Ginsenoside Rh4 Facilitates the Sensitivity of Renal Cell Carcinoma to Ferroptosis via the NRF2 Pathway.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary system and ferroptosis is considered as a promising therapeutic approach for treating RCC. Ginsenoside Rh4 (Rh4) was proved to have anticancer properties and play roles in ferroptosis. This study aimed to investigate the potential of ginsenoside Rh4 (Rh4) in enhancing the sensitivity of renal cell carcinoma (RCC) cells to ferroptosis and to elucidate the underlying mechanisms. METHODS: RCC cell lines of 786-O and ACHN were treated with RAS-selective lethal 3 (RSL3) and/or Rh4. Cell-viability assays were used to determine how Rh4 affected the sensitivity of RCC cells to RSL3-induced ferroptosis. Quantitative real-time polymerase chain reaction was conducted to examine the levels of ferroptosis-related genes. Additionally, the knockdown of nuclear factor E2-related factor 2 (NRF2) was performed to investigate the role of NRF2 in mediating the effects of Rh4. RESULTS: RSL3 suppressed the progression of RCC cells by inducing ferroptosis. Furthermore, Rh4 led to more RCC sensitivity to ferroptosis induced by RSL3. Rh4 downregulated the ferroptosis-related gene expression including superoxide dismutase 1 (p < 0.01), glutathione peroxidase 4 (p < 0.01), and catalase (p < 0.01), which was attenuated by NRF2 knockdown. This finding suggested that Rh4 exerted its sensitising effect on ferroptosis through the NRF2 pathway. CONCLUSIONS: Rh4 made RCC cells more sensitive to ferroptosis by inhibiting the NRF2 signaling and suppressing the expression of antioxidant enzymes. Therefore, combining Rh4 with ferroptosis-inducing reagents to treat RCC had potential therapeutic application.

Inspecting the "health poverty trap" mechanism: self-reinforcing effect and endogenous force.

INTRODUCTION: The term "health poverty trap" describes a vicious cycle in which developing countries or regions become trapped in low levels of health and poverty during the process of modernization. Although significant progress has been made in alleviating poverty in China, there is still a need to further enhance the living conditions of its impoverished population. METHODS: This research utilizes the data of the three national representative panel surveys from 2014 to 2020. The primary objective is to gain a better understanding of the intricate relationship between health and poverty. To examine the self-reinforcing effects of the cumulative cycle between health and poverty, we employ unconditional quantile regression analysis. RESULT: The low-income group exhibits lower overall health status compared to the average level. Economic constraints partially hinder the ability of low-income individuals to access healthcare resources, thereby reinforcing the cyclical relationship between health and poverty. Additionally, the unique psychological and behavioral preferences of individuals in health poverty act as indirect factors that further strengthen this cycle. Health poverty individuals can generate endogenous force to escape the "health poverty trap" by enhancing their confidence levels and digital literacy. CONCLUSIONS: The research examines the coexistence of health gradients and economic inequality among Chinese residents. Additionally, the study explores the endogenous force mechanism of escaping the health poverty trap from psychological and behavioral perspectives. This research also offers insights into optimizing government poverty alleviation programs to effectively address this issue.

Ginsenoside Rh4 Facilitates the Sensitivity of Renal Cell Carcinoma to Ferroptosis via the NRF2 Pathway

