Examining the Relationship Between Social Support, Self-Efficacy, Diabetes Self-Management, and Quality of Life Among Rural Individuals With Type 2 Diabetes in Eastern China: Path Analytical Approach.

BACKGROUND: Patients with type 2 diabetes (T2D) in rural China frequently exhibit inadequate diabetes self-management (DSM) and a reduced quality of life (QoL). Social support and self-efficacy are known to influence DSM and QoL. However, the pathways through which social support and self-efficacy impact DSM and QoL among patients with T2D in rural China has yet to be fully elucidated. OBJECTIVE: This study offers a foundation for developing policies in rural chronic disease management, thereby, contributing to the improvement of T2D prevention and control in China and other transitional countries. METHODS: This study used a cross-sectional design, collecting data from a survey conducted between May and July 2021 on DSM and QoL among rural patients diagnosed with T2D in 2 townships in East China. All patients with T2D were enrolled through cluster sampling from the township health center database, and a questionnaire survey was administered by investigators. Structural equation modeling and multiple regression analyses were used to explore the pathways through which social support influences DSM and QoL, as well as the mediating role of self-efficacy. RESULTS: It was found that the DSM score (mean 37.42, SD 7.70) was less than half of the maximum theoretical score. The QoL score (mean 48.92, SD 8.88) accounted for 36% of the maximum theoretical score. Social support directly and positively affected the DSM and QoL of Chinese rural patients with T2D (P<.01); an increase of 1 unit in social support was associated with a direct increment of 0.339 units in DSM and 0.397 units in QoL. Self-efficacy played a positive mediating role (P<.01), further increasing DSM and QoL by 0.147 and 0.159 units, respectively. The mediating effect of self-efficacy accounted for 30.2% and 28.6% of the total effect of social support on DSM and QoL. Furthermore, the family and friend dimension of social support, along with the symptom and disease management dimensions of self-efficacy, were significantly associated with DSM or QoL (P<.01). CONCLUSIONS: The study confirmed the direct and indirect influences of social support on DSM and QoL and elucidated the mediating effect of self-efficacy among rural patients with T2D in eastern China. Interventions should be developed to enhance both social support and self-efficacy, creating a positive cycle of mutual reinforcement to improve DSM and QoL among this group.

Changes and relevant factors in depressive and anxiety symptoms among Chinese adolescents after the "Double Reduction" policy: A repeated cross-sectional survey with a nested longitudinal subsample.

BACKGROUND: The Chinese government has enacted the "Double Reduction" Policy, which aims to reduce students' academic burden and promote their mental health, but there is limited research examining the policy's impact on students' well-being. This study aims to evaluate changes in students' mental health problems before and after the "Double Reduction" Policy and explore relevant influential factors. METHODS: A total of 101,976 elementary and junior high school students were recruited before the "Double Reduction" Policy, and 91,832 students were recruited one year later. Through data integration, a total of 36,637 students participated in both web-based surveys and provided complete data on all measures. RESULTS: As a whole, we found that the prevalence of students' depression (12.1 % to 9.2 %) and anxiety (8.9 % to 6.2 %) tended to decline after the "Double Reduction" Policy. Attending private school, reduced homework, more extracurricular activities, more time with parents, reduced academic stress, and sleep duration ≥8 h/n were associated with the decrease in the likelihood of mental health problems in students. Female gender, negative life events, and negative impact of COVID-19 as risk factors for mental health. CONCLUSIONS: These findings indicated that the "Double Reduction" Policy has improved the well-being of Chinese students. Reducing students' homework burden and alleviating their academic pressure are beneficial for their mental health. Increasing time for extracurricular activities and interaction with parents, as well as ensuring sufficient sleep for students, are also effective ways to prevent the onset and exacerbation of mental health symptoms in adolescents.

DB-1314, a novel DLL3-targeting ADC with DNA topoisomerase I inhibitor, exhibits promising safety profile and therapeutic efficacy in preclinical small cell lung cancer models.

