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The gut microbiota constitutes a complex ecosystem, comprising trillions of microbes that have co-evolved with their host over hundreds of millions of years. Over the past decade, a growing body of knowledge has underscored the intricate connections among diet, gut microbiota, and human health. Bioactive polysaccharides (BPs) from natural sources like medicinal plants, seaweeds, and fungi have diverse biological functions including antioxidant, immunoregulatory, and metabolic activities. Their effects are closely tied to the gut microbiota, which metabolizes BPs into health-influencing compounds. Understanding how BPs and gut microbiota interact is critical for harnessing their potential health benefits. This review provides an overview of the human gut microbiota, focusing on its role in metabolic diseases like obesity, type II diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular diseases. It explores the basic characteristics of several BPs and their impact on gut microbiota. Given their significance for human health, we summarize the biological functions of these BPs, particularly in terms of immunoregulatory activities, blood sugar, and hypolipidemic effect, thus providing a valuable reference for understanding the potential benefits of natural BPs in treating metabolic diseases. These properties make BPs promising agents for preventing and treating metabolic diseases. The comprehensive understanding of the mechanisms by which BPs exert their effects through gut microbiota opens new avenues for developing targeted therapies to improve metabolic health.

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BACKGROUND: Fournier's Gangrene is a severe surgical infectious disease, and various risk factors can increase its mortality rate. The purpose of this study is to retrospectively analyze the clinical characteristics and laboratory data of Fournier's Gangrene patients, followed by an analysis of mortality-related risk factors. This study has no secondary objectives. METHODS: This study included 46 hospitalized patients diagnosed with Fournier's Gangrene at Suzhou Traditional Chinese Medicine Hospital from December 2013 to March 2024. Clinical data for all patients were extracted from the electronic medical records system. The collected data included gender, age, duration of illness, length of hospital stay, sites of infection involvement, comorbidities, white blood cell count, hematocrit, albumin, blood glucose, creatinine, serum sodium, serum potassium upon admission, microbial culture results, and patient outcomes (survival/death). The Simplified Fournier Gangrene Severe Index (SFGSI) was used to score all patients. Patients were categorized into survival and death groups based on clinical outcomes. Differences between categorical variables were compared using the χ² test or Fisher's exact test. Differences between numerical variables were compared using Student's t-test or the Mann-Whitney U test. Binary logistic regression was employed to analyze the risk factors for mortality in Fournier's Gangrene. RESULTS: Among the 46 Fournier's Gangrene patients, 39 were male (84.8%) and 7 were female (15.2%). The age ranged from 17 to 86 years, with a median age of 61 years. Fourteen cases (30.4%) were confined to the perianal area, 26 cases (56.5%) had fascial necrosis involving the perianal, perineal, and genital regions, while 6 cases (13.0%) extended to the abdominal wall. At a 3-month postoperative follow-up, 43 patients (93.5%) survived, while 3 patients (6.5%) died shortly after admission due to severe illness. Based on the outcome, patients were divided into survival and death groups with 43 and 3 cases, respectively. Significant differences were observed between the two groups in terms of age (P<0.05), extension to the abdominal wall (P<0.01), hematocrit (P<0.01), albumin (P<0.01), SFGSI (P<0.01), and SFGSI>2 (P<0.01). Binary logistic regression analysis indicated that decreased hematocrit was an independent risk factor for mortality in Fournier's Gangrene patients. CONCLUSION: This study provides a detailed analysis of the clinical characteristics and risk factors for mortality in Fournier's Gangrene patients. The primary outcome of this study is that a decreased hematocrit is an independent risk factor for predicting mortality in FG patients. These findings offer valuable prognostic insights for clinicians, underscoring the importance of early identification and correction of reduced hematocrit to improve patient outcomes and survival rates.

