Sex disparity in the association between metabolic-anthropometric phenotypes and risk of obesity-related cancer: a prospective cohort study.

BACKGROUND: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex. METHODS: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models. RESULTS: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape. CONCLUSIONS: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.

Genetic Aspects of Necrobiotic Xanthogranuloma.

This genetic association study examines the genetic aspects of necrobiotic xanthogranuloma in 3 patients in China.

EAT-Lancet Diet Pattern, Genetic Predisposition, Inflammatory Biomarkers, and Risk of Lung Cancer Incidence and Mortality.

SCOPE: The association between a planetary and sustainable EAT-Lancet diet and lung cancer remains inconclusive, with limited exploration of the role of genetic susceptibility and inflammation. METHODS AND RESULTS: The study includes 175 214 cancer-free participants in the UK Biobank. Fourteen food components are collected from a 24-h dietary recall questionnaire. A polygenic risk score is constructed through capturing the overall risk variants for lung cancer. Sixteen inflammatory biomarkers are assayed in blood samples. Participants with the highest EAT-Lancet diet scores (≥12) have a lower risk of lung cancer incidence (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.51-0.80) and mortality (HR = 0.65, 95% CI: 0.48-0.88), compared to those with the lowest EAT-Lancet diet scores (≤8). Interestingly, there is a significantly protective trend against both lung adenocarcinoma and lung squamous cell carcinoma with higher EAT-Lancet diet scores. Despite no significant interactions, a risk reduction trend for lung cancer is observed with increasing EAT-Lancet diet scores and decreasing genetic risk. Ten inflammatory biomarkers partially mediate the association between the EAT-Lancet diet and lung cancer risk. CONCLUSION: The study depicts a lower risk of lung cancer conferred by the EAT-Lancet diet associated with lower inflammation levels among individuals with diverse genetic predispositions.

Artificial intelligence interpretation of touch print smear cytology of testicular specimen from patients with azoospermia.

PURPOSE: Identification of mature sperm at microdissection testicular sperm extraction (mTESE) is a crucial step of sperm retrieval to help patients with non-obstructive azoospermia (NOA) proceed to intracytoplasmic sperm injection. Touch print smear (TPS) cytology allows immediate interpretation and prompt sperm identification intraoperatively. In this study, we leverage machine learning (ML) to facilitate TPS reading and conquer the learning curve for new operators. MATERIALS AND METHODS: One hundred seventy-six microscopic TPS images from the testicular specimen of patients with azoospermia at Taipei Veterans General Hospital were retrospectively collected, including categories of Sertoli cell, primary spermatocytes, round spermatids, elongated spermatids, immature sperm, and mature sperm. Among them, 118 images were assigned as the training set and 29 images as the validation set. RetinaNet (Lin et al. in IEEE Trans Pattern Anal Mach Intell. 42:318-327, 2020), a one-stage detection framework, was adopted for cell detection. The performance was evaluated at the cell level with average precision (AP) and recall, and the precision-recall (PR) curve was displayed among an independent testing set that contains 29 images that aim to assess the model. RESULTS: The training set consisted of 4772 annotated cells, including 1782 Sertoli cells, 314 primary spermatocytes, 443 round spermatids, 279 elongated spermatids, 504 immature sperm, and 1450 mature sperm. This study demonstrated the performance of each category and the overall AP and recall on the validation set, which were 80.47% and 96.69%. The overall AP and recall were 79.48% and 93.63% on the testing set, while increased to 85.29% and 93.80% once the post-meiotic cells were merged into one category. CONCLUSIONS: This study proposed an innovative approach that leveraged ML methods to facilitate the diagnosis of spermatogenesis at mTESE for patients with NOA. With the assistance of ML techniques, surgeons could determine the stages of spermatogenesis and provide timely histopathological diagnosis for infertile males.

CRISPR/Cas9-mediated exon skipping to restore premature translation termination in a DFNB4 mouse model.

