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Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

Abstract Background Tuberculous meningitis (TBM) emerges as a grave complication of tuberculosis in people living with HIV (PLWH). The diagnosis and treatment of TBM pose significant challenges, leading to elevated mortality rates. To comprehensively grasp the epidemiological landscape of TBM in PLWH, a systematic review and meta-analysis were meticulously undertaken. Methods We performed a comprehensive search in PubMed, Embase, and Web of Science from database inception to September 19th, 2023, with no limitations on the publication type. The search terms were HIV/AIDS terms (AIDS OR HIV OR PLWH) and TBM-related terms (tuberculous meningitis OR TBM). Studies included in this meta-analysis evaluated the incidence of TBM among PLWH, or we were able to calculate the incidence of TBM among PLWH from the research. Results The analysis revealed that the prevalence of TBM among PLWH was 13.6% (95% CI: 6.6–25.9%), with an incidence rate of 1.5 cases per 1000 persons per year. The case fatality rate was found to be 38.1% (95% CI: 24.3–54.1%). No significant publication bias was observed. Meta-regression analysis identified the proportion of females and finance situation as factors influencing the outcomes. Conclusions Our study highlights TBM as a prevalent opportunistic infection that targets the central nervous system in PLWH. The elevated case fatality rate is especially prominent among PLWH in impoverished regions, underscores the pressing necessity for enhanced management strategies for PLWH suffering from TBM. Trial registration PROSPERO; No: CRD42022338586.

Abstract Background Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. Methods This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan–Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). Results We included 132 patients in this study, divided into RDI

Abstract Background Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in China. Microvascular invasion (MVI) often indicates poor prognosis and metastasis in HCC patients. 18F-FDG PET–CT is a new imaging method commonly used to screen for tumor occurrence and evaluate tumor stage. Purpose This study attempted to predict the occurrence of MVI in early-stage HCC through 18F-FDG positron emission tomography (PET)/computed tomography (CT) imaging findings and laboratory data. Patients and methods A total of 113 patients who met the inclusion criteria were divided into two groups based on postoperative pathology: the MVI-positive group and MVI-negative group. We retrospectively analyzed the imaging findings and laboratory data of 113 patients. Imaging findings included tumor size, tumor maximum standard uptake value (SUVmaxT), and normal liver maximum standard uptake value (SUVmaxL). The ratios of SUVmaxT to SUVmaxL (SUVmaxT/L) and an SUVmaxT/L > 2 were defined as active tumor metabolism. The tumor size was indicated by the maximum diameter of the tumor, and a diameter greater than 5 cm was defined as a mass lesion. The laboratory data included the alpha-fetoprotein (AFP) level and the HBeAg level. An AFP concentration > 20 ng/mL was defined as a high AFP level. A HBeAg concentration > 0.03 NCU/mL was defined as HB-positive. Results The SUVmaxT/L (p = 0.003), AFP level (p = 0.008) and tumor size (p = 0.015) were significantly different between the two groups. Patients with active tumor metabolism, mass lesions and high AFP levels tended to be MVI positive. Binary logistic regression analysis verified that active tumor metabolism (OR = 4.124, 95% CI, 1.566–10.861; p = 0.004) and high AFP levels (OR = 2.702, 95% CI, 1.214–6.021; p = 0.015) were independent risk factors for MVI. The sensitivity of the combination of these two independent risk factors predicting HCC with MVI was 56.9% (29/51), the specificity was 83.9% (52/62) and the accuracy was 71.7% (81/113). Conclusion Active tumor metabolism and high AFP levels can predict the occurrence of MVI in HCC patients.

