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Portal vein tumor thrombosis (PVTT), a severe complication of hepatocellular carcinoma (HCC), markedly influences patient prognosis by fostering a hypercoagulable state. However, its molecular underpinnings remain largely unexplored. This study sheds light on the critical role of the KIT ligand (KITLG) in modulating expression of the collagen gene COL4A1 via the STAT3-SMAD2 signaling pathway, thereby influencing platelet activation and PVTT development. Extensive analysis of PVTT tissue samples, alongside in vitro and in vivo experiments including cell-platelet interaction assays and PVTT animal models, revealed the mechanism through which KITLG regulates COL4A1 expression, as well as its downstream effects on platelet behavior and the coagulation cascade. Our findings revealed that marked upregulation of COL4A1 expression, mediated by KITLG through the STAT3-SMAD2 pathway, led to increased platelet activation and PVTT formation. KITLG and COL4A1 expression was markedly higher in PVTT tissues than primary HCC tissues, thus highlighting their critical role in the pathophysiological trajectory leading to thrombosis. The finding that the KITLG-COL4A1 signaling axis is a crucial mediator in PVTT development may offer promising new directions for developing targeted diagnostic and therapeutic strategies. This study underscores the importance of the KITLG-COL4A1 axis in PVTT formation and its potential as a therapeutic target in HCC treatment protocols.

Abstract Background The erector spinae plane block (ESPB) is a new analgesic method used in thoracic surgery. However, few studies have characterized their effects on perioperative opioid consumption. We aimed to evaluate the effects of ESPB on perioperative opioid consumption in patients who underwent video-assisted thoracoscopic surgery (VATS). Methods This was a randomized, observer-blinded clinical trial at a single-centre academic hospital. Eighty patients were scheduled for thoracoscopic segmentectomy or lobectomy by VATS for lung cancer. Forty participants were randomly assigned to ESPB or control group. All patients received intravenous patient-controlled postoperative analgesia. Perioperative opioid consumption, visual analogue scale (VAS) scores, and adverse events were recorded. Results Intraoperative and postoperative opioid consumption and static/dynamic VAS scores were significantly lower in the early hours after VATS in the ESPB group (p

Abstract Biodiversity often helps communities resist invasion. However, it is unclear whether this diversity–invasion relationship holds true under environmental changes. Here, we conduct a meta-analysis of 1010 observations from 25 grassland studies in which plant species richness is manipulated together with one or more environmental change factors to test invasibility (measured by biomass or cover of invaders). We find that biodiversity increases resistance to invaders across various environmental conditions. However, the positive biodiversity effect on invasion resistance is strengthened under experimental warming, whereas it is weakened under experimentally imposed drought. When multiple factors are imposed simultaneously, the positive biodiversity effect is strengthened. Overall, we show that biodiversity helps grassland communities resist plant invasions under multiple environmental changes. Therefore, investment in the protection and restoration of native biodiversity is not only important for prevention of invasions under current conditions but also under continued global environmental change.

Abstract Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.

Abstract Conducting polymer hydrogel can address the challenges of stricken biocompatibility and durability. Nevertheless, conventional conducting polymer hydrogels are often brittle and weak due to the intrinsic quality of the material, which exhibits viscoelasticity. This property may cause a delay in sensor response time due to hysteresis. To overcome these limitations, we have designed a wrinkle morphology three‐dimensional (3D) substrate using digital light processing technology and then followed by in situ polymerization to form interpenetrating polymer network hydrogels. This novel design results in a wrinkle morphology conducting polymer hydrogel elastomer with high precision and geometric freedom, as the size of the wrinkles can be controlled by adjusting the treating time. The wrinkle morphology on the conducting polymer hydrogel effectively reduces its viscoelasticity, leading to samples with quick response time, low hysteresis, stable cyclic performance, and remarkable resistance change. Simultaneously, the 3D gradient structure augmented the sensor's sensitivity under minimal stress while exhibiting consistent sensing performance. These properties indicate the potential of the conducting polymer hydrogel as a flexible sensor.

Abstract Background The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and “chaotic”. In the present study we discuss the management strategy for this group of patients. Methods We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. Results A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)‐CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. Conclusion Routine chest CT is needed for breast cancer patients before surgery, and PET‐CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer.