SLC26A4 encodes pendrin, a crucial anion exchanger essential for maintaining hearing function. Mutations in SLC26A4, including the prevalent c.919-2 A > G splice-site mutation among East Asian individuals, can disrupt inner ear electrolyte balance, leading to syndromic and non-syndromic hearing loss, such as Pendred syndrome and DFNB4. To explore potential therapeutic strategies, we utilized CRISPR/Cas9-mediated exon skipping to create a Slc26a4∆E8+E9/∆E8+E9 mouse model. We assessed pendrin expression in the inner ear and evaluated vestibular and auditory functions. The Slc26a4∆E8+E9/∆E8+E9 mice demonstrated reframed pendrin in the inner ear and normal vestibular functions, contrasting with severely abnormal vestibular functions observed in the Slc26a4 c.919-2 A > G splicing mutation mouse model. However, despite these molecular achievements, hearing function did not show the expected improvement, consistent with observed pathology, including cochlear hair cell loss and elevated hearing thresholds. Consequently, our findings highlight the necessity for alternative genetic editing strategies to address hearing loss caused by the SLC26A4 c.919-2 A > G mutation.

LUTS/BPH increases the risk of depressive symptoms among elderly adults: A 5-year longitudinal evidence from CHARLS.

OBJECTIVE: The prevalence of Lower Urinary Tract Symptoms suggestive of Benign Prostatic Hyperplasia (LUTS/BPH) is notably high and potentially elevates the likelihood of depressive symptoms. This study was designed to employ both cross-sectional and longitudinal methodologies to explore the correlation between LUTS/BPH and depressive symptoms among middle-aged and elderly men in China. METHODS: This investigation utilized data from the China Health and Retirement Longitudinal Study (CHARLS), with the initial dataset from 2015 serving as the baseline and subsequent data from 2018 and 2020 facilitating longitudinal analysis. The study encompassed a baseline cohort of 5156 men aged 45 years and above, and an expansive longitudinal analytical sample of 23,530 participants spanning from 2015 to 2020. The assessment of depressive symptoms was conducted using the 10-item Center for Epidemiological Studies Depressive Symptoms Scale (CESD-10). To investigate the factors associated with LUTS/BPH, the relationship between LUTS/BPH and depressive symptoms, and to evaluate the incidence rate of depressive symptoms onset based on LUTS/BPH status, multivariate logistic analyses and logistic regression models were employed. RESULTS: Our results reveal a markedly higher incidence of depressive symptoms among individuals with LUTS/BPH, at 30.16 %, compared to 22.94 % in those without LUTS/BPH. This pattern was consistent in both mild and moderate depressive symptoms categories. However, the prevalence of severe depressive symptoms did not exhibit a significant disparity between the two groups. Longitudinal analysis spanning from 2015 through 2018 and 2020 further corroborated these observations. Individuals with LUTS/BPH showed a substantially higher incidence of depressive symptoms across all severity levels compared to those without LUTS/BPH. Specifically, the presence of LUTS/BPH was linked to a 53 % heightened risk of mild depressive symptoms, a 45 % increase in moderate depressive symptoms, and an alarming 229 % surge in severe depressive symptoms risk between 2015 and 2018. Additionally, from 2015 to 2020, there was a 30 % increased risk for mild depressive symptoms, a 41 % rise for moderate depressive symptoms, and a 106 % escalation in the risk of severe depressive symptoms among those with LUTS/BPH. CONCLUSION: In middle-aged and older Chinese adults, LUTS/BPH were correlated with an elevated risk of depressive symptoms.

[Thinking on the application of reinforcing and reducing techniques of moxibustion in the staged differentiation and treatment of prostate cancer].

The effect of reinforcing and reducing techniques of moxibustion depends on types of moxibustion, operation methods and characteristics of acupoints. According to the ups and downs of pathogenic factors and healthy qi during the occurrence and development of prostate cancer, three stages are divided, namely, the stage of initial accumulation of cancer toxicity, the stage of the deficiency of healthy qi and toxin retention, and the stage of yang deficiency and cold stagnation. In the stage of initial accumulation of cancer toxicity, zangfu function is impaired and the dampness, heat and stasis toxin are accumulated in the body; due to which, the reducing technique of moxibustion should be dominant and the healthy qi be supported in combination. In treatment, the wheat-grain sized cone moxibustion, suppurative moxibustion and garlic-isolated moxibustion are applicable. The reducing purpose of moxibustion is obtained by delivering an appropriate increased number of moxa cones, large dosage and strong stimulation at acupoints. In the stage of the deficiency of healthy qi and toxin retention, qi movement is weakened and cancer toxin consumes yin; the reinforcing healthy qi and removing pathogenic factors should be operated simultaneously. In treatment, mild moxibustion and suppurative moxibustion can be used. The reduced number of moxa cones, moderate dosage of moxibustion and mild stimulation at acupoints should be considered to gently adjust the conditions of deficiency and excess. In the stage of yang deficiency and cold stagnation, spleen and kidney yang is deficient, and the meridians are blocked by cold and damp pathogens. In treatment, the reinforcing technique of moxibustion should be used specially and eliminating pathogenic factors be combined. Monkshood cake-insulated moxibustion, salt-insulated moxibustion and wheat-grain sized cone moxibustion can be adopted. The less number of moxa cones, small dosage and appropriately increased frequency of treatment should be considered to produce the gentle and sustained stimulation at acupoints so as to excite the healthy qi and promote the transformation of qi and blood.

