CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species.

DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions.

Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice.

Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent-the naked mole-rat1,2. To study whether the benefits of HMM-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2). nmrHas2 mice showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHas2 mice shifted towards that of longer-lived species. The most notable change observed in nmrHas2 mice was attenuated inflammation across multiple tissues. HMM-HA reduced inflammation through several pathways, including a direct immunoregulatory effect on immune cells, protection from oxidative stress and improved gut barrier function during ageing. These beneficial effects were conferred by HMM-HA and were not specific to the nmrHas2 gene. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new paths for using HMM-HA to improve lifespan and healthspan.

Characterization of naked mole-rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits.

Naked mole rats (NMRs) are the longest-lived rodents yet their stem cell characteristics remain enigmatic. Here, we comprehensively mapped the NMR hematopoietic landscape and identified unique features likely contributing to longevity. Adult NMRs form red blood cells in spleen and marrow, which comprise a myeloid bias toward granulopoiesis together with decreased B-lymphopoiesis. Remarkably, youthful blood and marrow single-cell transcriptomes and cell compositions are largely maintained until at least middle age. Similar to primates, the primitive stem and progenitor cell (HSPC) compartment is marked by CD34 and THY1. Stem cell polarity is seen for Tubulin but not CDC42, and is not lost until 12 years of age. HSPC respiration rates are as low as in purified human stem cells, in concert with a strong expression signature for fatty acid metabolism. The pool of quiescent stem cells is higher than in mice, and the cell cycle of hematopoietic cells is prolonged. By characterizing the NMR hematopoietic landscape, we identified resilience phenotypes such as an increased quiescent HSPC compartment, absence of age-related decline, and neotenic traits likely geared toward longevity.

Consistency Analysis of Programmed Death Ligand 1 Expression in Non-Small Cell Lung Cancer Between Pleural Effusion and Matched Primary Lung Cancer Tissues by Immunohistochemical Double Staining.

In clinical practice, programmed death ligand 1 (PD-L1) detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, diaminobenzidine (DAB) and 3-amino-9-ethylcarbazole (AEC) immunohistochemistry double staining was performed to investigate PD-L1 expression in tumor cells from malignant pleural effusion (MPE). MPE was considered as a metastasis in non-small cell lung cancer patients; thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks and matched primary lung cancer tissues from non-small cell lung cancer patients were subjected to PD-L1 and thyroid transcription factor-1(TTF-1)/p63 immunohistochemistry double staining. Two experienced pathologists independently evaluated PD-L1 expression using 3 cutoffs (1%, 10%, and 50%). PD-L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R = 0.813; P < .001). Using a 4-tier scale (cutoffs: 1%, 10%, and 50%), the concordance was 71.1% (Cohen's κ = .534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's κ = 0.53), 78.9% (10%, Cohen's κ = 0.574), and 95.6% (50%, Cohen's κ = 0.754). The rates of PD-L1 positivity in MPE (56.7%) were higher than that in lung tissues (32.2%). All 27 discordant cases had higher scores in MPE. The double-staining method provided superior identification of PD-L1-positive tumor cells on a background with nonspecific staining. In conclusion, PD-L1 expression was moderately concordant between metastatic MPE cell blocks and matched primary lung carcinoma tissues, with variability related to tumor heterogeneity. MPE should be considered to detect PD-L1 when histological specimens are unattainable, especially when PD-L1 expression is >50%. PD-L1 positivity rates were higher in MPE. Double staining can improve PD-L1 detection by reducing false-negative/positive results.

Underwater Bionic Self-Healing Superhydrophobic Coating with the Synergetic Effect Of Hydrogen Bonds and Self-Formed Bubbles.

The self-healing ability of superhydrophobic surfaces in air has attracted tremendous additions in recent years. Once the superhydrophobic surface is damaged underwater, water seeps into gaps among micro/nano structures. The air film diffuses into water and eventually disappears during immersion without actively replenishing the gas, which results in the impossible of self-healing. Here, an underwater self-healing superhydrophobic coating with the synergetic effect of hydrogen bonds and self-formed bubbles via the spraying method is fabricated. The movement of hydrogen bonds of the prepared polyurethane enables microstructures to reconstruct at room temperature and self-formed bubbles of effervescent materials underwater actively replenish gas before microstructures completely self-healing, achieving the self-healing property of the superhydrophobic coating. Moreover, the hydrophilic effervescent material is sprayed along with unmodified micron-scaled particles because modified nano-scale particles are key factors for the realization of superhydrophobic coating. An underwater stable superhydrophobic surface with pressure resistance (4.9 kPa) is demonstrated. This superhydrophobic coating also shows excellent drag reduction, anti-icing, and anti-corrosion properties. This facile and scalable method offers a new route that an underwater self-healing superhydrophobic coating executes the gas film recovery.