Background: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary system and ferroptosis is considered as a promising therapeutic approach for treating RCC. Ginsenoside Rh4 (Rh4) was proved to have anticancer properties and play roles in ferroptosis. This study aimed to investigate the potential of ginsenoside Rh4 (Rh4) in enhancing the sensitivity of renal cell carcinoma (RCC) cells to ferroptosis and to elucidate the underlying mechanisms. Methods: RCC cell lines of 786-O and ACHN were treated with RAS-selective lethal 3 (RSL3) and/or Rh4. Cell-viability assays were used to determine how Rh4 affected the sensitivity of RCC cells to RSL3-induced ferroptosis. Quantitative real-time polymerase chain reaction was conducted to examine the levels of ferroptosis-related genes. Additionally, the knockdown of nuclear factor E2-related factor 2 (NRF2) was performed to investigate the role of NRF2 in mediating the effects of Rh4. Results: RSL3 suppressed the progression of RCC cells by inducing ferroptosis. Furthermore, Rh4 led to more RCC sensitivity to ferroptosis induced by RSL3. Rh4 downregulated the ferroptosis-related gene expression including superoxide dismutase 1 (p < 0.01), glutathione peroxidase 4 (p < 0.01), and catalase (p < 0.01), which was attenuated by NRF2 knockdown. This finding suggested that Rh4 exerted its sensitising effect on ferroptosis through the NRF2 pathway. Conclusions: Rh4 made RCC cells more sensitive to ferroptosis by inhibiting the NRF2 signaling and suppressing the expression of antioxidant enzymes. Therefore, combining Rh4 with ferroptosis-inducing reagents to treat RCC had potential therapeutic application. (AU)

Spatial variations of DOM in a diverse range of lakes across various frozen ground zones in China: Insights into molecular composition.

Dissolved organic matter (DOM) plays a significant role in aquatic biogeochemical processes and the carbon cycle. As global climate warming continues, it is anticipated that the composition of DOM in lakes will be altered. This could have significant ecological and environmental implications, particularly in frozen ground zones. However, there is limited knowledge regarding the spatial variations and molecular composition of DOM in lakes within various frozen ground zones. In this study, we examined the spatial variations of in-lake DOM both quantitatively, focusing on dissolved organic carbon (DOC), and qualitatively, by evaluating optical properties and conducting molecular characterization using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Lakes in cold regions retained more organic carbon compared to those in warmer regions, the comparison of the mean value of DOC concentration of all sampling sites in the same frozen ground zone showed that the highest mean lake DOC concentration found in the permafrost zone at 21.4 ± 19.3 mg/L. We observed decreasing trends in E2:E3 and MLBL, along with increasing trends in SUVA254 and AImod, along the gradually warming ground. These trends suggest lower molecular weight, reduced aromaticity, and increased molecular lability of in-lake DOM in the permafrost zone compared to other frozen ground zones. Further FT-ICR MS characterization revealed significant molecular-level heterogeneity of DOM, with the lowest abundance of assigned DOM molecular formulas found in lakes within permafrost zones. In all studied zones, the predominant molecular formulas in-lake DOM were compounds consisted by CHO elements, accounting for 40.1 % to 63.1 % of the total. Interestingly, the percentage of CHO exhibited a gradual decline along the warming ground, while there was an increasing trend in nitrogen-containing compounds (CHON%). Meanwhile, a substantial number of polyphenols were identified, likely due to the higher rates of DOM mineralization and the transport of terrestrial DOM derived from vascular plants under the elevated temperature and precipitation conditions in the warming region. In addition, sulfur-containing compounds (CHOS and CHNOS) associated with synthetic surfactants and agal derivatives were consistently detected, and their relative abundances exhibited higher values in seasonal and short-frozen ground zones. This aligns with the increased anthropogenic disturbances to the lake's ecological environment in these two zones. This study reported the first description of in-lake DOM at the molecular level in different frozen ground zones. These findings underline that lakes in the permafrost zone serve as significant hubs for carbon processing. Investigating them may expand our understanding of carbon cycling in inland waters.

Curcumin Enhances the Anti-Cancer Efficacy of CDK4/6 Inhibitors in Prostate Cancer.

