Prolonged vs shorter awake prone positioning for COVID-19 patients with acute respiratory failure: a multicenter, randomised controlled trial.

PURPOSE: Awake prone positioning has been reported to reduce endotracheal intubation in patients with coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF). However, it is still unclear whether using the awake prone positioning for longer periods can further improve outcomes. METHODS: In this randomized, open-label clinical trial conducted at 12 hospitals in China, non-intubated patients with COVID-19-related AHRF were randomly assigned to prolonged awake prone positioning (target > 12 h daily for 7 days) or standard care with a shorter period of awake prone positioning. The primary outcome was endotracheal intubation within 28 days after randomization. The key secondary outcomes included mortality and adverse events. RESULTS: In total, 409 patients were enrolled and randomly assigned to prolonged awake prone positioning (n = 205) or standard care (n = 204). In the first 7 days after randomization, the median duration of prone positioning was 12 h/d (interquartile range [IQR] 12-14 h/d) in the prolonged awake prone positioning group vs. 5 h/d (IQR 2-8 h/d) in the standard care group. In the intention-to-treat analysis, intubation occurred in 35 (17%) patients assigned to prolonged awake prone positioning and in 56 (27%) patients assigned to standard care (relative risk 0.62 [95% confidence interval (CI) 0.42-0.9]). The hazard ratio (HR) for intubation was 0.56 (0.37-0.86), and for mortality was 0.63 (0.42-0.96) for prolonged awake prone positioning versus standard care, within 28 days. The incidence of pre-specified adverse events was low and similar in both groups. CONCLUSION: Prolonged awake prone positioning of patients with COVID-19-related AHRF reduces the intubation rate without significant harm. These results support prolonged awake prone positioning of patients with COVID-19-related AHRF.

Prevalence of burnout among military personnel in the plateau region of China: a cross-sectional survey.

OBJECTIVES: The geographical environment and military activities in the plateau area pose potential work-related stressors for military personnel, leading to burnout which is an external manifestation of internal energy exhaustion caused by stress. Without countermeasures, this can result in serious military problems. This study aims to examine the association between burnout and occupational stressors among military personnel stationed in the plateau area of China. MATERIAL AND METHODS: A stratified randomized cluster sampling survey was conducted among 2026 military personnel from 6 different troops stationed in the plateau area of China. The Chinese Maslach Burnout Inventory-General Survey(MBI-GS in Chinese) was administered from March 2022 to December 2023, and data were analyzed using SPSS version 25. RESULTS: A total of 2026 military personnel participated in the survey. The mean overall burnout score was 3.37 ± 0.73, with emotional exhaustion at 2.69 ± 0.89, depersonalization at 3.58 ± 0.92, and professional achievement at 3.81 ± 0.85 levels respectively reported by participants on average scale scores ranging from zero to six. Severe level of burnout was reported by 43.2% of participants while medium level of burnout was reported by 54 .3%. Age, education level, length of military service, and household income were identified as important factors influencing burnout. CONCLUSION: This study highlights a relatively high prevalence of burnout among military personnel stationed in plateau areas necessitating attention towards their occupational health particularly focusing on working hours and economic aspects so as to formulate effective policies and implement intervention measures that strengthen career development for soldiers deployed in such regions.

Effects of different parameters of Tai Chi on the intervention of chronic low back pain: A meta-analysis.

