Integration of Nontarget Screening and QSPR Models to Identify Novel Organophosphate Esters of High Priority in Aquatic Environment.

With the development of large numbers of novel organophosphate esters (OPEs) alternatives, it is imperative to screen and identify those with high priority. In this study, surface water, biofilms, and freshwater snails were collected from the flow-in rivers of Taihu Lake Basin, China. Screened by target, suspect, and nontarget analysis, 11 traditional and 14 novel OPEs were identified, of which 5 OPEs were first discovered in Taihu Lake Basin. The OPE concentrations in surface water ranged from 196 to 2568 ng/L, with the primary homologue tris(2,4-ditert-butylphenyl) phosphate (TDtBPP) being newly identified, which was likely derived from the transformation of tris(2,4-ditert-butylphenyl) phosphite. The majority of the newly identified OPEs displayed substantially higher bioaccumulation and biomagnification potentials in the biofilm-snail food chain than the traditional ones. Quantitative structure-property relationship models revealed both hydrophobicity and polarity influenced the bioaccumulation and biomagnification of the OPEs, while electrostatic attraction also had a contribution to the bioaccumulation in the biofilm. TDtBPP was determined as the utmost priority by toxicological priority index scheme, which integrated concentration, bioaccumulation, biomagnification, acute toxicity, and endocrine disrupting potential of the identified OPEs. These findings provide novel insights into the behaviors of OPEs and scientific bases for better management of high-risk pollutants in aquatic ecosystem.

Masks As a New Hotspot for Antibiotic Resistance Gene Spread: Reveal the Contribution of Atmospheric Pollutants and Potential Risks.

The consumption of disposable surgical masks (DSMs) considerably increased during the coronavirus pandemic in 2019. Herein, we explored the spread of antibiotic resistance genes (ARGs) and the potential risks of antibiotic resistant bacteria (ARB) on DSMs. At environmentally relevant concentrations, the conjugate transfer frequency (CTF) of ARGs increased by 1.34-2.37 folds by 20 µg/m3 of atmospheric water-soluble inorganic ions (WSIIs), and it increased by 2.62-2.86 folds by 80 ng/m3 of polycyclic aromatic hydrocarbons (PAHs). Total suspended particulates (TSP) further promoted the CTF in combination with WSIIs or PAHs. Under WSII and PAH exposure, gene expression levels related to oxidative stress, cell membrane, and the adenosine triphosphate (ATP) were upregulated. WSIIs predominantly induced cellular contact, while PAHs triggered ATP formation and membrane damage. Molecular dynamics simulations showed that WSIIs and PAHs reduced membrane lipid fluidity and increased membrane permeability through interactions with the phosphatidylcholine bilayer. DSM filtering performance decreased, and the CTF of ARGs increased with the wearing time. The gut simulator test showed that ARB disrupted the human gut microbial community and increased total ARG abundance but did not change the ARG abundance carried by ARB themselves. A mathematical model showed that long-term WSII and PAH exposure accelerated ARG dissemination in DSMs.

Phytochemistry, pharmacology, toxicology and detoxification of Polygonum multiflorum Thunb.: a comprehensive review.

Background: Polygonum multiflorum Thunb. (PM), a kind of perennial plant, belongs to the genus Polygonum of the family polygonaceae.The dry root of PM (also called Heshouwu), is a traditional Chinese medicine, which has a series of functions and is widely used in clinic for hair lossing, aging, and insomnia. While, PM also has some toxicity, its clinical drug safety has been concerned. In this paper, the chemical components, toxic mechanisms and detoxification strategies of PM were reviewed in order to provide evidence for its clinical application. Materials and methods: We conducted a systematic review of published literature of PM, including English and Chinese databases, such as PubMed, Web of Science, CNKI, and Wanfang. Results: PM contains a variety of chemical compounds, including stilbenes, quinones, flavonoids, phospholipids, and has many pharmacological activities such as anti-aging, wound healing, antioxidant, and anti-inflammatory properties. The PE has certain therapeutic effect, and it has certain toxicity like hepatotoxicity, nephrotoxicity, and embryotoxicity at the same time, but.these toxic effects could be effectively reduced by processing and compatibility. Conclusion: It is necessary to further explore the pharmacological and toxicological mechanisms of the main active compounds of PE.This article provides scientific basis for the safe clinical application of PM.