Half-dose ticagrelor versus standard-dose clopidogrel in a dual antiplatelet regimen for stent-assisted coiling or flow diversion of unruptured intracranial aneurysms: a cohort study.

BACKGROUND: Intracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in interventional cardiology. However, the preserved antithrombotic efficacy and better safety of half-dose (45 mg twice daily) ticagrelor remains unverified in patients undergoing stent-assist coiling (SAC) or flow diversion (FD) treating unruptured intracranial aneurysms (UIA). METHODS: A single-center, prospective, cohort study was conducted to compare DAPT with aspirin 100 mg daily plus half-dose ticagrelor vs standard-dose clopidogrel (75 mg daily) in UIA patients. The adenosine diphosphate inhibition (ADPi) rate was utilized to quantify the antagonization of adenosine diphosphate (ADP)-induced platelet aggregation. The patients were followed-up at 6 month after discharge. The primary efficacy outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), and the primary safety outcome was major bleeding. The secondary outcome was minor hemorrhage. RESULTS: Our study included 322 UIA patients, of which 254 patients were eventually enrolled after propensity score matching. The ADPi of half-dose ticagrelor (51.56%±31.46%) was comparable (P=0.089) to that of clopidogrel (57.44%±22.76%). The outcomes were also comparable. Five (3.94%) patients in the ticagrelor group and eight (6.30%) patients in the clopidogrel group reported MACCE (P=0.393). One patient in the ticagrelor group was diagnosed with asymptomatic intracranial hemorrhage 1 month after stenting. There were 36 (28.35%) minor hemorrhagic events in the ticagrelor group and 35 (27.56%) in the clopidogrel group, (P=0.889). CONCLUSION: Half-dose ticagrelor was effective and safe as a potential alternative to clopidogrel in the DAPT regimen for patients undergoing SAC/FD for UIA.

Diversified Reactivity of Triphenylphosphine: Reinvestigation of the Phosphine-Mediated Reductive Condensation Approach for the Synthesis of Substituted Furans.

A reinvestigation of "Phosphine-Mediated Reductive Condensation of γ-Acyloxy Butynoates: A Diversity Oriented Strategy for the Construction of Substituted Furans" (J. Am. Chem. Soc. 2004, 126, 4118-4119) revealed different chemoselectivity of triphenylphosphine in the reactions with the γ-acyloxy butynoate substrates of varying substitution patterns/electronics. Furthermore, the electronics of the triaryl phosphine reagent could be tuned to trap a putative intermediate such as A, leading to the semihydrogenation of propiolamide substrates.

Relationship between CCL2 gene 2518A/G (rs1024611) polymorphism and age-related macular degeneration susceptibility: meta-analysis and trial sequential analysis.

PURPOSE: This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD). METHODS: PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed. RESULTS: Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings. CONCLUSION: The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.

Axially-Polarized Excitonic Series and Anisotropic van der Waals Stacked Heterojunction in a Quasi-1D Layered Transition-Metal Trichalcogenide.

