Co-CoSe heterogeneous fibers with strong interfacial built-in electric field as bifunctional electrocatalyst for high-performance Zn-air battery.

The explorations of efficient electrocatalysts to accelerate oxygen reactions in a wide temperature range is a crucial issue to the development of zinc-air batteries (ZAB) for all-climate applications. Herein, the Co-CoSe heterogeneous furry fibers (Co-CoSe@NHF) are developed as a bifunctional oxygen electrocatalyst for ZAB towards wide-temperature range applications. The Co-CoSe heterostructure with large work function difference (ΔWF) endows interfacial electron redistribution, which builds strong interfacial built-in electric field (BIEF) and improves the oxygen reactions. Meanwhile, the Co-CoSe heterostructure is encapsulated by in-situ grown carbon nanotubes, and forms the hollow fiber (NHF) with furry surface and beads-on-string configuration. The highly porous and conductive NHF configuration facilitates the fast kinetics and favors to accommodates volume change during cycling. As a result, the Co-CoSe@NHF achieves the superior bifunctional properties and good reliability for oxygen reactions. Integrated with the Co-CoSe@NHF fiber, the ZAB cell delivers the superior power density (301 mW cm-2) and long-term cycling stability over 280 h at 25 °C, and maintains the power densities of 126 mW cm-2 even the temperature decreases to -25 °C. Moreover, the solid-state ZAB exhibits significant flexibility and superior properties in a wide temperature range. Therefore, this work not only proposes a new strategy to design the high-performance bifunctional electrocatalysts, but also propels the development of flexible power sources for all-climate applications.

Smart paper-based materials incorporating nitrogen and boron co-doped MXene quantum dots for rapid adsorption and sensitive detection of Cr2O72.

Dichromate ion (Cr2O72-) is a highly toxic chromium-containing compound that poses significant hazards to the digestive, respiratory systems, skin, and mucous membranes. Currently, the detection and adsorption of Cr2O72- face significant challenges, including the time-consuming and low sensitivity nature of traditional analytical methods. The limited efficiency and capacity of existing adsorbents hinder their practical application in real-time water quality monitoring and environmental remediation. Herein, using polyethyleneimine-functionalized (PEI) pulp fiber paper as the substrate, we developed smart paper-based materials (designated as NB-MQDs@PP) incorporated with nitrogen and boron co-doped MXene quantum dots (NB-MQDs) for rapid adsorption and sensitive detection of Cr2O72-. Compared to undoped MQDs, NB-MQDs exhibited longer excitation wavelength and enhanced oxidation stability. As anticipated, NB-MQDs achieved rapid (response time of 10 s) and sensitive (detection limit of 1.2 µM) recognition of Cr2O72- within a wide pH range with a quenching efficiency of 99.9%. Simultaneously, two on-site detection methods, immersion and cyclic filtration, were constructed based on NB-MQDs@PP. The detection limit of the immersion method was 17.0 nM, while the cyclic filtration method had a detection limit as low as 3.8 nM, surpassing the majority of those reported literatures. Remarkably, NB-MQDs@PP exhibited outstanding enrichment capacity towards Cr2O72-, with an adsorption capacity of up to 162.4 mg/g. This work provides a novel strategy for creating unique paper-based materials with excellent capture and monitoring dual-function, which can be customized according to the requirements of various application scenarios.

Pleiotropic role of CCR9/CCL25 signaling in adriamycin-induced cardiomyopathy.

