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Polymeric hydrogel materials with multiple functions are in great demand in practical biomedical scenarios. In this work, a self-healing hydrogel with both antimicrobial properties was prepared using a strategy that combines dynamic imine and borate ester bonds. In this hydrogel, polyvinyl alcohol (PVA) is used as the base network, and borax solution as the cross-linking agent, and borate ester bonds can be formed between these two. Dialdehyde carboxymethyl cellulose (DCMC) was selected to cross-link with the amino groups in carboxymethyl chitosan (CMCS) and polyethyleneimine (PEI) to form dynamic imine bonds. The PVA/PEI/DCMC/CMCS hydrogels prepared by double chemical cross-linking have good mechanical properties (maximum tensile strength up to 289 KPa and strain at the break up to 1025%). Due to the uniqueness of the two chemical bonds, the hydrogel material is self-healing at room temperature without additional stimulation. In addition, the inherent antibacterial properties of the raw materials in this hydrogel confer antibacterial properties, with a kill rate of up to 99% against E. coli and S. aureus. The multifunctional hydrogels developed in this study provide more ideas and references for the future application of hydrogel materials in practical scenarios., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 Elsevier B.V. All rights reserved.)

Hydrogel materials are gradually increasing research in biological aspects due to their unique properties. In order to prepare hydrogels with the potential to be used in clinical wound therapy, the authors prepared a bifunctional hydrogel with antibacterial and self-healing properties. The hydrogel was composed of borax cross-linked polyvinyl alcohol (PVA) and carboxymethyl chitosan (CMCS), which realizes self-healing between polymers through hydrogen bonds and borate ester bonds. The double cross-linking of hydrogen bonds and borate ester bonds also endows the hydrogel with better mechanical properties (toughness and tensile stress can reach 22.30 MJ/m 3 and 70.35 KPa, respectively). On this basis, adding highly stable silver nanoparticles (AgNPs) to the hydrogel can effectively inhibit the growth of E. coli and S. aureus. This idea provides the possibility for the application of hydrogels in the process of biological wound healing., Competing Interests: Declaration of competing interest The authors 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 © 2022 Elsevier B.V. All rights reserved.)

This study investigated the indigenous functional microbial communities associated with the degradation of chiral fungicide mandipropamid enantiomers in soils repeatedly treated with a single enantiomer. The R-enantiomer degraded faster than the S-enantiomer, with degradation half-lives ranging from 10.2 d to 79.2 d for the R-enantiomer and 10.4 d to 130.5 d for the S-enantiomer. Six bacterial genera, (Burkholderia, Paraburkholderia, Hyphomicrobium, Methylobacterium, Caballeronia, and Ralstonia) with R-enantiomer substrate preference and three bacterial genera (Haliangium, Sorangium, and Sandaracinus) with S-enantiomer substate preference were responsible for the preferential degradation of the R-enantiomer and S-enantiomer, respectively. KEGG analysis indicated that Burkholderia, Paraburkholderia, Hyphomicrobium, and Methylobacterium were the dominant contributors to soil microbial metabolic functions. Notably, six microbial metabolic pathways and twelve functional enzyme genes were associated with the preferential degradation of the R-enantiomer, whose relative abundances in the R-enantiomer treatment were higher than those in the S-enantiomer treatment. A constructed biodegradation gene (BDG) protein database analysis further confirmed that Burkholderia, Paraburkholderia, Hyphomicrobium, Methylobacterium, and Ralstonia were the potential hosts of five dominant BDGs, bphA1, benA, bph, p450, and ppah. We concluded that bacterial genera Burkholderia, Paraburkholderia, Hyphomicrobium, and Methylobacterium may play pivotal roles in the preferential degradation of mandipropamid R-enantiomer in repeatedly treated soils., (Copyright © 2022 Elsevier B.V. All rights reserved.)

