Geniposide ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-ß/Smad and p38MAPK signaling pathways.

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by inflammation and fibrotic changes, with an unknown cause. In the early stages of PF, severe inflammation leads to the destruction of lung tissue, followed by upregulation of fibrotic factors like Transforming growth factor-ß (TGF-ß) and connective tissue growth factor (CTGF), which disrupt normal tissue repair. Geniposide, a natural iridoid glycoside primarily derived from the fruits of Gardenia jasminoides Ellis, possesses various pharmacological activities, including liver protection, choleretic effects, and anti-inflammatory properties. In this study, we investigated the effects of Geniposide on chronic inflammation and fibrosis induced by bleomycin (BLM) in mice with pulmonary fibrosis (PF). PF was induced by intratracheal instillation of bleomycin, and Geniposide(100/50/25mg•kg-1) was orally administered to the mice once a day until euthanasia(14 day/28 day). The Raw264.7 cell inflammation induced by LPS was used to evaluate the effect of Geniposide on the activation of macrophage. Our results demonstrated that Geniposide reduced lung coefficients, decreased the content of Hydroxyproline, and improved pathological changes in lung tissue. It also reduced the number of inflammatory cells and levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) of bleomycin-induced PF mice. At the molecular level, Geniposide significantly down-regulated the expression of TGF-ß1, Smad2/3, p38, and CTGF in lung tissues of PF mice induced by bleomycin. Molecular docking results revealed that Geniposide exhibited good binding activity with TGF-ß1, Smad2, Smad3, and p38. In vitro study showed Geniposide directly inhibited the activation of macrophage induced by LPS. In conclusion, our findings suggest that Geniposide can ameliorate bleomycin-induced pulmonary fibrosis in mice by inhibiting the TGF-ß/Smad and p38MAPK signaling pathways.

Wolbachia modify host cell metabolite profiles in response to short-term temperature stress.

Wolbachia are common heritable endosymbionts that influence many aspects of ecology and evolution in various insects, yet Wolbachia-mediated intracellular metabolic responses to temperature stress have been largely overlooked. Here, we introduced the Wolbachia strain wLhui from the invasive Liriomyza huidobrensis (Blanchard) into a Drosophila Schneider 2 cell line (S2) and investigated the metabolite profile of wLhui-infected (S2_wLhui) and uninfected cell lines (S2_wu) under short-term exposure to either high (37°C), moderate (27°C), or low (7 and 17°C) temperatures. We find that Wolbachia infection, temperature stress, and their interactions significantly affect cellular metabolic profiles. Most significantly, when comparing the changes in metabolites between S2_wLhui and S2_wu, glycerophospholipids, amino acids, and fatty acids associated with metabolic pathways, microbial metabolism in diverse environments, and other pathways were significantly accumulated at either low or high temperatures. Our findings suggest Wolbachia-induced cellular physiological responses to short-term temperature stress, which may in turn affect the fitness and adaptive ability of its host as an invasive species.

Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial.

Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Ultrasound Diagnosis of Bilateral Primary Breast Burkitt Lymphoma in a 28-Year-Old Lactating Patient: A Case Report.

Primary breast Burkitt lymphoma (PB-BL) is an exceedingly rare form of primary breast lymphoma. Ultrasonography is the preferred modality for diagnosing breast diseases; however, the ultrasonic features of Burkitt lymphoma have rarely been reported. Herein, we report a case of ultrasonically diagnosed bilateral PB-BL in a lactating patient and present a literature review. A 28-year-old female patient experienced bilateral breast engorgement starting more than a month after childbirth. At three months postpartum, the patient experienced extreme bilateral breast engorgement, with the skin appearing dark purple and jaundiced. Based on the imaging diagnosis, pathological, immunohistochemical, and molecular biological findings, she was diagnosed with Burkitt lymphoma involves bilateral breasts, right adrenal glands, uterus, and multiple bones. After 4 cycles of combination chemotherapy, the tumor basically disappeared, and then after autologous stem cell transplantation and one cycle of combination chemotherapy, the patient is generally in good condition and is under follow-up. We found that the ultrasonic characteristics of PB-BL are different from those of common breast cancer or lactation mastitis. PB-BL lesions are often multiple, large masses, and even involve the whole breast. The characteristic reticular structures are common in lesions, and irregular hyperechoic masses can be seen around it. The mass has abundant peripheral and internal blood flow signals, but internal calcification and attenuated posterior echoes of masses are rarely observed. Thus, the ultrasonic features of breast Burkitt lymphoma are somewhat specific and understanding these features is conducive to its early identification.

