothermia (HT) on cognitive impairment and anxiety‐like behavior after subarachnoid hemorrhage (SAH) in rats. Methods Fifty male rats were randomly assigned to one of five groups: Sham group, SAH group, SAH + G1 group, SAH + HT group, and SAH + G1 + HT group. The SAH rat model was established by modified endovascular puncture in all groups except the Sham group. Neurological function after the operation was assessed by Garcia scoring. The degree of rat cerebral edema was determined using dry‐wet weighing method on the 28th day after operation. Moreover, the behavioral test was performed on rats on the 4th and 28th days after operation. Results Compared with Sham group, the Garcia score of each SAH rat model group decreased significantly on the first day and thereafter increased gradually. However, the recovery rate of each treatment group was higher than the SAH group (no treatment), and the Garcia score of SAH + G1 + HT group was much higher than the SAH group on the seventh day after operation. In addition, each treatment group could obviously reduce the cerebral edema degree of SAH rats, among which rats in SAH + G1 + HT group had lower cerebral edema degree than SAH + G1 group and SAH + HT group. Behavioral test results showed that the combination of GPR30 agonist G1 and HT markedly improved the learning and memory ability of SAH rats, alleviated their anxiety‐ and emotion‐related behavior, and enhanced their social interaction. Conclusion GPR30 agonist G1 combined with HT reduces cognitive impairment and anxiety‐like behavior in rats with SAH.

Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1β, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, and downregulated the abundance of Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury.

IntroductionGliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques.MethodsThe prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. ResultsExperimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. ConclusionsThe incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.

The frequent occurrence of global extreme weather conditions and the problem of lodging restrict crops’ stability and high-yield production, posing a serious threat to global food security. Although research on lodging resistance has been comprehensive, there are still relevant problems in individual plant genetic characteristics and global field management. This article reviews the latest progress on the endogenous molecular mechanisms and genetic breeding for crop lodging resistance. Interestingly, stem seems to be the main target tissue for crop lodging resistance. Endogenous sugar metabolism, enzyme synthesis, and phytohormones signaling affect the lodging status of crops such as rice, corn, soybeans and rapeseed by enhancing stem toughness. A successful crop lodging model and index were also proposed to explain the various factors influencing lodging types. Moreover, modern informative and intelligent remote sensing technology, including the unmanned aerial vehicle (UAV) and radar remote sensing, can effectively improve field lodging resistance and the yield of crops. We discussed applicable countermeasures, such as the exploration of key genes, development of advanced breeding strategy, scientific field management and application of intelligent monitoring technology. Consequently, we suggested some integrated strategies combining elite gene resources, appropriate agronomic management methods and the UAV technique, which provide rich genetic resources and a theoretical basis for improving genetics breeding for lodging resistance in crops, offers advanced agronomic management solutions and agricultural IoT system support for crop lodging resistance management, and suggests research directions and focus for the next Green Revolution.

Most waste sludge belongs to long sludge-retention-time (SRT) sludge in China, but its outlet is becoming a severe environmental problem nowadays. In this study, the characteristics of mesophilic and thermophilic anaerobic digestion of long SRT sludge was investigated under different total solid content (TSC) of 4%, 6%, and 8% in batch reactors. The results showed that the methane production potential (Po) and methane production rate (Rmax) of thermophilic anaerobic digestion (TAD) were increased by about 60% and 200% compared with that of the mesophilic anaerobic digestion (MAD) at 4% TSC. In TAD groups, the Po of 240.95 LCH4 kgVS-1added and Rmax of 22.17 LCH4 kgVS-1added day-1 were achieved in the reactor of 4% TSC while the inhibition concentration of propionate and free ammonia reached 1022 mg L-1 and 603 mg L-1 in the reactor of 8% TSC. Although the diversity of microbial communities were poor in TAD, Coprothermobacter was enriched in TAD, which could degrade protein efficiently. In addition, the dewaterability of digested sludge in TAD was poorer than that in MAD, and both got worse with the increased TSC. Therefore, it is appropriate for the long SRT sludge to anaerobic digestion under thermophilic condition and lower TSC. So, thermophilic anaerobic digestion with lower TSC might be an alternative approach for the treatment and resource utilization of long SRT sludge.

Abstract The quality of images generated by computer graphics rendering algorithms is mainly affected by visible distortion at some pixel locations. Image quality assessment (IQA) metrics are commonly utilized to assess the quality of rendered images, but their results are a global difference value, which does not provide pixel‐wise differences to optimize the renderings. In contrast, visibility difference models including visual perception models and deep learning models can calculate pixel‐wise visibility difference between distorted images and reference images. However, they either are only applied to a single type of visible distortion or are seriously dependent on datasets. To this end, the authors propose a novel model, dubbed Human Visual Perception and Deep Learning Image Difference Metric (HPDL‐IDM), which combines the Human Visual System (HVS) model and deep learning. HPDL‐IDM primarily consists of two modules: (i) the visual perception feature calculation module, which calculates difference maps between various kinds of features extracted from the reference image and the distorted image according to the visual characteristics of human eyes and concatenates them, and (ii) the deep learning module, which utilizes a neural network of encoder–decoder structure to train on the LocvisVC and VisTexRes datasets whose input and output are these concatenated feature difference maps and the final image distortion visibility difference map respectively. Additionally, the authors pool the final difference map into a global difference value between 0 and 1 to apply their model to many image processing tasks related to Image quality metrics (IQMs). Experimental results show that HPDL‐IDM's generalization capacity and accuracy are improved by a large margin compared to other models.

Abstract YTHDF1 is a well-characterized m6A reader protein that is essential for protein translation, stem cell self-renewal, and embryonic development. YTHDF1 regulates target gene expression by diverse molecular mechanisms, such as promoting protein translation or modulating the stability of mRNA. The cellular levels of YTHDF1 are precisely regulated by a complicated transcriptional, post-transcriptional, and post-translational network. Very solid evidence supports the pivotal role of YTHDF1 in embryonic development and human cancer progression. In this review, we discuss how YTHDF1 influences both the physiological and pathological biology of the central nervous, reproductive and immune systems. Therefore we focus on some relevant aspects of the regulatory role played by YTHDF1 as gene expression, complex cell networking: stem cell self-renewal, embryonic development, and human cancers progression. We propose that YTHDF1 is a promising future cancer biomarker for detection, progression, and prognosis. Targeting YTHDF1 holds therapeutic potential, as the overexpression of YTHDF1 is associated with tumor resistance to chemotherapy and immunotherapy.

Abstract Ischemic stroke (IS) has become a cerebrovascular disease of widespread concern. Overexpression of circUCK2 alleviates neuronal damage in IS. However, the specific regulatory mechanisms of circUCK2 are not fully understood. In this study, we found that circUCK2 and HECT domain E3 ubiquitin ligase 1 (HECTD1) were downregulated in IS models in vitro and in vivo. Overexpression of circUCK2 or HECTD1 inhibited endothelial‐mesenchymal transition (EndoMT) and protected the blood–brain barrier (BBB) in transient middle cerebral artery occlusion mice from damage. It was further discovered that circUCK2 regulated HECTD1 expressions by interacting with fused in sarcoma (FUS). Moreover, FUS overexpression partially restored the effect of circUCK2 on EndoMT, and overexpression of HECTD1 weakened the effect of FUS on EndoMT. Collectively, circUCK2 upregulates the expression of HECTD1 by combining with FUS and inhibits EndoMT to alleviate BBB damage in IS both in vivo and in vitro.

