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The onset of the Asian summer monsoon (ASM) starts the rainy season in one of the most world populous regions. The present study found that the stepwise ASM onset process (ASMOP) in the Bay of Bengal, South China Sea (SCS), and India exhibits three distinct interannual modes induced by different sea surface temperature anomalies (SSTAs). The first mode features are in‐phase variation of ASMOP in southern Asia, which originates from the ENSO‐related SSTAs and anomalous circulations in the tropical Indo‐Pacific Ocean. The second mode indicates the anomalous ASMOP in India and depends on the southwestern Indian SSTAs that alter the low‐level cross‐equatorial flow over the Arabian Sea. In the third mode, the western North Pacific SSTAs and their resultant circulation anomalies regulate ASMOP in the northern SCS. These extra‐equatorial SSTAs and their associated air‐sea interaction serve as an additional source of seasonal predictability for ASMOP besides El Niño–Southern Oscillation events. Plain Language Summary The onset of the Asian summer monsoon (ASM) begins the rainy season in South and East Asia, one of the world's most populous regions. In general, the ASM onset process (ASMOP) follows a stepwise progression over the Bay of Bengal (BOB), South China Sea (SCS), and India, in turn. The year‐by‐year relationship between the monsoon onset dates over these areas helps to predict the arrival of the monsoon in Asian countries. However, there is no consensus on the year‐by‐year relationship of ASMOP among these areas. The present study used a unified definition to revisit the distinct modes of interannual variation in ASMOP. The El Niño–Southern Oscillation (ENSO)–associated tropical sea surface temperature anomalies (SSTAs) in the Indian and Pacific oceans can modify ASMOP over BOB, the southern SCS, and India simultaneously. Besides the influence of ENSO, the SSTAs in the southwestern Indian Ocean can regulate ASMOP in India. At the same time, the SSTAs modulate ASMOP in the northern SCS in the western North Pacific. Results from numerical experiments verified that air–sea interaction is critical for the effect of extra‐equatorial SSTAs on ASMOP, which provides an additional source of seasonal predictability of ASMOP besides ENSO factors. Key Points The Asian summer monsoon onset process (ASMOP) shows distinct interannual modes in the tropics El Niño–Southern Oscillation determines the interannual variability in ASMOP over India, the Bay of Bengal, and the southern South China Sea (SCS) The southwestern Indian and western Pacific sea surface temperature anomalies modulate ASMOP over India and the northern SCS via air–sea interaction, respectively

Background Kawasaki disease (KD) mainly occurs in children under 5 years old, and the most common complication of KD is coronary artery lesion (CAL). In recent years, the incidence rate of KD has increased year by year worldwide, so it is particularly important to strengthen the diagnosis of KD and identify CAL early. Method This retrospective cohort study included a total of 436 children diagnosed with Kawasaki disease and aimed to develop a predictive model for CAL using early clinical symptoms and laboratory features. To reduce potential confounding, propensity score matching (PSM) was applied, and both univariate and multivariate analyses were conducted to identify significant predictors of CAL. Subsequently, through machine learning, a predictive column chart model was constructed using clinical features and routine laboratory blood indicators, and the model was evaluated using ROC curves, calibration curves, and DCA curves. Result This study found that gender, medical history, cough, diarrhea symptoms, and high CRP levels were independent risk factors for concurrent CAL. To further predict CAL risk, a column chart model was constructed based on LASSO regression and ten fold cross validation. The ROC curve in the training queue showed good discriminative ability (AUC: 0.879), while the ROC curve in the validation queue showed good discriminative ability (AUC: 0.859). This model exhibits good discriminative ability, high accuracy, and potential clinical benefits in both training and validation sets. Conclusion Through this study, we provide clinicians with a new tool to more accurately predict and manage CAL risk in children with KD, which can help optimize treatment strategies and improve efficacy.

Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders. Mesenchymal stem cells (MSC) are used for immunosuppressive therapy and a uniform source or heterogeneity characterisation is needed. Here the authors use multi-omics to compare human MSC from different sources and ages of donors and show differences in gene expression and immunosuppressive function.

For the clearing of hazy images, it is difficult to obtain dehazing datasets with paired mapping images. Currently, most algorithms are trained on synthetic datasets with insufficient complexity, which leads to model overfitting. At the same time, the physical characteristics of fog in the real world are ignored in most current algorithms; that is, the degree of fog is related to the depth of field and scattering coefficient. Moreover, most current dehazing algorithms only consider the image dehazing of land scenes and ignore maritime scenes. To address these problems, we propose a multi-scene image dehazing algorithm based on an improved cycle generative adversarial network (CycleGAN). The generator structure is improved based on the CycleGAN model, and a feature fusion attention module is proposed. This module obtains relevant contextual information by extracting different levels of features. The obtained feature information is fused using the idea of residual connections. An attention mechanism is introduced in this module to retain more feature information by assigning different weights. During the training process, the atmospheric scattering model is established to guide the learning of the neural network using its prior information. The experimental results show that, compared with the baseline model, the peak signal-to-noise ratio (PSNR) increases by 32.10%, the structural similarity index (SSIM) increases by 31.07%, the information entropy (IE) increases by 4.79%, and the NIQE index is reduced by 20.1% in quantitative comparison. Meanwhile, it demonstrates better visual effects than other advanced algorithms in qualitative comparisons on synthetic datasets and real datasets.

Background Apple replant disease is a soilborne disease caused by Fusarium proliferatum f. sp. malus domestica strain MR5 (abbreviated hereafter as Fpmd MR5) in China. This pathogen causes root tissue rot and wilting leaves in apple seedlings, leading to plant death. A comparative transcriptome analysis was conducted using the Illumina Novaseq platform to identify the molecular defense mechanisms of the susceptible M.26 and the resistant M9T337 apple rootstocks to Fpmd MR5 infection. Results Approximately 518.1 million high-quality reads were generated using RNA sequencing (RNA-seq). Comparative analysis between the mock-inoculated and Fpmd MR5 infected apple rootstocks revealed 28,196 significantly differentially expressed genes (DEGs), including 14,572 up-regulated and 13,624 down-regulated genes. Among them, the transcriptomes in the roots of the susceptible genotype M.26 were reflected by overrepresented DEGs. MapMan analysis indicated that a large number of DEGs were involved in the response of apple plants to Fpmd MR5 stress. The important functional groups identified via gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were responsible for fundamental biological regulation, secondary metabolism, plant-pathogen recognition, and plant hormone signal transduction (ethylene and jasmonate). Furthermore, the expression of 33 up-regulated candidate genes (12 related to WRKY DNA-binding proteins, one encoding endochitinase, two encoding beta-glucosidases, ten related to pathogenesis-related proteins, and eight encoding ethylene-responsive transcription factors) were validated by quantitative real-time PCR. Conclusion RNA-seq profiling was performed for the first time to analyze response of apple root to Fpmd MR5 infection. We found that the production of antimicrobial compounds and antioxidants enhanced plant resistance to pathogens, and pathogenesis-related protein (PR10 homologs, chitinase, and beta-glucosidase) may play unique roles in the defense response. These results provide new insights into the mechanisms of the apple root response to Fpmd MR5 infection.

