Time from waking to the first cigarette and mortality and incident cardiovascular disease.

BACKGROUND: This study aimed to investigate the associations of time from waking to the first cigarette (TWFC) with all-cause mortality, cardiovascular disease (CVD) mortality and incident CVD among people smoking. METHODS: Data were from the UK Biobank, including 32 519 people smoking aged 40-70 years. TWFC was investigated using a touch-screen questionnaire. Outcomes included all-cause mortality and mortality from and incidence of CVD, ischemic heart disease (IHD) and stroke. RESULTS: Compared with participants reporting TWFC >120 min, those reporting TWFC between 61 and 120 min (HR, 1.30; 95% CI, 1.10-1.53), TWFC between 5 and 60 min (1.48, 1.30-1.70) and TWFC <5 min (1.65, 1.42-1.93) had a higher risk of all-cause mortality. Compared with participants reporting TWFC >120 min, those reporting TWFC between 5 and 60 min and TWFC <5 min had higher risks of CVD and IHD mortality and incident CVD and IHD, but those reporting TWFC between 61 and 120 min did not. The associations of TWFC with stroke mortality and incident stroke were not observed. CONCLUSION: In this cohort study, a shorter TWFC was associated with higher risks of all-cause mortality, mortality from CVD and IHD, as well as incident CVD and IHD.

Erratum: Publisher Correction: Removal of the C4-domain preserves the drought tolerance enhanced by CsMYB4a and eliminates the negative impact of this transcription factor on plant growth.

[This corrects the article DOI: 10.1007/s42994-024-00149-5.].

Removal of the C4-domain preserves the drought tolerance enhanced by CsMYB4a and eliminates the negative impact of this transcription factor on plant growth.

The MYB4 transcription factor family regulates plant traits. However, their overexpression often results in undesirable side effects like growth reduction. We have reported a green tea (Camellia sinensis) MYB4 transcription factor (CsMYB4) that represses the phenylpropanoid and shikimate pathways and stunts plant growth and development. In the current study, we observed that in CsMYB4a transgenic tobacco (Nicotiana tabacum) plants, primary metabolism was altered, including sugar and amino acid metabolism, which demonstrated a pleiotropic regulation by CsMYB4a. The CsMYB4a transgenic tobacco plants had improved drought tolerance, which correlated to alterations in carbohydrate metabolism and an increase in proline content, as revealed by metabolic profiling and transcriptomic analysis. To mitigate the undesirable repressive side effects on plant traits, including dwarfism, shrunken leaves, and shorter roots of CsMYB4a transgenic plants, we deleted the C4 domain of CsMYB4a to obtain a CsMYB4a-DC4 variant and then overexpressed it in transgenic plants (CsMYB4a-DC4). These CsMYB4a-DC4 plants displayed a normal growth and had improved drought tolerance. Metabolite analysis demonstrated that the contents of carbohydrates and proline were increased in these transgenic plants. Our findings suggest that  an approriate modification of TFs can generate novel crop traits, thus providing potential agricultural benefits and expanding its application to various crops. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00149-5.

Research on carotid artery plaque anomaly detection algorithm based on ultrasound images.

Carotid artery plaque is a key factor in stroke and other cardiovascular diseases. Accurate detection and localization of carotid artery plaque are essential for early prevention and treatment of diseases. However, current carotid artery ultrasound image anomaly detection algorithms face several challenges, such as scarcity of anomaly data in carotid arteries and traditional convolutional neural networks (CNNs) overlooking long-distance dependencies in image processing. To address these issues, we propose an anomaly detection algorithm for carotid artery plaques based on ultrasound images. The algorithm innovatively introduces an anomaly sample pair generation method to increase dataset diversity. Moreover, it employs an improved adaptive recursive gating pyramid pooling module to extract image features. This module significantly enhances the model's capacity for high-order spatial interactions and adaptive feature fusion, thereby greatly improving the neural network's feature extraction ability. The algorithm uses a Sigmoid layer to map each pixel's feature vector to a probability distribution between 0 and 1, and anomalies are detected through probability threshold binarization. Experimental results show that our algorithm's AUROC index reached 90.7% on a carotid artery dataset, improving by 2.1% compared to the FPI method. This research is expected to provide robust support for the early prevention and treatment of cardiovascular diseases.