Abstract Background Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported. Method This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors. Result This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells. Conclusion In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.

Abstract Background In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. Results This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. Conclusion This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.

Abstract Blood transfusions from convalescent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients could be used to treat patients with severe infections or immunocompromised patients. However, it is necessary to select the optimal donors to maximize the utilization of resources. In this study, we investigated the associations among body mass index (BMI), tobacco smoking, exercise frequency and duration, and alcohol consumption with the SARS-CoV-2 immunoglobulin-G (IgG) antibody titer levels with in the Chinese convalescent blood donor population. Here we show that BMI, smoking habits, and exercise frequency appear to be predictive factors for IgG levels in convalescent male blood donors. However, these variables were not observed as predictive of IgG levels in female convalescent blood donors. The findings could be used to optimize the screening for potential blood donors to treat immunocompromised or severely ill COVID-19 patients.

The hetero-zone boundary affected region (HBAR), with a high strain gradient, plays a crucial role in the synergistic deformation of layered materials. Our previous experimental study demonstrated that a decreasing interfacial spacing leads to a higher fraction of HBAR and an enhanced combination of strength and ductility. In this work, a conventional mechanism-based strain gradient (CMSG) plasticity model is adopted to simulate the tensile behavior of Cu–Fe layered materials with three different interfacial spacings. The simulation results indicated that strain/stress partitioning and strain banding are the main factors for the synergistic deformation behavior. Strain bands are more likely to be activated in the Cu–Fe layered materials with smaller interfacial spacing. In addition, the formation of HBAR near the layer boundary can be observed, consistent with the previous experiments. During deformation, the HBAR induces back stress and forward stress to strengthen the Cu layer and weaken the Fe layer, respectively. The simulation results indicate the stress transfer between the Cu and Fe layers, which benefits the strain hardening and enhances synergistic deformation. This study provides a valuable insight into the strength-ductility synergy of layered materials. It demonstrates that increasing the HBAR fraction is a viable approach to enhance the mechanical properties of hetero-structured materials.

Objective: To comprehensively evaluate the hypoglycemic and antioxidant effects of Camellia nitidissima flower. Methods: The chemical constituents in the aqueous extract of C. nitidissima flower (CFA) were identified by high performance liquid chromatography-mass spectrometry (HPLC-MS). Next, a mouse model of type 2 diabetes was established, and the diabetic mice were randomly divided into five groups: model, positive control (acarbose at 20 mg/kg mb), low-, medium- and high-dose CFA (200, 400 and 800 mg/kg mb, respectively). After five weeks of intragastric intervention, general growth characteristics, serum glucose, fasting insulin (FINS) and lipid levels, oxidative stress in pancreas and liver tissues, tissue morphological changes and cell apoptosis were analyzed. Results: CFA had a high content of polyphenols and polysaccharides. The half-maximal inhibitory concentration (IC50) values for scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and α-glucosidase inhibition were (24.14 ± 0.64) and (69.99 ± 1.97) μg/mL, respectively. Seven compounds were identified from CFA. In addition, CFA could effectively improve the ‘three more and one less’ symptoms of diabetic mice, significantly reduce the levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA), increase the levels of insulin and high-density lipoprotein cholesterol (HDL-C), improve the activities of total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and alleviate pathological damage in pancreas and liver tissues. Conclusion: CFA has significant hypoglycemic and antioxidant effects on type 2 diabetic mice.

Abstract Gut microbiota and their metabolic products might play important roles in regulating the pathogenesis of autism spectrum disorder (ASD). The purpose of this study was to characterize gut microbiota and serum amino acid metabolome profiles in children with ASD. A non-randomized controlled study was carried out to analyze the alterations in the intestinal microbiota and their metabolites in patients with ASD (n = 30) compared with neurotypical controls (NC) (n = 30) by metagenomic sequencing to define the gut microbiota community and liquid chromatography/mass spectrometry (LC/MS) analysis to characterize the metabolite profiles. Compared with children in the NC group, those in the ASD group showed lower richness, higher evenness, and an altered microbial community structure. At the class level, Deinococci and Holophagae were significantly lower in children with ASD compared with TD. At the phylum level, Deinococcus-Thermus was significantly lower in children with ASD compared with TD. In addition, the functional properties (such as galactose metabolism) displayed significant differences between the ASD and NC groups. Five dominant altered species were identified and analyzed (LDA score > 2.0, P

