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Vincent Chin-Hung Chen,1,2 Tsu-Nai Wang,3 Ming-Chia Hsieh,4 Shih-Yong Chou,1 Meng-Chih Lee,5,6 Roger S McIntyre,7 Mong-Liang Lu,8 Yin-To Liao,9,10 Chih-Jung Yeh11,12 1Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 4U Come Joint Clinic, Taichung, Taiwan; 5Department of Family Medicine, Taichung Hospital, Taichung, Taiwan; 6College of Management, Chaoyang University of Technology, Taichung, Taiwan; 7University of Toronto, Toronto, ON, Canada; 8Department of Psychiatry, Wan-Fang Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan; 10Department of Psychiatry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 11Institute of Population Health Sciences, National Health Research Institutes, Taipei, Taiwan; 12School of Public Health, Chung Shan Medical University, Taichung, TaiwanCorrespondence: Yin-To Liao, Email je2tezy@yahoo.com.tw Chih-Jung Yeh, School of Public Health, Chung Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung, 402, Taiwan, Tel +886-4-24730022x12183, Fax +886-4-23248179, Email alexyeh@csmu.edu.twPurpose: Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period.Patients and Methods: A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of ≥ 8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups.Results: During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval [CI]: 2.02– 3.03), 1.95 (95% CI: 1.63– 2.32), and 1.23 (95% CI: 1.09– 1.39), respectively.Conclusion: The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex.Keywords: diabetes mellitus, depression, mortality, cohort

Chun-Hao Chen,1 Ming-Chyi Huang,2 Yi-Hang Chiu,3 I-Ming Chen,1,4 Chun-Hsin Chen,3,5 Mong-Liang Lu,3,5 Tsung-Yang Wang,1 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 3Department of Psychiatry, Wan-Fang Hospital, Taipei, Taiwan; 4Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 5Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen, Department of Psychiatry, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, 10002, Taiwan, Tel +886-2-2312-3456 ext. 66787, Fax +886-2-2381-3208, Email hsichungchen@ntu.edu.twObjective: This study aimed to investigate the relationship between eveningness preference and poor sleep quality and eventually examine the moderation effect of stress susceptibility.Methods: Individuals with non-acute major depressive disorder or bipolar affective disorder and healthy participants were recruited. The Composite Scale of Morningness (CSM) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate chronotype and sleep quality, respectively. Eysenck Personality Questionnaire, Tridimensional Personality Questionnaire, Perceived Stress Scale, and Beck Anxiety Inventory were used to formulate stress susceptibility and as indicator variables for empirical clustering by latent class analysis (LCA). Linear regression models were used to examine the relationship between chronotype preference and sleep quality. The interaction terms of CSM and stress susceptibility were examined for the moderation effect.Results: A total of 887 individuals were enrolled in this study, with 68.2% female and 44.1% healthy participants. Three subgroups were derived from LCA and designated as low stresssusceptibility (40.2%), moderate stress susceptibility (40.9%), and high stress susceptibility (18.8%) groups. After controlling for covariates, the CSM scores inversely correlated with PSQI scores [b (se)=− 0.02 (0.01), p=0.01], suggesting that individuals with eveningness preferences tend to have poor sleep quality. Moreover, stress susceptibility moderated the relationship between CSM and PSQI scores (p for interaction term = 0.04). Specifically, the inverse association between CSM and PSQI was more robust in the high stress susceptibility group than that in the low stress susceptibility group.Conclusion: Eveningness preference was associated with poor sleep quality, and this relationship was moderated by stress susceptibility.Keywords: chronotype, empirical clustering, moderation effect, stress susceptibility, sleep quality

Sze-Yu Chen,1 Chun-Hao Chen,1 Chen Lo,1 Mong-Liang Lu,2 Cheng-Dien Hsu,3 Yi-Hang Chiu,2 Chun-Hsin Chen,2 Shih-Ku Lin,4,5 Ming-Chyi Huang,5 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Wan-Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Psychosomatic Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; 4Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen Email hsichungchen@ntu.edu.twPurpose: This study aimed to elucidate the various co-occurring patterns of depressive symptomatology and sleep-wake-related disturbances (SWRDs) in patients with mood disorders.Patients and Methods: Individuals in non-acute states of major depressive disorder or bipolar disorder were recruited. The Beck Depression Inventory II (BDI-II) was utilized to evaluate depressive symptoms. BDI-II items were classified into three domains: cognitive, affective, and somatic. Between-domain differences with various SWRDs were examined. Latent class analysis was used to empirically classify participants using BDI-II items as indicator variables. Co-occurring patterns between domains of BDI-II items and SWRDs were re-examined in each subgroup to elucidate inter-individual differences.Results: In total, 657 participants were enrolled. Of participants, 66.8% were female, and 52.4% were diagnosed with major depressive disorder. Each BDI-II domain exhibited different co-occurring patterns. The somatic domain was most likely to co-occur with various SWRDs. Three subgroups were derived from latent class analysis and were designated as poor sleep quality and high insomnia (n=150), poor sleep quality and moderate insomnia (n=248), and poor sleep quality and low insomnia (n=159). The group with more severe insomnia presented with more severe depressive and anxiety symptoms. The three subgroups further differed in co-occurring patterns. From the low insomnia to high insomnia group, the associations with various SWRDs appeared in the sequence of somatic, affective, and cognitive domains.Conclusion: Co-occurring patterns between domains of depressive symptomatology with various SWRDs differ and may vary among individuals.Keywords: co-occurring, latent class analysis, mood disorders, sleep-wake-related disturbance, depression

