Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction.

BACKGROUND: The effects of air pollution on endothelial function remain unclear across populations. We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of air pollution exposure on endothelial dysfunction. METHODS: We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter < 2.5 µm aerodynamic diameter (PM2.5), inhalable particulate matter < 10 µm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratification by age and sex. RESULTS: This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 µg/m3 increase in 7-day exposure to PM2.5 and PM10 was significantly linearly associated with a 0.07% (ß = -0.07, 95% CI: -0.13 to -0.004) and 0.05% (ß = -0.05, 95% CI: -0.10 to -0.004) decrease in FMD in the fully adjusted model. After full adjustment, long-term exposure to all air pollutants was significantly associated with impaired FMD. Each 10 µg/m3 increase in long-term exposure to PM2.5 and PM10 was significantly associated with a -0.18% (95% CI: -0.34 to -0.03) and - 0.23% (95% CI: -0.40 to -0.06) change in FMD, respectively. After stratification, the associations of lower FMD with long-term exposure to PM2.5, PM10, SO2, NO2, and CO significantly persisted in men and participants younger than 65 years instead of women or older participants. For short-term exposure, we observed differences consistent with long-term exposure and a stronger effect of 7-day exposure to SO2 in men due to a significant interaction effect. CONCLUSION: Short- and long-term exposure to different air pollutants are strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex.

Perfusion drugs for non­muscle invasive bladder cancer (Review).

The high recurrence rate and poor prognosis of non-muscle invasive bladder cancer (BC) are challenges that need to be urgently addressed. Transurethral cystectomy for bladder tumors is often combined with bladder perfusion therapy, which can effectively reduce the recurrence and progression rates of BC. The present review integrated and analyzed currently available bladder perfusion drugs, mainly including chemotherapeutic agents, immunotherapeutic agents and other adjuvant perfusion drugs. Bacillus Calmette-Guerin (BCG) perfusion was the pioneering immunotherapy for early BC and still ranks high in the selection of perfusion drugs. However, BCG infusion has a high toxicity profile and has been shown to be ineffective in some patients. Due to the limitations of BCG, new bladder perfusion drugs are constantly being developed. Immunotherapeutic agents have opened a whole new chapter in the selection of therapeutic agents for bladder perfusion. The present review explored the mechanism of action, clinical dosage and adverse effects of a variety of bladder perfusion drugs currently in common use, described combined perfusion and compared the effects of certain drugs on BC.

Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids.

Background: Hypoxia is the typical characteristic of keloids. The development of keloids is closely related to the abnormal phenotypic transition of macrophages. However, the role of exosomal microRNAs (miRNAs) derived from hypoxic macrophages in keloids remains unclear. This study aimed to explore the role of hypoxic macrophage-derived exosomes (HMDE) in the occurrence and development of keloids and identify the critical miRNA. Methods: The expression of CD206+ M2 macrophage in keloids and normal skin tissues was examined through immunofluorescence. The polarization of macrophages under a hypoxia environment was detected through flow cytometry. The internalization of macrophage-derived exosomes in human keloid fibroblasts (HKFs) was detected using a confocal microscope. miRNA sequencing was used to explore the differentially expressed miRNAs in exosomes derived from the normoxic and hypoxic macrophage. Subsequently, the dual-luciferase reporter assay verified that phosphatase and tension homolog (PTEN) was miR-26b-5p's target. The biological function of macrophage-derived exosomes, miR-26b-5p and PTEN were detected using the CCK-8, wound-healing and Transwell assays. Western blot assay was used to confirm the miR-26b-5p's underlying mechanisms and PTEN-PI3K/AKT pathway. Results: We demonstrated that M2-type macrophages were enriched in keloids and that hypoxia treatment could polarize macrophages toward M2-type. Compared with normoxic macrophages-derived exosomes (NMDE), HMDE promote the proliferation, migration and invasion of HKFs. A total of 38 differential miRNAs (18 upregulated and 20 downregulated) were found between the NMDE and HMDE. miR-26b-5p was enriched in HMDE, which could be transmitted to HKFs. According to the results of the functional assay, exosomal miR-26b-5p produced by macrophages facilitated HKFs' migration, invasion and proliferation via the PTEN-PI3K/AKT pathway. Conclusions: The highly expressed miR-26b-5p in HMDE promotes the development of keloids via the PTEN-PI3K/AKT pathway.