INTRODUCTION: Adriamycin (ADR)-induced cardiomyopathy is a common problem in many cancer survivors. Recently, specific chemokine receptors have garnered interest as therapeutic targets in cardiovascular diseases. OBJECTIVES: This study aim to report the role of the C-C chemokine receptor 9 (CCR9)/C-C chemokine ligand 25 (CCL25) and its therapeutic potential in ADR-induced cardiomyopathy. METHODS: Functional gene knockout and overexpression mouse models were utilized to investigate the role of CCR9 against ADR-induced cardiomyopathy. Transcriptome sequencing was also performed to identify the downstream molecular mechanisms of CCR9. RESULTS: This study revealed that CCR9 and CCL25 levels were increased in mice and HL-1 cells injured by ADR, consistent with the results of patients with heart failure. Both in vivo and in vitro, CCR9 overexpression overtly aggravated cardiac dysfunction, accompanied by decreased AMPK activity and increased mitochondrial dysfunction, fibrosis, oxidative stress, and apoptosis. However, the cardiac harmful effects were reserved by CCR9 knockdown or AMPK agonist GSK621. By constructing different domain-missing CCR9 mutants, we suspected that the △4 region of CCR9 is important for AMPK activity. Furthermore, RNA-seq illustrated the CCR9-controlled transcriptome and genome in detail, pinpointing that CCR9 overexpression aggravated ADR-induced cardiotoxicity was associated with CYP1A1. Finally, lithospermic acid (LA) was screened and alleviated ADR-induced cardiotoxicity through regulation of CCR9/CCL25-AMPK signaling, bolstering CCR9-targeted potential clinical application. CONCLUSION: These findings present a promising target and drug for treating chemotherapy-induced cardiotoxicity.

Is the transection of the hernia sac during laparoscopic inguinal hernioplasty safe and feasible? An updated systematic review and meta-analysis.

There is a debate over whether to transect or completely reduce the hernia sac during laparoscopic tension-free repair of inguinal hernia. This study endeavors to systematically assess the efficacy and safety of two approaches, namely transected sac (TS) and completely reduced sac (RS), in laparoscopic tension-free repair of inguinal hernia. Utilizing a meta-analysis methodology, we aim to provide a comprehensive analysis of these techniques. A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases to identify comparative studies focusing on laparoscopic tension-free repair of inguinal hernia, specifically comparing TS and RS techniques. The selected studies were subjected to meta-analysis using RevMan 5.3 software. A total of 8 studies, involving 2995 patients with inguinal hernia, were included in the analysis. The meta-analysis results revealed that the TS group had a higher incidence of seroma compared to the RS group [OR = 1.74, 95% CI (1.35, 2.25), P < 0.0001], and a prolonged time to return to normal activity postoperatively [MD = 0.99, 95% CI (0.85, 1.14), P < 0.00001]. However, no statistically significant differences were observed between the two groups in terms of operation time [MD = -1.75, 95% CI (- 8.72, 5.22), P = 0.62], incidence of postoperative pain [OR = 1.00, 95% CI (0.41, 2.44), P = 1.00], overall postoperative complication rate [OR = 0.98, 95% CI (0.43, 2.20), P = 0.95], and recurrence rate fOR = 2.53, 95% CI (0.61, 10.39), P = 0.20]. Transected sac in laparoscopic inguinal hernia repair is associated with an increased incidence of seroma and a longer recovery time for patients to return to normal activity. Clinical trial registration Registration number is INPLASY20223110070.

Characterising core body temperature response of free-moving C57BL/6 mice to 1.95 GHz whole-body radiofrequency-electromagnetic fields.

The present study investigated the core body temperature (CBT) response of free-moving adult male and female C57BL/6 mice, during and following a 2-h exposure to 1.95 GHz RF-EMF within custom-built reverberation chambers, using temperature capsules implanted within the intraperitoneal cavity and data continuously logged and transmitted via radiotelemetry postexposure. Comparing RF-EMF exposures (WBA-SAR of 1.25, 2.5, 3.75, and 5 W/kg) to the sham-exposed condition, we identified a peak in CBT within the first 16 min of RF-EMF exposure (+0.15, +0.31, +0.24, +0.37°C at 1.25, 2.5, 3.75, and 5 W/kg respectively; statistically significant at WBA-SAR ≥ 2.5 W/kg only), which largely dissipated for the remainder of the exposure period. Immediately before the end of exposure, only the CBT of the 5 W/kg condition was statistically differentiable from sham. Based on our findings, it is apparent that mice are able to effectively compensate for the increased thermal load at RF-EMF strengths up to 5 W/kg. In addition, the elevated CBT at the end of the exposure period in the 5 W/kg condition was statistically significantly reduced compared to the sham condition immediately after RF-EMF exposure ceased. This would indicate that measures of CBT following the end of an RF-EMF exposure period may not reflect the actual change in the CBT of mice caused by RF-EMF exposure in mice.