Abstract Background Numerous pre-clinical studies showed that Qingda granule (QDG) was effective in treating hypertension. This study aims to evaluate the efficacy and safety of QDG in reducing blood pressure among patients with grade 1 hypertension at low-medium risk. Methods The study is designed as a randomized, multi-center, double-blinded, non-inferiority clinical trial. Five hundred fifty-two patients with grade 1 hypertension at low-medium risk from 13 hospitals will be recruited and randomly assigned to the QDG group (n = 276, treated with valsartan capsule simulation agent and QDG) or control group (n = 276, treated with valsartan capsule and QDG simulation agent). The treatment period will be 4 weeks and the follow-up period will last 4 weeks after treatment. Primary outcome will be a decreased value of systolic blood pressure and diastolic blood pressure after treatment. And second outcome will include the decreased value of diastolic blood pressure and systolic blood pressure at the end of follow-up, the percentage of participants achieving normal blood pressure at the end of treatment and follow-up, the Hamilton Anxiety Scale and TCM syndrome scores at the end of treatment and follow-up, and levels of hypertensive hormones at end of treatment and follow-up. Discussion This study will provide initial evidence regarding the clinical efficacy and safety of QDG in treating grade 1 hypertension at low-medium risk. Trial registration Chinese Clinical Trial Registry ChiCTR2000033890 . Registered on 15 June 2020.

Abstract Background An increasing number of studies have shown that microRNAs play an important role in the occurrence and development of small cell lung cancer, which mainly manifest as oncogenic and tumor inhibition. Therefore, microRNAs may affect the survival of patients with small cell lung cancer. In this meta-analysis, we will evaluate the role of microRNAs in the overall survival of patients with small cell lung cancer, which may provide valuable information for the treatment of small cell lung cancer. Methods We searched the PubMed, Embase, and Web of Science online databases to determine the effect of microRNAs on the prognosis of patients with small cell lung cancer. The data and characteristics of each study were extracted, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the effect. Results A total of 7 articles, involving 427 subjects and 15 studies, were included in this meta-analysis. The pooled HR of the relationship between the microRNA expression level and the overall survival rate of small cell lung cancer patients was 1.25 (95% CI: 1.06–1.47). There was a significant difference in the prognostic value of oncogenic and tumor inhibition microRNAs among patients with small cell lung cancer, with pooled HRs of 1.60 (95% CI: 1.35–1.90) and 0.42 (95% CI: 0.30–0.57), respectively. Conclusions MicroRNAs have a significant impact on the overall survival of small cell lung cancer patients, suggesting that microRNAs can be used as potential prognostic markers and may provide treatment strategies for small cell lung cancer patients. Trial registration The protocol was registered on PROSPERO website with the registration number of CRD42022334363. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced .

Soft pneumatic grippers can grasp soft or irregularly shaped objects, indicating potential applications in industry, agriculture, and healthcare. However, soft grippers rarely carry heavy and dense objects due to the intrinsic low modulus of soft materials in nature. This paper designed a soft robotic gripper with rigid supports to enhance lifting force by 150 ± 20% in comparison with that of the same gripper without supports, which successfully lifted a metallic wrench (672 g). The soft gripper also achieves excellent adaptivity for irregularly shaped objects. The design, fabrication, and performance of soft grippers with rigid supports are discussed in this paper.

Aeolian sediments accumulated along the desert-loess transition zone of the Tengger Desert include heterogeneous textures and complex component structures in their grain-size distributions (GSD). However, the sources of these aeolian sediments have not been resolved due to the lack of large reference GSD sample datasets from adjacent regions that contain various types of sediments; such datasets could be used for fingerprinting based on grain-size properties. This lack of knowledge hinders our understanding of the mechanism of aeolian dust releases in these regions and the effects of forcing of atmospheric circulations on the transportation and accumulation of sediments in this region. In this study, we employed a multi-scale grain-size analysis method, i.e., a combination of the single-sample unmixing (SSU) and the parametric end-member modelling (PEMM) techniques, to resolve the component structures of sediments that had accumulated along the desert-loess transition zone of the Tengger Desert. We have also analyzed the component structures of GSDs of various types of sediments, including mobile and fixed sand dunes, lake sediments, and loess sediments from surrounding regions. Our results demonstrate that the patterns observed in coarser fractions of sediments (i.e., sediments with a mode grain size of >100 μm) from the transition zone match well with the patterns of component structures of several types of sediments from the interior of the Tengger Desert, and the patterns seen in the finer fractions (i.e., fine, medium, and coarse silts with a modal size of

Pellet ore is an important raw material for blast furnace ironmaking, and its reduction and expansion performance directly affects the smooth operation and smelting indicators of the blast furnace. This paper quantitatively studied the effects of magnesium minerals such as dolomite and serpentinite on the pellet-forming performance, the microstructure after roasting, compressive strength, and the reduction expansion performance of Baiyun Ebo iron concentrate. The optimal ratio of dolomite and serpentinite to add was determined when preparing pellets using Baiyun Ebo iron concentrate powder. The results showed that the drop strength and compressive strength of the green pellet after adding serpentine were relatively higher than those after adding dolomite, indicating that controlling the MgO content in the green pellet at 2.5% using serpentine was beneficial for improving the drop strength and compressive strength. Under the condition of adding dolomite, when the MgO content was 2.5%, the compressive strength of the roasted pellet was the highest, which was 2192.6 N, and the volume expansion rate was 12.32%. Under the condition of adding serpentine, when the MgO content was 2.5%, the compressive strength of the roasted pellet was 2622.2 N, and the volume expansion rate was 9.71%. Compared with dolomite as a magnesium additive, when the reduction expansion rate of Baiyun Ebo iron concentrate was controlled within 20%, serpentine only needed to have a MgO content of about 1.5% in the pellets, while dolomite needed to have a MgO content of about 2.5%. Therefore, under the condition that the MgO contents of dolomite and serpentine were equivalent, the amount of serpentine used was lower.

The timely identification of rail internal defects and the application of corresponding preventive measures would greatly reduce catastrophic failures, such as rail breakage. Ultrasonic rail defect detection is the current mainstream rail defect detection method thanks to its advantages of strong penetration, high accuracy, and ease to deploy. The 2D B-scan image output by ultrasonic detectors contains rich features of defects; however, rail engineers manually identify and localize the defect image, which can be time-consuming, and the image may be subject to missing identification or mistakes. This paper adopted state-of-the-art deep learning algorithms for novel B-scan images for the automatic identification and localization of rail internal tracks. First, through image pre-processing of classification, denoising, and augmentation, four categories of defect image datasets were established, namely crescent-shaped fatigue cracks, fishbolt hole cracks, rail web cracks, and rail base transverse cracks; then, four representatives of deep learning object detection networks, YOLOv8, YOLOv5, DETR, and Faster R-CNN, were trained with the defects dataset and further applied to the testing dataset for defect identification; finally, the performances of the three detection networks were compared and evaluated at the data level, the network structure level, and the interference adaptability level, respectively. The results show that the YOLOv8 network can effectively classify and localize four categories of internal rail defects in B-scan images with a 93.3% mean average precision at three images per second, and the detection time is 58.9%, 376.8%, and 123.2% faster than YOLO v5, DETR, and Faster R-CNN, respectively. The proposed approach could ensure the real-time, accurate, and efficient detection and analysis of internal defects to a rail.

Background: Qing Hua Chang Yin (QHCY) is a famous formula of traditional Chinese medicine (TCM) and has been proven to have protective effect on ulcerative colitis. However, its protective effect and potential therapeutic mechanisms in chronic colitis remain unclear. The purpose of this study is to explore the effects and underlying mechanisms of QHCY on dextran sulfate sodium (DSS)-induced chronic colitis mice model.Methods: The chronic colitis model was established by administration of 2% DSS for three consecutive cycles of 7 days with two intervals of 14 days for recovery by drinking water. The experiment lasted 49 days. The DSS + QHCY group received QHCY administration by oral gavage at doses of 1.6 g/kg/d, DSS + Mesalazine group was administrated Mesalazine by oral gavage at doses of 0.2 g/kg/d. The control and DSS group were given equal volume of distilled water. The body weight, stool consistency and blood in stool were monitored every 2 days. The disease activity index (DAI) was calculated. The colon length was measured after the mice were sacrificed. The histomorphology of colonic tissues was checked by the HE and PAS staining. Immunohistochemistry was performed to detect the expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), tight junction proteins (ZO-1, occludin) and Mucin2 (MUC2). 16S rRNA sequencing analysis was conducted to study the diversity and abundance of gut microbiota changes.Results: QHCY treatment not only significantly attenuated DSS-induced the weight loss, DAI score increase, colon shortening and histological damage in mice, but also decreased the expression of pro-inflammatory cytokines in colonic tissues and increased the expression of ZO-1, occludin, and MUC2. Furthermore, QHCY enhanced the diversity of gut microbes and regulated the structure and composition of intestinal microflora in mice with chronic colitis.Conclusion: QHCY has a therapeutic effect on a murine model of chronic colitis. It can effectively reduce the clinical and pathological manifestations of colitis and prevent alterations in the gut microbiota.

