BF3·OEt2-mediated transamidation of unprotected primary amides under solvent-free conditions.

A BF3·OEt2-mediated transamidation between unactivated amides and amines is reported, enabling access to diverse secondary and tertiary amides under transition-metal-free and solvent-free conditions. The operationally simple procedure provides a novel manifold for converting amide-amide bonds with excellent chemoselectivity. In particular, a series of amides including challenging thioamides enable direct transamidation to products with modest to excellent yields. Meanwhile, additional experiments were conducted to elucidate the mechanism of this transformation, and a plausible mechanism was proposed based on the results and related literature.

The fibroblast heterogeneity across keloid, normal and tumor samples from single-cell resolution.

Keloids are defined as a benign dermal fibroproliferative disorder, with excessive fibroblast proliferation, and excessive overproduction of collagen. Although the heterogeneity during keloid development has been extensively studied, the heterogeneity across different skin states is still unclear. So, a global comparison across skin states is needed. In this study, we collected samples from 5 states of skin, including melanoma, cutaneous squamous cell carcinoma, keloid skin, scar skin, and healthy control samples. The heterogeneity of cell types and subtypes was analyzed and compared across 5 states, and we observed significant differences among them. Our results showed a cancer-like fibroblast, which is not in normal samples, may play an important role in antigen processing and presentation. We also noticed that the mesenchymal fibroblast increased in keloid samples, which highly expressed POSTN. And POSTN may participate in epithelial-mesenchymal transition and collagen overexpression to promote keloid growth. These findings help to understand the alteration among different skin states and provide potential genetic basis for keloid therapies.

Rescue path planning for urban flood: A deep reinforcement learning-based approach.

Urban flooding is among the costliest natural disasters worldwide. Timely and effective rescue path planning is crucial for minimizing loss of life and property. However, current research on path planning often fails to adequately consider the need to assess area risk uncertainties and bypass complex obstacles in flood rescue scenarios, presenting significant challenges for developing optimal rescue paths. This study proposes a deep reinforcement learning (RL) algorithm incorporating four main mechanisms to address these issues. Dual-priority experience replays and backtrack punishment mechanisms enhance the precise estimation of area risks. Concurrently, random noisy networks and dynamic exploration techniques encourage the agent to explore unknown areas in the environment, thereby improving sampling and optimizing strategies for bypassing complex obstacles. The study constructed multiple grid simulation scenarios based on real-world rescue operations in major urban flood disasters. These scenarios included uncertain risk values for all passable areas and an increased presence of complex elements, such as narrow passages, C-shaped barriers, and jagged paths, significantly raising the challenge of path planning. The comparative analysis demonstrated that only the proposed algorithm could bypass all obstacles and plan the optimal rescue path across nine scenarios. This research advances the theoretical progress for urban flood rescue path planning by extending the scale of scenarios to unprecedented levels. It also develops RL mechanisms adaptable to various extremely complex obstacles in path planning. Additionally, it provides methodological insights into artificial intelligence to enhance real-world risk management.

Soluble ST2 is a biomarker associated with left ventricular hypertrophy and concentric hypertrophy in patients with essential hypertension.

BACKGROUND: Elevated soluble stimulating factor 2 (sST2) level is observed in cardiovascular diseases, such as heart failure and acute coronary syndrome, which reflects myocardial fibrosis and hypertrophy, indicating adverse clinical outcomes. However, the association between sST2 and hypertensive heart disease are less understood. This study aimed to determine the relationship of sST2 with left ventricular hypertrophy (LVH) and geometric remodeling in essential hypertension (EH). METHODS: We enrolled 483 patients (aged 18-80 years; 51.35% female). sST2 measurements and echocardiographic analyses were performed. RESULTS: Stepwise multiple linear regression analysis showed significant associations between sST2, left ventricular (LV) mass, and LV mass index. The prevalence of LVH and concentric hypertrophy (CH) increased with higher sST2 grade levels (p for trend<0.05). Logistic regression analysis suggested that the highest tertile of sST2 was significantly associated with increased LVH risk, compared with the lowest tertile (multivariate-adjusted odds ratio [OR] of highest group: 6.61; p<0.001). Similar results were observed in the left ventricular geometric remodeling; the highest tertile of sST2 was significantly associated with increased CH risk (multivariate-adjusted OR of highest group: 5.80; p<0.001). The receiver operating characteristic analysis results revealed that sST2 had potential predictive value for LVH (area under the curve [AUC]: 0.752, 95% confidence interval [CI]: 0.704-0.800) and CH (AUC: 0.750, 95% CI: 0.699-0.802) in patients with EH. CONCLUSIONS: High sST2 level is strongly related to LVH and CH in patients with EH and can be used as a biomarker for the diagnosis and risk assessment of hypertensive heart disease.