Complexation with Metal Ions Affects Chlorination Reactivity of Dissolved Organic Matter: Structural Reactomics of Emerging Disinfection Byproducts.

Metal ions are liable to form metal-dissolved organic matter [dissolved organic matter (DOM)] complexes, changing the chemistry and chlorine reactivity of DOM. Herein, the impacts of iron and zinc ions (Fe3+ and Zn2+) on the formation of unknown chlorinated disinfection byproducts (Cl-DBPs) were investigated in a chlorination system. Fe3+ preferentially complexed with hydroxyl and carboxyl functional groups, while Zn2+ favored the amine functional groups in DOM. As a consequence, electron-rich reaction centers were created by the C-O-metal bonding bridge, which facilitated the electrophilic attack of α-C in metal-DOM complexes. Size-reactivity continuum networks were constructed in the chlorination system, revealing that highly aromatic small molecules were generated during the oxidation and decarbonization of metal-DOM complexes. Molecular transformation related to C-R (R represents complex sites) loss was promoted via metal complexation, including decarboxylation and deamination. Consequently, complexation with Fe3+ and Zn2+ promoted hydroxylation by the C-O-metal bonding bridge, thereby increasing the abundances of unknown polychlorinated Cl-DBPs by 9.6 and 14.2%, respectively. The study provides new insights into the regulation of DOM chemistry and chlorine reactivity by metal ions in chlorination systems, emphasizing that metals increase the potential health risks of drinking water and more scientific control standards for metals are needed.

Novel insights into the relationship between the functional groups and photoactivity of biochar-derived dissolved organic matter.

Due to the production of a large amount of biochar, highly photoactive biochar-derived dissolved organic matter (BDOM) from different sources is released into surface water. This study investigated the molecular composition of BDOM (sludge, bamboo and stalk BDOM) using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and used tetracycline (TC) as model pollutant to investigate the relationship between molecular composition and BDOM photoactivity, specifically focusing on reactive oxygen species (ROS) production. The results indicate that the fluorescence signal intensity of humic acid-like and aromatic proteins in the plant-derived BDOM are significantly higher than that derived from sewage sludge. FT-ICR MS results also showed that plant-derived BDOM contained more CHO molecular formula. Photodegradation experiments of TC mediated by various BDOM analogues demonstrated the photoactivity is highly correlated with the components and functional groups. The electrochemical experiments and density functional theory (DFT) calculations further verified that the aromatic moiety, sulfydryl group and amino group of BDOM affected the electronic supply and energy transfer. Higher electron and energy transfer favor the reaction of BDOM with the ground state oxygen to generate ROS, thus promoting photodegradation of TC. This study provides a new basis for better assessing the ecological risks of BDOM.

Insights into the Enhanced Bioavailability of Per- and Polyfluoroalkyl Substances in Food Caused by Chronic Inflammatory Bowel Disease.

Understanding the bioavailability of per- and polyfluoroalkyl substances (PFAS) in food is essential for accurate human health risk assessment. Given the rising incidence of inflammatory bowel disease (IBD), this study aimed to investigate the impacts of IBD on the bioavailability of PFAS in food using mice models. The relative bioavailability (RBA) of PFAS was the highest in the chronic IBD mice (64.3-144%), followed by the healthy (60.8-133%) and acute IBD mice (41.5-121%), suggesting that chronic IBD enhanced the PFAS exposure risk. In vitro tests showed that the intestinal micelle stability increased as a result of reduced content of short-chain fatty acids, thus promoting the PFAS bioaccessibility in the digestive fluid of chronic IBD. Additionally, increased pathogenic and decreased beneficial bacteria in the gut of IBD groups facilitated the intestinal permeability, thus enhancing PFAS absorption. These together explained the higher RBA of PFAS in the chronic IBD. However, remarkably lower enzymatic activities suggested severely impaired digestive ability in the acute IBD, which facilitated the excretion of PFAS from feces, thus lowering the RBA. Conversely, PFAS exposure might exacerbate IBD by changing the gut microbiota structures. This study hints that individuals with chronic intestinal inflammation might have higher PFAS exposure risk than the healthy population.