Yu-Hung Fang,1 Meng-Jer Hsieh,2,3 Ming-Szu Hung,1,4,5 Yu-Ching Lin,1,3– 5 Liang-Tseng Kuo,5,6 Mong-Liang Lu,7 Bor-Show Tzang,8– 10 Vincent Chin-Hung Chen5,11 1Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Respiratory Therapy, College of Medicine, Chang Gung University, Chiayi, Taiwan; 3Division of Pulmonary Infection and Critical Care Medicine, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 4Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 5Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 6Division of Sports Medicine, Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; 7Department of Psychiatry, Wan Fang Hospital, and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan; 9Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan; 10Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 11Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, TaiwanCorrespondence: Vincent Chin-Hung ChenDepartment of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, No. 6, W. Sec., Jiapu Road, Puzi City, Chiayi County 61363, Taiwan, Republic of ChinaTel +886-5-3621000 ext. 2315Email cch1966@gmail.comBackground: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) concentrations were reported to decrease in patients with advanced cancer. However, the clinical significance of DHEA and DHEAS concentrations in patients with NSCLC receiving chemotherapy (CT) has not been sufficiently documented.Objective: To evaluate the correlation between mental health and hormone concentrations on patients with advanced non-small-cell lung cancer (NSCLC).Materials and Methods: The present study was a cross-sectional analysis based on a self-reported psychological investigation. Salivary samples were collected from 22 patients with advanced NSCLC after CT and 17 healthy controls. The concentrations of DHEA, DHEAS, and cortisol were analyzed to investigate their associations with the results of self-reported questionnaires on psychological health.Results: Patients with advanced NSCLC exhibited significantly higher Patient Health Questionnaire (PHQ-9) and Startle, Physiological arousal, Anger, and Numbness-Chinese version (SPAN-C) scores, poorer health conditions, lower sleep quality, and more severe fatigue after CT than did healthy controls, and salivary concentrations of DHEA and DHEAS were significantly lower among patients after CT than among controls. DHEAS concentrations were negatively associated with depression scores (PHQ-9, r = − 0.496, P = 0.019) and fatigue scores (Brief Fatigue Inventory-Taiwan, r = − 0.562, P = 0.006).Conclusion: Patients with advanced NSCLC after CT had lower DHEA and DHEAS concentrations than did controls. Lower DHEAS concentrations were associated with higher fatigue and depression scores.Keywords: cancer-related fatigue, chemotherapy, DHEA, DHEAS, lung cancer

Pei-Lun Chung,1 Chien-Wei Huang,2 Min-Jing Lee,1,3 Yao-Hsu Yang,4,5 Ko-Jung Chen,4 Mong-Liang Lu,6 Jun-Cheng Weng,1,7 Vincent Chin-Hung Chen1,3 1Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 2Division of Nephrology, Department of Medicine, School of Medicine, Kaohsiung Veterans General Hospital, and National Yang-Ming University, Taiwan; 3School of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 5Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 6Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, TaiwanCorrespondence: Vincent Chin-Hung ChenDepartment of Psychiatry, Chang Gung Memorial Hospital, Chiayi, TaiwanEmail cch1966@gmail.comPurpose: This study explored and compared the effects of depression and antidepressants on sexual dysfunction in men with diabetes mellitus (DM).Patients and Methods: Patients older than 18 years who had been newly diagnosed with DM (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 250) between 1999 and 2010 were identified from Taiwan’s National Health Insurance Research Database and were followed up until 2013. Patients with preexisting depression or sexual dysfunction were excluded. A total of 636,210 patients with DM were enrolled. These patients were divided into two groups: DM with comorbid depression and a matched cohort without depression. The groups were followed up until the end of 2010 for the first diagnosis of sexual dysfunction (ICD-9-CM codes 302.70, 302.71, 302.72, 302.74, 302.75, 302.76, 302.79, 607.84, and V417). A Cox proportional hazard model and a Cox regression model with time-dependent covariates were applied.Results: Patients with DM and depression had a higher risk of sexual dysfunction than those with DM without depression (hazard ratio [HR] =  1.44; 95% confidence interval [CI], 1.33– 1.55). The risk of sexual dysfunction was lower in the subgroup who used antidepressants (per 28 cumulative defined daily doses [cDDDs]), HR = 0.96; 95% CI, 0.94– 0.97). A significantly lower incidence of sexual dysfunction was also associated with the use of selective serotonin reuptake inhibitors (SSRIs, per 28 cDDD). The adjusted HR was 0.95 (95% CI, 0.93– 0.97). Subgroup analysis indicated that SSRI use was significantly associated with an amelioration of erectile dysfunction (per 28 cDDD), with an HR of 0.95 (95% CI, 0.92– 0.97).Conclusion: Male patients with DM and depression are at increased risk of sexual dysfunction. Antidepressant use had a small inverse association with the risk of sexual dysfunction in men with DM and depression. Antidepressants, in particular SSRIs, did not increase the risk of sexual dysfunction in this population.Keywords: selective serotonin reuptake inhibitor, SSRI, sexual functioning, diabetes mellitus, depression

Ana Isabel Wu Chou,1 Mong-Liang Lu,1,2 Winston W Shen1,2 1Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, 2Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan Abstract: Clozapine is an effective antipsychotic drug but is associated with serious side effects. Most treatment guidelines give no clear recommendations on regular monitoring of liver function tests, even though up to 60% of patients experience elevations in hepatic transaminases, with 15% to 30% experiencing an elevation two to three times greater than normal. Though elevations in liver function tests are often transient and asymptomatic, there are many reported cases of clozapine-induced hepatotoxicity, with damage to the liver, involvement of multiple organs, and even fulminant liver failure arising with moderate clozapine doses. This case report describes a Chinese woman who developed hepatotoxicity on a low dose of clozapine, and reviews the relevant literature. Keywords: hepatitis, antipsychotic adverse effects, drug-induced liver injury

The impact of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism on bladder cancer is unknown. We found no clear correlations between the FGFR4 genotype and risk of bladder cancer or pathological parameters. Neither the polymorphism nor TP53 mutation status was an independent predictor of prognosis, but they might act jointly on the disease-specific survival of patients.

Nellowe Candelario, Marvin Louis Roy Lu Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA Abstract: Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of antineoplastic agents. Several treatment regimens are used to address this problem. Fosaprepitant is a neurokinin-1 receptor blocker used in the prevention and treatment of CINV, especially for moderately and severely emetogenic chemotherapy. It is highly effective in the treatment of delayed CINV. Data from previous studies show that fosaprepitant is noninferior to aprepitant in the management of CINV. Fosaprepitant is given as a single-dose intravenous infusion, thus offering better patient compliance. The dose-limiting side effect of fosaprepitant is infusion-related reaction, ranging from pain at the infusion site to thrombophlebitis. This side effect has been reported with coadministration of anthracycline agents. Keywords: chemotherapy nausea and vomiting, fosaprepitant, neurokinin inhibitor

