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Panax ginseng, a perennial medicinal plant, utilizes its dried roots and rhizomes for medicinal purposes. Currently, in China, ginseng cultivation employs two methods: under-forest and farmland planting. These methods create distinct habitats, significantly influencing the ginseng’s rhizome morphology and, consequently, its economic value. In this study, two-year-old ginsengs were transplanted into farmland (TCG), a larch forest (TLCG) and a Quercus mongolica forest (TQCG) to analyze the differences in rhizome phenotypes caused by habitat changes. The results showed that there were significant differences in light intensity and the soil’s available phosphorus and potassium contents between farmland and forest environments. The differences in habitats led to different adaptability of the ginseng’s rhizome morphology. Compared with TCG, the rhizomes of TLCG and TQCG were significantly elongated by 48.36% and 67.34%, respectively. After the rhizomes’ elongation in TLCG and TQCG, there was an increase in indole-3-acetic acid (IAA) contents and a decrease in lignin contents. By analyzing the expression of key genes, we found that, compared with TCG, the expression of key enzymes of lignin biosynthesis genes such as PgCOMT and PgCCR4 were down-regulated. The difference in ginseng’s rhizome length is related to the signal transduction pathway of auxin and gibberellin. In addition, we preliminarily screened out transcription factors PgWRKY75, PgDIV, and PgbHLH93.1, which can actively respond to habitat changes and play important roles in the elongation of ginseng rhizomes. In summary, this study elucidates the phenotypic plasticity strategy of ginseng rhizomes in response to habitat changes and delineates the regulatory mechanism behind phenotypic adaptation, offering novel insights into ginseng’s morphogenesis.

Abstract Background Mesenchymal stem cells (MSCs) have shown a positive effect on Osteoarthritis (OA), but the efficacy is still not significant in clinical. Conventional two-dimensional (2D) monolayer culture method is prone to cause MSCs undergoing replication senescence, which may affect the functions of MSCs. Three-dimensional (3D) culture strategy can sustain cell proliferative capacity and multi-differentiation potential. This study aimed to investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) cultured by 3D hanging drop method on OA. Methods hUC-MSCs were isolated from umbilical cord and cultured by 3D hanging drop method for 48 h. Scanning electron microscopy (SEM) was used to observe gross morphology 2D and 3D hUC-MSCs. Transcriptome comparison of gene expression differences between 2D and 3D hUC-MSCs. GO enrichment analysis, KEGG pathway enrichment analysis and GSEA enrichment analysis were used to analyze the impact of 3D hanging drop culture on the biological functions of hUC-MSCs. Female New Zealand rabbits (n = 12) were divided into 4 groups: Normal group, Model group, 2D hUC-MSCs treatment group and 3D hUC-MSCs treatment group. After 8 weeks, the gross and histological appearance of the cartilage was evaluated by safranin O-fast green staining and Mankin scoring system. The expression of type I collagen and type II collagen was detected by immunohistochemistry. The levels of IL-6, IL-7, TNFα, TGFβ1 and IL-10 in the knee joint fluid were tested by ELISA. Results 3D hanging drop culture changed cell morphology but did not affect phenotype. The MSCs transcriptome profiles showed that 3D hanging drop culture method enhanced cell-cell contact, improved cell responsiveness to external stimuli and immunomodulatory function. The animal experiment results showed that hUC-MSCs could promote cartilage regeneration compared with Model group. 3D hUC-MSCs treatment group had a higher histological score and significantly increased type II collagen secretion. In addition, 3D hUC-MSCs treatment group increased the expression of anti-inflammatory factors TGFβ1 and IL-10. Conclusion The above experimental results illustrated that 3D hanging drop culture method could enhance the therapeutic effect of hUC-MSCs, and showed a good clinical application prospect in the treatment of OA.

Abstract Background We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance. Methods Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab. Results Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P

Abstract Background Rapid sequence intubation (RSI) have been shown to be effective in preventing reflux aspiration in patients with a full stomach during anaesthesia induction and endotracheal intubation. However, there is currently no standardized operation protocol or anaesthesia induction drug standard for RSI. Furthermore, there is a lack of evidence regarding the use of RSI in patients older than 65. In this study, we aimed to investigate the cardiovascular effects of different doses of alfentanil combined with propofol and etomidate during RSI in elderly patients aged 65–80 years. Methods A total of 96 patients aged 65–80 years who underwent general anaesthesia with tracheal intubation were selected for this study. The patients were randomly assigned to one of four groups using a random number table. Group A patients received an induction dose of 10 µg/kg alfentanil, group B patients received 15 µg/kg alfentanil, group C patients received 20 µg/kg alfentanil, and group D patients received 25 µg/kg alfentanil. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and ejection fraction (EF) were measured at three time points: 5 min before anaesthesia induction (T0), 1 min after endotracheal intubation (T1), and 5 min after endotracheal intubation (T2). Concurrently, 4 ml of arterial blood was collected from patients at three time points, and the concentrations of norepinephrine (NE) and cortisol (Cor) in plasma were detected. Occurrences of hypertension, hypotension, bradycardia and tachycardia during anesthesia induction to 5 min after tracheal intubation were noted. Results Compared with T0, the HR, MAP, NE and Cor concentrations in group A and group B were increased at the T1 and T2 time points, CI and EF values were decreased (P 0.05). Additionally, they were not significant in group D at the T1 time point (P > 0.05), but decreased at the T2 time point (P

Abstract Investigating the anti‐inflammatory effects of bioactive components present in cold‐pressed rapeseed oil through the use of network pharmacology and molecular docking methods. The components of cold‐pressed rapeseed oil were identified by liquid chromatography‐mass spectrometry. We then conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using bioinformatics databases on overlapping targets affected by active components and inflammation. Finally, molecular docking was used to predict the interactions between core components and key targets. Analysis identified 13 phenols, four steroids, and one retinoid in cold‐pressed rapeseed oil, with 143 overlapping targets related to inflammation. Bioinformatics analysis revealed that 25‐Hydroxycholesterol, Rosmarinic acid, 9‐cis‐Retinoic acid, Soyasapogenol B and α‐Tocopherol in cold‐pressed rapeseed oil could play a positive role in treating inflammation. They achieved this by regulating key targets (MMP9, EGFR, AKT1, ESR1, and PTGS2) involved in the peroxisome proliferator‐activated receptor signaling pathway and other related pathways. The molecular docking binding energy of the core components and the key targets were less than −5.0 kcal/mol, indicating that the components and the targets can be stably bound. This result indicated that the active components found in cold‐pressed rapeseed oil may exert an anti‐inflammatory effect through a synergistic mechanism involving multicomponent, multitarget and multipathway interactions.