Association between triglyceride-glucose index and endothelial dysfunction.

BACKGROUND: Triglyceride-glucose (TyG) index, a simple surrogate marker for insulin resistance (IR), has been reported as an independent predictor of arterial structural damage and future cardiovascular events. The association between TyG index and endothelial dysfunction remains uncertain. OBJECTIVE: The purpose of this study was to investigate the association between TyG index and endothelial dysfunction. METHODS: Endothelial dysfunction was measured using flow-mediated dilation (FMD). A total of 840 subjects, who voluntarily accepted FMD measurement at the Health Management Department of Xuanwu Hospital from October 2016 to January 2020, were included in this study. TyG index was calculated as Ln [fasting triglyceride (TG)(mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: The mean age was 59.92 ± 10.28 years and 559 (66.55%) participants were male. The TyG index was correlated with FMD values (P = 0.022). Each unit increment in TyG index was associated with lower FMD values (ß = -0.330, 95%CI -0.609 to -0.052, P = 0.020) after adjusting for covariates. Age (ß = -0.069, 95%CI -0.088 to -0.051, P < 0.001), female (ß = 0.592, 95%CI 0.172 to1.012, P = 0.006), smoking (ß = -0.430, 95%CI -0.859 to -0.002, P = 0.049) and hypertension (ß = -0.741, 95%CI -1.117 to -0.365, P < 0.001) were also independent predictors for endothelial dysfunction. A significant association between the TyG index and endothelial dysfunction was found only in populations younger than 60 years (ß = -0.843, 95%CI -1.371 to -0.316, P = 0.002), females (ß = -0.612, 95%CI -1.147 to -0.077, P = 0.025), and populations without diabetes mellitus (DM) (ß = -0.594, 95%CI -1.042 to -0.147, P = 0.009). CONCLUSIONS: Subjects with an elevated TyG index are more likely to have endothelial dysfunction, particularly in populations without DM.

Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation­induced cardiomyocyte injury based on network pharmacology and in vitro validation.

Liquiritin (LIQ) is a flavonoid known for its cardioprotective properties, extracted from Glycyrrhiza uralensis Fisch. The purpose of the present study was to investigate the protective mechanism of LIQ against hypoxia/reoxygenation (H/R) injury through in vitro experiments, with the goal of enhancing its pharmacological effects. Initially, network pharmacology was employed to explore the targets and mechanisms of LIQ. Subsequently, an in vitro H/R model was established using H9c2 cells. Potential targets for LIQ and myocardial ischemia-reperfusion injury (MIRI) were identified through online databases. The STRING, Cytoscape and DAVID databases were used to extract intersecting targets and mechanisms. In vitro experiments were conducted to validate these findings, assessing cardiac enzymes, oxidative stress indicators, mitochondrial fluorescence, apoptotic fluorescence, inflammation and related protein expression. The network pharmacological analysis revealed that the protective effects of LIQ on MIRI involve oxidative stress, inflammation and apoptosis. The results of in vitro experimental validation demonstrated that LIQ significantly reduced the activities of lactated dehydrogenase and creatine kinase isoenzyme-MB (P<0.05 or 0.01), as well as the level of malondialdehyde (P<0.01). It also inhibited the production of reactive oxygen species (P<0.01), the release of inflammatory factors (P<0.05 or 0.01) and apoptosis (P<0.01). By contrast, the LIQ pre-treatment group exhibited a significant increase in mitochondrial membrane potential level (P<0.05 or 0.01) and the activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (P<0.05 or 0.01). Furthermore, LIQ reduced the protein expressions of TNF-α receptor type 1 (TNFR1) and MMP9, along with the level of NF-κB phosphorylation (P<0.05 or 0.01). In conclusion, LIQ mitigated H/R-induced cardiomyocyte injury through mechanisms that may involve antioxidants, anti-apoptotic effects, protection against mitochondrial damage and suppression of inflammatory levels. These effects are achieved via inhibition of the TNFR1/NF-κB/MMP9 pathway.

Controlling desertification brings positive socioeconomic benefits beyond regional environmental improvement: Evidence from China's Gonghe Basin.