Exposure assessment to areca alkaloids in the Chinese populations through areca nut chewing.

Chewing areca nuts is popular in China. Areca alkaloids are the major toxic compounds in areca nuts. In this study, the levels of four areca alkaloids (i.e. arecoline, arecaidine, guvacoline and guvacine) in 119 areca nut samples were analyzed and 3030 areca nut consumption questionnaires were collected to investigate the exposure to areca alkaloids in the Chinese populations through areca nut chewing. The levels of arecoline, arecaidine, guvacoline and guvacine in different areca nut products were 0.46-4.97 mg/g, 0.57-7.51 mg/g, 0.08-1.44 mg/g and 0.03-8.48 mg/g, respectively. Chewing fresh areca fruits was the main source of arecoline and the total areca alkaloids exposure. The estimated daily intake (EDI) of arecoline and the total areca alkaloids for the Chinese populations were 1.126 and 2.625 mg/kg BW/day for average exposure, 4.411 and 9.739 mg/kg BW/day for high exposure (P95th). The EDI varied with age and gender. The young male population (≤ 34 years) had the highest EDI than other populations. Concentrated and focused efforts are required to educate the general public, especially the young male population, about the risks of areca nut chewing to reduce exposure to areca alkaloids of the Chinese population. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05966-6.

A nomogram model for early recurrence of HBV-related hepatocellular carcinomas after radical hepatectomy.

Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.

TCTN1 Induces Fatty Acid Oxidation to Promote Melanoma Metastasis.

Metabolic reprogramming promotes and sustains multiple steps of melanoma metastasis. Identification of key regulators of metabolic reprogramming could lead to the development of treatments for preventing and treating metastatic melanoma. Here, we identified that the tectonic family member TCTN1 promotes melanoma metastasis by increasing fatty acid oxidation (FAO). In clinical melanoma samples, high expression of TCTN1 correlated with increased metastasis and shorter patient survival. Functionally, TCTN1 promoted melanoma invasion and migration in vitro and distant metastasis in vivo, and TCTN1 induced a mesenchymal-like phenotype switch. Mechanistically, TCTN1 acted as a protein scaffold to promote the binding of HADHA and HADHB, subunits of the mitochondrial trifunctional protein complex, thus leading to FAO activation. TCTN1-mediated FAO activated the p38/MAPK signaling pathway in melanoma cells, promoting tumor EMT and stemness. Molecular docking indicated that the prostaglandin F receptor agonist fluprostenol can block HADHA/HADHB binding, which was confirmed experimentally. Treatment with fluprostenol was able to inhibit TCTN1-induced melanoma invasion and metastasis. Taken together, these findings elucidate the mechanism of TCTN1-mediated promotion of melanoma metastasis and support the potential application of fluprostenol for targeted therapy of metastatic melanoma.

PDCD4 promotes inflammation/fibrosis by activating the PPAR­Î³/NF­κB pathway in mouse atrial myocytes.