A review on the advancement in photocatalytic degradation of poly/perfluoroalkyl substances in water: Insights into the mechanisms and structure-function relationship.

Poly/perfluoroalkyl substances (PFAS) are persistent organic pollutants and ubiquitous in aquatic environment, which are hazardous to organisms and human health. Several countries and regions have taken actions to regulate or limit the production and emission of some PFAS. Even though a series of water treatment technologies have been developed for removal of PFAS to eliminate their potential adverse effects, the removal and degradation performance are usually unsatisfactory. Photocatalytic degradation of PFAS is considered as one of the most effective approaches due to the mild operation conditions and environmental friendliness. This review systematically summarized the recent advances in photocatalytic degradation of PFAS based on heterogeneous photocatalysts, including TiO2-, Ga2O3-, In2O3-, ZnO-, Bi-based, and others. Overall, two mainly degradation mechanisms were involved, including photo-oxidation (involving the holes and oxidative radicals) and photo-reduction types (by e- and reductive radicals). The band structures of the photocatalysts, degradation pathways, structure-function relationship, and impacting factors were further discussed to elucidate the essential reasons for the enhanced degradation of PFAS. Furthermore, the review identified the major knowledge gaps to solve the issues of photocatalysis in real application. This paper also propounded several strategies to promote the design and optimization of high-efficient photocatalysts, and meet the challenges to remove PFAS through photodegradation technologies.

Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study.

Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.

EDTA enables to alleviate impacts of metal ions on conjugative transfer of antibiotic resistance genes.

Various heavy metals are reported to be able to accelerate horizontal transfer of antibiotic resistance genes (ARGs). In real water environmental settings, ubiquitous complexing agents would affect the environmental behaviors of heavy metal ions due to the formation of metal-organic complexes. However, little is known whether the presence of complexing agents would change horizontal gene transfer due to heavy metal exposure. This study aimed to fill this gap by investigating the impacts of a typical complexing agent ethylenediaminetetraacetic acid (EDTA) on the conjugative transfer of plasmid-mediated ARGs induced by a range of heavy metal ions. At the environmentally relevant concentration (0.64 mg L-1) of metal ions, all the tested metal ions (Mg2+, Ca2+, Co2+, Pb2+, Ni2+, Cu2+, and Fe3+) promoted conjugative transfer of ARGs, while an inhibitory effect was observed at a relatively higher concentration (3.20 mg L-1). In contrast, EDTA (0.64 mg L-1) alleviated the effects of metal ions on ARGs conjugation transfer, evidenced by 11 %-66 % reduction in the conjugate transfer frequency. Molecular docking and dynamics simulations disclosed that this is attributed to the stronger binding of metal ions with the lipids in cell membranes. Under metal-EDTA exposure, gene expressions related to oxidative stress response, cell membrane permeability, intercellular contact, energy driving force, mobilization, and channels of plasmid transfer were suppressed compared with the metal ions exposure. This study offers insights into the alleviation mechanisms of complexing agents on ARGs transfer induced by free metal ions.

Unlocking high-efficiency decontamination by building a novel heterogeneous catalytic reduction system of thiourea dioxide/biochar.

Herein, we reported a new contaminant purification paradigm, which enabled highly efficient reductive denitration and dechlorination using a green, stable reducing agent thiourea dioxide (TDO) coupled with biochar (BC) over a wide pH range under anoxic conditions. Specifically, BC acted as both activators and electron shuttles for TDO decomposition to achieve complete anoxic degradation of p-nitrophenol (PNP), p-nitroaniline, 4-chlorophenol and 2,4-dichlorophenol within 2 h. During this process, multiple strongly reducing species (i.e., SO22-, SO2•- and e-/H•) were generated in BC/TDO systems, accounting for 13.3%, 9.7% and 75.5% of PNP removal, respectively. While electron transfer between TDO and H+ or contaminants mediated by BC led to H• generation and contaminant reduction. These processes depended on the electron-accepting capacity and electron-conducting domains of biochar. Significantly, the BC/TDO systems were highly efficient at a pH of 2.0-8.0, especially under acidic conditions, which performed robustly in common natural water constituents.

Transformation of 6:6 PFPiA in the gut of Xenopus laevis: Synergistic effects of CYP450 enzymes and gut microflora.