Meta-analysis of RCTs on the safety of non-fixation of mesh in TAPP inguinal hernia repair: an updated meta-analysis.

OBJECTIVE: This meta-analysis aims to compare the clinical efficacy of mesh non-fixation and fixation in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair, systematically evaluating the application value of the mesh non-fixation technique in clinical settings. METHODS: A computerized search of PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases was conducted to identify randomized controlled trials (RCTs) comparing mesh non-fixation and fixation in TAPP inguinal hernia repair. Meta-analysis was performed using RevMan 5.3 software, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence grading system was employed for outcome quality assessment. Publication bias analysis was performed using Begg's test. A trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software. RESULTS: A total of nine RCTs involving 1,879 inguinal hernia patients were included. Meta-analysis results demonstrated that, compared to the fixation group, the non-fixation group exhibited significantly lower seroma occurrence rate [RR = 0.43, 95% CI (0.20, 0.89), P = 0.02, heterogeneity P = 0.28, I²=22%], Visual Analog Scale (VAS) pain score at 6 months postoperatively [MD=-0.21, 95% CI (-0.29, -0.12), P < 0.00001, heterogeneity P = 0.34, I²=0%], and cost [MD=-3.23 thousand yuan, 95% CI (-4.26, -2.19), P < 0.00001, heterogeneity P = 0.0003, I²=92%]. There were no statistically significant differences in overall complication rate [RR = 0.88, 95% CI (0.62, 1.23), P = 0.45, heterogeneity P = 0.11, I²=44%], overall infection event rate [RR = 0.96, 95% CI (0.36, 2.56), P = 0.93, heterogeneity P = 0.62, I²=0%] and recurrence rate [RR = 0.75, 95% CI (0.28, 1.99), P = 0.56, heterogeneity P = 0.44, I²=0%] between the two groups. The results of the TSA indicated that the observed lower seroma occurrence rate in the non-fixation group compared to the fixation group requires further validation through the inclusion of additional RCTs. CONCLUSION: Mesh non-fixation in TAPP inguinal hernia repair is deemed safe and does not elevate the risk of hernia recurrence. However, given certain limitations in this study, future comprehensive and reliable validation will require further multicenter, high-quality, large-sample double-blind RCTs.

Non-invasive metabolic biomarkers in initial cognitive impairment in patients with diabetes: A systematic review and meta-analysis.

AIM: Diabetic cognitive impairment (DCI), considered one of the most severe and commonly overlooked complications of diabetes, has shown inconsistent findings regarding the metabolic profiles in DCI patients. This systematic review and meta-analysis aimed to identify dysregulated metabolites as potential biomarkers for early DCI, providing valuable insights into the underlying pathophysiological mechanisms. MATERIALS AND METHODS: A systematic search of four databases, namely PubMed, Embase, Web of Science and Cochrane, was conducted up to March 2024. Subsequently, a qualitative review of clinical studies was performed followed by a meta-analysis of metabolite markers. Finally, the sources of heterogeneity were explored through subgroup and sensitivity analyses. RESULTS: A total of 774 unique publications involving 4357 participants and the identification of multiple metabolites were retrieved. Of these, 13 clinical studies reported metabolite differences between the DCI and control groups. Meta-analysis was conducted for six brain metabolites and two metabolite ratios. The results revealed a significant increase in myo-inositol (MI) concentration and decreases in glutamate (Glu), Glx (glutamate and glutamine) and N-acetylaspartate/creatine (NAA/Cr) ratios in DCI, which have been identified as the most sensitive metabolic biomarkers for evaluating DCI progression. Notably, brain metabolic changes associated with cognitive impairment are more pronounced in type 2 diabetes mellitus than in type 1 diabetes mellitus, and the hippocampus emerged as the most sensitive brain region regarding metabolic changes associated with DCI. CONCLUSIONS: Our results suggest that MI, Glu, and Glx concentrations and NAA/Cr ratios within the hippocampus may serve as metabolic biomarkers for patients with early-stage DCI.