OBJECTIVE: This study aimed to investigate the potential of combining cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with curcumin (Cur), a natural compound known for its anti-aging properties, to enhance the anti-cancer efficacy in prostate cancer (PCa). METHODS: The cell viability was determined by cell counting kit-8 assay, colony forming assay and cell invasion. The cell cycle and mRNA levels of p16 (cyclin dependent kinase inhibitor 2A, CDKN2A), p21 (cyclin dependent kinase inhibitor 1A, CDKN1A) and Rb (RB transcriptional corepressor) were detected by flow cytometry and quantitative real-time polymerase chain reaction, respectively. SA-ß-gal staining and interleukin 6 (IL6) mRNA levels were used to evaluate cell aging. Western blot was used to detect mechanistic targets of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) pathways. Moreover, Sphere formation assay and mRNA levels of aldehyde dehydrogenase (ALDH) 1A1, CD44 and Nanog were used to determine cell stemness. RESULTS: The combination of LY2835219 (LY, CDK4/6 inhibitor) and Cur exhibited a synergistic inhibitory effect on PCa cell proliferation (p < 0.01) and invasion (p < 0.01) and Rb gene expression (p < 0.05), as well as a synergistic promotive effect on p61 expression (p < 0.01), p21 expression (p < 0.01) and cell cycle G1 arrest in PCa cells (p < 0.05) compared with LY or Cur alone. LY and LY + Cur increased the SA-ß-gal-stained cells (p < 0.01). mTOR (p < 0.01) and STAT3 pathway (p < 0.01) were decreased by LY + Cur (p < 0.01). Furthermore, LY + Cur conditioned medium (CM) inhibited cell stemness by decreasing cell spheres (p < 0.05), ALDH1A1 (p < 0.01), CD44 (p < 0.01) and Nanog (p < 0.01) compared with LY CM. CONCLUSIONS: The findings of this study suggested that the combination of CDK4/6 inhibitor and curcumin may have clinical implications for the treatment of PCa.

Curcumin Enhances the Anti-Cancer Efficacy of CDK4/6 Inhibitors in Prostate Cancer

Objective: This study aimed to investigate the potential of combining cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with curcumin (Cur), a natural compound known for its anti-aging properties, to enhance the anti-cancer efficacy in prostate cancer (PCa). Methods: The cell viability was determined by cell counting kit-8 assay, colony forming assay and cell invasion. The cell cycle and mRNA levels of p16 (cyclin dependent kinase inhibitor 2A, CDKN2A), p21 (cyclin dependent kinase inhibitor 1A, CDKN1A) and Rb (RB transcriptional corepressor) were detected by flow cytometry and quantitative real-time polymerase chain reaction, respectively. SA-β-gal staining and interleukin 6 (IL6) mRNA levels were used to evaluate cell aging. Western blot was used to detect mechanistic targets of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) pathways. Moreover, Sphere formation assay and mRNA levels of aldehyde dehydrogenase (ALDH) 1A1, CD44 and Nanog were used to determine cell stemness. Results: The combination of LY2835219 (LY, CDK4/6 inhibitor) and Cur exhibited a synergistic inhibitory effect on PCa cell proliferation (p < 0.01) and invasion (p < 0.01) and Rb gene expression (p < 0.05), as well as a synergistic promotive effect on p61 expression (p < 0.01), p21 expression (p < 0.01) and cell cycle G1 arrest in PCa cells (p < 0.05) compared with LY or Cur alone. LY and LY + Cur increased the SA-β-gal-stained cells (p < 0.01). mTOR (p < 0.01) and STAT3 pathway (p < 0.01) were decreased by LY + Cur (p < 0.01). Furthermore, LY + Cur conditioned medium (CM) inhibited cell stemness by decreasing cell spheres (p < 0.05), ALDH1A1 (p < 0.01), CD44 (p < 0.01) and Nanog (p < 0.01) compared with LY CM. Conclusions: The findings of this study suggested that the combination of CDK4/6 inhibitor and curcumin may have clinical implications for the treatment of PCa (AU)

Effects of ozone dose on brominated DBPs in subsequent chlor(am)ination: A comprehensive study of aliphatic, alicyclic and aromatic DBPs.

