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Roxb. (named tufuling in Chinese, SGR) has both medicinal and edible value. SGR has obvious pharmacological activity, especially in anti-inflammation and treating immune system diseases. This study investigated differential protein expression and its relationship with immune infiltration in hypertension treated with SGR using proteomics and bioinformatics. N-Nitro L-arginine methyl ester (L-NAME) was used to replicate the hypertension model, with SGR administered by gavage for 4 weeks, and the systolic and diastolic blood pressure in each group of rats was measured using the tail-cuff method every 7 days. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) expressions in each group, followed by the detection of protein expression in rat liver samples using the tandem mass tag (TMT) technique. Additionally, hub targets were output using Cytoscape 3.9.1 software, and ALDH2 expression in the liver and serum in each group of rats was detected by ELISA. Moreover, R4.3.0 software was used to evaluate the relationship between acetaldehyde dehydrogenase 2 (ALDH2) and immune cells, and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was performed to identify the components of SGR. Furthermore, the association between components of SGR and ALDH2 was analyzed with molecular docking and LigPlot1.4.5 software. Compared with the model group (L-NAME), SGR at high and medium doses reduced systolic and diastolic blood pressure while reducing TC, TG, and LDL-C levels and increasing HDL-C levels in hypertensive rats ( < 0.05). Moreover, 92 differentially expressed proteins (DEPs) were identified using TMT. These DEPs participated in peroxisome functioning, fatty acid degradation, and other signaling pathways, with ALDH2 being the core target and correlated with various immune cells. In addition, 18 components were determined in SGR, with 8 compounds binding to ALDH2. Molecular docking was performed to confirm that SGR played a role in hypertension based on the combined action of multiple components. In conclusion, SGR has an antihypertensive effect on L-NAME-induced hypertension, with ALDH2 as its hub target. SGR may regulate neutrophil, regulatory T cell, and other cells' infiltration by targeting ALDH2, thereby contributing to the treatment of hypertension.

Observational studies have suggested a potential association between the gut microbiota and chronic obstructive pulmonary disease (COPD); however, the causal relationship between them, as well as the mediating roles of metabolites, inflammatory proteins, and immune cells, remain unclear. This study aims to elucidate the causal relationship between gut microbiota and COPD using genetic approaches and to explore the potential mediating roles of metabolites, inflammatory proteins, and immune cells. To investigate the causal association between gut microbiota and COPD, we first employed univariable Mendelian randomization (UVMR), using the inverse-variance weighted (IVW) method as the primary analytical approach. Robust IVW and penalized IVW methods were further applied to assess the stability of the findings. Subsequently, we performed a two-step multivariable Mendelian randomization (MVMR) analysis to evaluate the mediating effects of 233 metabolites, 91 inflammatory proteins, and 731 circulating immune cell types. Finally, horizontal pleiotropy was corrected using the MR-Egger intercept method, and potential outliers were identified and excluded through MR-PRESSO. The study adhered strictly to the STROBE-MR reporting guidelines. After adjusting for reverse causality, seven gut microbial taxa exhibited a significant causal relationship with COPD. In mediation analyses, CAG-475 was found to influence COPD risk through HLA DR⁺ CD4⁺ T cells (mediation proportion: 0.55%) and IL-10 (15.96%). The Desulfovibrionaceae family primarily mediated COPD risk via lipid metabolism pathways, with free cholesterol in large very-low-density lipoprotein (VLDL) particles accounting for 45.22% of the effect, along with six other lipid-related indicators. Lactobacillus B ruminis exerted its effects through immune markers such as CD19⁺ B cells and CD8dim T cells (mediation proportion: 0.42–0.85%). Conversely, no significant mediation pathways were identified for four microbial taxa, including CAG-485 sp002404675. This study represents the first genetic evidence supporting a causal framework linking gut microbiota to COPD through metabolic, immune, and inflammatory pathways. The findings highlight the critical roles of lipid metabolism dysregulation, immune markers, and inflammatory responses in COPD pathogenesis. However, further research is warranted to explore additional potential mediators and refine the proposed causal network.

Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague–Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder with environmental factors being the primary risk determinants. However, genetic factors also substantially contribute to the susceptibility and progression of COPD. Although genome-wide association studies (GWAS) have identified several loci associated with COPD susceptibility, the specific pathogenic genes underlying these loci, along with their biological functions and roles within regulatory networks, remain unclear. This lack of clarity constrains our ability to achieve a deeper understanding of the genetic basis of COPD. This study leveraged the FinnGen R11 genetic dataset, comprising 21,617 cases and 372,627 controls, along with GTEx V8 eQTLs data to conduct a cross-tissue transcriptome-wide association study (TWAS). Initially, we performed a cross-tissue TWAS analysis using the Unified Test for Molecular Signatures (UTMOST), followed by validation of the UTMOST findings in single tissues using the Functional Summary-based Imputation (FUSION) method and conditional and joint (COJO) analyses of the identified genes. Subsequently, candidate susceptibility genes were screened using Multi-marker Analysis of Genomic Annotation (MAGMA). The causal relationship between these candidate genes and COPD was further evaluated through summary data-based Mendelian randomization (SMR), colocalization analysis, and Mendelian randomization (MR). Additionally, the identified results were validated against the COPD dataset in the GWAS Catalog (GCST90399694). GeneMANIA was employed to further explore the functional significance of these susceptibility genes. In the cross-tissue TWAS analysis (UTMOST), we identified 17 susceptibility genes associated with COPD. Among these, a novel susceptibility gene, G protein-coupled receptor kinase 4 (GRK4), was validated through single-tissue TWAS (FUSION) and MAGMA analyses, with further confirmation via SMR, MR, and colocalization analyses. Moreover, GRK4 was validated in an independent dataset. This study identifies GRK4 as a potential novel susceptibility gene for COPD, which may influence disease risk by exacerbating inflammatory responses. The findings address gaps in previous single-tissue GWAS studies, revealing consistent expression and potential function of GRK4 across different tissues. However, considering the study’s limitations, further investigation and validation of GRK4 ’s role in COPD are warranted.

Background Leaf size affects crop canopy morphology and photosynthetic efficiency, which can influence forage yield and quality. It is of great significance to mine the key genes controlling leaf development for breeding new alfalfa varieties. In this study, we mapped leaf length (LL), leaf width (LW), and leaf area (LA) in an F1 mapping population derived from a cultivar named ZhongmuNo.1 with larger leaf area and a landrace named Cangzhou with smaller leaf area. Results This study showed that the larger LW was more conducive to increasing LA. A total of 24 significant quantitative trait loci (QTL) associated with leaf size were identified on both the paternal and maternal linkage maps. Among them, nine QTL explained about 11.50–22.45% phenotypic variation. RNA-seq analysis identified 2,443 leaf-specific genes and 3,770 differentially expressed genes. Combining QTL mapping, RNA-seq alalysis, and qRT-PCR, we identified seven candidate genes associated with leaf development in five major QTL regions. Conclusion Our study will provide a theoretical basis for marker-assisted breeding and lay a foundation for further revealing molecular mechanism of leaf development in alfalfa.

Urbanization intensifies cities' vulnerability to shocks like climate disasters, economic crises, and pandemics, making resilience critical for sustainable development. Digital intelligence—AI, IoT, blockchain, big data—transforms urban governance through data-driven decisions, real-time monitoring, and citizen engagement. This study analyses 232 peer-reviewed articles via bibliometric mapping and qualitative cluster analysis. Findings reveal three thematic clusters: technological innovations, economic resilience, and social resilience. Digital tools enhance robustness but risk excluding marginalized groups. Policy-technology alignment is paramount, yet gaps exist in equity frameworks, cultural embeddedness, and ethical governance. With 55% global urbanization (70% by 2050), integrating digital intelligence is indispensable for inclusive, adaptive cities. The findings are conducive to promoting inclusive digital resilience through multi-stakeholder co-design and algorithmic transparency.

Forage quality determined mainly by protein content and fiber composition has a crucial influence on digestibility and nutrition intake for animal feeding. To explore the genetic basis of quality traits, we conducted QTL mapping based on the phenotypic data of crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), and lignin of an F 1 alfalfa population generated by crossing of two alfalfa parents with significant difference in quality. In total, 83 QTLs were identified with contribution to the phenotypic variation (PVE) ranging from 1.45 to 14.35%. Among them, 47 QTLs interacted significantly with environment and 12 QTLs were associated with more than one trait. Epistatic effect was also detected for 73 pairs of QTLs with PVE of 1.08–14.06%. The results suggested that the inheritance of quality-related traits was jointly affected by additive, epistasis and environment. In addition, 83.33% of the co-localized QTLs were shared by ADF and NDF with the same genetic direction, while the additive effect of crude protein-associated QTLs was opposite to that fiber composition on the same locus, suggesting that the loci may antagonistically contribute to protein content and fiber composition. Further analysis of a QTL related to all the three traits of fiber composition ( qNDF1C, qADF1C-2 , and qlignin1C-2 ) showed that five candidate genes were homologs of cellulose synthase-like protein A1 in Medicago truncatula , indicating the potential role in fiber synthesis. For the protein-associated loci we identified, qCP4C-1 was located in the shortest region (chr 4.3 39.3–39.4 Mb), and two of the seven corresponding genes in this region were predicted to be E3 ubiquitin-protein ligase in protein metabolism. Therefore, our results provide some reliable regions significantly associated with alfalfa quality, and identification of the key genes would facilitate marker-assisted selection for favorable alleles in breeding program of alfalfa quality improvement.