As a frequently detected per- and polyfluoroalkyl substance in the environment, 6:6 perfluoroalkylhypophosphinic acid (6:6 PFPiA) is vulnerable to transformation in the liver of organisms, but the transformation in gut is still unclear. This study investigates the molecular mechanisms of 6:6 PFPiA transformation in the gut of Xenopus laevis upon a 28-day exposure in water. Before Day 16, a notable correlation (p = 0.03) was observed between the transformation product (PFHxPA) and cytochrome P450 (CYP450) enzyme concentration in gut. This suggests that CYP450 enzymes played an important role in the transformation of 6:6 PFPiA in the gut, which was verified by an in vitro incubation with gut tissues, and supported by the molecular docking results of 6:6 PFPiA binding with CYP450 enzymes. From the day 16, the CYP450 concentration in gut decreased by 31.3 % due to the damage caused by 6:6 PFPiA, leading to a decrease in the transformation capacity in gut, but the transformation rate was stronger than in liver. This was in contrast with the in vitro experiment, where transformation was stronger in liver. In the mean time, the abundance of Bacteroidota in gut increased, which released hydrolytic enzyme and then could participate in the transformation as well. This study reveals the potential of the gut in metabolizing environmental pollutants, and provides profound insights into the potential health risks caused by 6:6 PFPiA in organisms.

Serum untargeted lipidomic characterization in a general Chinese cohort with residual per-/polyfluoroalkyl substances by liquid chromatography-drift tube ion mobility-mass spectrometry.

Per- and polyfluoroalkyl substances (PFAS) remain controversial due to their high persistency and potential human toxicity. Although occupational exposure to PFAS has been widely investigated, the implications of PFAS occurrence in the general population remain to be unraveled. Considering that serum from most people contains PFAS, the aim of this study was to characterize the lipidomic profile in human serum from a general cohort (n = 40) with residual PFAS levels. The geometric means of ∑PFAS (11.8 and 4.4 ng/mL) showed significant differences (p < 0.05) for the samples with the highest (n = 20) and lowest (n = 20) concentrations from the general population respectively. Reverse-phase liquid chromatography coupled to drift tube ion mobility and high-resolution mass spectrometry using dual polarity ionization was used to characterize the lipid profile in both groups. The structural elucidation involved the integration of various parameters, such as retention time, mass-to-charge ratio, tandem mass spectra and collision cross section values. This approach yielded a total of 20 potential biomarkers linked to the perturbed glycerophospholipid metabolism, energy metabolism and sphingolipid metabolism. Among these alterations, most lipids were down-regulated and some specific lipids (PC 36:5, PC 37:4 and PI O-34:2) exhibited a relatively strong Spearman correlation and predictive capacity for PFAS contamination. This study could support further toxicological assessments and mechanistic investigations into the effects of PFAS exposure on the lipidome.

Care-seeking delay of patients with heart failure in China: a mixed-method study.

AIM: This study aims to explore the duration and influencing factors of care-seeking delay among patients with heart failure (HF) in China. METHODS AND RESULTS: A convergent mixed method containing a cross-sectional study and two parts of qualitative studies was designed, following the STROBE and COREQ guidelines. Convenience sampling was applied to recruit patients with HF from two general hospitals from December 2021 to December 2022. Purposive sampling was used to enrol healthcare professionals from two general hospitals and two community hospitals from June to November 2022. Among the 258 patients with HF in the cross-sectional study, the median duration of care-seeking delay was 7.5 days. The result integration indicated that the delay duration was influenced by the dyspnoea symptom burden, the oedema symptom burden, and the depression status. The lower dyspnoea symptom burden, the higher oedema symptom burden, and the higher depression score were related to the prolonged care-seeking delay duration. The duration was also affected by the COVID-19 pandemic, level of support from medical system, and the symptom management abilities of the caregivers. The COVID-19 pandemic, low level of support from medical system, and limited symptom management abilities of caregivers were related to the prolonged care-seeking delay duration. CONCLUSIONS: Care-seeking delay among patients with HF needs attention in China. The duration of care-seeking delay of patients with HF was influenced by the dyspnoea symptom burden, the oedema symptom burden, and depression status, as well as the COVID-19 pandemic, level of support from medical system, and the symptom management abilities of the caregivers.