Anisotropic optical 2D materials are crucial for achieving multiple-quanta functions within quantum materials, which enables the fabrication of axially polarized electronic and optoelectronic devices. In this work, multiple excitonic emissions owning polarization-sensitive orientations are clearly detected in a multilayered quasi-1D ZrS3 nanoribbon with respect to the nanostripe edge. Four excitons denoted as AS1, AS2, AS, and A2 with E ⊥ b polarized direction and one prominent A1 exciton with E || b polarized emission are simultaneously detected in the polarized micro-photoluminescence (µPL) measurement of 1.9-2.2 eV at 10 K. In contrast to light emission, polarized micro-thermoreflectance (µTR) measurements are performed to identify the polarization dependence and verify the excitons in the multilayered ZrS3 nanoribbon from the perspective of light absorption. At 10 K, a prominent and broadened peak on the lower-energy side, containing an indirect resonant emission (DI) observed by µPL and an indirect defect-bound exciton peak (AInd) observed by both µPL and µTR, is simultaneously detected, confirming the existence of a quasi-direct band edge in ZrS3. A van der Waals stacked p-GaSe/n-ZrS3 heterojunction solar cell is fabricated, which demonstrates a maximum axially-polarized conversion efficiency up to 0.412% as the E || b polarized light incident onto the device.

Cyanobacteria decay alters CH4 and CO2 produced hotspots along vertical sediment profiles in eutrophic lakes.

Cyanobacteria-derived organic carbon has been reported to intensify greenhouse gas emissions from lacustrine sediments. However, the specific processes of CH4 and CO2 production and release from sediments into the atmosphere remain unclear, especially in eutrophic lakes. To investigate the influence of severe cyanobacteria accumulation on the production and migration of sedimentary CH4 and CO2, this study examined the different trophic level lakes along the middle and lower reaches of the Yangtze River. The results demonstrated that eutrophication amplified CH4 and CO2 emissions, notably in Lake Taihu, where fluxes peaked at 929.9 and 7222.5 µmol/m2·h, mirroring dissolved gas levels in overlying waters. Increased sedimentary organic carbon raised dissolved CH4 and CO2 concentrations in pore-water, with isotopic tracking showing cyanobacteria-derived carbon specifically elevated CH4 and CO2 in surface sediment pore-water more than in deeper layers. Cyanobacteria-derived carbon deposition on surface sediment boosted organic carbon and moisture levels, fostering an anaerobic microenvironment conducive to enhanced biogenic CH4 and CO2 production in surface sediments. In the microcosm systems with the most severe cyanobacteria accumulation, average CH4 and CO2 concentrations in surface sediments reached 6.9 and 2.3 mol/L, respectively, surpassing the 4.7 and 1.4 mol/L observed in bottom sediments, indicating upward migration of CH4 and CO2 hotspots from deeper to surface layers. These findings enhance our understanding of the mechanisms underlying lake sediment carbon emissions induced by eutrophication and provide a more accurate assessment of lake carbon emissions.

Hypermethylation of the glutathione peroxidase 4 promoter predicts poor prognosis in patients with hepatitis B virus-associated acute-on-chronic liver failure.

Background: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a syn-drome with a high short-term mortality rate, and its prognosis is critical in clinical management. This study aimed to investigate the clinical significance of glutathione peroxidase 4 (GPX4) in the occurrence and development of HBV-ACLF and its prognostic value for 90-day mortality. Methods: The expression levels of GPX4, oxidative stress-related molecules and inflammatory cytokines in serum or peripheral blood mononuclear cells (PBMCs) of 289 participants were determined by RT-qPCR or ELISA, and the methylation level of GPX4 promoter in PBMCs was determined by MethyLight. Results: The expression levels of GPX4 in the PBMCs and serum of HBV-ACLF patients were lower than those in non-HBV-associated acute-on-chronic liver failure (non-HBV ACLF) patients, patients with chronic hepatitis B (CHB) and healthy control (HC) individuals, while the methylation level of the GPX4 promoter was greater. In HBV-ACLF patients, the methylation level of the GPX4 promoter is correlated with oxidative stress, inflammation-related molecules, and some clinicopathological indicators. The methylation level of the GPX4 promoter was identified as an independent risk factor for 90-day mortality in HBV-ACLF patients and yielded a larger area under the receiver operating characteristic curve (AUROC) than the model for end-stage liver disease (MELD) score in predicting 90-day mortality. Conclusion: The GPX4 promoter methylation level has promising potential as a predictor of 90-day mortality in patients with HBV-ACLF.

Identification of serum metabolites associated with aristolochic acid nephropathy severity and insights into the underlying mechanism.