Fibrosis is the basis of structural remodeling in atrial fibrillation (AF), during which inflammation is crucial. Programmed cell death factor 4 (PDCD4) is a newly identified inflammatory gene, with unknown mechanisms of action in AF. The present study aimed to elucidate the effects of PDCD4 on the inflammation and structural remodeling of atrial myocytes. For this purpose, a PDCD4 overexpression plasmid (oePDCD4) and PDCD4 small interfering (si)RNA (siPDCD4) were used to modulate PDCD4 expression in mouse atrial myocytes (HL­1 cells). The expression of PDCD4 was detected using reverse transcription­quantitative PCR and western blot analysis. The optimal drug concentrations of peroxisome proliferator­activated receptor γ (PPARγ) agonist (pioglitazone hydrochloride), NF­κB inhibitor (CBL0137), PPARγ inhibitor (GW9962) and NF­κB agonist (betulinic acid) were screened using a Cell Counting Kit­8 assay. The levels of inflammatory factors were detected using enzyme­linked immunosorbent assays, the expression levels of fibrosis­related proteins and NF­κB subunits were detected using western blot analysis, and the expression of phosphorylated (p­)p65/p65 was detected using immunofluorescence staining. The results revealed that PDCD4 overexpression increased the levels of fibrotic factors (collagen I, collagen III, fibronectin, α­smooth muscle actin and matrix metalloproteinase 2), pro­inflammatory cytokines (IFN­Î³, IL­6, IL­17A and TNF­α) and p­p65, whereas it reduced the levels of anti­inflammatory cytokines (IL­4) in HL­1 cells. Additionally, treatment with the PPARγ agonist and NF­κB inhibitor reversed the levels of fibrotic­, pro­inflammatory and anti­inflammatory factors in oePDCD4­HL­1 cells. By contrast, PDCD4 silencing exerted the opposite effects on fibrotic factors, pro­inflammatory cytokines, anti­inflammatory cytokines and p­p65. In addition, treatment with the PPARγ inhibitor and NF­κB agonist reversed the levels of fibrotic­, pro­inflammatory and anti­inflammatory factors in siPDCD4­HL­1 cells. In conclusion, the present study demonstrated that PDCD4 may induce inflammation and fibrosis by activating the PPARγ/NF­κB signaling pathway, thereby promoting the structural remodeling of atrial myocytes in AF.

Evidence summary on the rehabilitative management of dysphagia during radiotherapy for head and neck cancer patients.

Objective: To retrieve, extract, integrate and evaluate evidence on the rehabilitation of dysphagia in patients undergoing radiotherapy for head and neck cancer (HNC), and to provide a basis for the development of a rehabilitation management protocol for dysphagia in patients undergoing radiotherapy for HNC. Methods: An evidence-based systematic search of the literature related to the rehabilitation of dysphagia in patients with HNC during radiotherapy was conducted from January 2013 to March 2023, and the corresponding evaluation tools were selected according to the different types of literature for quality evaluation. "The Joanna Briggs Institute (JBI) evidence pre-grading system was used to evaluate the quality of the evidence. Results: A total of 17 articles were included, including 3 guidelines, 5 expert articles, 1 clinical decision, 1 practice recommendation, 2 evidence summaries and 5 systematic evaluations. A final total of 28 pieces of evidence were summarised, including 6 areas of swallowing disorder screening and assessment, physiotherapy, preventive swallowing function training, feeding management, pain control, and oral care. Conclusion: This study forms a multidisciplinary collaborative evidence summary for the rehabilitation management of dysphagia in patients undergoing radiotherapy for HNC, but the application of some of the evidence needs to be carried out in the context of the clinical setting and patient-specific circumstances for the rehabilitation evidence selected for patients' dysphagia to improve their swallowing function and their swallowing-related quality of life and reduce the occurrence of related complications.

Pulmonary fibrosis: pathogenesis and therapeutic strategies.

Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by extensive alterations of cellular fate and function and excessive accumulation of extracellular matrix, leading to lung tissue scarring and impaired respiratory function. Although our understanding of its pathogenesis has increased, effective treatments remain scarce, and fibrotic progression is a major cause of mortality. Recent research has identified various etiological factors, including genetic predispositions, environmental exposures, and lifestyle factors, which contribute to the onset and progression of PF. Nonetheless, the precise mechanisms by which these factors interact to drive fibrosis are not yet fully elucidated. This review thoroughly examines the diverse etiological factors, cellular and molecular mechanisms, and key signaling pathways involved in PF, such as TGF-ß, WNT/ß-catenin, and PI3K/Akt/mTOR. It also discusses current therapeutic strategies, including antifibrotic agents like pirfenidone and nintedanib, and explores emerging treatments targeting fibrosis and cellular senescence. Emphasizing the need for omni-target approaches to overcome the limitations of current therapies, this review integrates recent findings to enhance our understanding of PF and contribute to the development of more effective prevention and management strategies, ultimately improving patient outcomes.

Observation of Spin Splitting in Room-Temperature Metallic Antiferromagnet CrSb.