The Grip Strength Loss Rate and the Subsequent Cognitive Decline Rate in Older Adults: The Moderating Role of Social Isolation.

Background and Objectives: Accumulating evidence suggests that low grip strength (GS) is associated with a faster cognitive decline, but most previous studies have measured GS at a single time point, ignoring changes in GS. We aimed to explore the association of the GS loss rate with the sequent cognitive decline, as well as the moderating role of social isolation in older adults. Research Design and Methods: Data were from the English Longitudinal Study of Ageing. Absolute and relative GS loss rates were calculated as the annual losses from Wave 2 (2004-05) to Wave 4 (2008-09). Participants were divided into 3 groups according to the tertiles of GS loss rates. Linear mixed models were used to assess the association of the GS loss rate during Waves 2-4 with the cognitive decline rate during Waves 4-9 (Wave 9, 2018-19). Results: Of the 4 356 participants included in analyses, 1 938 (44.5%) were men, with a mean age of 68.4 (SD: 8.4) years. Compared with Tertile 1 of the absolute GS loss rate, Tertile 2 (ß = -0.009 [95% CI: -0.018 to -0.001] SD/year) and Tertile 3 (ß = -0.018 [95% CI: -0.027 to -0.010] SD/year) were associated with a faster cognitive decline rate. The results of relative GS were similar to those of absolute GS. Social isolation was a significant modifier in the associations of the absolute GS loss rate with decline rates in global cognition and episodic memory, but not in temporal orientation. We did not observe that social isolation moderated the association of the relative GS loss rate with the cognitive decline rate. Discussion and Implications: Both absolute and relative GS loss rates were positively associated with the cognitive decline rate in older adults. Low social isolation scores attenuated the association of the absolute GS loss rate with the cognitive decline rate.

Hydroxysafflor yellow A exerts anti-fibrotic and anti-angiogenic effects through miR-29a-3p/PDGFRB axis in liver fibrosis.