Abstract The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

ABSTRACT Yersinia enterocolitica, a species within the genus Yersinia, thrives optimally at 22–25°C but can also grow at the mammalian core body temperature of 37°C. This dual temperature adaptability necessitates establishing both temperature conditions in research to examine the effects on various biological processes. In quantitative real-time PCR (qRT-PCR) assays, the selection of appropriate housekeeping genes is vital for data accuracy. Nevertheless, the lack of alternatives and information often leads to the default use of the 16S rRNA gene despite potential limitations. This investigation sourced 16 potential reference genes through a comprehensive review of the literature and transcriptome sequencing data analysis. We validated the expression stability of these genes via qRT-PCR across 12 Y. enterocolitica strains, representing the four prevalent serotypes O:3, O:5,27, O:8, and O:9, isolated from diarrheal patient stool samples. This approach aimed to minimize the impact of serotype heterogeneity. After acquiring Cq values, gene stability was evaluated using four established algorithms—ΔCq, geNorm, NormFinder, and BestKeeper—and subsequently synthesized into a consolidated ranking through the Robust Rank Aggregation (RRA) method. Our study suggests that the genes glnS, nuoB, glmS, gyrB, dnaK, and thrS maintain consistent expression across varying culture temperatures, supporting their candidacy as robust housekeeping genes. We advise against the exclusive use of 16S rRNA for this purpose. Should tradition prevail in its utilization, it must be employed with discernment, preferably alongside one or two of the housekeeping genes identified in this study as internal controls.IMPORTANCEIn our study, we focused on identifying stable reference genes for quantitative real-time PCR (qRT-PCR) experiments on Y. enterocolitica cultured at different temperatures (22°C and 37°C). After thoroughly evaluating 16 candidate genes, we identified six genes—glnS, nuoB, glmS, gyrB, dnaK, and thrS—as exhibiting stable expression across these temperature conditions, making them ideal reference genes for Y. enterocolitica studies. This discovery is crucial for ensuring the accuracy and reliability of qRT-PCR data, as the choice of appropriate reference genes is key to normalizing expression data and minimizing experimental variability. Importantly, our research extended beyond bioinformatics analysis by incorporating validation with clinical strains, bridging the gap between theoretical predictions and practical application. This approach not only underscores the robustness and reliability of our findings but also directly addresses the critical need for experimental validation in the field. By providing a set of validated, stably expressed reference genes, our work offers valuable guidance for designing experiments involving Y. enterocolitica, enhancing the reliability of research outcomes, and advancing our understanding of this significant pathogen.

AimThis study aimed to investigate the effects of low-dose dextran sulfate sodium (DSS) on the induction of chronic mild inflammation in mice and to evaluate the therapeutic potential of Lacticaseibacillus rhamnosus LRa05 (LRa05) to ameliorate the associated effects. The focus was on investigating changes in inflammatory, gut microbiota, serum lipopolysaccharide (LPS) and inflammatory cytokines.MethodsMice were exposed to a low-dose of DSS to induce chronic mild inflammation and LRa05 was administered as a probiotic intervention. The experiment included determination of body weight, colon length, histological examinations, and analysis of LPS and inflammatory cytokines in serum over 12 weeks. In addition, liver function, oxidative stress and intestinal microbiota were examined to understand the comprehensive effects of DSS and LRa05.ResultsLow-dose DSS did not lead to significant changes in body weight, colon length or histologic signs of inflammation. However, it led to a significant increase in serum levels of LPS, tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL6). Intervention with LRa05 effectively attenuated these changes, particularly by lowering LPS levels and normalizing inflammatory cytokines. In addition, LRa05 protected against DSS-induced liver function damage and attenuated oxidative stress in the liver. Analysis of the gut microbiota demonstrated dynamic regulatory effects, where LRa05 intervention led to significant shifts in microbial populations, promoting a balanced microbiota profile. These changes are indicative of dynamic regulation by LRa05 in response to chronic mild inflammation, highlighting the probiotic’s role in modulating the gut environment.ConclusionThe LRa05 intervention showed multi-layered regulation in the chronic mild inflammation model by reducing inflammatory cytokines, maintaining liver function and restoring the balance of the gut microbiota. This provides experimental support for the potential use of LRa05 in chronic inflammation-related diseases and emphasizes the importance of probiotics for overall health. The study suggests that LRa05 is a potential therapeutic agent for the treatment of chronic inflammation associated with gut dysbiosis.

Since the large-scale oil exploration and development in the 1960 s, the Yellow River Delta (YRD) has undergone rapid industrialization and urbanization. Concurrently, the regional landscape ecological structure has experienced significant changes, and the degree of landscape fragmentation has increased. Therefore, a comprehensive assessment of the spatiotemporal dynamics and formation mechanisms of landscape fragmentation is crucial for the protection and restoration of natural ecosystem in the YRD. This study constructs an evaluation index system for landscape fragmentation in the YRD from three perspectives: quantitative characteristics, shape features, and spatial distribution. By combining inflection point analysis, landscape area loss index, and geostatistical models, the optimal spatial scale of landscape fragmentation from 2000 to 2020 is determined. Additionally, the study analyzes the spatiotemporal changes in landscape fragmentation and employs the optimal parameters-based geographical detector (OPGD) model to reveal the formation mechanisms of spatial heterogeneity in landscape fragmentation. The study findings are as follows: (1) The optimal spatial resolution for analyzing landscape fragmentation in the YRD was 80 m, and the extent was 880 m. (2) Between 2000 and 2020, landscape fragmentation in the YRD increased, with the highest level recorded in 2020. Highly fragmented areas, particularly inland regions, expanded remarkably, whereas coastal areas experienced lower fragmentation levels. (3) Distance to rivers and ditch density were the primary factors affecting landscape fragmentation, followed by land-use type and average land gross domestic product. The influence of natural factors was relatively minimal. The interaction between factors had a greater influence on landscape fragmentation compared to individual factors. The distance to rivers and land-use type exhibited the most substantial enhancement effects following interaction with other factors. This study provides valuable insights into the spatiotemporal dynamics and mechanisms of landscape fragmentation in the YRD, providing valuable guidance for the sustainable management and ecological restoration of the region and other similar ecologically sensitive areas.

BackgroundThe actual situation and influencing factors of prophylactic use of proton pump inhibitors (PPIs) in internal medicine inpatients receiving glucocorticoid therapy are rarely reported. This study aimed to investigate the current status and influencing factors of prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy to provide a basis for rational prophylactic use of PPIs.MethodsInternal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Information on the prophylactic use of PPIs was collected and analyzed by clinical pharmacists. Associated factors with prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression.Results980 inpatients were finally included in our study, of which 271 (27.7%) inpatients received prophylactic use of PPIs. Among the inpatients prescribed PPIs, 90 inpatients received a standard dose of PPIs twice a day. Multiple logistic regression analysis showed that age ≥80 years [OR = 7.009, 95% CI (1.424, 34.495), p = 0.017], history of gastroesophageal reflux disease (GERD) [OR = 2.047, 95% CI (1.338, 3.133), p = 0.001], low platelet count [OR = 0.997, 95% CI (0.994, 0.999), p = 0.004], number of concomitant diseases [OR = 1.104, 95% CI (1.056, 1.153), p < 0.001], junior doctors [OR = 1.755, 95% CI (1.248, 2.468), p = 0.001], glucocorticoid dose (higher than 50 mg, measured by methylprednisolone) [OR = 2.455, 95% CI (1.371, 4.395), p = 0.003], antiplatelet agents [OR = 2.567, 95% CI (1.456, 4.524), p = 0.001], immunosuppressants [OR = 1.477, 95% CI (1.014, 2.153), p = 0.042], and betahistine [OR = 5.503, 95% CI (1.124, 26.950), p = 0.035] were associated with more prophylactic use of PPIs.ConclusionThe prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy is common in China. Clinical pharmacists will take targeted measures to promote the rational use of PPIs according to the results of this study.