BACKGROUND: Delta-like ligand 3 (DLL3) is highly expressed on the cell surface of small cell lung cancer (SCLC), one of the most lethal malignancies, but minimally or not in normal tissues, making it an attractive target for SCLC. However, none of the DLL3-targeting antibody-drug conjugates (ADCs) have been approved for SCLC therapy yet. We developed DB-1314, the new anti-DLL3 ADC composed of a novel humanized anti-DLL3 monoclonal antibody (DB131401) conjugated with eight molecules of P1021 (topoisomerase I inhibitor), and described its preclinical profiles. METHODS: The binding epitope for DB131401 and Rovalpituzumab was tested by biolayer interferometry. The binding affinity and specificity of DB-1314 to DLL3 and other homologous proteins were respectively measured by surface plasmon resonance and enzyme-linked immunosorbent assay. Internalization, bystander effects, and antibody-dependent cell-mediated cytotoxicity (ADCC) were assessed by respective assay. DLL3 was quantified by antibodies bound per cell assay and immunohistochemistry. In vitro and in vivo growth inhibition studies were evaluated in SCLC cell lines, and cell line/patient-derived xenograft models. The safety profile was measured in cynomolgus monkeys. RESULTS: DB-1314 induces potent, durable, and dose-dependent antitumor effects in cells in vitro and in cell/patient-derived xenograft models in vivo. The killing activity of DB-1314 mechanically arises from P1021-induced DNA damage, whereby P1021 is delivered and released within tumor cells through DLL3-specific binding and efficient internalization. Bystander effects and ADCC also contribute to the antitumor activity of DB-1314. DB-1314 displays favorable pharmacokinetic and toxicokinetic profiles in rats and cynomolgus monkeys; besides, DB-1314 is well-tolerated at a dose of up to 60 mg/kg in monkeys. CONCLUSIONS: These results suggest that DB-1314 may be a candidate ADC targeting DLL3 for the treatment of DLL3-positive SCLC, supporting further evaluation in the clinical setting.

Farmland's silent threat: Comprehensive multimedia assessment of micropollutants through non-targeted screening and targeted analysis in agricultural systems.

Intricate agricultural ecosystems markedly influence the dynamics of organic micropollutants, posing substantial threats to aquatic organisms and human health. This study examined the occurrence and distribution of organic micropollutants across soils, ditch sediment, and water within highly intensified farming setups. Using a non-targeted screening method, we identified 405 micropollutants across 10 sampling sites, which mainly included pesticides, pharmaceuticals, industrial chemicals, and personal care products. This inventory comprised emerging contaminants, banned pesticides, and controlled pharmaceuticals that had eluded detection via conventional monitoring. Targeted analysis showed concentrations of 3.99-1021 ng/g in soils, 4.67-2488 ng/g in sediment, and 12.5-9373 ng/L in water, respectively, for Σ40pesticides, Σ8pharmaceuticals, and Σ3industrial chemicals, indicating notable spatial variability. Soil organic carbon content and wastewater discharge were likely responsible for their spatial distribution. Principal component analysis and correlation analysis revealed a potential transfer of micropollutants across the three media. Particularly, a heightened correlation was decerned between soil and sediment micropollutant levels, highlighting the role of sorption processes. Risk quotients surpassed the threshold of 1 for 13-23 micropollutants across the three media, indicating high environmental risks. This study highlights the importance of employing non-targeted and targeted screening in assessing and managing environmental risks associated with micropollutants.

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer.

OBJECTIVES: The study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. METHODS: Differentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. RESULTS: Upregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. CONCLUSIONS: ECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

A large-aperture, high-power ultrawideband radiation system with beam broadening capacity.

Due to the limited maximum output power of the pulsers based on avalanche transistors, high-power ultrawideband (UWB) radiation systems usually synthesize plenty of modules simultaneously to achieve a high peak effective potential (rEp). However, this would lead to an increased aperture size as well as a narrower beam, which would limit their applications in intentional electromagnetic interference fields. In this paper, a high-power UWB radiation system with beam broadening capacity is developed. To achieve beam broadening in the time domain, a power-law time delay distribution method is proposed and studied by simulation, and then the relative excitation time delays of the modules are optimized to achieve higher rEp and avoid beam splitting in the beam broadening mode. In order to avoid false triggering of the pulser elements when implementing the beam broadening, the mutual coupling effect in the system is analyzed and suppressed by employing onboard high-pass filters, since the mutual coupling effect is much more severe in the low-frequency range. Finally, a radiation system with 36 modules is developed. Measuring results indicate that in the high-rEp mode, the developed system could achieve a maximum effective potential rEp of 313.6 kV and a maximum pulse-repetition-rate of 20 kHz. In the beam broadening mode, its half-peak-power beam width in the H-plane is broadened from the original value of 3.9° to 7.9°, with a maximum rEp of 272.9 kV. The polarization direction of the system could be flexibly adjusted by a built-in motor.

The protective effects of Kefir extract (KE) on intestinal damage in larval zebrafish induced by Oxytetracycline: Insights into intestinal function, morphology, and molecular mechanisms.

