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Abstract Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors’ feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.

Abstract Background Animal experiments have confirmed that remote ischemic preconditioning (RIPC) can reduce hepatic ischemia-reperfusion injuries (HIRIs), significantly improving early tissue perfusion and oxygenation of the residual liver after resections, accelerating surgical prognoses, and improving survival rates. However, there is still controversy over the role of RIPC in relieving HIRI in clinical studies, which warrants clarification. This study aimed to evaluate the beneficial effects and applicability of RIPC in hepatectomy and to provide evidence-based information for clinical decision-making. Methods Randomized controlled trials (RCTs) evaluating the efficacy and safety of RIPC interventions were collected, comparing RIPC to no preconditioning in patients undergoing hepatectomies. This search spanned from database inception to January 2024. Data were extracted independently by two researchers according to the PRISMA guidelines. The primary outcomes assessed were postoperative alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) levels. The secondary outcomes assessed included duration of surgery and Pringle, length of postoperative hospital stay, intraoperative blood loss and transfusion, indocyanine green (ICG) clearance, hepatocyte apoptosis index, postoperative complications, and others. Results Ten RCTs were included in this meta-analysis, with a total of 865 patients (428 in the RIPC group and 437 in the control group). ALT levels in the RIPC group were lower than those in the control group on postoperative day (POD) 1 (WMD = − 59.24, 95% CI: − 115.04 to − 3.45; P = 0.04) and POD 3 (WMD = − 27.47, 95% CI: − 52.26 to − 2.68; P = 0.03). However, heterogeneities were significant (I 2 = 89% and I 2 = 78%), and ALT levels on POD 3 were unstable based on a sensitivity analysis. AST levels on POD 1 in the RIPC group were lower than those in the control group (WMD = − 50.03, 95% CI: - 94.35 to − 5.71; P = 0.03), but heterogeneity was also significant (I 2 = 81%). A subgroup analysis showed no significant differences in ALT and AST levels on POD 1 between groups, regardless of whether the Pringle maneuver or propofol was used for anesthesia (induction only or induction and maintenance, P > 0.05). The remaining outcome indicators were not statistically significant or could not be analyzed due to lack of sufficient data. Conclusion RIPC has some short-term liver protective effects on HIRIs during hepatectomies. However, there is still insufficient evidence to encourage its routine use to improve clinical outcomes. Trial registration The protocol of this study was registered with PROSPERO (CRD42022333383).

Abstract Objective This study aimed to develop and validate an artificial intelligence radiopathological model using preoperative CT scans and postoperative hematoxylin and eosin (HE) stained slides to predict the pathological staging of gastric cancer (stage I-II and stage III). Methods This study included a total of 202 gastric cancer patients with confirmed pathological staging (training cohort: n = 141; validation cohort: n = 61). Pathological histological features were extracted from HE slides, and pathological models were constructed using logistic regression (LR), support vector machine (SVM), and NaiveBayes. The optimal pathological model was selected through receiver operating characteristic (ROC) curve analysis. Machine learnin algorithms were employed to construct radiomic models and radiopathological models using the optimal pathological model. Model performance was evaluated using ROC curve analysis, and clinical utility was estimated using decision curve analysis (DCA). Results A total of 311 pathological histological features were extracted from the HE images, including 101 Term Frequency-Inverse Document Frequency (TF-IDF) features and 210 deep learning features. A pathological model was constructed using 19 selected pathological features through dimension reduction, with the SVM model demonstrating superior predictive performance (AUC, training cohort: 0.949; validation cohort: 0.777). Radiomic features were constructed using 6 selected features from 1834 radiomic features extracted from CT scans via SVM machine algorithm. Simultaneously, a radiopathomics model was built using 17 non-zero coefficient features obtained through dimension reduction from a total of 2145 features (combining both radiomics and pathomics features). The best discriminative ability was observed in the SVM_radiopathomics model (AUC, training cohort: 0.953; validation cohort: 0.851), and clinical decision curve analysis (DCA) demonstrated excellent clinical utility. Conclusion The radiopathomics model, combining pathological and radiomic features, exhibited superior performance in distinguishing between stage I-II and stage III gastric cancer. This study is based on the prediction of pathological staging using pathological tissue slides from surgical specimens after gastric cancer curative surgery and preoperative CT images, highlighting the feasibility of conducting research on pathological staging using pathological slides and CT images.

Abstract Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Abstract Background The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. Methods We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of allo-HSCT. Results The 2-year rates of relapse, non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) were 10.9% (95% confidence interval [CI] 5.9%–17.7%), 16.3% (95% CI 10.2%–23.6%), 76.6% (95% CI 69.0%–85.1%), and 72.8% (95% CI 65.0%–81.5%) in the MF-0/1 cohort, and 16.9% (95% CI 5.8%–32.9%), 14.7% (95% CI 5.3%–28.7%), 71.8% (95% CI 57.6%–89.6%), and 68.4% (95% CI 53.6%–87.2%) in the MF-2/3 cohort, respectively. No significant difference in the outcomes of allo-HSCT was observed between the two cohorts. Both univariate and multivariate analyses confirmed that MF-2/3 in patients with MDS had no effect on the prognosis of transplantation. In addition, major/bidirectional ABO blood type between donors and recipients was an independent risk factor for OS (hazard ratio [HR], 2.55; 95% CI 1.25–5.21; P = 0.010) and PFS (HR, 2.21; 95% CI 1.10–4.42; P = 0.025) in the multivariate analysis. In the subgroup of patients diagnosed with MDS with increased blasts (MDS-IB), it was consistently demonstrated that the clinical outcomes of the MF-2/3 cohort were comparable with those of the MF-0/1 cohort. The risk factors for OS and PFS in patients with MDS-IB were non-complete remission at transplantation and major/bidirectional ABO blood type. Conclusions In conclusion, MF grade had no significant effect on prognosis of allo-HSCT in patients diagnosed with MDS. Major/bidirectional ABO blood type should be carefully considered in the context of more than one available donor.