Drought, excessive use of nitrogen fertilizer, and decline in soil organic matter threaten corn production. This study investigated the potential of water retaining agents, inhibitors, and corn stalks in enhancing soil physicochemical properties to bolster corn yield in semi-arid farmlands. In our study, polyacrylamide addition increased the content of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) in the seedling stage, exchangeable potassium (K) in the mature stage but decreased the content of available phosphorus (P) in the seedling stage. Potassium polyacrylate addition increased the content of NH4+-N and decreased the content of available P in the seedling stage. The addition of inhibitors decreased the content of NH4+-N and available P in the seedling stage, NO3--N and available P in the jointing stage, and NH4+-N in the mature stage, respectively. Corn stalks returning could maintain soil moisture, decrease the content of NH4+-N in the seedling stage and exchangeable K in the mature stage, and increase the content of available P and exchangeable K in the seedling stage. Combined application of inhibitors and corn stalks could increase soil organic carbon (SOC) and ensure corn yield, which was the best fertilization mode in semi-arid cropland.

Abstract Background The prevalence and characteristics of inappropriate use of proton pump inhibitors (PPIs) to prevent stress-related mucosal disease (SRMD) during the perioperative period and its associated factors are rarely reported. This study aimed to investigate the prevalence and characteristics of inappropriate prophylactic use of proton pump inhibitors (PPIs) during the perioperative period and identify its associated factors in a tertiary care and academic teaching hospital in China and to provide evidence for regulation authorities and pharmacists to take targeted measures to promote rational drug use. Methods Inpatients who underwent surgical operations and received prophylactic use of PPIs from June 2022 to November 2022 were included in this retrospective study. The appropriateness of perioperative prophylactic use of PPIs was evaluated by clinical pharmacists. Associated factors with inappropriate perioperative prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression. Results Four-hundred seventy-two patients were finally included in this study, of which 131 (27.75%) patients had at least one problem with inappropriate perioperative prophylactic use of PPIs. The three most common problems were drug use without indication (52.0%), inappropriate usage and dosage (34.6%), and inappropriate duration of medication (6.7%). Multiple logistic regression analysis showed that oral dosage form of PPIs [OR = 18.301, 95% CI (7.497, 44.671), p

Aim: Chemotherapy has been well shown to enhance life expectancy in patients with malignancy. However, conventional chemotherapy drugs, particularly cisplatin, are highly associated with nephrotoxicity, which limits therapeutic efficacy and impairs quality of life. Histone deacetylases (HDACs) are proteases that play significant roles in diseases by influencing protein post-translational modification and gene expression. Agents that inhibit HDAC enzymes have been developed and approved by the FDA as anticancer drugs. It is worth noting that in certain preclinical studies with tumour cell lines, the integration of HDAC modulators and cisplatin not only exerts synergistic or additive tumour-killing effects but also alleviates cisplatin nephrotoxicity. The aim of this review is to discuss the role of HDACs in cisplatin nephrotoxicity.Methods: After searching in PubMed and Web of Science databases using ‘Histone deacetylase’, ‘nephrotoxicity’, ‘cisplatin’, and ‘onconpehrology’ as keywords, studies related was compiled and examined.Results: HDAC inhibitors exert renal protective effects by inhibiting inflammation, apoptosis, oxidative stress, and promoting autophagy; whereas sirtuins play a renal protective role by regulating lipid metabolism, inhibiting inflammation and apoptosis, and protecting mitochondrial biosynthesis and mitochondrial dynamics. These potential interactions provide clues concerning targets for molecular treatment.Conclusion: This review encapsulates the function and molecular mechanisms of HDACs in cisplatin nephrotoxicity, providing the current view by which HDACs induce different biological signaling in the regulation of chemotherapy-associated renal injury. More importantly, this review exhaustively elucidates that HDACs could be targeted to develop a new therapeutic strategy in treating cisplatin nephrotoxicity, which will extend the knowledge of the biological impact and clinical implications of HDACs.

The Hulunbuir region, known for its diverse terrain and rich wildlife, is a hotspot for various natural epidemic diseases. Between 2021 and 2023, we collected 885 wild rodent samples from this area, representing three families, seven genera, and eleven species. Metagenomic analysis identified three complete nucleic acid sequences from the S, M, and L segments of the Hantaviridae family, which were closely related to the Khabarovsk virus. The nucleotide coding sequences for S, M, and L (1392 nt, 3465 nt, and 6491 nt, respectively) exhibited similarities of 82.34%, 81.68%, and 81.94% to known sequences, respectively, while protein-level analysis indicated higher similarities of 94.92%, 94.41%, and 95.87%, respectively. Phylogenetic analysis placed these sequences within the same clade as the Khabarovsk, Puumala, Muju, Hokkaido, Topografov, and Tatenalense viruses, all of which are known to cause febrile diseases in humans. Immunofluorescence detection of nucleic acid-positive rodent kidney samples using sera from patients with hemorrhagic fever and renal syndrome confirmed the presence of viral particles. Based on these findings, we propose that this virus represents a new member of the Hantaviridae family, tentatively named the Amugulang virus, after its primary distribution area.

Extracellular histones are crucial damage-associated molecular patterns involved in the development and progression of multiple critical and inflammatory diseases, such as sepsis, pancreatitis, trauma, acute liver failure, acute respiratory distress syndrome, vasculitis and arthritis. During the past decade, the physiopathologic mechanisms of histone-mediated hyperinflammation, endothelial dysfunction, coagulation activation, neuroimmune injury and organ dysfunction in diseases have been systematically elucidated. Emerging preclinical evidence further shows that anti-histone strategies with either their neutralizers (heparin, heparinoids, nature plasma proteins, small anion molecules and nanomedicines, etc.) or extracorporeal blood purification techniques can significantly alleviate histone-induced deleterious effects, and thus improve the outcomes of histone-related critical and inflammatory animal models. However, a systemic evaluation of the efficacy and safety of these histone-targeting therapeutic strategies is currently lacking. In this review, we first update our latest understanding of the underlying molecular mechanisms of histone-induced hyperinflammation, endothelial dysfunction, coagulopathy, and organ dysfunction. Then, we summarize the latest advances in histone-targeting therapy strategies with heparin, anti-histone antibodies, histone-binding proteins or molecules, and histone-affinity hemoadsorption in pre-clinical studies. Finally, challenges and future perspectives for improving the clinical translation of histone-targeting therapeutic strategies are also discussed to promote better management of patients with histone-related diseases.

Abstract Understanding the microstructure of materials and their impact on performance is crucial for new electronic devices design. The strong interaction between multiple degrees of freedom (spin, orbit, charge, and lattice) within perovskite type oxides can generate rich electron phase diagrams. The microscopic modulation of manganese ions electron states in rare earth manganate perovskites is the root of many novel macroscopic quantum behaviors, such as giant magnetoresistance phenomenon. For ABO3 type perovskites, the differences of radii and valence states of A‐site ions are used to regulate the coexistence of B site manganese multivalent states (Mn3+, Mn4+, Mn5+), and its ordered structure in the metastable state will create a new combination of electronic states. The ordered arrangement of the multi‐dimensional space of electronic states can induce unique transport properties. Therefore, the preparation of manganate perovskites will provide strong chemical support to construct new generation quantum devices. This review summarizes the challenges and difficulties on constructing trivalent coexisting metastable phase in manganate perovskites through disproportionation reactions, and discusses the status and potential of designing ideal rectified p‐n junctions taking advantage of this unique structure. Finally, the foregrounds of new quantum states driven by this chemical reaction are prospected.

