The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives.

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Research progress on morphology and mechanism of programmed cell death.

Programmed cell death (PCD) is a basic process of life that is closely related to the growth, development, aging and disease of organisms and is one of the hotspots of life science research today. PCD is a kind of genetic control, autonomous and orderly important cell death that involves the activation, expression, and regulation of a series of genes. In recent years, with the deepening of research in this field, new mechanisms of multiple PCD pathways have been revealed. This article reviews and summarizes the multiple PCD pathways that have been discovered, analyses and compares the morphological characteristics and biomarkers of different types of PCD, and briefly discusses the role of various types of PCD in the diagnosis and treatment of different diseases, especially malignant tumors.

Solar-assisted selective separation and recovery of precious group metals from deactivated air purification catalysts.

The mitigation of environmental and energy crises could be advanced by reclaiming platinum group precious metals (PGMs) from decommissioned air purification catalysts. However, the complexity of catalyst composition and the high chemical inertness of PGMs significantly impede this process. Consequently, recovering PGMs from used industrial catalysts is crucial and challenging. This study delves into an environmentally friendly approach to selectively recover PGMs from commercial air purifiers using photocatalytic redox technology. Our investigation focuses on devising a comprehensive strategy for treating three-way catalysts employed in automotive exhaust treatment. By meticulously pretreating and modifying reaction conditions, we achieved noteworthy results, completely dissolving and separating rhodium (Rh), palladium (Pd), and platinum (Pt) within a 12-h time frame. Importantly, the solubility selectivity persists despite the remarkably similar physicochemical properties of Rh, Pd, and Pt. To bolster the environmental sustainability of our method, we harness sunlight as the energy source to activate the photocatalysts, facilitating the complete dissolution of precious metals under natural light irradiation. This eco-friendly recovery approach demonstrated on commercial air purifiers, exhibits promise for broader application to a diverse range of deactivated air purification catalysts, potentially enabling implementation on a large scale.

Anaerobic cyanides oxidation with bimetallic modulation of biological toxicity and activity for nitrite reduction.

Cyanide is a typical toxic reducing agent prevailing in wastewater with a well-defined chemical mechanism, whereas its exploitation as an electron donor by microorganisms is currently understudied. Given that conventional denitrification requires additional electron donors, the cyanide and nitrogen can be eliminated simultaneously if the reducing HCN/CN- and its complexes are used as inorganic electron donors. Hence, this paper proposes anaerobic cyanides oxidation for nitrite reduction, whereby the biological toxicity and activity of cyanides are modulated by bimetallics. Performance tests illustrated that low toxicity equivalents of iron-copper composite cyanides provided higher denitrification loads with the release of cyanide ions and electrons from the complex structure by the bimetal. Both isotopic labeling and Density Functional Theory (DFT) demonstrated that CN--N supplied electrons for nitrite reduction. The superposition of chemical processes reduces the biotoxicity and enhances the biological activity of cyanides in the CN-/Fe3+/Cu2+/NO2- coexistence system, including complex detoxification of CN- by Fe3+, CN- release by Cu2+ from [Fe(CN)6]3-, and NO release by nitrite substitution of -CN groups. Cyanide is the smallest structural unit of C/N-containing compounds and serves as a probe to extend the electron-donating principle of anaerobic cyanides oxidation to more electron-donor microbial utilization.

Release of damaged mitochondrial DNA: A novel factor in stimulating inflammatory response.

Mitochondrial DNA (mtDNA) is a circular double-stranded genome that exists independently of the nucleus. In recent years, research on mtDNA has significantly increased, leading to a gradual increase in understanding of its physiological and pathological characteristics. Reactive oxygen species (ROS) and other factors can damage mtDNA. This damaged mtDNA can escape from the mitochondria to the cytoplasm or extracellular space, subsequently activating immune signaling pathways, such as NLR family pyrin domain protein 3 (NLRP3), and triggering inflammatory responses. Numerous studies have demonstrated the involvement of mtDNA damage and leakage in the pathological mechanisms underlying various diseases including infectious diseases, metabolic inflammation, and immune disorders. Consequently, comprehensive investigation of mtDNA can elucidate the pathological mechanisms underlying numerous diseases. The prevention of mtDNA damage and leakage has emerged as a novel approach to disease treatment, and mtDNA has emerged as a promising target for drug development. This article provides a comprehensive review of the mechanisms underlying mtDNA-induced inflammation, its association with various diseases, and the methods used for its detection.