This paper describes experimental and theoretical investigations on behaviour of short bamboo scrimber box columns under compression. In the experimental programme, six groups of short columns with different width-to-thickness ratios of plates were tested and the load capacity and failure modes of the columns were determined. Test results indicated that when the width-to-thickness ratio of plates was less than or equal to 10, box columns exhibited compression failure and the ultimate compressive strength of bamboo scrimber was reached at failure. However, local buckling of bamboo scrimber plates was observed instead of compression failure once the width-to-thickness ratio of plates exceeded 11, and the ultimate compressive stress decreased with increasing width-to-thickness ratio. Based on the experimental data, theoretical analyses were also performed by considering the nonlinear stress-strain relationship to quantify the buckling stress of bamboo scrimber plates with four simply-supported edges. Comparisons between experimental and theoretical results suggest that when the theoretical equation yields reasonably good estimations of the local buckling stress of columns with the width-to-thickness ratio of plates greater than 10.

Background: 5-Fluorouracil (5-FU) is one of the most commonly prescribed anticancer agents. However, intestinal mucositis is a well-known adverse event, which limits its therapeutic use. Refined Baohe formula (RBF) is derived from Baohe Pills with a potent gastrointestinal protective effect. However, the effects of RBF on 5-FU-induced intestinal mucositis remain unknown. Thus, this study investigated the effects and mechanism of RBF on 5-FU-induced intestinal mucositis in a CT-26 xenograft mice colorectal cancer (CRC) model. Methods: The composition of the RBF preparation was analyzed by high-pressure liquid chromatography. CT-26 cells bearing mice were intraperitoneally administered 150 mg/kg of 5-FU on day 1 to construct a 5-FU-induced intestinal injury model. Mice in the 5-FU + RBF group were intragastrically administrated with RBF (12.4 g/kg) for 4 days. Tumor volume and weight were determined, body weight and diarrhea scores were monitored, leukocytes were calculated, and hematoxylin-eosin staining, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to investigate the therapeutic efficiency and underlying mechanisms of RBF on 5-FU-induced intestinal mucositis mice. Results: RBF didn`t affect the effect of tumor suppression, while attenuated diarrhea associated with 5-FU-induced intestinal mucositis and significantly reduced leucocyte toxicity. Additionally, RBF significantly promoted cell proliferation and inhibited cell apoptosis, and up-regulated CDK4, c-Myc, and B-cell lymphoma-2 expression, while down-regulated Bax expression, as well as enhanced both p-AKT and AKT expression in intestinal crypts of 5-FU-treated mice. Conclusions: RBF attenuated 5-FU-induced intestinal mucositis by inhibiting apoptosis and promoting cell proliferation by modulating the AKT pathway and its downstream effectors in a CT-26 xenograft mouse CRC model.

Introduction. Urotensin II (U II) is a kind of active peptide with a variety of biological effects, such as promoting cell proliferation and endocrine effects. The aim of this study is to investigate the effect of urotensin II on the proliferation and secretion of vascular endothelial growth factor (VEGF) in cultured rat dermal papilla cells (DPCs), and to explore its molecular mechanism. Materials and Methods. We used the DPCs isolated from the thoracic aortas of Wistar-Kyoto rats to run the CCK8 and ELISA assay, RC-PCR and Western blotting techniques to identify the effect of Urotensin II on the proliferation and secretion of VEGF in DPCs, data were analyzed by one-way ANOVA or t-test. Results. U II can increase the mRNA expression of proliferation markers Ki67 and PCNA. In addition, the Wnt/β-catenin pathway was activated by U II, but Wnt inhibitor DKK1 reversed the effect of U II. Conclusions. U II promoted the proliferation and secretion of VEGF in rat DPCs through activation of the Wnt-β-catenin signaling pathway.

ObjectiveThis study aims to investigate the distribution and drug resistance of bacteria in clinical blood culture specimens from children in Jiangxi province in recent years and to provide a foundation for preventing and treating bloodstream infection diseases in children.MethodsThe study involved a statistical analysis of the isolation and drug resistance of bacterial strains obtained from blood culture specimens of children in Jiangxi province between 2017 and 2021. The analysis was performed using the WHONET 5.6 software.ResultsA total of 7,977 bacterial strains were isolated from the blood samples of children between 2017 and 2021. Of these, 2,334 strains (29.3%) were identified as Gram-negative bacteria, and 5,643 strains (70.7%) were identified as Gram-positive bacteria. The most commonly isolated pathogens were coagulase-negative Staphylococcus, Escherichia coli, and Staphylococcus aureus. Among the Gram-negative bacteria, Escherichia coli (840 strains, 36.0%), Klebsiella pneumoniae (385 strains), Salmonella (283 strains), Acinetobacter baumannii (137 strains), and Pseudomonas aeruginosa (109 strains) were the most prevalent. Among the Gram-positive bacteria, coagulase-negative Staphylococcus (3,424 strains, 60.7%), Staphylococcus aureus (679 strains), Streptococcus pneumoniae (432 strains), Enterococcus sp. (292 strains), and Streptococcus agalactiae (192 strains) were the most common. Resistance to third-generation cephalosporins (cefotaxime/ceftriaxone) was observed in 45.9% and 56.0% of Escherichia coli and Klebsiella pneumoniae strains, respectively, while resistance to carbapenems was observed in 4.6% and 20.3% of these strains, respectively. Resistance to third-generation cephalosporins (cefotaxime/ceftriaxone) was observed in 15.5% of Salmonella strains, while resistance to imipenem was absent. Carbapenem resistance was observed in 17.1% (20/117) and 13% (14/108) of Acinetobacter baumannii and Pseudomonas aeruginosa strains, respectively. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 32.7% of the strains, while methicillin-resistant coagulase-negative Staphylococcus was detected in 64.3% of the coagulase-negative Staphylococcus strains. No Staphylococcus bacteria resistant to vancomycin were detected. Four strains of vancomycin-resistant Enterococcus faecium were detected over the 5-year period, and one strain of linezolid-resistant Enterococcus faecalis was detected.ConclusionGram-positive cocci were the most commonly isolated clinical pathogens in blood specimens from children in Jiangxi province. The composition of the pathogen species showed a slight change over the years. The detection ratios of pathogens varied with age group and season. Although the isolation rate of common carbapenem-resistant Enterobacter bacteria has decreased, it remains high. It is necessary to monitor the antimicrobial resistance of pathogens causing bloodstream infections in children more closely, and antimicrobial agents should be used with caution.

African swine fever (ASF) is a disease that causes severe economic losses to the global porcine industry. As no vaccine or drug has been discovered for the prevention and control of ASF virus (ASFV), accurate diagnosis and timely eradication of infected animals are the primary measures, which necessitate accurate and effective detection methods. In this study, the truncated ASFV I329L (amino acids 70–237), was induced using IPTG and expressed in Escherichia coli cells. The highly antigenic viral protein I329L was used to develop an indirect enzyme-linked immunosorbent assay (iELISA), named I329L-ELISA, which cut-off value was 0.384. I329L-ELISA was used to detect 186 clinical pig serum samples, and the coincidence rate between the indirect ELISA developed here and the commercial kit was 96.77%. No cross-reactivity was observed with CSFV, PRRSV, PCV2, or PRV antibody-positive pig sera, indicating good specificity. Both intra- assay and inter-assay coefficients were below 10%, and the detection sensitivity of the iELISA reached 1:3200. In this study, an iELISA for ASFV antibody detection was developed based on the truncated ASFV I329L protein. Overall, the I329L-ELISA is a user-friendly detection tool that is suitable for ASFV antibody detection and epidemiological surveillance.