Abstract Background Pichia pastoris (Komagataella phaffii) is a promising production host, but the usage of methanol limits its application in the medicine and food industries. Results To improve the constitutive expression of heterologous proteins in P. pastoris, four new potential transcription regulators (Loc1p, Msn2p, Gsm1p, Hot1p) of the glyceraldehyde triphosphate dehydrogenase promoter (pGAP) were revealed in this study by using cellulase E4 as reporter gene. On this basis, a series of P. pastoris strains with knockout or overexpression of transcription factors were constructed and the deletion of transcription factor binding sites on pGAP was confirmed. The results showed that Loc1p and Msn2p can inhibit the activity of pGAP, while Gsm1p and Hot1p can enhance the activity of pGAP; Loc1p, Gsm1p and Hot1p can bind directly to pGAP, while Msn2p must be treated to expose the C-terminal domain to bind to pGAP. Moreover, manipulating a single transcription factor led to a 0.96-fold to 2.43-fold increase in xylanase expression. In another model protein, aflatoxin oxidase, knocking out Loc1 based on AFO-∆Msn2 strain resulted in a 0.63-fold to 1.4-fold increase in expression. It can be demonstrated that the combined use of transcription factors can further improve the expression of exogenous proteins in P. pastoris. Conclusion These findings will contribute to the construction of pGAP-based P. pastoris systems towards high expression of heterologous proteins, hence improving the application potential of yeast.

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.

MXenes, a novel class of two-dimensional (2D) materials, have attracted considerable attention in various fields, especially in drug delivery, wound healing, bone tissue engineering, biosensing, and cancer treatment. Thanks to their remarkable physicochemical properties, MXenes hold great promise for biomedical applications. Concurrently, hydrogels composed of polymers have been extensively utilized in biomedical contexts. The unique properties of MXenes facilitate their integration into various bioactive hydrogels with enhanced functions and properties, thereby endowing the composites with multifunctional capabilities. MXene-reinforced polymer hydrogels (MRPHs) synergistically combine the advantageous characteristics of both MXenes and hydrogels, making them highly adaptable for integration with other theranostic strategies in medical applications. In this comprehensive review, we demonstrate recent advances in the design and synthesis of MRPHs for biomedical applications. Specifically, we introduce the unique functions and properties of MRPHs and analyze the methods for tailoring the functions of MRPHs by incorporating them with other active components, including functional molecules, 2D materials, metal ions, natural polymers, and drugs/genes. We then discuss the biomedical applications of the designed bioactive MRPHs in wound healing, tissue engineering, biosensors, and cancer therapy. We hope that this work provides valuable guidance and inspiration for readers to develop novel MRPHs for advanced applications.

Anthocyanins are plant secondary metabolites belonging to the polyphenol class of natural water-soluble phytopigments. The accumulation of anthocyanins in different plant tissues can improve plant survival under adverse conditions. In addition, plants with the resulting colorful morphology can be utilized as landscape plants. Triticum boeoticum (syn. Triticum monococcum ssp. aegilopoides, 2n=2x=14, AbAb) serves as a valuable genetic resource for the improvement of its close relative common wheat in terms of enhancing resilience to various biotic and abiotic stresses. In our previous study, the EMS-mutagenized mutant Z2921 with a red glume, stem, and rachis was generated from T. boeoticum G52, which has a green glume, stem, and rachis. In this study, the F1, F2, and F2:3 generations of a cross between mutant-type Z2921 and wild-type G52 were developed. A single recessive gene, tentatively designated RgM4G52, was identified in Z2921 via genetic analysis. Using bulked segregant exome capture sequencing (BSE-Seq) analysis, RgM4G52 was mapped to chromosome 6AL and was flanked by the markers KASP-58 and KASP-26 within a 3.40-cM genetic interval corresponding to 1.71-Mb and 1.61-Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Triticum boeoticum (TA299) reference genomes, respectively, in which seven and four genes related to anthocyanin synthesis development were annotated. Unlike previously reported color morphology-related genes, RgM4G52 is a recessive gene that can simultaneously control the color of glumes, stems, and rachis in wild einkorn. In addition, a synthetic Triticum dicoccum–T. boeoticum amphiploid Syn-ABAb-34, derived from the colchicine treatment of F1 hybrids between tetraploid wheat PI 352367 (T. dicoccum, AABB) and Z2921, expressed the red stems of Z2921. The flanking markers of RgM4G52 developed in this study could be useful for developing additional common wheat lines with red stems, laying the foundation for marker-assisted breeding and the fine mapping of RgM4G52.