Large-scale desertification combatting programs (DCPs) are crucial tools for addressing climate change and improving the ecological environment. Despite existing research having predominantly focused on assessing the ecological benefits of DCPs, the understanding of their impacts on surrounding socioeconomic aspects remains limited, particularly at the household level. To comprehensively evaluate the returns of DCPs, this study chose the representative desertification control area of the Gonghe Basin on the Qinghai-Tibet Plateau as the research region and identified the dual benefits in terms of ecological environment and socioeconomic gains. Firstly, two essential ecosystem services, carbon sequestration (CS) and wind erosion prevention (WEP), were assessed using the MODIS NPP dataset and the RWEQ model from 2001 to 2021. Household surveys were conducted in 36 villages across 14 townships within the Gonghe Basin to gain a deeper understanding of the residents' socioeconomic conditions. Through regression analysis, the study assessed the impact of DCPs on the regional ecological environment and household socioeconomic status. The research findings revealed significant improvements in CS and WEP across a significant portion of the study area from 2001 to 2021. Upon analyzing data from 401 household questionnaires, it was generally perceived by residents in the Gonghe Basin that the implementation of DCPs led to environmental improvements and increased their income levels. Further regression analysis revealed a significant impact of both natural factors and the extent of resident participation in the projects on the ecological environment surrounding the villages and on household socioeconomic aspects. With increased resident engagement in the projects, the likelihood of increased household income and life satisfaction was higher. The diverse array of DCPs implemented in the Gonghe Basin not only improved the regional ecological environment but also stimulated socioeconomic development. In future projects, it is imperative to consider regional characteristics, align ecological effects, ensure the sustainability of livelihoods, and maximize the role of social capital.

Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.

A female-specific odorant receptor mediates oviposition deterrence in the moth Helicoverpa armigera.

Finding ideal oviposition sites is a task of vital importance for all female insects. To ensure optimal conditions for their progeny, females of herbivorous insects detect not only the odors of a relevant host plant but also chemicals released by eggs, named oviposition-deterring pheromones (ODPs). It is reported that such chemicals play critical roles in suppressing female oviposition behavior; however, the molecular mechanism underlying the detection of egg-derived ODPs remains elusive. Here, we have identified three specific fatty acid methyl esters from the surface of eggs of Helicoverpa armigera serving as ODPs-methyl oleate (C18:1ME), methyl palmitate (C16:0ME), and methyl stearate (C18:0ME). We demonstrated that these ODPs are detected by the receptor, HarmOR56, exclusively expressed in sensilla trichodea on female antennae. To assess the significance of this receptor, we disrupted HarmOR56 in H. armigera using CRISPR-Cas9 and found that mutant females did not respond to the ODPs, neither in behavioral nor in electrophysiological tests. We therefore conclude that HarmOR56 is indispensable for identifying the ODPs. This study explores, for the first time, how a female-specific odorant receptor detects chemicals from conspecific eggs. Our data elucidate the intriguing biological phenomenon of repulsion to conspecific eggs during oviposition and contribute new insight into a female-specific olfactory pathway linked to reproduction.

Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Development of a diagnostic and risk prediction model for Alzheimer's disease through integration of single-cell and bulk transcriptomic analysis of glutamine metabolism.

Background: In this study, we present a novel system for quantifying glutamine metabolism (GM) to enhance the effectiveness of Alzheimer's disease (AD) diagnosis and risk prediction. Methods: Single-cell RNA sequencing (scRNA-seq) analysis was utilized to comprehensively assess the expression patterns of GM. The WGCNA algorithm was applied to investigate the most significant genes related to GM. Subsequently, three machine learning algorithms (Boruta, LASSO, and SVM-RFE) were employed to identify GM-associated characteristic genes and develop a risk model. Patients were divided into high- and low-risk groups based on this model. Moreover, we explored biological properties, distinct signaling pathways, and immunological characteristics of AD patients at different risk levels. Finally, in vitro and in vivo models of AD were constructed to validate the characteristics of the feature genes. Results: Both scRNA-seq and bulk transcriptomic analyses revealed increased GM activity in AD patients, specifically in certain cell subsets (pDC, Tem/Effector helper T cells (LTB), and plasma cells). Cells with higher GM scores demonstrated more significant numbers and strengths of interactions with other cell types. The WGCNA algorithm identified 360 genes related to GM, and a risk score was constructed based on nine characteristic genes (ATP13A4, PIK3C2A, CD164, PHF1, CES2, PDGFB, LCOR, TMEM30A, and PLXNA1) identified through multiple machine learning algorithms displayed reliable diagnostic efficacy for AD onset. Nomograms, calibration curves, and decision curve analysis (DCA) based on these characteristic genes provided significant clinical benefits for AD patients. High-risk AD patients exhibited higher levels of immune-related functions and pathways, increased immune cell infiltration, and elevated expressions of immune modulators. RT-qPCR analysis revealed that the majority of the nine characteristic genes were differentially expressed in AD-induced rat neurons. Knocking down PHF1 could protect against neurite loss and alleviate cell injury in AD neurons. In vivo, down-regulation of PHF1 in AD models decreases GM metabolism levels and modulates the immunoinflammatory response in the brain. Conclusion: This comprehensive identification of gene expression patterns contributes to a deeper understanding of the underlying pathological mechanisms driving AD pathogenesis. Furthermore, the risk model based on the nine-gene signature offers a promising theoretical foundation for developing individualized treatments for AD patients.