Abstract Although the efficacy of chimeric antigen receptor (CAR)-T cell therapy has been widely demonstrated, its clinical application is hampered by the complexity and fatality of its side effects. Cytokine release syndrome (CRS) is the most common toxicity following CAR-T cell infusion, and its symptoms substantially overlap with those of infection. Whereas, current diagnostic techniques for infections are time-consuming and not highly sensitive. Thus, we are aiming to develop feasible and efficient models to optimize the differential diagnosis in clinical practice. This study included 191 febrile patients from our center, including 85 with CRS-related fever and 106 with infectious fever. By leveraging the serum cytokine profile at the peak of fever, we generated differential models using a classification tree algorithm and a stepwise logistic regression analysis, respectively. The first model utilized three cytokines (IFN-β, CXCL1, and CXCL10) and demonstrated high sensitivity (90% training, 100% validation) and specificity (98.44% training, 90.48% validation) levels. The five-cytokine model (CXCL10, CCL19, IL-4, VEGF, and CCL20) also showed high sensitivity (91.67% training, 95.65% validation) and specificity (98.44% training, 100% validation). These feasible and accurate differentiation models may prompt early diagnosis of infections during immune therapy, allowing for early and appropriate intervention.

Abstract Evidence for the involvement of N6-Methyladenosine (m6A) modification in the etiology and progression of liver fibrosis has emerged and holds promise as a therapeutic target. Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a newly identified m6A-binding protein that functions to enhance mRNA stability and translation. However, its role as an m6A-binding protein in liver fibrosis remains elusive. Here, we observed that IGF2BP2 is highly expressed in liver fibrosis and activated hepatic stellate cells (HSCs), and inhibition of IGF2BP2 protects against HSCs activation and liver fibrogenesis. Mechanistically, as an m6A-binding protein, IGF2BP2 regulates the expression of Aldolase A (ALDOA), a key target in the glycolytic metabolic pathway, which in turn regulates HSCs activation. Furthermore, we observed that active glycolytic metabolism in activated HSCs generates large amounts of lactate as a substrate for histone lactylation. Importantly, histone lactylation transforms the activation phenotype of HSCs. In conclusion, our findings reveal the essential role of IGF2BP2 in liver fibrosis by regulating glycolytic metabolism and highlight the potential of targeting IGF2BP2 as a therapeutic for liver fibrosis.

Abstract Background Eicosapentaenoic acid (EPA) is widely used in the functional food and nutraceutical industries due to its important benefits to human health. Oleaginous microorganisms are considered a promising alternative resource for the production of EPA lipids. However, the storage of EPA in triglyceride (TG) becomes a key factor limiting its level. Results This study aimed to incorporate more EPA into TG storage through metabolic engineering. Firstly, key enzymes for TG synthesis, the diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (GPAT) genes from Schizochytrium sp. HX-308 were expressed in Yarrowia lipolytica to enhance lipid and EPA accumulation. In addition, engineering the enzyme activity of DGATs through protein engineering was found to be effective in enhancing lipid synthesis by replacing the conserved motifs “HFS” in ScDGAT2A and “FFG” in ScDGAT2B with the motif “YFP”. Notably, combined with lipidomic analysis, the expression of ScDGAT2C and GPAT2 enhanced the storage of EPA in TG. Finally, the accumulation of lipid and EPA was further promoted by identifying and continuing to introduce the ScACC, ScACS, ScPDC, and ScG6PD genes from Schizochytrium sp., and the lipid and EPA titer of the final engineered strain reached 2.25 ± 0.03 g/L and 266.44 ± 5.74 mg/L, respectively, which increased by 174.39% (0.82 ± 0.02 g/L) and 282.27% (69.70 ± 0.80 mg/L) compared to the initial strain, respectively. Conclusion This study shows that the expression of lipid synthesis genes from Schizochytrium sp. in Y. lipolytica effectively improves the synthesis of lipids and EPA, which provided a promising target for EPA-enriched microbial oil production.

Abstract Hematopoietic stem and progenitor cells generate all the lineages of blood cells throughout the lifespan of vertebrates. The emergence of hematopoietic stem and progenitor cells is finely tuned by a variety of signaling pathways. Previous studies have revealed the roles of pattern-recognition receptors such as Toll-like receptors and RIG-I-like receptors in hematopoiesis. In this study, we find that Nlrc3, a nucleotide-binding domain leucine-rich repeat containing family gene, is highly expressed in hematopoietic differentiation stages in vivo and vitro and is required in hematopoiesis in zebrafish. Mechanistically, nlrc3 activates the Notch pathway and the downstream gene of Notch hey1. Furthermore, NF-kB signaling acts upstream of nlrc3 to enhance its transcriptional activity. Finally, we find that Nlrc3 signaling is conserved in the regulation of murine embryonic hematopoiesis. Taken together, our findings uncover an indispensable role of Nlrc3 signaling in hematopoietic stem and progenitor cell emergence and provide insights into inflammation-related hematopoietic ontogeny and the in vitro expansion of hematopoietic stem and progenitor cells.