BACKGROUND: Liver fibrosis is a prevalent pathological process in chronic liver diseases characterized by excessive extracellular matrix (ECM) deposition and abnormal angiogenesis. Notably, hepatic stellate cells (HSCs) are the primary source of ECM. Activated HSCs not only secrete numerous pro-fibrotic cytokines but also are endowed with a pro-angiogenic phenotype to promote pathological angiogenesis. Therefore, targeted modulation of HSCs has emerged as a pivotal strategy for addressing liver fibrosis. Hydroxysafflor yellow A (HSYA) is a homology of medicine and food colourant with good pharmacological activity. However, the precise mechanisms of HSYA against liver fibrosis remain unclear. PURPOSE: The objective of this study was to elucidate the impact of HSYA on liver fibrosis and pathological angiogenesis, as well as the underlying mechanisms in vitro and in vivo studies. METHODS: The efficacy and mechanisms of HSYA on TGF-ß1-induced HSCs and VEGFA-induced endothelial cells were investigated by MTT assay, EdU cell proliferation assay, cell scratch assay, Elisa assay, immunofluorescence assay, molecular docking, cell transfection assay, western blot analysis and RT-qPCR analysis. In CCl4-induced liver fibrosis mice model, H&E, Masson, and Sirius red staining were used to observe histopathology. Serum transaminase activity and liver biochemical indexes were tested by biochemical kit. Immunohistochemical, fluorescence in situ hybridization (FISH), western blot analysis and RT-qPCR analysis were implemented to determine the mechanism of HSYA in vivo. RESULTS: Herein, our findings confirmed that HSYA inhibited the proliferation, migration and activation of HSCs, as evidenced by a reduction in cell viability, relative migration rate, EdU staining intensity, and pro-fibrotic mRNAs and proteins expression in vitro. Mechanistically, HSYA played an anti-fibrotic and anti-angiogenic role by partially silencing PDGFRB in activated HSCs, thereby disrupting PDGFRB/MEK/ERK signal transduction and inhibiting the expression of HIF-1α, VEGFA and VEGFR2 proteins. Importantly, PDGFRB was a target gene of miR-29a-3p. Treatment with HSYA reversed the down-regulation of miR-29a-3p and antagonized PDGFRB signaling pathway in TGF-ß1-induced HSCs transfected with miR-29a-3p inhibitor. Consistent with our in vitro study, HSYA exhibited a good hepatoprotective effect in CCl4-induced liver fibrosis mice by reducing serum ALT and AST levels, decreasing the contents of four fibrosis indicators (HA, PIIIP, ColIV and LN) and hydroxyproline, and inhibiting the TGF-ß1/TGFBR signaling pathway. In terms of mechanisms, HSYA alleviated pathological angiogenesis in fibrotic liver by deactivating PDGFRB signaling pathway and impairing the positive expression of CD31. Subsequently, FISH results further corroborated HSYA affected the activation of HSCs and angiogenesis achieved by the concurrent upregulation of miR-29a-3p and downregulation of α-SMA and VEGFA. Additionally, treatment with HSYA also forged a link between HSCs and endothelial cells, as supported by inhibiting the aberrant proliferation of endothelial cells. CONCLUSION: Fundamentally, the current study has illustrated that HSYA ameliorates liver fibrosis by repressing HSCs-mediated pro-fibrotic and pro-angiogenic processes, which is contingent upon the regulatory effect of HSYA on the miR-29a-3p/PDGFRB axis. These findings provide compelling evidence bolstering the potential of HSYA as a therapeutic agent in liver fibrosis.

Palladium-Catalyzed O-Glycosylation through π-π Interactions.

A stereodivergent synthesis of ß- and α-O-glycosides using 3-O-quinaldoyl glucals was developed by palladium catalysis at 60 and 110 °C respectively. Various alcohols, monosaccharides, and amino acid were glycosylated to form ß- and α- products in good yields with high stereoselectivity. Mechanistic studies indicated no classic Pd-N (quinoline) coordination, but π-π stacking interactions promoted the anomeric stereodiversity. The practicality was demonstrated by glycosylating natural products/drugs and synthesizing a complex tetrasaccharide.

A comprehensive review of miR-21 in liver disease: Big impact of little things.

microRNAs (miRNAs), a class of non-coding RNA with 20-24 nucleotides, are defined as the powerful regulators for gene expression. miR-21 is a multifunctional miRNA enriched in the circulatory system and multiple organs, which not only serves as a non-invasive biomarker in disease diagnosis, but also participates in many cellular activities. In various chronic liver diseases, the increase of miR-21 affects glycolipid metabolism, viral infection, inflammatory and immune cell activation, hepatic stellate cells activation and tissue fibrosis, and autophagy. Moreover, miR-21 is also a liaison in the deterioration of chronic liver disease to hepatocellular carcinoma (HCC), and it impacts on cell proliferation, apoptosis, migration, invasion, angiogenesis, immune escape, and epithelial-mesenchymal transformation by regulating target genes expression in different signaling pathways. In current research on miRNA therapy, some natural products can exert the hepatoprotective effects depending on the inhibition of miR-21 expression. In addition, miR-21-based therapeutic also play a role in regulating intracellular miR-21 levels and enhancing the efficacy of chemotherapy drugs. Herein, we systemically summarized the recent progress of miR-21 on biosynthesis, biomarker function, molecular mechanism and miRNA therapy in chronic liver disease and HCC, and looked forward to outputting some information to enable it from bench to bedside.