Aristolochic acid nephropathy (AAN) is a rapidly progressive kidney disease caused by medical or environmental exposure to aristolochic acids (AAs). This study aimed to identify serum metabolites associated with the severity of acute AAN and investigate the underlying mechanisms. Male C57BL/6 mice were treated with vehicle and 3 doses of aristolochic acid I (AAI) (1.25, 2.5, and 5 mg/kg/d) for 5 days by intraperitoneal injection. The results showed that AAI dose-dependently increased blood urea nitrogen (BUN) and serum creatinine (Scr) levels and renal pathological damage. Non-targeted metabolomics revealed that differences in serum metabolite profiles from controls increased with increasing AAI doses. Compared with the control group, 56 differentially expressed metabolites (DEMs) that could be affected by all 3 doses of AAI were obtained. We further identified 13 DEMs whose abundance significantly correlated with Scr and BUN levels and had good predictive values for diagnosing AAI exposure. Among the 13 DEMs, lipids and lipid-like molecules constituted the majority. Western blotting found that AAI suppressed renal fatty acid oxidation (FAO)-related enzymes expression. In conclusion, these findings provided evidence for developing biomarkers for monitoring AAs exposure and AAN diagnosis and indicated activation of FAO as a potential direction for the treatment of AAN.

Scutellaria barbata D.Don and Scleromitrion diffusum (Willd.) R.J.Wang inhibits the progression of triple negative breast cancer though the activation inhibition of NF-κB triggered by CAFs-derived IL6.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment options for triple-negative breast cancer (TNBC) are limited. Traditional Chinese Medicine (TCM) plays an important role in the treatment of TNBC. The herb pair Scutellaria barbata D.Don and Scleromitrion diffusum (Willd.) R.J.Wang (SH) is commonly used in clinical practice for its anti-tumor properties. It has been proven to have good therapeutic effects on tumor-related diseases, but the underlying molecular mechanisms are not yet fully explained. AIM OF STUDY: Through bioinformatics, it was validated that IL6, primarily derived from cancer-associated fibroblasts (CAFs), is associated with poor prognosis. Additionally, cell and animal experiments confirmed that SH inhibits tumor proliferation, migration, and growth in an orthotopic tumor model by suppressing the IL6/NF-κB pathway. MATERIALS AND METHODS: GEO, TCGA and HPA databases were used to analyze the prognostic value of CAFs and IL6, then IL6 resource was detected. After the bioinformatics, the influence of CAFs and CAFs-derived IL6 on TNBC was verified by experiments both in vitro and in vivo. Cell clone formation assay, wound-Healing assay, and Transwell assay were used to detect the promotion of CAFs and CAFs-derived IL6 and the inhibition of SH in vitro. TNBC model in mice was used to prove the promotion of CAFs and CAFs-derived IL6 and the inhibition of SH in vivo. The biological pathway of NF-κB was explored by western blotting through detecting unique molecules. RESULTS: Bioinformatics analysis revealed that higher proportion of CAFs and elevated level of IL6 were significantly associated with poor prognosis in TNBC. At the same time, IL6 was proved predominantly derived from CAFs. After the indication of bioinformatics, experiments in vitro demonstrated that both CAFs and IL6 could enhance the clone formation and migration ability of MDA-MD-231 cells (231), furthermore, the promotion of CAFs was related with the level of IL6. Based on these data, mechanism was detected that CAFs-derived IL6 enhancement was closely related to the activation of NF-κB signaling pathway, while the activation can be reduced by SH. In the end, the promotion of CAFs/CAFs-derived IL6/NF-κB and the efficacy of SH inhibition were both confirmed by experiments in vivo. CONCLUSIONS: Bioinformatics data indicates that higher proportion of CAFs and higher level of CAFs-derived IL6 are significantly related to poorer survival of TNBC. CAFs and CAFs-derived IL6 were proved to promote the progression of TNBC both in vitro and in vivo, and the process of which was significantly related to the activation of NF-κB. SH inhibited the progress of TNBC, which was proved to be closely related to CAFs/CAFs-derived IL6/NF-κB.

Cardiovascular health, polygenic risk score, and cancer risk: a prospective cohort study.