The antibiotic oxytetracycline (OTC) can be detected in contemporary natural aquatic environments and has been implicated in causing intestinal damage in humans exposed to OTC-contaminated food or water. The irreversible damage caused by high concentrations of OTC to the intestine suggests that treatment through dietary means could still be necessary. This study proved the effectiveness of kefir extract (KE) in reversing intestinal damage caused by oxytetracycline (OTC) exposure. Following a 24-hour KE treatment subsequent to OTC exposure from 3 to 8 days post-fertilization of zebrafish larvae, molecular-level and microbiomic assessments revealed significant improvements. These included reduced expression of proinflammatory factors (IL-8 and IL-1ß), increased antioxidant levels, and reversed unhealthy distribution of intestinal microbiota. Furthermore, KE supplementation showed potential in enhancing intestinal motility in the experiment of Nile red staining and fluorescent microbead transit. However, histological analysis showed that this short-term treatment with KE only partially reversed the intestinal morphological changes induced by OTC, suggesting that a longer treatment period might be necessary for complete restoration.

Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration.

Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.

Effects of miR-29c on proliferation and adipogenic differentiation of porcine bone marrow mesenchymal stromal cells.

microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.

All-silicon metalens for broadband achromatic polarization multiplexing in long-wave infrared wavelengths.

Traditional long-wave infrared polarimetry usually relies on complex optical setups, making it challenging to meet the increasing demand for system miniaturization. To address this problem, we design an all-silicon broadband achromatic polarization-multiplexing metalens (BAPM) operating at the wavelength range of 9-12 µm. A machine-learning-based design method is developed to replace the tedious and computationally intensive simulation of a large number of meta-atoms. The results indicate that the coefficients of variation in focal length of the BAPM are 3.95% and 3.71%, and the average focusing efficiencies are 41.3% and 40.5% under broadband light incidence with x- and y-polarizations, respectively.

Waveguide-integrated van der Waals heterostructure photodetector on a lithium niobate on insulator platform.

Lithium niobate (LN) photonics has gained significant interest for their distinct material properties. However, achieving monolithically integrated photodetectors on lithium niobate on an insulator (LNOI) platform for communication wavelengths remains a challenge due to the large bandgap and extremely low electrical conductivity of LN material. A two-dimensional (2D) material photodetector is an ideal solution for LNOI photonics with a strong light-matter interaction and simple integration technique. In this work, a van der Waals heterostructure photodiode composed of a p-type black phosphorus layer and an n-type MoS2 layer is successfully demonstrated for photodetection at communication wavelengths on a LNOI platform. The LNOI waveguide-integrated BP-MoS2 photodetector exhibits a dark current as low as 0.21 nA and an on/off ratio exceeding 200 under zero voltage bias with an incident power of 13.93 µW. A responsivity as high as 1.46 A/W is achieved at -1 V bias with a reasonable dark current around 2.33 µA. With the advantages of high responsivity, low dark current, and simple fabrication process, it is promising for the monolithically integrated photodetector application for LNOI photonic platforms at communication wavelengths.

Aluminum scandium nitride on 8-inch Si wafers: material characterization and photonic device demonstration.

The anisotropic optical properties of aluminum scandium nitride (Al1-xScxN) thin films for both ordinary and extraordinary light are investigated. A quantitative analysis of the band structures of the wurtzite Al1-xScxN is carried out. In addition, Al1-xScxN photonic waveguides and bends are fabricated on 8-inch Si substrates. With x = 0.087 and 0.181, the light propagation losses are 5.98 ± 0.11 dB/cm and 8.23 ± 0.39 dB/cm, and the 90° bending losses are 0.05 dB/turn and 0.08 dB/turn at 1550 nm wavelength, respectively.

An investigation of the prevalence and diversity of Anisakis in China: marine food safety implications.

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.

Segment anything with inception module for automated segmentation of endometrium in ultrasound images.

Purpose: Accurate segmentation of the endometrium in ultrasound images is essential for gynecological diagnostics and treatment planning. Manual segmentation methods are time-consuming and subjective, prompting the exploration of automated solutions. We introduce "segment anything with inception module" (SAIM), a specialized adaptation of the segment anything model, tailored specifically for the segmentation of endometrium structures in ultrasound images. Approach: SAIM incorporates enhancements to the image encoder structure and integrates point prompts to guide the segmentation process. We utilized ultrasound images from patients undergoing hysteroscopic surgery in the gynecological department to train and evaluate the model. Results: Our study demonstrates SAIM's superior segmentation performance through quantitative and qualitative evaluations, surpassing existing automated methods. SAIM achieves a dice similarity coefficient of 76.31% and an intersection over union score of 63.71%, outperforming traditional task-specific deep learning models and other SAM-based foundation models. Conclusions: The proposed SAIM achieves high segmentation accuracy, providing high diagnostic precision and efficiency. Furthermore, it is potentially an efficient tool for junior medical professionals in education and diagnosis.

Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes.