Establishment of RNAi-Mediated Pest Control Method for Red Imported Fire Ant, Solenopsis invicta.

RNAi plays a crucial role in insect gene function research and pest control field. Nonetheless, the variable efficiency of RNAi across diverse insects and off-target effects also limited its further application. In this study, we cloned six essential housekeeping genes from Solenopsis invicta and conducted RNAi experiments by orally administering dsRNA. Then, we found that mixing with liposomes significantly enhanced the RNAi efficiency by targeting for SiV-ATPaseE. Additionally, we observed a certain lethal effect of this dsRNA on queens by our established RNAi system. Furthermore, no strict sequence-related off-target effects were detected. Finally, the RNAi effect of large-scale bacteria expressing dsRNA was successfully confirmed for controlling S. invicta. In summary, this study established an RNAi system for S. invicta and provided a research template for the future development of nucleic acid drugs based on RNAi.

Transcriptomic and metabolomic insights into the antimony stress response of tall fescue (Festuca arundinacea).

Antimony (Sb) is a toxic heavy metal that severely inhibits plant growth and development and threatens human health. Tall fescue, one of the most widely used grasses, has been reported to tolerate heavy metal stress. However, the adaptive mechanisms of Sb stress in tall fescue remain largely unknown. In this study, transcriptomic and metabolomic techniques were applied to elucidate the molecular mechanism of the Sb stress response in tall fescue. These results showed that the defense process in tall fescue was rapidly triggered during the early stages of Sb stress. Sb stress had toxic effects on tall fescue, and the cell wall and voltage-gated channels are crucial for regulating Sb permeation into the cells. In addition, the pathway of glycine, serine and threonine metabolism may play key roles in the Sb stress response of tall fescue. Genes such as ALDH7A1 and AGXT2 and metabolites such as aspartic acid, pyruvic acid, and biuret, which are related to biological processes and pathways, were key genes and compounds in the Sb stress response of tall fescue. Therefore, the regulatory mechanisms of specific genes and pathways should be investigated further to improve Sb stress tolerance.

Development and validation of a nomogram to predicting the efficacy of PD-1/PD-L1 inhibitors in patients with nasopharyngeal carcinoma.

PURPOSE: With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed to develop a nomogram to evaluate the efficacy of anti-PD-1/PD-L1 in NPC patients. METHODS: Totally 160 NPC patients were enrolled in the study. Patients were measured before the first PD-1/PD-L1 inhibitors treatment and after 8-12 weeks of immunotherapy by radiological examinations to estimate the effect. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen hematological markers and establish a predictive model. The nomogram was internally validated by bootstrap resampling and externally validated. Performance of the model was evaluated using concordance index, calibration curve, decision curve analysis and receiver operation characteristic curve. RESULTS: Patients involved were randomly split into training cohort ang validation cohort. Based on Lasso logistic regression, systemic immune-inflammation index (SII) and ALT to AST ratio (LSR) were selected to establish a predictive model. The C-index of training cohort and validating cohort was 0.745 and 0.760. The calibration curves and decision curves showed the precise predictive ability of this nomogram. The benefit of the model showed in decision curve was better than TNM stage. The area under the curve (AUC) value of training cohort and validation cohort was 0.745 and 0.878, respectively. CONCLUSION: The predictive model helped evaluating efficacy with high accuracy in NPC patients treated with PD-1/PD-L1 inhibitors.

Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer.