Nitrogen (N) is the primary essential nutrient for ginseng growth, and a reasonable nitrogen application strategy is vital for maintaining the stability of soil microbial functional communities. However, how microbial-mediated functional genes involved in nitrogen cycling in the ginseng rhizosphere respond to nitrogen addition is largely unknown. In this study, metagenomic technology was used to study the effects of different nitrogen additions (N0: 0, N1: 20, N2: 40 N g/m2) on the microbial community and functional nitrogen cycling genes in the rhizosphere soil of ginseng, and soil properties related to the observed changes were evaluated. The results showed that N1 significantly increased the soil nutrient content compared to N0, and the N1 ginseng yield was the highest (29.90% and 38.05% higher than of N0 and N2, respectively). N2 significantly decreased the soil NO3–N content (17.18 mg/kg lower than N0) and pH. This resulted in a decrease in the diversity of soil microorganisms, a decrease in beneficial bacteria, an increase in the number of pathogenic microorganisms, and an significant increase in the total abundance of denitrification, assimilatory nitrogen reduction, and dissimilatory nitrogen reduction genes, as well as the abundance of nxrA and napA genes (17.70% and 65.25% higher than N0, respectively), which are functional genes involved in nitrification that promote the soil nitrogen cycling process, and reduce the yield of ginseng. The results of the correlation analysis showed that pH was correlated with changes in the soil microbial community, and the contents of soil total nitrogen (TN), ammonium nitrogen (NH4+-N), and alkaline-hydrolyzed nitrogen (AHN) were the main driving factors affecting the changes in nitrogen cycling functional genes in the rhizosphere soil of ginseng. In summary, nitrogen addition affects ginseng yield through changes in soil chemistry, nitrogen cycling processes, and functional microorganisms.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. Methods: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. Results: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). Conclusion: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.

Green technological innovation (GTI) has the dual externalities of promoting technological advancements and facilitating environmental protection. GTI assists manufacturing clusters respond to emission reduction and environmental protection challenges. Non-geographic proximity is vital in promoting knowledge sharing among organizations, facilitating GTI’s effective implementation; in this regard, a gap exists in the current literature. Using data from 330 cluster firms in China’s fine chemical industry and drawing on the knowledge-based view, this study explores how cognitive and social proximities affect GTI in cluster firms. The key findings are as follows: First, cognitive and social proximities are crucial factors driving GTI. Second, knowledge sharing mediates the relationship between proximity and GTI. Third, technological distance positively moderates the relationship between social proximity and green product innovation, and that between social proximity and end-of-pipe technological innovation. These findings have critical implications for cluster firms looking to cultivate network relationships based on distinct types of GTI.

Background and objectivesUpwards of 50% of acute ischemic stroke (AIS) survivors endure varying degrees of disability, with a recurrence rate of 17.7%. Thus, the prediction of outcomes in AIS may be useful for treatment decisions. This study aimed to determine the applicability of a machine learning approach for forecasting early outcomes in AIS patients.MethodsA total of 659 patients with new-onset AIS admitted to the Department of Neurology of both the First and Second Affiliated Hospitals of Bengbu Medical University from January 2020 to October 2022 included in the study. The patient’ demographic information, medical history, Trial of Org 10,172 in Acute Stroke Treatment (TOAST), National Institute of Health Stroke Scale (NIHSS) and laboratory indicators at 24 h of admission data were collected. The Modified Rankine Scale (mRS) was used to assess the 3-mouth outcome of participants’ prognosis. We constructed nine machine learning models based on 18 parameters and compared their accuracies for outcome variables.ResultsFeature selection through the Least Absolute Shrinkage and Selection Operator cross-validation (Lasso CV) method identified the most critical predictors for early prognosis in AIS patients as white blood cell (WBC), homocysteine (HCY), D-Dimer, baseline NIHSS, fibrinogen degradation product (FDP), and glucose (GLU). Among the nine machine learning models evaluated, the Random Forest model exhibited superior performance in the test set, achieving an Area Under the Curve (AUC) of 0.852, an accuracy rate of 0.818, a sensitivity of 0.654, a specificity of 0.945, and a recall rate of 0.900.ConclusionThese findings indicate that RF models utilizing general clinical and laboratory data from the initial 24 h of admission can effectively predict the early prognosis of AIS patients.

IntroductionKnowledge on spatiotemporal heterogeneity of plant root microbiomes is lacking. The diversity of the root microbiome must be revealed for understanding plant–microbe interactions and the regulation of functionally crucial microbial taxa.MethodsWe here investigated the dynamics of microbial group characteristics within each soil ecological compartment [rhizoplane (B), rhizosphere (J), and bulk soil (T)] across different cultivation years (year 4: F4 and year 5: F5) by using high-throughput sequencing (16S and ITS).ResultsAccording to the species diversity, microbiome diversity and the ASV (amplified sequence variant) number in the rhizoplane ecotone increased significantly with an increase in the planting years. By contrast, the microbiome diversity of the rhizosphere soil remained relatively stable. PCoA and PERMANOVA analyses revealed that microbial taxa among different planting years and ecological compartments varied significantly. Planting years exerted the least effect on the rhizosphere microbiome, but their impact on fungi in the rhizoplane and bacteria in the bulk soil was the most significant.DiscussionPlanting years influenced the microbial community composition in various ecological compartments of ginseng root soil. Potentially harmful fungi such as Cryptococcus (2.83%), Neonectria (0.89%), llyonectria (0.56%), Gibberella (0.41%), Piloderma (4.44%), and Plectosphaerella (3.88%) were enriched in F5B with an increase in planting years, whereas the abundance of potentially beneficial Mortierella increased. Correlation analysis indicated associations between bacterial taxa and soil pH/S-CAT, and between fungal taxa and soil moisture content/total potassium. Our study highlights the significance of changes in rhizoplane fungi and the stability of the rhizosphere microbial community in comprehending plant ecological sustainability.

Farmers are considered a high-risk group for intentional and unintentional injuries. This review identified significant risk factors for agricultural injuries in farmers and explored injury prevention countermeasures based on the literature. Therefore, CiteSpace software was used to analyze the relevant literature in this field. Additionally, we identified both key risk factors and countermeasures using the Haddon matrix and the 5 E’s risk reduction strategies conceptual framework, respectively. The risk factors were identified from four categories (host, agent, physical environment, and social environment) corresponding to three phases (pre-event, event, and post-event). Interventions of 5 E’s risk reduction strategies including education, engineering, enforcement, economic, and emergency response have been proven effective in preventing injuries or reducing their severity. Our findings provide a comprehensive foundation and research direction for the study and prevention of injuries among farmers.