Background: Myocardial infarction (MI) is the leading cause of deaths worldwide, triggering widespread and irreversible damage to the heart. Currently, there are no drugs that can reverse ischemic damage to the myocardium and hence, finding novel therapeutic agents that can limit the extent of myocardial damage following MI is crucial. Liensinine (LSN) is a naturally derived bisbenzylisoquinoline alkaloid that is known to exhibit numerous antioxidative and cardiovascular beneficial effects. However, the role of LSN in MI-induced injury and its underlying mechanisms remain unexplored. Purpose: Our study aims to evaluate the cardioprotective effects of LSN following MI and its underlying molecular mechanisms. Methods: We constructed murine models of MI in order to examine the potential cardioprotective effects and mechanisms of LSN in protecting against myocardial ischemic damage both in vivo and in vitro. Results: Administration with LSN strongly protected against cardiac injuries following MI by decreasing the extent of ischemic damage and improving cardiac function. Additionally, LSN was found to be a potent inhibitor of Wnt/β‑catenin signaling pathway. Hence, the beneficial effects of LSN in preventing oxidative and DNA damage following ischemia was due to its ability to inhibit aberrant activation of Wnt/β‑catenin signaling. Conclusions: Our findings reveal for the first time a novel cardioprotective role of LSN during myocardial infarction and most notably, its ability to protect cardiomyocytes against oxidative stress-induced damage via inhibiting Wnt/β-catenin signaling. Our study therefore suggests new therapeutic potential of LSN or plants that contain the natural alkaloid LSN in ischemic heart diseases.

Abstract Background In our previous study, a strain EBS03 with good biocontrol potential was screened out of 48 strains of cotton endophyte Bacillus subtilis by evaluating the controlling effect against cotton Verticillium wilt. However, its mechanism for controlling Verticillium wilt remains unclear. The objective of this study was to further clarify its controlling effect and mechanism against cotton Verticillium wilt. Results The results of confrontation culture test and double buckle culture test showed that the inhibitory effects of EBS03 volatile and nonvolatile metabolite on mycelium growth of Verticillium dahliae were 70.03% and 59.00%, respectively; the inhibitory effects of sporulation and microsclerotia germination were 47.16% and 70.06%, respectively. In the greenhouse test, the EBS03 fermentation broth root irrigation had the highest controlling effect at 87.11% on cotton Verticillium wilt, and significantly promoted the growth of cotton seedlings. In the field experiment, the controlling effect of EBS03 fermentation broth to cotton Verticillium wilt was 42.54% at 60 days after cotton sowing, and the boll number per plant and boll weight in EBS03 fermentation broth seed soaking, root irrigation, and spraying treatments significantly increased by 19.48% and 7.42%, 30.90% and 2.62%, 15.99% and 9.20%, respectively. Furthermore, EBS03 improved the resistance of cotton leaves against the infection of V. dahliae, and induced the outbreak of reactive oxygen species and accumulation of callose. In addition, the results of real time fluorescent quantitative polymerase chain reaction (RT-qPCR) detection showed that EBS03 significantly induced upregulation expression level of defense-related genes PAL, POD, PPO, and PR10 in cotton leaves, enhanced cotton plant resistance to V. dahliae, and inhibited colonization level of this fungal pathogen in cotton. Conclusion Bacillus subtilis EBS03 has a good biological defense capability, which can inhibit the growth and colonization level of V. dahliae, and activate the resistance of cotton to Verticillium wilt, thus increase cotton yield.

Abstract Immune thrombocytopenia (ITP) is an autoimmune disorder, in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia, although the underlying mechanisms remain unclear. Here, we performed single-cell transcriptome profiling of bone marrow CD34+ hematopoietic stem and progenitor cells (HSPCs) to determine defects in megakaryopoiesis in ITP. Gene expression, cell-cell interactions, and transcriptional regulatory networks varied in HSPCs of ITP, particularly in immune cell progenitors. Differentially expressed gene (DEG) analysis indicated that there was an impaired megakaryopoiesis of ITP. Flow cytometry confirmed that the number of CD9+ and HES1+ cells from Lin−CD34+CD45RA− HSPCs decreased in ITP. Liquid culture assays demonstrated that CD9+Lin−CD34+CD45RA− HSPCs tended to differentiate into megakaryocytes; however, this tendency was not observed in ITP patients and more erythrocytes were produced. The percentage of megakaryocytes differentiated from CD9+Lin−CD34+CD45RA− HSPCs was 3-fold higher than that of the CD9− counterparts from healthy controls (HCs), whereas, in ITP patients, the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9− HSPCs. Additionally, when co-cultured with pre-B cells from ITP patients, the differentiation of CD9+Lin−CD34+CD45RA− HSPCs toward the megakaryopoietic lineage was impaired. Further analysis revealed that megakaryocytic progenitors (MkP) can be divided into seven subclusters with different gene expression patterns and functions. The ITP-associated DEGs were MkP subtype-specific, with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation. This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP.

Abstract Background The novel TTC gene, tetratricopeptide repeat domain 39 C (Ttc39c), mainly mediates the interaction between proteins. It is involved in the progression of various tumors. In this study, we determined the effect of Ttc39c on lung adenocarcinoma and found that it might be used as a potential intervention target. Methods We performed a difference analysis of Ttc39c samples from the TCGA database. Transwell experiments were conducted to determine the ability of cell metastasis. Celigo and MTT assays were performed to determine the effect of Ttc39c gene subtraction on cell proliferation. FACS was performed to determine the effect of Ttc39c gene subtraction on apoptosis. Clone-formation experiments were conducted to determine the effect of Ttc39c gene subtraction on cloning ability. Transcriptomics, proteomics, and metabolomics were used to elucidate the enrichment pathway of the Ttc39c gene in the progression of lung adenocarcinoma. Results The expression of Ttc39c increased significantly in lung adenocarcinoma. The proliferation, metastasis, and cloning ability of human lung cancer cells were inhibited, while the apoptosis of cells increased significantly after the depletion of Ttc39c. Our results based on the transcriptomics, proteomics, and metabolomics analyses indicated that Ttc39c might be involved in the progression of lung adenocarcinoma (LUAD) mainly through the metabolic pathway and the p53 pathway. Conclusion To summarize, Ttc39c strongly regulates the proliferation and metastasis of lung adenocarcinoma cells. The main pathways involved in Ttc39c in lung adenocarcinoma include the energy metabolism and p53 pathways.

Abstract Supercapacitors undergo wide terminal voltage fluctuations, which makes it difficult to maintain a stable bus voltage and develop a satisfactory dynamic response. To solve this problem, a fast adaptive bus voltage regulation strategy is proposed in this paper. Firstly, the dual‐loop controller with an external voltage loop and an internal current loop is applied to the supercapacitor energy storage systems. Secondly, an adaptive proportional–integral controller is designed for the outer voltage loop to accommodate the variations of the system characteristics. Furthermore, in order to improve the dynamic response, the set‐point automatic modulation is integrated into the voltage control loop to compensate the stochastic load demanded fluctuations. The simulation and experimental results show that the proposed method ensures the stability of the bus voltage and provides a lower fluctuation and shorter settling time compared with the conventional method.

