The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Objective:To explore the status of psychological resilience in female infertility patients and analyze its influencing factors, providing a basis for developing effective intervention measures in clinical practice.Methods:A convenient sampling method was used to select female infertility patients who visited the Reproductive Medicine Center of the First Affiliated Hospital of the University of South China from March to October 2024 as the research objects. A cross-sectional survey was conducted using the General Data Questionnaire, Connor-Davidson Resilience Scale, Herth Hope Index, the Infertility Stigma Scale, Family Resilience Scale and Perceived Social Support Scale. The random forest algorithm was used to rank the importance of variables, Lasso regression was used to further screen variables, and the selected variables were included in multiple stepwise regression analysis to analyze the influencing factors.Results:Ultimately, 322 female infertility patients aged (30.40 ± 4.50) were included. The psychological resilience score was (64.29 ± 10.05) points, which was above the medium level. The top 6 influential factors in the importance of variables were stigma, family resilience, age, social support, infertility cause and hope level. Multiple stepwise regression analysis showed that age, infertility cause, hope level, stigma, family resilience and social support were the main influencing factors of mental resilience of female infertility patients ( t values were -8.32 to 6.85, all P<0.05). Conclusions:The psychological resilience of female infertility patients is above the medium level, and the psychological resilience of infertile women is affected by many factors such as individual characteristics, family environment and social support. Medical staff should take targeted intervention measures to improve the psychological resilience of female infertility patients.

Objective:To explore the status of psychological resilience in female infertility patients and analyze its influencing factors, providing a basis for developing effective intervention measures in clinical practice.Methods:A convenient sampling method was used to select female infertility patients who visited the Reproductive Medicine Center of the First Affiliated Hospital of the University of South China from March to October 2024 as the research objects. A cross-sectional survey was conducted using the General Data Questionnaire, Connor-Davidson Resilience Scale, Herth Hope Index, the Infertility Stigma Scale, Family Resilience Scale and Perceived Social Support Scale. The random forest algorithm was used to rank the importance of variables, Lasso regression was used to further screen variables, and the selected variables were included in multiple stepwise regression analysis to analyze the influencing factors.Results:Ultimately, 322 female infertility patients aged (30.40 ± 4.50) were included. The psychological resilience score was (64.29 ± 10.05) points, which was above the medium level. The top 6 influential factors in the importance of variables were stigma, family resilience, age, social support, infertility cause and hope level. Multiple stepwise regression analysis showed that age, infertility cause, hope level, stigma, family resilience and social support were the main influencing factors of mental resilience of female infertility patients ( t values were -8.32 to 6.85, all P<0.05). Conclusions:The psychological resilience of female infertility patients is above the medium level, and the psychological resilience of infertile women is affected by many factors such as individual characteristics, family environment and social support. Medical staff should take targeted intervention measures to improve the psychological resilience of female infertility patients.

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Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Objective To investigate the influence of rutin on neuroinflammation in rats with hydraulic shock brain injury by regulating thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods Rats were randomly separated into model group and sham operation group;the rats in the model group were established by hydraulic impact method.After modeling,they were randomly separated into rutin low(rutin-L,25 mg·kg-1 rutin)and medium(rutin-M,50 mg·kg-1 rutin).D),high(rutin-H,100 mg·kg-1 rutin)dose groups,model group and positive control group(dexamethasone group,0.1 mg·kg-1 dexamethasone),18 animals/group.Each group was intervened with drugs and normal saline once a day,and after continuous intervention for 3 days,the neurological deficit(neurological severity score,NSS)of the rats was scored;the rats were sacrificed by decapitation,the cerebral edema was determined,the brain tissue around the contusion was separated,and the histological changes,inflammatory cytokine indicators-tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)levels and TXNIP,NLRP3 protein expression levels were measured.Results The rats in the sham operation group had no injury.The integrity of brain tissue in model group was damaged,cell wrinkly nuclei were deeply stained,interstitial edema was accompanied by holes and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP and NLRP3 protein expression levels were all increased compared with those in the sham operation group(P<0.05);after rutin intervention,the pathological injury of rat brain tissue was relieved,and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP,and NLRP3 protein expression levels were all lower than those in the model group(P<0.05),there was no significant difference between the rutin-H group and the dexamethasone group(P>0.05).Conclusion Rutin can inhibit the inflammatory response of hydraulic shock brain injury rats,improve brain tissue injury and edema,which may be related to the inhibition of TXNIP/NLRP3 signaling pathway.

Objective To investigate the influence of rutin on neuroinflammation in rats with hydraulic shock brain injury by regulating thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods Rats were randomly separated into model group and sham operation group;the rats in the model group were established by hydraulic impact method.After modeling,they were randomly separated into rutin low(rutin-L,25 mg·kg-1 rutin)and medium(rutin-M,50 mg·kg-1 rutin).D),high(rutin-H,100 mg·kg-1 rutin)dose groups,model group and positive control group(dexamethasone group,0.1 mg·kg-1 dexamethasone),18 animals/group.Each group was intervened with drugs and normal saline once a day,and after continuous intervention for 3 days,the neurological deficit(neurological severity score,NSS)of the rats was scored;the rats were sacrificed by decapitation,the cerebral edema was determined,the brain tissue around the contusion was separated,and the histological changes,inflammatory cytokine indicators-tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)levels and TXNIP,NLRP3 protein expression levels were measured.Results The rats in the sham operation group had no injury.The integrity of brain tissue in model group was damaged,cell wrinkly nuclei were deeply stained,interstitial edema was accompanied by holes and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP and NLRP3 protein expression levels were all increased compared with those in the sham operation group(P<0.05);after rutin intervention,the pathological injury of rat brain tissue was relieved,and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP,and NLRP3 protein expression levels were all lower than those in the model group(P<0.05),there was no significant difference between the rutin-H group and the dexamethasone group(P>0.05).Conclusion Rutin can inhibit the inflammatory response of hydraulic shock brain injury rats,improve brain tissue injury and edema,which may be related to the inhibition of TXNIP/NLRP3 signaling pathway.

Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.

Lipotoxicity,caused by intracellular lipid accumulation,accelerates the degenerative process of cellular senescence,which has implications in cancer development and therapy.Previously,camitine palmi-toyltransferase 1C (CPT1C),a mitochondrial enzyme that catalyzes carnitinylation of fatty acids,was found to be a critical regulator of cancer cell senescence.However,whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown.An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231,HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C.Cellular lipotoxicity was further confirmed by lipotoxicity assays.Significant changes were found in the lipidome of CPT1 C-depleted cells,including major alterations in fatty acid,diacylglycerol,triacylglycerol,oxidative lipids,cardiolipin,phosphatidylglycerol,phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin.This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialde-hyde and reactive oxygen species,signatures of lipid peroxidation and oxidative stress.Reduction of ATP synthesis,loss of mitochondrial transmembrane potential and down-regulation of expression of mito-chondriogenesis gene mRNAs indicated mitochondrial dysfunction induced by lipotoxicity,which could further result in cellular senescence.Taken together,this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence,suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.