Recently, unconventional antiferromagnets that enable the spin splitting (SS) of electronic states have been theoretically proposed and experimentally realized, where the magnetic sublattices containing moments pointing at different directions are connected by a novel set of symmetries. Such SS is substantial, k-dependent, and independent of the spin-orbit coupling (SOC) strength, making these magnets promising materials for antiferromagnetic spintronics. Here, combined with angle-resolved photoemission spectroscopy (ARPES) and density functional theory (DFT) calculations, a systematic study on CrSb, a metallic spin-split antiferromagnet candidate with Néel temperature TN = 703 K, is conducted. The data reveal the electronic structure of CrSb along both out-of-plane and in-plane momentum directions, rendering an anisotropic k-dependent SS that agrees well with the calculational results. The magnitude of such SS reaches up to at least 0.8 eV at non-high-symmetry momentum points, which is significantly higher than the largest known SOC-induced SS. This compound expands the choice of materials in the field of antiferromagnetic spintronics and is likely to stimulate subsequent investigations of high-efficiency spintronic devices that are functional at room temperature.

Research status of polycystic ovary syndrome treatment: a mini review and a bibliometric analysis from 2010 to 2023.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in premenopausal women, often linked to abdominal obesity, insulin resistance, and metabolic issues. With its heterogeneous nature, PCOS treatment should be tailored to individual symptoms and patient preferences. This study examines collaboration networks among countries, institutions, authors, references, and journals related to PCOS treatment. METHODS: Web of Science data was analyzed using VOSviewer and CiteSpace for bibliometric visualization. Chinese and Western medicine treatments for PCOS were reviewed, emphasizing symptom-targeted solutions. RESULTS: Data from 4682 records authored by 400 individuals from 515 institutes in 62 countries revealed China as the leading contributor. Notable authors include Monash University and Richard S. Legro. Common research themes include adipocytes, inflammation, insulin sensitivity, oxidative stress, and the gut microbiome. Tailoring treatment to individual needs is essential, focusing on hyperandrogenism, ovulation, and insulin resistance, with lifestyle counseling to address obesity. CONCLUSION: This bibliometric analysis provides valuable insights into the research status of PCOS treatment. China has made significant contributions, and complementary and alternative therapies, such as traditional Chinese medicine and acupuncture, have also shown beneficial effects recently. The research on inflammation, oxidative stress, and the gut microbiome may provide new targets and strategies for the treatment of PCOS. The recognition of the metabolic problems in PCOS patients facilitates the formulation of more personalized treatment plans to improve the prognosis of patients.

Effectiveness of acceptance commitment therapy for head and neck cancer patients with body image distress in China: a study protocol for randomised controlled trial.

INTRODUCTION: The head and neck comprise vital organs and are apparent human body parts. Tumours here impair physical and sensory functions as well as appearance and social interactions, leading to body image distress (BID) and threatening mental health and quality of life. Acceptance and commitment therapy has shown effectiveness in improving BID in groups such as breast cancer patients. This study aims to apply this therapy to intervene in head and neck cancer (HNC) patients, aiming to improve BID and promote better psychological well-being. METHODS AND ANALYSIS: This study is a prospective, parallel-group, randomised controlled trial. A total of 64 HNC patients will be allocated to either an intervention group or a control group. The intervention group will engage in a 3 week, six-session group-based acceptance and commitment therapy programme, while the control group will receive standard treatment. The primary outcome is cancer-related BID, and secondary outcomes are HNC-related BID, psychological flexibility, coping style and psychological distress. These indicators will be measured at baseline, postintervention and 1 month following the intervention's completion. ETHICS AND DISSEMINATION: The trial has received approval from the Institutional Review Board of Shanghai Proton and Heavy Ion Hospital (2308-67-02). The study results will be shared through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077863.

Relationship between the atherogenic index of plasma and the prevalence of kidney stones: insights from a population-based cross-sectional study.