Mechanisms of ROS-mediated interactions between Bacillus aryabhattai LAD and maize roots to promote plant growth.

BACKGROUND: Plant growth-promoting rhizobacteria (PGPR), as a group of environmentally friendly bacteria growing in the rhizosphere of plants, play an important role in plant growth and development and resistance to environmental stresses. However, their limited understanding has led to the fact that their large-scale use in agriculture is still scarce, and the mechanisms by which beneficial bacteria are selected by plants and how they interact with them are still unclear. METHOD: In this study, we investigated the interaction between the auxin-producing strain Bacillus aryabhattai LAD and maize roots, and performed transcriptomic and metabolomic analyses of Bacillus aryabhattai LAD after treatment with maize root secretions(RS). RESULTS: Our results show that there is a feedback effect between the plant immune system and bacterial auxin. Bacteria activate the immune response of plant roots to produce reactive oxygen species(ROS), which in turn stimulates bacteria to synthesize IAA, and the synthesized IAA further promotes plant growth. Under the condition of co-culture with LAD, the main root length, seedling length, root surface area and root volume of maize increased by 197%, 107%, 89% and 75%, respectively. In addition, the results of transcriptome metabolome analysis showed that LAD was significantly enriched in amino acid metabolism, carbohydrate metabolism and lipid metabolism pathways after RS treatment, including 93 differentially expressed genes and 45 differentially accumulated metabolites. CONCLUSION: Our findings not only provide a relevant model for exploring the effects of plant-soil microbial interactions on plant defense functions and thereby promoting plant growth, but also lay a solid foundation for the future large-scale use of PGPR in agriculture for sustainable agricultural development.

Smart Cellulose-Based Janus Fabrics with Switchable Liquid Transportation for Personal Moisture and Thermal Management.

The Janus fabrics designed for personal moisture/thermal regulation have garnered significant attention for their potential to enhance human comfort. However, the development of smart and dynamic fabrics capable of managing personal moisture/thermal comfort in response to changing external environments remains a challenge. Herein, a smart cellulose-based Janus fabric was designed to dynamically manage personal moisture/heat. The cotton fabric was grafted with N-isopropylacrylamide to construct a temperature-stimulated transport channel. Subsequently, hydrophobic ethyl cellulose and hydrophilic cellulose nanofiber were sprayed on the bottom and top sides of the fabric to obtain wettability gradient. The fabric exhibits anti-gravity directional liquid transportation from hydrophobic side to hydrophilic side, and can dynamically and continuously control the transportation time in a wide range of 3-66 s as the temperature increases from 10 to 40 °C. This smart fabric can quickly dissipate heat at high temperatures, while at low temperatures, it can slow down the heat dissipation rate and prevent the human from becoming too cold. In addition, the fabric has UV shielding and photodynamic antibacterial properties through depositing graphitic carbon nitride nanosheets on the hydrophilic side. This smart fabric offers an innovative approach to maximizing personal comfort in environments with significant temperature variations.