Abstract Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

Background & Aims: Transforming growth factor-β1 (TGF-β1) plays important roles in chronic liver diseases, including metabolic dysfunction–associated steatotic liver disease (MASLD). MASLD involves various biological processes including dysfunctional cholesterol metabolism and contributes to progression to metabolic dysfunction–associated steatohepatitis and hepatocellular carcinoma. However, the reciprocal regulation of TGF-β1 signaling and cholesterol metabolism in MASLD is yet unknown. Methods: Changes in transcription of genes associated with cholesterol metabolism were assessed by RNA sequencing of murine hepatocyte cell line (alpha mouse liver 12/AML12) and mouse primary hepatocytes treated with TGF-β1. Functional assays were performed on AML12 cells (untreated, TGF-β1 treated, or subjected to cholesterol enrichment [CE] or cholesterol depletion [CD]), and on mice injected with adenovirus-associated virus 8–control/TGF-β1. Results: TGF-β1 inhibited messenger RNA expression of several cholesterol metabolism regulatory genes, including rate-limiting enzymes of cholesterol biosynthesis in AML12 cells, mouse primary hepatocytes, and adenovirus-associated virus–TGF-β1–treated mice. Total cholesterol levels and lipid droplet accumulation in AML12 cells and liver tissue also were reduced upon TGF-β1 treatment. Smad2/3 phosphorylation after 2 hours of TGF-β1 treatment persisted after CE or CD and was mildly increased after CD, whereas TGF-β1–mediated AKT phosphorylation (30 min) was inhibited by CE. Furthermore, CE protected AML12 cells from several effects mediated by 72 hours of incubation with TGF-β1, including epithelial–mesenchymal transition, actin polymerization, and apoptosis. CD mimicked the outcome of long-term TGF-β1 administration, an effect that was blocked by an inhibitor of the type I TGF-β receptor. In addition, the supernatant of CE- or CD-treated AML12 cells inhibited or promoted, respectively, the activation of LX-2 hepatic stellate cells. Conclusions: TGF-β1 inhibits cholesterol metabolism whereas cholesterol attenuates TGF-β1 downstream effects in hepatocytes.

The skeleton-based action recognition technology can effectively avoid the background interference and occlusion problems in the image. However, the recognition of similar actions is still a challenge. In this paper, a multi-scale dynamic topological modeling method (MDTM) is proposed to solve this problem. The topological modeling through the convolution kernel generated from the original data, increases the connection of the convolution process to the original data compared to the previous randomly generated ones, effectively distinguishing similar actions. In addition, MDTM uses a multi-scale temporal convolutional network to obtain a wider receptive field, which can effectively extract the temporal information in the action. At the same time, a dynamic topology learning method is utilized to design a spatiotemporal information extractor that can effectively extract the spatiotemporal information in the action to dynamically adjust the topology structure. Extensive experiments have performed on three large-scale datasets, NTU RGB + D 60, NTU RGB + D 120, and NW-UCLA to validate the effectiveness of MDTM. The results show that MART-GCN performs better than the others in terms of accuracy and number of parameters.

Objective: To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. Methods: This study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. Conclusion: Positive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

PurposeChronic inflammation contributes to the decline in muscle strength and cognitive abilities associated with aging. This study aims to clarify the effects of oral administration of Lacticaseibacillus paracasei LC86 on these age-related declines, as well as its impact on the composition of gut microbiota.MethodsSenescence-accelerated mouse prone 8 (SAMP8) mice received a 12 week regimen of LC86 (1 × 109 CFU/day). Muscle strength was assessed through forelimb grip strength and four-limb hanging tests. Cognitive function was evaluated through behavioral performance tests, and changes in gut microbiota were analyzed.ResultsAdministration of LC86 significantly enhanced muscle strength, demonstrated by increased grip strength and higher glycogen content in the gastrocnemius muscle (p = 0.041, p = 0.017, and p = 0.000, respectively). Behavioral tests suggested that LC86 mitigated age-related cognitive decline. Furthermore, there was a significant decrease in serum pro-inflammatory cytokines, such as IL-6, TNF-α, and MCP-1 (p = 0.002, p = 0.000, and p = 0.005, respectively), and an elevation in the anti-inflammatory cytokine IL-10 level (p = 0.000). An increase in hepatic antioxidant capacity was observed. Significant changes in the gut microbiota composition were noted, including increased populations of Bifidobacterium and Lactobacillus and decreased levels of Escherichia/Shigella and Bacteroides.ConclusionThe findings suggest that LC86 supplementation mitigates muscle weakness and cognitive impairment in aging SAMP8 mice, potentially through the modulation of inflammation and gut microbiota composition. LC86 emerges as a promising candidate for ameliorating the decline of muscular and cognitive functions associated with aging.

Alterations in the microbial community significantly impact the yield and quality of ginseng. Yet, the dynamics of microbial community shifts within the root endophytes of ginseng across varying cultivation periods remain inadequately understood. This study zeroes in on the microbial community variations within the xylem (M), phloem (R), and fibrous roots (X) of ginseng during the fourth (F4) and fifth (F5) years of cultivation, aiming to bridge this research gap. We assessed soil physicochemical properties, enzyme activities, and nine individual saponins, complemented by high-throughput sequencing techniques (16S rDNA and ITS) to determine their profiles. The results showed that cultivation years mainly affected the microbial diversity of endophytic bacteria in ginseng fibrous roots compartment: the ASVs number and α-diversity Chao1 index of bacteria and fungi in F5X compartment with higher cultivation years were significantly higher than those in F4X compartment with lower cultivation years. It is speculated that the changes of fibrous roots bacterial groups may be related to the regulation of amino acid metabolic pathway. Such as D-glutamine and D-glutamate metabolism D-glutamine, cysteine and methionine metabolism regulation. The dominant bacteria in ginseng root are Proteobacteria (relative abundance 52.07–80.35%), Cyanobacteria (1.97–42.52%) and Bacteroidota (1.11–5.08%). Firmicutes (1.28–3.76%). There were two dominant phyla: Ascomycota (60.10–93.71%) and Basidiomycota (2.25–30.57%). Endophytic fungi were more closely related to soil physicochemical properties and enzyme activities. AN, TK, OP, SWC and EC were the main driving factors of endophytic flora of ginseng root. Tetracladium decreased with the increase of cultivation years, and the decrease was more significant in phloem (F4R: 33.36%, F5R: 16.48%). The relative abundance of Bradyrhizobium, Agrobacterium and Bacillus in each ecological niche increased with the increase of cultivation years. The relative abundance of Bradyrhizobium and Agrobacterium in F5X increased by 8.35 and 9.29 times, respectively, and Bacillus in F5M increased by 5.57 times. We found a variety of potential beneficial bacteria and pathogen antagonists related to ginseng biomass and saponins, such as Bradyrhizobium, Agrobacterium, Bacillus and Exophiala, which have good potential for practical application and development.

Objective: Food accumulation fever (FAF), a common clinical disease in children, is generally induced by the excessive intake of high-calorie or high-fat foods. Zhiqiao Chuanlian decoction (ZQCLD) is a classical traditional Chinese medicine (TCM) that may have therapeutic effects on FAF. Methods: Network pharmacological analyses of ZQCLD and FAF were conducted. Animal experiments lasted for 14 days. Rats in the model, positive control, and low-, medium-, and high-dose groups were fed a high-calorie diet. On days 11–14, the positive group was given a domperidone solution. The low-, medium-, and high-dose groups were administered different concentrations of ZQCLD. The body temperature, gastric emptying rate, and intestinal propulsion rate were measured. Relevant indicators were determined by ELISA. Results: The main target proteins included IL-1β, C–C motif chemokine 2 (CCL2), prostaglandin G/H synthase 2 (PTGS2), transcription factor AP-1 (JUN), haem oxygenase 1 (HMOX1), interferon-gamma (IFN-γ), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and inducible nitric oxide synthase (NOS2/iNOS). Compared with those in the control group, body weight, gastric emptying rate, intestinal propulsion rate, and neuronal nitric oxide synthase (NOS1/nNOS) levels were significantly lower in the model group, whereas body temperature and endotoxin, interleukin-1β (IL-1β), PGE2, and iNOS levels were increased. In each treatment group, body temperature and PGE2 levels returned to normal levels. Compared with those in the model group, the gastric emptying rates in the positive group and the low- and medium-dose groups increased; the intestinal propulsion rates were higher in the medium- and high-dose groups, whereas the endotoxin and IL-1β levels were lower; and the nNOS level was higher in the high-dose group, whereas the iNOS level was lower. Conclusions: ZQCLD may treat FAF by regulating jejunal IL-1β and nNOS, serum endotoxin, and hypothalamic PGE2 and iNOS levels.