IntroductionYeast culture (YC) enhances ruminant performance, but its functional mechanism remains unclear because of the complex composition of YC and the uncertain substances affecting rumen fermentation. The objective of this study was to determine the composition of effective metabolites in YC by exploring its effects on rumen fermentation in vitro, growth and slaughter performance, serum index, rumen fermentation parameters, rumen microorganisms, and metabolites in lambs.MethodsIn Trial 1, various YCs were successfully produced, providing raw materials for identifying effective metabolites. The experiment was divided into 5 treatment groups with 5 replicates in each group: the control group (basal diet without additives) and YC groups were supplemented with 0.625‰ of four different yeast cultures, respectively (groups A, B, C, and D). Rumen fermentation parameters were determined at 3, 6, 12, and 24 h in vitro. A univariate regression model multiple factor associative effects index (MFAEI; y) was established to correlate the most influential factors on in vitro rumen fermentation with YC metabolites (x). This identified the metabolites promoting rumen fermentation and optimal YC substance levels. In Trial 2, metabolites in YC not positively correlated with MFAEI were excluded, and effective substances were combined with pure chemicals (M group). This experiment validated the effectiveness of YC metabolites in lamb production based on their impact on growth, slaughter performance, serum indices, rumen parameters, microorganisms, and metabolites. Thirty cross-generation rams (Small tail Han-yang ♀ × Australian white sheep ♂) with good body condition and similar body weight were divided into three treatment groups with 10 replicates in each group: control group, YC group, pure chemicals combination group (M group).ResultsGrowth performance and serum index were measured on days 30 and 60, and slaughter performance, rumen fermentation parameters, microorganisms, and metabolites were measured on day 60. The M group significantly increased the dressing percentage, and significantly decreased the GR values of lambs (p < 0.05). The concentration of growth hormone (GH), Cortisol, insulin (INS), and rumen VFA in the M group significantly increased (p

BackgroundSome observational studies and clinical experiments suggest a close association between gut microbiota and metabolic diseases. However, the causal effects of gut microbiota on adrenal diseases, including Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism, remain unclear.MethodsThis study conducted a two-sample Mendelian randomization analysis using summary statistics data of gut microbiota from a large-scale genome-wide association study conducted by the MiBioGen Consortium. Summary statistics data for the three adrenal diseases were obtained from the FinnGen study. The study employed Inverse variance weighting, MR-Egger, and MR-PRESSO methods to assess the causal relationship between gut microbiota and these three adrenal diseases. Additionally, a reverse Mendelian randomization analysis was performed for bacteria found to have a causal relationship with these three adrenal diseases in the forward Mendelian randomization analysis. Cochran’s Q statistic was used to test for heterogeneity of instrumental variables.ResultsThe IVW test results demonstrate that class Deltaproteobacteria, Family Desulfovibrionaceae, and Order Desulfovibrionales exhibit protective effects against adrenocortical insufficiency. Conversely, Family Porphyromonadaceae, Genus Lachnoclostridium, and Order MollicutesRF9 are associated with an increased risk of adrenocortical insufficiency. Additionally, Family Acidaminococcaceae confers a certain level of protection against Cushing syndrome. In contrast, Class Methanobacteria, Family Lactobacillaceae, Family Methanobacteriaceae, Genus. Lactobacillus and Order Methanobacteriales are protective against Hyperaldosteronism. Conversely, Genus Parasutterella, Genus Peptococcus, and Genus Veillonella are identified as risk factors for Hyperaldosteronism.ConclusionsThis two-sample Mendelian randomization analysis revealed a causal relationship between microbial taxa such as Deltaproteobacteria and Desulfovibrionaceae and Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism. These findings offer new avenues for comprehending the development of adrenal diseases mediated by gut microbiota.

