The inverted U-shaped relationship between corporate social responsibility and default risk: The role of financing constraints.

With increased corporate liquidity and debt repayment pressure, CSR's "insurance" role has received more attention. We conducted a comprehensive empirical analysis of 4988 listed companies in the Chinese context during 2011-2020. Our research has three findings: First, the initial increase in CSR will lead to a rise in default risk. However, once the CSR level exceeds a specific threshold, the default risk decreases as the CSR rises. We tested the robustness of the results by replacing the explanatory and the explained variables and taking into account the lag time effect, which proved the reliability of our research conclusions. Second, the mediation analysis shows financing constraints play an important mediating role in this inverted U-shaped relationship. On the left side of the U-shape, CSR performance intensifies financing constraints, while on the right side, increasing CSR reduces financing constraints. Finally, we confirm heterogeneity in the impact of CSR on the default risk of different enterprises' ownership and size. Our study complements the current literature on the effects of CSR on default risk. We are making policymakers and stakeholders aware of the importance of mandatory CSR disclosure.

The analgesic effects of Yu-Xue-Bi tablet (YXB) on mice with inflammatory pain by regulating LXA4-FPR2-TRPA1 pathway.

BACKGROUND: Oxylipins including lipoxin A4 (LXA4) facilitate the resolution of inflammation and possess analgesic properties by inhibiting macrophage infiltration and transient receptor potential (TRP) protein expression. Yu-Xue-Bi Tablet (YXB) is a traditional Chinese patent medicine used to relieve inflammatory pain. Our previous research has shown that the analgesic effect of YXB is related to inhibiting peripheral inflammation and regulating macrophage infiltration, but the mechanism is not yet clear. The purpose of this study is to explore the mechanisms of YXB on mice models with Complete Freund's Adjuvant (CFA)-induced inflammatory pain from the perspective at the resolution of inflammation. METHODS: Mechanical allodynia thresholds and heat hypersensitivity were measured using the Von Frey test and the hot plate test respectively. The open field test and the tail suspension test were employed to measure anxiety and depressive behaviors respectively. The expression of CD68+ and the proportion of F4/80+CD11b+ cells were measured by immunofluorescence staining and flow cytometry. The expression of transient receptor potential ankyrin 1(TRPA1) was measured by immunofluorescence staining and western blotting. Oxylipins omics analysis provided quantitative data on oxylipins in the paws, and enzyme linked immunosorbent assay (ELISA) was used to measure the levels of LXA4 there. Immunofluorescence staining was used to perform the expression of Leukotriene A4 hydroxylase (LTA4H) in the paws of mice. The impact of injecting the formyl peptide receptor 2(FPR2) antagonist WRW4 and the TRPA1 agonist AITC into the left paws was observed, focusing on the expression of mechanical allodynia thresholds, the expression of CD68+, TRPA1 in the paws, and Calcitonin gene-related peptide (CGRP) in the L5 spinal dorsal horn. RESULTS: YXB elevated mechanical allodynia thresholds, alleviated heat hypersensitivity and anxiety and depressive behaviors in CFA mice. It significantly reduced the number of CD68+ and proportion of F4/80+CD11b+ within the paws, thereby decreasing macrophage infiltration. Additionally, it diminished the expression of TRPA1 in the paws and TRPV1 in the DRG, leading to an inhibition of peripheral sensitization. Through quantitative analysis, it was found that YXB could modulate DHA-derived oxylipins and LXA4. ELISA results indicated that YXB elevated the levels of LXA4 and inhibited the expression of LAT4H in the paws. Furthermore, the pro-resolution and analgesic effects of YXB were hindered after administration of the FPR2 antagonist. Compared with the AITC group, YXB showed no significant improvement in anti-inflammatory and analgesic effects. CONCLUSIONS: YXB can regulate the oxylipins of paws in CFA mice to promote the resolution of inflammation. The LXA4-FPR2-TRPA1 pathway is a key mechanism for the resolution of inflammation and analgesic effects.

Ultrasound-stimulated microbubbles enhances radiosensitivity in cervical cancer.

BACKGROUND: Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation. METHODS: Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry. RESULTS: USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models. CONCLUSION: In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.

Second-trimester triglyceride-glucose index to predict adverse outcomes in women with gestational diabetes mellitus: A retrospective multicenter cohort study.