Abstract Background The diagnostic accuracy of computed tomography (CT)-guided percutaneous core needle biopsy (CNB) for small (≤ 20 mm) ground-glass opacity (GGO) lesions has not been reported in detail. Objectives To evaluate factors that affect the diagnostic accuracy of CT-guided percutaneous CNB for small (≤ 20 mm) GGO pulmonary lesions. Methods From January 2014 to February 2018, 156 patients with a small (≤ 20 mm) GGO pulmonary lesion who underwent CT-guided CNB were enrolled in this study. Factors affecting diagnostic accuracy were evaluated by analyzing patient and lesion characteristics and technical factors. Significant factors were identified by multivariate logistic regression. Results The diagnostic accuracy of CT-guided percutaneous CNB was 90.4% for small (≤ 20 mm) GGO pulmonary lesions. The diagnostic accuracy was higher for larger lesions (72.5% for lesions ≤ 10 mm, 96.6% for lesions between 11 and 20 mm [P 90% GGO components and 97.2% for lesions with 50–90% GGO components (P 90% GGO components; 95% CI: 1.4 to 25.7). Conclusions Lesion size and GGO component are factors affecting diagnostic accuracy. The diagnostic accuracy was higher for larger lesions and lesions with 50–90% GGO components.

Abstract Background DNA N4-methylcytosine is part of the restrictive modification system, which works by regulating some biological processes, for example, the initiation of DNA replication, mismatch repair and inactivation of transposon. However, using experimental methods to detect 4mC sites is time-consuming and expensive. Besides, considering the huge differences in the number of 4mC samples among different species, it is challenging to achieve a robust multi-species 4mC site prediction performance. Hence, it is of great significance to develop effective computational tools to identify 4mC sites. Results This work proposes a flexible deep learning-based framework to predict 4mC sites, called Hyb4mC. Hyb4mC adopts the DNA2vec method for sequence embedding, which captures more efficient and comprehensive information compared with the sequence-based feature method. Then, two different subnets are used for further analysis: Hyb_Caps and Hyb_Conv. Hyb_Caps is composed of a capsule neural network and can generalize from fewer samples. Hyb_Conv combines the attention mechanism with a text convolutional neural network for further feature learning. Conclusions Extensive benchmark tests have shown that Hyb4mC can significantly enhance the performance of predicting 4mC sites compared with the recently proposed methods.

Abstract Background Exposure to sunlight may decrease the risk of developing Alzheimer’s disease (AD), and visible and near infrared light have been proposed as a possible therapeutic strategy for AD. Here, we investigated the effects of the visible, near infrared and far infrared (FIR) light on the cognitive ability of AD mice, and found that FIR light also showed potential in the improvement of cognitive dysfunction in AD. However, the related mechanism remains to be elucidated. Methods Morris water maze was used to evaluate the cognitive ability of APPswe/PSEN1dE9 double-transgenic AD mice after light treatment. Western blot was carried out to detect the expression of protein involved in synaptic function and amyloid-β (Aβ) production. The protein amount of interleukin (IL)-1β, IL-6, Aβ1-40 and Aβ1-42 were determined using enzyme-linked immunosorbent assay. The mRNA level of receptors was performed using real-time quantitative polymerase chain reaction. Immunostaining was performed to characterize the Aβ burden and microglial Aβ phagocytosis in the brain of AD mice. The Aβ phagocytosis of primary cultured microglia and BV2 were assessed by flow cytometry. The energy metabolism changes were evaluated using related assay kits, including adenosine triphosphate (ATP), lactate content, mitochondrial respiratory chain complex enzymatic activity and oxidized/reduced nicotinamide adenine dinucleotide assay kits. Results Our results showed that FIR light reduced Aβ burden, a hallmark of AD neuropathology, alleviated neuroinflammation, restored the expression of the presynaptic protein synaptophysin, and ameliorated learning and memory impairment in the AD mice. FIR light enhanced mitochondrial oxidative phosphorylation pathway to increase ATP production. This increased intracellular ATP promoted the extracellular ATP release from microglia stimulated by Aβ, leading to the enhanced Aβ phagocytosis through phosphoinositide 3-kinase/mammalian target of rapamycin pathways for Aβ clearance. Conclusions Our findings have uncovered a previously unappreciated function of FIR light in inducing microglial phagocytosis to clean Aβ, which may be the mechanisms for FIR light to improve cognitive dysfunction in AD mice. These results suggest that FIR light treatment is a potential therapeutic strategy for AD.

Background: Cancer cachexia is a common but severe condition that causes muscle wasting, body weight loss, and progressive functional impairment, affecting over 50% of cancer patients. Currently, there are no effective treatments that can alleviate cachexia, and hence the discovery of new therapeutics that can effectively prevent or even reverse cancer cachexia is crucial. Babao Dan (BBD) is a Traditional Chinese Medicine (TCM) formula that has been used clinically in combating various cancers, however, its therapeutic potential in alleviating cancer cachexia remains unexplored. Our current study aims to determine the anti-cachectic effects of BBD treatment in alleviating cancer cachexia, as well as determining the underlying mechanisms involved. Methods: Mouse models of cancer cachexia were induced via implantation of CT26 colon adenocarcinoma cells, and the anti-cachectic effects and mechanisms of BBD were determined via examinations of body weight and muscle mass, as well as serum and muscle markers of cachexia and muscle atrophy. Results: CT26 tumor implantation reduced in the rapid occurrence of cancer cachexia characterized by marked reductions in body weight and muscle mass, functional decrease in muscle function and accelerated deaths. BBD administration not only demonstrated robust anti-cachectic ability via preventing decreases in body weight, muscle mass, and muscle atrophy, but also markedly prolonged survival. The effects of BBD in alleviating cancer cachexia and its associated adverse effects were due to its ability in preventing the activation of IL-6/STAT3 signaling post-CT26 tumor implantation. Conclusion: Our findings demonstrated the robust ability of BBD in preventing cancer cachexia and alleviating the main cachexia-induced symptoms as well as prolonging survival via inhibiting activation of IL-6/STAT3 signaling pathway. Therefore, our study demonstrating the strong anti-cachectic effects of BBD in mice may provide a theoretical basis for the use of BBD as a safe and effective drug in the treatment of cancer cachexia.

IntroductionPeripheral nerve defect is a difficult disease to treat in clinical practice. End-to-side anastomosis is a useful method to treat it. At present, the end-to-side anastomosis method does not involve the proximal nerve, which results in a waste of proximal donor nerves, and even the formation of traumatic neuromas at the proximal end. The patients suffer from traumatic neuralgia and the curative effect is unsatisfactory.MethodsIn this study, an improved end-to-side anastomosis technique was proposed in this study: both the proximal and distal ends of the damaged common peroneal nerve were sutured to an adjacent normal tibial nerve. Moreover, the possible role and mechanism of the proposed technique were explained at the physiological and anatomical levels. In this study, a 10 mm common peroneal nerve defect was made in SD rats, and the rats were randomly divided into three groups. In Group I, the distal end of the common peroneal nerve was attached end-to-side to the fenestrated tibial nerve adventitia, and the proximal end was ligated and fixed in the nearby muscle. In Group II, the tibial nerve adventitia was fenestrated and the epineurial end-to-end anastomosis surgery was performed to suture the proximal and distal ends of the common peroneal nerve. Rats in Group III were taken as control and received sham operation. Twelve weeks after the operation, the recovery of the repaired nerve and distal effector functions were examined by the sciatic functional index, electrophysiology, osmic acid staining, the muscle wet weight ratio, and the muscle fiber cross-sectional area.ResultsIt was found that these results in Group II were similar to those in Group III, but better than those in Group I. Through retrograde tracing of neurons and Electrophysiological examination in Group II, the study also found that the proximal common peroneal nerve also could establish a connection with tibialis anterior, even gastrocnemius.DiscussionTherefore, it is inferred that fostering both the proximal and distal ends of defective peripheral nerves on normal peripheral nerves using the end-to-side anastomosis technique is a more effective approach to repairing injured nerves.