Background: Both lipid metabolism and cyclic RNAs (circRNAs) have been found to be involved in pancreatic adenocarcinoma (PAAD) progression, but the relationship between lipid metabolism and circRNAs remains unclear., Methods: The expression levels of miR-223-3p, circ_0124346, and acyl-CoA synthetase long chain family member 3 (ACSL3) were determined through qRT-PCR and Western blot analysis. Cell proliferation was evaluated using the CCK-8 and EdU incorporation assays. Cholesterol (CH) and triglyceride (TG) levels were quantified using relevant kits. The relationships between miR-223-3p and circ_0124346 or ACSL3 mRNA were examined by bioinformatics analysis, luciferase reporter, RNA-RNA pull-down, and RIP assays., Results: We observed a significant elevation in circ_0124346 expression in both pancreatic adenocarcinoma (PAAD) tissues and cell lines, and its expression level was shown to be correlated with tumor size. Circ_0124346 stimulated cell proliferation and facilitated lipid synthesis in PAAD cells. Additionally, we found that circ_0124346 functioned as a sponge for miR-223-3p, preventing miR-223-3p's binding to the 3'-UTR of ACSL3 mRNA, which subsequently led to an elevation in ACSL3 expression and promoted lipid synthesis. Accordingly, circ_0124346 knockdown resulted in a significant decrease in lipid synthesis and cell proliferation in PAAD cells, with partial reversal of these effects achieved via inhibiting miR-223-3p or overexpressing ACSL3., Conclusion: Our study demonstrated that circ_0124346 regulates lipid metabolism in PAAD cells via the miR-223-3p/ACSL3 axis, suggesting that targeting circ_0124346 may serve as a potential strategy for treating PAAD and assisting in its diagnosis., Competing Interests: Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Ethics Committee of the Taizhou Central Hospital (Taizhou University Hospital) (approval no. 2021 K-11–13). Informed consent was obtained from all individual participants included in the study. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Mild Cognitive Impairment (MCI) and dementia are becoming more common with an aging population, and the numbers are expected to rise. These conditions can have a significant impact on patients, family, and health care systems. Lifestyle changes including physical activity, nutrition, quality sleep, socialization, cognitive activity and mental stimulation, routine medical care, and mental health care have the potential to prevent cognitive and functional decline and optimize daily living in all individuals, including those with MCI and early neurodegenerative disease. Brain Boosters is an important group intervention used to provide psychoeducation on lifestyle factors and strategies that can improve brain health, cognition, and functioning., Competing Interests: Disclosure The authors have nothing to disclose., (Published by Elsevier Inc.)

Introduction: The study aimed to evaluate the effects of Pleurotus Spent Mushroom Substrate (P.SMS) on the rumen microbiota, encompassing bacteria and fungi, as well as their interactions in Hu sheep., Methods: A total of forty-five 3-month-old Hu sheep were randomly assigned to five groups. Each group was fed diets in which whole-plant corn silage (WPCS) was substituted with P.SMS at varying levels: 0% (CON), 5% (PSMS5), 10% (PSMS10), 15% (PSMS15), or 20% (PSMS20)., Results: The results indicated that higher proportions of P.SMS during the experimental period might have a detrimental effect on feed utilization efficiency, kidney function, and blood oxygen-carrying capacity. Notably, moderate levels of P.SMS, specifically below 15%, were associated with improvements in rumen NH 3 -N levels and absorption capacity. The results indicated that (1) PSMS20 exhibited a significantly higher feed-to-gain ratio compared to CON ( P  < 0.05); (2) PSMS15 showed a significantly higher NH 3 -N content than CON, PSMS5, and PSMS20. Additionally, PSMS10 and PSMS20 had elevated concentrations of NH 3 -N compared to CON and PSMS5 ( P  < 0.05); (3) The length and width of rumen papillae were significantly greater in PSMS20 compared to CON and PSMS5 ( P  < 0.05); (4) Creatinine levels were significantly higher in PSMS20 than in CON, PSMS5, and PSMS10 ( P  < 0.05); (5) By the conclusion of the experiment, hemoglobin concentration in PSMS20 showed a significant increase compared to CON ( P  < 0.05). Furthermore, the addition of P.SMS influenced microorganisms at both the phylum and genus levels: (1) At the phylum level, the prevalence of Patescibacteria was significantly lower in PSMS20 compared to the other groups; (2) PSMS15 exhibited significantly higher relative abundances of Basidiomycota compared to CON and PSMS10, while PSMS20 also demonstrated significantly higher relative abundances compared to CON ( P  < 0.05); (3) At the genus level, the prevalence of Candidatus&#95;Saccharimonas in PSMS20 was significantly lower than in PSMS5, PSMS10, and PSMS15. Conversely, the prevalence of Phanerochaete in PSMS15 was notably higher than in CON and PSMS10, and it was also significantly elevated in PSMS20 compared to CON ( P  < 0.05); (4) Correlation analysis indicated no significant correlation between changes in the structure of bacterial and fungal communities., Discussion: Considering these findings, a high percentage of P.SMS negatively impacted feed utilization efficiency, blood oxygen carrying capacity, and kidney function, while a moderate percentage of P.SMS promotes rumen absorption capacity, indicating that feeding 10% P.SMS is optimal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Yuan, Rehemujiang, Li, Hu, Duan, Zhang, Diao, Deng and Xu.)

P21 activated kinase 6 (PAK6) is a serine-threonine kinase with physiological expression enriched in the brain and overexpressed in a number of human tumors. While the role of PAK6 in cancer cells has been extensively investigated, the physiological function of the kinase in the context of brain cells is poorly understood. Our previous work uncovered a link between PAK6 and the Parkinson's disease (PD)-associated kinase LRRK2, with PAK6 controlling LRRK2 activity and subcellular localization via phosphorylation of 14-3-3 proteins. Here, to gain more insights into PAK6 physiological function, we performed protein-protein interaction arrays and identified a subgroup of PAK6 binders related to ciliogenesis. We confirmed that endogenous PAK6 localizes at both the centrosome and the cilium, and positively regulates ciliogenesis not only in tumor cells but also in neurons and astrocytes. Notably, PAK6 rescues ciliogenesis and centrosomal cohesion defects associated with the G2019S but not the R1441C LRRK2 PD mutation. Since PAK6 binds LRRK2 via its GTPase/Roc-COR domain and the R1441C mutation is located in the Roc domain, we used microscale thermophoresis and AlphaFold2-based computational analysis to demonstrate that PD mutations in LRRK2 affecting the Roc-COR structure substantially decrease PAK6 affinity, providing a rationale for the differential protective effect of PAK6 toward the distinct forms of mutant LRRK2. Altogether, our study discloses a novel role of PAK6 in ciliogenesis and points to PAK6 as the first LRRK2 modifier with PD mutation-specificity., (© 2024. The Author(s).)

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI treatment., 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 © 2024 Elsevier B.V. All rights reserved.)

The mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults. Whether targeting this pathway is beneficial to brain injury remains unclear. In this study, we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis, tauopathy, lesion size, and behavioral deficits. Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain. Mechanistically, the Citron homology domain acted as a dominant-negative mutant, impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway. These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

The term "schizophrenia" can indeed carry stigmatizing connotations. Proposals to rename schizophrenia have emerged as a potential strategy to alleviate this stigma, but the impact of such a change is not yet fully understood. In several Asian countries that have adopted a new name for schizophrenia, there is evidence that renaming is associated with improved attitudes towards individuals with schizophrenia and an increased willingness to disclose diagnoses. However, the portrayal of schizophrenia in the media seems unaffected by these name changes. In other countries where "schizophrenia" is still the standard term, alternative names have been suggested, but research on their effectiveness in reducing stigma shows mixed results. Mental health professionals frequently support a name change, recognizing the term's negative implications. However, it is crucial to recognize that a mere semantic revision, devoid of substantial conceptual alterations, may only offer a temporary decrease in stigma. Thus, renaming schizophrenia, coupled with a re-conceptualization of the disorder, may be a constructive step toward reducing its stigmatization., Competing Interests: Declaration of Competing Interest The authors declare no competing interests, (Copyright © 2024. Published by Elsevier B.V.)

Valproic acid (VPA) has broad efficacy against several seizures but causes liver injury limiting its prolonged clinical use. Some studies have demonstrated that VPA-induced hepatotoxicity is characterized by microvesicular hepatic steatosis. However, novel detailed mechanisms to explain VPA-induced hepatic steatosis and experimentally rigorously validated protective agents are still lacking. In this study, 8-week-old C57BL/6J mice were gavaged with VPA (500 mg/kg/d) for 4 weeks to establish an in vivo model of VPA-induced chronic liver injury. Quantitative proteomic and non-targeted lipidomic analyses were performed to explore the underlying mechanisms of VPA-induced hepatotoxicity. As a result, VPA-induced hepatotoxicity is associated with impaired autophagic flux, which is attributed to lysosomal dysfunction. Further studies revealed that VPA-induced lysosomal membrane permeabilization (LMP), allows soluble lysosomal enzymes to leak into the cytosol, which subsequently led to impaired lysosomal acidification. A lower abundance of glycerophospholipids and an increased abundance of lysophospholipids in liver tissues of mice in the VPA group strongly indicated that VPA-induced LMP may be mediated by the activation of phospholipase PLA2G4A. Metformin (Met) acted as a potential protective agent attenuating VPA-induced liver dysfunction and excessive lipid accumulation. Molecular docking and cellular thermal shift assays demonstrated that Met inhibited the activity of PLA2G4A by directly binding to it, thereby ameliorating VPA-induced LMP and autophagic flux impairment. In conclusion, this study highlights the therapeutic potential of targeting PLA2G4A-mediated lysosomal dysfunction in VPA-induced hepatotoxicity., 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 © 2024. Published by Elsevier Inc.)

Carbon based materials are widely used in the preparation of microwave absorption materials due to their low density, high attenuation loss and large specific surface area. However, their high conductivity usually leads to high reflection loss. In this study, multi-layer heterogeneous interfaces were constructed in liquid metal graphite hybrid powder to reduce reflection loss and enhance microwave absorption performance. Gallium oxide (Ga 2 O 3 ) layer was formed in Ga coated graphite powder to improve impedance matching and attenuation constant via an annealing treatment. Specifically, the hybrid particles with 50 wt% Ga and being annealed at 120 °C for 2 h have a minimum reflection loss (RL min ) value of -42.68 dB and a maximum effective absorption bandwidth (EAB) of 4.11 GHz at a thickness of 3.3 mm. The hybrid particles not only have multi-layer structures with different electrical conductivity, but also form heterojunctions between different interfaces, which can further enhance dipole and interfacial polarization., 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 © 2024 Elsevier Inc. All rights reserved.)

Background: The prevention of coronary artery disease (CAD) faces dual challenges: the aspirin-induced gastrointestinal injury, and the residual cardiovascular risk after statin treatment. Geraniol acetate (Gefarnate) is an anti-ulcer drug. It was reported that geraniol might participate in lipid metabolism through a variety of pathways. The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia., Methods: In this prospective, open-label, randomized, controlled trial, 69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group, received gefarnate (100 mg/3 times a day) combined with statin and statin alone, respectively. At baseline and after one-month treatment, the levels of plasma triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol were tested., Results: After one-month gefarnate treatment, triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L ( P = 0.0018), LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L ( P = 0.0004), HDL-C level increased from 0.97 mmol/L to 1.17 mmol/L ( P = 0.0228). Based on statin therapy, gefarnate could significantly reduce the plasma triglyceride level ( P = 0.0148) and increase the plasma HDL-C level ( P = 0.0307). Although the LDL-C and total cholesterol levels tended to decrease, there was no statistically significant difference., Conclusions: The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia. This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients., (© 2024 JGC All rights reserved; www.jgc301.com.)

Background: This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting., Methods: This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety., Results: A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients., Conclusions: Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality., (© 2024. The Author(s).)