BACKGROUND: In 2014, the US Food and Drug Administration approved the first glucagon-like peptide-1 (GLP-1) receptor agonist product, liraglutide injection, for obesity treatment. Many GLP-1 obesity treatment clinical trials report significant weight loss and medication adherence at more than 85%. Little is known about the real-world GLP-1 obesity treatment adherence, persistence, and switch rates. OBJECTIVE: To measure GLP-1 therapy persistence, adherence, and switch rates in a real-world cohort of members without diabetes using these drugs for obesity treatment. METHODS: Integrated pharmacy and medical claims data from 16.5 million average monthly commercially insured membership were used to identify obese members without diabetes newly initiating GLP-1 therapy between January 1, 2021, and December 31, 2021. Members were required to be continuously enrolled 1-year before and after the GLP-1 therapy start date and aged 19 years of age or older. Persistence was measured as no greater than or equal to 60-day gap with allowance for GLP-1 switching. Adherence was measured as the proportion of days covered (PDC) and members with a PDC greater than or equal to 80% were considered adherent. GLP-1 product switching was also assessed descriptively. RESULTS: 4,066 commercially insured obese members without diabetes that newly initiated GLP-1 therapy met all study criteria. The mean age was 46 years, and 81% were female. Overall, GLP-1 persistence was 46.3% at 180 days and 32.3% at 1 year. The highest and lowest persistence rates at 1 year were observed for semaglutide (Ozempic) at 47.1% and liraglutide (Saxenda) 19.2%, respectively. Average PDC during the 1-year assessment was 51.0% with 27.2% adherent to therapy and 11.1% switched GLP-1 drugs. CONCLUSIONS: This GLP-1 weight loss treatment real-world analysis, among obese individuals without diabetes, found poor 1-year persistence and adherence and low rates of switching between products. These findings will aid in assessing products cost-effectiveness, understanding obesity care management program needs, forecasting future GLP-1 use and cost trends, and negotiating GLP-1 pharmaceutical manufacturer value-based purchasing agreements.

Design of antiviral AGO2-dependent short hairpin RNAs.

The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV), dengue virus 2 (DENV2), mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and transformed them into agshRNAs. We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses. Using the agshRNA targeting EV71 as an example, we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA. Moreover, the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA, which can load into the RNA-induced silencing complex (RISC). We also confirmed the antiviral effect of agshRNA in vivo. Together, this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.

Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

Overcoming barriers to improved decision-making for battery deployment in the clean energy transition.

Decarbonization plans depend on the rapid, large-scale deployment of batteries to sufficiently decarbonize the electricity system and on-road transport. This can take many forms, shaped by technology, materials, and supply chain selection, which will have local and global environmental and social impacts. Current knowledge gaps limit the ability of decision-makers to make choices in facilitating battery deployment that minimizes or avoids unintended environmental and social consequences. These gaps include a lack of harmonized, accessible, and up-to-date data on manufacturing and supply chains and shortcomings within sustainability and social impact assessment methods, resulting in uncertainty that limits incorporation of research into policy making. These gaps can lead to unintended detrimental effects of large-scale battery deployment. To support decarbonization goals while minimizing negative environmental and social impacts, we elucidate current barriers to tracking how decision-making for large-scale battery deployment translates to environmental and social impacts and recommend steps to overcome them.

Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Causal relationship between dyslipidemia and risk of facial aging: Insights from Mendelian randomization in East Asian populations.

BACKGROUND: Emerging observational studies showed an association between dyslipidemia and aging. However, it remains unclear whether this association is causal, particularly in the case of Asians, which are aging more rapidly than other continents. Given the visible manifestations of aging often include changes in facial appearance, the objective of this study is to assess the causal relationship between dyslipidemia and facial aging in East Asian populations. METHODS: SNPs related to dyslipidemia in East Asian people such as Total cholesterol (TC), High-density-lipoprotein cholesterol (HDL), Low-density-lipoprotein cholesterol (LDL), and Triglyceride (TG) along with outcomes data on facial aging, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse variance weighted (IVW) method. RESULTS: Totally, 88 SNPs related to HDL among 70657 East Asian participants in GWAS. Based on the primary causal effects model using MR analyses with the IVW method, high HDL level was demonstrated as significantly related to the risk of facial aging (OR, 1.060; 95% CI, 1.005-1.119, p = 0.034), while high TC level (OR, 0.995; 95% CI, 0.920-1.076, p = 0.903), high LDL level (OR, 0.980, 95% CI, 0.924-1.041, p = 0.515), as well as high TG level (OR, 0.999, 95% CI, 0.932-1.071, p = 0.974), showed no significant correlation with facial aging. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between high HDL levels and facial aging. In contrast, facial aging demonstrated no significant correlation with high levels of TC, LDL, or TG. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding nutrition management to delay the aging process among old patients in East Asia.