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Sonodynamic therapy (SDT) represents a promising, noninvasive, and precise treatment modality for tumors, demonstrating significant potential in clinical applications. However, the efficiency of sonosensitizers in generating reactive oxygen species (ROS) is often limited by rapid electron-hole recombination. In this study, BiF3@BiOI is synthesized via a co-precipitation method, followed by in-situ reduction to decorate it with Pt nanoparticles, resulting in BiF3@BiOI@Pt-PVP (BBP) nanocomposite for enhancing SDT efficacy. The formation of the BiF3@BiOI heterojunction enhances charge separation ability. The decoration of Pt nanoparticles narrows the bandgap and alters the band positions and Fermi level of BBP, which can effectively mitigate the rapid recombination of electron-hole pairs and facilitate a cascade reaction of ROS, thereby improving ROS generation efficiency with ultrasound excitation. Additionally, bismuth ions in BBP and the generated holes consume glutathione, exacerbating cellular oxidative damage, and triggering PANoptosis and ferroptosis. Furthermore, Pt nanoparticles demonstrate peroxidase-like activity, catalyzing endogenous hydrogen peroxide to oxygen. These functions are helpful against tumors for alleviating hypoxic conditions, reshaping the microenvironment, modulating immune cell infiltration capacity, and enhancing the efficacy of immunotherapy. The dual strategy of forming heterojunctions and sensitization with noble metals effectively enhances the efficacy of sono-catalytic therapy-induced immune activation in tumor treatment.

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ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Rubi (FR), a food material with medicinal value, is used in traditional Chinese medicine (TCM) for treatment of various kidney-related problems, such as impotence, spermatorrhea, and frequent urination. It is also frequently used to produce diverse functional foods in China. AIM OF STUDY: The purpose of this research was to assess the therapeutic effects of FR diterpene glycosides on RWPE-1 epithelial cell (RWPE-1), a human normal prostatic epithelial cell, and benign prostate hyperplasia (BPH) rats, both of which had been exposed to dihydrotestosterone (DHT) and testosterone propionate (TP), respectively, and to investigate the mechanism of action. METHODS: Target proteins that could stably bind to certain diterpene glycosides were screened through drug affinity responsive target stability combined with mass spectrometry (DARTS/MS). DHT-induced RWPE-1 cells were used to detect drug activity. TP was subcutaneously injected to induce BPH in rats. The extract of diterpene glycosides from FR (FDS) was orally administered for 28 days. The DHT levels in the serum and prostate tissue of the rats were measured through enzyme-linked immunosorbent assay (ELISA), and to analyze cell proliferation and epithelial-mesenchymal transition (EMT), the protein expression of prostate-specific antigen (PSA), androgen receptor (AR), steroid 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen (PCNA), S100 calcium-binding protein A2 (S100A2), transforming growth factor-ß1 (TGF-ß1), E-cadherin, vimentin, and Smad4 was determined through western blotting (WB), immunohistochemistry (IHC), or immunofluorescence (IF). RESULTS: FDS reduced the proliferation of DHT-induced RWPE-1 cells. It also significantly inhibited rat prostate enlargement; decreased DHT levels in the serum and prostate tissue; inhibited the protein expression of AR, PSA, PCNA, S100A2, TGF-ß1, E-cadherin, and Smad4; and increased the protein expression of E-cadherin. CONCLUSION: The present study is the first to report that diterpene glycosides isolated from FR inhibited BPH at the cellular level, regulated the proliferation of prostate cells through the androgen signaling pathway, and prevented EMT in the prostate through the S100A2-mediated TGF-ß/Smad signaling pathway. These results indicate that FDS is a promising multitarget therapy for BPH.

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BACKGROUD: Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue. METHODS: A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR. RESULTS: Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping. CONCLUSION: These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.

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BACKGROUND: The novel phthalein component QBT, extracted from Ligusticum chuanxiong, shows promising biological activity against cerebrovascular diseases. This study focused on ferroptosis and pyroptosis to explore the effects of QBT on nerve injury, cognitive dysfunction, and related mechanisms in a rat model of vascular dementia (VaD). METHODS: We established a rat model of VaD and administered QBT as a treatment. Cognitive dysfunction in VaD rats was evaluated using novel object recognition and Morris water maze tests. Neuronal damage and loss in the brain tissues of VaD rats were assessed with Nissl staining and immunofluorescence. Furthermore, we investigated the neuroprotective mechanisms of QBT by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/cystine-glutamate antiporter (xCT)/glutathione peroxidase 4 (GPX4) and Nod-like receptor family pyrin domain-containing 3 (NLRP3)/cysteine-requiring aspartate protease-1 (Caspase-1)/Gasdermin D (GSDMD) pathways to inhibit ferroptosis and pyroptosis both in vivo and in vitro. RESULTS: Our findings indicated that QBT significantly ameliorated neuronal damage and cognitive dysfunction in VaD rats. Additionally, QBT reversed abnormal changes associated with ferroptosis and pyroptosis in the brains of VaD rats, concurrently up-regulating the Nrf2/xCT/GPX4 pathway and down-regulating the NLRP3/Caspase-1/GSDMD pathway to inhibit ferroptosis and pyroptosis in neuronal cells, thereby exerting a neuroprotective role. CONCLUSION: In summary, QBT effectively mitigated neuronal damage and cognitive dysfunction in VaD rats, demonstrating a neuroprotective effect by inhibiting ferroptosis and pyroptosis in neuronal cells. This study offers a novel perspective and theoretical foundation for the future development of drugs targeting VaD.

