Distribution, mobilization, risk assessment and source identification of heavy metals and nutrients in surface sediments of three urban-rural rivers after long-term water pollution treatment.

Sediments are critical pollution carriers in urban-rural rivers, which can threaten the water quality of the river and downstream lakes for a long time. However, it is still not clear whether conventional water pollution treatments could abate sediment pollution or not. In this study, heavy metals (HMs) and nutrient salts in the surface sediments and overlying water were investigated after decades' water pollution treatment in three urban-rural rivers. HM speciation was determined by the sequential extraction; diffusion fluxes were estimated using Fick's first law; HM ecological risk and nutrient pollution were evaluated; and pollution sources were identified by statistical analysis and GIS. The results showed that the HMs and nutrients were extremely serious in the urban regions. The accumulation level of Pb, Cu and Cd in the sediments of the three rivers were all much higher than the soil background value, and the labile fractions accounted for high proportions (57 % for Pb, 55 % for Cu and 43 % for Cd), which could be easily eluate from the sediments and caused hazards to the aquatic environment. The sediment diffusion fluxes of HMs and ammonia nitrogen were mostly positive, which indicated these sites currently released these pollutants from sediment to overlying water. Cd, Pb, Cu and Cr may mainly originate from industrial discharge and domestic sewage, while Cr was also greatly affected by crustal weathering; nutrient pollution may originate from agricultural activities and domestic sewage. Our study demonstrated that after decades' conventional water treatment in these rivers, the sediment pollution was still in a serious level with high ecological risk, and Cd was the dominant pollutant. At present, the external point source pollution has been effectively controlled, thus, the in-depth understanding of the sediment pollution characteristics after long-term water treatment could provide a scientific basis for the accurate elimination of river pollution.

Biosynthesis and Anticancer Activity of Genistein Glycoside Derivatives.

As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. PubMed/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein's clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.

Environmental exposure to polycyclic aromatic hydrocarbons: An underestimated risk factor for systemic lupus erythematosus onset and progression.

OBJECTIVE: To investigate the link between systemic lupus erythematosus (SLE) incidence and exposure to environmental polycyclic aromatic hydrocarbons (PAH). METHODS: A case-control study (ChiCTR2000038187) involving 316 SLE patients and 851 healthy controls (HCs) was executed. Environmental exposure was assessed via a questionnaire, stratified by gender and age (females <35 and ≥35 years, males). Blood samples collected from 89 HCs, 85 inactive, and 95 active SLE patients were used to measure serum benzo[a]pyrene diol epoxide -albumin (BPDE-Alb) adducts and PAH concentrations, indicating long-term and short-term exposure respectively. Intergroup comparisons and statistical analyses were conducted using R version 4.3.1. RESULTS: Diverse patterns were found in how environmental factors affect SLE onset across different demographics. Lifestyle exposure factors were found to be a stronger determinant of SLE onset than occupational exposure factors in women under 35. Indoor air pollution had a significant impact on SLE incidence, potentially comparable to outdoor air pollution. Lifestyle-related PAH exposure had a greater impact on SLE than occupational PAH exposure. PAH exposure levels progressively increase from HCs to inactive and active SLE patients. Active SLE patients show markedly higher BPDE-Alb levels than HCs. CONCLUSIONS: Environmental PAH, particularly lifestyle-related, are significant, yet under-recognized, risk factors for SLE. STATEMENT OF ENVIRONMENTAL IMPLICATION: We examined the relationship between exposure to environmental polycyclic aromatic hydrocarbons (PAH) and the incidence of systemic lupus erythematosus (SLE). PAH, prevalent in sources such as cigarette smoke, air pollution, and charred food, pose significant health hazards. This study is the first to investigate specific PAH exposure levels in SLE patients. We determined actual PAH exposure levels in both SLE patients and healthy individuals and indicated that long-term PAH exposure biomarker is more reliable for evaluating exposure in non-occupationally exposed groups like SLE, compared to short-term markers. These findings provide valuable insights for future research on similar non-occupationally exposed populations.

Effects and mechanisms of polycyclic aromatic hydrocarbons in inflammatory skin diseases.