Huang-Lian-Jie-Du Decoction alleviates diabetic encephalopathy by regulating inflammation and pyroptosis via suppression of AGEs/RAGE/NF-κB pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Cognitive dysfunction associated with diabetes, known as diabetic encephalopathy (DE), is a grave neurodegenerative condition triggered by diabetes, and persistent inflammation plays a vital role in its development. The renowned traditional Chinese medicine Huang-Lian-Jie-Du Decoction (HLJDD) is clinically proven to manage diabetes mellitus and Alzheimer's disease and is famous for its heat-clearing and detoxifying effects. However, the underlying mechanisms through which HLJDD affects DE remain to be elucidated. AIM OF THE STUDY: To explore the beneficial effects of HLJDD on improving cognitive dysfunction in DE mice. STUDY DESIGN AND METHODS: A diabetic mouse was established through a high-fat diet and subsequent administration of streptozotocin over five consecutive days. After the animals were confirmed to have diabetes, they were treated with HLJDD. After oral administration of HLJDD or metformin for 14 weeks, behavioral tests were used to assess their cognitive capacity. Biochemical analyses were then performed to detect levels of glucose metabolism, followed by histological analyses to assess pathological damage. Furthermore, AGEs/RAGE/NF-κB axis related proteins were detected by Western blot or immunofluorescence techniques. An advanced UPLC-Q-Orbitrap HRMS/MS analytical technique utilizing a chemical derivatization strategy was employed for comprehensive metabolic profiling of carbonyl compounds in the plasma of DE mice. RESULTS: Pharmacological assessment revealed that HLJDD effectively mitigated cognitive dysfunction, normalized glucose metabolic imbalances, and repaired neuronal damage in DE mice. It reduced neuroinflammation by attenuating carbonyl stress, deactivating astrocytes and microglia, and preserving dopaminergic neurons. Additionally, metabolomics analysis revealed 18 carbonyl compounds with marked disparities between DE and control mice, with 12 metabolites approaching normal levels post-HLJDD intervention. Further investigations showed that HLJDD regulated inflammation and pyroptosis through suppressing AGEs/RAGE/NF-κB pathways. CONCLUSION: Our study indicated that HLJDD could ameliorate carbonyl stress via the regulation of carbonyl compound metabolism profiling, and inhibiting the AGEs/RAGE/NF-κB pathway, thereby alleviating inflammation and pyroptosis to exert beneficial effects on DE.

[3 + 2] Annulation of Vinyl Azides with Aldehydes for the Synthesis of 3-Oxazolines via the [CO + CCN] Strategy.

Despite the widespread utilizable value of 3-oxazolines, mild and efficient access to such a class of unique structures still remains, to date, a challenge. Herein, we present a [3 + 2] annulation strategy, guided by the retrosynthetic principle of [CO + CCN], that utilizes vinyl azides as the CCN module and aldehydes as the CO module. This approach enables the efficient construction of the 3-oxazoline framework with remarkable features, including operational simplicity, environmental friendliness, and high efficiency. Notably, it solely requires the addition of inexpensive and readily available N-hydroxyphthalimide (NHPI) and air oxygen to obtain the desired product. It also provides a new way to generate the hydroxyl radical, which is produced by the homolysis of peroxycarboxylic acid. In addition, control experiments, X-ray crystallographic analysis, high-resolution mass spectrometry (HRMS), and density functional theory (DFT) calculations afford evidence for the key intermediates (hydroxyl radical, carboxyl radical, imine radical, hydroxyl substituted amide derivatives), further confirming the path for realization of 3-oxazolines.

Risk variables of heart failure among patients in China: grey relational approach based multi-dimensional assessment study.

BACKGROUND: Understanding the potential risk factors of heart diseases is key to effectively managing cardiac diseases. The present study quantifies the association of identified risk factors. In addition, the study has compared the association of mortality with hypertension, uncontrolled diabetes, and uncontrolled hyperlipidemia using Grey Relational Approach (GRA) for stroke, lung diseases, smoking, stress, obesity, and lack of exercise. METHOD: Data on risk factors of heart failure were collected from the Global Burden of Disease (GBD) study (2001-2017). From the GBD database, variables have selected the top leading risk factors responsible for mortality from cardiac diseases. Data on risk factors was analyzed using the GRA procedure (utilizing Grey [8.0] software). In the GRA method, the correlation was categorized into three components: GRA - Deng (assesses the effect of one variable specified by data on the other variables), GRA- absolute (assesses the association between variables measured), and GRA-SS (assessed the overall association between the variables measured). Stroke, lung diseases, smoking, stress, obesity, and lack of exercise were taken as dependent variables and their impact was assessed. Hypertension (high grade) uncontrolled diabetes, and uncontrolled hyperlipidemia were considered as independent variables. The relationship between dependent and independent variables was assessed. RESULTS: Overall correlational analysis showed that type 2 diabetes (T2DM) is the risk factor that has a strong relationship with causing heart failure and thereby increases morbidity and mortality among Chinese patients. After T2DM, the second highest risk factor associated was severe dyslipidemia which is responsible for causing heart failure. High-grade hypertension is one-third most common risk factor in causing heart failure. GRA - Deng analysis showed that T2DM is the top risk factor associated with heart failure, followed by high-grade hypertension and severe dyslipidemia (uncontrolled). GRA-absolute analysis showed that severe dyslipidemia is the top risk factor associated with heart failure, followed by high-grade hypertension and T2DM (uncontrolled). GRA-SS analysis showed that high-grade hypertension is the top risk factor associated with heart failure, followed by severe dyslipidemia and T2DM (uncontrolled). CONCLUSIONS: The study reported that T2DM, severe dyslipidemia, and high-grade hypertension as strongly correlated with the development of heart failure after considering other several key risk factors (stroke, lung diseases, smoking, stress, obesity, and lack of exercise). LEVEL OF EVIDENCE: IV. TECHNICAL EFFICACY: Stage 5.