Electrophysiological activity pattern of mouse hippocampal CA1 and dentate gyrus under isoflurane anesthesia.

General anesthesia can impact a patient's memory and cognition by influencing hippocampal function. The CA1 and dentate gyrus (DG), serving as the primary efferent and gateway of the hippocampal trisynaptic circuit facilitating cognitive learning and memory functions, exhibit significant differences in cellular composition, molecular makeup, and responses to various stimuli. However, the effects of isoflurane-induced general anesthesia on CA1 and DG neuronal activity in mice are not well understood. In this study, utilizing electrophysiological recordings, we examined neuronal population dynamics and single-unit activity (SUA) of CA1 and DG in freely behaving mice during natural sleep and general anesthesia. Our findings reveal that isoflurane anesthesia shifts local field potential (LFP) to delta frequency and reduces the firing rate of SUA in both CA1 and DG, compared to wakefulness. Additionally, the firing rates of DG neurons are significantly lower than CA1 neurons during isoflurane anesthesia, and the recovery of theta power is slower in DG than in CA1 during the transition from anesthesia to wakefulness, indicating a stronger and more prolonged impact of isoflurane anesthesia on DG. This work presents a suitable approach for studying brain activities during general anesthesia and provides evidence for distinct effects of isoflurane anesthesia on hippocampal subregions.

Recent advances for enhanced photodynamic therapy: from new mechanisms to innovative strategies.

Photodynamic therapy (PDT) has been developed as a potential cancer treatment approach owing to its non-invasiveness, spatiotemporal control and limited side effects. Currently, great efforts have been made to improve the PDT effect in terms of safety and efficiency. In this review, we highlight recent advances in innovative strategies for enhanced PDT, including (1) the development of novel radicals, (2) design of activatable photosensitizers based on the TME and light, and (3) photocatalytic NADH oxidation to damage the mitochondrial electron transport chain. Additionally, the new mechanisms for PDT are also presented as an inspiration for the design of novel PSs. Finally, we discuss the current challenges and future prospects in the clinical practice of these innovative strategies. It is hoped that this review will provide a new angle for understanding the relationship between the intratumoural redox environment and PDT mechanisms, and new ideas for the future development of smart PDT systems.

[Effect of Peitu Yifei Granules on autophagy mechanism in rats with idiopathic pulmonary fibrosis based on PI3K/Akt/mTOR signaling pathway].

To investigate the mechanism by which Peitu Yifei Granules inhibit idiopathic pulmonary fibrosis(IPF) in rats, fifty specific-pathogen-free(SPF) grade male Wistar rats were randomly divided into blank group and modeling group. IPF was induced in the modeling group rats by tracheal infusion of 5 mg·kg~(-1) bleomycin(BLM) and then randomly divided into model group, pirfenidone group, and high-dose, medium-dose, and low-dose groups treated with Peitu Yifei Granules. After 24 hours of modeling, the treatment groups received intragastric administration of either Peitu Yifei Granules or pirfenidone as a positive control drug; meanwhile, the model group received an equal volume of normal saline. After 21 days of treatment administration, lung tissue samples were collected for analysis. Pathological changes in lung tissues were assessed using hematoxylin-eosin(HE) staining and Masson's trichrome staining. The expression levels of protein kinase B(Akt), mammalian target of rapamycin(mTOR), their phosphorylated forms, and sequestosome 1(p62) were determined through Western blot(WB). Fluorescent quantitative real-time polymerase chain reaction(RT-qPCR) was used to measure messenger ribonucleic acid(mRNA) expression levels of Beclin-1, microtubule-associated proteins 1A/1B light chain 3B(LC3B), and p62. Immunohistochemistry was performed to assess protein expression levels of Beclin-1 and LC3B in lung tissue samples. RESULTS:: demonstrated that lung tissue structure appeared normal without significant collagen deposition in the blank group rats. In contrast, rats from the model group exhibited thickened alveolar septa along with evident inflammatory changes and collagen deposition. Compared to the model group rats, those treated with Peitu Yifei Granules or pirfenidone showed significantly improved lung tissue structure with reduced inflammation and collagen deposition observed histologically. Furthermore, compared with those of the blank group, the expressions of p62 and its mRNA, p-Akt and p-mTOR protein in lung tissues of the model group were significantly increased, while Beclin-1, LC3B and their mRNA levels were significantly decreased. Compared with those of the model group, the expressions of p62 and its mRNA, p-Akt and p-mTOR in lung tissues of the pirfenidone group and Peitu Yifei Granules high-dose and medium-dose groups were significantly decreased, while Beclin-1, LC3B and their mRNA expressions were significantly increased. The above results indicate that Peitu Yifei Granules can improve autophagy levels in lung tissues by inhibiting the phosphoinositide 3-kinase(PI3K)/Akt/mTOR signaling pathway and delay the development of IPF disease.