Abstract Background Primary pulmonary artery sarcoma (PAS) is an extremely rare malignant tumor with a poor prognosis. The clinical manifestations of PAS are diverse, including dyspnea, chest pain, cough, and hemoptysis. The poor prognosis is often due to delayed diagnosis caused by similarity in imaging findings with pulmonary thromboembolism (PTE). These cues of diagnosis include the “wall eclipsing sign”, lobulated bulging margins, gadolinium enhancement during MRI imaging, and FDG uptake during PET/CT imaging. However, there are still many misdiagnoses. Case presentation This article reports a woman of reproductive age presenting with a pulmonary artery mass. The computed tomographic pulmonary angiography and positron emission tomography/computed tomography did not show obvious signs of pulmonary artery sarcoma, however, contrast-enhanced echocardiography showed moderate perfusion, which helped differentiate between pulmonary artery sarcoma and pulmonary artery thrombosis, leading to timely surgical treatment. Conclusions PAS is a rare form of cancer that can occasionally be visually similar to PTE on radiographic images. Early diagnosis of PAS is of vital importance to the prognosis of the patients. There are several visual cues that can help differentiate between the two conditions. Additionally, contrast-enhanced echocardiography provides additional information on tumor perfusion, offering another effective approach for a prompt and accurate diagnosis.

Abstract Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.

Background: Chimeric antigen receptor (CAR)-T cell therapy represents a significant advancement in the field of immunotherapy, providing targeted eradication of abnormal cells through the recognition between CAR and target antigens. This approach has garnered considerable attention due to its promising results in the clinical treatment of hematological malignancies and autoimmune diseases. As the focus shifts toward exploring novel targets and expanding the application of CAR-T cell therapy to solid tumors, including renal malignancies, researchers are pushing the boundaries of this innovative treatment. However, it is crucial to address the observed comorbidities associated with CAR-T cell therapy, particularly nephrotoxicity, due to the superseding release of cytokines and impairment of normal tissue. Summary: Our review discusses the research strategies and nephrotoxicity related to CAR-T cell therapy in various kidney-related diseases and provides insights into enhancing investigation and optimization. Key Messages: CAR-T cell therapy has captured the attention of researchers and clinicians in the treatment of renal malignancies, multiple myeloma, systemic lupus erythematosus, and acquired immunodeficiency syndrome, which may lead to potential nephrotoxicity as they involve primary or secondary kidney complications. Understanding and summarizing the current research progress of CAR-T cell therapies can provide valuable insights into novel targets and combinations to optimize research models and enhance their clinical value.

Vancomycin (VAN) treatment in Clostridioides difficile infection (CDI) suffers from a relatively high rate of recurrence, with a variety of reasons behind this, including biofilm-induced recurrent infections. C. difficile can form monophyletic or symbiotic biofilms with other microbes in the gut, and these biofilms protect C. difficile from being killed by antibiotics. In this study, we analyzed the ecological relationship between Bacteroides thetaiotaomicron and C. difficile and their formation of symbiotic biofilm in the VAN environment. The production of symbiotic biofilm formed by C. difficile and B. thetaiotaomicron was higher than that of C. difficile and B. thetaiotaomicron alone in the VAN environment. In symbiotic biofilms, C. difficile was characterized by increased production of the toxin protein TcdA and TcdB, up-regulation of the expression levels of the virulence genes tcdA and tcdB, enhanced bacterial cell swimming motility and c-di-GMP content, and increased adhesion to Caco-2 cells. The scanning electron microscope (SEM) combined with confocal laser scanning microscopy (CLSM) results indicated that the symbiotic biofilm was elevated in thickness, dense, and had an increased amount of mixed bacteria, while the fluorescence in situ hybridization (FISH) probe and plate colony counting results further indicated that the symbiotic biofilm had a significant increase in the amount of C. difficile cells, and was able to better tolerate the killing of the simulated intestinal fluid. Taken together, C. difficile and B. thetaiotaomicron become collaborative in the VAN environment, and targeted deletion or attenuation of host gut B. thetaiotaomicron content may improve the actual efficacy of VAN in CDI treatment.

ABSTRACTObjectives This study aims to investigate the role of excessive Protein Tyrosine Phosphatase Non-Receptor Type 21 (PTPN21) in the proliferation of Acute Lymphoblastic Leukemia (ALL) cells with EGF stimulation.Methods PTPN21 was overexpressed in ALL cell lines by lentiviral transfection. Apoptosis was assayed by Annexin V/7-AAD staining. The proliferation and cell cycle of EGF-treated ALL cells were assessed by MTT and Ki-67/7-AAD staining respectively. The phosphorylation of Src tyrosine kinase and mediators of distinct MAPK pathways were assessed by Western blot.Results Overexpression of PTPN21 had minimal effect on the apoptosis of ALL cells, but significantly promoted the proliferation and cell cycle progression of ALL cells stimulated with EGF. The activity of Src tyrosine kinase and the MAPK pathways was elevated. Inhibition of MAPK pathways by specific inhibitors mitigated this pro-proliferative effect of excessive PTPN21 on EGF-stimulated ALL cells.Conclusion PTPN21 may facilitate ALL progression by promoting cell proliferation via the Src/MAPK signaling pathways.