Polycyclic aromatic hydrocarbons (PAHs) are hydrocarbons characterized by the presence of multiple benzene rings. They are ubiquitously found in the natural environment, especially in environmental pollutants, including atmospheric particulate matter, cigarette smoke, barbecue smoke, among others. PAHs can influence human health through several mechanisms, including the aryl hydrocarbon receptor (AhR) pathway, oxidative stress pathway, and epigenetic pathway. In recent years, the impact of PAHs on inflammatory skin diseases has garnered significant attention, yet many of their underlying mechanisms remain poorly understood. We conducted a comprehensive review of articles focusing on the link between PAHs and several inflammatory skin diseases, including psoriasis, atopic dermatitis, lupus erythematosus, and acne. This review summarizes the effects and mechanisms of PAHs in these diseases and discusses the prospects and potential therapeutic implications of PAHs for inflammatory skin diseases.

Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain.

Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including jaundice and liver disease. Bilirubin is conjugated in hepatocytes and excreted to bile duct via the ATP-binding cassette transporter ABCC2, dysfunction of which would lead to Dubin-Johnson syndrome. Here we determine the structures of ABCC2 in the apo, substrate-bound and ATP/ADP-bound forms using the cryo-electron microscopy, exhibiting a full transporter with a regulatory (R) domain inserted between the two half modules. Combined with substrate-stimulated ATPase and transport activity assays, structural analysis enables us to figure out transport cycle of ABCC2 with the R domain adopting various conformations. At the rest state, the R domain binding to the translocation cavity functions as an affinity filter that allows the substrates of high affinity to be transported in priority. Upon substrate binding, the R domain is expelled from the cavity and docks to the lateral of transmembrane domain following ATP hydrolysis. Our findings provide structural insights into a transport mechanism of ABC transporters finely tuned by the R domain.

Study on the improvement of complexation efficiency and anti-digestibility of phenolic acids based on electrospun starch fibers.

Phenolic acids can be encapsulated by starch electrospun fibers, and the structural and functional properties of the electrospun fiber are affected by the chemical structure of phenolic acid. In this study, five phenolic acids (protocatechuic acid (PA), p-hydroxybenzoic acid (PHBA), p-coumaric acid (PCA), ferulic acid (FA), and caffeic acid (CA)) were chosen to prepare electrospun fibers with high amylose corn starch (HACS) at different voltages. Morphology and complexation efficiency results revealed that the electrospun fibers prepared at 21.0 kV were smooth and continuous with high encapsulation efficiency (EE) and loading efficiency (LE). The chemical structure of phenolic acid played an important role in the structure and properties of electrospun fibers by influencing the complexation of HACS with phenolic acids and the inhibitory effect of amylase. As a result, electrospun fibers containing HACS-CA inclusion complex had higher relative crystallinity (25.47 %), higher thermal degradation temperatures (356.17 °C), and the strongest resistance to digestion (starch digestive ratio = 22.98 %). It is evident that electrospun fibers containing HACS-phenolic acid inclusion complexes not only achieve high phenolic acid complexation efficiency, but also resist the effects of the gastric and small intestinal environment on phenolic acids, thereby improving the bioaccessibility of phenolic acids.

Propionate alleviates itch in murine models of atopic dermatitis by modulating sensory TRP channels of dorsal root ganglion.

BACKGROUND: Itch is the most common symptom of atopic dermatitis (AD) and significantly decreases the quality of life. Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism. METHODS: Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology/immunofluorescent analysis. Primary-cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in vitro calcium imaging/in vivo miniature two-photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism. RESULTS: Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro, attenuated the hyper-excitability in sensory neurons in MC903-induced AD model, and inhibited capsaicin-evoked hTRPV1 currents (IC50 = 20.08 ± 1.11 µM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene-related peptide by nerves in MC903-induced AD mouse model, which further attenuated itch and skin inflammation. CONCLUSION: Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD.

Advances in ß-Diketocyclisation of Curcumin Derivatives and their Antitumor Activity.

