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A comprehensive understanding of the hydrochemical evolution and spatial patterns of shallow groundwater systems is essential for water resource management and wetland ecological restoration. The Baiyangdian Wetland is one of the most concerning areas because of the development of the Xiong'an New Area. The spatial characteristics of groundwater hydrochemistry and potential controlling factors associated with hydrochemical evolution remain unclear. In this study, hydrogeochemistry together with the hierarchical cluster analysis were used to elucidate the hydrochemical processes and hydrological zoning patterns of shallow groundwater systems in the Baiyangdian Wetland, North China Plain. The results showed that hydrochemical compositions of shallow groundwater had considerable spatial variations, which was closely related to the inflow rivers hydrochemistry and the dynamics of groundwater–surface water interactions. A significant increase in SO42− concentration occurring at the cone of the depression was related to extensive pumping caused by anthropogenic activities. Anthropogenic activities were also a major factor controlling the spatial distribution patterns of shallow groundwater hydrochemistry. Ca2+, Mg2+, and SO42− in the wetland and shallow groundwater were primarily derived from carbonate and gypsum dissolution, while Na+ and Cl− originated from halite and silicate dissolution. Rock weathering predominated the geochemical evolution of shallow groundwater in conjunction with carbonate precipitation and cation exchange. The hydrochemistry of the shallow groundwater system presented distinct spatial zonation patterns that were classified into four clusters corresponding to seven subzones. In Zones I–IV, water‐rock interaction was the dominant factor controlling shallow groundwater chemistry, which was driven by the positive groundwater–surface water exchange. The coupled effects of anthropogenic activities and river infiltration and mixing caused the high levels of dissolved components in Zones V–VII. This study contributes to have a better understanding of the water cycle and hydraulic connections among different bodies, and will benefit the rational evaluation of hydrochemical evolution and wetland ecological restoration in the Baiyangdian Wetland. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus (JEV) belongs to the Flaviviridae family and is a representative mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans. Despite the availability of vaccines, JEV remains a major public health threat with the potential to spread globally. According to the World Health Organization (WHO), there are an estimated 69,000 cases of JE each year, and this figure is probably an underestimate. The majority of JE victims are children in endemic areas, and almost half of the surviving patients have motor or cognitive sequelae. Thus, the absence of a clinically approved drug for the treatment of JE defines an urgent medical need. Recently, several promising and potential drug candidates were reported through drug repurposing studies, high-throughput drug library screening, and de novo design. This review focuses on the historical aspects of JEV, the biology of JEV replication, targets for therapeutic strategies, a target product profile, and drug development initiatives. [ABSTRACT FROM AUTHOR]

Does entering the labour market via precarious employment have a long-term scarring effect on one's career? Prior research proposes diverse arguments, but firm conclusions remain elusive. Using panel data from Hong Kong, this study rekindles this debate by revealing the long-lasting effect of first job precarity on workers' subsequent career prospects. A comprehensive measure of precarious employment is constructed to simultaneously account for employment status, contractual status and occupational status, and random effects models are used to test the scarring effect of first job precarity on subsequent monthly income, job satisfaction and fringe benefits. It is also observed that macroeconomic situations, particularly periods of economic crisis, have a detrimental effect on entry into precarious employment. Importantly, the results show the substantial negative consequences of initial precarious employment, highlighting the adverse impact of economic crises on first job precarity and the subsequent scarring effect on career prospects. [ABSTRACT FROM AUTHOR]

