Association between bedtime and female infertility: a secondary analysis from a cross-sectional study.

Objective: To evaluate the association between bedtime and infertility and to identify the optimal bedtime for women of reproductive age. Methods: We conducted a cross-sectional study using data from 3,903 female participants in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2020. The effect of bedtime on female infertility was assessed using the binary logistic regression in different models, including crude model and adjusted models. To identify the non-linear correlation between bedtime and infertility, generalized additive models (GAM) were utilized. Subgroup analyses were conducted by age, body mass index (BMI), waist circumference, physical activity total time, marital status, smoking status, drinking status and sleep duration. Results: After adjusting for potential confounders (age, race, sleep duration, waist circumference, marital status, education, BMI, smoking status, drinking status and physical activity total time), a non-linear relationship was observed between bedtime and infertility, with the inflection point at 22:45. To the left side of the inflection point, no significant association was detected. However, to the right of it, bedtime was positively related to the infertility (OR: 1.22; 95% CI: 1.06 to 1.39; P = 0.0049). Subgroup analyses showed that late sleepers with higher BMI were more prone to infertility than those with a lower BMI (BMI: 25-30 kg/m2: OR: 1.26; 95% CI: 1.06 to 1.51; P = 0.0136; BMI ≥ 30 kg/m²: OR: 1.21, 95% CI: 1.09 to 1.34; P = 0.0014). Conclusion: Bedtime was non-linearly associated with infertility, which may provide guidance for sleep behavior in women of childbearing age.

Integrating network pharmacology and experimental verification to reveal the anti-inflammatory ingredients and molecular mechanism of pycnogenol.

Introduction: Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined. Methods: This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments. Results: 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1ß to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells. Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.

Metformin improves insulin resistance, liver healthy and abnormal hepatic glucolipid metabolism via IR/PI3K/AKT pathway in Ctenopharyngodon idella fed a high-carbohydrate diet.

The effects and underlying mechanisms of metformin which can improve glucose homeostasis of fish have rarely been explored. This experiment aimed to explore the influence of metformin on growth performance, body composition, liver health, hepatic glucolipid metabolic capacity and IR/PI3K/AKT pathway in grass carp (Ctenopharyngodon idella) fed high-carbohydrate diets. A normal diet (Control) and high carbohydrate diets with metformin supplementation (0.00 %, 0.20 %, 0.40 %, 0.60 % and 0.80 %) were configured. Six groups of healthy fish were fed with the experimental diet for eight weeks. The results showed that the growth performance of grass carp was impaired in high carbohydrate diet. Impairment of IR/PI3K/AKT signalling pathway reduced insulin sensitivity, while hepatic oxidative stress damage and decreased immunity affected liver metabolic function. The glycolysis and lipolysis decrease while the gluconeogenesis and fat synthesis increase, which triggers hyperglycaemia and lipid deposition in the body. Metformin supplementation restored the growth performance of grass carp. Metformin improved IR/PI3K/AKT pathway signalling and alleviated insulin resistance, while liver antioxidant capacity and immunity were enhanced resulting in the restoration of liver health. The elevation of glycolysis and lipolysis maintains glycaemic homeostasis and reduces lipid deposition, respectively. These results suggest that metformin supplementation restores liver health and activates the IR/PI3K/AKT signalling pathway, ameliorating insulin resistance and glucose-lipid metabolism disorders caused by a high-carbohydrate diet. As judged by HOMA-IR, the optimum supplementation level of metformin in grass carp (C. idella) fed a high-carbohydrate diet is 0.67 %.

Identification of Hypoxia and Mitochondrial-related Gene Signature and Prediction of Prognostic Model in Lung Adenocarcinoma.