Ozone‒chlor(am)ine is a commonly used combination of disinfectants in drinking water treatment. Although there are quite a few studies on the formation of some individual DBPs in the ozone‒chlor(am)ine disinfection, an overall picture of the DBP formation in the combined disinfection is largely unavailable. In this study, the effects of ozone dose on the formation and speciation of organic brominated disinfection byproducts (DBPs) in subsequent chlorination, chloramination, or chlorination‒chloramination of simulated drinking water were investigated. High-molecular-weight, aliphatic, alicyclic and aromatic brominated DBPs were selectively detected and studied using a powerful precursor ion scan method with ultra performance liquid chromatography/electrospray ionization triple quadrupole mass spectrometry (UPLC/ESI-tqMS). Two groups of unregulated yet relatively toxic DBPs, dihalonitromethanes and dihaloacetaldehydes, were detected by the UPLC/ESI-tqMS for the first time. With increasing ozone dose, the levels of high-molecular-weight (m/z 300-500) and alicyclic and aromatic brominated DBPs generally decreased, the levels of brominated aliphatic acids were slightly affected, and the levels of dihalonitromethanes and dihaloacetaldehydes generally increased in the subsequent disinfection processes. Despite different molecular compositions of the detected DBPs, increasing ozone dose generally shifted the formation of DBPs from chlorinated ones to brominated analogues in the subsequent disinfection processes. This study provided a comprehensive analysis of the impact of ozone dose on the DBP formation and speciation in subsequent chlor(am)ine disinfection.

Multi-omics reveal neuroprotection of Acer truncatum Bunge Seed extract on hypoxic-ischemia encephalopathy rats under high-altitude.

Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.

Danxiaibacter flavus gen. nov., sp. nov., a novel bacterium of the family Chitinophagaceae isolated from forest soil on Danxia Mountain.

A Gram-stain-negative, aerobic, short rod-shaped, yellow bacterium, designated SYSU DXS3180T, was isolated from forest soil of Danxia Mountain in PR China. Growth occurred at 15-37 °C (optimum, 28-30 °C), pH 6.0-10.0 (optimum, pH 7.0-8.0) and with 0-2.0 % NaCl (optimum, 0-0.5 %, w/v). Strain SYSU DXS3180T was positive for hydrolysis of Tween 20, Tween 60, Tween 80 and starch, but negative for urease, H2S production, nitrate reduction, Tween 40 and gelatin. Phylogenetic analysis based on 16S rRNA gene and genome sequences showed that SYSU DXS3180T belonged to the family Chitinophagaceae. The closely related members were Foetidibacter luteolus YG09T (94.2 %), Limnovirga soli KCS-6T (93.9 %) and Filimonas endophytica SR 2-06T (93.7 %). The genome of strain SYSU DXS3180T was 7287640 bp with 5782 protein-coding genes, and the genomic DNA G+C content was 41.4 mol%. The main respiratory quinone was MK-7 and the major fatty acids (>10 %) were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The major polar lipids consisted of phosphatidylethanolamine, two unidentified aminolipids and two unidentified polar lipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain SYSU DXS3180T is proposed to represent a novel species of a novel genus named Danxiaibacter flavus gen. nov., sp. nov., within the family Chitinophagaceae. The type strain is SYSU DXS3180T (=KCTC 92895T=GDMCC 1.3825 T).

Telluribacter roseus sp. nov., Isolated from the Kumtag Desert Soil.

A pink-pigmented bacterium, designated as strain SYSU D00476T, was isolated from sandy soil collected from the Kumtag Desert in China. Colonies were opaque, smooth and of a slight convexity with a clearly defined border. Cells were rod-shaped, Gram-stain-negative, catalase- and oxidase-positive. Growth occurred at 4-45 ℃ (optimum at 28-30 ℃), pH 6.0-8.0 (optimum at 7.0), and with 0-3.0% NaCl (w/v, optimum at 0-2.0%). Major fatty acids (> 10%) were C16:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), iso-C17:0 3-OH and iso-C15:0. Polar lipids comprised of three unidentified polar aminolipids (ALs), two unidentified aminophosphoglycolipids (APLs), one unidentified glycolipid (GL) and three unidentified phospholipids (PLs). The predominant respiratory quinone was MK-7. The genomic DNA G + C content was 50.5%. The low digital DNA-DNA hybridization (dDDH, 27.4%) and average nucleotide identity (ANI, 85%) values between strain SYSU D00476T and Telluribacter humicola KCTC 42819T indicated that SYSU D00476T represent a distinct species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00476T belonged to the genus Telluribacter, showing 97.5% similarity with T. humicola KCTC 42819T. All these data support that strain SYSU D00476T represent a novel species of the genus Telluribacter within the family Spirosomataceae, named as Telluribacter roseus sp. nov. The type strain is SYSU D00476T (= KCTC 82285T = CGMCC 1.18647T = MCCC 1K04983T).

