D-dimer is a prognostic marker for 1-year mortality in patients with chronic liver failure and hepatic encephalopathy.

Background and Aim: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver failure with poor outcomes. The present study aimed to evaluate the predictive values of D-dimer in patients with HE. Materials and Methods: Patients with chronic liver failure (CLF) and HE were enrolled. Univariate and multivariate logistic analysis was performed to investigate the risk factors for 1-year mortality of HE. Results: During the first year after diagnosis, 39.2% (65/166) of the patients died. D-dimer was significantly higher in non-survivors (Z=2.617, p<0.01). Both D-dimer and international normalized ratio (INR) positively correlated with Child-Pugh and MELD scores, and negatively correlated with sodium (all p<0.01). Moreover, there was a negative relationship between D-dimer and HE grades (r=-0.168, p=0.031), while the relationship between INR and HE grades was not significant (r=0.083, p=0.289). Multivariate analysis showed that age (odds ratio (OR):1.035, 95% CI:1.004-1.067, p=0.03), D-dimer (OR=1.138, 95% CI:1.030-1.258, p=0.01), ALT (OR=1.012, 95% CI:1.001-1.022, p=0.03), and sodium (OR=0.920, 95% CI:0.858-0.986, p=0.02) were independent risk factors for 1-year mortality. Then, a new model Model(Age_DD_ALT_Na) incorporating age, D-dimer, ALT, and sodium was developed. AUROC of Model(Age_DD_ALT_Na) was 0.732, which was significantly higher than MELD and Child-Pugh scores (AUROC: 0.602 and 0.599, p=0.013 and 0.022). Conclusion: D-dimer is a prognostic marker for 1-year mortality in patients with CLF and HE.

Causal relationship between systemic circulatory inflammatory regulators and intervertebral disc degeneration: A bidirectional 2-sample Mendelian randomization study.

In the context of the development of intervertebral disc degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. The understanding of the causal relationship between inflammatory mediators and IDD is of great importance in preventing and delaying disc degeneration in the future. We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8293 individuals from Finland. The genetic data for IDD were derived from the most recent GWAS summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional 2-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted, weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR-Egger intercept analysis was performed to assess pleiotropy. We established causal relationships between 3 specific inflammatory factors and IDD. Elevated levels of MIP-1ß (OR = 0.956, 95% CI: -0.08 to -0.006; P = .02) and IFN-G (OR = 0.915, 95% CI: -0.16 to -0.02; P = .01) expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL-13 levels (OR = 0.967, 95% CI: -0.063 to -0.004; P = .03). In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.

Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: A retrospective cohort study: A Staging System for Hepatoid Adenocarcinoma of the Stomach.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC). METHODS: The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at 2 centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival. RESULTS: After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the 8th American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the 8th AJCC staging system (0.667, 95% CI: 0.610-0.723, P<0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the 8th AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively the mpTNM staging system outperformed the 8th AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P<0.05). Time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the 8th AJCC staging system with increasing observation time. CONCLUSION: The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the 8th AJCC staging system.

Defect Engineering of Ultrasmall TiO2 Nanoparticles Enables Highly Efficient Photocatalysts for Solar H2 Production from Woody Biomass.

The conversion of woody biomass to H2 through photocatalysis provides a sustainable strategy to generate renewable hydrogen fuel but was limited by the slow decomposition rate of woody biomass. Here, we fabricate ultrasmall TiO2 nanoparticles with tunable concentration of oxygen vacancy defects (VO-TiO2) as highly efficient photocatalysts for photocatalytic conversion of woody biomass to H2. Owing to the positive role of oxygen vacancy in reducing energy barrier for the generation of •OH which was the critical species to oxidize woody biomass, the obtained VO-TiO2 achieves rapid photocatalytic conversion of α-cellulose and poplar wood chip to H2 in the presence of Pt nanoclusters as the cocatalyst. As expected, the highest H2 generation rate in α-cellulose and poplar wood chip system respectively achieve 1146 and 59 µmol h-1 g-1, and an apparent quantum yield of 4.89% at 380 nm was obtained in α-cellulose aqueous solution.

Enhanced skin benefits of EGCG loaded in nonapeptide-1-conjugated mesoporous silica nanoparticles to reverse skin photoaging.