Trends in Cardiovascular Health Among US Adolescents Aged 12-19 Years Using the New "Life's Essential 8" Metrics, 2007-2018.

PURPOSE: The American Heart Association recently issued a substantial update to the definition and scoring of cardiovascular health (CVH), now called "Life's Essential 8" (LE8). We aimed to assess the trends in overall and individual LE8 CVH metrics among adolescents in the United States. METHODS: A total of 6,999 United States adolescents aged 12-19 years from six cycles of the National Health and Nutrition Examination Survey from 2007-2008 to 2017-2018 were included in this study. The individual LE8 metrics included diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood lipids, blood glucose, and blood pressure (BP). A higher CVH score indicates better CVH health. RESULTS: The mean score of overall CVH significantly increased from 72.8 (95% confidence interval: 71.2-74.3) in 2007-2008 to 77.3 (76.1-78.5) in 2017-2018 in US adolescents (p-trend < .001). From 2007-2008 to 2017-2018, the mean scores increased from 75.5 (72.0-79.1) to 90.0 (88.0-91.9) for nicotine exposure, from 65.2 (61.6-68.8) to 73.3 (69.9-76.8) for sleep health, from 69.9 (67.1-72.8) to 73.0 (69.1-76.9) for blood lipids, and from 94.4 (93.0-95.9) to 96.2 (95.2-97.3) for BP (all p-trend < .05). However, the mean scores for diet, physical activity, and blood glucose did not significantly change (all p-trend > .05), whereas the mean score decreased from 81.4 (78.9-84.0) to 78.6 (76.4-80.8) for BMI (p-trend = .023). DISCUSSION: In United States adolescents, the overall CVH and four components (nicotine exposure, sleep health, blood lipids, and BP) significantly improved over time, diet, physical activity, and blood glucose remained unchanged, whereas BMI worsened.

Coalescence-Induced Self-Propelled Particle Transport with Asymmetry Arrangement.

We experimentally investigated the coalescence-induced droplet-particle jumping phenomenon on a submillimeter scale in symmetric and asymmetric particle arrangements with poly(methyl methacrylate) (PMMA) particles and stainless steel (SS) particles. Coalescence-induced droplet-particle jumping exhibited excellent capability and interesting behavior for both droplet jumping enhancement and particle transport. The particle increased the normalized droplet jumping velocity from 0.250 for no particle case to 0.315 and 0.320 for symmetric and asymmetric particle cases. Compared with similar-sized macrostructures fixed between droplets, better jumping performance with particles may be attributed to avoiding the work of adhesion during droplet-macrostructure separation. Besides, all particles always sunk at the bottom in the symmetric cases, while the stick mode for PMMA particles and sink, wander, and jet modes for SS particles appeared in the asymmetry cases. We revealed that the asymmetric particle arrangement induces an unbalanced surface tension force, which may provide a driving force in the vertical direction. Additionally, a small enough resistive force caused by hydrophobic particles is another necessary condition for the wonder and jet mode. Finally, we realized a significantly superior particle transport in the asymmetric SS particle cases with maximum particle height reaching ∼2.1 mm, ∼12.4 times the particle radius, the most significant vertical self-propelled transport distance currently.

Associations of rumination with suicidal ideation and suicide attempts amongst individuals with major depressive disorder: A 12-month longitudinal study in China.

BACKGROUND: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD). METHODS: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations. RESULTS: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01-1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96-1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02-1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82-1.01). CONCLUSION: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small.

Associations between somatic symptoms and remission of major depressive disorder: A longitudinal study in China.