OBJECTIVE: To evaluate the effects of Tai Chi in the treatment of patients with chronic low back pain by Meta-analysis and to investigate its influencing factors. METHODS: The study searched eight databases (PubMed, Embase, The Cochrane Library, Web of Science, China Knowledge Network, Wanfang, VIP, and CBM) from inception to October 2023. Two investigators independently selected 10 eligible randomized controlled trials (RCT) against inclusion and exclusion criteria, followed by data extraction and study quality assessment by ROB 2. The outcomes of interest were pain intensity and disability. The studies were combined using meta-analysis when statistical pooling of data was possible. The quality of the evidence was assessed using the GRADE approach. RESULTS: 10 randomized controlled studies with a total sample of 886 cases were included, of which 4 (40%) were assessed as low risk of bias. The effect size of Tai Chi for chronic low back pain was [Weighted Mean Difference (WMD) with 95% Confidence Interval (CI) = -1.09 (-1.26, -0.92), p < 0.01], all achieving large effect sizes and statistically significant; the effect size for disability was [Standard Mean Difference (SMD) with 95% CI = -1.75 (-2.02, -1.48), p < 0.01], and the combined effect sizes of physical health and mental health for quality of life were [WMD (95% CI) = 4.18 (3.41, 4.95), p < 0.01; WMD (95% CI) = 3.23 (2.42, 4.04), p < 0.01] respectively. The incidence of adverse reactions was low. Meta regression and subgroup analysis showed that there was no significant effect on intervention measures (Tai Chi alone, Tai Chi as additional therapy, water Tai Chi), Tai Chi school (Chen and Yang) and the number of total intervention sessions (> 30 and ≤ 30). The evidence quality evaluation showed that the evidence of pain, physical health of quality of life and mental health score was medium quality, while the evidence of disability and adverse reactions was low quality. CONCLUSIONS: Tai Chi has an obvious effect of in relieving chronic low back pain. Tai Chi alone and Tai Chi as supplementary therapy have good effects. Tai Chi in water have not been verified. Chen style Tai Chi and Yang's Tai Chi, intervention more than 30 times or less than 30 times had no significant difference in the effect of intervention on CLBP.

FAM20A: a potential diagnostic biomarker for lung squamous cell carcinoma.

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC. Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, and TIMER database, were employed to assess the diagnostic and prognostic value of FAM20A in LUSC. These tools also helped evaluate immune cell infiltration, immune checkpoint genes, DNA repair-related genes, DNA methylation, and tumor-related pathways. Results: FAM20A expression was found to be significantly reduced in LUSC, correlating with lower survival rates. It exhibited a negative correlation with key proteins in DNA repair signaling pathways, potentially contributing to LUSC's radiotherapy resistance. Additionally, FAM20A showed a positive correlation with immune checkpoints like CTLA-4, indicating potential heightened sensitivity to immunotherapies targeting these checkpoints. Conclusion: FAM20A emerges as a promising diagnostic and prognostic biomarker for LUSC, offering potential clinical applications.

Dosing Strategies and Quantitative Clinical Pharmacology for Bispecific T-Cell Engagers Development in Oncology.

Bispecific T-cell Engagers (TCEs) are promising anti-cancer treatments that bind to both the CD3 receptors on T cells and an antigen on the surface of tumor cells, creating an immune synapse, leading to killing of malignant tumor cells. These novel therapies have unique development challenges, with specific safety risks of cytokine release syndrome. These on-target adverse events fortunately can be mitigated and deconvoluted from efficacy via innovative dosing strategies, making clinical pharmacology key in the development of these therapies. This review assesses dose selection and the role of quantitative clinical pharmacology in the development of the first eight approved TCEs. Model informed drug development (MIDD) strategies can be used at every stage to guide TCE development. Mechanistic modeling approaches allow for (1) efficacious yet safe first-in-human dose selection as compared with in vitro minimum anticipated biological effect level (MABEL) approach; (2) rapid escalation and reducing number of patients with subtherapeutic doses through model-based adaptive design; (3) virtual testing of different step-up dosing regimens that may not be feasible to be evaluated in the clinic; and (4) selection and justification of the optimal clinical step-up and full treatment doses. As the knowledge base around TCEs continues to grow, the relevance and utilization of MIDD strategies for supporting the development and dose optimization of these molecules are expected to advance, optimizing the benefit-risk profile for cancer patients.

Integrated multi-omics profiling landscape of organising pneumonia.

BACKGROUND: Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis. METHODS: Comprehensive multi-omics profiling approaches, including single-cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages. RESULTS: The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis. CONCLUSIONS: CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti-ferroptosis and anti-fibrosis effect of CD36 mediated, at least in part, by ceramides. HIGHLIGHTS: Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.

Recent Progress in Free Radical Transformations of Allenamides.

Allenamides are special allenes, and the unique reactivity, selectivity (both stereoselective and regionally selective) and stability of allenamides have been widely studied. In this review, the development of the free radical transformation of allenamides over the last few years will be summarized. This review discusses in detail in three parts: intermolecular radical addition to C- X (X = N, S, O, Se) bonds, metal salt mediated cyclization of allenamides, and photocatalytic cyclization of allenamides. In addition, reasonable details of the mechanisms are provided for the vast majority of these transformations.