Role of diet in the risks of esophageal adenocarcinoma and squamous cell carcinoma: an updated umbrella review.

PURPOSE: This updated umbrella review aimed to evaluate the evidence regarding the associations between dietary factors and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant studies. The quality of the included meta-analyses was evaluated using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). For each association, the number of cases, random effects pooled effect size, 95% confidence intervals (CIs), heterogeneity, 95% prediction interval (PrI), small-study effect, and excess significance bias were recalculated to determine the evidence level. RESULTS: We identified 33 meta-analyses describing 58 dietary factors associated with ESCC and 29 meta-analyses describing 38 dietary factors associated with EAC. There was convincing evidence regarding the association of 2 dietary factors (areca nut and high alcohol) with the risk of ESCC. There was highly suggestive evidence regarding the association of only 1 dietary factor (healthy pattern) with the risk of ESCC. There was suggestive evidence regarding the association of 11 dietary factors with the risk of ESCC, including fruit, citrus fruit, vegetables, pickled vegetables, maté tea, moderate alcohol, hot beverages and foods, hot tea, salt, folate, and vitamin B6. There was convincing evidence regarding the association of one dietary factor (vitamin B6) with the risk of EAC. There was suggestive evidence regarding the association of 4 dietary factors with the risk of EAC, including processed meat, dietary fibre, carbohydrate, and vitamin B12. The convincing evidence regarding the associations between dietary factors and the risks of ESCC and EAC remained robust in sensitivity analyses. CONCLUSIONS: This umbrella review highlighted convincing evidence regarding the associations of areca nut and high alcohol with a higher risk of ESCC. Additionally, an association between vitamin B6 and a decreased risk of EAC was observed. Further research is needed to examine the dietary factors with weak evidence regarding their associations with ESCC and EAC.

Penetration pathways, influencing factors and predictive models for dermal absorption of exobiotic molecules: A critical review.

This review provides a comprehensive summary of the skin penetration pathways of xenobiotics, including metals, organic pollutants, and nanoparticles (NPs), with a particular focus on the methodologies employed to elucidate these penetration routes. The impacts of the physicochemical properties of exogenous substances and the properties of solvent carriers on the penetration efficiencies were discussed. Furthermore, the review outlines the steady-state and transient models for predicting the skin permeability of xenobiotics, emphasizing the models which enable realistic visualization of pharmaco-kinetic phenomena via detailed geometric representations of the skin microstructure, such as stratum corneum (SC) (bricks and mortar) and skin appendages (hair follicles and sebaceous gland units). Limitations of published research, gaps in current knowledge, and recommendations for future research are highlighted, providing insight for a better understanding of the skin penetration behavior of xenobiotics and associated health risks in practical application contexts.

Unveiling behaviors of 8:2 fluorotelomer sulfonic acid (8:2 FTSA) in Arabidopsis thaliana: Bioaccumulation, biotransformation and molecular mechanisms of phytotoxicity.

8:2 fluorotelomer sulfonic acid (8:2 FTSA) has been commonly detected in the environment, but its behaviors in plants are not sufficiently known. Here, the regular and multi-omics analyses were used to comprehensively investigate the bioaccumulation, biotransformation, and toxicity of 8:2 FTSA in Arabidopsis thaliana. Our results demonstrated that 8:2 FTSA was taken up by A. thaliana roots and translocated to leaves, stems, flowers, and seeds. 8:2 FTSA could be successfully biotransformed to several intermediates and stable perfluorocarboxylic acids (PFCAs) catalyzed by plant enzymes. The plant revealed significant growth inhibition and oxidative damage under 8:2 FTSA exposure. Metabolomics analysis showed that 8:2 FTSA affected the porphyrin and secondary metabolisms, resulting in the promotion of plant photosynthesis and antioxidant capacity. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were related to transformation and transport processes. Integrative transcriptomic and metabolomic analysis revealed that DEGs and differentially expressed metabolites (DEMs) in plants were predominantly enriched in the carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways, resulting in greater energy consumption, generation of more nonenzymatic antioxidants, alteration of the cellular membrane composition, and inhibition of plant development. This study provides the first insights into the molecular mechanisms of 8:2 FTSA stress response in plants.

Body mass index modifies the effect of urinary protein-to-creatinine ratio on chronic kidney disease progression.