Prior research explored the individual contributions of grandparents, domestic workers, and preschool institutions in supporting maternal employment, yet few have examined them simultaneously. More importantly, the increasing diversity and multiplicity in childcare arrangement throughout different stages of childrearing has been largely overlooked. Utilizing data from the Hong Kong Panel Study of Social Dynamics (HKPSSD), this study examines the effects of diverse childcare combinations on women's labor supply from a life course perspective. Our findings reveal that mothers with younger children are considerably less likely to remain in the workforce and work fewer hours than their childless counterparts. Nevertheless, grandparental co-residence, outsourcing and center-based care can all significantly alleviate such motherhood penalty, albeit to different extents. Notably, during the initial years of motherhood, solely relying on either grandparental care or center-based care yields limited effects, but these options become advantageous for mothers when paired with assistance from domestic workers. These findings highlight the potential for policy interventions that directly subsidize parents for marketized approaches to childcare, particularly in societies experiencing a decline in multigenerational households and rising costs for formal childcare. [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the important factors in the development of alcoholic liver disease. The production of reactive oxygen species and other free radicals is an important feature of alcohol metabolism in the liver and an important substance in liver injury. When large amounts of ROS are produced, the homeostasis of the liver REDOX system will be disrupted and liver injury will be caused. Oxidative stress can damage proteins, nucleic acids and lipids, liver dysfunction. In addition, damaging factors produced by oxidative damage to liver tissue can induce the occurrence of inflammation, thereby aggravating the development of ALD. This article reviews the oxidative damage of alcohol on liver proteins, nucleic acids, and lipids, and provides new insights and summaries of the oxidative stress process. We also discussed the relationship between oxidative stress and inflammation in alcoholic liver disease from different perspectives. Finally, the research status of antioxidant therapy in alcoholic liver disease was summarized, hoping to provide better help for learning and developing the understanding of alcoholic liver disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhengquan Su reports that funding was provided by Guangdong Pharmaceutical University. Zhengquan Su reports a relationship with Guangdong Pharmaceutical University that includes: If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Fufang Zhenzhu Tiaozhi (FTZ) capsule is a hospital preparation of a patented traditional Chinese medicine compound. FTZ has been clinically used for nearly 13 years in the treatment of diabetes and glycolipid metabolic diseases. With the significant benefits of SGLT2 inhibitor in patients with diabetic kidney disease (DKD), it provides a research avenue to explore the mechanism of FTZ in treating this disease based on glycolysis pathway., Aim of the Study: To explore the pharmacological characteristics of FTZ in DKD mice and its impact on the glycolysis pathway., Materials and Methods: We induced a DKD model in C57BL/6 mice by injection of streptozotocin (STZ) combined with long-term high-fat diet. We administered three doses of FTZ for 12 weeks of treatment. Kidney function, blood lipid levels, glucose tolerance, and key glycolytic enzymes were evaluated. Renal pathological changes were observed using HE, MASSON, and PAS staining. The potential targets of the active ingredients of FTZ in the glycolysis pathway were predicted using network pharmacology and molecular docking. Validation was performed using immunohistochemistry and Western blotting., Results: FTZ effectively reduces blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, 24 h proteinuria, serum creatinine, blood urea nitrogen, and increases urinary glucose levels. Glucose tolerance and renal pathological changes were significantly improved by FTZ treatment. Pinusolidic acid, a component of FTZ, shows good binding affinity with three active pockets of SGLT2. WB and immunohistochemistry revealed that FTZ significantly inhibits the expression of SGLT2 and its glycolytic related proteins (GLUT2/PKM2/HK2). Hexokinase, pyruvate kinase, and lactate dehydrogenase in the kidney were also significantly inhibited by FTZ in a dose-dependent manner., Conclusion: FTZ may alleviate the progression of DKD by inhibiting the activation of the SGLT2/glycolytic pathway. Our study provides new insights into the clinical application of FTZ in DKD., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gallic acid (GA) and β-glucogallin (BGG) are natural products with diverse uses in pharmaceutical, food, chemical and cosmetic industries. They are valued for their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, and anticancer properties. Despite their significant importance, microbial production of GA and BGG faces challenges such as limited titers and yields, along with the incomplete understanding of BGG biosynthesis pathways in microorganisms. To address these challenges, we developed a recombinant Escherichia coli strain capable of efficiently producing GA. Our approach involved screening efficient pathway enzymes, integrating biosynthetic pathway genes into the genome while balancing carbon flux via adjusting expression levels, and strengthening the shikimate pathway to remove bottlenecks. The resultant strain achieved impressive results, producing 51.57 g/L of GA with a carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, we extended this microbial platform to biosynthesize BGG by screening GA 1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. This work establishes an efficient chassis for producing GA at an industrial level and provides a microbial platform for generating GA derivatives., (© 2024 Wiley Periodicals LLC.)

Amelioration of hypercholesterolemia is essential for the treatment of atherosclerotic cardiovascular disease. Sodium sulphate is the effective component of mirabilite, which has been used in traditional Chinese medicine for the treatment of various diseases. In the present study, C57BL/6 mice were fed with a high-cholesterol diet (HCD) for 7 weeks and were treated with sodium sulphate in the last three of those weeks. Sodium sulphate significantly reduced the total cholesterol level and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in the serum of mice fed the HCD. In addition, cytochrome P450 7a1 and 39a1 were significantly upregulated in the livers of mice treated with sodium sulphate. Furthermore, tribbles pseudokinase 3 expression was significantly increased in the livers of mice fed the HCD, but was significantly reduced by sodium sulphate treatment. In terms of the insulin signaling pathway, the ratio of phosphorylated AKT to total AKT in the livers of mice fed the HCD was significantly lower compared with that of control mice fed a normal diet, but was significantly increased by sodium sulphate treatment. Sodium sulphate treatment also reduced the levels of fibroblast growth factor (FGF)15 in the ileum and inhibited the FGF15/FGF receptor 4-Klotho β/c-Jun N-terminal kinase/c-Jun signaling pathway in the livers of mice fed the HCD. In addition, sodium sulphate changed the composition of the gut microbiota of mice fed the HCD. In conclusion, sodium sulphate may mitigate hypercholesterolemia and hepatic insulin resistance in mice fed an HCD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Yang et al.)

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO 2 ) nanospheres (NPs) (ICG@MnO 2 ), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO 2 @Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO 2 @Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO 2 catalyzes the conversion of H 2 O 2 to O 2 , thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O 2 to produce singlet oxygen ( 1 O 2 ) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H 2 O 2 reduces MnO 2 to Mn 2+ , which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO 2 @Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC., Competing Interests: The authors declare no competing interest., (© 2024 The Authors.)

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34 + hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.