Epigallocatechin-3-gallate (EGCG), a catechin present in green tea, has been studied extensively for its potential as a cosmetic ingredient due to its various biological properties. However, the low stability and bioavailability of EGCG have hindered its effective utilization in cosmetic applications. This study, to improve the stability and bioavailability of EGCG for reversing skin photo-aging, nonapeptide-1-conjugated mesoporous silica nanoparticles (EGCG@NP-MSN) were fabricated to load EGCG. MSNs can regulate the EGCG release and provide ultraviolet light (UV) protection to possess excellent photostability. Nonapeptide-1 exhibits melanin transfer interference properties and reduces the melanin content in treated skin areas. In vitro and in vivo results confirmed that the EGCG-loaded MSNs retained antioxidant properties, effectively scavenged the melanin and significantly reduced the deoxyribonucleic acid (DNA) damage in skin cells exposed to UV irradiation. The melanin inhibition rate is 5.22 times and the tyrosinase inhibition rate is 1.57 times that of free EGCG. The utilization of this innovative platform offers the potential for enhanced stability, controlled release, and targeted action of EGCG, thereby providing significant advantages for skin application.This delivery system combines the advantages of antioxidant, anti-aging, and anti-UV radiation properties, paving the way for the cosmetics development with improved efficacy and better performance in promoting skin health and appearance.

Fat Mass Index Predicts the Effect of Weight Loss and Quality of Life Early After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Fat mass index (FMI) is a body composition indicator that reflects body fat content. Laparoscopic sleeve gastrectomy (LSG) is widely performed in patients with obesity. OBJECTIVE: This study aimed to evaluate the value of the FMI in predicting weight loss effect and quality of life early after LSG. MATERIAL AND METHODS: From January 2014 to July 2022, the clinical data and computed tomography (CT) images of patients who underwent LSG at a tertiary referral teaching hospital were analyzed. Body composition indicators were calculated using the SliceOmatic software. Achieving initial body mass index within 6 months postoperatively was defined as early eligible weight loss (EEWL). The relationship between body composition and EEWL was analyzed. RESULTS: A total of 243 patients were included. Receiver operating characteristic (ROC) curve analysis showed that the predictive value of the FMI for EEWL in patients after LSG was higher than that of other indicators (all P < 0.05; area under the curve = 0.813). The best FMI cut-off point was 13.662. Accordingly, the patients were divided into the high-FMI group and low-FMI group. The %EWL and BMI of patients in the low-FMI group at 1, 3, 6, 9, 12, and 24 months after surgery were better than those in the high-FMI group (all P < 0.001). Patients in the low-FMI group had higher BAROS (Bariatric Analysis and Reporting Outcome System) scores than those in the high-FMI group (P < 0.001). CONCLUSION: Compared with other body composition indicators, FMI can effectively predict the early effect of weight loss and quality of life after LSG.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

BACKGROUND: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear. METHODS: A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up. RESULTS: During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P=0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P=0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P<0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P=0.005). These findings remained robust across a series of sensitivity and subgroup analyses. CONCLUSIONS: Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

GPR50 regulates neuronal development as a mitophagy receptor.

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

Comprehensive Multiple Risk Factor Control in Type 2 Diabetes to Mitigate Heart Failure Risk: Insights From a Prospective Cohort Study.

OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

The double-edged nature of nicotine: toxicities and therapeutic potentials.

Nicotine is the primary addictive component of cigarette smoke and is associated with various smoking-related diseases. However, recent research has revealed its broader cognitive-enhancing and anti-inflammatory properties, suggesting its potential therapeutic applications in several conditions. This review aims to examine the double-edged nature of nicotine, encompassing its positive and negative effects. We provide a concise overview of the physiochemical properties and pharmacology of nicotine, including insights into nicotine receptors. Therefore, the article is divided into two main sections: toxicity and therapeutic potential. We comprehensively explored nicotine-related diseases, focusing on specific signaling pathways and the underlying mechanisms that contribute to its effects. Furthermore, we addressed the current research challenges and future development perspectives. This review aims to inspire future researchers to explore the full medical potential of nicotine, which holds significant promise for the clinical management of specific diseases.

Identification and Functional Characterization of Carboxylesterase Genes Involved in Spirodiclofen Resistance in Panonychus citri (McGregor).

Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Shape and Size of the Annulus Fibrosus Excision Alters the Biomechanics of the Intervertebral Disc.

STUDY DESIGN: Biomechanical testings and finite element analysis. OBJECTIVES: This study aims to investigate how annulus fibrosus (AF) incision size (RIS, Ratio of incision width to AF height) and shape affect intervertebral disc (IVD) biomechanics. METHODS: A validated finite element model of lumbar spines simulated various incisions in the middle-right posterior region of the AF, with different sizes and shapes. Simulations included axial compression, flexion, extension, bending, and rotation. Parameters assessed included stability, re-herniation, and IVD degeneration by analyzing stress, height, Intradiscal pressure (IDP), and the range of motion (ROM). RESULTS: Incision increased AF stress and ROM under 3 Nm moment, with values rising as RIS increased. RIS exceeding 40% resulted in a 20% AF stress increase during compression and extension, while RIS over 50% led to over 20% AF stress increase during other motions. Incision stress also increased with higher RIS, particularly surpassing 50% RIS. IDP rose across all incision shapes. Endplate stress increased (9.9%-48.9%) with larger incisions, with average increases of 12.8%, 12.7%, 30.5%, and 22.8% for circular, oval, square, and rectangular incisions. Compression and rotation minimally affected NP pressure (<15%), while flexion (19.8%-38.8%) and bending (18.5%-43.9%) had a more pronounced effect. ROM increased with RIS (20.0% ∼ 77.4%), especially with an incision RIS exceeding 40%. CONCLUSIONS: AF injury elevates AF stress, reduces spine stability, heightens degeneration risk with increasing RIS. Reherniation risk rises when RIS exceeds 40%. Circular or oval incisions maintain spine biomechanics better than square or rectangular ones.