Treatment, Prognostic Markers, and Survival in Thymic Neuroendocrine Tumors, with Special Reference to Temozolomide-Based Chemotherapy.

BACKGROUND: Thymic neuroendocrine tumors (Th-NETs) are rare and aggressive, with a scarcity of research on predicting patient prognosis. Our study aimed to assess the impact of prognostic markers and temozolomide (TMZ)-based chemotherapy on survival in Th-NETs. METHODS: We retrospectively reviewed the medical records of patients diagnosed with Th-NETs between 2013 and 2023 at our institution. We collected clinicopathological data, including tumor pathological grading, staging, serum concentrations of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide, levels of inflammatory factors, and expression of oxygen 6-methylguanine-DNA methyltransferase (MGMT). Treatment details (such as surgery and chemotherapy) and survival outcomes were also documented. RESULTS: A total of 32 patients were included in our study after excluding those without complete available information. The median progression-free survival (PFS) was 12.5 months (95%CI, 8-16 months) for 19 patients who received TMZ-based chemotherapy. Twenty-one patients underwent surgery as the primary treatment, demonstrating a median disease-free survival (DFS) of 51.0 months. The inflammatory factor neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic indicator of DFS in postoperative patients and PFS in TMZ-treated patients. The overall 3-, 5-, and 10-year survival rates were 86.6%, 69.5%, and 33.8%, respectively. Ki67 level exceeding 10% (p = 0.048) and absence of surgical resection (p = 0.003) were significantly associated with worse overall survival (OS). CONCLUSION: Surgical treatment was currently the primary method for treating Th-NETs, and postoperative adjuvant therapy was an essential consideration for specific patient cohorts. Despite widespread positive MGMT expression, TMZ-based chemotherapy showed promise. Some potential prognostic biomarkers such as NLR and NSE need more attention.

Rod-Shaped Mesoporous Zinc-Containing Bioactive Glass Nanoparticles: Structural, Physico-Chemical, Antioxidant, and Immuno-Regulation Properties.

Bioactive glass nanoparticles (BGNs) are applied widely in tissue regeneration. Varied micro/nanostructures and components of BGNs have been designed for different applications. In the present study, nanorod-shaped mesoporous zinc-containing bioactive glass nanoparticles (ZnRBGNs) were designed and developed to form the bioactive content of composite materials for hard/soft tissue repair and regeneration. The nanostructure and components of the ZnRBGNs were characterized, as were their cytocompatibility and radical-scavenging activity in the presence/absence of cells and their ability to modulate macrophage polarization. The ZnRBGNs possessed a uniform rod shape (length ≈ 500 nm; width ≈ 150 nm) with a mesoporous structure (diameter ≈ 2.4 nm). The leaching liquid of the nanorods at a concentration below 0.5 mg/mL resulted in no cytotoxicity. More significant improvements in the antioxidant and M1-polarization-inhibiting effects and the promotion of M2 polarization were found when culturing the cells with the ZnRBGNs compared to when culturing them with the RBGNs. The doping of the Zn element in RBGNs may lead to improved antioxidant and anti-inflammatory effects, which may be beneficial in tissue regeneration/repair.