Soil microbial carbon use efficiency (CUE) is a key parameter controlling the short-term carbon (C) cycle in terrestrial ecosystems. The effect of urea application (156 kg N ha-1) and corn stalks returning (9.0 tons ha-1) on soil microbial CUE and corn yield in semi-arid cropland was studied using the 18O-labeled water approach during a one-year experiment. In semi-arid cropland, applying urea reduced soil microbial CUE by 44%, while the soil microbial CUE was increased significantly by 34% after returning corn stalks to the field. The application of urea increased the total nitrogen content of soil by 23%, and corn stalks returning further increased nitrate nitrogen (NO3--N) by 45%, dissolved organic carbon (DOC) by 53%, and dissolved organic nitrogen (DON) by 122%. Compared with no fertilization, urea application increased the corn height by 4% and the corn yield by 21%. Corn stalks returning combined with urea reduced the corn stalks by 37% compared with no fertilizer. There was no significant difference in corn yield between corn stalks returning combined with urea and single urea application. Therefore, corn stalks returning combined with urea may be an effective agronomic measure to increase soil carbon sequestration, improve soil fertility, maintain corn yield, restore soil fertility, and improve production capacity.

Abstract Introduction This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). Methods This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73–34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or

Abstract Background Regulator of G protein signaling 5 (RGS5), as a negative regulator of G protein-coupled receptor (GPCR) signaling, is highly expressed in arterial VSMCs and pericytes, which is involved in VSMC phenotypic heterogeneity and vascular remodeling in tumors. However, its role in normal and tumor vascular remodeling is controversial. Methods RGS5 knockout (Rgs5-KO) mice and RGS5 overexpression or knockdown in VSMCs in vivo by adeno-associated virus type 9 (AAV) carrying RGS5 cDNA or small hairpin RNA (shRNA) targeting RGS5 were used to determine the functional significance of RGS5 in vascular inflammation. RGS5 expression in the triple-negative (TNBCs) and non-triple-negative breast cancers (Non-TNBCs) was determined by immunofluorescent and immunohistochemical staining. The effect of breast cancer cell-conditioned media (BC-CM) on the pro-inflammatory phenotype of VSMCs was measured by phagocytic activity assays, adhesion assay and Western blot. Results We identified that knockout and VSMC-specific knockdown of RGS5 exacerbated accumulation and pyroptosis of pro-inflammatory VSMCs, resulting in vascular remodeling, which was negated by VSMC-specific RGS5 overexpression. In contrast, in the context of breast cancer tissues, the role of RGS5 was completely disrupted. RGS5 expression was increased in the triple-negative breast cancer (TNBC) tissues and in the tumor blood vessels, accompanied with an extensive vascular network. VSMCs treated with BC-CM displayed enhanced pro-inflammatory phenotype and higher adherent with macrophages. Furthermore, tumor-derived RGS5 could be transferred into VSMCs. Conclusions These findings suggest that tumor microenvironment shifts the function of RGS5 from anti-inflammation to pro-inflammation and induces the pro-inflammatory phenotype of VSMCs that is favorable for tumor metastasis.

Objective: To systematically evaluate the efficacy and safety of Gong Liu Ning as a complimentary therapy in treatment for uterine fibroids. Methods: Randomized controlled trials on Gong Liu Ning for uterine fibroids from China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, PubMed, Cochrane Library, Embase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were retrieved from inception to March 20, 2023. The risk of bias tool was used to evaluate the quality of the selected studies after they met inclusion and exclusion criteria. The GRADE tool was used to evaluate the quality of evidence, and the RevMan5.3 software was used for data analysis. Results: Twenty studies with 1907 patients were analyzed. The meta-analysis results of 15 studies showed that Gong Liu Ning combined with mifepristone was more efficacious than those observed in controls taking only Western medicine (risk ratio [RR] = 1.22, 95% confidence interval [CI] = [1.11, 1.33], P

Abstract Gut dysbiosis causes damage to the intestinal barrier and is associated with type 2 diabetes mellitus (T2DM). We tested the potential protective effects of probiotic BL21 and LRa05 on gut microbiota in type 2 diabetes mellitus mice and determined whether these effects were related to the modulation of gut microbiota.Thirty specific pathogen-free C57BL/6J mice were randomly allocated to three groups—the (CTL) control group, HFD/STZ model (T2DM) group, and HFD/STZ-probiotic intervention (PRO) group—and intragastrically administered strains BL21 and LRa05 for 11 weeks. The administration of strains BL21 and LRa05 significantly regulated blood glucose levels, accompanied by ameliorated oxidative stress in mice. The BL21/LRa05-treated mice were protected from liver, cecal, and colon damage. Microbiota analysis showed that the cecal and fecal microbiota of the mice presented significantly different spatial distributions from one another. Principal coordinate analysis results indicated that both T2DM and the BL21/LRa05 intervention had significant effects on the cecal contents and fecal microbiota structure. In terms of the fecal microbiota, an abundance of Akkermansia and Anaeroplasma was noted in the PRO group. In terms of the cecal content microbiota, enrichment of Akkermansia, Desulfovibrio, Bifidobacterium, Lactobacillus, and Limosilactobacillus was noted in the PRO group. The probiotics BL21 and LRa05 prevent or ameliorate T2DM by regulating the intestinal flora and reducing inflammation and oxidative stress. Our results suggest that BL21 and LRa05 colonize in the cecum. Thus, BL21/LRa05 combined with probiotics having a strong ability to colonize in the colon may achieve better therapeutic effects in T2DM. Our study illustrated the feasibility and benefits of the combined use of probiotics and implied the importance of intervening at multiple intestinal sites in T2DM mice.

Panax ginseng taproot serves as a crucial storage organ and constitutes a significant component of Chinese herbal medicine. In China, ginseng is cultivated using two primary methods: under-forest planting and farmland planting. These methods create distinct habitats that notably influence the morphology of ginseng taproots. However, the precise regulatory mechanisms governing ginseng taproot expansion remain to be fully elucidated. This study aimed to delineate the patterns of ginseng taproot expansion by examining taproots transplanted into farmland (TCG) and forest environments (TLCG and TQCG). Our findings indicate that light intensity and soil available potassium levels in TCG plots significantly exceed those in TLCG and TQCG plots. Compared with TLCG and TQCG, the taproot diameter of TCG increased by 11.54% and 27.73%, respectively. At the same time, combined with the microstructure of the transverse section of the taproot, it showed that the expansion of the TCG taproot was closely related to cell expansion. During TCG taproot expansion, there was an increase in indole-3-acetic acid (IAA) content, significant starch accumulation, and a decrease in lignin content. By analyzing the expression of key genes, we found that compared with TLCG and TQCG, the expression of genes PgTPS1 and PgALDH1 was upregulated, and the expression of genes PgHCT1, PgPAL3, PgPER3, and PgPER51 were downregulated in TCG taproot. Additionally, the transcription factors PgARF18.1 and PgbHLH42 were identified as responsive to habitat changes, playing pivotal roles in taproot expansion. In conclusion, this study provides foundational insights into the regulatory mechanisms of ginseng taproot expansion, offering significant implications for enhancing the quality and value of ginseng.