The stability of soil organic carbon (SOC) is crucial for the global carbon cycle and serves as a key indicator of soil quality and eco-system function. In Karst areas, SOC stability is influenced by unique geological conditions. Studying SOC stability in these regions is significant for understanding regional ecosystem functions and the role of SOC in mitigating global climate change. This review examines the fractions and stability of SOC in Karst areas, analyzing the impacts of key factors such as rocky desertification, land use changes, and vegetation restoration on SOC stability, along with their underlying mechanisms. It also discusses the current challenges and opportunities in SOC stability. This review aims to guide the development of effective ecological rehabilitation and management strategies for degraded ecosystems in Karst areas.

ObjectiveThe aim of this study was to compare hematological parameters pre- and early post-chemotherapy, and evaluate their values for predicting febrile neutropenia (FN).MethodsPatients diagnosed with malignant solid tumors receiving chemotherapy were included. Blood cell counts peri-chemotherapy and clinical information were retrieved from the hospital information system. We used the least absolute shrinkage and selection operator (LASSO) method for variable selection and fitted selected variables to a logistic model. We assessed the performance of the prediction model by the area under the ROC curve.ResultsThe study population consisted of 4,130 patients with common solid tumors receiving a three-week chemotherapy regimen in Sichuan Cancer Hospital from February 2019 to March 2022. In the FN group, change percentage of neutrophil count decreased less (−0.02, CI: −0.88 to 3.48 vs. −0.04, CI: −0.83 to 2.24). Among hematological parameters, lower post-chemotherapy lymphocyte count (OR 0.942, CI: 0.934–0.949), change percentage of platelet (OR 0.965, CI: 0.955–0.975) and higher change percentage of post-chemotherapy neutrophil count (OR 1.015, CI: 1.011–1.018), and pre-chemotherapy NLR (OR 1.002, CI: 1.002–1.002) predicted an increased risk of FN. These factors improved the predicting model based on clinical factors alone. The AUC of the combination model was 0.8275.ConclusionPeri-chemotherapy hematological markers improve the prediction of FN.

Aeolian sandy soil and loess soil of the Mu Us Sandy Land are used as the research material in this study to investigate the effect of soil compounding on the improvement of aeolian sandy soil and to provide a feasible approach for sand prevention and sand control. In particular, loess soils were compounded at 0%, 20%, 40%, 60%, 80%, and 100% by volume percentage of the compounded soils. The improvement benefits of compounded soils on their textural properties, water-holding capacity, and fertilizer-retention capacity at different blending ratios were evaluated. The results showed that following the compounding of aeolian sandy and loess soils, with the increase of the loess proportion, the texture type of the compounded soil transforms from sandy soil to loamy sandy soil to sandy loam to loamy soil to powdery loam. Moreover, granular gradation was observed, the bulk density gradually decreased, the capillary porosity gradually increased, and the performance of water- and fertilizer-holding properties gradually increased and strengthened. The spatial variability of compounded soil bulk density, capillary porosity, and the water-holding and fertilizer-retention properties was almost entirely controlled by the proportion of loess soil. A theoretical basis is provided in this study for aeolian sandy soil improvement in the Mu Us Sandy Land that can be extended to similar areas, providing a feasible sand management approach.

Objectives: To evaluate the effectiveness of music therapy in reducing anxiety, pain, and vital sign changes in ophthalmic surgery patients. Methods: An extensive search of databases, including PubMed, Embase, Cochrane, Web of Science, and Google Scholar, identified relevant studies up to Jan 2024. Selection of studies was conducted based on the PICOS criteria. The quality of methodology was assessed using the Cochrane risk-of-bias assessment tool and Review Manager 5.4. Meta-analysis comparing the control group and the music therapy group was performed using R and Stata/SE 15.1 random or fixed effects model. Results: This meta-analysis included fifteen studies comprising 2098 participants. The analysis revealed that music therapy significantly reduced the risk of high anxiety levels as measured by Visual Analogue Scale (VAS) (I2 = 0 %, RR(95 %CI): 0.75(0.63, 0.88), p = 0.0006), indicating a substantial effect without heterogeneity. The Anxiety scores determined by State-Trait Anxiety Inventory-State (STAI-S) also showed a significant decrease (SMD(95 %CI): −0.75(−0.88, −0.61), 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 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

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.