Curcumin, derived from the popular spice turmeric, is a pharmacologically active polyphenol. Curcumin's therapeutic activity has been extensively studied in recent decades, with reports implicating curcumin in many biological activities, particularly, its significant anticancer activity. However, its potential as an oral administration product is hampered by poor bioavailability, which is associated with a variety of factors, including low water solubility, poor intestinal permeability, instability, and degradation at alkaline pH. To improve its bioavailability, modifying ß-diketone curcumin with heterocycles, such as pyrazole, isoxazole and triazole is a powerful strategy. Derivatives are synthesized while maintaining the basic skeleton of curcumin. The ß-diketone cyclized curcumin derivatives are regulators of multiple molecular targets, which play vital roles in a variety of cellular pathways. In some literatures, structurally modified curcumin derivatives have been compared with curcumin, and the former has enhanced biological activity, improved water solubility and stability. Therefore, the scope of this review is to report the most recently synthesized heterocyclic derivatives and to classify them according to their chemical structures. Several of the most important and effective compounds are reviewed by introducing different active groups into the ß-diketone position to achieve better therapeutic efficacy and bioavailability.

Screening of heat stress-related biomarkers in chicken serum through label-free quantitative proteomics.

Heat stress (HS) can result in sudden death and is one of the most stressful and costly events in chicken. Currently, biomarkers used clinically to detect heat stress state in chickens are not optimal, especially for living ones. Analysis of changes in serum proteins of heat-stressed chickens can help to identify some novel convenient biomarkers for this. Twenty-four chickens were exposed to HS at 42°C ± 1°C with a relative humidity of 65% for continuous 5 h in a single day, and 10 birds were used as controls (Con). During HS, 15 dead chickens were categorized as heat stress death group (HSD), and 9 surviving ones served as heat stress survivor group (HSS). Label-free quantitative proteomics (LFQP) was used to analyze differentially expressed proteins (DEPs) in serum of tested animals. Candidate proteins associated with HS were validated by enzyme-linked immunosorbent assay (ELISA). Diagnostic value of candidate biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Source of the selected proteins was analyzed in liver tissues with immunohistochemistry and in cell culture supernatant of primary chicken hepatocytes (PCH) using ELISA. In this study, compared to Con, LFQP identified 123 and 53 significantly different serum proteins in HSD and HSS, respectively. Bioinformatics analysis showed that XDH, POSTN, and HSP90 were potential HS biomarkers in tested chickens, which was similar with results from serum ELISAs and immunohistochemistry in liver tissues. The ROC values of 0.793, 0.752, and 0.779 for XDH, POSTN, and HSP90, respectively, permitted the distinction of heat-stressed chickens from the control. Levels of 3 proteins above in the cell culture supernatant of PCH showed an increasing trend as HS time increased. Therefore, considering that mean concentration of POSTN in serum was higher than that of HSP90, XDH, and POSTN may be optimal biomarkers in serum for detecting HS level in chickens, and mainly secreted from hepatocytes. The former indicates that heat-stressed chickens are in a damaged state, and the latter implies that chickens can repair heat stress damage.

Experimental investigation on the aero-optical effects of supersonic gas films with various cooling fluids.

Despite the fact that a supersonic cooling gas film can efficiently insulate aerodynamic heating, its interaction with the mainstream generates a sophisticated flow structure which may cause significant aero-optical ramifications. This study aims to analyze the fluid structure and wavefront distortion of supersonic gas film when subjected to varying nozzle pressure ratios (NPR) by employing two distinct cooling refrigerants, namely C O 2 and air. Within the NPR range of 0 to 2, a linear relationship exists between the wavefront distortion of both C O 2 and air films, while the C O 2 film exhibits higher wavefront distortion than the air. Additionally, the influence of condensation on the discrepancies in aero-optical effects of the two refrigerants is discussed.

Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine.

Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.

Ph3P/ICH2CH2I-promoted reductive deoxygenation of alcohols.

Owing to the ubiquity of the hydroxyl group, reductive deoxygenation of alcohols has become an active research area. The classic Barton-McCombie reaction suffers from a tedious two-step procedure. New efficient methods have been developed, but they have some limitations, such as a narrow substrate scope and the use of moisture-sensitive Lewis acids. In this work, we describe the Ph3P/ICH2CH2I-promoted reductive deoxygenation of alcohols with NaBH4. The process is applicable to benzyl, allyl and propargyl alcohols, and also to primary and secondary alcohols, demonstrating a wide substrate scope and a good level of functional group tolerance. This protocol features convenient operation and low cost of all reagents.