Association between blood lipid levels and the risk of liver cancer: a systematic review and meta-analysis.

PURPOSE: The association between blood lipid levels and the risk of developing liver cancer remains a subject of ongoing debate. To elucidate this association, we conducted a meta-analysis by systematically incorporating data from all relevant prospective cohort studies. METHODS: We conducted a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases covering studies published from database inception through July 2023. This study included prospective cohort studies related to lipid profiles (e.g., total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels) that reported hazard ratios (HRs) or relative risks (RRs) with corresponding 95% confidence intervals (95% CIs) to investigate their association with the risk of liver cancer. During the analysis process, we used fixed-effects or random-effects models based on the level of heterogeneity among the studies and obtained pooled risk ratios using these models. To ensure the robustness and reliability of the study findings, we also conducted sensitivity analyses and publication bias analyses. RESULTS: After conducting a systematic search, 12 studies were identified from a total of 11,904 articles and were included in the meta-analysis. These studies included a combined population of 10,765,221 participants, among whom 31,055 cases of liver cancer were reported. The analysis revealed that the pooled HR for the serum TC concentration (highest versus lowest) was 0.45 (95% CI = 0.35-0.58, I2 = 78%). For TGs, the HR was 0.67 (95% CI = 0.46-0.96, I2 = 86%), while for HDL-C, the HR was 0.72 (95% CI = 0.58-0.90, I2 = 65%). The HR for LDL-C was 0.51 (95% CI = 0.23-1.13, I2 = 93%). CONCLUSION: The findings of this study indicate that serum TC, TG, and HDL-C levels are negatively associated with liver cancer risk, suggesting that higher concentrations of these lipids are associated with a reduced risk of liver cancer. However, no significant association has been found between LDL-C levels and liver cancer risk.

Association of the triglyceride-glucose index with all-cause and cardiovascular mortality in patients with cardiometabolic syndrome: a national cohort study.

OBJECTIVE: This study aimed to evaluate the association of triglyceride-glucose (TyG) index with all-cause and cardiovascular mortality risk among patients with cardiometabolic syndrome (CMS). METHODS: We performed a cohort study of 5754 individuals with CMS from the 2001-2018 National Health and Nutrition Examination Survey. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models assessed the associations between TyG index and mortality . Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: Over a median follow-up of 107 months, 1201 all-cause deaths occurred, including 398 cardiovascular disease-related deaths. The multivariate Cox proportional hazards regression model showed a positive association between the TyG index and all-cause and cardiovascular mortality. Each one-unit increase in the TyG index was associated with a 16% risk increase in all-cause mortality (HR: 1.16, 95% CI 1.03, 1.31, P = 0.017) and a 39% risk increase in cardiovascular mortality (HR: 1.39, 95% CI 1.14, 1.71, P = 0.001) after adjusting for confounders. The restricted cubic splines revealed a U-shaped association between the TyG index and all-cause (P for nonlinear < 0.001) and cardiovascular mortality (P for nonlinear = 0.044), identifying threshold values (all-cause mortality: 9.104; cardiovascular mortality: 8.758). A TyG index below these thresholds displayed a negative association with all-cause mortality (HR: 0.58, 95% CI 0.38, 0.90, P = 0.015) but not with cardiovascular mortality (HR: 0.39, 95% CI 0.12, 1.27, P = 0.119). Conversely, a TyG index exceeding these thresholds was positively associated with all-cause and cardiovascular mortality (HR: 1.35, 95% CI 1.17, 1.55, P < 0.001; HR: 1.54, 95% CI 1.25, 1.90, P < 0.001, respectively). Notably, a higher TyG index (≥ threshold values) was significantly associated with increased mortality only among individuals aged under 55 compared to those with a lower TyG index (< threshold values). CONCLUSIONS: The TyG index demonstrated a U-shaped correlation with all-cause and cardiovascular mortality in individuals with CMS. The thresholds of 9.104 and 8.758 for all-cause and cardiovascular mortality, respectively, may be used as intervention targets to reduce the risk of premature death and cardiovascular disease.

Constructing Lanthanide-Organic Complexes for X-ray Scintillation and Imaging.