Abstract Background Hearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counselling for the patient's family. Methods We detected and analysed 362 Chinese non‐syndromic HL patients by screening of variants in 15 hot spot mutations. Subsequently, 40 patients underwent further whole‐exome sequencing (WES) to determine genetic aetiology. The candidate variants were verified using Sanger sequencing. Twenty‐three carrier couples with pathogenic variants or likely pathogenic variants chose to proceed with prenatal diagnosis using Sanger sequencing. Results Among the 362 HL patients, 102 were assigned a molecular diagnosis with 52 different variants in 22 deafness genes. A total of 41 (11.33%) cases with the biallelic GJB2 (OMIM # 220290) gene mutations were detected, and 21 (5.80%) had biallelic SLC26A4 (OMIM # 605646) mutations. Mitochondrial gene (OMIM # 561000) mutations were detected in seven (1.93%) patients. Twenty of the variants in 15 deafness genes were novel. SOX10 (OMIM # 602229), MYO15A (OMIM # 602666) and WFS1 (OMIM # 606201) were each detected in two patients. Meanwhile, OSBPL2 (OMIM # 606731), RRM2B (OMIM # 604712), OTOG (OMIM # 604487), STRC (OMIM # 606440), PCDH15 (OMIM # 605514), LOXHD1 (OMIM # 613072), CDH23 (OMIM # 605516), TMC1 (OMIM # 606706), CHD7 (OMIM # 608892), DIAPH3 (OMIM # 614567), TBC1D24 (OMIM # 613577), TIMM8A (OMIM # 300356), PTPRQ (OMIM # 603317), SALL1 (OMIM # 602218), and GSDME (OMIM # 608798) were each detected in one patient. In addition, as regards one couple with a heterozygous variant of CDH23 and PCDH15, respectively, prenatal diagnosis results suggest that the foetus had double heterozygous (DH) variants of CDH23 and PCDH15, which has a high risk to cause ID/F type Usher syndrome. Conclusion Our study expanded the spectrum of deafness gene variation, which will contribute to the genetic diagnosis, prenatal diagnosis and the procreation guidance of deaf couple. In addition, the deafness caused by two genes should be paid attention to in the prenatal diagnosis of families with both deaf patients.

Abstract Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non‐reproductive tissue‐originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single‐cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR‐211‐5p in gut‐derived circulating exosomes, which inhibited the expression of meiosis‐specific with coiled‐coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut‐derived exosomes in connecting the “gut‐testis” axis.

Microorganisms residing in the cecum of donkeys are crucial for physiological processes, nutrient metabolism, and immune function. Feeding methods can affect the dynamic balance of animal gut microbiota, thereby affecting indicators such as volatile fatty acids. This study explores suitable feeding methods to promote actual production by changing the feeding order of concentrate. Fifteen Dezhou donkeys with similar age and weight profiles were randomly divided into three groups with the concentrate feeding sequence: fiber-to-concentrate (FC), concentrate-to-fiber (CF), and total mixed ration (TMR). The experiment spanned a duration of 82 days. The analyses conducted were primarily aimed at determining the effects of feeding on gut microbes, primarily using metagenomic sequencing techniques. The experimental findings revealed that the levels of valeric acid were notably higher in the CF and TMR groups compared to the FC group (p < 0.05). These results suggest that the feeding sequence exerts a certain impact on the microbial composition within the cecum of Dezhou donkeys. At the phylum level, the predominant microbiota consisted of Firmicutes and Bacteroidetes, with the CF group displaying a higher relative abundance of Firmicutes compared to both the FC and TMR groups. At the genus level, Prevotella, Bacteroides, and Fibrobacter were the dominant bacterial genera identified in cecum. The functional gene annotation analysis indicated a significantly lower abundance of lacZ (K01190), Por/nifJ (K03737), and ppdK (K01006) genes in CF group relative to the FC and TMR groups (p < 0.05), highlighting their roles in galactose metabolism and glycolysis, respectively. Moreover, the CF group exhibited a higher concentration of antibiotic resistance genes (tetO and tet44) in the gut microbiota compared to the TMR and FC groups (p < 0.05), underscoring the presence of numerous antibiotic resistance genes within the phyla Bacteroidetes, Firmicutes, and Proteobacteria. In conclusion, different precision feed sequences significantly impact the levels of volatile fatty acids in Dezhou fattening donkeys, modify the composition and functional genes of the cecal microbiota, and elucidate the microbial mechanisms influenced by the feeding sequence on the growth and metabolism. These insights are anticipated to provide a foundation for the rational design of precision feed sequences in practical agricultural settings.