ABSTRACTIntestinal microbiota dysbiosis and metabolic disruption are considered essential characteristics in inflammatory bowel disorders (IBD). Reasonable butyrate supplementation can help patients regulate intestinal flora structure and promote mucosal repair. Here, to restore microbiota homeostasis and butyrate levels in the patient’s intestines, we modified the genome of Saccharomyces cerevisiae to produce butyrate. We precisely regulated the relevant metabolic pathways to enable the yeast to produce sufficient butyrate in the intestine with uneven oxygen distribution. A series of engineered strains with different butyrate synthesis abilities was constructed to meet the needs of different patients, and the strongest can reach 1.8 g/L title of butyrate. Next, this series of strains was used to co-cultivate with gut microbiota collected from patients with mild-to-moderate ulcerative colitis. After receiving treatment with engineered strains, the gut microbiota and the butyrate content have been regulated to varying degrees depending on the synthetic ability of the strain. The abundance of probiotics such as Bifidobacterium and Lactobacillus increased, while the abundance of harmful bacteria like Candidatus Bacilloplasma decreased. Meanwhile, the series of butyrate-producing yeast significantly improved trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice by restoring butyrate content. Among the series of engineered yeasts, the strain with the second-highest butyrate synthesis ability showed the most significant regulatory and the best therapeutic effect on the gut microbiota from IBD patients and the colitis mouse model. This study confirmed the existence of a therapeutic window for IBD treatment by supplementing butyrate, and it is necessary to restore butyrate levels according to the actual situation of patients to restore intestinal flora.

ABSTRACTConstructing synthetic microbial consortia is a challenging task but holds enormous potential for various applications. Our previous droplet-based microfluidic approach allowed for the isolation of bacteria that could utilize metabolites from an engineered bacterium BsS-RS06551 with anti-obesity potential, facilitating the construction of synthetic microbial consortia. Here, we identified a strain of Bifidobacterium pseudocatenulatum JJ3 that interacted with BsS-RS06551, and in vitro coculture showed that BsS-RS06551 was likely to interact with JJ3 through five dipeptides. Pathway analysis revealed that the vitamin B6 metabolism pathway was enriched in the coculture of BsS-RS06551 and JJ3 compared with the individual culture of BsS-RS06551. Additionally, we confirmed that the administration of JJ3 significantly alleviated obesity and related disorders in mice fed a high-fat diet. Notably, continuous ingestion of the synthetic microbial consortium comprising BsS-RS06551 and JJ3 not only exhibited a more pronounced impact on alleviating obesity compared to the individual administration of BsS-RS06551 or JJ3 but also enriched the population of Bifidobacterium longum and perturbed the vitamin B6 metabolism pathway in the gut. Synthetic microbial consortia represent a promising frontier for synthetic biology, and our strategy provides guidance for constructing and applying such consortia.

Due to differences in raw materials and production processes, different spirits exhibit various flavor even if undergo distillation operation. In this study, sensory analysis could clearly distinguish 5 types spirits, and had been validated through quantitative targeted flavoromics analysis. Consequently, 44 potential differential markers between 5 types spirits were screened. Among, 34 definite differential markers were further confirmed to be highly correlated with target sensory attributes and could effectively distinguish types of spirits. Ultimately, 14 key differential markers (including 2-methylbutane, linalool, acetaldehyde, d-limonene, β-myrcene, phenylethyl alcohol, phenethyl acetate, heptyl formate, ethyl octanoate, ethyl decanoate, ethyl pentanoate, ethyl hexanoate, hexanoic acid, and ethyl hexadecanoate) could reveal the chemical sources of spirit sensory and serve as targets for identifying different types of spirits. Overall, the results of flavoromic characterization of 5 types spirits provided a significant step forwards in understanding of differentiation of spirits by sensory coupled with quantitative, and statistical analysis

Effectively monitoring pest-infested areas by computer vision is essential in precision agriculture in order to minimize yield losses and create early scientific preventative solutions. However, the scale variation, complex background, and dense distribution of pests bring challenges to accurate detection when utilizing vision technology. Simultaneously, supervised learning-based object detection heavily depends on abundant labeled data, which poses practical difficulties. To overcome these obstacles, in this paper, we put forward innovative semi-supervised pest detection, PestTeacher. The framework effectively mitigates the issues of confirmation bias and instability among detection results across different iterations. To address the issue of leakage caused by the weak features of pests, we propose the Spatial-aware Multi-Resolution Feature Extraction (SMFE) module. Furthermore, we introduce a Region Proposal Network (RPN) module with a cascading architecture. This module is specifically designed to generate higher-quality anchors, which are crucial for accurate object detection. We evaluated the performance of our method on two datasets: the corn borer dataset and the Pest24 dataset. The corn borer dataset encompasses data from various corn growth cycles, while the Pest24 dataset is a large-scale, multi-pest image dataset consisting of 24 classes and 25k images. Experimental results demonstrate that the enhanced model achieves approximately 80% effectiveness with only 20% of the training set supervised in both the corn borer dataset and Pest24 dataset. Compared to the baseline model SoftTeacher, our model improves mAP@0.5 (mean Average Precision) at 7.3 compared to that of SoftTeacher at 4.6. This method offers theoretical research and technical references for automated pest identification and management.