Brown adipose tissue (BAT) dissipates metabolic energy and mediates non-shivering thermogenesis, thereby boosting energy expenditure. Increasing BAT mass and activity is expected to be a promising strategy for combating obesity; however, few medications effectively and safely recruit and activate BAT in humans. Berberine (BBR), a natural compound, is commonly used as a nonprescription drug to treat diarrhea. Here, we reported that 1-month BBR intervention increased BAT mass and activity, reduced body weight, and improved insulin sensitivity in mildly overweight patients with non-alcoholic fatty liver disease. Chronic BBR treatment promoted BAT development by stimulating the expression of brown adipogenic genes, enhanced BAT thermogenesis, and global energy expenditure in diet-induced obese mice and chow-fed lean mice, Consistently, BBR facilitated brown adipocyte differentiation in both mouse and human primary brown preadipocytes. We further found that BBR increased the transcription of PRDM16, a master regulator of brown/beige adipogenesis, by inducing the active DNA demethylation of PRDM16 promoter, which might be driven by the activation of AMPK and production of its downstream tricarboxylic acid cycle intermediate α-Ketoglutarate. Moreover, chronic BBR administration had no impact on the BAT thermogenesis in adipose-specific AMPKa1 and AMPKa2 knockout mice. In summary, we found that BBR intervention promoted recruitment and activation of BAT and AMPK–PRDM16 axis was indispensable for the pro-BAT and pro-energy expenditure properties of BBR. Our findings suggest that BBR may be a promising drug for obesity and related metabolic disorders in humans partially through activating BAT.

Background Endometriosis (EM) is a prevalent gynecological condition impacting roughly 10% of women of reproductive age worldwide, causing chronic pain, infertility, and menstrual irregularities. Traditional diagnosis typically relies on invasive surgical methods, and non-invasive diagnostic techniques remain underdeveloped. This study seeks to investigate the association between creatinine levels and endometriosis through cross-sectional analysis and mendelian randomization (MR) analysis, while also developing and assessing diagnostic models. Method This research integrates data from the NHANES database (1999–2006) and the affiliated hospital of Jining Medical College in China. The study cohort consists of women aged 20–60, with data collection covering age, race, education level, marital status, family income, weight, height, body mass index(BMI), and serum creatinine levels. Logistic regression models were used for univariate and multivariate analyses. Bidirectional MR analysis, utilizing genetic variation data from Large Genome Association Studies (GWAS), was performed to evaluate causal relationships using the inverse variance weighted (IVW) method, complemented by sensitivity analysis. A diagnostic model based on data from top-tier hospitals in China was constructed and its performance assessed through receiver operating characteristic(ROC) curves, area under the curve(AUC) values, and calibration curves. Result In the NHANES dataset, univariate analysis indicated a significant correlation between creatinine levels and endometriosis (OR = 1.01, 95% CI: 1.00–1.01, P  = 0.0048), while multivariate analysis maintained significant results after adjustment (OR = 1.00, 95% CI: 1.00–1.01, P  = 0.0431). Bidirectional MR analysis demonstrated a causal relationship between creatinine levels and endometriosis, with a positive IVW result of 1.001 (95% CI: 1.00–1.002, P  = 0.0350). In the chinese tertiary hospital dataset, the AUC for the diagnostic model on both training and validation sets were 0.721 and 0.730, respectively. An increase of 10 μmol/L in creatinine levels raised the risk of endometriosis by approximately 8% (OR = 1.08, 95% CI: 1.07–1.09, P  < 0.001). Conclusion This study establishes a significant link between creatinine levels and endometriosis, confirming creatinine as an independent risk factor. Elevated creatinine levels could be used as non-invasive biomarkers for the early detection and diagnosis of endometriosis. Future research should aim to validate these findings in larger, multicenter studies and delve into the specific biological mechanisms, paving the way for novel therapeutic strategies.