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 μM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg -1 ·d -1 , i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Photothermal immunotherapy has shown great promise in the treatment of tumor metastasis. However, the thermal resistance of tumor cells substantially compromises the treatment effect of photothermal immunotherapy. Herein, a high-performance organic pyroelectric nanoplatform, t Bu-TPAD-BF 2 nanoparticles (NPs), is rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible t Bu-TPAD-BF 2 NPs with excellent pyroelectric and photothermal conversion properties are constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with t Bu-TPAD-BF 2 NPs causes an apparent temperature elevation upon near-infrared (NIR) laser irradiation, inducing potent immunogenic cell death (ICD). Additionally, the temperature variations under alternating NIR laser irradiation facilitate reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrate that t Bu-TPAD-BF 2 NPs in combination with NIR laser exposure notably inhibit primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling reveals that treatment with t Bu-TPAD-BF 2 NPs markedly suppresses metastasis under NIR laser illumination by downregulating metastasis-related genes and upregulating immune response-associated pathways. Therefore, this study provides a strategy for designing high-performance pyroelectric nanoplatforms to effectively cure tumor metastasis, thereby overcoming the inherent shortcomings of photothermal immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Danjiangkou Reservoir is a critical water source for the South-to-North Water Diversion Project, which harbors a diverse bacterioplankton community with varying depths, and the understanding of its nitrogen and phosphorus cycle and associated driving factors remains limited. In this study, we selected five ecological sites within Danjiangkou Reservoir and conducted metagenomics analysis to investigate the vertical distribution of bacterioplankton communities in the surface, middle, and bottom layers. Furthermore, we analyzed and predicted the function of nitrogen and phosphorus cycles, along with their driving factors. Our findings revealed the dominance of Proteobacteria, Actinobacteria, and Planctomycetes in the Danjiangkou Reservoir. Significant differences were observed in the structure of bacterioplankton communities across different depths, with temperature （ T ）, oxidation-reduction potential （ORP）, dissolved oxygen （DO）, and Chla identified as primary factors influencing the bacterioplankton composition. Analysis of nitrogen cycle functional genes identified 39 genes, including gltB , glnA , gltD , gdhA , NRT , etc., which were involved in seven main pathways, encompassing nitrogen fixation, nitrification, denitrification, and dissimilatory nitrate reduction. Phosphorus cycle function gene analysis identified 54 genes, including pstS , ppx - gppA , glpQ , ppk1 , etc., primarily participating in six main pathways, including organic P mineralization, inorganic P solubilization, and regulatory. Cluster analysis indicated that different depths were significant factors influencing the composition and abundance of nitrogen and phosphorus cycle functional genes. The composition and abundance of nitrogen and phosphorus cycle functional genes in the surface and bottom layers differed and were generally higher than those in the middle layer. Deinococcus , Hydrogenophaga , Limnohabitans , Clavibacter , and others were identified as key species involved in the nitrogen and phosphorus cycle. Additionally, we found significant correlations between nitrogen and phosphorus cycle functional genes and environmental factors such as DO, pH, T , total dissolved solids （TDS）, electrical conductivity （EC）, and Chla. Furthermore, the content of these environmental factors exhibited depth-related changes in the Danjiangkou Reservoir, resulting in a distinct vertical distribution pattern of bacterioplankton nitrogen and phosphorus cycle functional genes. Overall, this study sheds light on the composition, function, and influencing factors of bacterioplankton communities across different layers of Danjiangkou Reservoir, offering valuable insights for the ecological function and diversity protection of bacterioplankton in this crucial reservoir ecosystem.

Background: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency., Objectives: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life., Methods: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway., Results: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1β), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks., Conclusions: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between workplace psychosocial, organization, and physical risk factors with low back pain (LBP) among US workers., Methods: 2015 National Health Interview Survey data were analyzed to calculate the prevalence rates and prevalence ratios for LBP across levels of workplace psychosocial and organizational risk factors among 17,464 US adult workers who worked ≥20 hours per week. Results were also stratified by workplace physical exertion., Results: The adjusted prevalence rates of LBP were significantly elevated for workers reporting high job demand, low job control, work-family imbalance, bullying, job insecurity, working alternate shifts, and physical exertion. Job control and nonstandard shifts were significantly associated with LBP only among those who reported low/no physical exertion., Conclusions: LBP prevalence was associated with select workplace psychosocial and organization risk factors. Stratification by physical exertion modified multiple associations., Competing Interests: Conflict of Interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 μg/mL) alleviated Aβ and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD., 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 © 2024 Elsevier B.V. All rights reserved.)

Objective: A decline in musculoskeletal health during pregnancy is an underappreciated adverse outcome of pregnancy that can have immediate and long-term health consequences. High physical job demands are known risk factors for nontraumatic musculoskeletal disorders in the general working population. Evidence from meta-analyses suggest that occupational lifting and prolonged standing during pregnancy may increase risk of adverse pregnancy outcomes. This systematic review examined associations between occupational lifting or postural load in pregnancy and associated musculoskeletal disorders and related sequalae., Data Sources: Five electronic databases (Medline, Embase, CINAHL, NIOSHTIC-2, and Ergonomic Abstracts) were searched from 1990 to July 2022 for studies in any language. A Web of Science snowball search was performed in December 2022. Reference lists were manually reviewed., Study Eligibility Criteria: Eligible studies reported associations between occupational lifting or postural load and musculoskeletal health or sequelae (eg, employment outcomes) among pregnant and postpartum workers., Methods: Data were extracted using a customized form to document study and sample characteristics; and details of exposures, outcomes, covariates, and analyses. Investigators independently assessed study quality for 7 risk-of-bias domains and overall utility, with discrepant ratings resolved through discussion. A narrative synthesis was conducted due to heterogeneity., Results: Sixteen studies (11 cohort studies, 2 nested case-control studies, and 3 cross-sectional studies) from 8 countries were included (N=142,320 pregnant and N=1744 postpartum workers). Limited but consistent evidence with variable quality ratings, ranging from critical concern to high, suggests that pregnant workers exposed to heavy lifting (usually defined as ≥22 lbs or ≥10 kg) may be at increased risk of functionally limiting pelvic girdle pain and antenatal leave. Moreover, reports of dose-response relationships suggest graded risk levels according to lifting frequency, ranging from 21% to 45% for pelvic girdle pain and 58% to 202% for antenatal leave. Limited but consistent evidence also suggests that postural load increases the risk of employment cessation., Conclusion: Limited but consistent evidence suggests that pregnant workers exposed to heavy lifting and postural load are at increased risk of pelvic girdle pain and employment cessation. Job accommodations to reduce exposure levels may promote safe sustainable employment for pregnant workers., (Published by Elsevier Inc.)

Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.

Background: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups., Aims: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan., Method: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses., Results: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values., Conclusions: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD., 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 © 2024 Elsevier Inc. All rights reserved.)

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a 99m Tc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration.