BackgroundSome recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis.MethodsThis study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p

Benggang, an erosional phenomenon located in southern China, exhibits distinctive characteristics that can have profound ecological and agricultural consequences as well as pose risks to human life. Previous investigations have primarily focused on elucidating the relationships between the physical and chemical attributes of soils collected from Benggang. However, the precise role of free iron oxides in the surface properties of Benggang soil and its contribution to the formation of Benggang remains largely unexplored. In this study, we aim to investigate the role of free iron oxides in Benggang soil by removing them and subsequently introducing goethite to evaluate their impact on the soil’s surface properties. Our results reveal a decrease in the surface charge density of soil colloidal particles with increasing soil depth. Specifically, the uppermost red soil layer exhibits the highest value, followed by the sandy soil and the lowermost clastic layer. Upon removing free iron oxide, we documented reductions of 44.28% (red soil), 20.62% (sandy soil), and 8.70% (clastic layer) in the surface charge density of colloidal particles. The red soil layer presented an over 18-fold increase compared to the initial linear shrinkage, followed by the sandy soil and clastic layer. Notably, the addition of goethite to the iron oxide-free soil layers resulted in the recovery of approximately 81.93%, 121.13%, and 104.35% of the initial surface charge density, respectively. Moreover, significant changes in volume shrinkage were observed, with approximately 97.54% (red soil), 94.75% (sandy soil), and 89.72% (clastic layer) of the initial values being influenced. These findings underscore the substantial influence of free iron oxide on the physicochemical properties of Benggang soil and contribute to a comprehensive understanding of the erosive mechanisms underlying Benggang formation.

IntroductionThis study aims to evaluate the qualifications and identify skill enhancement areas for epidemiological investigators in Centers for Disease Control and Prevention (CDCs) in Guizhou’s, informing future training and policy initiatives to strengthen public health responses.MethodsA cross-sectional survey was conducted in August 2022, and an online, self-designed questionnaire on the Epidemiological Dynamic Data Collection platform was administered to evaluate the professional staff in CDCs. The responses were scored and presented using descriptive statistical methods, and the factors influencing the total score were analyzed by one-way ANOVA and linear regression.Results and discussionA total of 1321 questionnaires were collected, yielding an average score of 14.86±3.49 and a qualification rate of 29.9%. The scoring rate of ability of individual protection and coordination in epidemic control was high (87.25%). Meanwhile, improvements in further training were needed in areas such as data analysis ability (23.67%), knowledge of site disinfection (40.40%), and epidemiological investigation skills (42.50%). No significant difference was observed between the scores of city and county CDCs, (t = 1.071, p =0.284). The effects of gender and age could be disregarded, and the experience in epidemiological work and training (including investigation on COVID-19 cases and contacts), educational background, and professional title partially explained the survey outcome (R Square of the linear regression model was 0.351). The survey indicated the need for additional well-trained epidemiologic investigators in Guizhou. Specified training was effective in improving epidemiologic investigation, and enhancement in data analysis ability and knowledge of field disinfection are recommended in professional staff cultivation.

Aim: To explore the abundance and diversity of the gut microbiota in patients with lung cancer accompanied by chronic obstructive pulmonary disease (LC-COPD). Methods: The study cohort comprised 15 patients with LC-COPD, 49 patients with lung cancer, and 18 healthy control individuals. ELISA was used to detect inflammatory factors in venous blood. 16S rDNA sequencing was performed to determine the abundance and diversity of the gut microbiota. Gas chromatography–mass spectrometry was used to determine the concentration of short-chain fatty acids (SCFAs) in feces samples. Results: The α-diversity index indicated that the richness and diversity of the gut microbiota were lower in patients with LC-COPD compared with patients with lung cancer and controls. Principal component analysis revealed significant differences among the three groups (P 0.05). Patients with lung cancer had the lowest serum concentration of tumor necrosis factor (TNF)-a. There were no intergroup differences in the concentrations of other inflammatory factors. Conclusions: The present study indicated that the abundance and structure of the gut microbiota is altered, and the concentrations of SCFAs may be decreased in patients with LC-COPD. In addition, patients with lung cancer had the lowest serum concentration of TNF-a.

Machine learning methods have been widely used in the investigations of the complex plasmas. In this paper, we demonstrate that the unsupervised convolutional neural network can be applied to obtain the melting line in the two-dimensional complex plasmas based on the Langevin dynamics simulation results. The training samples do not need to be labeled. The resulting melting line coincides with those obtained by the analysis of hexatic order parameter and supervised machine learning method.