The tRNA-GCN2-FBXO22-axis-mediated mTOR ubiquitination senses amino acid insufficiency.

Mammalian target of rapamycin complex 1 (mTORC1) monitors cellular amino acid changes for function, but the molecular mediators of this process remain to be fully defined. Here, we report that depletion of cellular amino acids, either alone or in combination, leads to the ubiquitination of mTOR, which inhibits mTORC1 kinase activity by preventing substrate recruitment. Mechanistically, amino acid depletion causes accumulation of uncharged tRNAs, thereby stimulating GCN2 to phosphorylate FBXO22, which in turn accrues in the cytoplasm and ubiquitinates mTOR at Lys2066 in a K27-linked manner. Accordingly, mutation of mTOR Lys2066 abolished mTOR ubiquitination in response to amino acid depletion, rendering mTOR insensitive to amino acid starvation both in vitro and in vivo. Collectively, these data reveal a novel mechanism of amino acid sensing by mTORC1 via a previously unknown GCN2-FBXO22-mTOR pathway that is uniquely controlled by uncharged tRNAs.

Estrogen receptor alpha-mediated mitochondrial damage in intrahepatic bile duct epithelial cells leading to the pathogenesis of primary biliary cholangitis.

This study investigated the effects of estrogen and estrogen receptor alpha (ERα) on the pathogenesis of primary biliary cholangitis (PBC) in human intrahepatic bile duct epithelial cells (HiBECs). The researchers measured serum levels of ERα, oxidative stress indicators, and cytokines in PBC patients and healthy controls. They examined the expression of ERα, pyruvate dehydrogenase complex E2-component (PDC-E2), and apoptosis-related proteins in the small bile ducts. In vitro experiments with HiBECs showed that estrogen had a dual effect on cell viability, increasing it at low concentrations but reducing it at higher concentrations. ERα activation led to mitochondrial damage, apoptosis, and upregulation of ERα and PDC-E2 expression. These findings suggest that the high expression of ERα in the bile ducts contributes to mitochondrial damage, inflammation, and apoptosis in PBC. The study highlights ERα as a potential target for understanding and treating estrogen-mediated PBC pathogenesis.

Association of variability in metabolic parameters with the incidence of type 2 diabetes: evidence from a functional community cohort.

BACKGROUND: To investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D. METHODS: Based on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D. RESULTS: During a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1-2, 3, 4-5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses. CONCLUSIONS: High variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.

The incidence of subclinical atherosclerosis in subjects with low and moderate cardiovascular risk.