AIMS/INTRODUCTION: Women with gestational diabetes mellitus are at high risk for adverse maternal and neonatal outcomes. The study aimed to evaluate the performance of the triglyceride-glucose index in predicting the risk of developing adverse outcomes in women with gestational diabetes mellitus. MATERIALS AND METHODS: This retrospective multicenter cohort study included 8,808 pregnant women with gestational diabetes mellitus in two grade-A tertiary hospitals in China during 2018-2022. The triglyceride-glucose index was defined as ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Significant adverse gestational diabetes mellitus outcomes were chosen by generalized linear models as the main outcomes. Multivariable logistic regression models evaluated their association with the triglyceride-glucose index. Areas under the receiver operating characteristic curves predicted adverse pregnancy outcomes. The prediction efficiency was validated in the sensitivity analysis dataset and validation cohort. RESULTS: The triglyceride-glucose index was associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia before and after adjusting for confounding factors (P < 0.05). The predictive performance of the triglyceride-glucose index was relatively moderate. Incorporating the triglyceride-glucose index into the baseline clinical risk model improved the area under curves for the diagnosis of preeclampsia (0.749 [0.714-0.784] vs 0.766 [0.734-0.798], P = 0.033) and macrosomia (0.664 [0.644-0.685] vs 0.676 [0.656-0.697], P = 0.002). These predictive models exhibited good calibration and robustness. CONCLUSIONS: The triglyceride-glucose index is positively associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia and is useful for the early prediction and prevention of adverse outcomes in women with gestational diabetes mellitus.

Source localization comparison and combination of OPM-MEG and fMRI to detect sensorimotor cortex responses.

BACKGROUND AND OBJECTIVES: The exploration of various neuroimaging techniques have become focal points within the field of neuroscience research. Magnetoencephalography based on optically pumped magnetometers (OPM-MEG) has shown significant potential to be the next generation of functional neuroimaging with the advantages of high signal intensity and flexible sensor arrangement. In this study, we constructed a 31-channel OPM-MEG system and performed a preliminary comparison of the temporal and spatial relationship between magnetic responses measured by OPM-MEG and blood-oxygen-level-dependent signals detected by functional magnetic resonance imaging (fMRI) during a grasping task. METHODS: For OPM-MEG, the ß-band (15-30 Hz) oscillatory activities can be reliably detected across multiple subjects and multiple session runs. To effectively localize the inhibitory oscillatory activities, a source power-spectrum ratio-based imaging method was proposed. This approach was compared with conventional source imaging methods, such as minimum norm-type and beamformer methods, and was applied in OPM-MEG source analysis. Subsequently, the spatial and temporal responses at the source-level between OPM-MEG and fMRI were analyzed. RESULTS: The effectiveness of the proposed method was confirmed through simulations compared to benchmark methods. Our demonstration revealed an average spatial separation of 10.57 ± 4.41 mm between the localization results of OPM-MEG and fMRI across four subjects. Furthermore, the fMRI-constrained OPM-MEG localization results indicated a more focused imaging extent. CONCLUSIONS: Taken together, the performance exhibited by OPM-MEG positions it as a potential instrument for functional surgery assessment.

Cobalt-Catalyzed Borylative Reduction of Azobenzenes to Hydrazobenzenes via a Diborylated-Hydrazine Intermediate.

Cobalt-catalyzed borylative reduction of azobenzenes using pinacolborane is developed. The simple cobalt chloride catalyst and reaction conditions make this protocol attractive for hydrazobenzene synthesis. This borylative reduction shows good functional group compatibility and can be readily scaled up to the gram scale. Preliminary mechanistic studies clarified the proton source of the hydrazine products. This cobalt-catalyzed azobenzene borylative reaction provides a practical protocol to prepare synthetically useful diborylated hydrazines.

Compatible multilayer magnetic field system for quantum sensing with atoms.

Magnetic fields provide a valuable method to manipulate atomic energy levels and interactions in quantum precision measurements, but achieving precise measurements requires collaboration between the magnetic field system and the optical detection system. We propose a magnetic field system that incorporates a fast-switching magnetic field and an alternating magnetic field. Specifically, we enhance the switching speed by making structural improvements during the switching operation. An independent control approach is employed to reduce the switching time caused by electromagnetic induction across the coil using multilayer coils. The results demonstrate an inverse correlation between the rise and fall times of the magnetic field switch and the number of independently stacked coil layers, indicating the possibility of achieving further improvements in switching speed through structural enhancements. The system developed here has considerable potential for application to diverse quantum systems.