BACKGROUND: This study aimed to determine the association between the urinary protein-to-creatinine ratio (UPCR) and chronic kidney disease (CKD) progression in a cohort study, and to determine whether body mass index (BMI) modifies this association. METHODS: The study population consisted of 856 hypertensive patients with CKD stages 2-5, enrolled between 2010 and 2011 in Japan. Generalized linear models with a logit link were used to evaluate the independent and combined effects of the UPCR and BMI on CKD progression RESULTS: During a median follow-up of 25 months, 242 patients developed CKD progression during follow-up. A notably higher risk of CKD progression was found in participants in tertiles 2 [odds ratio (OR): 5.46, 95% confidence interval (95% CI): 2.49-11.99] and 3 (OR 27.74, 95% CI 12.34-62.38) comparing with tertiles 1 for UPCR levels. Moreover, an interaction was found between UPCR and BMI on CKD progression (P for interaction = 0.006). Participants in both the highest tertile of UPCR and overweight (UPCR ≥ 248.9 mg/mmol and BMI ≥ 25 kg/m2) had a 45.59-times higher risk of CKD progression compared with those in the lowest tertile of UPCR and nonoverweight (UPCR < 36.2 mg/mmol and BMI < 25 kg/m2) CONCLUSIONS: The present study demonstrates that the combination of elevated UPCR and BMI may contribute to an increased risk of CKD progression.

Arsenite adsorption and oxidation affected by soil humin: The significant role of persistent free radicals and reactive oxygen species.

Humin (HM), as the main component of soil organic matter, carries various reactive groups and plays a crucial regulatory role in the transformation of arsenic (As). However, current research on the redox pathway of As and its interactions with HM is relatively limited. This study aimed to explore the impact of different HM samples on the redox characteristics of As. The results showed that HM can not only adsorb arsenite [As(III)] but also oxidize As(III) into arsenate [As(V)]. However, once As(III) is adsorbed on the HM, it cannot undergo further oxidation. HMNM (extracted from peat soil) exhibited the highest adsorption capacity of As(III), with a maximum amount of 1.95 mg/kg. The functional groups of HM involved in As complexation were primarily phenolic hydroxyl and carboxyl groups. The adsorption capacity of HM samples for As(III) was consistent with their carboxyl group contents. The oxygen-containing functional groups and environmentally persistent free radicals (EPFRs) on HM can directly oxidize As(Ⅲ) through electron transfer, or indirectly induce the production of reactive oxygen species (ROS), such as hydroxyl radicals, to further oxidize As(Ⅲ). This study provides new insight into the transport and transformation process of As mediated by soil HM, and establishes a theoretical basis for As remediation.

Macrophages regulate healing-associated fibroblasts in diabetic wound.

BACKGROUND: Recovery from a foot ulcer is compromised in a diabetic status, due to the impaired tissue microenvironment that consists of altered inflammation, angiogenesis and fibrosis. Phenotypic alterations in both macrophages and fibroblasts have been detected in the diabetic wound. Recently, a fibroblast subpopulation that expresses high matrix metalloproteinase 1 (MMP1), MMP3, MMP11 and Chitinase-3-Like Protein 1 (CHI3L1) was associated with a successful diabetic wound healing. However, it is not known whether these healing-associated fibroblasts are regulated by macrophages. METHODS AND RESULTS: We used bioinformatic tools to analyze selected public databases on normal and diabetic skin from patients, and identified genes significantly altered in diabetes. In a mouse model for diabetic wound healing, we detected not only a loss of the spatiotemporal changes in interleukin 1ß (IL1ß), IL6, IL10 and vascular endothelial growth factor A (VEGF-A) in wound macrophages, but also a compromised expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in healing-associated wound fibroblasts in a diabetic status. Co-culture with diabetic macrophages significantly reduced the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from non-diabetic wound. Co-culture with non-diabetic macrophages or diabetic macrophages supplied with IL6 significantly increased the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from diabetic wound. Moreover, macrophage-specific expression of IL6 significantly improved wound healing and angiogenesis in diabetic mice. CONCLUSIONS: Macrophages may induce the activation of wound-healing-associated fibroblasts, while the defective macrophages in diabetes may be corrected with IL6 treatment as a promising therapy for diabetic foot disease.