INTRODUCTION: Ovarian cancer (OC) is known for its high mortality rate. Although sodium citrate has anti-tumor effects in various cancers, its effect and mechanism in OC remain unclear. OBJECTIVES: To analyze the inhibitory effect of sodium citrate on ovarian cancer cells and the underlying mechanism. METHODS: Cell apoptosis was examined by TUNEL staining, flow cytometry and ferroptosis was examined intracellular Fe2+, MDA, LPO assays respectively. Cell metabolism was examined by OCR and ECAR measurements. Immunoblotting and immunoprecipitation were used to elucidate the mechanism. RESULTS: This study suggested that sodium citrate not only promoted ovarian cancer cell apoptosis but also triggeredferroptosis, manifested as elevated levels of Fe2+, LPO, MDA andlipid ROS production. On one hand, sodium citrate treatment led to a decrease of Ca2+ content in the cytosol by chelatingCa2+, which further inhibited the Ca2+/CAMKK2/AKT/mTOR signaling, thereby suppressing HIF1α-dependent glycolysis pathway and inducing cell apoptosis. On the other hand, the chelation of Ca2+ by sodium citrate resulted in inactivation of CAMKK2 and AMPK, leading to increase of NCOA4-mediated ferritinophagy, causing increased intracellular Fe2+ levels. More importantly, the inhibition of Ca2+/CAMKK2/AMPK signaling pathway reduced the activity of the MCU and Ca2+ concentration within the mitochondria, resulting in an increase in mitochondrial ROS. Additionally, metabolomic analysis indicated that sodium citrate treatment significantly increased de novo lipid synthesis. Altogether, these factors contributed to ferroptosis. As expected, Ca2+ supplementation successfully reversed the cell death and decreased tumor growth induced by sodium citrate. Inspiringly, it was found that coadministration of sodium citrate increased the sensitivity of OC cells to chemo-drugs. CONCLUSION: These results revealed that the sodium citrate exerted its anti-cancer activity by inhibiting Ca2+/CAMKK2-dependent cell apoptosis and ferroptosis. Sodium citrate will hopefully serve as a prospective compound for OC treatment and for improvingthe efficacy of chemo-drugs.

Neurological or Psychiatric Disorders After Dengue Fever.

This cohort study investigates the association between dengue fever and risk of neurological and psychiatric disorders among adults in Taiwan.

Associations Between Neuroinflammation-Related Conditions and Alzheimer's Disease: A Study of US Insurance Claims Data.

Background: Early detection of Alzheimer's disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD. Objective: Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI). Methods: We used Optum's de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); 2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD. Results: We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p <  0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p <  0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations. Conclusions: Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions.

Widespread Adoption of Microincision Vitrectomy Surgery Improves Visual Outcomes in Endogenous Endophthalmitis with Poor Initial Vision: A 21-Year Experience in Taiwan.

PURPOSE: To review the presentation and visual prognostic factors of patients with endogenous endophthalmitis before and after the introduction of microincision vitrectomy surgery (MIVS), at a tertiary referral hospital in Taiwan, over a 21-year period. METHODS: We retrospectively analyzed medical records of patients diagnosed with endogenous endophthalmitis before and after the introduction of MIVS between January 2002 and December 2022. RESULTS: Data were collected from 147 patients. Diabetes mellitus was the most common comorbidity (59.9%). Liver abscess (32.7%) was the leading source of infection, followed by urinary tract infection (15.0%), and infective endocarditis (5.4%). Klebsiella pneumoniae (50.4%) was the most common pathogen, followed by Staphylococcus aureus (13.5%), and Candida albicans (8.3%). Poor initial visual acuity worse than counting fingers (CF) (p < 0.001) and diabetes mellitus (p = 0.008) were significantly associated with poor visual outcomes. In the treatment of 98 patients with poor initial visual acuity worse than CF, the proportion of vitrectomy surgeries performed increased from 13/56 (23.2%) to 24/42 (57.1%) (p = 0.001) after the introduction of MIVS. Final visual acuity of CF or better increased from 7/56 (12.5%) to 12/42 (28.6%) after the introduction of MIVS (p = 0.046). Vitrectomy was a better prognostic factor for final visual outcome in patients with poor initial visual acuity of worse than CF (p = 0.011) than other factors. CONCLUSION: In endogenous endophthalmitis patients presenting with poor initial visual acuity, vitrectomy was a better visual prognostic factor. MIVS has allowed more patients to undergo vitrectomy and improved visual outcomes.

Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application.

Triazole demonstrates distinctive physicochemical properties, characterized by weak basicity, various dipole moments, and significant dual hydrogen bond acceptor and donor capabilities. These features are poised to play a pivotal role in drug-target interactions. The inherent polarity of triazole contributes to its lower logP, suggesting the potential improvement in water solubility. The metabolic stability of triazole adds additional value to drug discovery. Moreover, the metal-binding capacity of the nitrogen atom lone pair electrons of triazole has broad applications in the development of metal chelators and antifungal agents. This Perspective aims to underscore the unique physicochemical attributes of triazole and its application. A comparative analysis involving triazole isomers and other heterocycles provides guiding insights for the subsequent design of triazoles, with the hope of offering valuable considerations for designing other heterocycles in medicinal chemistry.

Trajectory Planning on Rolling Locomotion of Spherical Movable Tensegrity Robots with Multi-Gait Patterns.

Spherical movable tensegrity robots, resorting to the intrinsic hallmark of being lightweight and resilient, have exhibited tremendous potential in exploring unpredictable terrains and extreme environments where traditional robots often struggle. The geometry of spherical tensegrities is suitable for rolling locomotion, which guarantees the system to react to changing demands, navigate unexplored terrain, and perform missions even after suffering massive damage. The objective of this article is to enrich the type of spherical movable tensegrity robots with multiple kinematic gait patterns and to gain superior motion paths that are in conformity with the intrinsic features of structural rolling locomotion. Aiming at this purpose, three 12-rod spherical tensegrities with multi-gait patterns are investigated, and the dynamic simulation on independent (or evolutionary) gait patterns is conducted and testified on ADAMS. The routing spaces and the blind zones formed by single kinematic gait are compared to assess the suitability of the assigned kinematic gait pattern. Accordingly, we develop a trajectory planning method with the embedding of the steering control strategy into a modified rapidly exploring random tree (MRRT) algorithm to produce qualified marching routes. In the meantime, two momentous evaluation indictors, applicable to multi-gaits tensegrities, are introduced in searching the corresponding optimal gait patterns that conform to specified needs. The techniques are illustrated and validated in simulation with comparisons on several prototypes of tensegrity robots, indicating that the proposed method is a viable means of attaining marching routes on rolling locomotion of spherical movable tensegrity robots.

A meta-analysis of bariatric surgery in patients with obesity and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease, which is closely related to obesity. This study evaluated the efficacy of bariatric surgery on obesity complicated with PCOS through meta-analysis. PubMed, Cochrane, EMbase, and WOS databases were searched from 2012 to November 2022. Studies on the efficacy of bariatric surgery in the treatment of obesity combined with PCOS were included. Outcome indicators included menstrual abnormalities, BMI, free testosterone, hypertrichosis, and ovarian volume. Methodological quality of the included studies was evaluated, and statistical analysis was performed using RevMan 5.3 software. Finally, 9 studies were included, and the results of meta-analysis were as follows: After weight loss surgery, menstrual irregularity decreased (RR = -0.83, 95%CI:-1.00∼-0.65, P < 0.00001), and BMI decreased significantly (MD = -13.64, 95%CI:-16.29∼-10.99, P < 0.00001). Free testosterone levels decreased (MD = -22.70, 95 % CI: -36.07 âˆ¼ -9.34, P < 0.00001), the incidence of hypertrichosis decreased (RR = 0.63, 95%CI: 0.45-0.88, p = 0.007 < 0.01), and the ovarian volume decreased (MD = -3.09, 5%CI: -5.76 âˆ¼ -0.42, P < 0.00001).

A Retrospective Analysis: Investigating Factors Linked to High Lung-RADS Scores in a Nonsmoking, Non-Family History Population.