Abstract Background Cigarette smoking (CS) is a strong risk factor for idiopathic pulmonary fibrosis (IPF). It can activate lung fibroblasts (LF) by inducing redox imbalance. We previously showed that clearing mitochondrial reactive oxygen species (mtROS) protects against CS-induced pulmonary fibrosis. However, the precise mechanisms of mtROS in LF need further investigation. Here we focused on mtROS to elucidate how it was regulated by CS in LF and how it contributed to LF activation. Methods We treated cells with 1% cigarette smoking extract (CSE) and examined mtROS level by MitoSOX™ indicator. And the effect of CSE on expression of SIRT1, SOD2, mitochondrial NOX4 (mtNOX4), fatty acid oxidation (FAO)-related protein PPARα and CPT1a and LF activation marker Collagen I and α-SMA were detected. Nile Red staining was performed to show cellular lipid content. Then, lipid droplets, autophagosome and lysosome were marked by Bodipy 493/503, LC3 and LAMP1, respectively. And lipophagy was evaluated by the colocalization of lipid droplets with LC3 and LAMP1. The role of autophagy on lipid metabolism and LF activation were explored. Additionally, the effect of mitochondria-targeted ROS scavenger mitoquinone and SIRT1 activator SRT1720 on mitochondrial oxidative stress, autophagy flux, lipid metabolism and LF activation were investigated in vitro and in vivo. Results We found that CS promoted mtROS production by increasing mtNOX4 and decreasing SOD2. Next, we proved mtROS inhibited the expression of PPARα and CPT1a. It also reduced lipophagy and upregulated cellular lipid content, suggesting lipid metabolism was disturbed by CS. In addition, we showed both insufficient FAO and lipophagy resulted from blocked autophagy flux caused by mtROS. Moreover, we uncovered decreased SIRT1 was responsible for mitochondrial redox imbalance. Furthermore, we proved that both SRT1720 and mitoquinone counteracted the effect of CS on NOX4, SOD2, PPARα and CPT1a in vivo. Conclusions We demonstrated that CS decreased SIRT1 to activate LF through dysregulating lipid metabolism, which was due to increased mtROS and impaired autophagy flux. These events may serve as therapeutic targets for IPF patients.

Abstract Background The diversified and high value-added utilization of cotton by products can promote the sustainable development of modern agriculture. Differences in potential nutrients among varieties can be explained by variations in the composition and abundance of fatty acids, polyphenols, carbohydrates, amino acids, and organic acids. Therefore, the analysis of metabolite species and relationships in cottonseed is meaningful for the development of cotton byproducts. Results In this study, the metabolomes of three representative cotton cultivars of different species were compared using untargeted GC-TOF/MS analysis. A total of 263 metabolites were identified from 705 peaks, and their levels were compared across cultivars. Principal component analysis and OPLS-DA clearly distinguish these samples based on metabolites. There were significant differences in the contents of amino acids, carbohydrates, organic acids, flavonoids, and lipids in G. hirsutum TM-1 compared with G. arboreum Shixiya1 and G. barbadense Hai7124. Notably, the bioactive nutrient compound catechin obtained from the differential metabolites significantly accumulated in TM-1. Furthermore, a comprehensive analysis using catechin and oil-related traits was conducted in core collections of Gossypium hirsutum. The results revealed the reliability of the GC-TOF/MS analysis, as well as that catechin content has a negative association with myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, and total fatty acids. Conclusion These findings suggest that untargeted GC-TOF/MS analysis could provide a new method for investigating the underlying plant biochemistry of nutrient variation in cottonseed, and that catechin content has a negative association with oil-related traits in cottonseed. This study may pave the way to exploit the value of cotton byproducts.

Platelets regulate multiple aspects of CD4+ T cell immunity, and may exert distinct regulations among different T cell subsets. Our aim was to investigate how platelets regulate CD4+ central memory T cell (Tcm) responses. αCD3/αCD28-stimulated human CD4+ Tcm cells were cultured without or with platelets or platelet-derived mediators. Polyclonal stimulation induced cell proliferation and Th1 and Treg cell activation of Tcm cells. Platelet factor 4/PF4 neutralization abolished platelet-enhanced Tcm effector responses, whilst TGFβ neutralization only partially inhibited platelet-enhanced Treg cell activation. PF4 supplementation mimicked the effects of platelet co-cultures, while PF4 receptor CXCR3 blockade and CXCR3 knockdown with siRNAs inhibited or abolished PF4-enhanced Th1 and Treg cell responses. Platelet co-cultures or PF4-treatment increased Tcm cell proliferation, whilst CXCR3 blockade counteracted. PF4-enhanced Tcm proliferation and effector cell responses were associated with mitochondrial biogenesis. Overexpression of mitochondrial transcription factor A (TFAM) mimicked PF4 effects, and PF4 treatment attenuated Akt phosphorylation of activated Tcm cells, leading to mitochondrial biogenesis. Impacts of platelets and PF4 on Tcm proliferation were further confirmed by that CXCR3 knockdown/blockade counteracted PF4-enhanced Tcm cell proliferation. In conclusion, platelets enhance Th1 and Treg cell responses of CD4+ Tcm cells, via PF4-dependent mitochondrial biogenesis and cell proliferation of Tcm cells.

BackgroundCandida albicans is a commensal yeast that may cause life-threatening infections. Studies have shown that the cytochrome b-c1 complex subunit 7 gene (QCR7) of C. albicans encodes a protein that forms a component of the mitochondrial electron transport chain complex III, making it an important target for studying the virulence of this yeast. However, to the best of our knowledge, the functions of QCR7 have not yet been characterized.MethodsA QCR7 knockout strain was constructed using SN152, and BALb/c mice were used as model animals to determine the role of QCR7 in the virulence of C. albicans. Subsequently, the effects of QCR7 on mitochondrial functions and use of carbon sources were investigated. Next, its mutant biofilm formation and hyphal growth maintenance were compared with those of the wild type. Furthermore, the transcriptome of the qcr7Δ/Δ mutant was compared with that of the WT strain to explore pathogenic mechanisms.ResultsDefective QCR7 reduced recruitment of inflammatory cells and attenuated the virulence of C. albicans infection in vivo. Furthermore, the mutant influenced the use of multiple alternative carbon sources that exist in several host niches (GlcNAc, lactic acid, and amino acid, etc.). Moreover, it led to mitochondrial dysfunction. Furthermore, the QCR7 knockout strain showed defects in biofilm formation or the maintenance of filamentous growth. The overexpression of cell-surface-associated genes (HWP1, YWP1, XOG1, and SAP6) can restore defective virulence phenotypes and the carbon-source utilization of qcr7Δ/Δ.ConclusionThis study provides new insights into the mitochondria-based metabolism of C. albicans, accounting for its virulence and the use of variable carbon sources that promote C. albicans to colonize host niches.

IntroductionAfrican swine fever virus (ASFV) infection is one of the most complex and fatal hemorrhagic viral diseases, causing a devastating loss to the swine industry. Since no effective vaccine is available, prevention and control of ASFV heavily depends on early diagnostic detection.MethodsIn this study, a novel indirect ELISA was established for detecting antibodies against ASFV using dual-proteins, p22 and p30. Recombinants p22 and p30 were expressed and purified from E.coli vector system by recombined plasmids pET-KP177R and pET-CP204L. p22 and p30 were mixed as antigens for developing the indirect ELISA.ResultsThrough optimizing coating concentrations of p30 and p22, coating ratio (p30: p22 = 1:3), and serum dilution (as 1:600), the established ELISA performed higher specificity, sensitivity, and repeatability against ASFV-positive serum. Furthermore, 184 clinical serum samples from suspected diseased pigs were verified the established ELISA in clinical diagnosis. The results showed that compared with two commercial ELISA kits, the established ELISA possessed higher sensitivity and almost uniform coincidence rate.ConclusionThe novel indirect ELISA based on dual-proteins p30 and p22 performed a valuable role in diagnostic detection of ASFV, providing a broad insight into serological diagnostic methods of ASFV.