IntroductionMorchella esculenta is a popular edible fungus with high economic and nutritional value. However, the rot disease caused by Lecanicillium aphanocladii, pose a serious threat to the quality and yield of M. esculenta. Biological control is one of the effective ways to control fungal diseases.Methods and resultsIn this study, an effective endophytic B. subtilis A9 for the control of M. esculenta rot disease was screened, and its biocontrol mechanism was studied by transcriptome analysis. In total, 122 strains of endophytic bacteria from M. esculenta, of which the antagonistic effect of Bacillus subtilis A9 on L. aphanocladii G1 reached 72.2% in vitro tests. Biological characteristics and genomic features of B. subtilis A9 were analyzed, and key antibiotic gene clusters were detected. Scanning electron microscope (SEM) observation showed that B. subtilis A9 affected the mycelium and spores of L. aphanocladii G1. In field experiments, the biological control effect of B. subtilis A9 reached to 62.5%. Furthermore, the transcritome profiling provides evidence of B. subtilis A9 bicontrol at the molecular level. A total of 1,246 differentially expressed genes (DEGs) were identified between the treatment and control group. Gene Ontology (GO) enrichment analysis showed that a large number of DEGs were related to antioxidant activity related. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the main pathways were Nitrogen metabolism, Pentose Phosphate Pathway (PPP) and Mitogen-Activated Protein Kinases (MAPK) signal pathway. Among them, some important genes such as carbonic anhydrase CA (H6S33_007248), catalase CAT (H6S33_001409), tRNA dihydrouridine synthase DusB (H6S33_001297) and NAD(P)-binding protein NAD(P) BP (H6S33_000823) were found. Furthermore, B. subtilis A9 considerably enhanced the M. esculenta activity of Polyphenol oxidase (POD), Superoxide dismutase (SOD), Phenylal anineammonia lyase (PAL) and Catalase (CAT).ConclusionThis study presents the innovative utilization of B. subtilis A9, for effectively controlling M. esculenta rot disease. This will lay a foundation for biological control in Morchella, which may lead to the improvement of new biocontrol agents for production.

Abstract Objective Sepsis is an organ malfunction disease that may become fatal and is commonly accompanied by severe complications such as multiorgan dysfunction. Patients who are already hospitalized have a high risk of death due to sepsis. Even though early diagnosis is very important, the technology and clinical approaches that are now available are inadequate. Hence, there is an immediate necessity to investigate biological markers that are sensitive, specific, and reliable for the prompt detection of sepsis to reduce mortality and improve patient prognosis. Mounting research data indicate that ferroptosis contributes to the occurrence, development, and prevention of sepsis. However, the specific regulatory mechanism of ferroptosis remains to be elucidated. This research evaluated the expression profiles of ferroptosis‐related genes (FRGs) and the diagnostic significance of the ferroptosis‐related classifiers in sepsis. Methods and Results We collected three peripheral blood data sets from septic patients, integrated the clinical examination data and mRNA expression profile of these patients, and identified 13 FRGs in sepsis through a co‐expression network and differential analysis. Then, an optimal classifier tool for sepsis was constructed by integrating a variety of machine learning algorithms. Two key genes, ATG16L1 and SRC, were shown to be shared between the algorithms, and thus were identified as the FRG signature of classifier. The tool exhibited satisfactory diagnostic efficiency in the training data set (AUC = 0.711) and two external verification data sets (AUC = 0.961; AUC = 0.913). In the rat cecal ligation puncture sepsis model, in vivo experiments verified the involvement of ATG16L1 and SRC in the early sepsis process. Conclusion These findings confirm that FRGs may participate in the development of sepsis, the ferroptosis related classifiers can provide a basis for the development of new strategies for the early diagnosis of sepsis and the discovery of new potential therapeutic targets for life‐threatening infections.