The photoluminescent properties of lanthanide complexes have been thoroughly investigated; however, there have been much fewer studies showcasing their potential use in ionizing radiation detection. In this work, we delve into the photo- and radio-induced luminescence of a series of lanthanide-bearing organic-inorganic hybrids and their potential as a platform for X-ray scintillation and imaging. The judicious synergy between lanthanide cations and 2,6-di(1H-pyrazol-1-yl)isonicotinate (bppCOO-) ligands affords six new materials with three distinct structures. Notably, Eu-bppCOO-1 and Tb-bppCOO-2 display sharp fingerprint X-ray-excited luminescence (XEL), the intensities of which can be linearly correlated with the X-ray dose rates over a broad dynamic range (0.007-4.55 mGy s-1). Moreover, the X-ray sensing efficacies of Eu-bppCOO-1 and Tb-bppCOO-2 were evaluated, showing that Tb-bppCOO-2 features a lower detection limit of 4.06 µGy s-1 compared to 14.55 µGy s-1 of Eu-bppCOO-1. Given the higher X-ray sensitivity and excellent radiation stability of Tb-bppCOO-2, we fabricated a flexible scintillator film for X-ray imaging by embedding finely ground Tb-bppCOO-2 in the polydimethylsiloxane (PDMS) polymer. The resulting scintillator film can be utilized for high-resolution X-ray imaging with a spatial resolution of approximately 7 lp mm-1.

Liquid-based cytology specimens for next-generation sequencing in lung adenocarcinoma: challenges and evaluation of targeted therapy.

BACKGROUND: To explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy. METHODS: A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method. RESULTS: There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with < 20% tumor cellularity was significantly lower than that in specimens with ≥ 20% tumor cellularity. Among 22 cases with matched histological specimens, 72.7% (16/22) of LBC specimens were completely consistent with results of histological specimens. Among 92 patients with EGFR-mutant lung adenocarcinoma treated with EGFR-TKIs in the two cohorts, 88 cases experienced progression, and the median progression-free survival (PFS) was 12.1 months. CONCLUSIONS: Cytological specimens are important sources for gene detection of advanced lung adenocarcinoma. When using LBC specimens for molecular testing, it is recommended to fully evaluate the tumor cellularity of the specimens.

Deep Learning Image Recognition-Assisted Atomic Force Microscopy for Single-Cell Efficient Mechanics in Co-culture Environments.

Atomic force microscopy (AFM)-based force spectroscopy assay has become an important method for characterizing the mechanical properties of single living cells under aqueous conditions, but a disadvantage is its reliance on manual operation and experience as well as the resulting low throughput. Particularly, providing a capacity to accurately identify the type of the cell grown in co-culture environments without the need of fluorescent labeling will further facilitate the applications of AFM in life sciences. Here, we present a study of deep learning image recognition-assisted AFM, which not only enables fluorescence-independent recognition of the identity of single co-cultured cells but also allows efficient downstream AFM force measurements of the identified cells. With the use of the deep learning-based image recognition model, the viability and type of individual cells grown in co-culture environments were identified directly from the optical bright-field images, which were confirmed by the following cell growth and fluorescent labeling results. Based on the image recognition results, the positional relationship between the AFM probe and the targeted cell was automatically determined, allowing the precise movement of the AFM probe to the target cell to perform force measurements. The experimental results show that the presented method was applicable not only to the conventional (microsphere-modified) AFM probe used in AFM indentation assay for measuring the Young's modulus of single co-cultured cells but also to the single-cell probe used in AFM-based single-cell force spectroscopy (SCFS) assay for measuring the adhesion forces of single co-cultured cells. The study illustrates deep learning imaging recognition-assisted AFM as a promising approach for label-free and high-throughput detection of single-cell mechanics under co-culture conditions, which will facilitate unraveling the mechanical cues involved in cell-cell interactions in their native states at the single-cell level and will benefit the field of mechanobiology.

Optical Information Transmission and Multimode Fluorescence Anticounterfeiting of Ca2-xMgxGe7O16:Mn2.

Multimode emission of Mn2+ for multimode fluorescence anticounterfeiting is achieved by cation site and interstitial occupancy in Ca2-xMgxGe7O16. The rings in Ca2-xMgxGe7O16 have a significant distortion for Mn2+ ions to enter the ring interstitials with a luminescence center at 665 nm, which is supported by XRD refinement results and first-principles calculations. The interstitial Mn2+ ion has good thermal stability with an activation energy of 0.36 eV. Surprisingly, these two luminescence centers, the cation site Mn and the interstitial Mn, have an obvious afterglow, and the disappearing afterglow will reappear by heating or irradiating with the 980 nm laser. The afterglow is significantly enhanced, as MnO2 is used as the manganese source, which is explained in detail by the thermal luminescence spectrum. Finally, Ca2-xMgxGe7O16:Mn2+ fully demonstrates its excellent prospects in fluorescent anticounterfeiting, information encryption, and optical information storage.