BACKGROUND: The cardiovascular risk models and subclinical atherosclerotic indicators are both recommended for cardiovascular risk stratification. The accordance between the incidence of subclinical atherosclerosis and subjects with low and moderate cardiovascular risk is unclear. HYPOTHESIS: Subjects with low and moderate cardiovascular risk have a lower incidence of subclinical atherosclerosis compared with subjects with high risk. METHODS: Brachial-ankle pulse wave velocity (BaPWV) and brachial flow-mediated dilation (BFMD) were measured in 421 subjects without a history of atherosclerotic cardiovascular disease (ASCVD) from October 2016 to January 2020. All subjects were classified into low, moderate, and high risk based on Framingham and China-par risk models respectively. RESULTS: Mean age was 57.05 ± 9.35 years and 248 (58.9%) were male. In subjects with low, moderate, and high risk assessed by Framingham and China-par risk models, the percentage of abnormal BaPWV ( > 1400 cm/s) was 42.9%, 70.1%, 85.7%, and 40.4%, 71.4%, 89.7%, respectively. Meanwhile, the percentage of abnormal BFMD ( ≤ 7%) was 43.8%, 68.5%, 77.3%, and 44.9%,72.1%, and 76.6%. According to Framingham-based high-risk categories, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for BaPWV abnormality were 85.7%, 39.4%, 36.1%, and 87.5%, respectively. For BFMD abnormality, the values were 77.3%, 40.1%, 34.1%, and 81.8%, respectively. According to China-par high-risk categories, the values for BaPWV abnormality were 89.7%, 43.8%, 45.6%, and 89.0%, respectively. For BFMD abnormality, the values were 76.6%, 41.3%, 40.7%, and 77%, respectively. In multivariate analysis, age and blood pressure were the independent predictors for subclinical atherosclerosis in subjects with low-moderate risk. CONCLUSIONS: More than one-half of subjects with low and moderate risk already have detectable subclinical atherosclerosis, indicating higher cardiovascular risk beyond the traditional stratification.

miR-656-3p inhibits melanomas in vitro and in vivo by inducing senescence via inhibiting LMNB2.

BACKGROUND: Ultra-Violet Radiation (UVR) is the most significant exogenous contributor to skin aging. UVB causes the senescence of melanocytes, which results in a permanent arrest in the proliferative process. Senescence is also regarded as a physiological tumor-suppressing mechanism of normal cells. However, the mechanism of the relationship between melanocyte senescence and melanoma was not sufficiently clarified. METHODS: Melanocytes and melanoma cells were irradiated with UVB for the indicated time. The miRNA expression profile of melanocytes were obtained by miRNA sequencing and confirmed by real-time PCR. Cell count kit-8 assays, cell cycle assays were also employed to explore the effect of miR-656-3p and LMNB2 on senescence. Dual-luciferase reporter assays were applied to determine the miRNA targets. Finally, a xenograft model and a photoaging model of mice were conducted to verified the function of miR-656-3p in vivo. RESULTS: Melanoma cells did not alter into a senescence stage and the expressions of miR-656-3p had no significant changes under the same intensity of UVB radiation. miR-656-3p appeared to be upregulated in melanocytes rather than melanoma cells after UVB radiation. miR-656-3p could promote the photoaging of human primary melanocytes by targeting LMNB2. Finally, overexpression of miR-656-3p significantly induced senescence and inhibited the growth of melanomas in vitro and in vivo. CONCLUSION: Our work not only demonstrated the mechanism by which miR-656-3p induced the senescence of melanocytes but also proposed a treatment strategy for melanomas by using miR-656-3p to induce senescence.

High Tg, Bio-Based Isosorbide Methacrylate Resin Systems for Vat Photopolymerization.

The use of isosorbide-derived polymers has garnered significant attention in recent decades as a high-performance, renewable material sourced from biomass. Of particular interest is isosorbide methacrylate, which possesses low viscosity (<500 cps), high thermal properties (Tg ≈ 220 °C), and high modulus (>4 GPa). These characteristics present a promising opportunity to replace BPA-derived methacrylate compounds in various applications. This investigation aims to synthesize and characterize isosorbide-based low-viscosity resin systems for 3D printing. The resin blends are composed of isosorbide methacrylate and two bio-renewable methacrylates, furfuryl methacrylate (FM) and bis-hydroxymethyl-furan methacrylate (BHMF-M), polymerized through a digital light processing (DLP) technique. The addition of the bio-based co-monomers serves to enhance the fracture toughness of the brittle isosorbide methacrylate crosslinked homopolymer (GIc = 37 J/m2). The resulting polymers exhibit Tg values greater than 200 °C and GIc around 100 J/m2. These resin systems hold potential for imparting high bio-based content to polymers used in additive manufacturing for high-performance applications.

Safety and efficacy of endovascular recanalization for symptomatic non-acute atherosclerotic intracranial large artery occlusion.