A tremendous amount of research has witnessed the exploration of two-dimensional (2D) materials with intrinsic ferromagnetism and diverse physical properties. However, the low Curie temperature and deficient magnetic anisotropy hinder their practical applications in nanoscale spintronics. Based on first-principles calculations, we propose a new family of 2D ternary transition metal tellurides, CrX2Te4 (X = Al, Ga, and In), with both structural and magnetic stabilities at room temperature. Our calculations demonstrate that the 2D CrX2Te4 crystal exhibits the intrinsic 100% spin-polarized half-metallic feature with spin-up metallic and spin-down semi-conducting properties. With the remarkable magnetic moment of 4 μB per Cr atom, both 2D CrAl2Te4 and CrGa2Te4 crystals perform robust ferromagnetism with the out-of-plane magnetic anisotropy, while the 2D CrIn2Te4 crystal prefers the in-plane easy magnetization axis. The Monte Carlo simulation based on the 2D Heisenberg model shows that the critical Curie temperatures of the 2D CrAl2Te4, CrGa2Te4, and CrIn2Te4 crystals could reach 466, 431, and 536 K, respectively. Moreover, the magnetic exchange strength and magnetic anisotropy could be further enhanced by the in-plane biaxial strain. The novel electronic and magnetic features promote 2D CrX2Te4 (X = Al, Ga, and In) crystals as a new family of two-dimensional intrinsic ferromagnetic materials for next-generation advanced spintronics.

In the context of sustainable development, market competition is intensifying, and financial constraints have emerged as a significant hindrance to green project investment. Green Supply Chain Finance (GSCF), characterized by long-term collaboration, has emerged as a crucial financial approach to mitigate corporate financial limitations and channel capital flows into environmentally friendly industries. We propose a two-echelon supply chain with one supplier and two competing retailers over a single period and investigate ordering, sales, and financing decisions simultaneously under competition. Retailers constrained by financial considerations may secure GSCF or traditional bank financing (BF) loans. This study investigates the influence of competition on pricing and sales strategies during the selling season. The results demonstrate that retailers select between clearance and responsive selling strategies based on the level of market competition. During the ordering season, retailers share the product market equally when interest rates are uniform, and the supplier formulates a supply chain contract while considering the financing interest rate. In the presence of differential interest rates, retailers may not always opt for the GSCF, even when they offer an interest rate advantage, due to the comprehensive impacts of operational and financial strategies. Remarkably, competitive retailers do not choose the GSCF when their initial green investment capital surpasses a certain threshold.

According to Milankovitch’s theory, periodic climate change in Earth’s history is controlled by the periodic changes in the Earth’s orbit and axis of rotation. Milankovitch cycle include eccentricity, obliquity, and precession cycles. In addition to them, there are also some amplitude modulation (AM) cycles that affect the climate system through a series of “nonlinear” feedback processes, such as the 173 kyr obliquity AM cycle. Previous studies have demonstrated that the ∼170 kyr cycle modulate the paleoclimate and carbon cycle at mid-high latitude regions in the Meso-Cenozoic. However, due to the limitation of astronomical solutions and the lack of high-resolution geological records, the ∼170 kyr cycle has been less reported in the Paleozoic Era. In this study, cyclostratigraphic analysis of natural gamma ray (GR) logging data from four wells (Ji30, Ji31, Ji32, and Ji174) and total organic carbon (TOC) data from well Ji174 penetrating the Early Permian Lucaogou Formation in Jimusar Sag, Junggar Basin suggests preservation of eccentricity, obliquity, and precession cycles, and the ∼170 kyr AM cycle. Through the astronomical tuning of GR logging data obtained from four wells to eccentricity target cycles, we established the floating astronomical time scale (ATS). The results indicate an average sedimentation rate ranging from 7.4 to 9.5 cm/kyr and a duration from 2.8 to 3.2 million years (Myr) for the Lucaogou Formation. The differences in sedimentation rate and duration among these four wells may result from different well locations. Moreover, the ∼170 kyr cycle signal has been identified in the detrended GR logging and TOC data series, and its obliquity AM series. This signal might be attributed to the obliquity AM cycles originated from the interaction between s3 and s6 (s3 and s6 represent the precession of nodes of Earth and Saturn), which was recorded in the GR logging and TOC data time series due to nonlinear responses within the depositional system.

Summary: Epigenetic modification shapes differentiation trajectory and regulates the exhaustion state of chimeric antigen receptor T (CAR-T) cells. Limited efficacy induced by terminal exhaustion closely ties with intrinsic transcriptional regulation. However, the comprehensive regulatory mechanisms remain largely elusive. Here, we identify class I histone deacetylase inhibitors (HDACi) as boosters of CAR-T cell function by high-throughput screening of chromatin-modifying drugs, in which M344 and chidamide enhance memory maintenance and resistance to exhaustion of CAR-T cells that induce sustained antitumor efficacy both in vitro and in vivo. Mechanistically, HDACi decrease HDAC1 expression and enhance H3K27ac activity. Multi-omics analyses from RNA-seq, ATAC-seq, and H3K27ac CUT&Tag-seq show that HDACi upregulate expression of TCF4, LEF1, and CTNNB1, which subsequently activate the canonical Wnt/β-catenin pathway. Collectively, our findings elucidate the functional roles of class I HDACi in enhancing CAR-T cell function, which provides the basis and therapeutic targets for synergic combination of CAR-T cell therapy and HDACi treatment.