Abstract Constructing a conductive carbon‐based artificial interphase layer (AIL) to inhibit dendritic formation and side reaction plays a pivotal role in achieving longevous Zn anodes. Distinct from the previously reported carbonaceous overlayers with singular dopants and thick foreign coatings, a new type of N/O co‐doped carbon skin with ultrathin feature (i.e., 20 nm thickness) is developed via the direct chemical vapor deposition growth over Zn foil. Throughout fine‐tuning the growth conditions, mosaic nanocrystalline graphene can be obtained, which is proven crucial to enable the orientational deposition along Zn (002), thereby inducing a planar Zn texture. Moreover, the abundant heteroatoms help reduce the solvation energy and accelerate the reaction kinetics. As a result, dendrite growth, hydrogen evolution, and side reactions are concurrently mitigated. Symmetric cell harvests durable electrochemical cycling of 3040 h at 1.0 mA cm−2/1.0 mAh cm−2 and 136 h at 30.0 mA cm−2/30.0 mAh cm−2. Assembled full battery further realizes elongated lifespans under stringent conditions of fast charging, bending operation, and low N/P ratio. This strategy opens up a new avenue for the in situ construction of conductive AIL toward pragmatic Zn anode.

Background: Neferine exhibits therapeutic effects on anti-hypertension. However, the effect of neferine on hypertensive vascular remodeling remains unexplored. Therefore, the current study was to investigate the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms. Methods: Total 30 male spontaneously hypertensive rats (SHRs) were divided randomly into five groups, including SHR, Neferine-L (2.5 mg/kg/day), Neferine-M (5 mg/kg/day), Neferine-H (10 mg/kg/day), and Valsartan (10 mg/kg/day) groups (n = 6 for each group). Wistar Kyoto (WKY) rats were set as control group (n = 6). Noninvasive blood pressure system, ultrasound, hematoxylin and eosin staining, masson trichrome staining were used to detect the blood pressure, pulse wave velocity (PWV), pathological changes and collagen content in abdominal aortas of SHRs. RNA-sequencing and immunohistochemistry(IHC) analyses were used to identify and verify the differentially expressed transcripts and activation of associated signaling pathways in SHRs. Results: Various concentrations of neferine or valsartan treatment substantially reduced the elevation of blood pressure, PWV, and abdominal aortic thickening of SHRs. RNA-sequencing and KEGG analyses recognized 441 differentially expressed transcripts and several enriched pathways (including PI3K/AKT and TGF-β/Smad2/3 signaling pathways) after neferine treatment. Masson trichromatic staining and IHC analysis demonstrated that neferine treatment decreased the collagen content and down-regulated the protein expression of PCNA, collagen I & III, and fibronectin, as well as p-PI3K, p-AKT, TGF-β1 and p-Smad2/3 in abdominal aortic tissues of SHRs. Conclusion: Neferine treatment exhibits therapeutic effects on anti-hypertension and reduces vascular remodeling, as well as suppresses the abnormal activation of multiple signaling pathways, including PI3K/AKT and TGF-β1/Smad2/3 pathways.

Liver-expressed antimicrobial peptide 2 (LEAP-2) is an important component of innate immunity, a well-conserved, evolutionarily ancient host defensive mechanism. In this study, three novel full-length LEAP-2 cDNAs were identified and characterized from G. zanaensis. The deduced precursors of GzLEAP-2A, GzLEAP-2B and GzLEAP-2 C, are composed of 94, 74, and 83 amino acids, which possess four, three, and four conserved cysteine residues in the mature peptide, respectively. GzLEAP-2 s are highly conserved in evolution, with GzLEAP-2A and GzLEAP-2 C showing a close topologic relationship with LEAP-2 from Ictalurus furcatus and Danio rerio, respectively. Quantitative real-time polymerase chain reaction analysis indicated that GzLEAP-2 s ubiquitously existed in all examined tissues, with higher mRNA expression levels observed in muscle, intestine, and liver. Antimicrobial assay showed that synthetic GzLEAP-2A and GzLEAP-2B displayed specific antimicrobial activity against aquatic strains, whereas GzLEAP-2 C did not show any detectable antimicrobial activity. All GzLEAP-2 s were found to possess potent 2,2-diphenyl-1-picrythydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)+ radical scavenging activities, and high doses of GzLEAP-2B and GzLEAP-2 C pre-treatment significantly promoted macrophage phagocytic activity. Moreover, no toxicity of GzLEAP-2 s against tested cells was observed at the effective concentrations. The distinct tissue distribution and pleiotropic roles of GzLEAP-2 s suggest a sophisticated and multilevel antimicrobial defensive network of G. zanaensis.

Summary: Background: Immune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in randomised controlled trials (RCTs). We aimed to compare the efficacy and safety of different treatments in newly diagnosed adult primary immune thrombocytopenia. Methods: We did a systematic review and network meta-analysis of RCTs involving treatments for newly diagnosed primary immune thrombocytopenia. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched up to April 31, 2022. The primary outcomes were 6-month sustained response and early response. Secondary outcome was grade 3 or higher adverse events. This study is registered with PROSPERO (CRD42022296179). Findings: Eighteen RCTs (n = 1944) were included in this study. Pairwise meta-analysis showed that the percentage of patients achieving early response was higher in the dexamethasone-containing doublet group than in the dexamethasone group (79.7% vs 68.7%, odds ratio [OR] 1.82, 95% CI 1.10–3.02). The difference was more profound for sustained response (60.5% vs 37.4%, OR 2.57, 95% CI 1.95–3.40). Network meta-analysis showed that dexamethasone plus recombinant human thrombopoietin ranked first for early response, followed by dexamethasone plus oseltamivir or tacrolimus. Rituximab plus prednisolone achieved highest sustained response, followed by dexamethasone plus all-trans retinoic acid or rituximab. Rituximab plus dexamethasone showed 15.3% of grade 3 or higher adverse events, followed by prednis(ol)one (4.8%) and all-trans retinoic acid plus dexamethasone (4.7%). Interpretation: Our findings suggested that compared with monotherapy dexamethasone or prednis(ol)one, the combined regimens had better early and sustained responses. rhTPO plus dexamethasone ranked top in early response, while rituximab plus corticosteroids obtained the best sustained response, but with more adverse events. Adding oseltamivir, all-trans retinoic acid or tacrolimus to dexamethasone reached equally encouraging sustained response, without compromising safety profile. Although this network meta-analysis compared all the therapeutic regimens up to date, more head-to-head RCTs with larger sample size are warranted to make direct comparison among these strategies. Funding: National Natural Science Foundation of China, Major Research Plan of National Natural Science Foundation of China, Shandong Provincial Natural Science Foundation and Young Taishan Scholar Foundation of Shandong Province.

ObjectivesDiabetic retinopathy (DR) is a retinal microvascular disease associated with diabetes. Ferroptosis is a new type of programmed cell death that may participate in the occurrence and development of DR. Therefore, this study aimed to identify the DR ferroptosis-related genes by bioinformatics methods.MethodsThe RNAseq data of DR and healthy control retinas were downloaded from the gene expression synthesis (GEO) database and analyzed using the R package DESeq2. The key modules were obtained using the WGCNA algorithm, and their genes were intersected with ferroptosis-related genes in the FerrDb database to obtain differentially expressed ferroptosis-related genes (DE-FRGs). Enrichment analysis was conducted to understand the function and enrichment pathways of ferroptosis genes in DR, and hub genes were identified by protein-protein interaction (PPI) analysis. The diagnostic accuracy of hub genes for DR was evaluated according to the area under the ROC curve. The TRRUST database was then used to predict the regulatory relationship between transcription factors and target genes, with the mirDIP, ENCORI, RNAnter, RNA22, miRWalk and miRDB databases used to predict the regulatory relationship between miRNAs and target genes. Finally, another data set was used to verify the hub genes.ResultsIn total, 52 ferroptosis-related DEGs (43 up-regulated and 9 down-regulated) were identified using 15 DR samples and 3 control samples and were shown to be significantly enriched in the intrinsic apoptotic signaling pathway, autophagosome, iron ion binding and p53 signaling pathway. Seven hub genes of DR ferroptosis were identified through PPI network analysis, but only HMOX1 and PTGS2 were differentially expressed in another data set. The miRNAs prediction showed that hsa-miR-873-5p was the key miRNA regulating HMOX1, while hsa-miR-624-5p and hsa-miR-542-3p were the key miRNAs regulating PTGS2. Furthermore, HMOX1 and PTGS2 were regulated by 13 and 20 transcription factors, respectively.ConclusionThe hub genes HMOX1 and PTGS2, and their associated transcription factors and miRNAs, may be involved in ferroptosis in diabetic retinopathy. Therefore, the specific mechanism is worthy of further investigation.