Background: The correlation between hypoxia and tumor development is widely acknowledged. Meanwhile, the foremost organelle affected by hypoxia is mitochondria. This study aims to determine whether they possess prognostic characteristics in lung adenocarcinoma (LUAD). For this purpose, a bioinformatics analysis was conducted to assess hypoxia and mitochondrial scores related genes, resulting in the successful establishment of a prognostic model. Methods: Using the single sample Gene Set Enrichment Analysis algorithm, the hypoxia and mitochondrial scores were computed. Differential expression analysis and weighted correlation network analysis were employed to identify genes associated with hypoxia and mitochondrial scores. Prognosis-related genes were obtained through univariate Cox regression, followed by the establishment of a prognostic model using least absolute shrinkage and selection operator Cox regression. Two independent validation datasets were utilized to verify the accuracy of the prognostic model using receiver operating characteristic and calibration curves. Additionally, a nomogram was employed to illustrate the clinical significance of this study. Results: 318 differentially expressed genes associated with hypoxia and mitochondrial scores were identified for the construction of a prognostic model. The prognostic model based on 16 genes, including PKM, S100A16, RRAS, TUBA4A, PKP3, KCTD12, LPGAT1, ITPRID2, MZT2A, LIFR, PTPRM, LATS2, PDIK1L, GORAB, PCDH7, and CPED1, demonstrates good predictive accuracy for LUAD prognosis. Furthermore, tumor microenvironments analysis and drug sensitivity analysis indicate an association between risk scores and certain immune cells, and a higher risk scores suggesting improved chemotherapy efficacy. Conclusion: The research established a prognostic model consisting of 16 genes, and a nomogram was developed to accurately predict the prognosis of LUAD patients. These findings may contribute to guiding clinical decision-making and treatment selection for patients with LUAD, ultimately leading to improved treatment outcomes.

Myofibroblasts derived type V collagen promoting tissue mechanical stress and facilitating metastasis and therapy resistance of lung adenocarcinoma cells.

Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM_Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM_Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM_Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM_Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications.

SIGIRR suppresses hepatitis B virus X protein-induced chronic inflammation in hepatocytes.

Although antiviral drugs can effectively inhibit hepatitis B virus (HBV) replication, the maintenance of chronic inflammation in the liver is still considered to be an important cause for the progression of HBV-related liver disease to liver fibrosis and advanced liver disease. As an endogenous inhibitory receptor of IL-1R and TLR signaling pathways, single immunoglobulin interleukin-1-related receptor (SIGIRR) has been proven to reduce inflammation in tissues to maintain system homeostasis. However, the relationship between SIGIRR expression and HBV replication and inflammatory pathway activation in hepatocytes remains unclear. In this study, hepatitis B virus X protein (HBx) upregulated MyD88 in liver cells, promoting NF-κB signaling and inflammatory factor production with LPS treatment, and the cell supernatant accelerated the activation and collagen secretion of hepatic stellate cells. However, SIGIRR overexpression suppressed HBx-mediated MyD88/NF-κB inflammatory signaling activation and inflammatory cytokine production induced by LPS in hepatocytes and HBV replication hepatocytes. Although we did not find any effect of SIGIRR on HBV replication in vitro, this study investigated the role of SIGIRR in blocking the proinflammatory function of HBx, which may provide a new idea for the treatment of chronic hepatitis B.

Effects of hydroxyproline supplementation in low fish meal diets on collagen synthesis, myofiber development and muscular texture of juvenile Pacific white shrimp (Litopenaeus vannamei).

This experiment aimed to evaluate the impact of dietary hydroxyproline (Hyp) supplementation on the muscle quality of juvenile Pacific white shrimp (Litopenaeus vannamei) fed a low fishmeal diet. Six formulated diets included one high fishmeal (HF; 25% fishmeal content) and five low fishmeal diets (10% fishmeal content) with 0%, 0.2%, 0.4%, 0.6% and 0.8% Hyp (LF0, LF2, LF4, LF6 and LF8, respectively). Each diet was assigned to four replicates, and 40 shrimp (0.32 ± 0.00 g) per replicate were fed four times a day for 8 weeks. Dietary Hyp supplementation had little effects on growth performance, but increased the contents of Hyp, prolyl 4-hydroxylases (P4Hs), and collagen. The meat yield, springiness, hardness, chewiness, and cohesiveness of muscle were the highest in the LF4 group among the low fishmeal groups (P < 0.05). Cooking loss and freezing loss of muscle were the lowest in the LF4 group (P < 0.05). Dietary supplementation with 0.4% Hyp increased the myofiber density and decreased the myofiber diameter of muscle (P < 0.05). Supplementation of Hyp in the diet up-regulated the mRNA expression of smyhc5, smyhc15, col1a1, col1a2, igf-1f, tgf-ß and tor and down-regulated the mRNA expression of smyhc 1, smyhc 2, smyhc 6a (P < 0.05). Supplementation of Hyp in the diet up-regulated the protein expression of P-4E-BP1, P-AKT, AKT and P-AKT/AKT (P < 0.05). These results suggested that the addition of 0.4% Hyp to low fishmeal diets improved the muscle quality of L. vannamei.