Uphill walking is a common task encountered in daily life, with steeper inclines potentially imposing greater biomechanical and neuromuscular demands on the human body. The heel-to-toe drop (HTD) in footwear may influence the biomechanical and neuromuscular pattern of uphill walking; but the impact remains unclear. Adjustments in HTD can modulate biomechanical and neuromuscular patterns, mitigating the demands and optimizing the body’s response to different inclinations. We hypothesize that adjustments in HTD can modulate biomechanical and neuromuscular patterns, mitigating the demands and optimizing the body’s response to different inclinations. Nineteen healthy men walked on an adjustable slope walkway, with varied inclinations (6°, 12°, 20°) and HTD shoes (10mm, 25mm, 40 mm), while the marker positions, ground reaction forces and electromyography data were collected. Our study reveals that gait temporo-spatial parameters are predominantly affected by inclination over HTD. Inclination has a more pronounced effect on kinematic variables, while both inclination and HTD significantly modulate kinetic and muscle synergy parameters. This study demonstrates that an increase in the inclination leads to changes in biomechanical and neuromuscular responses during uphill walking and the adjustment of HTD can modulate these responses during uphill walking. However, the present study suggests that an increased HTD may lead to elevated loads on the knee joint and these adverse effects need more attention.

Background and purposeEarly blood–brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption.MethodsWe retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction.ResultsA total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54–70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10–15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02–3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00–1.05). High Blood–brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01–1.05).ConclusionEarly BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.

Abstract Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC–microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO’s m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.

Generally, high-strength metallic materials with large ductility are of technological importance in various engineering fields, including aerospace, fuel efficiency, and emission reduction. This work developed a new type of steel with exceptional yield strength (1.5∼2.0 GPa) and high total elongation (11∼26%) through a simple three-step process involving cold-rolling, warm-rolling and annealing treatments. Microstructural analysis revealed that the steel is composed of nano platelets made up of austenite and martensite. These platelets aggregate within elongated prior austenite grains, forming hierarchical lamellar structures. The study thoroughly investigated the anisotropic mechanical properties of the steel, particularly its strength and yield point behavior in rolling and transverse directions. The primary sources of strength were mainly originated from nano lamellae and high density of dislocations, while the anisotropic strengthening and yield point behavior was attributed to the textures and lamellar boundaries. With increasing warm-rolling reduction, the anisotropy level of dislocation strengthening gradually decreases, while the anisotropy level of boundary strengthening significantly increases. The discrepancy in yield point behavior along the rolling and transverse directions is ascribed to the differing number of boundaries per unit area of cross-section perpendicular to the tensile direction and the shear stress required for dislocation slip. This study provides a deep insight into understanding the anisotropy of strengthening and yield point behavior in nanolamellar steel so as to contribute to its future applications in engineering structural components.

Abstract Background Postoperative pain remains a significant concern following uniportal thoracoscopic surgery. The analgesic efficacy of erector spinae plane block (ESPB) and serratus anterior plane block (SAPB) in terms of postoperative opioid consumption in uniportal thoracoscopic surgery still needs further studies. Methods A randomized controlled trial was conducted, enrolling 150 patients who underwent uniportal thoracoscopic lobectomy. The patients were randomly allocated to three groups in a 1:1:1 ratio: the ESPB group (administered 20 ml of 0.5% ropivacaine), the SAPB group (administered 20 ml of 0.5% ropivacaine), and the standard care (control) group. The primary endpoint was the consumption of sufentanil during the first 24 h following surgery. Secondary endpoints assessed the area under the curve (AUC) of pain numerical rating scale (NRS) scores, occurrence of moderate to severe pain, time to initial sufentanil request, and postoperative adverse events. Results No significant difference was observed in the consumption of sufentanil during the first 24 h following surgery between the ESPB and SAPB groups (adjusted difference, 1.53 [95% CI, -5.15 to 2.08]). However, in comparison to the control group, both intervention groups demonstrated a significant decrease in sufentanil consumption, with adjusted differences of -9.97 [95% CI, -13.10 to -6.84] for the ESPB group and -12.55 [95% CI, -15.63 to -9.47] for the SAPB group. There were no significant differences in AUC of NRS scores during rest and movement between the ESPB and SAPB groups, with adjusted differences of -7.10 [95% CI, 1.33 to -15.55] for the rest condition and 5.61 [95% CI, -13.23 to 2.01] for the movement condition. At 6 h postoperatively, there were fewer patients with moderate to severe pain in the ESPB group compared with those in the SAPB group (adjusted difference, -1.37% [95% CI, -2.29% to -0.45%]. The time to first sufentanil request significantly differed among the three groups (ESPB vs Control P