Previous studies have documented negative associations between somatic symptoms and remission of major depressive disorder (MDD). However, the correlations of specific somatic symptoms with remission remain uncertain. We aimed to explore the associations between specific somatic symptoms and remission focusing on sex differences among patients with MDD. We used data from patients with MDD in the Depression Cohort in China. At baseline, total somatic symptoms were evaluated using the 28-item Somatic Symptoms Inventory and were categorized into pain, autonomic, energy, and central nervous system (CNS) symptoms. To measure remission of MDD, depressive symptoms were evaluated using the Patient Health Questionnaire-9 after 3 months of treatment. We ultimately included 634 patients. Compared with quartile 1 of total somatic symptom scores, the full-adjusted ORs (95% CIs) for remission from quartile 2 to quartile 4 were 0.52 (0.30, 0.90), 0.44 (0.23, 0.83), and 0.36 (0.17, 0.75), respectively (P-value for trend = 0.005). The restricted cubic spline showed no non-linear associations between total somatic symptoms with remission (P-value for non-linear = 0.238). Pain, autonomic, and CNS symptoms showed similar results. Sex-stratified analysis showed that total somatic symptoms, pain symptoms, and autonomic symptoms were negatively correlated with remission in females, whereas CNS symptoms were negatively associated with remission in males. Our findings indicate that specific somatic symptoms exert differential effects on remission of MDD. Therapeutic interventions that target pain, autonomic, and CNS symptoms may increase the probability of remission. Furthermore, interventions for somatic symptoms should be tailored by sex, and females deserve more attention.

Phillygenin Inhibits TGF-ß1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/ß-catenin Pathways.

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C21H24O6) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-ß1 (TGF-ß1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-ß1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-ß1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/ß-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.

Moving beyond traditional therapies: the role of nanomedicines in lung cancer.

Amidst a global rise in lung cancer occurrences, conventional therapies continue to pose substantial side effects and possess notable toxicities while lacking specificity. Counteracting this, the incorporation of nanomedicines can notably enhance drug delivery at tumor sites, extend a drug's half-life and mitigate inadvertent toxic and adverse impacts on healthy tissues, substantially influencing lung cancer's early detection and targeted therapy. Numerous studies signal that while the nano-characteristics of lung cancer nanomedicines play a pivotal role, further interplay with immune, photothermal, and genetic factors exist. This review posits that the progression towards multimodal combination therapies could potentially establish an efficacious platform for multimodal targeted lung cancer treatments. Current nanomedicines split into active and passive targeting. Active therapies focus on a single target, often with unsatisfactory results. Yet, developing combination systems targeting multiple sites could chart new paths in lung cancer therapy. Conversely, low drug delivery rates limit passive therapies. Utilizing the EPR effect to bind specific ligands on nanoparticles to tumor cell receptors might create a new regime combining active-passive targeting, potentially elevating the nanomedicines' concentration at target sites. This review collates recent advancements through the lens of nanomedicine's attributes for lung cancer therapeutics, the novel carrier classifications, targeted therapeutic modalities and their mechanisms, proposing that the emergence of multi-target nanocomposite therapeutics, combined active-passive targeting therapies and multimodal combined treatments will pioneer novel approaches and tools for future lung cancer clinical therapies.

Stigma and its associations with medication adherence in major depressive disorder.

This study sought to evaluate internalized stigma (IS) and perceived stigma (PS), in persons (n = 522) living with major depressive disorder (MDD), with a view to analyzing the association of IS and PS with medication adherence in a cohort of participants with MDD in China. Perceived stigma is the awareness of societal negative views and attitudes towards depression, and IS is applying others' attitudes to oneself, both measured by the Depression Stigma Scale (DSS). Medication adherence was assessed using the Medication Adherence Rating Scale (MARS). We observed that 76.0 % of participants reported IS and 84.5 % reported PS. Factors associated with increased IS included older age, marital status, disease history, and a higher baseline Patient Health Questionnaire-9 (PHQ-9). Higher education level, family income, and scores on the Connor-Davidson Resilience Scale (CD-RISC) were associated with lower levels of IS. Higher education levels, Childhood Trauma Questionnaire (CTQ) scores, and living with others were also associated with higher PS, while engagement in exercise and higher number of prior episodes were associated with lower PS. IS had a negative association with medication adherence, whereas PS did not significantly associate with adherence. In conclusion, a testable hypothesis is derived from our data that strategies targeting IS amongst persons with MDD may improve overall rates of adherence to antidepressant treatment, a necessary prelude to improving recovery.