Identifying differentially expressed genes in goat mammary epithelial cells induced by overexpression of SOCS3 gene using RNA sequencing.

The suppressor of cytokine signaling 3 (SOCS3) is a key signaling molecule that regulates milk synthesis in dairy livestock. However, the molecular mechanism by which SOCS3 regulates lipid synthesis in goat milk remains unclear. This study aimed to screen for key downstream genes associated with lipid synthesis regulated by SOCS3 in goat mammary epithelial cells (GMECs) using RNA sequencing (RNA-seq). Goat SOCS3 overexpression vector (PC-SOCS3) and negative control (PCDNA3.1) were transfected into GMECs. Total RNA from cells after SOCS3 overexpression was used for RNA-seq, followed by differentially expressed gene (DEG) analysis, functional enrichment analysis, and network prediction. SOCS3 overexpression significantly inhibited the synthesis of triacylglycerol, total cholesterol, non-esterified fatty acids, and accumulated lipid droplets. In total, 430 DEGs were identified, including 226 downregulated and 204 upregulated genes, following SOCS3 overexpression. Functional annotation revealed that the DEGs were mainly associated with lipid metabolism, cell proliferation, and apoptosis. We found that the lipid synthesis-related genes, STAT2 and FOXO6, were downregulated. In addition, the proliferation-related genes BCL2, MMP11, and MMP13 were upregulated, and the apoptosis-related gene CD40 was downregulated. In conclusion, six DEGs were identified as key regulators of milk lipid synthesis following SOCS3 overexpression in GMECs. Our results provide new candidate genes and insights into the molecular mechanisms involved in milk lipid synthesis regulated by SOCS3 in goats.

Procyanidin B2 improves developmental capacity of bovine oocytes via promoting PPARγ/UCP1-mediated uncoupling lipid catabolism during in vitro maturation.

Metabolic balance is essential for oocyte maturation and acquisition of developmental capacity. Suboptimal conditions of in vitro cultures would lead to lipid accumulation and finally result in disrupted oocyte metabolism. However, the effect and mechanism underlying lipid catabolism in oocyte development remain elusive currently. In the present study, we observed enhanced developmental capacity in Procyanidin B2 (PCB2) treated oocytes during in vitro maturation. Meanwhile, reduced oxidative stress and declined apoptosis were found in oocytes after PCB2 treatment. Further studies confirmed that oocytes treated with PCB2 preferred to lipids catabolism, leading to a notable decrease in lipid accumulation. Subsequent analyses revealed that mitochondrial uncoupling was involved in lipid catabolism, and suppression of uncoupling protein 1 (UCP1) would abrogate the elevated lipid consumption mediated by PCB2. Notably, we identified peroxisome proliferator-activated receptor gamma (PPARγ) as a potential target of PCB2 by docking analysis. Subsequent mechanistic studies revealed that PCB2 improved oocyte development capacity and attenuated oxidative stress by activating PPARγ mediated mitochondrial uncoupling. Our findings identify that PCB2 intricately improves oocyte development capacity through targeted activation of the PPARγ/UCP1 pathway, fostering uncoupling lipid catabolism while concurrently mitigating oxidative stress.

Emerging strategies for combating Fusobacterium nucleatum in colorectal cancer treatment: Systematic review, improvements and future challenges.

Colorectal cancer (CRC) is generally characterized by a high prevalence of Fusobacterium nucleatum (F. nucleatum), a spindle-shaped, Gram-negative anaerobe pathogen derived from the oral cavity. This tumor-resident microorganism has been closely correlated with the occurrence, progression, chemoresistance and immunosuppressive microenvironment of CRC. Furthermore, F. nucleatum can specifically colonize CRC tissues through adhesion on its surface, forming biofilms that are highly resistant to commonly used antibiotics. Accordingly, it is crucial to develop efficacious non-antibiotic approaches to eradicate F. nucleatum and its biofilms for CRC treatment. In recent years, various antimicrobial strategies, such as natural extracts, inorganic chemicals, organic chemicals, polymers, inorganic-organic hybrid materials, bacteriophages, probiotics, and vaccines, have been proposed to combat F. nucleatum and F. nucleatum biofilms. This review summarizes the latest advancements in anti-F. nucleatum research, elucidates the antimicrobial mechanisms employed by these systems, and discusses the benefits and drawbacks of each antimicrobial technology. Additionally, this review also provides an outlook on the antimicrobial specificity, potential clinical implications, challenges, and future improvements of these antimicrobial strategies in the treatment of CRC.