Efficacy and Safety of a Novel Hexaspline Pulsed Field Ablation System in Patients with Paroxysmal Atrial Fibrillation: The PLEASE-AF Study.

BACKGROUND: Pulsed field ablation (PFA) is an emerging non-thermal ablative modality demonstrating considerable promise for catheter ablation of atrial fibrillation (AF). However, these PFA trials have almost universally included only caucasian populations, with little data on its effect on other races/ethnicities. OBJECTIVE: The PLEASE-AF trial sought to study 12-month efficacy and the safety of a multielectrode hexaspline PFA catheter in treating a predominatly Asian/Chinese population of patients with drug-refractory paroxysmal AF. METHODS: Patients underwent pulmonary vein (PV) isolation by delivering different pulse intensities at the PV ostium (1800V) and atrium (2000V). Acute success was defined as no PV potentials and entrance/exit conduction block of all PVs after a 20-min waiting period. Follow-up at 3, 6, and 12 months included 12-ECG and 24-hour Holter examinations. The primary efficacy endpoint was 12-month freedom from any atrial arrhythmias lasting at least 30 seconds. RESULTS: The cohort included 143 patients from 12 hospitals treated by 28 operators: age 60.2±10.0 years, 65.7% male, Asian/Chinese 100%, and left atrial diameter 36.6±4.9 mm. All PVs (565/565, 100%) were successfully isolated. The total procedure, catheter dwell, total PFA application, and total fluoroscopy times were 123.5±38.8 minutes, 63.0±30.7 minutes, 169.7±34.6 seconds and 27.3±10.1 minutes, respectively. The primary endpoint was observed in 124 of 143 patients (86.7%). One patient (0.7%) developed a small pericardial effusion 1-month post-procedure, not requiring intervention. CONCLUSIONS: The novel hexaspline PFA catheter demonstrated universal acute PVI with an excellent safety profile and promising 12-month freedom from recurrent atrial arrhythmias in an Asian/Chinese population with paroxysmal AF. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT05114954.

Self-assembly mechanism, physicochemical analyses and application performance investigations of branched alkyl glycosides with alcohol ether carboxylic acids of varied epoxide numbers.

Green surfactants, specifically alkyl glycosides and fatty alcohol ether carboxylic acids, are known for their biocompatibility, multiresponsiveness, and versatile applications, garnering significant attention in the realms of green and colloid chemistry. This study systematically investigated the mechanism underlying micelle formation within aqueous solutions comprising alcohol ether carboxylic acids featuring diverse EO group chain quantities (AEC-nH, where n equals 5, 7, and 9) and branched alkyl glycosides (IG). The elucidation of these mechanisms sheds light on their prospective application properties. It was observed that the self-assembly of micelles in these hybrid systems is predominantly influenced by hydrogen bonding, electrostatic interactions, and hydrophobic forces. The spherical-rod morphology of the micelles responds to the varying numbers of EO group chains, with an increased number of EO leading to the formation of rod-like micelles, which exhibit relative instability, while a decreased number of EO results in the formation of spherical micelles with relative stability. Additionally, by means of kinetic analysis, it was determined that the micelle formation process of the three hybrid systems is driven by enthalpy, and a mixed diffusion-kinetics adsorption mechanism is involved in the adsorption process. These findings significantly impact their application properties. This report stands as the first exploration of the synergistic mechanisms and application performance of two types of green surfactants in aqueous solutions, considering the influence of different numbers of EO group chains. Not only does it provide fundamental insights into their properties, but it also offers novel perspectives on the applications of green surface activation.

Comparison of surgical effect in active and inactive Dysthyroid Optic Neuropathy after Endoscopic Transnasal Medial Orbital Decompression.

PURPOSE: To evaluate and compare the changes in orbital soft tissue volume and visual function after endoscopic transnasal medial orbital decompression in patients with active and inactive dysthyroid optic neuropathy (DON). METHODS: This prospective, cohort study recruited 112 patients (112 eyes) with DON who were divided into an active and inactive DON group (56 eyes each) by clinical activity scores. All patients underwent endoscopic transnasal medial orbital decompression. The pre- and post-operative orbital soft tissue volumes were measured with high-resolution computed tomography (CT) using Mimics software. Visual function, including best-corrected visual acuity (BCVA), visual field (VF), and visual evoked potential (VEP), was recorded before and after surgery. RESULTS: Preoperatively, compared with the inactive DON group, the active DON group had greater extraocular muscle volume (EMV) and EMV/orbital volume (OV) ratio, but worse BCVA, VF, and exophthalmos. Postoperatively, although the EMV slightly increased, with the enlarged medial rectus muscle contributing dramatically, the EMV/OV ratio decreased in patients with DON. Besides, visual function including BCVA, VF, VEP and exophthalmos was also improved in both groups after surgery. There were no significant differences in postoperative OV; EMV; EMV/OV ratio; and the BCVA, VF, and VEP parameters between both groups (all P > 0.05). CONCLUSION: Patients with DON who did not respond well to steroids, regardless of disease activity, may benefit from orbital decompression via the decrease in the proportion of EMV in OV, especially patients with active DON, who showed more improved visual function than patients with inactive DON.

Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Associations between non-insulin-based insulin resistance indices and heart failure prevalence in overweight/obesity adults without diabetes mellitus: evidence from the NHANES 2001-2018.

BACKGROUND: The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes. METHODS: This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose-response relationships. RESULTS: A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4-4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1-1.3, p < 0.001) both increased the prevalence of HF, especially in the non-Hispanic population. Dose-response relationships suggested nonlinear relationships between these two indicators and HF. CONCLUSION: Our study demonstrated that elevated TyG index and TG/HDL-C ratio were closely associated with the prevalence of HF, and both exhibited nonlinear relationships with HF prevalence in overweight/obesity adults without diabetes. Based on these findings, additional prospective studies are needed for further validation.

Surgical Outcomes of Standardized Endoscopical Deep Medial Orbital Decompression in Dysthyroid Optic Neuropathy.

INTRODUCTION: The aim of the study was to standardize the endoscopic deep medial orbital decompression surgery for better relief of optic nerve compression in dysthyroid optic neuropathy (DON). METHODS: A total of 128 eyes from patients received the standardized endoscopic deep medial orbital decompression surgery were recruited in this study. The efficacy of the procedure was assessed at a 1-month follow-up by the best-corrected visual acuity (VA), visual field (VF), and visual evoked potential (VEP). Clinical data were collected to explore the factors that affected visual recovery. Oxygen saturation of retinal blood vessels, retinal thickness, and vessel density were measured to demonstrate the potential recovery mechanisms. RESULTS: After surgery, the ratio of extraocular muscle volume in the orbital apex to orbital apex volume significantly decreased from 44.32 ± 22.31% to 36.82 ± 12.02% (p < 0.001). 96.87% of eyes' final VA improved; average VA improved from 0.93 ± 0.73 to 0.50 ± 0.60 at 1 week (p < 0.001) and 0.40 ± 0.53 at 1 month (p < 0.001). Postoperatively, VF and VEP also improved, the oxygen saturation of retinal arteries increased, and the retinal thickness was reduced. Preoperative VA, visual impairment duration, and clinical activity score evaluation were associated with visual recovery. CONCLUSION: In this study, we standardized the endoscopic deep medial orbital decompression, of which key point was to relieve pressure in the orbital apex and achieved satisfactory visual recovery in DON patients.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Sublethal effects of chlorantraniliprole on immunity in Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae): Promote encapsulation by upregulating a heat shock protein 70 family gene SfHSP68.1.

As an agricultural pest, the fall armyworm (FAW), Spodoptera frugiperda, poses a severe threat to agriculture in China. Chlorantraniliprole has been widely used to control this pest. In our previous studies, we discovered that LD10, LD20, and LD30 chlorantraniliprole promoted encapsulation in the 4th instar larvae of the FAW, with LD30 chlorantraniliprole having the most significant effect. To further investigate the molecular mechanism underlying the sublethal effects of chlorantraniliprole on encapsulation in the FAW, this study conducted the effects of encapsulation in 4th instar larvae of the FAW exposed to LD30 chlorantraniliprole. Then, we analyzed the transcriptome of the FAW hemolymph treated with LD30 chlorantraniliprole and identified genes related to encapsulation using RNAi. Our results showed that the encapsulation in the FAW was enhanced at 6, 12, 18, 24, and 48 h after exposure to LD30 chlorantraniliprole. Additionally, LD30 chlorantraniliprole significantly affected the expression of certain immune-related genes, with the heat shock protein 70 family gene SfHSP68.1 showing the most significant upregulation. Subsequent interference with SfHSP68.1 resulted in a significant inhibition of encapsulation in FAW. These findings suggested that LD30 chlorantraniliprole can promote encapsulation in the FAW by upregulating SfHSP68.1 expression. This study provides valuable insights into the sublethal effects of chlorantraniliprole on encapsulation in the FAW and the interaction between encapsulation and heat shock proteins (HSPs).