The progression from cirrhosis to hepatocellular carcinoma (HCC) is a key outcome in the management of chronic liver disease. This process has a long incubation period and significant individual differences, making early warning still difficult. Clinical follow-up mainly relies on imaging examinations and alpha fetoprotein, but the ability to identify high risk precancerous states is limited. The imbalance of gut microbiota and its metabolites may occur earlier than the visible stage of tumors. They can affect barrier integrity, chronic inflammation, immune surveillance, and metabolic homeostasis through the gut liver axis, and participate in the formation of a pro tumor microenvironment. Therefore, such changes may provide more upstream risk stratification clues for the population with cirrhosis. This article summarizes previous research evidence and summarizes the common microbiome and metabolite characteristics of cirrhosis and high-risk populations, including a decrease in short chain fatty acid (SCFA) related symbiotic bacteria, an increase in inflammation related bacteria, bile acid spectrum shift, and other intestinal derived metabolite abnormalities. This article also outlines the key mechanisms that these features may correspond to, such as barrier damage and microbial translocation, immune suppression, etc. There are still significant uncertainties at present. The effect of SCFA is context dependent. Different etiologies, diets, medications, and complications can lead to significant confounding and affect cross cohort consistency. Subsequent research requires longitudinal cohort validation and the promotion of multi omics integration and the construction of interpretable predictive models to support clinical translation.

Background Autoimmune uveitis is a sight-threatening intraocular inflammation mainly caused by immune dysregulation. The development of safe and effective therapeutic approaches is urgently needed. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have been demonstrated to inhibit autoimmune responses; however, the immunosuppressive effect of MSC-sEVs is too weak for clinical transfer. In the current study, we investigated the therapeutic effect of IL-10-overexpressing MSC-sEVs (sEV-IL10) on experimental autoimmune uveitis (EAU) and studied the underlying mechanism. Methods Mice were randomly grouped and received a single tail vein injection of different sEVs (50 μg) or PBS on day 11 post-immunization. The clinical and histological scores were graded, and the percentage of T helper cell was measured. To investigate the effect of sEVs on the proliferation of T-cells and the differentiation of Th1, Th17 and Treg cells, T-cells were cocultured with sEVs under the corresponding culture conditions. After labeled with PKH-26, sEVs were traced both in vivo and in vitro. Results Compared with normal or vector sEV-treated groups, mice in the sEV-IL10-treated group had lower clinical and histological scores with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the spleen and draining lymph nodes (LN). Furthermore, sEV-IL10 enhanced the suppressive effect of MSC-sEVs on the proliferation of T-cells and differentiation of Th1 and Th17 cells, whereas upregulated the differentiation of Treg cells. Both in vivo and in vitro experiments demonstrated that MSC-sEVs were rapidly enriched in target tissues and internalized by T-cells. Conclusion These results suggested that sEV-IL10 effectively ameliorates EAU by regulating the proliferation and differentiation of T-cells, indicating sEVs as a potential novel therapy for autoimmune uveitis or other autoimmune diseases.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency has a distinct regional and ethnic heterogeneity in distribution, and information on the molecular characteristics of G6PD deficiencies in the Heze area, Shandong Province, China, is limited. We aimed to explore the incidence and genetic mutations characteristic of G6PD enzyme deficiencies in newborns in the Heze area to investigate the pathogenicity of new G6PD mutations. We measured G6PD activity in 114,285 neonates born in the Heze area and identified 80 patients with G6PD deficiencies. The genetic mutations in G6PD in these patients were analyzed using Sanger sequencing. Functional studies were conducted by constructing eukaryotic expression vectors, transfecting them into HEK-293T and HELA cells, and measuring the mRNA and protein levels and G6PD enzymatic activity. The incidence of G6PD deficiency in the study population was 0.07% (80/114,285). We identified 17 mutation types with a 100% G6PD mutation detection rate, with four of them being significant: c.479G>A, c.404A>T, and c.486-7C>G being globally novel mutations, while c.682G>A has never been reported in China before. Functional studies revealed that the heterozygous missense mutations c.479G>A/p.S160N and c.404A>T/p.N135I increased mRNA levels, decreased protein expression, and reduced G6PD activity. The incidence of neonatal G6PD deficiency in the Heze area is low, and the most commonly mutated loci were c.1388G>A, c.487G>A, and c.1376G>T. Among these mutations, c.479G>A/p.S160N, and c.404A>T/p.N135I are potentially pathogenic. These mutations may cause G6PD deficiency via different mechanisms, thereby requiring further experimental investigation.