Identification and validation of COL6A1 as a novel target for tumor electric field therapy in glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy. Novel therapeutic modalities like tumor electric field therapy (TEFT) have shown promise, but underlying mechanisms remain unclear. The extracellular matrix (ECM) is implicated in GBM progression, warranting investigation into TEFT-ECM interplay. METHODS: T98G cells were treated with TEFT (200 kHz, 2.2 V/m) for 72 h. Collagen type VI alpha 1 (COL6A1) was identified as hub gene via comprehensive bioinformatic analysis based on RNA sequencing (RNA-seq) and public glioma datasets. TEFT intervention models were established using T98G and Ln229 cell lines. Pre-TEFT and post-TEFT GBM tissues were collected for further validation. Focal adhesion pathway activity was assessed by western blot. Functional partners of COL6A1 were identified and validated by co-localization and survival analysis. RESULTS: TEFT altered ECM-related gene expression in T98G cells, including the hub gene COL6A1. COL6A1 was upregulated in GBM and associated with poor prognosis. Muti-database GBM single-cell analysis revealed high-COL6A1 expression predominantly in malignant cell subpopulations. Differential expression and functional enrichment analyses suggested COL6A1 might be involved in ECM organization and focal adhesion. Western blot (WB), immunofluorescence (IF), and co-immunoprecipitation (Co-IP) experiments revealed that TEFT significantly inhibited expression of COL6A1, hindering its interaction with ITGA5, consequently suppressing the FAK/Paxillin/AKT pathway activity. These results suggested that TEFT might exert its antitumor effects by downregulating COL6A1 and thereby inhibiting the activity of the focal adhesion pathway. CONCLUSION: TEFT could remodel the ECM of GBM cells by downregulating COL6A1 expression and inhibiting focal adhesion pathway. COL6A1 could interact with ITGA5 and activate the focal adhesion pathway, suggesting that it might be a potential therapeutic target mediating the antitumor effects of TEFT.

Pan-cancer analysis predict that FAT1 is a therapeutic target and immunotherapy biomarker for multiple cancer types including non-small cell lung cancer.

FAT1, a substantial transmembrane protein, plays a pivotal role in cellular adhesion and cell signaling. Numerous studies have documented frequent alterations in FAT1 across various cancer types, with its aberrant expression being linked to unfavorable survival rates and tumor progression. In the present investigation, we employed bioinformatic analyses, as well as in vitro and in vivo experiments to elucidate the functional significance of FAT1 in pan-cancer, with a primary focus on lung cancer. Our findings unveiled FAT1 overexpression in diverse cancer types, including lung cancer, concomitant with its association with an unfavorable prognosis. Furthermore, FAT1 is intricately involved in immune-related pathways and demonstrates a strong correlation with the expression of immune checkpoint genes. The suppression of FAT1 in lung cancer cells results in reduced cell proliferation, migration, and invasion. These collective findings suggest that FAT1 has potential utility both as a biomarker and as a therapeutic target for lung cancer.

Safety and efficacy of multi-target TKI combined with nivolumab in check-point inhibitor-refractory patients with advanced NSCLC: a prospective, single-arm, two-stage study.

BACKGROUND: Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. METHODS: This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. RESULTS: Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. CONCLUSION: Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. TRIAL REGISTRATION: NCT04507906 August 11, 2020.

Auditory change detection and visual selective attention: association between MMN and N2pc.

While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.

SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to ß-cypermethrin with stereoselectivity.

Carboxylesterases (CarEs) is an important detoxification enzyme system in phase Ⅰ participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to ß-cypermethrin showed stereoselectivity, with higher metabolic activity to θ-cypermethrin than the enantiomer α-cypermethrin. The metabolite of ß-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that ß-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of ß-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in ß-cypermethrin resistance in S. litura.

Corrigendum: ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates.

[This corrects the article DOI: 10.3389/fimmu.2024.1382231.].

Effects of intensive psychological intervention on treatment compliance, psychological status, and quality of life of patients with epilepsy.