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BACKGROUND: Significant progress has been made in the diagnosis and treatment of pediatric syncope since the publication of the "2018 Chinese Pediatric Cardiology Society (CPCS) guideline for diagnosis and treatment of syncope in children and adolescents" ("2018 Edition Guidelines"). Therefore, we have revised and updated it to assist pediatricians in effectively managing children with syncope. DATA SOURCES: According to the "2018 Edition Guidelines", the expert groups collected clinical evidence, evaluated preliminary recommendations, and then organized open-ended discussions to form the recommendations. This guideline was developed by reviewing the literature and studies in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to April 2024. Search terms included "syncope", "children", "adolescents", "diagnosis", and "treatment." RESULTS: The guidelines were based on the latest global research progress and were evidence-based. The classification of syncope etiology, diagnostic procedures, postural tests, such as the active standing test, head-up tilt test, and active sitting test, clinical diagnosis, and individualized treatment for neurally mediated syncope in pediatric population were included. CONCLUSIONS: The guidelines were updated based on the latest literature. The concepts of sitting tachycardia syndrome and sitting hypertension were introduced and the comorbidities of neurally mediated syncope were emphasized. Some biomarkers used for individualized treatment were underlined. Specific suggestions were put forward for non-pharmacological therapies as well as the follow-up process. The new guidelines will provide comprehensive guidance and reference for the diagnosis and treatment of neurally mediated syncope in children and adolescents.

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Given the limited treatment options and high mortality rates associated with gastric cancer, there is a need to explore novel therapeutic options. The present study aimed to investigate the efficacy of lenvatinib, a multi-target tyrosine kinase inhibitor, in mitigating the progress of gastric cancer in vitro. Comprehensive analyses were conducted to assess the impact of lenvatinib on gastric cancer cells, focusing on the inhibition of viability, suppression of proliferation, induction of apoptosis and reduction of metastatic potential. The effects of lenvatinib on these activities were determined using 5-ethynyl-2'-deoxyuridine staining, colony formation assay, flow cytometry, western blotting, scratch assay and Transwell assay. In addition, bioinformatics analyses were employed to identify key regulatory targets of lenvatinib, with particular attention given to platelet-derived growth factor receptor ß (PDGFRB). In addition, the effects of PDGFRB overexpression on the regulation of lenvatinib were explored. Lenvatinib demonstrated significant inhibitory effects on the viability, proliferation and metastatic capabilities of MKN45 and HGC27 gastric cancer cell lines. Bioinformatics analyses identified PDGFRB as a crucial target of lenvatinib, with its downregulation showing promise in enhancing overall survival rates of patients with gastric cancer. By contrast, PDGFRB overexpression reversed the effects of lenvatinib on cells. The present findings underscore the potential of lenvatinib as a promising therapeutic option in the treatment of gastric cancer. By elucidating its mechanism of action and identifying PDGFRB as a primary target, the present study may aid further clinical advancements.

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Background: The long-term impact of COVID-19 on the mental health and well-being of college students, specifically trends over time after full removal of COVID-19 restrictions, has not been well-studied. Methods: Four consecutive cross-sectional surveys were conducted in December 2022 (N = 689), March 2023 (N = 456), June 2023 (N = 300), and November 2023 (N = 601) at a university in Sichuan Province, China. Results: The proportion of students with COVID-19 panic decreased from 95.1 to 77.3% (p < 0.001). The prevalence of moderate anxiety and above decreased from 18 to 13.6% (p < 0.001), and the prevalence of moderate and above depression decreased from 33.1 to 28.1% (p < 0.001), while the prevalence of post-traumatic stress disorder (PTSD) increased from 21.5 to 29.6% (p < 0.005). Further, the proportion of suicidal thoughts increased from 7.7 to 14.8% (p < 0.001). Suicidal thoughts and self-injuries were significantly associated with COVID-19 panic, depression, anxiety, and PTSD. Students who reported being in close contact with COVID-19 patients in the past were more likely to develop PTSD. Further, COVID-19-induced panic was a risk factor for self-injury. Conclusion: One year after the COVID-19 pandemic, the overall mental health of college students was not optimal. Hence, we can conclude that the long-term impacts of COVID-19 on the mental health of college students may have already occurred. To mitigate this impact and prepare for the next major public health event, strengthening college students' mental health curricula and promoting healthy behaviors among college students should be a priority for universities and education authorities.