Capturing the microbial dark matter in desert soils using culturomics-based metagenomics and high-resolution analysis.

Deserts occupy one-third of the Earth's terrestrial surface and represent a potentially significant reservoir of microbial biodiversity, yet the majority of desert microorganisms remain uncharacterized and are seen as "microbial dark matter". Here, we introduce a multi-omics strategy, culturomics-based metagenomics (CBM) that integrates large-scale cultivation, full-length 16S rRNA gene amplicon, and shotgun metagenomic sequencing. The results showed that CBM captured a significant amount of taxonomic and functional diversity missed in direct sequencing by increasing the recovery of amplicon sequence variants (ASVs) and high/medium-quality metagenome-assembled genomes (MAGs). Importantly, CBM allowed the post hoc recovery of microbes of interest (e.g., novel or specific taxa), even those with extremely low abundance in the culture. Furthermore, strain-level analyses based on CBM and direct sequencing revealed that the desert soils harbored a considerable number of novel bacterial candidates (1941, 51.4%), of which 1095 (from CBM) were culturable. However, CBM would not exactly reflect the relative abundance of true microbial composition and functional pathways in the in situ environment, and its use coupled with direct metagenomic sequencing could provide greater insight into desert microbiomes. Overall, this study exemplifies the CBM strategy with high-resolution is an ideal way to deeply explore the untapped novel bacterial resources in desert soils, and substantially expands our knowledge on the microbial dark matter hidden in the vast expanse of deserts.

Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach.

Objective: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. Methods: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. Results: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. Conclusion: The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

Contributions of Pharmaceuticals to DBP Formation and Developmental Toxicity in Chlorination of NOM-containing Source Water.

Pharmaceuticals have been considered a priority group of emerging micropollutants in source waters in recent years, while their role in the formation and toxicity of disinfection byproducts (DBPs) during chlorine disinfection remains largely unclear. In this study, the contributions of natural organic matter (NOM) and pharmaceuticals (a mixture of ten representative pharmaceuticals) to the overall DBP formation and toxicity during drinking water chlorination were investigated. By innovatively "normalizing" chlorine exposure and constructing a kinetic model, we were able to differentiate and evaluate the contributions of NOM and pharmaceuticals to the total organic halogen (TOX) formation for source waters that contained different levels of pharmaceuticals. It was found that at a chlorine contact time of 1.0 h, NOM (2 mg/L as C) and pharmaceuticals (total 0.0062-0.31 mg/L as C) contributed 79.8-99.5% and 0.5-20.2%, respectively, of TOX. The toxicity test results showed that the chlorination remarkably increased the toxicity of the pharmaceutical mixture by converting the parent compounds into more toxic pharmaceutical-derived DBPs, and these DBPs might contribute significantly to the overall developmental toxicity of chlorinated waters. This study highlights the non-negligible role of pharmaceuticals in the formation and toxicity of overall DBPs in chlorinated drinking water.

Rubellimicrobium arenae sp. nov., isolated from desert soil.