The green and efficient remediation of soil cadmium (Cd) is an urgent task, and plant-microbial joint remediation has become a research hotspot due to its advantages. High-throughput sequencing and metabolomics have technical advantages in analyzing the microbiological mechanism of plant growth-promoting bacteria in improving phytoremediation of soil heavy metal pollution. In this experiment, a pot trial was conducted to investigate the effects of inoculating the plant growth-promoting bacterium Enterobacter sp. VY on the growth and Cd remediation efficiency of the energy plant Hybrid pennisetum . The test strain VY-1 was analyzed using high-throughput sequencing and metabolomics to assess its effects on microbial community composition and metabolic function. The results demonstrated that Enterobacter sp. VY-1 effectively mitigated Cd stress on Hybrid pennisetum , resulting in increased plant biomass, Cd accumulation, and translocation factor, thereby enhancing phytoremediation efficiency. Analysis of soil physical-chemical properties revealed that strain VY-1 could increase soil total nitrogen, total phosphorus, available phosphorus, and available potassium content. Principal coordinate analysis (PCoA) indicated that strain VY-1 significantly influenced bacterial community composition, with Proteobacteria, Firmicutes, Chloroflexi, among others, being the main differential taxa. Redundancy analysis (RDA) revealed that available phosphorus, available potassium, and pH were the primary factors affecting bacterial communities. Partial Least Squares Discriminant Analysis (PLS-DA) demonstrated that strain VY-1 modulated the metabolite profile of Hybrid pennisetum rhizosphere soil, with 27 differential metabolites showing significant differences, including 19 up-regulated and eight down-regulated expressions. These differentially expressed metabolites were primarily involved in metabolism and environmental information processing, encompassing pathways such as glutamine and glutamate metabolism, α-linolenic acid metabolism, pyrimidine metabolism, and purine metabolism. This study utilized 16S rRNA high-throughput sequencing and metabolomics technology to investigate the impact of the plant growth-promoting bacterium Enterobacter sp. VY-1 on the growth and Cd enrichment of Hybrid pennisetum , providing insights into the regulatory role of plant growth-promoting bacteria in microbial community structure and metabolic function, thereby improving the microbiological mechanisms of phytoremediation.

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings., Competing Interests: None., (AJCR Copyright © 2024.)

The citrus industry loses a significant amount of mandarin fruits either before or shortly after harvesting due to rind disorder. Different citrus cultivars are impacted by a physiological rind disorder that lowers fruit quality and marketability. Although the primary etiology of this condition is unknown, changes in relative humidity (RH) and rind water status can make it worse. The damage is initiated in the fall, especially following rain. It begins with irregular water-soaked areas that develop into dark-brown, necrotic lesions covering large portions of the fruit's surface. The damage is evident in some citrus types such as Satsuma Owari mandarins and other cultivars. In this study, we attempted to understand and control the occurrence of this kind of rind disorder in Satsuma Owari mandarins growing under California conditions. Our data showed that fruit located in the outer part of the canopy suffer more than fruit in the interior canopy. We were able to reduce this damage in Satsuma Owari mandarins by applying 2,4-dichlorophenoxyacetic acid (2,4-D) at 16 milligrams/Liter (mg/L), gibberellic acid (GA 3 ) at 20 mg/L, or Vapor Gard ® at 0.5 percent ( v / v ) at the color break stage. However, GA 3 caused a delay in color development by approximately four weeks. GA 3 -treated fruit changed their color completely four weeks after the control, and the rind damage was at a very low percentage. Delaying rind senescence could be a good strategy to reduce the damage in mandarin orchards. Data showed that in addition to the benefits of the different treatments on preventing rind disorder at harvest, they have some beneficial effects during storage for four weeks either at 0.5 or 7.5 °C.

Introduction: Autologous fat grafting is a method of improving aesthetic outcomes after both breast reconstruction and aesthetic surgery through volume enhancement and tissue contouring. Long-lasting effects are linked to greater patient satisfaction and more optimal augmentation results. Harvesting, processing, and injection techniques may all affect the longevity of deformity filling. Our objective is to evaluate the effect of lipoaspirate processing modality on longitudinal volume retention after surgery., Methods: A prospective, single-institution, randomized control trial placed consented postmastectomy fat grafting patients into 1 of 3 treatment arms (active filtration, low-pressure decantation, and standard decantation) in a 1:1:1 ratio. A preoperative 3-dimensional scan of the upper torso was taken as baseline. At the 3-month postoperative visit, another 3D scan was taken. Audodesk Meshmixer was used to evaluate the volume change., Results: The volume of fat injected during the initial procedure did not differ significantly between the treatment arms (P > 0.05). Both active filtration and low-pressure decantation resulted in higher percentage volume retention than traditional decantation (P < 0.05). Active filtration and low-pressure decantation exhibited comparable degrees of fat maintenance at 3 months (P > 0.05)., Discussion: Compared with using traditional decantation as the lipoaspirate purification technique, active filtration and low-pressure decantation may have led to higher levels of cell viability by way of reduced cellular debris and other inflammatory components that may contribute to tissue resorption and necrosis. Further immunohistochemistry studies are needed to examine whether active filtration and low-pressure decantation lead to lipoaspirates with more concentrated viable adipocytes, progenitor cells, and factors for angiogenesis., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Childhood trauma has been linked to increased risk of schizophrenia and social dysfunction, and oxytocin and its receptor gene have been implicated in regulating social behavior. This study investigated the potential role of oxytocin and oxytocin receptor gene (OXTR) in mediating the effects of childhood trauma on social functioning in schizophrenia., Methods: The study consisted of 382 patients with schizophrenia and 178 healthy controls who were assessed using the Taiwanese version of the Childhood Trauma Questionnaire (CTQ-SF), the Social Functioning Scale (SFS), and plasma oxytocin levels. DNA was extracted to genotype the OXTR and ten single-nucleotide polymorphisms (SNPs; rs2254298, rs237885, rs237887, rs237899, rs53576, rs9840864, rs13316193, rs7632287, rs1042778, and rs237895) were selected., Results: Patients with schizophrenia showed higher CTQ-SF scores ( t = 12.549, p < 0.001), lower SFS scores ( t = -46.951, p < 0.001), and lower plasma oxytocin levels ( t = -5.448, p < 0.001) compared to healthy controls. The study also found significant differences in OXTR SNPs between both groups, with risk alleles being more prevalent in patients with schizophrenia ( t = 2.734, p = 0.006). Results indicated a significant moderated mediation effect, with oxytocin and the OXTR SNPs partially mediating the relationship between childhood trauma exposure and social functioning in patients with schizophrenia (index of mediation = 0.038, 95% CI [0.033-0.044])., Conclusions: The findings suggest that oxytocin and its receptor gene may be promising targets for interventions aimed at improving social functioning in patients with a history of childhood trauma and schizophrenia. However, further research is needed to fully understand these effects and the potential of oxytocin-based interventions in this population.

