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Objective To explore the influence of calcium channel blocker(CCB), verapamil, on steroid hormone profile of primary cultured aldosterone producing adenoma(APA)cells. Methods The adrenal tumor tissues of 6 APA patients with hypokalemia operated in Peking Union Medical College Hospital were cultured and treated with different concentrations of verapamil. The steroid hormone profile was detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS). Results The level of aldosterone in 50 μmol/L verapamil group was lower than that in 10 μmol/L verapamil group and control group(P＜0.01). The levels of aldosterone precursor, 11-deoxycorticosterone in verapamil 10 μmol/L group was lower than that in control group (P＜0.05). The levels of 18-oxocortisol(18-OXOF) and 18-hydroxycortisol(18-OHF) in verapamil 50 μmol/L group and verapamil 10 μmol/L group were lower than that in the control group (P＜0.05). In addition, verapamil also had some inhibitory effects on glucocorticoids such as cortisol and cortisone, and adrenal derived sex hormones such as dehydroepiandrosterone sulfate(DHEA-S) and 11 beta-hydroxytestosterone(11β-OHT). Conclusions In addition to inhibit-ing aldosterone secretion in primary cultured APA cells, CCB has significant inhibitory effects on a variety of other steroid hormones, such as precursor 11-deoxycorticosterone, cortisol, metabolites, 18-OXOF and 18-OHF.

Objective To investigate the effects of lncRNA-ATB on the proliferation and collagen synthesis of human keloid fibroblast (KFB) and its possible molecular mechanism. Methods Human KFB and normal fibroblasts (NFB) were isolated and cultured in vitro, KFB was divided into NC group, si-NC group, si-lncRNA-ATB group, si-lncRNA-ATB+TNF-α group. RT-qPCR was used to detect the expression of lncRNA-ATB in NFB and KFB. MTT was used to detect cell activity. Flow cytometry was used to detect cell cycle. Western blot was used to detect expression of cyclinD1, collagen synthesis and NF-κB signaling pathway related protein. Results The expression of lncRNA-ATB in KFB cells was significantly increased (P＜0.05). Knock-down lncRNA-ATB expression decreased the A value of KFB cells, the expression of cyclinD1 and the percentageof S phase cells,but increased the percent- age of G0/G1 phase cells (P＜0.05); the expression of Col-Ⅰ and Col-Ⅲ of collagen was decreased(P＜0.05); the expression of p-p65 and p-IκBα in NF-κB signaling pathway was inhibited(P＜0.05); NF-κB activation activator TNF-α alleviated the inhibitory effect of knock-down lncRNA-ATB expression on KFB cell proliferation and collagen synthesis (P＜0.05). Conclusions Knock-down of lncRNA-ATB expression may inhibit KFB proliferation and collagen synthesis by down-regulating NF-κB signaling pathway.

Context.--Neutralizing antibody detection can assess the incidence of COVID-19 and the effectiveness of vaccines. However, commercial reagents for neutralizing antibodies were developed after the anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies. Therefore, some laboratories did not perform neutralizing antibody testing services because of multiple factors. Objective.--To find a fast, accurate, and economic alternative for the detection of neutralizing antibodies for the development of COVID-19 screening programs. Design.--The response and correlation of 3 antibodies (anti-spike protein neutralizing antibody, total anti-receptor-binding domain [RBD] antibody, and anti-RBD IgG) were determined by observing the dynamics in 61 participants for 160 days after vaccination. Results.--The levels of neutralizing and anti-RBD IgG antibodies reached their peak values on day 42 after vaccination (120.75 IU/mL and 14.38 signal-to-cutoff ratio [S/CO], respectively). The total antibody levels peaked at 138.47 S/CO on day 35 after vaccination. The strongest correlation was found between neutralizing and anti-RBD IgG antibody levels (r = 0.894, P Conclusions.--Neutralizing and anti-RBD IgG antibody levels were strongly correlated, and thus anti-RBD IgG antibody levels can be used for the accurate assessment of immunity following SARS-CoV-2 infection or vaccination., SARS-CoV-2 is a highly transmissible and pathogenic virus that has caused serious harm to human health and public safety during the ongoing COVID-19 global pandemic. (1,2) Global COVID-19 cases now [...]

The cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is an important insect pest of cotton crops worldwide. The objectives of this study were to determine the acute toxicity of afidopyropen and whether there are any effects of sublethal concentrations of afidopyropen on the biological characteristics of A. gossypii. The results showed that afidopyropen possesses high acute toxicity to adult A. gossypii with a 72 h LC50 value of 1.062 mg L–1. A sublethal concentration (LC10) of afidopyropen significantly decreased adult longevity, fecundity and oviposition days of female adults in both F0 and F1 generations. The total pre-adult survival of F1 progeny was also significantly reduced by 30% at the LC10 of afidopyropen. In addition, the nymph developmental time, pre-adult period, adult pre-reproductive period (APRP), and total pre-reproductive period (TPRP) of the F1 progeny were significantly prolonged compared with the control. Several population parameters, including the net reproductive rate (R0), intrinsic rate of increase (r) and finite rate of increase (λ) of F1 progeny were significantly decreased by a sublethal afidopyropen concentration exposure. These results indicated that sublethal concentration of afidopyropen can significantly suppress A. gossypii population growth. It would be useful for assessing the overall effects of afidopyropen on A. gossypii.

Major depressive disorder is a common and devastating psychiatric disease, and the prevalence and burden are substantially increasing worldwide. Multiple studies of depression patients have implicated glucose metabolic dysfunction in the pathophysiology of depression. However, the molecular mechanisms by which glucose and related metabolic pathways modulate depressive-like behaviors are largely uncharacterized. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a donor molecule for O-GlcNAcylation. O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, catalyzes protein posttranslational modification by O-GlcNAc and acts as a stress sensor. Here, we show that Ogt mRNA was increased in depression patients and that astroglial OGT expression was specifically upregulated in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social-defeat stress. The selective deletion of astrocytic OGT resulted in antidepressant-like effects, and moreover, astrocytic OGT in the mPFC bidirectionally regulated vulnerability to social stress. Furthermore, OGT modulated glutamatergic synaptic transmission through O-GlcNAcylation of glutamate transporter-1 (GLT-1) in astrocytes. OGT astrocyte–specific knockout preserved the neuronal morphology atrophy and Ca2+ activity deficits caused by chronic stress and resulted in antidepressant effects. Our study reveals that astrocytic OGT in the mPFC regulates depressive-like behaviors through the O-GlcNAcylation of GLT-1 and could be a potential target for antidepressants.

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress‐related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome‐related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte‐specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive‐like behaviors by inhibiting lysosomal exocytosis‐mediated adenosine 5′‐triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive‐like behaviors induced by astrocyte‐specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress‐sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) has a postoperative recurrence rate of up to 50%. Local treatment at the surgical site offers a new strategy to prevent recurrence, minimizing systemic side effects. However, these treatments often face issues like poor stability, insufficient targeting, and significant local side effects. Research shows glucose starvation can induce disulfidptosis, a novel cell death pathway, in CRC cells, suitable for precise intervention in residual tumor cells postsurgery. This study develops a biocompatible 2D therapeutic platform using amyloid‐like protein nanofilm technology for precise local synergistic intervention in disulfidptosis and photodynamic therapy (PDT) after CRC surgery. The nanofilm boasts excellent drug‐loading capacity, enzyme activity retention, ultrathin dimensions, wet adhesion, and biocompatibility. A model simulating incomplete tumor resection post‐CRC surgery shows that the GCI@nanofilm effectively inhibits recurrence through an enzyme‐catalyzed cascade reaction inducing disulfidptosis and synergizing with PDT. In summary, GCI@nanofilm overcomes multiple challenges in local postsurgical intervention, providing a foundation for precise and efficient treatment of residual tumors. [ABSTRACT FROM AUTHOR]