Two Gram-stain-negative strains, designated as SYSU D00286T and SYSU D00782, were isolated from a sand sample collected from the Kumtag Desert in Xinjiang, north-west China. Cells were aerobic, non-motile and positive for both oxidase and catalase. Growth occurred at 4-37 °C (optimum, 28-30 °C), pH 6.0-7.0 (optimum, pH 7.0) and NaCl concentration of 0-1.5 % (w/v; optimum, 0%). Growth was observed on Reasoner's 2A agar and nutrient agar, but not on Luria-Bertani agar and trypticase soy agar. The polar lipids were identified as diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, three unidentified aminolipids, one unidentified glycolipid and two unidentified phospholipids. The major respiratory quinone was ubiquinone-10 and the major fatty acids (>10 %) were C16 : 0 and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The 16S rRNA gene sequence similarity between strains SYSU D00286T and SYSU D00782 was 100%, and their average nucleotide identity (ANI), average amino acid identity and (AAI) digital DNA-DNA hybridization (dDDH) values were all 100.0 %. Phylogenetic analysis indicated that these two strains belong to the same species of the genus Rubellimicrobium and show the highest sequence similarity to Rubellimicrobium rubrum KCTC 72461T (98.2 %) and Rubellimicrobium roseum CCTCC AA 208029T (97.5 %). The ANI, AAI and dDDH values between SYSU D00286T (as well as SYSU D00782) and the other five Rubellimicrobium type strains were all less than or equal to 83.2, 80.1 and 23.6 %, respectively. Based on their phylogenetic, phenotypic and chemotaxonomical features, strains SYSU D00286T and SYSU D00782 represent a novel species of the genus Rubellimicrobium, for which the name Rubellimicrobium arenae sp. nov. is proposed. The type strain is SYSU D00286T (=MCCC 1K04981T=CGMCC 1.8626T=KCTC 82271T).

NaHCO3 addition enhances water permeance and Ca/haloacetic acids selectivity of nanofiltration membranes for drinking water treatment.

The existence of disinfection by-products such as haloacetic acids (HAAs) in drinking water severely threatens water safety and public health. Nanofiltration (NF) is a promising strategy to remove HAAs for clean water production. However, NF often possesses overhigh rejection of essential minerals such as calcium. Herein, we developed highly selective NF membranes with tailored surface charge and pore size for efficient rejection of HAAs and high passage of minerals. The NF membranes were fabricated through interfacial polymerization (IP) with NaHCO3 as an additive. The NaHCO3-tailored NF membranes exhibited high water permeance up to ∼24.0 L m - 2 h - 1 bar-1 (more than doubled compared with the control membrane) thanks to the formation of stripe-like features and enlarged pore size. Meanwhile, the tailored membranes showed enhanced negative charge, which benefitted their rejection of HAAs and passage of Ca and Mg. The higher rejection of HAAs (e.g., > 90%) with the lower rejection of minerals (e.g., < 30% for Ca) allowed the NF membranes to achieve higher minerals/HAAs selectivity, which was significantly higher than those of commercially available NF membranes. The simultaneously enhanced membrane performance and higher minerals/HAAs selectivity would greatly boost water production efficiency and water quality. Our findings provide a novel insight to tailor the minerals/micropollutants selectivity of NF membranes for highly selective separation in membrane-based water treatment.

CMKLR1 Antagonist Alpha-NETA Protects against Diabetic Nephropathy in Mice.

INTRODUCTION: Diabetic nephropathy (DN) is a common complication in diabetic patients. Chemerin, a novel adipokine, has been associated with renal damage in DN. The chemerin chemokine-like receptor 1 (CMKLR1) has been reported to participate in DN. In this study, we aimed to investigate the effect of a CMKLR1 antagonist, 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA), on DN. METHODS: To induce diabetes, 8-week-old male C57BL/6J mice were given a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Diabetic mice were randomly assigned to receive daily doses of 0, 5, or 10 mg/kg α-NETA for 4 weeks. RESULTS: α-NETA dose-dependently induced body weight and reduced fasting blood glucose levels in STZ-induced diabetic mice. Furthermore, α-NETA significantly reduced the expressions of renal injury markers, including serum creatinine, kidney weight/body weight, urine volume, total proteins, and albumin in the urine, and increased creatinine clearance. Periodic acid-Schiff staining also indicated that α-NETA could effectively ameliorate renal injuries in DN mice. In addition, α-NETA inhibited renal inflammation and the expressions of chemerin and CMKLR1 in mice with DN. CONCLUSION: In summary, our findings suggested that α-NETA has beneficial effects on the management of DN. Specifically, α-NETA effectively ameliorated renal damage and inflammation in a dose-dependent manner in mice with DN. Thus, targeting the chemerin and CMKLR1 axis with α-NETA may be a promising therapeutic strategy for the treatment of DN.