The article discusses the peculiarities of the terminology of traditional Chinese medicine and the problems that arise during its translation into Russian. The author shows that the most common model for creating terms in this field is represented by two-word and four-word phrases. It is noted that their translation cannot be limited to traditional methods. It is asserted that the conceptual meaning of terms in traditional Chinese medicine has historical, philosophical, and humanistic foundations. It is emphasized that the translation of terms in traditional Chinese medicine should include issues of cultural communication. Examples of successful and unsuccessful translations of terms into Russian demonstrate that the rich cultural subtext contained in them determines the difficulty of their perception. The reasons for incorrect translations of terms in traditional Chinese medicine are indicated, among which their non-equivalence, historical-cultural context, differences in content when there are differences in expression, etc. It is concluded that an important issue in translating terms in traditional Chinese medicine is the need to formulate unified rules for translating texts in this field into a foreign language.

AbstractContext As a major risk factor for cardiovascular diseases (CVD), Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). Recent studies indicated that the increased cardiovascular risk in patients with OSA may be mediated by accelerated vascular senescence. Danggui-Buxue decoction (DBD) has been used for treating cardiovascular diseases, but its mechanism of vascular senescence regulation is still unclear.Objective To investigate the effect of DBD on vascular senescence in mice exposed to CIH and to explore the role of the Nrf2/HO-1 pathway.Materials and methods C57BL/6N mice were randomly divided into Normoxia control group (CON), CIH (21%-5% O2, 20 times/h, 8 h/d) exposed group (CIH), and DBD treatment group (intragastrically treated with 2.34, 4.68, or 9.36 g/kg/day of DBD separately for 12 weeks as DBL, DBM, or DBH). Blood pressure, cardiac and vascular function, vascular senescence, inflammation response, oxidative stress, and Nrf2/HO-1 expression were determined.Results DBD (4.68 and 9.36 g/kg) significantly decreased Tail-cuff blood pressure, increased left ventricular systolic function, and alleviated arterial stiffness and vasorelaxation dysfunction in mice exposed to CIH. DBD treatment reduced SA-β-gal activity, decreased p16 (0.68-fold, 0.62-fold), P21 (0.58-fold, 0.52-fold), and p53 expressions (0.67-fold, 0.65-fold), and increased SIRT1 expression (2.22-fold, 2.98-fold) in the aortic. DBD treatment decreased IL-6, NF-κB, and TNF-α expressions, decreased MDA but increased SOD levels, and increased Nrf2 (1.8-fold, 1.89-fold) and HO-1 (2.25-fold, 2.43-fold) expression.Discussion and conclusions DBD could attenuate vascular senescence accelerated by CIH exposure through inhibiting inflammatory response and oxidative stress by activating the Nrf2/HO-1 pathway.

Abstract Osteoporosis is a prevalent bone disease with multigene involved, and the molecular mechanisms of its pathogenesis are not entirely understood. This study aims to identify novel key genes involved in osteoporosis to discover potential pharmacological targets. We analyzed three microarray datasets and identified four differentially expressed genes. The LASSO model indicated that RNA-binding motif protein 5 (RBM5) is associated with osteoporosis and is a potential drug target. We conducted the Spearman correlation analysis and found 52 genes that were significantly related to RBM5. Enrichment analysis showed that these genes were primarily involved in RNA splicing and osteoclast differentiation pathways. By using lentivirus-based shRNA, we successfully knocked down RBM5 expression in RAW264.7 cell line, which showed that RBM5 knockdown significantly impaired their differentiation potential to mature osteoclasts and significantly inhibited bone-resorbing activity. RT-qPCR analyses revealed the expression of osteoclastogenesis marker genes was downregulated along with RBM5 expression. These findings suggest that RBM5 plays a crucial role in the pathogenesis of osteoporosis and provides a new potential pharmacological target.