OBJECTIVE: To investigate the association between atherogenic index of plasma (AIP) and kidney stones (KS) occurrence and recurrence. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. Non-pregnant adults who provided complete information on AIP and KS were included in the analyses. AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). KS was ascertained with questionnaires. Weighted multivariable logistic regression model and restricted cubic spline (RCS) were applied to examine the associations between AIP and KS occurrence and recurrence. RESULTS: A total of 6488 subjects (weighted mean age 43.19 years and 49.26% male) with a weighted mean AIP of 0.66 were included in this study. The multivariable-adjusted OR for nephrolithiasis occurrence across consecutive tertiles was 1.00 (reference), 1.21 (95% CI: 0.90-1.62), and 1.85 (95% CI: 1.39-2.48), respectively. Moreover, each SD increment of AIP was associated with a 50% (OR:1.50, 95% CI: 1.25-1.81) higher risk of nephrolithiasis recurrence. RCSs showed significant and linear dose-response relationships between AIP and nephrolithiasis occurrence (p-overall = 0.006, p-nonlinear = 0.689) and recurrence (p-overall = 0.001, p-nonlinear = 0.848). The positive associations between AIP and nephrolithiasis occurrence and recurrence persisted in sensitivity analyses, suggesting the robustness of the results. CONCLUSION: In the current US nationally representative cross-sectional study, AIP was positively associated with KS occurrence and recurrence.

Electrosynthesis of adipic acid with high faradaic efficiency within a wide potential window.

Electrosynthesis of adipic acid (a precursor for nylon-66) from KA oil (a mixture of cyclohexanone and cyclohexanol) represents a sustainable strategy to replace conventional method that requires harsh conditions. However, its industrial possibility is greatly restricted by the low current density and competitive oxygen evolution reaction. Herein, we modify nickel layered double hydroxide with vanadium to promote current density and maintain high faradaic efficiency (>80%) within a wide potential window (1.5 ~ 1.9 V vs. reversible hydrogen electrode). Experimental and theoretical studies reveal two key roles of V modification, including accelerating catalyst reconstruction and strengthening cyclohexanone adsorption. As a proof-of-the-concept, we construct a membrane electrode assembly, producing adipic acid with high faradaic efficiency (82%) and productivity (1536 µmol cm-2 h-1) at industrially relevant current density (300 mA cm-2), while achieving >50 hours stability. This work demonstrates an efficient catalyst for adipic acid electrosynthesis with high productivity that shows industrial potential.

Psychological status of medical security teams in Winter Olympic Games and Paralympics under COVID-19.

Background: Medical security work for the 2022 Beijing Winter Olympic and Paralympics faced enormous challenges under COVID-19. This study aimed to investigate the mental status of those medical team members to provide a reference for scientifically implementing medical security services for large-scale events. Methods: In this prospective cohort study, the Patient Health Questionnaire-9, Self-rating Anxiety Scale, General Self-Efficacy Scale, and Psychological Questionnaire for Emergent Events of Public Health (PQEEPH) were administered to 145 members of the medical team. A generalized mixed linear model was used to analyze the impact of work duration, position, on/off rotation, and gender on psychological status. Results: Work duration significantly impacted depression, anxiety, self-efficacy, and all dimensions of PQEEPH. Women scored higher than men in the PQEEPH dimensions of depression, neurasthenia, fear, and total score. Working status affected the dimensions of depression, neurasthenia, and total score. Deterioration in emotional state became apparent in the fourth week and recovered 1 week after the task concluded, while self-efficacy decreased from beginning to end. Conclusion: All the medical team members experienced emotional deterioration and decreased self-efficacy in medical security tasks. To maintain a medical team's psychological wellbeing during large-scale activities, rotation times should be set reasonably, and adequate mental health services should be provided.

Association analyses between urinary concentrations of multiple trace elements and gastric precancerous lesions and gastric cancer in Anhui province, eastern China.

Background: Limited epidemiological evidence suggests that exposure to trace elements adversely impacts the development of gastric precancerous lesions (GPL) and gastric cancer (GC). This study aimed to estimate the association of individual urinary exposure to multiple elements with GPL and GC. Methods: A case-control investigation was conducted in Anhui Province from March 2021 to December 2022. A total of 528 subjects (randomly sampled from 1,020 patients with GPL, 200 patients with GC, and 762 normal controls) were included in our study. Urinary levels of iron (Fe), copper (Cu), zinc (Zn), nickel (Ni), strontium (Sr), and Cesium (Cs) were measured using inductively coupled plasma mass spectrometry (ICP-MS). Four different statistical approaches were employed to explore the risk of GPL and GC with mixed exposure, including multivariate logistic regression, weighted quantile regression (WQS), quantile g-computation (Qgcomp), and the Bayesian kernel machine regression (BKMR) model. Results: The WQS model indicated that urinary exposure to a mixture of elements is positively correlated with both GPL and GC, with ORs for the mixture exposure of 1.34 (95% CI: 1.34-1.61) for GPL and 1.38 (95% CI: 1.27-1.50) for GC. The Qgcomp and BKMR models also demonstrated a statistically significant positive correlation between the mixture and both GPL and GC. Conclusion: Considering the limitations of case-control studies, future prospective studies are warranted to elucidate the combined effects and mechanisms of trace elements exposure on human health.