BACKGROUND: Epilepsy is a nervous system disease characterized by recurrent attacks, a long disease course, and an unfavorable prognosis. It is associated with an enduring therapeutic process, and finding a cure has been difficult. Patients with epilepsy are predisposed to adverse moods, such as resistance, anxiety, nervousness, and anxiety, which compromise treatment compliance and overall efficacy. AIM: To explored the influence of intensive psychological intervention on treatment compliance, psychological status, and quality of life (QOL) of patients with epilepsy. METHODS: The clinical data of 105 patients with epilepsy admitted between December 2019 and July 2023 were retrospectively analyzed, including those of 50 patients who underwent routine intervention (control group) and 55 who underwent intensive psychological intervention (research group). Treatment compliance, psychological status based on the Self-Rating Anxiety Scale (SAS) and Depression Scale Self-Rating Depression Scale (SDS) scores, hope level assessed using the Herth Hope Scale (HHS), psychological resilience evaluated using the Psychological Resilience Scale, and QOL determined using the QOL in Epilepsy-31 Inventory (QOLIE-31) were comparatively analyzed. RESULTS: Treatment compliance in the research group was 85.5%, which is significantly better than the 68.0% of the control group. No notable intergroup differences in preinterventional SAS and SDS scores were identified (P > 0.05); however, after the intervention, the SAS and SDS scores decreased significantly in the two groups, especially in the research group (P < 0.05). The two groups also exhibited no significant differences in preinterventional HHS, Connor-Davidson Resilience Scale (CD-RISC), and QOLIE-31 scores (P > 0.05). After 6 months of intervention, the research group showed evidently higher HHS, CD-RISC, tenacity, optimism, strength, and QOLIE-31 scores (P < 0.05). CONCLUSION: Intensive psychological intervention enhances treatment compliance, psychological status, and QOL of patients with epilepsy.

Effect of gut hormones on bone metabolism and their possible mechanisms in the treatment of osteoporosis.

Bone is a highly dynamic organ that changes with the daily circadian rhythm. During the day, bone resorption is suppressed due to eating, while it increases at night. This circadian rhythm of the skeleton is regulated by gut hormones. Until now, gut hormones that have been found to affect skeletal homeostasis include glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), which exerts its effects by binding to its cognate receptors (GLP-1R, GLP-2R, GIPR, and Y1R). Several studies have shown that GLP-1, GLP-2, and GIP all inhibit bone resorption, while GIP also promotes bone formation. Notably, PYY has a strong bone resorption-promoting effect. In addition, gut microbiota (GM) plays an important role in maintaining bone homeostasis. This review outlines the roles of GLP-1, GLP-2, GIP, and PYY in bone metabolism and discusses the roles of gut hormones and the GM in regulating bone homeostasis and their potential mechanisms.

Dynamic analysis and optimal control of stochastic information cross-dissemination and variation model with random parametric perturbations.

Information dissemination has a significant impact on social development. This paper considers that there are many stochastic factors in the social system, which will result in the phenomena of information cross-dissemination and variation. The dual-system stochastic susceptible-infectious-mutant-recovered model of information cross-dissemination and variation is derived from this problem. Afterward, the existence of the global positive solution is demonstrated, sufficient conditions for the disappearance of information and its stationary distribution are calculated, and the optimal control strategy for the stochastic model is proposed. The numerical simulation supports the results of the theoretical analysis and is compared to the parameter variation of the deterministic model. The results demonstrate that cross-dissemination of information can result in information variation and diffusion. Meanwhile, white noise has a positive effect on information dissemination, which can be improved by adjusting the perturbation parameters.

Pan-cancer analysis combined with experiments predicts NNMT as a therapeutic target for human cancers.

The identification of effective therapeutic targets plays a pivotal role in advancing cancer treatment outcomes. We employed a comprehensive pan-cancer analysis, complemented by experimental validation, to explore the potential of Nicotinamide N-methyltransferase (NNMT) as a promising therapeutic strategy for human cancers. By analyzing large-scale transcriptomic datasets across various cancer types, we consistently observed upregulated expression of NNMT. Furthermore, elevated NNMT expression correlated with inferior overall survival in multiple cancer cohorts, underscoring its significance as a prognostic biomarker. Additionally, we investigated the relationship between NNMT expression and the tumor immune microenvironment, which plays a crucial role in regulating anti-tumor immune responses. To confirm the malignant functions of NNMT in tumor cells, we conducted a series of cell-based experiments, revealing that NNMT promotes cancer cell proliferation and invasion, indicative of its oncogenic properties. The integration of computational analysis and experimental validation in our study firmly establishes NNMT as a potential therapeutic target for human cancers. Specifically, targeting NNMT holds promise for the development of innovative and effective cancer treatments. Further investigations into NNMT's role in cancer pathogenesis could potentially pave the way for groundbreaking advancements in cancer treatment.