Effective and green in-situ remediation strategies based on TEMPO-nanocellulose/lignin/MIL-100(Fe) hydrogel nanocomposite adsorbent for lead and copper in agricultural soils.

Hydrogel adsorbents are promising tools for reducing heavy metals' bioavailability in contaminated soil. However, their practical feasibility remains limited by the low stability, inefficient removal efficiency, and potential secondary pollution. Optimizing the adsorption operation and the functional properties of hydrogel adsorbents could eliminate this method's drawbacks. Herein, three innovative in-situ remediation strategies for Pb/Cu-contaminated soil were adopted based on the concept of novel TEMPO-cellulose (TO-NFCs)/lignin/acrylamide@MIL-100(Fe) nanocomposite hydrogel adsorbent (NCLMH). Characteristic analyses revealed ideal Pb/Cu adsorption mechanisms by swelling, complexation, electrical attraction, and ion exchange via carboxyl/hydroxyl/carbonyl groups and unsaturated Fe(III) sites on ANCMH besides FeOOH formation. The highest maximum theoretical adsorption capacities of Pb(II) and Cu(II) on ANCMH were 416.39 and 133.98 mg/g, under pH 6.5, governed by pseudo-second-order/Freundlich models. Greenhouse pot experiments with contaminated soils amended with two-depth layers of 0.5% NCLMHs (SA@NCLMH) displayed a decline in Pb and Cu bioavailability up to 85.9% and 74.5% within 45 d. Soil column studies simulating continuous water soil flushing coupled with NCLMH layers, instead of conventional extractant fluids, and connected to NCLMH-sand column as purification unit (CF@NCLMH) achieved higher removal rates for Pb, and Cu of 89.5% and 77.2% within 24 h. Alternatively, conducting multiple-pulse soil flushing mode (MF@NCLMH) gained the highest Pb and Cu removal of 96.5% and 85.4%, as the water flushing-stop flux events allowed adequate water movement/residence period, promoting Pb/Cu desorption-adsorption from soil to NCLMH. Also, the NCLMH-sand column conducting and easy separation of the stable/reusable NCLMHs prevented the potential secondary pollution. Interestingly, the three remediated soils reached the corresponding regulation of the permissible limits for Pb and Cu residential scenarios in medium-to-heavily agricultural polluted soils, alleviating the Pb/Cu bioaccumulation and phytotoxicity symptoms in cultivated wheat, especially after MF@NCLMH treatment. This study introduces promising alternative remediation strategies with high sustainability and feasibility in acidic-to-neutral heavy metal-contaminated agricultural soil.

Enhancing General Surgery Clerkships: The Application and Value of Standardized Patient-Based Situational Simulation Teaching.

OBJECTIVE: We explored the value of a standardized patient-based situational simulation teaching method in general surgery internships. METHODS: A prospective, single-blind, randomized controlled trial was conducted with clinical medicine undergraduates from the 2020 cohort of our university as subjects. These students were randomly divided into a traditional teaching (TT) group and a combined teaching (CT) group based on their internship schedules. The TT group followed the conventional teaching model, while the CT group engaged in the standardized patient-based situational simulation teaching method. The study compared differences in pre-internship theoretical scores, post-internship theoretical scores, medical record writing quality, and student satisfaction between the two groups. RESULTS: The CT group (n=108) significantly outperformed the TT group (n=104) in post-internship theoretical scores and medical record writing quality (all P<0.05) and showed marked improvement in stimulating students' interest in learning (P=0.015), enhancing clinical diagnostic and treatment abilities (P<0.001), improving doctor‒patient communication skills (P<0.001), strengthening medical mission sense (P<0.001), reinforcing physicians' sense of responsibility (P<0.001), and facilitating the application of learned knowledge (P<0.001). These differences were statistically significant. CONCLUSION: The standardized patient-based situational simulation teaching method (CT) in general surgery internships has been highly recognized by students and can enhance their clinical competency, offering considerable value for broader.

Homotherapy for heteropathy: therapeutic effect of Butein in NLRP3-driven diseases.