Background and objective: The optimal treatment for patients with symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) despite medical treatment is not well established. We aimed to assess the safety, efficacy, and feasibility of angioplasty and stenting for these patients. Methods: A total of 251 consecutive patients with symptomatic non-acute atherosclerotic ILAO treated with interventional recanalization were retrospectively collected in our center from March 2015 to August 2021. The rate of successful recanalization, perioperative complications, and follow-up outcomes were evaluated. Results: Successful recanalization was achieved in 88.4% (222/251) of the patients. A total of 24 (24/251, 9.6%) symptomatic complications occurred among 251 procedures. In the 193 patients with clinical follow-up during 19.0 ± 14.7 months, 11 (11/193, 5.7%) patients developed ischemic stroke and four (4/193, 2.1%) patients developed transient ischemic attack (TIA). In the 106 patients with vascular imaging follow-up during 6.8 ± 6.6 months, seven (7/106, 6.6%) patients had restenosis and 10 (10/106, 9.4%) patients had reocclusion. Conclusion: This study suggests that interventional recanalization may be a feasible, basically safe, and an effective alternative in carefully selected patients with symptomatic non-acute atherosclerotic ILAO who have failed medical management.

Chronic Remote Ischemic Conditioning on Mild Hypertension in the Absence of Antihypertensive Medication: A Multicenter, Randomized, Double-Blind, Proof-of-Concept Clinical Trial.

BACKGROUND: Exploratory studies have shown that remote ischemic conditioning (RIC) has the potential to lower blood pressure (BP). We investigated whether chronic RIC reduces BP for hypertension. METHODS: This is a multicenter, randomized, double-blind, parallel-controlled trial. Patients with an office BP of 130/80 to 160/100 mm Hg and a 24-hour average BP ≥125/75 mm Hg not on antihypertensive medications were recruited. After a 1-week compliance screening phase, they were randomly assigned in a 1:1 ratio to receive RIC or sham RIC twice daily for 4 weeks. The primary efficacy outcome was the change in 24-hour average systolic BP from baseline to 4 weeks. Safety events were assessed over the study period. RESULTS: Ninety-five participants were randomly allocated to the RIC (n=49) and sham RIC (n=46) groups. In the intention-to-treat analysis, the reduction in 24-hour average systolic BP was greater in the RIC group than the sham RIC group (-4.6±9.5 versus -0.9±6.8 mm Hg; baseline-adjusted between-group mean difference: -3.6 mm Hg [95% CI, -6.9 to -0.3 mm Hg]; adjusted P=0.035). The per-protocol analysis showed that 24-hour average systolic BP reduced -5.9±8.6 mm Hg in the RIC group and -0.7±6.7 mm Hg in the sham RIC group (baseline-adjusted between-group mean difference: -5.2 mm Hg [95% CI, -8.5 to -1.9 mm Hg]; adjusted P=0.002). No major adverse events were reported in both groups. CONCLUSIONS: RIC is safe in patients with mild hypertension and may lower BP in the absence of antihypertensive medications. However, the effects of RIC on clinical outcomes in these patients require further investigation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04915313.

Occupational stress is associated with insulin resistance and incident type 2 diabetes: A prospective cohort study of functional community.

BACKGROUND: To exploit the association of occupational stress with the development of insulin resistance (IR) and type 2 diabetes (T2D) in a Chinese population-based cohort. METHODS: A total of 6109 participants from a functional community cohort in Beijing were enrolled in 2015 and followed up until 2021. Copenhagen Psychosocial Questionnaire (COPSOQ) were used to evaluate occupational stress. RESULTS: At baseline, increase values of all five scales of COPSOQ and total COPSOQ were significantly associated with IR. During an average 5.63 y follow-up, 732 individuals developed T2D. Increasing in values of "Demands at work", "Insecurity at work", "Job satisfaction" and total COPSOQ were significantly associated with incident T2D (P < 0.01). Mediation analysis showed that subjectively perceived occupational stress promoted T2D mainly by affecting plasma cortisol and the mediation effects of HOMA-IR, SBP, DBP, TG, Urea and UA were significant on the association between cortisol and incident T2D, with proportion mediated of 37.1%, 8.12%, 2.02%, 2.94%, 2.35% and 2.70%. CONCLUSION: Occupational stress was independently associated with the development of IR and T2D. IR, BP, TG, Urea and UA all partly mediated the association between occupational stress and incident T2D.