A fracture is a severe trauma that causes dramatic pain. Appropriate fracture pain management not only improves the patient’s subjective perception, but also increases compliance with rehabilitation training. However, current analgesics for fracture pain are unsatisfactory because of their negative effects on fracture healing or addiction problems. Bulleyaconitine A (BLA), a non-addictive analgesic medicine, is used for the treatment of chronic pain of musculoskeletal disorders in clinical practice, whereas the effects of BLA on fracture pain is undefined. To evaluate the analgesic effects of BLA on fracture, we generated tibial fracture mice here. It is found that oral administration of BLA to mice alleviates fracture-induced mechanical and thermal hyperalgesia. Interestingly, BLA significantly increases locomotor activity levels and reduces anxiety-like behaviors in fractured mice, as determined by open-field test. Notably, BLA treatment promotes bone mineralization and therefore fracture healing in mice, which may be attributed to the increase in mechanical stimulation caused by exercise. Our study suggests that BLA can be used as a promising analgesic agent for the treatment of fracture pain.

Background: Gastrodin has been widely used clinically in China as an antihypertensive drug. However, its effect on hypertensive renal injury is yet to be elucidated. The current study aimed to investigate the effects of gastrodin on hypertensive renal injury and its underlying mechanisms by network pharmacology analysis and validation in vivo and in vitro.Methods: A total of 10 spontaneously hypertensive rats (SHRs) were randomly categorized into the following two groups: SHR and SHR + Gastrodin groups. Wistar Kyoto (WKY) rats were used as the control group (n = 5). The SHR + Gastrodin group was intragastrically administered gastrodin (3.5 mg/kg/day), and the rats in both WKY and SHR groups were intragastrically administered an equal amount of double-distilled water for 10 weeks. Hematoxylin-eosin, Masson’s trichrome, and Sirius red staining were used to detect the pathological changes and collagen content in the renal tissues. Network pharmacology analysis was performed to explore its potential targets and related pathways. In vitro, the CCK-8 assay was used to determine the cell viability. Immunohistochemistry and western-blotting analyses were employed to assess the protein expression associated with renal fibrosis and transforming growth factor-β1 (TGF-β1) pathway-related proteins in the renal tissues or in TGF-β1-stimulated rat kidney fibroblast cell lines (NRK-49F).Results: Gastrodin treatment attenuates renal injury and pathological alterations in SHRs, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilation. Gastrodin also reduced the accumulation of collagen in the renal tissues of SHRs, which were confirmed by downregulation of α-SMA, collagen I, collagen III protein expression. Network pharmacology analysis identified TGFB1 and SMAD2 as two of lead candidate targets of gastrodin on against hypertensive renal injury. Consistently, gastrodin treatment downregulated the increase of the protein expression of TGF-β1, and ratios of both p-Smad2/Smad2 and p-Samd3/Smad3 in renal tissues of SHRs. In vitro, gastrodin (25–100 μM) treatment significantly reversed the upregulation of α-SMA, fibronectin, collagen I, as well as p-Smad2 and p-Smad3 protein expressions without affecting the cell viability of TGF-β1 stimulated NRK-49F cells.Conclusion: Gastrodin treatment significantly attenuates hypertensive renal injury and renal fibrosis and suppresses TGF-β1/Smad2/3 signaling in vivo and in vitro.

Of the more than 370 000 species of higher plants in nature, fewer than 0.1% can be genetically modified due to limitations of the current gene delivery systems. Even for those that can be genetically modified, the modification involves a tedious and costly tissue culture process. Here, we describe an extremely simple cut–dip–budding (CDB) delivery system, which uses Agrobacterium rhizogene to inoculate explants, generating transformed roots that produce transformed buds due to root suckering. We have successfully used CDB to achieve the heritable transformation of plant species in multiple plant families, including two herbaceous plants (Taraxacum kok-saghyz and Coronilla varia), a tuberous root plant (sweet potato), and three woody plant species (Ailanthus altissima, Aralia elata, and Clerodendrum chinense). These plants have previously been difficult or impossible to transform, but the CDB method enabled efficient transformation or gene editing in them using a very simple explant dipping protocol, under non-sterile conditions and without the need for tissue culture. Our work suggests that large numbers of plants could be amenable to genetic modifications using the CDB method.

ABSTRACT 5-Fluorouracil (5-FU), irinotecan (CPT-11), oxaliplatin (L-OHP), and calcium folinate (CF) are widely used chemotherapeutic drugs to treat colorectal cancer. However, chemotherapeutic use is often accompanied by intestinal inflammation and gut microbiota disorder. Changes in gut microbiota may destroy the intestinal barrier, which contributes to the severity of intestinal injury. However, intestinal injury and gut microbiota disorder have yet to be compared among 5-FU, CPT-11, L-OHP, and CF in detail, thereby limiting the development of targeted detoxification therapy after chemotherapy. In this study, a model of chemotherapy-induced intestinal injury in tumor-bearing mice was established by intraperitoneally injecting chemotherapeutic drugs at a clinically equivalent dose. 16S rRNA gene sequencing was used to detect gut microbiota. We found that 5-FU, CPT-11, and l-OHP caused intestinal injury, inflammatory cytokine (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and IL-6) secretion, and gut microbiota disorder. We established a complex but clear network between the pattern of changes in gut microbiota and degree of intestinal damage induced by different chemotherapeutic drugs. L-OHP caused the most severe damage in the intestine and disorder of the gut microbiota and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Analysis by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt v.1.0) showed that the microbiota disorder pattern induced by 5-FU, CPT-11, and L-OHP was related to the NOD-like signaling pathway. Therefore, we detected the protein expression of the NOD/RIP2/NF-κB signaling pathway and found that L-OHP most activated this pathway. Redundancy analysis/canonical correlation analysis (RDA/CCA) revealed that Bifidobacterium, Akkermansia, Allobaculum, Catenibacterium, Mucispirillum, Turicibacter, Helicobacter, Proteus, Escherichia Shigella, Alloprevotealla, Vagococcus, Streptococcus, and “Candidatus Saccharimonas” were highly correlated with the NOD/RIP2/NF-κB signaling pathway and influenced by chemotherapeutic drugs. IMPORTANCE Chemotherapy-induced intestinal injury limits the clinical use of drugs. Intestinal injury involves multiple signaling pathways and gut microbiota disruption. Our results suggested that the degree of intestinal injury caused by different drugs of the first-line colorectal chemotherapy regimen is related to the pattern of changes in microbiota. The activation of the NOD/RIP2/NF-κB signaling pathway was also related to the pattern of changes in microbiota. l-OHP caused the most severe damage to the intestine and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Thirteen bacterial genera were related to different levels of intestinal injury and correlated with the NOD/RIP2/NF-κB pathway. Here, we established a network of different chemotherapeutic drugs, gut microbiota, and the NOD/RIP2/NF-κB signaling pathway. This study likely provided a new basis for further elucidating the mechanism and clinical treatment of intestinal injury caused by chemotherapy.