An experimental validation of a filtering approach for prompt gamma prediction in a research proton treatment planning system.

Objective.Prompt gamma (PG) radiation generated from nuclear reactions between protons and tissue nuclei can be employed for range verification in proton therapy. A typical clinical workflow for PG range verification compares the detected PG profile with a predicted one. Recently, a novel analytical PG prediction algorithm based on the so-called filtering formalism has been proposed and implemented in a research version of RayStation (RaySearch Laboratories AB), which is a widely adopted treatment planning system. This work validates the performance of the filtering PG prediction approach.Approach.The said algorithm is validated against experimental data and benchmarked with another well-established PG prediction algorithm implemented in a MATLAB-based software REGGUI. Furthermore, a new workflow based on several PG profile quality criteria and analytical methods is proposed for data selection. The workflow also calculates sensitivity and specificity information, which can help practitioners to decide on irradiation course interruption during treatment and monitor spot selection at the treatment planning stage. With the proposed workflow, the comparison can be performed on a limited number of selected high-quality irradiation spots without neighbouring-spot aggregation.Main results.The mean shifts between the experimental data and the predicted PG detection (PGD) profiles (ΔPGD) by the two algorithms are estimated to be1.5±2.1mm and-0.6±2.2mm for the filtering and REGGUI prediction methods, respectively. The ΔPGD difference between two algorithms is observed to be consistent with the beam model difference within uncertainty. However, the filtering approach requires a much shorter computation time compared to the REGGUI approach.Significance.The novel filtering approach is successfully validated against experimental data and another widely used PG prediction algorithm. The workflow designed in this work selects spots with high-quality PGD shift calculation results, and performs sensitivity and specificity analyses to assist clinical decisions.

Life's Essential 8, Genetic Susceptibility, and Incident Cardiac Arrhythmias: A Population-Based Prospective Cohort Study.

BACKGROUND: Ideal cardiovascular health (CVH) has been associated with reduced cardiovascular disease risk and mortality, but its association with cardiac arrhythmias was still unsettled. In this prospective cohort study, we investigated the relationship between CVH and subsequent arrhythmias risk, including atrial fibrillation (AF)/flutter, ventricular arrhythmias, and bradyarrhythmias. METHODS: Data from 287,264 participants initially free of arrhythmias in the UK Biobank were included in the analysis. Cox regression models were used to examine the relationship between CVH levels calculated by the American Heart Association's Life's Essential 8 (LE8) metrics, with cardiac arrhythmias risk. RESULTS: During a median follow-up period of 12.8 years, 16,802 incident AF, 2186 incident ventricular arrhythmias, and 4128 incident bradyarrhythmias were identified. After adjustment for confounding factors, participants with high initial CVH levels had significantly lower risks for AF (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.59-0.68), ventricular arrhythmias (HR, 0.48; 95% CI, 0.40-0.59), and bradyarrhythmias (HR, 0.64; 95% CI, 0.55-0.74) compared with those with low CVH levels. Furthermore, each standard deviation (SD) increase in LE8 scores was associated with a 15% lower risk of AF, 21% for ventricular arrhythmias, and 13% for bradyarrhythmias, respectively. In addition, a significant interaction was observed between CVH levels and the genetic risk of AF (P for interaction, 0.021). The reverse correlation seemed to be more noticeable in individuals with a lower genetic susceptibility to AF. CONCLUSIONS: We concluded that higher levels of CVH, estimated by the LE8 metrics, were associated with significantly reduced risks of AF, ventricular arrhythmias, and bradyarrhythmias.

Innovative hydrogel-patch combination for large annulus fibrosus defects: a prospective approach to address herniation recurrence.