Exploring the effect and mechanism of cucurbitacin B on cholestatic liver injury based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. AIM OF THE STUDY: The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. METHODS: First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. RESULTS: A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. CONCLUSION: By combining network pharmacology with in vivo and in vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI.

Mediation and interaction of problematic internet use in the relationship between sexual minority status and depressive symptoms: Gender-based analysis.

BACKGROUND: Previous studies have demonstrated that sexual minorities are at a higher risk of experiencing depressive symptoms. However, few prior investigations have examined the potential mechanisms involved. This study aimed to employ the four-way decomposition approach that integrates the analysis of mediation and interaction to investigate the potential role of problematic internet use between sexual orientation and depressive symptoms. METHODS: The participants were recruited through a multi-stage, stratified cluster, and random sampling method in China. Students who identified as "gay or lesbian" and "bisexual" were defined as "sexual minorities". The Young's Internet Addiction Test (IAT) was used to evaluate problematic internet use. The Center for Epidemiologic Studies Depression Scale (CESD-20) was used to evaluate depressive symptoms. RESULTS: A total of 59,859 adolescents were included in this study, with 30,180 (53.25 %) boys and 29,679 (46.75 %) girls. Of these, 7263 (12.13 %) were identified as sexual minorities. Gender differences were observed in the association between sexual orientation, problematic internet use, and depressive symptoms. The mediating effect of problematic internet use was 28.80 % for boys and 36.84 % for girls, respectively. The interaction effect between problematic internet use and sexual minority status on depressive symptoms was 21.19 % and 9.65 % for boys and girls, respectively. LIMITATIONS: The current study was limited by the cross-sectional design. CONCLUSION: These findings suggest that prevention and intervention programs aimed at improving mental health outcomes among sexual minority adolescents should prioritize considering the impact of problematic internet use and potential gender differences.

Trajectories of spherical equivalent refraction from grades 1 to 4 in Chinese children.

BACKGROUND: The development trajectories of children's SER remain unknown. This study aimed to characterize spherical equivalent refraction (SER) trajectories during grades 1-4 in Chinese children. METHODS: This prospective cohort study included 1226 first-grade non-myopic children from 12 public primary schools, randomly selected in two districts in Guangzhou, China. From November 2018 to March 2022, four-wave ocular examinations and questionnaire surveys have been completed. The group-based trajectory modeling was used to explore SER trajectories in grades 1-4. RESULTS: All five trajectories showed an upward trend and rose faster after grade 2. Children in the sharp-developing (n = 44), high-developing (n = 136), and rapid-developing (n = 237) myopia groups developed myopia before grades 2, 3, and 4, respectively. Their SER development speed remained at a relatively high level after myopia, almost consistent with that before myopia. Children in the moderate-developing (n = 418) and low-developing (n = 391) non-myopia groups did not develop myopia before grade 4. Some characteristics in grade 1 were independently associated with SER trajectories, including sex, axial length, number of parents with myopia, residence, academic achievement, and the duration of outdoor activity. Based on the baseline characteristics, we established the model predicting the probability of children belonging to each group. CONCLUSIONS: Myopia interventions are best started in grade 1 or preschool age. If interventions are not taken in time, the latest intervention window might be in grades 1, 2, and 3 for children with a high probability of belonging to the sharp-developing, high-developing, and rapid-developing myopia groups, respectively. The above probabilities might be predicted using the model we established. Moreover, the interventions for myopic children shouldn't be ignored.

Pet Ownership, Living Alone, and Cognitive Decline Among Adults 50 Years and Older.