As a novel chiral amide fungicide, the enantioselective behaviors of mandipropamid in the soil environment are unclear. Furthermore, there is a need to understand the stress response mechanisms of soil organisms exposed to mandipropamid isomers. Therefore, the selective bioaccumulation of mandipropamid isomers and detoxification mechanisms of earthworms (Eisenia fetida) were investigated in this study. Our results suggested that the enantioselective bioaccumulation of mandipropamid in earthworms occurred with the preferential enrichment of S-(+)-isomer. The activities of detoxification enzymes, such as cytochrome P450 (CYP450), glutathione-S-transferases (GST), and carboxylesterase (CarE), changed significantly upon exposure to S-(+)- and R-(-)-mandipropamid (particularly for CYP450 and GST). A transcriptome analysis revealed that more differentially expressed genes (DEGs) were observed under S-(+)-isomer exposure (15,798) than those under R-(-)-isomer exposure (12,222), as compared to the control group. These DEGs were mainly enriched in bile secretion and thyroid hormone signaling pathways, which were related to the detoxification process in earthworms. Moreover, the 20 DEGs, which exhibited the most profound changes (such as CYP2 and CYP3A4) in these pathways, were screened, clustered, and observed to be mainly involved in regulating the detoxification function of earthworm cells. These results indicated that detoxification systems played an essential role in the stress response to mandipropamid exposure. Additionally, earthworms were more sensitive to the stress induced by S-(+)-mandipropamid than that induced by R-(-)-mandipropamid. This is the first study to elucidate the mandipropamid detoxification mechanism of earthworms at the enantiomer level, which can be beneficial for remediating chiral pollutants., Competing Interests: Declaration of competing interest The authors 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 © 2021. Published by Elsevier B.V.)

This study investigated the effects of earthworms on the enantioselective degradation of chloroacetamide herbicide acetochlor with soil microorganisms in repeatedly treated soils. The S-enantiomer degraded more slowly and exerted stronger inhibition on soil microbial functions than the R-enantiomer in single soil system. A synergistic effect was observed between soil microorganisms and earthworms that accelerated the degradation of both the enantiomers, particularly the highly toxic S-enantiomer, which resulted in the preferential degradation of S-enantiomer in soil-earthworm system. Earthworms stimulated five potential indigenous degraders (i.e. Lysobacter, Kaistobacter, Flavobacterium, Arenimonas, and Aquicell), induced two new potential degraders (i.e. Aeromonas and Algoriphagus), and also significantly strengthened the correlations among these seven dominant potential degraders and other microorganisms. Notably, the relative abundances of Flavobacterium and Aeromonas in soil treated with earthworms for S-enantiomer were higher than those for R-enantiomer. Furthermore, earthworms significantly stimulated overall soil microbial activity and improved three microbial metabolic pathways, and xenobiotics biodegradation and metabolism, signal transduction, cell motility, particularly for the S-enantiomer treatment with earthworms, which alleviated the strong inhibition of S-enantiomer on microbial community functions. This study confirmed that earthworms accelerated the degradation of the highly toxic acetochlor S-enantiomer in soil, providing a potential approach in chloroacetamide herbicide-polluted soil remediation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acetochlor (ACT) as a widely used chiral chloroacetamide herbicide is appropriate to evaluate the potential toxicity in soil ecosystems at enantiomeric level. The acute and subchronic toxicities of R-acetochlor (R-ACT) and S-acetochlor (S-ACT) on earthworms (Eisenia fetida) were investigated in the present study. Residual analyses showed that S-ACT degraded faster than R-ACT in artificial soil with half-lives of 16.5 and 21.7 d, respectively. Additionally, significant enantioselective acute toxicity in earthworms from between S-ACT and R-ACT (p < 0.05) was observed, and the acute toxicity of R-ACT were 1.9 and 1.5 times higher than those of S-ACT in the filter paper test and artificial soil test. The hydroxyl radical (OH - ) content, superoxide dismutase (SOD) and antioxidant enzyme catalase (CAT) activities, and cytochrome P450 content in earthworms significantly increased under the influence of ACT enantiomers; however, the acetylcholinesterase (AchE) activity was significantly inhibited after exposure to the two enantiomers. Moreover, lipid peroxidation and DNA damage were induced by ACT enantiomers. The results of transcriptome sequencing indicated that R-ACT induced a stronger oxidative stress effect than S-ACT in earthworms by mediating signaling pathways, which may be the primary reason for the enantioselective toxicity between S-ACT and R-ACT. Overall, the results demonstrated that R-ACT has a higher risk than S-ACT in the soil environment, which is important for understanding the enantioselective behavior of chloroacetamide pesticides., Competing Interests: Declaration of competing interest The authors 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 © 2020 Elsevier B.V. All rights reserved.)