Septic cardiomyopathy (SCM) is associated with an imbalance in mitochondrial quality and high mortality rates, with no effective treatment developed to date. Curcumin provides antioxidant, anti-inflammatory, cardiovascular, and mitochondrial protection. However, curcumin has not been confirmed to improve cardiac dysfunction in sepsis. We hypothesized that curcumin can reduce abnormal inflammatory responses by improving mitochondrial function as a novel mechanism to improve SCM. To explore this hypothesis, we used an in vivo male C57BL/6 mouse sepsis model and an in vitro model of lipopolysaccharide-stimulated HL-1 cells. The effects of curcumin on sepsis-induced cardiac dysfunction, inflammatory responses, and mitochondrial quality of cardiac cells were observed using quantitative polymerase chain reaction, western blotting, echocardiography, and transmission electron microscopy. Curcumin activated sirtuin 1 (SIRT1); increased expression of the mitochondrial biogenesis-related genes Pgc1α, Tfam, and Nrf2; reduced dynamin-related protein 1 translocation from the cytoplasm to mitochondria; and restored the mitochondrial morphology and function in cardiac cells. Accordingly, curcumin protected heart function after septic shock and alleviated the effects of SCM. SIRT1 knockdown reversed the protective effects of curcumin on mitochondria. Therefore, curcumin promotes mitochondrial biogenesis and inhibits mitochondrial fragmentation by activating SIRT1, thereby improving the mitochondrial quality and reducing oxidative stress in cardiomyocytes and sepsis-induced cardiac dysfunction. These findings provide new evidence supporting the use of curcumin to treat SCM.

Purpose: TNF family members (TFMs) play a crucial role in different types of cancers, with TNF Receptor Superfamily Member 19 (TNFRSF19) standing out as a particularly important member in this category. Further research is necessary to investigate the potential impact of TFMs on prognosis prediction and to elucidate the function and potential therapeutic targets linked to TNFRSF19 expression in gliomas. Methods: Three databases provided the data on gene expression and clinical information. Fourteen prognostic members were found through univariate Cox analysis and subsequently utilized to construct TFMs-based model in LASSO and multivariate Cox analyses. TFMs-based subtypes based on the expression profile were identified using an unsupervised clustering method. Machine learning algorithm identified key genes linked to prognostic model and subtype. A sequence of immune infiltrations was evaluated using the ssGSEA and ESTIMATE algorithms. Immunohistochemistry was used to examine the patterns of expression and the clinical significance of TNFRSF19. Results: Our development of a prognostic model and subtypes based on the TNF family was successful, resulting in accurate predictions of prognosis. The findings indicate that TNFRSF19 exhibited strong performance. Upregulation of TNFRSF19 was correlated with malignant phenotypes and poor prognosis, which was confirmed through immunohistochemistry. TNFRSF19 played a role in reshaping the immunosuppressive microenvironment in gliomas, and multiple drug-targeted TNFRSF19 molecules were identified. Conclusions: The TMF-based prognostic model and subtype can facilitate treatment decisions for glioma. TNFRSF19 is an outstanding representative of a predictor of prognosis and immunotherapy effect in gliomas.

Abstract Background Mitophagy is a process of selectively degrading damaged mitochondria, which has been found to be related to immunity, tumorigenesis, tumor progression, and metastasis. However, the role of mitophagy-related genes (MRGs) in the tumor microenvironment (TME) of ovarian cancer (OV) remains largely unexplored. Methods We analyzed the expression, prognosis, and genetic alterations of 29 MRGs in 480 OV samples. Unsupervised clustering was used to classify OV into two subtypes (clusters A and B) based on MRG changes. We compared the clinical features, differential expressed genes (DEGs), pathways, and immune cell infiltration between the two clusters. We constructed a mitophagy scoring system (MRG_score) based on the DEGs and validated its ability to predict overall survival of OV patients. Results We found that patients with high MRG_scores had better survival status and increased infiltration by immune cells. Further analysis showed that these patients may be more sensitive to immune checkpoint inhibitor (ICI) treatment. Additionally, the MRG_score significantly correlated with the sensitivity of chemotherapeutic drugs and targeted inhibitors. Conclusion Our comprehensive analysis of MRGs in the TME, clinical features, and patient prognosis revealed that the MRG_score is a potentially effective prognostic biomarker and predictor of treatment. This study provides new insights into the role of MRGs in OV and identifies patients who may benefit from ICI treatment, chemotherapy, or targeted treatment.

Abstract The consumption of alcohol reflects both societal norms and personal choices and has major clinical implications. Long‐term excess alcohol consumption leads to a domino effect of pathological outcomes and onset of chronic illness. However, the risks of alcohol consumption extend beyond long‐term health issues. Because habitual alcohol drinkers reach a state of systemic homeostasis, when they attempt withdrawal, they experience many negative physiological effects and may develop alcohol withdrawal syndrome. The complex interplay between alcohol consumption and withdrawal does not result solely in behavioral issues. Rather, a substantial number of important physiological adaptations and potential problems underly habitual drinking. Addressing these issues requires comprehensive medical observation and intervention. Here, we summarize the pathophysiological mechanisms, clinical diseases, and related treatment methods of alcohol consumption and withdrawal. The aim was to provide a reference to improve understanding of alcohol use and promote an informed approach to alcohol withdrawal.