Upconversion luminescence nanosensor for detection of Fe3+ and phosphate ion based on the inner-filter effect.

In this work, an upconversion luminescence (UCL) nanosensor for fast detection of ferric ion (Fe3+) and phosphate ion (Pi) is developed based on the inner-filter effect (IFE) between NaYF4:Yb/Er upconversion nanoparticles (UCNPs) and Fe3+-hypocrellin B (HB) complex. Fe3+-HB complex has strong absorption band (450-650 nm), which overlaps with the green emission peak of UCNPs at 545 nm. By adding Fe3+ and Pi, the UCNPs-HB system produces the red-shift change of absorption spectrum, which leads to the "on-off-on" process of IFE. So, with the specific recognition ability of HB for Fe3+ and the competitive complexation of Pi for Fe3+, the proposed nanosensor utilizes the UCL change to achieve the detection of the targets. For the detections of Fe3+, the linear range is 10-600 µM with a limit of detection (LOD) of 2.62 µM, and for Pi, the linear range is 5-100 µM with a LOD of 1.25 µM. The results for selectivity, precision, and recovery test are also satisfactory. Furthermore, the real sample detection shows that the proposed nanaosensor has a great potential in environmental and biological systems. An upconversion luminescence (UCL) nanosensor based on the inner-filter effect (IFE) between upconversion nanoparticles (UCNPs) and Fe3+-hypocrellin B (HB) complex for the detection of Fe3+ and phosphate ion has been proposed, which is promising to be a convenient and sensitive assay for monitoring Fe3+ and phosphate ion in different environments and biological systems.

Selection of indicators reporting response rate in pharmaceutical trials for systemic lupus erythematosus: preference and relative sensitivity.

OBJECTIVE: SLE is a common multisystem autoimmune disease with chronic inflammation. Many efficacy evaluation indicators of randomised clinical trials (RCTs) for SLE have been proposed but the comparability remains unknown. We aim to explore the preference and comparability of indicators reporting response rate and provide basis for primary outcome selection when evaluating the efficacy of SLE pharmaceutical treatment. METHODS: We systematically searched three databases and three registries to identify pharmacological intervention-controlled SLE RCTs. Relative discriminations between indicators were assessed by the Bayesian hierarchical linear mixed model. RESULTS: 33 RCTs met our inclusion criteria and we compared eight of the most commonly used indicators reporting response rate. SLE Disease Activity Index 4 (SLEDAI-4) and SLE Responder Index 4 were considered the best recommended indicators reporting response rate to discriminate the pharmacological efficacy. Indicator preference was altered by disease severity, classification of drugs and outcome of trials, but SLEDAI-4 had robust efficacy in discriminating ability for most interventions. Of note, BILAG Index-based Combined Lupus Assessment showed efficacy in trials covering all-severity patients, as well as non-biologics RCTs. The British Isles Lupus Assessment Group response and Physician's Global Assessment response were more cautious in evaluating disease changes. Serious adverse event was often applied to evaluate the safety and tolerability of treatments rather than efficacy. CONCLUSIONS: The impressionable efficacy discrimination ability of indicators highlights the importance of flexibility and comprehensiveness when choosing primary outcome(s). As for trials that are only evaluated by SLEDAI-4, attention should be paid to outcome interpretation to avoid the exaggeration of treatment efficacy. Further subgroup analyses are limited by the number of included RCTs. PROSPERO REGISTRATION NUMBER: CRD42022334517.

[Content, Distribution, Source Analysis, and Risk Assessment of PAHs in Arable Soils of Taiyuan].