The role of corporate governance structures in mediating the relationship between external supervision, credit appraisal measurement, capital adequacy, and performance of commercial banks in Nepal.

This study investigates the role of corporate governance structures as mediators between external supervision, credit appraisal measurement, capital adequacy, and the performance of commercial banks in Nepal. This research sheds light on the significance of effective corporate governance practices within Nepali commercial banks and how certain governance mechanisms may impact bank performance. A quantitative research design was employed, using data from commercial banks in Nepal for this study. Surveys were utilized to collect quantitative data. Structural equation modeling was used as a primary tool to assess the data. The findings add to existing literature about corporate governance and its effects on bank performance in emerging economies such as Nepal. The study's findings offer valuable insights into the significance of corporate governance structures, external supervision, credit appraisal measurement systems, and capital adequacy for commercial banks' performance in Nepal. The research methodology adds value to the existing literature using quantitative data collection methods. Its results may have practical ramifications for banks, regulators, and policymakers, suggesting effective governance practices as essential measures for increasing stability and performance at commercial banks.

LightGBM is an Effective Predictive Model for Postoperative Complications in Gastric Cancer: A Study Integrating Radiomics with Ensemble Learning.

Postoperative complications of radical gastrectomy seriously affect postoperative recovery and require accurate risk prediction. Therefore, this study aimed to develop a prediction model specifically tailored to guide perioperative clinical decision-making for postoperative complications in patients with gastric cancer. A retrospective analysis was conducted on patients who underwent radical gastrectomy at the First Affiliated Hospital of Nanjing Medical University between April 2022 and June 2023. A total of 166 patients were enrolled. Patient demographic characteristics, laboratory examination results, and surgical pathological features were recorded. Preoperative abdominal CT scans were used to segment the visceral fat region of the patients through 3Dslicer, a 3D Convolutional Neural Network (3D-CNN) to extract image features and the LASSO regression model was employed for feature selection. Moreover, an ensemble learning strategy was adopted to train the features and predict postoperative complications of gastric cancer. The prediction performance of the LGBM (Light Gradient Boosting Machine), XGB (XGBoost), RF (Random Forest), and GBDT (Gradient Boosting Decision Tree) models was evaluated through fivefold cross-validation. This study successfully constructed a model for predicting early complications following radical gastrectomy based on the optimal algorithm, LGBM. The LGBM model yielded an AUC value of 0.9232 and an accuracy of 87.28% (95% CI, 75.61-98.95%), surpassing the performance of other models. Through ensemble learning and integration of perioperative clinical data and visceral fat radiomics, a predictive LGBM model was established. This model has the potential to facilitate individualized clinical decision-making and the early recovery of patients with gastric cancer post-surgery.

NEK2 promotes the migration, invasion, proliferation of ESCC and mediates ESCC immunotherapy.

Purpose: Esophageal squamous cell carcinoma (ESCC) is a disease with a high incidence rate and high mortality worldwide. The Never in Mitosis A (NIMA) family member NIMA-related kinase 2 (NEK2) plays an important role in mitosis. However, the role of NEK2 in the pathogenesis of ESCC remains unclear. Patients and methods: The expression and function of NEK2 in TCGA and GEO data sets were analyzed by bioinformatics. We verified the expression of NEK2 in ESCC tissues and cell lines by Western blotting and immunohistochemical methods and further explored the relationship between tumor stage and NEK2 expression. The differences in NEK2 expression and survival in patients with EC were verified by bioinformatics analysis. ESCC cell lines with stable knockdown of NEK2 were established by lentivirus-mediated shRNA delivery. The effects of NEK2 on ESCC cells were analyzed on the cytological level with assays including CCK-8, EdU, cell scratch, Transwell migration and invasion, colony formation, flow cytometry and apoptosis assays. Tumor growth was measured in a mouse xenograft model. Results: We found that NEK2 is highly expressed in ESCC tissues and ESCC cells and that the high expression of NEK2 is associated with poor tumor healing. Knockdown of the NEK2 gene inhibits the migration, proliferation, invasion and cell cycle of ESCC cells. Biologic analysis shows that NEK2 is involved in biological processes such as progression and apoptosis of esophageal cancer, and is related to E2F.Mechanistically, NEK2 knockdown decreases the expression levels of E2F1 and IGF2. NEK2 competes with the transcription factor E2F1 to bind CDC20, resulting in decreased degradation and increased expression of E2F1. IGF2 expression is also increased, which promotes the expression of thymidylate synthase, further promoting the drug resistance of ESCC cells. NEK2 is associated with immune infiltration in esophageal cancer. Conclusion: NEK2 is highly expressed in ESCC and can promote the migration, proliferation and invasion of ESCC cells. NEK2 mediates ESCC immunotherapy.