Drought stress is one of the main factors affecting the growth and secondary metabolism of plants. Iris domestica, rich in isoflavones, is a common herbal medicine in China. In this study, the effects of drought stress and rehydration on resistance physiological characteristics and the secondary metabolism of two-year-old I. domestica during the vegetative and reproductive growth period were investigated. The results showed that the dry weight and fresh weight of rhizomes and roots under severe drought stress were significantly decreased, while those under moderate drought stress were not significantly changed. Meanwhile, the SOD activities, POD activities, MDA content and Pro content increased to resist drought at D1 and D2. In the vegetative growth period, the changes in isoflavone concentration and the expression levels of genes in isoflavone synthesis were more dramatic. Isoflavone accumulation was promoted, to some extent, in the reproductive growth period under the D1 drought treatment. In the actual production process, different measures, namely short-term stress regulation in the vegetative growth period and moderate drought stress (13.44% < soil water content ≤ 16.8%) in the reproductive growth period, need to be adopted to regulate isoflavone biosynthesis.

Platycodon grandiflorum, a dual-purpose herb for food and medicine, is widely distributed in Asia. Although P. grandiflorum has relatively low requirements for its growing environment, temperature remains an important ecological factor affecting its growth, development, and quality formation. In order to explore the effect of different temperatures on P. grandiflorum during their growth period, the diversity in growth physiology, platycodin contents, and gene expression of key enzymes were investigated under constant (8 °C, 18 °C, and 28 °C) and variable (8–18 °C, 8–28 °C, and 18–28 °C) temperature conditions at each of the three levels. The results suggested that both constant and variable temperatures at high levels significantly increased the aboveground fresh weight of P. grandiflorum. However, the low–variable temperature was beneficial for the accumulation of dry and fresh weight in the roots. Regardless of whether temperatures were constant or variable at low levels, this increased the content of soluble sugars, proline, and peroxidase in P. grandiflorum, while upregulating the expression levels of key enzyme genes involved in platycodin synthesis. Meanwhile, a low–constant temperature inhibited the photosynthetic rate of P. grandiflorum. Furthermore, medium–constant and large-scale variable temperatures were conducive to the accumulation of platycodins in the roots. This research provides a theoretical basis and data support for the influence of temperature variations on P. grandiflorum quality formation.

Monitoring air pollution is important for human health and the environment. Previous studies on the prediction of air pollutants from satellite images have employed machine learning, yet there are few enhancements to the constructure of model. Moreover, the existing models have been successful in predicting pollutants like PM2.5, PM10, and O3. They have not been as effective in predicting other primary air pollutants. To improve the overall prediction performance of the existing model, a novel residual learning backpropagation model, abs. as BresNet, has been proposed in this research. This model has revealed the availability to precisely predict the ground-surface concentration of the six primary air pollutants, PM2.5, PM10, O3, NO2, CO, and SO2, based on the satellite imagery of MODIS AOD. Two of the most commonly used machine learning models so far, viz. the multilayer backpropagation neural network (MLBPN) and random forest (RF), were employed as the control. In the conducted experiments, the proposed BresNet model demonstrated significant improvements of 18.75%/31.94%, 33.82%/85.71%, 15.00%/35.29%, 39.06%/134.21%, 23.23%/68.00%, and 137.14%/260.87% in terms of R2 for the six primary air pollutants, compared to the RF/MLBPN model. Moreover, the convergence speed and loss function of the BresNet model compared to that of the MLBPN decreased by 55.15%, revealing superior convergence speed with the lower loss function.

Olanzapine is an atypical antipsychotic drug and a potent muscarinic M3 receptor (M3R) antagonist. Olanzapine has been reported to cause metabolic disorders, including dyslipidemia. Anaplastic lymphoma kinase (Alk), a tyrosine kinase receptor well known in the pathogenesis of cancer, has been recently identified as a key gene in the regulation of thinness via the regulation of adipose tissue lipolysis. This project aimed to investigate whether Olanzapine could modulate the hepatic Alk pathway and lipid metabolism via M3R. Female rats were treated with Olanzapine and/or Cevimeline (an M3R agonist) for 9 weeks. Lipid metabolism and hepatic Alk signaling were analyzed. Nine weeks’ treatment of Olanzapine caused metabolic disturbance including increased body mass index (BMI), fat mass accumulation, and abnormal lipid metabolism. Olanzapine treatment also led to an upregulation of Chrm3, Alk, and its regulator Ptprz1, and a downregulation of Lmo4, a transcriptional repressor of Alk in the liver. Moreover, there were positive correlations between Alk and Chrm3, Alk and Ptprz1, and a negative correlation between Alk and Lmo4. However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders.

Abstract Background Physical activity and eating behavior are associated with hypertension in children and adolescents. Revealing the associations between physical activity patterns, eating behavior patterns and high blood pressure (HBP) could help improve the problem of hypertension from the actual children’s physical activities and eating behaviors. Methods A total of 687 students aged 8–15 years were selected from two nine-year primary and secondary schools using stratified cluster random sampling method. The students’ body height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and their physical activity time and eating behaviors were surveyed by using CLASS questionnaire and self-made eating behavior questionnaire, respectively. Exploratory factor analysis (EFA) was used to extract moderate to vigorous physical activity factor (MVPAF), sedentary activity factor (SAF), healthy eating behavior factor (HEBF), unhealthy eating behavior factor (UHEBF). MVPAF ≥ SAF was defined as moderate to vigorous physical activity pattern (MVPAP), MVPAF

Objective: To assess the quality of systematic reviews assessing the effects of traditional Chinese exercises on controlling blood indices, anthropometric indices, psychological indices, and quality of life in patients with diabetes. Methods: Systematic studies/meta-analyses of intervention with traditional Chinese exercises on diabetes mellitus were searched in the PubMed, Web of Science, the China National Knowledge Infrastructure Databases (CNKI), Wan Fang Database, and Chinese Scientific Journal Database (VIP). Two researchers independently screened the studies and extracted the data. The methodology and quality of evidence of the included studies were assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, respectively. Results: A total of 32 systematic reviews/meta-analyses were included in the present study. Of them, the methodological quality of 4 studies was graded as low, while that of the other 28 was graded as extremely low. The most common quality flaws in key items included a lack of preliminary proposals for systematic reviews, failure to explain the reasons for the inclusion criteria, failure to provide a list of excluded studies and reasons for exclusion, failure to report potential conflicts of interest, and inadequate assessment of publication bias. The quality of evidence for most of the 18 outcomes was subsequently graded as medium or low. Overall, the results of these studies indicated that Tai Chi, health qigong, and other traditional Chinese exercises lowered fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), hemoglobin A1c (HbA1c), and body mass index, and relieved anxiety and depression in patients with diabetes. Conclusion: Our findings indicate that the methodological quality of systematic reviews related to traditional Chinese exercises in the diabetic population is generally low, and the quality of evidence is also relatively poor. Therefore, we suggest that the quality of systematic reviews and meta-analyses on traditional Chinese exercises for controlling diabetes mellitus needs to be improved. In the future, researchers should conduct higher-quality clinical studies with reference to the AMSTAR2 checklist and GRADE system.

IntroductionPharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort.MethodsBuffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models’ performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites.ResultsOverall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model.DiscussionThe development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.

Conclusion: UC-MSCs inhibit autophagy and improve sperm quality in AS rats through the AKT/mTOR pathway, highlighting a new idea for the treatment of AS.

Conducting ecological sensitivity assessment is a crucial approach for pinpointing regional ecological environmental issues, which can offer a scientific basis to aid in the prevention of regional ecological degradation and ensuring regional ecological security. With the protection and high-quality development of the Yellow River Basin (YRB) at the level of a national strategy in China, there is a critical need for a comprehensive assessment of the YRB’s ecological sensitivity. To this end, this study aimed to construct a new ecological sensitivity evaluation index system from three perspectives: natural ecosystem, natural-social ecosystem, and social ecosystem. The ecological sensitivity index was quantified using the entire-array-polygon indicator method, and the spatiotemporal changes of ecological sensitivity in the YRB and its sub-basins were analyzed from 2000 to 2020. The optimal parameters-based geographical detector model was employed to delve into the mechanisms driving the spatial variation in ecological sensitivity. We found that (1) from 2000 to 2020, ecological sensitivity in the YRB exhibited a bimodal trend. Spatially, it tended to be low in the western and eastern parts while it was relatively high in the southern and central regions. (2) The YRB displayed notable clustering effects in terms of ecological sensitivity. The source area showed both “high-high” and “low-low” groupings, the upstream area showed a predominance of “low-low” clusters, while the midstream area and downstream area were demonstrated by concentrated “high-high” clusters. However, the clustering effect in downstream gradually weakened over time. (3) The ecological sensitivity of the YRB was primarily driven by factors like shifts in climate change and soil erosion. There were also marked differences in spatial heterogeneity of ecological sensitivity across different sub-basins. Moreover, the influence of interactive factors on the YRB's ecological sensitivity and its sub-basins was enhanced. The research findings enhance our understanding of ecological issues faced by the YRB and establish a foundation for developing strategies to protect and manage its environmental ecosystem effectively.

Background Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified.Methods The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles.Results A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN.Conclusions Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.

Camellia seed oil (CSO), as a nutrient-rich edible oil, is widely used in foods, cosmetics, and other fields. In this work, the extraction, deacidification, decolorization, and deodorization processes of CSO were respectively optimized for meeting injectable oil standards. The results showed that the CSO extraction rate reached the highest level of 94% at optimized conditions (ultrasonic time, 31.2 min; reaction pH, 9.2; and reaction time, 3.5 h). The physicochemical indexes of CSO and 10 other vegetable oils were evaluated by the principal component analysis method, and the overall scores of vegetable oils were ranked as camellia seed oil > olive oil > rice oil > peanut oil > sesame oil > corn oil > soybean oil > sunflower oil > rapeseed oil > walnut oil > flaxseed oil. The physicochemical indicators of CSO were the most ideal among the 11 vegetable oils, which means that CSO is suitable as an injectable oil. Through the optimized processes of the deacidification, decolorization, and deodorization, the CSO acid value was reduced to 0.0515 mg KOH/g, the decolorization rate reached a maximum of 93.86%, and the OD430 was 0.015, meeting the requirement (≤0.045 of OD430) of injectable oil. After the deodorization process, these parameters of the refractive index, acid value, saponification value, iodine value, absorbance, unsaponifiable, moisture and volatiles, fatty acid composition, and heavy metal limits all met the pharmacopoeia standards of injectable oil in many countries and regions. The possibility of CSO as an injectable oil was first verified through refining-process optimization and nutritional index analysis, providing an important technical reference for the high-value utilization of vegetable oil.

Extensive industrial activities and anthropogenic agricultural practices have led to substantial ammonia release to the environment. Although croplands can act as ammonia sinks, reduced crop production under high concentrations of ammonium has been documented. Alpha-ketoglutarate (AKG) is a critical carbon source, displaying pleiotropic physiological functions. The objective of the present study is to disclose the potential of AKG to enhance ammonium assimilation in poplars. It showed that AKG application substantially boosted the height, biomass, and photosynthesis activity of poplars exposed to excessive ammonium. AKG also enhanced the activities of key enzymes involved in nitrogen assimilation: glutamine synthetase (GS) and glutamate synthase (GOGAT), elevating the content of amino acids, sucrose, and the tricarboxylic acid cycle (TCA) metabolites. Furthermore, AKG positively modulated key genes tied to glucose metabolism and ATP synthesis, while suppressing ATP-depleting genes. Correspondingly, both H+-ATPase activity and ATP content increased. These findings demonstrate that exogenously applying AKG improves poplar growth under a high level of ammonium treatment. AKG might function through sufficient carbon investment, which enhances the carbon–nitrogen balance and energy stability in poplars, promoting ammonium assimilation at high doses of ammonium. Our study provides novel insight into AKG’s role in improving poplar growth in response to excess ammonia exposure.

Panax ginseng C.A. Meyer is a shade plant, and its leaves are an important medicinal part of P. ginseng. Light intensity plays a crucial role in physiological activities and metabolite accumulation in P. ginseng. Currently, little is known about the molecular mechanisms underlying physiological changes and quality under different light intensities in P. ginseng leaves. Therefore, we investigated the changes in photosynthetic physiology, secondary metabolism, transcriptomics, and metabolomics of P. ginseng leaves under different light intensities [T20 (20 µmol m-2·s-1), T50 (50 µmol m-2·s−1), T100 (100 μmol m−2·s−1)]]. Higher light intensity positively influenced the yield, photosynthesis, and accumulation of polysaccharides, soluble sugars, terpenoids, and ginsenosides in P. ginseng leaves. The T100 treatment notably promoted the accumulation of ginsenosides in the leaves, resulting in a 68.32% and 45.55% increase in total ginsenosides compared to the T20 and T50 treatments, respectively. Ginsenosides Rg1, Re, Rb1, Rc, Rg2, Rb2, Rb3, and Rd were 1.28-, 1.47-, 2.32-, 1.64-, 1.28-, 2.59-, 1.66-, and 2.28-times higher than in the T20 treatment. Furthermore, 285 differentially accumulated metabolites (DAMs) and 4218 differentially expressed genes (DEGs) in the metabolome and transcriptome of P. ginseng leaves, respectively, were identified. 13 triterpenoid saponins were significantly upregulated, and three were downregulated. The expression of genes encoding photosystem II reaction center proteins was upregulated under the T100 treatment, thereby increasing photosynthetic activity. The T100 treatment enhanced the expression of genes involved in photosynthetic carbon and energy metabolism in P. ginseng. The expression of antenna protein synthesis genes was upregulated under the T20, which increased the ability to capture light in P. ginseng leaves. T100 upregulated the expression of HMGR, SS, CYP716A53v2, UGT74AE, PgUGT1, and UGTPg45, thereby promoting terpene and ginsenoside synthesis. In summary, 100 µmol m−2·s−1 was conducive to quality formation of P. ginseng leaves. This study elucidates molecular mechanisms underlying the photosynthetic physiology and ginsenoside synthesis in P. ginseng under varying light intensities and provides a theoretical basis for the P. ginseng cultivation and its industrial production of secondary metabolites.