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The ample peptide field is the best source for discovering clinically available novel antimicrobial peptides (AMPs) to address emerging drug resistance. However, discovering novel AMPs is complex and expensive, representing a major challenge. Recent advances in artificial intelligence (AI) have significantly improved the efficiency of identifying antimicrobial peptides from large libraries, whereas using random peptides as negative data increases the difficulty of discovering antimicrobial peptides from random peptides using discriminative models. In this study, we constructed three multi-discriminator models using deep learning and successfully screened twelve AMPs from a library of 30,000 random peptides. three candidate peptides (P2, P11, and P12) were screened by antimicrobial experiments, and further experiments showed that they not only possessed excellent antimicrobial activity but also had extremely low hemolytic activity. Mechanistic studies showed that these peptides exerted their bactericidal effects through membrane disruption, thus reducing the possibility of bacterial resistance. Notably, peptide 12 (P12) showed significant efficacy in a mouse model of Staphylococcus aureus wound infection with low toxicity to major organs at the highest tested dose (400 mg/kg). These results suggest deep learning-based multi-discriminator models can identify AMPs from random peptides with potential clinical applications.

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Adverse events of atrial fibrillation (AF) have been commonly reported in lymphoma patients in treating Bruton's tyrosine kinase inhibitors (BTKi). The incidence rate of AF can vary depending on the specific types of BTKi and the patient population. Totally 45 published studies have revealed that the overall incidence rate of AF is 5% (95% CI 4%-7%). By performing a subtype single-rate analysis, the second-generation BTKi shows a lower AF incidence rate and lower cardiovascular toxicity. In the subtype single-rate analysis, we conclude the different AF incidence rates of Ibrutinib (10%, 95% CI 7%-13%), Acalabrutinib (4%, 95% CI 1%-6%), Orelabrutinib (0%, 95% CI 0%-1%), and Zanubrutinib (0%, 95% CI 0%-1%). The comprehensive analysis of AF inspires us to better predict and manage AF and other cardiovascular events in treating lymphoma. Meticulous evaluation, collaboration between cardiologists and hematologists, and discovery of new biomarkers are essential for its management.

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With the growth of the magnitude of multiagent networks, distributed optimization holds considerable significance within complex systems. Convergence, a pivotal goal in this domain, is contingent upon the analysis of infinite products of stochastic matrices (IPSMs). In this work, the convergence properties of inhomogeneous IPSMs are investigated. The convergence rate of inhomogeneous IPSMs toward an absolute probability sequence π is derived. We also show that the convergence rate is nearly exponential, which coincides with existing results on ergodic chains. The methodology employed relies on delineating the interrelations among Sarymsakov matrices, scrambling matrices, and positive-column matrices. Based on the theoretical results on inhomogeneous IPSMs, we propose a decentralized projected subgradient method for time-varying multiagent systems with graph-related stretches in (sub)gradient descent directions. The convergence of the proposed method is established for convex objective functions and extended to nonconvex objectives that satisfy Polyak-Lojasiewicz (PL) conditions. To corroborate the theoretical findings, we conduct numerical simulations, aligning the outcomes with the established theoretical framework.