BACKGROUND: Aberrant inflammatory responses drive the initiation and progression of various diseases, and hyperactivation of NLRP3 inflammasome is a key pathogenetic mechanism. Pharmacological inhibitors of NLRP3 represent a potential therapy for treating these diseases but are not yet clinically available. The natural product butein has excellent anti-inflammatory activity, but its potential mechanisms remain to be investigated. In this study, we aimed to evaluate the ability of butein to block NLRP3 inflammasome activation and the ameliorative effects of butein on NLRP3-driven diseases. METHODS: Lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages were pretreated with butein and various inflammasome stimuli. Intracellular potassium levels, ASC oligomerization and reactive oxygen species production were also detected to evaluate the regulatory mechanisms of butein. Moreover, mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis were used to test whether butein has protective effects on these NLRP3-driven diseases. RESULTS: Butein blocks NLRP3 inflammasome activation in mouse macrophages by inhibiting ASC oligomerization, suppressing reactive oxygen species production, and upregulating the expression of the antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Importantly, in vivo experiments demonstrated that butein administration has a significant protective effect on the mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis. CONCLUSION: Our study illustrates the connotation of homotherapy for heteropathy, i.e., the application of butein to broaden therapeutic approaches and treat multiple inflammatory diseases driven by NLRP3.

Mycobacterium tuberculosis FadD18 Promotes Proinflammatory Cytokine Secretion to Inhibit the Intracellular Survival of Bacillus Calmette-Guérin.

Mycobacterium tuberculosis causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a Bacillus Calmette-Guérin (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive fadD18 gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that fadD18 expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1ß, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines.

The different association between fat mass distribution and intake of three major nutrients in pre- and postmenopausal women.

BACKGROUND: Obesity, characterized by excessive body fat accumulation, is associated with various chronic health conditions. Body fat plays a crucial role in health outcomes, and nutrient intake is a contributing factor. Menopause further influences body fat, but the precise relationships between nutrients and fat mass distribution in pre- and post-menopausal women are unclear. METHODS: Data from 4751 adult women aged ≥18 years old (3855 pre-menopausal, 896 post-menopausal) with completed information were obtained from the National Health and Examination Survey (NHANES) from 2011 to 2018. Multivariate linear regression models were used to examine the associations between protein, carbohydrate, fat intake and total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android to gynoid ratio (A/G), subcutaneous adipose tissue mass (SAT), visceral adipose tissue mass (VAT). Subgroup analyses, stratified by menopausal status, were also conducted. Additionally, we employed smoothing curve fitting techniques to investigate potential non-linear relationships between fat mass distribution and nutrient intake. RESULTS: Compared with pre-menopausal women, post-menopausal women had higher body fat, BMI, and metabolic indicators but lower nutrient intake (All p<0.05). In the overall analysis, we found significant correlations between nutrient intake and fat mass. Specifically, protein intake was negatively correlated with TPF (ß = -0.017, 95% CI: -0.030, -0.005), APF (ß = -0.028, 95% CI: -0.044, -0.012), GPF (ß = -0.019, 95% CI: -0.030, -0.008), while fat intake showed positive correlations with these measures (SAT: ß = 2.769, 95% CI: 0.860, 4.678). Carbohydrate intake exhibited mixed associations. Notably, body fat mass-nutrient intake correlations differed by menopausal status. Generally speaking, protein intake showed negative correlations with body fat distribution in pre-menopausal women but positive correlations in post-menopausal women. Carbohydrate intake revealed significant negative associations with abdominal and visceral fat in post-menopausal women, while fat intake was consistently positive across all fat distribution indices, especially impacting visceral fat in post-menopausal women. CONCLUSION: Dietary intake plays a crucial role in body fat distribution, with menopausal status significantly influencing the impact of nutrients on specific fat distribution metrics. The study emphasizes the need for dietary guidelines to consider the nutritional needs and health challenges unique to women at different life stages, particularly concerning menopausal status, to effectively manage obesity.

Endothelial cell-derived extracellular vesicles modulate the therapeutic efficacy of mesenchymal stem cells through IDH2/TET pathway in ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms. METHODS: EVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms. RESULTS: Compared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs. CONCLUSIONS: This study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic.