Obesity is one of the most important health problems worldwide. Panax ginseng has been reported to exert anti-obesity effect. However, the active constituents and the underlying mechanism remained uncertain. This study uncovered the anti-obesity effect of protopanaxadiol (PPD) and its potential mechanism. To investigate the anti-obesity effect of PPD, high-fat diet induced obesity (DIO) C57BL/6 mice were treated with PPD by both intraperitoneal injection (i.p.) and oral administration. Body weight and food intake were recorded. Energy expenditure was measured by CLAMS metabolic cages. For mechanism study, C-Fos in the hypothalamus of the mice was stained following the intracerebroventricular (i.c.v.) injection of PPD. Our results showed that with both injection and feeding, PPD reduced body weight, inhibited food intake, increased energy expenditure and improved liver damage in DIO mice. Mechanistically, i.c.v. injection of PPD inhibited feeding and increased C-Fos expression in paraventricular nucleus of the hypothalamus (PVH). The results suggest that PPD may reduce body weight of DIO mice via the activation of PVH neurons and PPD is a potential therapeutic candidate for the treatment of obesity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The pathophysiological mechanism underlying Hashimoto's thyroiditis (HT) is still unclear. Thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) are diagnostic hallmarks of HT. These IgG antibodies regulate the balance of immunologic tolerance and autoimmunity via Fcγ receptors (FcγRs). The aim of our study was to investigate the role of FcγRs in the pathogenesis of HT. The percentage of peripheral blood mononuclear cells (PBMCs) from HT patients bearing FcγRII was significantly lower than that seen in healthy donors, and the mean fluorescence intensity (MFI) value of FcγRII on PBMCs from HT patients was significantly higher. The percentage of PBMCs positive for FcγRIII also was significantly higher in HT patients, and the percentage of B cells bearing FcγRIIB in HT patients was significantly lower than that seen in healthy donors. Our study therefore provides evidence for FcγRs, especially FcγRIIB, being involved in the pathogenesis of HT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The identification of a new series of selective nonsteroidal progesterone receptor (PR) agonists is reported. Using a high-throughput screening assay based on the measurement of transactivation of a mouse mammary tumor virus promoter-driven luciferase reporter (MMTV-Luc) in human breast cancer T47D cells, a benzimidazole-2-thione analog was identified. Compound 1 showed an apparent EC50 of 53 nM and efficacy of 93% with respect to progesterone. It binds to PR with high affinity (Ki nM), but had no or very low affinity for other steroid hormone receptors. Structure-activity relationship studies of a series of benzimidazole-2-thione analogs revealed critical positions for high PR binding affinity and transactivation potency as well as receptor selectivity, as exemplified by 25. Compound 25 binds to human PR with high affinity (Ki nM) and had at least > 1000-fold selectivity for PR versus other steroid receptors. Molecular modeling studies suggested that these agonists overlap favorably with progesterone in the ligand-binding domain of PR. In T47D cells, compound 25 acted as a full agonist in the MMTV-Luc reporter assay, as well as in the induction of endogenous alkaline phosphatase activity with apparent EC50 values of 4 and 9 nM, respectively. In the immature rat model, compound 25 provided a significant suppression of estrogen-induced endometrium hypertrophy as measured by luminal epithelial height. In contrast, compound 25 was inactive in the luteinizing hormone release assay in young ovariectomized rats. These benzimidazole-2-thione analogs constitute a new series of nonsteroidal PR agonists with an excellent steroid receptor selectivity profile. The differential activities observed in the in vivo progestogenic assays in rat models suggest that these analogs can act as selective PR modulators.