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AIM: To investigate the incidence and high-risk factors associated with the surgical treatment of acute female pelvic inflammatory disease (PID). METHODS: A retrospective analysis was conducted on all inpatients diagnosed with acute female PID, encompassing conditions such as endometritis, salpingitis, tubo-ovarian abscess, ovarian abscess, and pelvic peritonitis, at Dongyang Hospital of Wenzhou Medical University from January 2013 to December 2021. Patients were categorized into two groups: the surgery group (n = 58) and the non-surgery group (n = 399), based on the necessity of surgical intervention (refer to Materials and Methods for surgical indications). Collected data included patient demographics (age, body mass index (BMI)), comorbidities (hypertension, diabetes mellitus), initial laboratory findings upon admission (white blood cell count, absolute neutrophil count, hemoglobin, platelet count, blood urea nitrogen/creatinine, prothrombin time (PT), international normalized ratio (INR), fibrinogen, albumin), surgical records, and postoperative pathology. Univariate and multivariate logistic regression analyses were conducted to ascertain the risk factors associated with the surgical treatment of acute female PID. RESULTS: Out of 457 hospitalized patients with acute female PID, 58 cases (12.7%) required surgical intervention. Univariate and multivariate logistic regression analyses indicated that advancing age correlated with an increased likelihood of surgical intervention in women with acute PID (odds ratio (OR) = 1.052, 95% Confidence Interval (CI) 1.022-1.082, p = 0.001). Additionally, lower serum albumin levels upon admission were associated with a heightened risk of surgery (OR = 0.913, 95% CI 0.859-0.970, p = 0.003), while elevated fibrinogen levels amplified the risk of surgical intervention in these patients (OR = 1.193, 95% CI 1.008-1.411, p = 0.04). CONCLUSIONS: Elderly women diagnosed with acute PID, especially those presenting with abscess formation, should undergo prompt surgical intervention if they display high-risk factors such as low albumin levels and elevated fibrinogen levels upon admission.

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BACKGROUND & AIMS: Skeletal muscle is an important contributor to joint health. Previous studies have shown that age-related muscle mass and strength loss are closely associated with the development of knee osteoarthritis. The objective of this study is to investigate whether a high plant protein/peptide nutrition supplementation can alleviate knee osteoarthritis by improving muscle mass and strength. METHODS: This randomized, double-blind, placebo-controlled trial that included participants aged 50-70 years diagnosed with knee osteoarthritis and sarcopenia was conducted in China from February 2022 to September 2022 (ChiCTR2200056415). Participants were randomly assigned to receive either a 12-week high plant protein/peptide nutrition supplementation or a placebo twice daily, with one serving each after breakfast and dinner, respectively. The primary outcome analyzed using intention-to-treat analysis was difference in Short Physical Performance Battery (SPPB) from baseline to week 12 between the two groups. The secondary outcomes included changes in muscle mass, strength, symptom and imaging of knee osteoarthritis, body composition, biochemical parameters, and health quality scores. RESULTS: After 12 weeks, a total of 124 participants (38.7% male) completed the trial and were included in the final analysis. Over the 12-week follow-up, the experimental group showed a significant improvement in the SPPB total score (1.03, 95% CI, 0.69 to 1.38, P < 0.0001) compared with the placebo group. Grip strength (2.83 kg, 95% CI, 2.13 to 3.53, P < 0.0001) and skeletal muscle mass index (0.66 kg/m2, 95% CI, 0.45 to 0.86, P < 0.0001) were also significantly increased in the experimental group relative to the placebo group. The mean change in Western Ontario and McMaster Universities Osteoarthritis Index total score was -3.95 points (95% CI, -5.02 to -2.89, P < 0.0001) in the experimental group and 0.23 points (95% CI, -0.17 to 0.63, P = 0.253) in the placebo group. Additionally, within the experimental group, nine participants experienced an improvement in osteophyte magnetic resonance imaging results, while no improvement was observed in the placebo group. The experimental group also exhibited significant improvements in health quality compared with the placebo group as assessed by Short Form 36, the World Health Organization Quality of Life Brief Scale, and the Chalder Fatigue Scale. No serious adverse events were reported during the trial. CONCLUSION: Oral supplementation with high levels of plant protein/peptides can alleviate symptoms of osteoarthritis in elderly individuals with minor or mild knee osteoarthritis and sarcopenia. This improvement may be attributed to the enhancements of muscle mass, strength, and physical performance.

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Nanoplastics (NPs), which belong to emerging environmental pollutants, threaten environmental sustainability and human health. Despite recent studies have reported that NPs damage the gastrointestinal tract and immune homeostasis, the underlying mechanisms remain unclear. Polyphenols have been found to promote NPs excretion by interacting with intestinal flora (IF). However, the potential mechanisms and action targets of this are still poorly understood. To address these knowledge gaps, we investigated the impact of quercetin and three concentrations of polystyrene nanoplastics (PS-NPs) in mice using an integrated phenotypic and multi-omics analysis. Our findings demonstrated that PS-NPs accumulate within the intestine, resulting in impairments to intestinal tissue and barrier function, as well as disturbing the expression of immune-response small intestinal genes and composition of IF. Exposure to PS-NPs significantly elevate the level of intestinal IgG and CD20+ B cells, while inhibiting T cells activation. Furthermore, PS-NPs could induce systemic immune and serum insulin level disorders. Quercetin might mitigate PS-NPs-induced intestinal damage and immune disorders though reversing IF disorders, gene expression changes, and their interaction.