Importance: It remains unclear whether pet ownership is associated with cognitive decline and to what extent pet ownership mitigates the association between living alone and cognitive decline. Objective: To explore the association of pet ownership with cognitive decline, the interaction between pet ownership and living alone, and the extent to which pet ownership mitigates the association between living alone and cognitive decline in older adults. Design, Setting, and Participants: This cohort study used data from waves 5 (June 2010 to July 2011) to 9 (from June 2018 to July 2019) in the English Longitudinal Study of Ageing. Participants included adults 50 years and older. Data were analyzed from April 1 to June 30, 2023. Exposures: Pet ownership and living alone in wave 5. Main Outcomes and Measures: In waves 5 to 9, verbal memory and verbal fluency were assessed, and composite verbal cognition was further calculated. Results: Of the 7945 participants included, the mean (SD) age was 66.3 (8.8) years, and 4446 (56.0%) were women. Pet ownership was associated with slower rates of decline in composite verbal cognition (ß = 0.008 [95% CI, 0.002-0.014] SD/y), verbal memory (ß = 0.006 [95% CI, 0.001-0.012] SD/y), and verbal fluency (ß = 0.007 [95% CI, 0.001-0.013] SD/y). Three-way interaction tests showed that living alone was a significant modifier in all 3 associations. Stratified analyses showed that pet ownership was associated with slower rates of decline in composite verbal cognition (ß = 0.023 [95% CI, 0.011-0.035] SD/y), verbal memory (ß = 0.021 [95% CI, 0.008-0.034] SD/y), and verbal fluency (ß = 0.018 [95% CI, 0.005-0.030] SD/y) among individuals living alone, but not among those living with others. Joint association analyses showed no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others. Conclusions and Relevance: In this cohort study, pet ownership was associated with slower rates of decline in verbal memory and verbal fluency among older adults living alone, but not among those living with others, and pet ownership offset the associations between living alone and declining rates in verbal memory and verbal fluency. Further studies are needed to assess whether pet ownership slows the rate of cognitive decline in older adults living alone.

Associations of physical activity and screen time with adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common type of idiopathic scoliosis, affecting approximately 0.61%-6.15% adolescents worldwide. To date, the results on the relationship between moderate-to-vigorous physical activity (MVPA) and AIS were inconsistent, and the association between screen time (ST) and AIS remained unclear. This study aimed to describe MVPA and ST among adolescents, and to explore the independent and joint associations between PA, ST, and AIS. METHODS: A frequency-matched case-control study based on the 2021 Chinese School-based Scoliosis Screening Program in Shenzhen city, south China, was conducted. The research involved 494 AIS patients (aged 9-17 years) and 994 sex- and age-matched healthy controls. MVPA and ST were measured using a self-administered questionnaire. Logistic regression models estimated associations between PA, ST, and AIS. RESULTS: Compared to subjects meeting the recommended 60-min daily of MVPA, adolescents reporting daily MVPA time less than 60 min had 1.76 times higher odds of experiencing AIS (95% CI: 1.32-2.35) and adolescents reporting daily MVPA in inactive status had 2.14 times higher odds of experiencing AIS (95% CI: 1.51-3.03). Moreover, participants reporting ST for 2 hours or more had 3.40 times higher odds of AIS compared with those reporting ST less than 2 hours (95% CI: 2.35-4.93). When compared with the adolescents reporting both ST and MVPA meeting the guidelines recommended times (ST < 2 h and MVPA ≥ 60 min/day), those reporting both ST ≥ 2 h and MVPA in inactive status are 8.84 times more likely to develop AIS (95% CI: 3.99-19.61). CONCLUSIONS: This study reported that the insufficient MVPA, especially MVPA in inactive status, and excessive ST were risk factors for AIS. Additionally, the joint effects of insufficient MVPA and excessive ST probably increase the risk of AIS.