Low-dose computed tomography screening for lung cancer is currently targeted at heavy smokers or those with a family history of lung cancer. This study aimed to identify risk factors for lung cancer in individuals who do not meet the current lung cancer screening criteria as stipulated by the Taiwan Health Promotion Agency's low-dose computed tomography (LDCT) screening policy. A cohort analysis was conducted on 12,542 asymptomatic healthy subjects aged 20-80 years old who voluntarily underwent LDCT scans from January 2016 to December 2021. Logistic regression demonstrated that several factors, including age over 55 years, female gender, a body mass index (BMI) less than 23, a previous history of respiratory diseases such as tuberculosis or obstructive respiratory diseases (chronic obstructive pulmonary disease [COPD], asthma), and previous respiratory symptoms such as cough or dyspnea, were associated with high-risk lung radiology scores according to LDCT scans. These findings indicate that risk-based assessments using primary data and questionnaires to identify risk factors other than heavy smoking and a family history of lung cancer may improve the efficiency of lung cancer screening.

Differential susceptibility of BRL cells with/without insulin resistance and the role of endoplasmic reticulum stress signaling pathway in response to acrylamide-exposure toxicity effects in vitro.

Acrylamide (ACR) is an endogenous food contaminant, high levels of ACR have been detected in a large number of foods, causing widespread concern. Since different organism states respond differently to the toxic effects of pollutants, this study establishes an insulin-resistant BRL cell model to explore the differential susceptibility of BRL cells with/without insulin resistance in response to acrylamide-exposure (0.0002, 0.02, or 1 mM) toxicity effects and its mechanism. The results showed that ACR exposure decreased glucose uptake and increased intracellular lipid levels by promoting the expression of fatty acid synthesis, transport, and gluconeogenesis genes and inhibiting the expression of fatty acid metabolism genes, thereby further exacerbating disorders of gluconeogenesis and lipid metabolism in insulin-resistant BRL cells. Simultaneously, its exposure also exacerbated BRL cells with/without insulin-resistant damage. Meanwhile, insulin resistance significantly raised susceptibility to BRL cell response to ACR-induced toxicity. Furthermore, ACR exposure further activated the endoplasmic reticulum stress (ERS) signaling pathway (promoting phosphorylation of PERK, eIF-2α, and IRE-1α) and the apoptosis signaling pathway (activating Caspase-3 and increasing the Bax/Bcl-2 ratio) in BRL cells with insulin-resistant, which were also attenuated after ROS scavenging or ERS signaling pathway blockade. Overall results suggested that ACR evokes a severer toxicity effect on BRL cells with insulin resistance through the overactivation of the ERS signaling pathway.

Industrial Distillation Fractions of Garlic Essential Oil, Design, Synthesis, and Antifungal Activity Evaluation of Aliphatic Substituted Trisulfide Derivatives.

Garlic oil has a wide range of biological activities, and its broad-spectrum activity against phytopathogenic fungi still has the potential to be explored. In this study, enzymatic treatment of garlic resulted in an increase of approximately 50 % in the yield of essential oil, a feasible GC-MS analytical program for garlic oil was provided. Vacuum fractionation of the volatile oil and determination of its inhibitory activity against 10 fungi demonstrated that garlic oil has good antifungal activity. The antifungal activity levels were ranked as diallyl trisulfide (S-3)>diallyl disulfide (S-2)>diallyl monosulfide (S-1), with an EC50 value of S-3 against Botrytis cinerea reached 8.16 mg/L. Following the structural modification of compound S-3, a series of derivatives, including compounds S-4~7, were synthesized and screened for their antifungal activity. The findings unequivocally demonstrated that the compound dimethyl trisulfide (S-4) exhibited exceptional antifungal activity. The EC50 of S-4 against Sclerotinia sclerotiorum reached 6.83 mg/L. SEM, In vivo experiments, and changes in mycelial nucleic acids, soluble proteins and soluble sugar leakage further confirmed its antifungal activity. The study indicated that the trisulfide bond structure was the key to good antifungal activity, which can be developed into a new type of green plant-derived fungicide for plant protection.