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Nickel and chromium are both common heavy metals that pose serious environmental and health hazards. However, the exact mechanism by which nickel and/or chromium cause renal injury is unclear. Therefore, we explored the molecular mechanisms of renal injury caused by nickel and/or chromium poisoning from the perspective of mitochondrial dynamics and the Nrf2 antioxidant pathway. In this study, eighty 6-week-old C57BL/6J mice were randomly divided into four groups: control (Con, untreated), nickel (Ni, 110 mg/L Ni2+), chromium (Cr, 50 mg/L Cr6+), and combined nickel-chromium (Ni + Cr, 110 mg/L Ni2+, 50 mg/L Cr6+). The results showed that chronic nickel and/or chromium exposure inhibited body weight gain and impaired kidney function and structure in mice. Chronic nickel and/or chromium exposure led to the disruption of mitochondrial dynamics and thus induced oxidative stress. On the other hand, the Nrf2 antioxidant pathway may play an important regulatory role in mitigating oxidative stress-induced oxidative damage in kidney. The present study partially elucidated the molecular mechanism of renal injury induced by nickel and/or chromium exposure in mice and the regulatory role of the Nrf2 pathway in inducing oxidative injury from the perspective of mitochondrial dynamics. This provides a theoretical basis for the development of prevention and control strategies, and environmental protection measures.

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Mild cognitive impairment poses an increasing challenge to middle-aged and elderly populations. Traditional Chinese medicinal herbs like Cistanche tubulosa and Ginkgo biloba (CG) have been proposed as potential agents to improve cognitive and memory functions. A randomized controlled trial involving 100 Chinese middle-aged and elderly participants was conducted to investigate the potential synergistic effects of CG on cognitive function in individuals at risk of neurodegenerative diseases. Over 90 days, both CG group and placebo group received two tablets daily, with each pair of CG tablets containing 72 mg echinacoside and 27 mg flavonol glycosides. Cognitive functions were assessed using multiple scales and blood biomarkers were determined at baseline, Day 45, and Day 90. The CG group exhibited significant improvements in the scores of Mini-Mental State Examination (26.5 at baseline vs. 27.1 at Day 90, p < 0.001), Montreal Cognitive Assessment (23.4 at baseline vs. 25.3 at Day 90, p < 0.001), and World Health Organization Quality of Life (81.6 at baseline vs. 84.2 at Day 90, p < 0.001), all surpassing scores in placebo group. Notably, both the Cognitrax matrix test and the Wechsler Memory Scale-Revised demonstrated enhanced memory functions, including long-term and delayed memory, after CG intervention. Moreover, cognitive-related blood biomarkers, including total tau, pT181, pS199, pT231, pS396, and thyroid-stimulating hormone, significantly decreased, whereas triiodothyronine and free triiodothyronine significantly increased. No treatment-related adverse events were reported, and routine blood and urine tests remained stable. These findings indicated that CG supplementation could potentially serve as an effective supplementary solution for enhancing cognitive and memory functions.

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BACKGROUND: Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation. METHODS: UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein-protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments. RESULTS: A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression. CONCLUSIONS: This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway.

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To create complementary metal oxide semiconductor compatible molecular devices, more insights into the electrode property regarding its metal/semiconductor doping level and creating a functional molecular device are required. In this work, we constructed an EGaIn/alkanethiol/Au-Si molecular diode (with a rectification ratio R of 50.70) induced by Schottky barriers within a gold-silicon doped electrode instead of the functional property of molecules. The relationship between the rectification ratio and the number of methylene units in alkanethiol was analyzed, revealing a gradual increase in the ratio from 3.33 for C6H14S to 50.70 for C16H34S. The rectification ratio of the junction is well modulated by the temperature due to the change in the Schottky barrier. Such a mechanism is explained by the energy band diagrams of the surface space charge region and a combination of density functional theory and Keldysh-Green formalism calculations.