Special environmental microorganisms are considered to be of great industrial application value because of their special genotypes, physiological functions and metabolites. The research and development of special environmental microorganisms will certainly bring about some innovations in biotechnology processes and change the face of bioengineering. The Special Environmental Microbial Database (DSEMR) is a comprehensive database that provides information on special environmental microbial resources and correlates them with synthetic biological parts. DSEMR aggregates information on specific environmental microbial genomes, physiological properties, culture media, biological parts, and metabolic pathways, and provides online tool analysis data, including 5268 strains from 620 genera, 31 media, and 42,126 biological parts. In short, DSEMR will become an important resource for the study of microorganisms in special environments and actively promote the development of synthetic biology.

Abstract Background Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era. Methods A total of 5089 newly diagnosed DLBCL patients treated with rituximab‐containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group‐affiliated institutes were identified, of whom 135 diagnosed with PB‐DLBCL were eligible for this analysis. Results PB‐DLBCL accounted for 2.7% of all DLBCLs. With a median follow‐up of 4.2 years, the 5‐year overall survival and progression‐free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5‐year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high‐dose methotrexate (HD‐MTX) than for patients who did not (5‐year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB‐DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD‐MTX did not experience CNS relapse. Conclusion Collectively, our results indicate combined modality therapy including rituximab‐containing immunochemotherapy and consolidative breast RT is a promising approach for PB‐DLBCL, while HD‐MTX is useful for preventing CNS relapse.

ABSTRACTThe aging process is crucial to improve the harmony and fullness of the flavor of baijiu. Nevertheless, the traditional aging process consumes space and times and significantly increased the loss of baijiu. Hence, how to shorten the aging time through manual intervention becomes the research hotspot. Thus, a new aging method of exposure to sunlight was established to accelerate the balance of flavor compounds in baijiu. It was still unclear about the quality variance factors and its influence on the flavor quality of BCSGB (banchengshaoguo baijiu) during the sun-exposure process. Hence, adsorption pen combined with GC–MS were utilized to identify trace components, and pH liquid–liquid extraction and GC–O–MS were employed to screen and assess flavor compounds. Afterward, based on the sensory evaluation of BCSGB, three assessment systems (sensory evaluation, mental test, and random forest) were created to screen the quality variance factors. Thus, the quality variance factors were responsive to changes in the flavor quality of BCSGB during the sun-exposure process, which support process quality monitoring and aging process optimization.

Background Mechanical ventilation, particularly one-lung ventilation (OLV), can cause pulmonary dysfunction. This meta-analysis assessed the effects of dexmedetomidine on the pulmonary function of patients receiving OLV. Methods The Embase, PubMed, MEDLINE, Cochrane Library, ClinicalTrials.gov, and Chinese Clinical Trial Registry databases were systematically searched. The primary outcome was oxygenation index (OI). Other outcomes including the incidence of postoperative complications were assessed. Results Fourteen randomized controlled trials involving 845 patients were included in this meta-analysis. Dexmedetomidine improved the OI at 30 (mean difference [MD]: 40.49, 95% CI [10.21, 70.78]), 60 (MD: 60.86, 95% CI [35.81, 85.92]), and 90 min (MD: 55, 95% CI [34.89, 75.11]) after OLV and after surgery (MD: 28.98, 95% CI [17.94, 40.0]) and improved lung compliance 90 min after OLV (MD: 3.62, 95% CI [1.7, 5.53]). Additionally, dexmedetomidine reduced the incidence of postoperative pulmonary complications (odds ratio: 0.44, 95% CI [0.24, 0.82]) and length of hospital stay (MD: −0.99, 95% CI [−1.25, −0.73]); decreased tumor necrosis factor-α, interleukin (IL)-6, IL-8, and malondialdehyde levels; and increased superoxide dismutase levels. However, only the results for the OI and IL-6 levels were confirmed by the sensitivity and trial sequential analyses. Conclusions Dexmedetomidine improves oxygenation in patients receiving OLV and may additionally decrease the incidence of postoperative pulmonary complications and shorten the length of hospital stay, which may be related to associated improvements in lung compliance, anti-inflammatory effects, and regulation of oxidative stress reactions. However, robust evidence is required to confirm these conclusions.

Abstract Background Daylength is a key seasonal cue for animals and plants. In cereals, photoperiodic responses are a major adaptive trait, and alleles of clock genes such as PHOTOPERIOD1 (PPD1) and EARLY FLOWERING3 (ELF3) have been selected for in adapting barley and wheat to northern latitudes. How monocot plants sense photoperiod and integrate this information into growth and development is not well understood. Results We find that phytochrome C (PHYC) is essential for flowering in Brachypodium distachyon. Conversely, ELF3 acts as a floral repressor and elf3 mutants display a constitutive long day phenotype and transcriptome. We find that ELF3 and PHYC occur in a common complex. ELF3 associates with the promoters of a number of conserved regulators of flowering, including PPD1 and VRN1. Consistent with observations in barley, we are able to show that PPD1 overexpression accelerates flowering in short days and is necessary for rapid flowering in response to long days. PHYC is in the active Pfr state at the end of the day, but we observe it undergoes dark reversion over the course of the night. Conclusions We propose that PHYC acts as a molecular timer and communicates information on night-length to the circadian clock via ELF3.