Dynamic development of microglia and macrophages after spinal cord injury.

Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin ß2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.

Comparing the diagnostic value of 68Ga-prostate-specific membrane antigen PET/CT and multiparametric MRI in pelvic lymph node metastasis of locally advanced prostate cancer.

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5±10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7±12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions: 68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC.

WRKY75 regulates anthocyanin accumulation in juvenile citrus tissues.

The anthocyanin accumulation in juvenile tissues can enhance the ornamental value, attract pollinators, and help improve abiotic stress. Although transcriptional regulation studies of anthocyanin have been relatively extensive, there are few reports on the mechanism of anthocyanin accumulation in young tissues. This study reveals that many juvenile citrus tissues (flowers, leaves, and pericarp) undergo transient accumulation of anthocyanins, exhibiting a red coloration. Using weighted gene co-expression network analysis (WGCNA) identified CitWRKY75 as a candidate gene. After detecting the expression levels of CitWRKY75 in various citrus juvenile tissues, the expression trend of CitWRKY75 was highly consistent with the red exhibiting and fading. Overexpression of CitWRKY75 in tobacco significantly increased the anthocyanin content. LUC and yeast one-hybrid assay demonstrated that CitWRKY75 could bind to the promoter of CitRuby1(encoding the key transcription factor promoting anthocyanin accumulation) and promote its expression. Finally, comparing the expression levels of CitWRKY75 and CitRuby1 in the late development stage of blood orange found that CitWRKY75 was not the main regulatory factor for anthocyanin accumulation in the later stage. This study used reverse genetics to identify a transcription factor, CitWRKY75, upstream of CitRuby1, which promotes anthocyanin accumulation in citrus juvenile tissues. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01490-9.

Insights into the microbial assembly and metabolites associated with ginger (Zingiber officinale L. Roscoe) microbial niches and agricultural environments.

Ginger, a vegetable export from China, is well-known for its spicy flavour and use in traditional Chinese medicine. By examining the interactions of ginger plants' microbiome and metabolome, we can gain insights to advance agriculture, the environment, and other fields. Our study used metataxonomic analysis to investigate ginger plants' prokaryotic and fungal microbiomes in open fields and greenhouses. We also conducted untargeted metabolomic analysis to identify specific metabolites closely associated with ginger microbiome assembly under both agricultural conditions. Various bacteria and fungi were classified as generalists or specialists based on their ability to thrive in different environments and microbial niches. Our results indicate that ginger plants grown in greenhouses have a greater prokaryotic diversity, while those grown in open fields exhibit a greater fungal diversity. We have identified specific co-occurring prokaryotic and fungal genera associated with ginger plant agroecosystems that can enhance the health and growth of ginger plants while maintaining a healthy environment. In the open field these genera include Sphingomonas, Methylobacterium-Methylorubrum, Bacillus, Acidovorax, Rhizobium, Microbacterium, unclassified_f_Comamonadaceae, Herbaspirillum, Klebsiella, Enterobacter, Chryseobacterium, Nocardioides, Subgroup_10, Enterococcus, Pseudomonas, Devosia, g_unclassified_f_Chaetomiaceae, Pseudaleuria, Mortierella, Cheilymenia, and Pseudogymnoascus. In the greenhouse, the enriched genera were Rhizobium, Stenotrophomonas, Aureimonas, Bacillus, Nocardioides, Pseudomonas, Enterobacter, Delftia, Trichoderma, Mortierella, Cheilymenia, Schizothecium, and Actinomucor. Our research has identified several previously unknown microbial genera for ginger plant agroecosystems. Furthermore, our study has important implications for understanding the correlation between ginger's microbiome and metabolome profiles in diverse environments and may pave the way for future research. Specific microbial genera in crop production environments are associated with essential metabolites, including Safingol, Docosatrienoic acid, P-acetaminophen, and Hypoglycin B.

Clinical features, treatment and prognosis of patients with endogenous infectious endophthalmitis.