Olanzapine Modulate Lipid Metabolism and Adipose Tissue Accumulation via Hepatic Muscarinic M3 Receptor-Mediated Alk-Related Signaling.

Olanzapine is an atypical antipsychotic drug and a potent muscarinic M3 receptor (M3R) antagonist. Olanzapine has been reported to cause metabolic disorders, including dyslipidemia. Anaplastic lymphoma kinase (Alk), a tyrosine kinase receptor well known in the pathogenesis of cancer, has been recently identified as a key gene in the regulation of thinness via the regulation of adipose tissue lipolysis. This project aimed to investigate whether Olanzapine could modulate the hepatic Alk pathway and lipid metabolism via M3R. Female rats were treated with Olanzapine and/or Cevimeline (an M3R agonist) for 9 weeks. Lipid metabolism and hepatic Alk signaling were analyzed. Nine weeks' treatment of Olanzapine caused metabolic disturbance including increased body mass index (BMI), fat mass accumulation, and abnormal lipid metabolism. Olanzapine treatment also led to an upregulation of Chrm3, Alk, and its regulator Ptprz1, and a downregulation of Lmo4, a transcriptional repressor of Alk in the liver. Moreover, there were positive correlations between Alk and Chrm3, Alk and Ptprz1, and a negative correlation between Alk and Lmo4. However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders.

The efficacy of postoperative radiotherapy in resected pâ ¢A-N2 EGFR mutant and wild-type lung adenocarcinoma.

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Identifying new cancer genes based on the integration of annotated gene sets via hypergraph neural networks.

MOTIVATION: Identifying cancer genes remains a significant challenge in cancer genomics research. Annotated gene sets encode functional associations among multiple genes, and cancer genes have been shown to cluster in hallmark signaling pathways and biological processes. The knowledge of annotated gene sets is critical for discovering cancer genes but remains to be fully exploited. RESULTS: Here, we present the DIsease-Specific Hypergraph neural network (DISHyper), a hypergraph-based computational method that integrates the knowledge from multiple types of annotated gene sets to predict cancer genes. First, our benchmark results demonstrate that DISHyper outperforms the existing state-of-the-art methods and highlight the advantages of employing hypergraphs for representing annotated gene sets. Second, we validate the accuracy of DISHyper-predicted cancer genes using functional validation results and multiple independent functional genomics data. Third, our model predicts 44 novel cancer genes, and subsequent analysis shows their significant associations with multiple types of cancers. Overall, our study provides a new perspective for discovering cancer genes and reveals previously undiscovered cancer genes. AVAILABILITY AND IMPLEMENTATION: DISHyper is freely available for download at https://github.com/genemine/DISHyper.

TU-LESS procedure for acute abdomen in late pregnancy: a retrospective study.

BACKGROUND: Acute abdominal conditions during pregnancy are significant risks to maternal and fetal health, necessitating timely diagnosis and intervention. The choice of surgical approach is a major concern for obstetricians. OBJECTIVE: To evaluate the safety and efficacy of the TU-LESS procedure for acute abdomen in late pregnancy. METHODS: We retrospectively analyzed 12 patients who underwent TU-LESS for acute abdominal conditions in the third trimester from 2020 to 2023. We reviewed medical records for clinical characteristics, surgical interventions, postoperative complications, and pregnancy outcomes. RESULTS: The study included patients with a median age of 27 (range 20-35) and a BMI of 24.33 kg/m2 (range 21.34-31.96). The median gestational age at surgery was 30 weeks (range, 28 + 3-32 + 4 weeks), with surgeries lasting an average of 60 min (range, 30-163 min). Blood loss was 2-20 mL, and the median hospital stay post-surgery was 6 days (range, 2-16 days). There were no significant complications. The median time to delivery after TU-LESS was 56 days (range, 26-66 days), resulting in 8 full-term deliveries, 2 preterm cesareans, and 2 preterm vaginal deliveries. All newborns were healthy, with no fetal losses or neonatal deaths. CONCLUSION: TU-LESS, performed by experienced obstetricians and gynecologists with proper preoperative preparation, is safe and effective for managing acute abdomen in late pregnancy, without the need to delay surgery due to gestational age.