BACKGROUND: Cancer and cardiovascular disease share common lifestyle risk factors. However, it remains unclear whether cardiovascular health (CVH) evaluated by Life's Essential 8 can predict cancer risk, and attenuate the influence of genetic susceptibility on cancer. OBJECTIVES: We aimed to evaluate independent and joint associations of CVH and polygenic risk score (PRS) with risks of overall and site-specific cancers. METHODS: We undertook a population-based cohort study based on the UK Biobank. The CVH score was constructed by physical activity, body mass index, nicotine exposure, sleep, diet, blood pressure, lipid profile, and blood glucose. PRSs were assessed individually for 18 cancer types by their independent single-nucleotide polymorphisms previously identified in genome-wide association studies. Multivariable Cox proportional-hazards models were applied to explore the independent and joint associations of CVH and PRS with cancer incidence risk. The results were displayed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with low CVH, high CVH was associated with decreased risks of overall cancer and the majority of common cancers, including digestive system [HRs (95% CI): 0.33 (0.23, 0.45)-0.66 (0.58, 0.75)], lung (HR: 0.25; 95% CI: 0.21, 0.31), renal (HR: 0.42; 95% CI: 0.32, 0.56), bladder (HR: 0.55; 95% CI: 0.44, 0.69), breast (HR: 0.83; 95% CI: 0.74, 0.92), and endometrial cancers (HR: 0.39; 95% CI: 0.30, 0.51). For overall cancer in males, there was an interaction between CVH and PRS. Notably, individuals with high CVH across all levels of PRS had lower risks of overall cancer for females and 8 site-specific cancers than those with low CVH and high PRS [HRs (95% CIs): 0.18 (0.12, 0.25)-0.79 (0.71, 0.87)]. CONCLUSIONS: High CVH was related to decreased risks of overall cancer and multiple cancers regardless of genetic predispositions. Our findings underscored the value of improving CVH for cancer prevention in the general population.

Preoperative prediction model of lymph node metastasis in the inguinal and femoral region based on radiomics and artificial intelligence.

OBJECTIVE: To predict preoperative inguinal lymph node metastasis in vulvar cancer patients using a machine learning model based on imaging features and clinical data from pelvic magnetic resonance imaging (MRI). METHODS: 52 vulvar cancer patients were divided into a training set (n=37) and validation set (n=15). Clinical data and MRI images were collected, and regions of interest were delineated by experienced radiologists. A total of 1688 quantitative imaging features were extracted using the Radcloud platform. Dimensionality reduction and feature selection were applied, resulting in a radiomics signature. Clinical characteristics were screened, and a combined model integrating the radiomics signature and significant clinical features was constructed using logistic regression. Four machine learning classifiers (K nearest neighbor, random forest, adaptive boosting, and latent dirichlet allocation) were trained and validated. Model performance was evaluated using the receiver operating characteristic curve and the area under the curve (AUC), as well as decision curve analysis. RESULTS: The radiomics score significantly differentiated between lymph node metastasis positive and negative patients in both the training and validation sets. The combined model demonstrated excellent discrimination, with AUC values of 0.941 and 0.933 in the training and validation sets, respectively. The calibration curve and decision curve analysis confirmed the model's high predictive accuracy and clinical utility. Among the machine learning classifiers, latent dirichlet allocation and random forest models achieved AUC values >0.7 in the validation set. Integrating all four classifiers resulted in a total model with an AUC of 0.717 in the validation set. CONCLUSION: Radiomics combined with artificial intelligence can provide a new method for prediction of inguinal lymph node metastasis of vulvar cancer before surgery.

The new pattern for dual NOTCH pathway involving nuclear transcription and mitochondrial regulation supports therapeutic mechanism of 4-butyl benzophenone derivatives against SIRS.