Aridibaculum aurantiacum gen. nov., sp. nov., isolated from the Kumtag Desert soil.

A novel orange-coloured bacterium, designated strain SYSU D00508T, was isolated from a sandy soil sampled from the Kumtag Desert in China. Strain SYSU D00508T was aerobic, Gram-stain-negative, oxidase-positive, catalase-positive and non-motile. Growth occurred at 4-45°C (optimum 28-30°C), pH 6.0-9.0 (optimum pH 7.0-8.0) and with 0-2.5 % NaCl (w/v, optimum 0-1.0 %). The major polar lipids consisted of phosphatidylethanolamine (PE), unidentified aminolipids (AL1-3) and unidentified polar lipids (L1-5) were also detected. The major respiratory quinone was MK-7 and the major fatty acids (>10 %) were iso-C17 : 0 3-OH, iso-C15 : 0 and iso-C15 : 1 G. The genomic DNA G+C content was 42.6 %. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00508T belonged to the family Chitinophagaceae and showed 93.9 % (Segetibacter koreensis DSM18137T), 92.9 % (Segetibacter aerophilus NBRC 106135T), 93.0 % (Terrimonas soli JCM 32095T) and 92.8 % (Parasegetibacter terrae JCM 19942T) similarities. Based on the phylogenetic, phenotypic and chemotaxonomic data, strain SYSU D00508T is proposed to represent a novel species of a new genus, named Aridibaculum aurantiacum gen. nov., sp. nov., within the family Chitinophagaceae. The type strain is SYSU D00508T (=KCTC 82286T=CGMCC 1.18648T=MCCC 1K05005T).

Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)-/- (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1ß. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

Formation of Larger Molecular Weight Disinfection Byproducts from Acetaminophen in Chlorine Disinfection.

Acetaminophen is widely used to treat mild to moderate pain and to reduce fever. Under the worldwide COVID-19 pandemic, this over-the-counter pain reliever and fever reducer has been drastically consumed, which makes it even more abundant than ever in municipal wastewater and drinking water sources. Chlorine is the most widely used oxidant in drinking water disinfection, and chlorination generally causes the degradation of organic compounds, including acetaminophen. In this study, a new reaction pathway in the chlorination of acetaminophen, i.e., oxidative coupling reactions via acetaminophen radicals, was investigated both experimentally and computationally. Using an ultraperformance liquid chromatograph coupled to an electrospray ionization-triple quadrupole mass spectrometer, we detected over 20 polymeric products in chlorinated acetaminophen samples, some of which have structures similar to the legacy pollutants "polychlorinated biphenyls". Both C-C and C-O bonding products were found, and the corresponding bonding processes and kinetics were revealed by quantum chemical calculations. Based on the product confirmation and intrinsic reaction coordinate computations, a pathway for the formation of the polymeric products in the chlorination of acetaminophen was proposed. This study suggests that chlorination may cause not only degradation but also upgradation of a phenolic compound or contaminant.

How smart senior care can achieve value co-creation: Evidence from China.

With the rapid rise of artificial intelligence, smart senior care has become a new trend for future development. The collection of "Typical Cases of Chinese Elderly Service Industry Development" is selected by the script materials. The main purpose of this article is to investigate how smart senior care can achieve value co-creation by grounded theory. This study explores the phenomenon of value co-creation in the participation of multiple actors in smart senior care services. Findings show that institutional guarantee, technical intake, market empowerment, emotional support, service interaction, and reciprocity norm are identified as the driving factors for value co-creation. In addition, the behavioral processes of value co-creation include multi-actor value consensus, co-creation environment establishment, practical value co-creation, public value sharing, and diffusion of service added value in smart senior care. Finally, this study constructs a practical logic model of achieving value co-creation. It extends and enriches the scope of the value co-creation theory. This study confirms that value co-creation can be effectively achieved in smart senior care by the above-mentioned ways, revealing its driving factors and behavioral processes. The article expands on the application of value co-creation in the field of public healthcare. The results have important theoretical and practical significance for narrowing the public service equalization gap.