Distribution characteristics, sources and risk assessment of heavy metals in the surface sediments from the largest tributary of the Lancang River in the Tibet Plateau, China.

Angqu, positioned in the eastern expanse of the Tibet Plateau, claims the title of the largest tributary to the Lancang River. In October and December of 2018, in the sediment of Angqu, a comprehensive investigation was conducted on nine heavy metals-arsenic (As), manganese (Mn), chromium (Cr), cadmium (Cd), lead (Pb), mercury (Hg), copper (Cu), zinc (Zn), and nickel (Ni). This investigation aimed to scrutinize the spatial and temporal distribution patterns of these metals, assess the pollution status and ecological risks associated with the sediments, and delve into the sources contributing to their presence. The research results indicate that the average concentrations of As, Hg, and Cd in Angqu sediments exceed the soil background values of Tibet, while the concentrations of other heavy metals are below the soil background values of Tibet. Notably, arsenic poses potential ecological risks. In Angqu sediments, the concentrations of Mn, Cu, Ni, and Pb are generally higher in the wet season, but the seasonal variations of heavy metals in Angqu sediments are not significant. The sediments in the Angqu Basin are predominantly affected by mercury Hg, Cd, and As, with varying degrees of pollution at different sampling points. In the main stream of Angqu (City section), Hg pollution has reached above a moderate level, whereas As pollution near the tributary is only slightly polluted. The analysis of heavy metal sources reveals that there are five primary contributors to heavy metals in surface sediments of Angqu: parent material, agricultural activities, groundwater, atmospheric deposition, and other unidentified sources. Mn, Cr, Pb, and Ni are mainly derived from soil parent material, accounting for more than 50%. About 60.82% of As comes primarily from groundwater. Zn and Cd are mainly sourced from agricultural activities, accounting for 41.25% and 34.33%, respectively. Additionally, 20.6% of Hg originates from atmospheric deposition.

Uncovering the mechanisms of diosmin in treating obesity-related kidney injury based on network pharmacology, molecular docking, and in vitro validation.

Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3ß, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney.

Generational Specific Recruitment of Arsenic- and Antimony-Reducing Microorganisms in Plant Root-Associated Niches for Adapting to Metalloid-Metal Pollution.

The recruitment of microorganisms by plants can enhance their adaptability to environmental stressors, but how root-associated niches recruit specific microorganisms for adapting to metalloid-metal contamination is not well-understood. This study investigated the generational recruitment of microorganisms in different root niches of Vetiveria zizanioides (V. zizanioides) under arsenic (As) and antimony (Sb) stress. The V. zizanioides was cultivated in As- and Sb-cocontaminated mine soils (MS) and artificial pollution soils (PS) over two generations in controlled conditions. The root-associated microbial communities were analyzed through 16S rRNA, arsC, and aioA gene amplicon and metagenomics sequencing. V. zizanioides accumulated higher As(III) and Sb(III) in its endosphere in MS in the second generation, while its physiological indices in MS were better than those observed in PS. SourceTracker analysis revealed that V. zizanioides in MS recruited As(V)- and Sb(V)-reducing microorganisms (e.g., Sphingomonales and Rhodospirillaceae) into the rhizoplane and endosphere. Metagenomics analysis further confirmed that these recruited microorganisms carrying genes encoding arsenate reductases with diverse carbohydrate degradation abilities were enriched in the rhizoplane and endosphere, suggesting their potential to reduce As(V) and Sb(V) and to decompose root exudates (e.g., xylan and starch). These findings reveal that V. zizanioides selectively recruits As- and Sb-reducing microorganisms to mitigate As-Sb cocontamination during the generational growth, providing insights into novel strategies for enhancing phytoremediation of metalloid-metal contaminants.