High prevalence of gastrointestinal disorders in a large cohort of patients with joint hypermobility.

The gastrointestinal (GI) manifestations in children with hypermobile Ehlers-Danlos syndrome/joint hypermobility syndrome (hEDS/JHS) are not well described. We investigated the prevalence of GI disorders in children and young adults with hEDS/JHS through a single-center retrospective review. Demographic data, clinical history, symptoms, and diagnostic studies were reviewed. Of 435 patients with hEDS/JHS, 66% were females (age 5-28 years). We noted a high prevalence of constipation (61%), dysphagia (32%), dyspepsia and/or gastroparesis (25%), eosinophilic esophagitis (EoE) (21%), and celiac disease (4%) in our cohort. Upper endoscopy and gastric emptying scans had the highest yield to detect abnormalities. Motility studies were abnormal in 31% of the 80 patients who underwent them. Dysphagia symptoms are significantly associated with EoE. Thirty-three percent of dysphagia patients had EoE, versus 16% of non-dysphagia patients (p < 0.001). Screening hEDS/JHS patients for GI issues should be routine, with further investigations and referrals guided by identified symptoms.

Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy and Oxidative Stress In vitro and In vivo.

OBJECTIVE: Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. RESULTS: After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. CONCLUSION: ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.

Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome.

Background: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood. Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration. Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46±4.40 vs 11.65±6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand-receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS. Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.

Efficacy and safety of Piwei Peiyuan Prescription in the treatment of chronic atrophic gastritis: A multicenter, double-blind, double-simulated, randomized, controlled clinical trial.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.

Root-mediated acidification, phosphatase activity and the phosphorus-cycling microbial community enhance phosphorus mobilization in the rhizosphere of wetland plants.

Rhizoremediation of wetland plants is an environmentally friendly strategy for sediment phosphorous (P) removal, the basic underlying principle of which is the complex interactions between roots and microorganisms. This study investigated the immobilization and mobilization mechanisms of P in the rhizosphere of wetland plants using high-resolution spatial visualization techniques and metagenomic sequencing. Two-dimensional visualization of the spatial distribution of P, iron (Fe) and manganese (Mn) indicated that the sequestration of Fe-oxides rather than Mn-oxides caused the depletion of labile P, resulting in an increase in the Fe-adsorbed P fraction. Plants altered the rhizospheric environments and P-cycling microbial community to mobilize low-availability P from sediments. Mineral P solubilization and organic P mineralization were enhanced by local acidification and increased phosphatase activity, respectively. Microbial P mobilization also increased with increasing relative abundances of P solubilization and mineralization genes (gcd and phnW) and decreasing P transportation genes (ugpA, ugpB, and pit) genes in the rhizosphere. These processes led to the remobilization of 10.04 % of inorganic P, and 15.23 % of organic P, in the rhizosphere during the incubation period. However, the resupply of P via the above processes did not compensate for the depletion of rhizospheric P via root uptake and mineral sequestration. Our results provide novel insights into the mechanisms of rhizospheric P cycling, which will help to inform future phytoremediation strategies.

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation.

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.

Glycyrrhizin and the Related Preparations: An Inspiring Resource for the Treatment of Liver Diseases.

Liver diseases and their related complications endanger the health of millions of people worldwide. The prevention and treatment of liver diseases are still serious challenges both in China and globally. With the improvement of living standards, the prevalence of metabolic liver diseases, including non-alcoholic fatty liver disease and alcoholic liver disease, has increased at an alarming rate, resulting in more cases of end-stage liver disease. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently needed. Glycyrrhizin (GL), a triterpene glycoside from the roots of licorice plants, possesses a wide range of pharmacological and biological activities. Currently, GL preparations (GLPs) have certain advantages in the treatment of liver diseases, with good clinical effects and fewer adverse reactions, and have shown broad application prospects through multitargeting therapeutic mechanisms, including antisteatotic, anti-oxidative stress, anti-inflammatory, immunoregulatory, antifibrotic, anticancer, and drug interaction activities. This review summarizes the currently known biological activities of GLPs and their medical applications in the treatment of liver diseases, and highlights the potential of these preparations as promising therapeutic options and their alluring prospects for the treatment of liver diseases.