The systemic inflammatory response syndrome (SIRS) represents a self-amplifying cascade of inflammatory reactions and pathophysiological states triggered by infectious or non-infectious factors. The identification of disease targets and differential proteins in the liver (the unique and important immune organ) of SIRS mice treated with the lead compound D1 was conducted using the Genecards database and proteomic analysis, respectively. Subsequently, NOTCH1 was identified as the potential hub target via an intersection analysis between the aforementioned differentially expressed proteins and disease targets. Based on our previous research on the structure-activity relationship, we designed and synthesized a series of SIRS-related derivatives, wherein butyl, halogen, and ester groups were incorporated into benzophenone, aiming at exploring the anti-inflammatory protective action from the perspective of macrophage polarization. Notably, these derivatives exhibited a direct binding capability to the O-glucosylation site (SER496) or its vicinities (such as SER492, VAL485) of NOTCH1 using docking, SPR, DARTS, and CETSA techniques. Mechanistically, derivative D6 exerted anti-inflammatory effects via the dual NOTCH pathway. Firstly, it could inhibit NOTCH1 nuclear transcriptional activity, attenuate the interaction between NICD and RBPJK, concurrently suppress NF-κB and NLRP3 inflammasome (NLRP3, ASC, and cleaved CASP1) activation, and promote NICD (NOTCH1 active fragments) ubiquitination metabolism (the nuclear transcriptional pathway). Secondly, it might possess the ability to increase PGC1α level, subsequently, enhance ATP and MMP levels, mitigate ROS production, increase mitochondrial numbers, and ameliorate mitochondrial inflammatory damage (the mitochondrial pathway). Importantly, the activator Jagged1 could effectively reverse the aforementioned effects, while the inhibitor DAPT exhibited a synergistic effect, suggesting that the nuclear transcriptional regulation and mitochondrial regulation were both in a NOTCH1-dependent manner. Subsequently, it effectively alleviated the inflammatory response and preserved organ function as evidenced by up-regulating M2-type macrophage-related anti-inflammatory cytokines (IL10, TGFß, CD206, and ARG1) and down-regulating M1-type macrophage-related pro-inflammatory cytokines (NO, IL6, IL18, iNOS, TNFα, CD86, and IL1ß). In a word, derivative D6 modulated macrophage polarization and effectively mitigated SIRS by targeting inhibition of the dual NOTCH pathway.

Investigation of the effects of biochar amendment on soil under freeze‒thaw cycles and the underlying mechanism.

Biochar (BC) is widely utilized as a soil amendment; however, for widely distributed seasonally frozen soils, the effect of BC on soil and the optimal utilization of BC during the freeze‒thaw process are still unclear. In this study, the effects of freeze‒thaw aged biochar (FT-BC) and BC on soil properties and wheat cultivation were systematically investigated, and the underlying interaction mechanism between BC and soil was explored. The results show that FT-BC dramatically reduces the adverse effects of freeze‒thaw cycles on soil, enhances wheat growth, and increases dry matter yield by 17.5 %, which is mainly attributed to the ability of FT-BC to maintain soil structure, reduce water loss rates to below 0.20 g/h, and decrease nitrogen leaching by more than 20 % during freeze‒thaw cycles. Additionally, fresh BC had a greater effect on the fixation of cadmium than FT-BC in the soil, reducing its accumulation in wheat by 22.5 %. Multiple characterizations revealed that the freeze‒thaw process increased the porosity and specific surface area of FT-BC, providing more sites for water and nitrogen adsorption, whereas the dissolved organic matter released from fresh BC had a better ability to trap cadmium. These findings provide insights into the interactions between BC and soil components during the freeze‒thaw process and suggest the optimized utilization of fresh BC and FT-BC for different soil repair purposes.

Risk Factors for Post-Stroke Depression Following the Lifting of COVID-19 Restrictions.

Purpose: Research on post-stroke depression (PSD) following the lifting of coronavirus disease 2019 (COVID-19) restrictions remains sparse. This study aimed to investigate the factors associated with PSD after the easing of COVID-19 restriction measures. Patients and Methods: This cross-sectional study was conducted with 947 stroke patients (cerebral hemorrhage and cerebral infarction) meeting the inclusion criteria. Participants completed a demographic questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Additionally, data were collected on C-reactive protein (CRP), homocysteine (Hcy), modified Rankin Scale (mRS), stroke site, National Institutes of Health Stroke Scale (NIHSS), thyroid-stimulating hormone (TSH), and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. This study assessed correlations between these indices and PSD. Results: Stroke patients with a PHQ-9 score ≥5 were identified as having PSD, with a prevalence rate of 14.15%. No significant correlation was found between previous COVID-19 infection and PSD. However, multiple regression analysis revealed associations between PSD and the following factors: TSH (OR: 0.87, 95% CI: 0.76-1), CRP levels (OR: 1.01, 95% CI: 1-1.02), family history of stroke (OR: 4.25, 95% CI: 1.66-10.88), migraine history (OR: 8.63, 95% CI: 2.49-29.85), and shorter sleep duration (OR: 0.6, 95% CI: 0.51-0.71) (all P < 0.05). Conclusion: CRP, family history of stroke, migraine, sleep duration, and TSH are identified as independent risk factors for PSD following the lifting of COVID-19 restrictions.