C634Y mutation in RET-induced multiple endocrine neoplasia type 2A: A case report.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an RET carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners. CASE SUMMARY: Herein, we present RET proto-oncogene mutations, clinical characteristics, and treatment strategies in a family with MEN2A. A family study was conducted on patients diagnosed with MEN2A. DNA was extracted from the peripheral blood of family members, and first-generation exon sequencing of the RET proto-oncogene was conducted. The C634Y mutation was identified in three family members spanning three generations. Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas. A 9-year-old child harboring the gene mutation was diagnosed with medullary thyroid carcinoma. Surgical resection of the tumors was performed. All family members were advised to undergo complete genetic testing related to the C634Y mutation, and the corresponding treatments administered based on test results and associated clinical guidelines. CONCLUSION: Advancements in MEN2A research are important for familial management, assessment of medullary thyroid cancer invasive risk, and deciding surgical timing.

Mitochondrial Targeted Thermosensitive Nanocarrier for Near-Infrared-Triggered Precise Synergetic Photothermal Nitric Oxide Chemotherapy.

Nitric oxide (NO) intervenes, that is, a potential treatment strategy, and has attracted wide attention in the field of tumor therapy. However, the therapeutic effect of NO is still poor, due to its short half-life and instability. Therapeutic concentration ranges of NO should be delivered to the target tissue sites, cell, and even subcellular organelles and to control NO generation. Mitochondria have been considered a major target in cancer therapy for their essential roles in cancer cell metabolism and apoptosis. In this study, mesoporous silicon-coated gold nanorods encapsulated with a mitochondria targeted and the thermosensitive lipid layer (AuNR@MSN-lipid-DOX) served as the carrier to load NO prodrug (BNN6) to build the near-infrared-triggered synergetic photothermal NO-chemotherapy platform (AuNR@MSN(BNN6)-lipid-DOX). The core of AuNR@MSN exhibited excellent photothermal conversion capability and high loading efficiency in terms of BNN6, reaching a high value of 220 mg/g (w/w), which achieved near-infrared-triggered precise release of NO. The outer biocompatible lipid layer, comprising thermosensitive phospholipid DPPC and mitochondrial-targeted DSPE-PEG2000-DOX, guided the whole nanoparticle to the mitochondria of 4T1 cells observed through confocal microscopy. In the mitochondria, the nanoparticles increased the local temperature over 42 °C under NIR irradiation, and a high NO concentration from BNN6 detected by the NO probe and DSPE-PEG2000-DOX significantly inhibited 4T1 cancer cells in vitro and in vivo under the synergetic photothermal therapy (PTT)-NO therapy-chemotherapy modes. The built NIR-triggered combination therapy nanoplatform can serve as a strategy for multimodal collaboration.

[Interventional effect and inflammatory regulation mechanism of dihydroartemisinin combined with pregabalin on neuropathic pain mice].

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

Novel Umami Peptides from Mushroom (Agaricus bisporus) and Their Umami Enhancing Effect via Virtual Screening and Molecular Simulation.