Microplastics are generated from plastic waste in landfills due to physical, chemical, and biological effects, and eventually enter into the leachate. Leachate is a potential source of environmental microplastics which has not been emphasized. Here, we summarized the investigation of microplastics in leachate in 9 countries from 28 papers, provided a comprehensive review of the sampling, detection, and separation of microplastics in leachate, and elaborated on the quality control in each process. There are more than forty types of microplastics in leachate, with diverse shapes, wide size distribution, and concentrations of 0–25 items/L. Commonly used techniques are FTIR, Raman, SEM, and py-GC–MS for characterizing microplastics, while standardization of micro- or nanoplastics for leachate with a complex composition should be further studied. We also discussed in depth the degradation mechanism of microplastics in advanced oxidation processes (AOPs). Microplastics can be decomposed into small molecules such as aldehydes and ketones, and some can even eventually be degraded into CO2 and H2O in AOPs, which may be further implemented in leachate treatment plants. This review provides the scientific fundamentals for understanding the microplastics in landfill leachate and proposes removal strategies for future research.

Alfalfa ( Medicago sativa L.) is a perennial forage crop known as the “Queen of Forages.” To dissect the genetic mechanism of flowering time (FT) in alfalfa, high−density linkage maps were constructed for both parents of an F1 mapping population derived from a cross between Cangzhou (P1) and ZhongmuNO.1 (P2), consisting of 150 progenies. The FT showed a transgressive segregation pattern in the mapping population. A total of 13,773 single-nucleotide polymorphism markers was obtained by using restriction-site associated DNA sequencing and distributed on 64 linkage groups, with a total length of 3,780.49 and 4,113.45 cM and an average marker interval of 0.58 and 0.59 cM for P1 and P2 parent, respectively. Quantitative trait loci (QTL) analyses were performed using the least square means of each year as well as the best linear unbiased prediction values across 4 years. Sixteen QTLs for FT were detected for P1 and 22 QTLs for P2, accounting for 1.40–16.04% of FT variation. RNA-Seq analysis at three flowering stages identified 5,039, 7,058, and 7,996 genes that were differentially expressed between two parents, respectively. Based on QTL mapping, DEGs analysis, and functional annotation, seven candidate genes associated with flowering time were finally detected. This study discovered QTLs and candidate genes for alfalfa FT, making it a useful resource for breeding studies on this essential crop.

Background. Asthma and diabetes are both diseases that affect a wide range of people worldwide. As a common treatment for diabetes, metformin has also been reported to be effective in improving asthma outcomes. We conducted a combined analysis to examine the efficacy of metformin in reducing asthma exacerbation in patients with concurrent asthma and diabetes. Methods. We searched the PubMed, Embase, and CENTRAL databases for articles published prior to April 2020 to find observational studies of individuals with concurrent asthma and diabetes that compared the risk of asthma exacerbation between metformin users and nonusers. Two researchers separately screened the studies, extracted data, and evaluated the risk of bias. The primary outcome was the adjusted risk of asthma exacerbation. The secondary outcomes were the adjusted risk of asthma-related hospitalization and emergency room visits. Review Manager was used for data analysis and plotting. I2 and χ2 tests were used to estimate heterogeneity. A random effects or fixed effects model was used depending on the heterogeneity. Odds ratios were calculated for dichotomous variables. Results. We included two studies with a total of 25252 patients. The pooled effect size showed that metformin was inversely associated with a risk of asthma exacerbation (OR = 0.65, 95% CI 0.28–1.48; χ2 = 5.42, P=0.02; I2 = 82%), asthma-related emergency department visits (OR = 0.81, 95% CI 0.74–0.89; χ2 = 0.36, P=0.55; I2 = 0%), and hospitalizations (OR = 0.43, 95% CI 0.14–1.29; χ2 = 4.01, P=0.05; I2 = 75%). Conclusion. This meta-analysis suggested that metformin decreased the risk of asthma-related emergency room visits for patients with concurrent asthma and diabetes. Metformin reduced the risk of asthma-related hospitalization and exacerbation but was not statistically significant. More randomized trials involving larger samples should be considered, and the mechanisms of these effects need to be fully elucidated.