PURPOSE: To investigate whether the clinical characteristics, treatment and prognosis of endogenous infectious endophthalmitis (EIE) have changed over the past 5 years. METHODS: Retrospectively analyze all articles about EIE published in the PubMed, Web of Science, and Embase databases from 2017 to 2021. RESULTS: A total of 128 patients and 147 eyes (46 left and 60 right) were included in the study. The mean age at diagnosis was 51 ± 19 years. The most common risk factors were diabetes and intravenous drug use. From 2017 to 2021, Klebsiella was the most common pathogenic microorganism (22%), and vitreous culture had the highest positivity rate. The most common complaint was blurred vision. The mean visual acuity (logMAR) at onset was 2.84, and the clinical symptoms were vitreal inflammation and opacity (63%), ocular pain (37%), and conjunctival congestion (36%). The ocular inflammation could be reduced by intraocular antibiotics or vitrectomy. However, the visual prognosis, with a mean logMAR of 2.73; only 50% of the eyes reached a visual acuity level of finger count and above. Changes in diagnostics over the past 5 years have mainly manifested as more diverse microorganism culture methods. In addition to conventional culture methods, PCR, sputum culture and aqueous humour culture are also commonly used for the diagnosis of pathogenic bacteria, improving the positive culture rate and visual prognosis. CONCLUSION: The prognosis of EIE is poor. It is recommended to pay attention to the pathogenic bacteria culture results and accompanying systemic diseases and to diagnose and treat patients as soon as possible.

The Impact of Proton Pump Inhibitors on the Efficacy of Immune Checkpoint Inhibitor Combinations in Patients with HBV-Associated Advanced Hepatocellular Carcinoma.

Purpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs. Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients' survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated. Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient's OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024). Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.

Oxytocin Alleviates Colitis and Colitis-Associated Colorectal Tumorigenesis via Noncanonical Fucosylation.

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus-hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through ß1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin's promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

Long-term herbicide residues affect soil multifunctionality and the soil microbial community.

Residues of herbicides with the extensive applications may impact the soil ecosystem and ultimately threaten agricultural sustainability. However, the effects of long-term herbicide residues on soil multifunctionality and the soil microbial community remain poorly understood. Here, we evaluated relationships between soil multifunctionality and soil microbial communities with residual herbicide concentrations by surveying and analyzing 62 black soil samples collected from an agricultural area in northeastern China. Total residual herbicide concentrations varied from 35 to 568 µg/kg in the soil samples. The response of soil multifunctionality to increasing residual herbicide concentrations exhibited an inverted U-shaped relationship with a peak at approximately 310 µg/kg, with net mineralized organic nitrogen (Nm) and total nitrogen (TN) exhibiting the same trend. Microbial community richness was significantly lower in soil samples with high residual herbicide concentrations (> 310 µg/kg, HG) compared to low residual herbicide concentrations (< 310 µg/kg, LG). In addition, the relative abundances of specific keystone microbial genera differed significantly between LG and HG: norank_f_Acetobacteraceae, norank_f_Caldilineaceae, Candidatus_Alysiosphaera, and Gonytrichum. The relative abundances of these genera were also significantly correlated with soil multifunctionality. Structural equation models (SEMs) further showed that herbicide residues influenced soil multifunctionality by affecting these specific keystone genera. Our study demonstrates that long-term herbicide residues significantly impact the multifunctionality of agricultural black soil, where low concentrations stimulate while high concentrations inhibit, underscoring the need for reasonable application of herbicides to maintain soil ecosystem health.

Role of Cardiolipin in regulating and treating atherosclerotic cardiovascular diseases.

Cardiovascular diseases, mainly caused by atherosclerosis, are the leading causes of morbidity and mortality worldwide. Despite the discrepancies in clinical manifestations between different abnormalities, atherosclerosis shares similar pathophysiological processes, such as mitochondrial dysfunction. Cardiolipin (CL) is a conserved mitochondria-specific lipid that contributes to the cristae structure of the inner mitochondrial membrane (IMM). Alterations in the CL, including oxidative modification, reduced quantity, and abnormal localization, contribute to the onset and progression of atherosclerosis. In this review, we summarize the knowledge that CL is involved in the pathogenesis of atherosclerosis. On the one hand, CL and its oxidative modification promote the progression of atherosclerosis via several mechanisms, including oxidative stress, apoptosis, and inflammation in response to stress. On the other hand, CL externalizes to the outer mitochondrial membrane (OMM) and acts as the pivotal "eat-me" signal in mitophagy, removing dysfunctional mitochondria and safeguarding against the progression of atherosclerosis. Given the imbalance between proatherogenic and antiatherogenic effects, we provide our understanding of the roles of the CL and its oxidative modification in atherosclerotic cardiovascular diseases, in addition to potential therapeutic strategies aimed at restoring the CL. Briefly, CL is far more than a structural IMM lipid; broader significances of the evolutionarily conserved lipid need to be explored.