This study aimed to identify novel umami peptides in Agaricus bisporus and investigate their umami enhancing effect. We virtually screened 155 potential umami peptides from the ultrasound-assisted A. bisporus hydrolysate according to Q values, iUmami-SCM, Umami_YYDS, and Tastepeptides_DM models, and molecular docking. Five peptides (AGKNTNGSQF, DEAVARGATF, REESDFQSSF, SEETTTGVHH, and WNNDAFQSSTN) were synthesized for sensory evaluation and kinetic analysis. The result showed that the umami thresholds of the five peptides were in the range of 0.21-0.40 mmol/L. Notably, REESDFQSSF, SEETTTGVHH, and WNNDAFQSSTN had low dissociation constant (KD) values and high affinity for the T1R1-VFT receptor. The enhancing effect of the three peptides with MSG or IMP was investigated by sensory evaluation, kinetic analysis, and molecular dynamics simulations. In stable complexes, ARG_277 in T1R1 played a major role in umami peptide binding to T1R1-VFT. These results provide a theoretical basis for future screening of umami peptides and improving the umami taste of food containing mushrooms.

Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment.

SCOPE: This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. METHODS AND RESULTS: Mature milk is collected from the mothers of term and preterm infants. Using high-throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let-7 and miR-148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR-3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR-3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). CONCLUSION: This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.

QTL Mapping of Adult Plant Resistance to Powdery Mildew in Chinese Wheat Landrace Baidatou.

Wheat powdery mildew, caused by the biotrophic fungus Blumeria graminis f. sp. tritici (Bgt), is one of the most devastating diseases affecting wheat throughout the world. Breeding and growing resistant wheat cultivars is one of the most economic and effective methods to control the disease, and as such, identifying and mapping the new and effective resistance genes is critical. Baidatou, a Chinese wheat landrace, shows excellent field resistance to powdery mildew. To identify the resistance gene(s) in Baidatou, 170 F7:8 recombinant inbred lines (RILs) derived from the cross Mingxian 169/Baidatou were evaluated for powdery mildew response at the adult-plant stage in the experimental fields in Yangling (YL) of Shaanxi Province and Tianshui (TS) in Gansu Province in 2019, 2020, and 2021. The relative area under disease progress curve (rAUDPC) of Mingxian 169/Baidatou F7:8 RILs indicated that the resistance of Baidatou to powdery mildew was controlled by quantitative trait loci (QTLs). Based on bulk segregation analysis combined with the 660K single nucleotide polymorphism (SNP) array and genotyping by target sequencing (16K SNP) of the entire RIL population, two QTLs, QPmbdt.nwafu-2AS and QPmbdt.nwafu-3AS, were identified, and these accounted for up to 44.5% of the phenotypic variation. One of the QTLs was located on the 3.32 cM genetic interval on wheat chromosome 2AS between the kompetitive allele-specific PCR markers AX-111012288 and AX_174233809, and another was located on the 9.6 cM genetic interval on chromosome 3AS between the SNP markers 3A_684044820 and 3A_686681822. These markers could be useful for successful breeding of powdery mildew resistance in wheat.

Natural polysaccharides and their derivatives targeting the tumor microenvironment: A review.

Polysaccharides have gained attention as valuable supplements and natural medicinal resources, particularly for their anti-tumor properties. Their low toxicity and potent anti-tumor effects make them promising candidates for cancer prevention and treatment. The tumor microenvironment is crucial in tumor development and offers potential avenues for novel cancer therapies. Research indicates that polysaccharides can positively influence the tumor microenvironment. However, the structural complexity of most anti-tumor polysaccharides, often heteropolysaccharides, poses challenges for structural analysis. To enhance their pharmacological activity, researchers have modified the structure and properties of natural polysaccharides based on structure-activity relationships, and they have discovered that many polysaccharides exhibit significantly enhanced anti-tumor activity after chemical modification. This article reviews recent strategies for targeting the tumor microenvironment with polysaccharides and briefly discusses the structure-activity relationships of anti-tumor polysaccharides. It also summarises the main chemical modification methods of polysaccharides and discusses the impact of chemical modifications on the anti-tumor activity of polysaccharides. The review aims to lay a theoretical foundation for the development of anti-tumor polysaccharides and their derivatives.

Identification of important genes related to anoikis in acute myocardial infarction.