Abstract Cross-country sit-skiers use double poling (DP) technique to drive the slide. The aim of this study is to analyze how poling camber angle affect the capacity of power output and biomechanical parameters of the DP process. Twenty-four non-disabled college students (24.67 ± 1.46 years old) were recruited to perform three successive 30-s maximal effort tests with different poling camber angles of 0°, 15°, 24° and 30° using a sit-skiing ergometer. The biomechanical parameters, output power and muscle activation of the subjects were analyzed. The results showed that DP output power increased with the increase of poling camber angle at 15° (597.78 ± 150.31 J), 24° (610.94 ± 158.96 J, P = 0.011) and 30° (629.10 ± 168.78 J, P

Abstract Background Herein, the effect of pre-use of Dexmedetomidine(Dex) on the half-effective dose (ED50) and 95%-effective dose (ED95) of Remimazolam tosilate(RT) in inhibiting the positive cardiovascular response(CR) which means blood pressure or heart rate rises above a critical threshold induced by double-lumen bronchial intubation was evaluated. Methods Patients who underwent video-assisted thoracic surgery were divided into groups A (0), B (0.5 µg/kg), and C (1 µg/kg) based on different Dex doses. Group A included subgroups comprising young (A-Y) and elderly (A-O) patients. Neither groups B nor C included elderly patients due of the sedative effect of Dex. Based on the previous subject’s CR, the dose of RT was increased or decreased in the next patient using the sequential method. This trial would be terminated when the seventh crossover occurred, at which point the sample size met the stable estimate of the target dose. Heart rate (HR) and mean arterial pressure (MAP) were monitored throughout the trial, and sedation was assessed using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale. HR and MAP were recorded at baseline (T1), the end of Dex (T2), and the end of RT (T3), the maximum HR and MAP were recorded within 3 min of intubation from beginning to end (T4). There was a positive CR when the T4 levels rose above 15% of the baseline. The ED50/ED95 and corresponding confidence interval were calculated using probability regression. Results In total, 114 patients completed the trial. Without the use of Dex, the ED50/ED95 of TR inhibiting the positive CR caused by double-lumen bronchial intubation was 0.198/0.227 and 0.155/0.181 mg/kg in groups A-Y and A-O, respectively. The changes in vital signs from T1 to T3 were similar in the subgroups, indicating that the elderly patients were more sensitive to the dose of RT. The ED50/ED95 of RT inhibiting the positive CR caused by double-lumen endobronchial intubation was 0.122/0.150 and 0.068/0.084 mg/kg in groups B and C, respectively. And, the fluctuation of blood pressure from T3 to T4 was reduced by using Dex. RT was 100% effective in sedation with no significant inhibition of circulation. Apart from one case of hypotension occurred in group A-Y, two cases of low HR in group B, and one case of low HR in group C, no other adverse events were noted. Conclusions The optimal dose of RT to inhibit positive CR induced by double-lumen bronchial intubation in elderly patients was 0.18 mg/kg and 0.23 mg/kg in younger patients. When the pre-use dose of Dex was 0.5 µg/kg, the optimal dose to inhibit positive CR of RT was 0.15 mg/kg. And, when the pre-use dose of Dex was 1 µg/kg, the optimal dose of RT was 0.9 mg/kg. Clinical trial registration NCT05631028.

Abstract To explore the factors influencing recent construction collapse accidents, this study utilizes a sample of 355 reports on building collapse accidents from 2012 to 2022. The investigation employs the systems-theoretic accident modeling and processes (STAMP) model to retrieve 22 key causal factors of accidents from the physical, operational, managerial, and supervisory layers. Subsequently, an improved decision-making trial and evaluation laboratory (DEMATEL)-interpretive structural modeling (ISM) method is used to analyze the relationships and strengths of these influencing factors, providing a comprehensive understanding of the logical connections between the causes of building collapse accidents. The results indicate that the deep-rooted causes of building collapse accidents are primarily lax safety management at the enterprise level and the exchange of interests at the government regulatory level, which in turn affect workers at the operational level and the physical aspects of accidents on-site. Furthermore, integrating the STAMP model and the triangular fuzzy DEMATEL-ISM model overcomes the limitations of the traditional STAMP model, allowing for a more focused identification of key factors.