Seasonal variations in soil microbial community co-occurrence network complexity respond differently to field-simulated warming experiments in a northern subtropical forest.

Global warming may reshape seasonal changes in microbial community diversity and co-occurrence network patterns, with significant implications for terrestrial ecosystem function. We conducted a 2-year in situ field simulation of the effects of warming on the seasonal dynamics of soil microbial communities in a northern subtropical Quercus acutissima forest. Our study revealed that warming had no significant effect on the richness or diversity of soil bacteria or fungi in the growing season, whereas different warming gradients had different effects on their diversity in the nongrowing season. Warming also changed the microbial community structure, increasing the abundance of some thermophilic microbial species and decreasing the abundance of some symbiotrophic microorganisms. The co-occurrence network analysis of the microbial community showed that warming decreased the complexity of the intradomain network in the soil bacterial community in the growing and nongrowing seasons but increased it in the fungal community. Moreover, increasing warming temperatures increased the complexity of the interdomain network between bacteria and fungi in the growing season but decreased it in the nongrowing season, and the keystone species in the interdomain network changed with warming. Warming also reduced the proportion of positive microbial community interactions, indicating that warming reduced the mutualism, commensalism, and neutralism of microorganisms as they adapted to soil environmental stress. The factors affecting the fungal community varied considerably across warming gradients, with the bacterial community being significantly affected by soil temperature, MBC, NO3--N and NH4+-N, moreover, SOC and TN significantly affected fungal communities in the 4 °C warming treatment. These results suggest that warming increases seasonal differences in the diversity and complexity of soil microbial communities in the northern subtropical region, significantly influencing soil dynamic processes regulating forest ecosystems under global warming.

Correlation between Metabolic Parameters and Warfarin Dose in Patients with Heart Valve Replacement of Different Genotypes.

Background: Warfarin has become the first choice for anticoagulation in patients who need lifelong anticoagulation due to its clinical efficacy and low price. However, the anticoagulant effect of warfarin is affected by many drugs, foods, etc. accompanied by a high risk of bleeding and embolism. The Vitamin K epoxide reductase complex 1 (VKORC1) and Cytochrome P450 2C9 (CYP2C9) genotypic variation can influence the therapeutic dose of warfarin. However, it is not clear whether there is a correlation between warfarin dose and liver function, kidney function and metabolic markers such as uric acid (UA) in patients with different genotypes. We performed a single-center retrospective cohort study to evaluate the factors affecting warfarin dose and to establish a dose conversion model for warfarin patients undergoing heart valve replacement. Methods: We studied 343 patients with a mechanical heart valve replacement, compared the doses of warfarin in patients with different warfarin-related genotypes (CYP2C9 and VKORC1), and analyzed the correlation between liver function, kidney function, UA and other metabolic markers and warfarin dose in patients with different genotypes following heart valve replacement. Results: Genotype analysis showed that 72.01% of patients had CYP2C9*1/*1 and VKORC1 mutant AA genotypes. Univariate regression analysis revealed that the warfarin maintenance dose was significantly correlated with gender, age, body surface area (BSA), UA and genotype. There was no correlation with liver or kidney function. Multiple linear regression analysis showed that BSA, genotype and UA were the independent factors influencing warfarin dose. Conclusions: There is a significant correlation between UA content and warfarin dose in patients with heart valve replacement genotypes CYP2C9*1/*1/VKORC1(GA+GG), CYP2C9*1/*1/VKORC1AA and CYP2C9*1/*1/VKORC1AA.

Insight into endothelial cell-derived extracellular vesicles in cardiovascular disease: Molecular mechanisms and clinical implications.

The endothelium is crucial in regulating vascular function. Extracellular vesicles (EVs) serve as membranous structures released by cells to facilitate intercellular communication through the delivery of nucleic acids, lipids, and proteins to recipient cells in an paracrine or endocrine manner. Endothelial cell-derived EVs (EndoEVs) have been identified as both biomarkers and significant contributors to the occurrence and progression of cardiovascular disease (CVD). The impact of EndoEVs on CVD is complex and contingent upon the condition of donor cells, the molecular cargo within EVs, and the characteristics of recipient cells. Consequently, elucidating the underlying molecular mechanisms of EndoEVs is crucial for comprehending their contributions to CVD. Moreover, a thorough understanding of the composition and function of EndoEVs is imperative for their potential clinical utility. This review aims provide an up-to-date overview of EndoEVs in the context of physiology and pathophysiology, as well as to discuss their prospective clinical applications.