Acute myocardial infarction (AMI) increasingly precipitates severe heart failure, with diagnoses now extending to progressively younger demographics. The focus of this study was to pinpoint critical genes linked to both AMI and anoikis, thereby unveiling potential novel biomarkers for AMI detection and intervention. Differential analysis was performed to identify significant differences in expression, and gene functionality was explored. Weighted gene coexpression network analysis (WGCNA) was used to construct gene coexpression networks. Immunoinfiltration analysis quantified immune cell abundance. Protein-protein interaction (PPI) analysis identified the proteins that interact with theanoikis. MCODE identified key functional modules. Drug enrichment analysis identified relevant compounds explored in the DsigDB. Through WGCNA, 13 key genes associated with anoikis and differentially expressed genes were identified. GO and KEGG pathway enrichment revealed the regulation of apoptotic signalling pathways and negative regulation of anoikis. PPI network analysis was also conducted, and 10 hub genes, such as IL1B, ZAP70, LCK, FASLG, CD4, LRP1, CDH2, MERTK, APOE and VTN were identified. IL1B were correlated with macrophages, mast cells, neutrophils and Tcells in MI, and the most common predicted medications were roxithromycin, NSC267099 and alsterpaullone. This study identified key genes associated with AMI and anoikis, highlighting their role in immune infiltration, diagnosis and medication prediction. These findings provide valuable insights into potential biomarkers and therapeutic targets for AMI.

The A2 haplotype of Echinococcus multilocularis is the predominant variant infecting humans and dogs in Yili Prefecture, Xinjiang.

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is an important zoonotic disease. Yili Prefecture in Xinjiang is endemic for AE, however the molecular variability of E. multilocularis in this region is poorly understood. In this study, 127 samples were used for haplotypes analysis, including 79 tissues from humans, 43 liver tissues from small rodents, and 5 fecal samples from dogs. Genetic variability in E. multilocularis was studied using complete sequences of the mitochondrial (mt) genes of cytochrome b (cob), NADH dehydrogenase subunit 2 (nad2), and cytochrome c oxidase subunit 1 (cox1), using a total of 3558 bp per sample. The Asia haplotype 2 (A2) was the dominant haplotype, with 72.15% (57/79) prevalence in humans, 2.33% (1/43) in small rodents, and 80.00% (4/5) in dogs, followed by A5, the second most common haplotype, which infected 27.91% (12/43) small rodents. Haplotype network analysis showed that all haplotypes clustered together with the Asian group. Pairwise fixation index (FST) values showed lower level of genetic differentiation between different regions within the country. Compared with the sequences of E. multilocularis from North America and Europe, all concatenated sequences isolated from Yili Prefecture were highly differentiated and formed a single population. The A2 haplotype, analyzed using the cob, nad2, and cox1 genes of E. multilocularis, is the predominant variant in humans and dogs in Yili Prefecture.

Epigallocatechin-3-gallate-induced tolerance to cadmium stress involves increased flavonoid synthesis and nutrient homeostasis in tomato roots.

Cadmium (Cd) is a toxic heavy metal, increasingly accumulating in the environment and its presence in various environmental compartments represents a significant risk to human health via the food chain. Epigallocatechin-3-Gallate (EGCG) is a prominent secondary metabolite, which can safeguard plants from biotic and abiotic stress. However, the role of EGCG in flavonoid synthesis, nutrient acquisition and reactive oxygen species (ROS) metabolism under Cd stress remains unclear. Here, we examined the effects of EGCG and Cd treatment on leaf photochemical efficiency, cell ultrastructure, essential element acquisition, antioxidant system, and secondary metabolism in tomato (Solanum lycopersicum L.). The results showed that O2•-, H2O2, and malondialdehyde levels increased after Cd treatment, but Fv/Fm decreased significantly, suggesting that Cd induced oxidative stress and photoinhibition. However, EGCG mitigated the adverse effects of Cd-induced phytotoxicity in both the roots and leaves. A decrease in ROS accumulation under EGCG + Cd treatment was mainly attributed to the significant enhancement in antioxidant enzyme activity, flavonoid content, and PHENYLALANINE AMMONIA-LYASE expression in roots. Moreover, EGCG reduced Cd content but increased some essential nutrient contents in tomato plants. Transmission electron microscopy-based observations revealed that EGCG treatment safeguards leaf and root cell ultrastructure under Cd stress. This implies that tomato plants subjected to Cd stress experienced advantageous effects upon receiving EGCG treatment. The present work elucidated critical mechanisms by which EGCG induces tolerance to Cd, thereby providing a basis for future investigations into environmentally sustainable agricultural practices in areas contaminated with heavy metals, for utilizing naturally occurring substances found in plants.