BACKGROUND CONTEXT: Large annulus fibrosus (AF) defects often lead to a high rate of reherniation, particularly in the medial AF region, which has limited self-healing capabilities. The increasing prevalence of herniated discs underscores the need for effective repair strategies. PURPOSE: The objectives of this study were to design an AF repair technique to reduce solve the current problems of insufficient mechanical properties and poor sealing capacity. STUDY DESIGN: In vitro biomechanical experiments and finite element analysis. METHODS: The materials used in this study were patches and hydrogels with good biocompatibility and sufficient mechanical properties to withstand loading in the lumbar spine. Five repair techniques were assessed in this study: hydrogel filler (HF), AF patch medial barrier (MB), AF patch medial barrier and hydrogel filler (MB&HF), AF patch medial-lateral barrier (MLB), and AF patch medial-lateral barrier and hydrogel filler (MLB&HF). The repair techniques were subjected to in vitro testing (400 N axial compression and 0-500 N fatigue loading at 5Hz) and finite element analysis (400 N axial compression) to evaluate the effectiveness at repairing large AF defects. The evaluation included repair tightness, spinal stability, and fatigue resistance. RESULTS: From the in vitro testing, the failure load of the repair techniques was in the following order HF MLB >MB&HF >MLB&HF. CONCLUSIONS: The combined use of patches and hydrogels exhibited promising mechanical properties postdiscectomy, providing a promising solution for addressing large AF defects and improving disc stability. CLINICAL SIGNIFICANCE: This study introduces a promising method for repairing large annular fissure (AF) defects after disc herniation, combining patch repair with a hydrogel filler. These techniques hold potential for developing clinical AF repair products to address this challenging issue.

Endoscopic Bilateral Nipple-sparing Mastectomy via a Single Axillary Incision with Immediate Pre-pectoral Implant-based Breast Reconstruction.

Oncoplastic breast surgery, with its focus on improving cosmetic outcomes while maintaining oncological safety, has fundamentally transformed the landscape of breast cancer surgical treatment, giving rise to an array of techniques for breast reconstruction. Nipple-sparing mastectomy (NSM) with immediate implant-based breast reconstruction (IBBR) has emerged as a cornerstone in managing early breast cancer. Aligned with the principles of minimally invasive surgery, recent years have witnessed the widespread integration of endoscopic approaches in breast surgery, encompassing procedures like endoscopic breast-conserving surgery (E-BCS) and endoscopic nipple-sparing mastectomy (E-NSM), among others. Capitalizing on the advantages of inconspicuous and shorter incisions, improved visibility, and the avoidance of radiation therapy, the popularity of E-NSM with IBBR is on the rise. However, conventional E-NSM with IBBR often requires two or more incisions, which can result in suboptimal cosmetic outcomes and even prosthesis loss.This paper presents a comprehensive account of the intricate surgical procedures involved in endoscopic bilateral nipple-sparing mastectomy with immediate pre-pectoral implant-based breast reconstruction. The insights shared are drawn from the collective experience of our institution. Notable benefits associated with the described surgical approach encompass enhanced cosmetic outcomes, improved postoperative quality of life, and enhanced physiological functions attributable to the application of pre-pectoral implant-based breast reconstruction through a single incision.

Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target.

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Overexpression of a nuclear receptor HR96 contributes to spirodiclofen susceptibility in Panonychus citri (McGregor).

The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.

[Effects and Mechanisms of Polystyrene Microplastics on Extracellular Antibiotic Resistance Genes in Wastewater].

Microplastics (MPs) and antibiotic resistance genes (ARGs) are typical co-existing emerging pollutants in wastewater treatment plants. MPs have been shown to alter the distribution pattern of ARGs in sludge, but their effects on free extracellular ARGs (feARGs) in wastewater remain unclear. In this study, we used fluorescence quantitative PCR to investigate the dynamics of feARGs (including tetC, tetO, sul1, and sul2) in wastewater and their transition mechanisms after 60 d of exposure to typical MPs (polystyrene, PS). The results showed that the absolute abundance of tetracycline feARGs decreased by 28.4 %-76.0 % and 35.2 %-96.2 %, respectively, under nm-level and mm-level PS exposure and changed by -55.4 %-122.4 % under µm-level PS exposure. The abundance of sul1 showed a trend of nm-level > µm-level > mm-level upon PS exposure, and the changes in sul1 abundance was greater with ρ(PS)=50 mg·L-1 exposure. The relative abundance of sul2 was reduced by 25.4 %-42.6 % and 46.1 %-90.3 % after µm-level and mm-level PS exposure, respectively, and increased by 1.9-3.9 times after nm-level PS exposure, and the sul2 showed a higher reduction at ρ (PS)=50 mg·L-1 exposure than that at ρ (PS)=0.5 mg·L-1. The Pearson correlation analysis showed that the relative abundance of feARGs during PS exposure was positively correlated with cell membrane permeability and typical mobile genetic elements (intI1) abundance and negatively correlated with reactive oxygen species level. Our findings elucidated the effects and corresponding mechanisms of PS on the growth and mobility of feARGs in wastewater, providing a scientific basis for the control of the combined MPs and ARGs pollution in wastewater.