PAHs (polycyclic aromatic hydrocarbons) accumulated in arable soils have significant impacts on farmland quality and human health, which has attracted wide attention from scientists and the public. A total of 22 arable soil samples were collected from Taiyuan, an old industrial city, including three districts (industrial zones, hilly areas, and sewage irrigation area), and the contents of 21 PAHs were detected using the GC-MS method. The sources of PAHs in soils were analyzed using the diagnostic ratios (DRs) method and positive matrix factorization (PMF) model, and the soil health risks were analyzed using the incremental lifetime cancer risk (ILCR) model. The results indicated that the average concentrations of Σ21PAHs and Σ16PAHs in arable soils of Taiyuan were 934.6 ng·g-1 and 787.7 ng·g-1, respectively, which were lower than the soil pollution risk screening value of agricultural land stipulated in GB 15168-2018. 3-5 rings PAHs were the dominant components, accounting for~90% of the Σ21PAHs. Approximately 60% of sites in industrial zones, 13% in hilly areas, and 33% in the sewage irrigation area had high PAHs contents larger than 1000 ng·g-1. The spatial distribution of PAHs showed that more severe PAHs pollution in the soil occurred in industrial areas than that in the other two districts. The DRs suggested that the combustion of coals, bio-masses, and traffic emissions were the dominant sources for PAHs pollution in arable soils in Taiyuan. The simulation results of the PMF model indicated that the sources and contribution rates of PAHs in cultivated soils were coal and biomass burning sources (59%), traffic sources (22%), and coking sources (19%). The risk assessment confirmed that the arable soils in Taiyuan had high potential carcinogenic risks; thus, more attention should be paid to the PAHs pollutions in arable soils.

Recent progress in the development of ursolic acid derivatives as anti-diabetes and anti-cardiovascular agents.

Ursolic acid (UA) is a pentacyclic triterpenoid, which exhibits many biological activities, particularly in anti-cardiovascular and anti-diabetes. The further application of UA is greatly limited due to its low bioavailability and poor water solubility. Up to date, various UA derivatives have been designed to overcome these shortcomings. In this paper, the authors reviewed the development of UA derivatives as the anti-diabetes anti-cardiovascular reagents.

Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study.

BACKGROUND: Atopic dermatitis (AD) is the leading cause of the global burden from skin disease; no study has provided global and country-specific epidemiological estimates of AD. OBJECTIVES: To quantify global, regional and country-specific estimates of the epidemiology of AD. METHODS: A comprehensive search for epidemiological studies in AD was conducted in four electronic databases (PubMed, Embase, Web of Science and China National Knowledge Infrastructure). A Bayesian hierarchical linear mixed model was constructed to calculate epidemiological estimates of AD considering the heterogeneity of regions, countries, type of diagnoses and age strata. RESULTS: In total, 344 studies met the inclusion criteria. Incidence varied substantially with the location and age of the surveyed participants. The global prevalence of AD and the population affected by AD were estimated to be 2.6% [95% uncertainty interval (UI) 1.9-3.5] and 204.05 million people, respectively. Around 101.27 million adults and 102.78 million children worldwide have AD, corresponding to prevalence rates of 2.0% (95% UI 1.4-2.6) and 4.0% (95% UI 2.8-5.3), respectively. Females were more likely to suffer from AD than males: the global prevalence of AD in females was 2.8% (95% UI 2.0-3.7%) and affected 108.29 million people, while in males the corresponding estimates were 2.4% (95% UI 1.7-3.3%) and 95.76 million people. CONCLUSIONS: Epidemiological AD data are lacking in 41.5% of countries worldwide. The epidemiology of AD varies substantially with age and sex and is distributed unequally across geographical regions.

Differential changes in the gut microbiota between extrinsic and intrinsic atopic dermatitis.

Elevated serum level of total and (or) allergen-specific IgE is one of the key features of atopic dermatitis (AD). Previous studies have shown that the gut microbiome mediates interactions between external exposures and the immune system in AD; however, the relationship between the gut microbiota and IgE remains unclear. In the present study, analyses of environmental exposures for 250 AD patients and 138 healthy volunteers revealed an association between hygiene levels in the residential environment and the occurrence of AD and the IgE level. Metagenomic sequencing of the gut microbiota from 68 AD patients and 77 healthy controls showed that AD patients had a distinct gut microbiota composition; moreover, while L-histidine degradation was enriched in healthy controls, L-histidine biosynthesis was enriched in AD patients. Extrinsic and intrinsic AD showed different enrichment patterns of specific microbes and differential associations of functional pathways. Our study indicated that elevated levels of IgE in AD were related to specific microbes in the gut microbiota, which showed extensive interactions with environmental factors.