Purpose: Breast anesthesia after mastectomy and reconstruction has been an ongoing concern with few improvements made in recent years. At present, there is a lack of studies evaluating the impact of comorbidities on sensation restoration. Identifying risk factors (RF) will be helpful with preoperative counseling., Methods: This was a prospective study on patients who underwent mastectomy and immediate implant-based or neurotized deep inferior epigastric perforator (DIEP) flap-based reconstruction. Neurosensory testing was performed at predefined time points using a pressure specified device. Patients were stratified based on reconstruction type and comorbidities, including obesity (≥30 kg/m2), age (>55 years), hypertension, alcohol use, and smoking status. Sensory comparisons among the comorbidity groups were conducted using unpaired 2-sample t tests., Results: A total of 239 patients were included in this study with 109 patients in the implant cohort and 131 patients in the DIEP cohort. One patient underwent bilateral reconstruction using both reconstructive modalities. Preoperatively, age older than 55 years was identified as an RF for reduced breast sensation in the implant cohort (difference in threshold, 10.7 g/mm2), whereas obesity was identified as an RF in the DIEP cohort (difference in threshold, 8 g/mm2). During the first 2 years postreconstruction, age older than 55 years and tobacco use history were found to be negatively correlated with breast sensation for both cohorts. With DIEP reconstruction specifically, obesity was identified as an additional RF during the early postoperative period. Of note, none of the comorbidities were found to be long-term RFs for reduced breast sensitivity. All breast sensation levels returned to comparable levels across all comorbidities by 4 years postreconstruction., Conclusions: Currently, various comorbidities have been recognized as RFs for several postoperative complications including extended postoperative stay, necrosis, infection, and reoperation. However, our findings suggest that, although age, smoking history, and obesity showed transient associations with reduced breast sensation during the initial years postreconstruction, they play no role in the long-term potential of sensory nerve regeneration., Competing Interests: Conflicts of interest and source of funding: Dr Otterburn formerly received research support from AxoGen Inc (Alachua, FL) to evaluate return of sensation after breast reconstruction. All other authors have no personal financial disclosures or commercial associations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Loss of breast sensation after mastectomy has been well documented. Postoperative reinnervation of the breast is influenced by factors including reconstructive technique, patient comorbidities, and adjuvant treatment. However, little attention has been paid to the differences in sensation across regions of the breast and the impact of reconstructive method on these regional differences over time., Methods: Patients undergoing nipple-sparing mastectomy with immediate autologous or alloplastic reconstruction were prospectively followed. Neurosensory testing was performed in 9 breast regions using a pressure-specified sensory device. Patients were stratified by reconstructive technique, and regional sensation was compared at different preoperative and postoperative time points using Student t tests., Results: One hundred ninety-two patients were included; 106 underwent autologous reconstruction via neurotized deep inferior epigastric artery perforator flap, and 86 underwent 2-stage alloplastic reconstruction. Preoperative sensation thresholds did not differ between reconstructive cohorts in any region and averaged 18.1 g/mm2. In the first year after mastectomy, decreased sensation was most pronounced in the inner breast regions and at the nipple areolar complex (NAC) in both reconstructive cohorts. At 4 years postoperatively, sensation increased the most at the NAC in the alloplastic cohort (34.0 g/mm2 decrease) and at the outer lateral region in the autologous cohort (30.4 g/mm2 threshold decrease). The autologous cohort experienced improved sensation compared with the alloplastic cohort in 5 of 9 regions at 1 year postoperatively, and in 7 of 9 regions at 4 years postoperatively; notably, only sensation at the outer superior and outer medial regions did not differ significantly between cohorts at 4 years postoperatively., Conclusions: Although patients undergoing breast reconstruction experience increased breast sensation over time, the return of sensation is influenced by type of reconstruction and anatomic region. Regions closer to and at the NAC experience the greatest loss of sensation after mastectomy, although the NAC itself undergoes the most sensation recovery of any breast region in those with alloplastic reconstruction.Autologous reconstruction via a neurotized deep inferior epigastric artery perforator flap results in increased return of sensation compared with alloplastic reconstruction, particularly in the inferior and lateral quadrants of the breast., Competing Interests: Conflicts of interest and sources of funding: D.M.O. formerly received research support from AxoGen Inc (Alachua, FL) to evaluate return of sensation after autologous perforator flap breast reconstruction. All other authors have no personal financial disclosures or commercial associations. No funding was received for this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Clozapine is the primary antipsychotic (APD) for treatment-resistant schizophrenia (TRS). However, only 40% of patients with TRS respond to clozapine, constituting a subgroup of clozapine-resistant patients. Recently, the neuropeptide orexin-A was shown to be involved in the pathophysiology of schizophrenia. This study evaluated the association of orexin-A levels with the clozapine response in patients with TRS., Methods: We recruited 199 patients with schizophrenia, including 37 APD-free and 162 clozapine-treated patients. Clozapine-treated patients were divided into clozapine-responsive ( n  = 100) and clozapine-resistant ( n  = 62) groups based on whether they had achieved psychotic remission defined by the 18-item Brief Psychiatric Rating Scale (BPRS-18). We compared blood orexin-A levels among the three groups and performed regression analysis to determine the association of orexin-A level with treatment response in clozapine-treated patients. We also explored the correlation between orexin-A levels and cognitive function, assessed using the CogState Schizophrenia Battery., Results: Clozapine-responsive patients had higher orexin-A levels than clozapine-resistant and APD-free patients. Orexin-A level was the only factor significantly associated with treatment response after adjustment. Orexin-A levels were negatively correlated with BPRS-18 full scale and positive, negative, and general symptoms subscale scores. We also observed a positive correlation between orexin-A levels and verbal memory, visual learning and memory, and working memory function., Conclusions: This cross-sectional study showed that higher levels of orexin-A are associated with treatment response to clozapine in patients with TRS. Future prospective studies examining changes in orexin-A level following clozapine treatment and the potential benefit of augmenting orexin-A signaling are warranted., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We previously identified solute carrier family 7 member 2 (SLC7A2) as one of the top upregulated genes when normal Huntingtin was deleted. SLC7A2 has a high affinity for L-arginine. Arginine is implicated in inflammatory responses, and SLC7A2 is an important regulator of innate and adaptive immunity in macrophages. Although neuroinflammation is clearly demonstrated in animal models and patients with Huntington's disease (HD), the question of whether neuroinflammation actively participates in HD pathogenesis is a topic of ongoing research and debate. Here, we studied the role of SLC7A2 in mediating the neuroinflammatory stress response in HD cells. RNA sequencing (RNA-seq), quantitative RT-PCR and data mining of publicly available RNA-seq datasets of human patients were performed to assess the levels of SLC7A2 mRNA in different HD cellular models and patients. Biochemical studies were then conducted on cell lines and primary mouse astrocytes to investigate arginine metabolism and nitrosative stress in response to neuroinflammation. The CRISPR-Cas9 system was used to knock out SLC7A2 in STHdhQ7 and Q111 cells to investigate its role in mediating the neuroinflammatory response. Live-cell imaging was used to measure mitochondrial dynamics. Finally, exploratory studies were performed using the Enroll-HD periodic human patient dataset to analyze the effect of arginine supplements on HD progression. We found that SLC7A2 is selectively upregulated in HD cellular models and patients. HD cells exhibit an overactive response to neuroinflammatory challenges, as demonstrated by abnormally high iNOS induction and NO production, leading to increased protein nitrosylation. Depleting extracellular Arg or knocking out SLC7A2 blocked iNOS induction and NO production in STHdhQ111 cells. We further examined the functional impact of protein nitrosylation on a well-documented protein target, DRP-1, and found that more mitochondria were fragmented in challenged STHdhQ111 cells. Last, analysis of Enroll-HD datasets suggested that HD patients taking arginine supplements progressed more rapidly than others. Our data suggest a novel pathway that links arginine uptake to nitrosative stress via upregulation of SLC7A2 in the pathogenesis and progression of HD. This further implies that arginine supplements may potentially pose a greater risk to HD patients., (© 2024. The Author(s).)

Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in RAB31 expression in the oxaliplatin-resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight RAB31's powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta-databases, RAB31 RNA levels were continually detected in colorectal tissue arrays. Additionally, RAB31 protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. RAB31 expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial-type marker CDH1 was suppressed in RAB31 overexpression models, whereas the expression of the mesenchymal-type markers SNAI1 and SNAI2 increased. Notably, RAB31 -induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that RAB31 /AGR2 axis-mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that RAB31 alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer., Competing Interests: The authors disclosed no conflicts. CRC tissues were recovered from the Department of Pathology, Taipei Municipal Wan Fang Hospital (Taipei, Taiwan), with approval from the Institutional Review Board (TMU‐IRB 99049)., (© 2024 The Authors. Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Childhood trauma has been linked to schizophrenia, but underlying biological mechanisms remain elusive. This study explored the potential role of plasma oxytocin as a mediator in the relationship between childhood trauma and the psychopathology of schizophrenia. 160 patients with schizophrenia and 80 age- and sex-matched healthy controls were assessed for childhood trauma experiences using the Childhood Trauma Questionnaire and structured interviews. Psychopathology was evaluated using the Positive and Negative Syndrome Scale and plasma oxytocin levels were measured. Results showed that patients with schizophrenia had lower oxytocin levels and higher childhood trauma scores than healthy controls. There was a significant correlation between childhood trauma scores and psychopathology, with plasma oxytocin levels being inversely associated with psychopathology, except for positive symptoms. Hierarchical regression analysis indicated that both childhood trauma scores and plasma oxytocin levels significantly predicted psychopathology. Plasma oxytocin levels partially mediated the relationship between childhood trauma and schizophrenia psychopathology. This study underscores the potential role of oxytocin in bridging the gap between childhood trauma and schizophrenia., (© 2024. The Author(s).)

Since the coronavirus disease 2019 (COVID-19) epidemic, insomnia has become one of the longer COVID-19 symptoms. This study aimed to investigate insomnia among COVID-19 survivors and explore the occurrence and influencing factors of insomnia. A cross-sectional study was performed from December 2022 to February 2023 through an online questionnaire star survey with 8 questions. The insomnia severity index scale (ISI) was used to assess the severity of insomnia. Univariate analysis was used to analyze the factors related to COVID-19 infection. A total of 564 participants (183 males and 381 females) were surveyed in the present study. The prevalence of insomnia was 63.12%. Among these insomnia patients, there were 202 (35.82%) with sub-threshold symptoms, 116 (20.57%) with moderate symptoms, and 38 (6.74%) with severe symptoms. Univariate analysis indicated that there were statistically significant differences in the prevalence of insomnia among COVID-19 survivors of different ages, occupations, and educational levels (P < .05). Of the 356 insomnia patients, 185 (51.97%) did not take any measures against insomnia, while those who took drugs only, physical exercise only, drugs and physical exercise, and other measures were 90 (25.28%), 42 (11.80%), 17 (4.78%), and 22 (6.18%), respectively. Additionally, of the 107 insomnia patients with drug therapy, 17 (15.89%) took estazolam, 16 (14.95%) took alprazolam, 39 (36.45%) took zopiclone, and 35 (32.71%) took other drugs to improve insomnia symptoms. The prevalence of insomnia symptoms remains high among COVID-19 survivors in China. Education level and occupation may be the influencing factors. Unfortunately, most patients with insomnia do not take corresponding treatment measures., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa&#95;circ&#95;0002395 (circ&#95;0002395) in both PAAD tissues and cell lines. This up-regulation of circ&#95;0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ&#95;0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ&#95;0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ&#95;0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The lymphocyte-related ratios, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) are new measures of inflammation within the body. Few studies have investigated the inflammatory response of patients with methamphetamine-induced psychotic disorder. Clinically, the psychotic symptoms and behavioural manifestation of methamphetamine-induced psychotic disorder are often indistinguishable from paranoid schizophrenia. We aimed to determine the differences in these inflammatory markers between patients with methamphetamine-induced psychotic disorder, patients with schizophrenia and healthy individuals. A total of 905 individuals were recruited. The NLR and MLR were found to be higher in both patients with methamphetamine-induced psychotic disorders and patients with schizophrenia compared with healthy controls. There was no significant difference between the three groups in PLR. When compared with the control group, the methamphetamine-induced psychotic disorder group was significantly higher in NLR 27% (95%CI = 11 to 46%, p = 0.001), MLR 16% (95%CI = 3% to 31%, p = 0.013) and PLR 16% (95%CI = 5% to 28%, p = 0.005). NLR of the group with methamphetamine-induced psychotic disorder was 17% (95%CI = 73% to 94%, p = 0.004) less than the group with schizophrenia, while MLR and PLR did not differ significantly between the two groups. This is the first study that investigated the lymphocyte-related ratios in methamphetamine-induced psychotic disorder when compared with patients with schizophrenia and healthy individuals. The results showed that both patients with methamphetamine-induced psychotic disorder and patients with schizophrenia had stronger inflammatory responses than the healthy control. Our finding also indicated that the inflammatory response of methamphetamine-induced psychotic disorder was between those of patients with schizophrenia and healthy individuals., (© 2024 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and significantly extends animal lifespan., (© 2024. The Author(s).)