Do social economic status modify the association between air pollution and depressive or anxiety symptoms? A big sample cross-sectional study from the rural areas of Central China.

BACKGROUND: Fewer studies have examined the relationship between air pollution and depressive or anxiety symptoms in rural residents. Social economic status (SES), as an important indicator of the current state of socioeconomic development, we know little about how it modifies the relationship between air pollution and symptoms of depression or anxiety. METHODS: The patient health questionnaire (PHQ-2) and generalized anxiety scale (GAD-2) were used to learn about the prevalence of depressive and anxiety symptoms, the social economic status of the participants was categorized into two levels: lower and higher, and a binary logistic regression model was used to analyze the relationship between air pollution and residents' symptoms of depression or anxiety. RESULTS: A total of 10,670 adults were enrolled in this study, of which a total of 1292 participants suffered from depressive symptoms and 860 suffered from anxiety symptoms. Short-term exposure to PM2.5 and O3, singly or in combination, may be associated with the onset of depression symptoms, and there was a significant interaction between SES and exposure to PM2.5 or O3. Residents of areas with higher SES may have a lower risk of suffering from anxiety symptoms after O3 exposure compared to participants living in lower SES. LIMITATIONS: The study was a cross-sectional study, which may have lowered the quality level of the evidence. CONCLUSIONS: Short-term PM2.5 and O3 exposure may be associated with an increased prevalence risk of depressive symptoms. Higher levels of SES may reduce the adverse effects of air pollution on depressive or anxiety symptoms.

ZP1-Y262C mutation causes abnormal zona pellucida formation and female infertility in humans.

Defective oocyte maturation is a common cause of female infertility. The loss of the zona pellucida (ZP) represents a specific condition of impaired oocyte maturation. The extracellular matrix known as the ZP envelops mammalian oocytes and preimplantation embryos, exerting significant influence on oogenesis, fertilization, and embryo implantation. However, the genetic factors leading to the loss of the ZP in oocytes are not well understood. This study focused on patients who underwent oocyte retrieval surgery after ovarian stimulation and were found to have abnormal oocyte maturation without the presence of the ZP. Ultrasonography was performed during the surgical procedure to evaluate follicle development. Peripheral blood samples from the patient were subjected to exome sequencing. Here, a novel, previously unreported heterozygous mutation in the ZP1 gene was identified. Within the ZP1 gene, we discovered a novel heterozygous mutation (ZP1 NM_207341.4:c.785A>G (p.Y262C)), specifically located in the trefoil domain. Bioinformatics comparisons further revealed conservation of the ZP1-Y262C mutation across different species. Model predictions of amino acid mutations on protein structure and cell immunofluorescence/western blot experiments collectively confirmed the detrimental effects of the ZP1-Y262C mutation on the function and expression of the ZP1 protein. The ZP1-Y262C mutation represents the novel mutation in the trefoil domain of the ZP1 protein, which is associated with defective oocyte maturation in humans. Our report enhances comprehension regarding the involvement of ZP-associated genes in female infertility and offers enriched understanding for the genetic diagnosis of this condition.

SP1 promotes high glucose-induced lens epithelial cell viability, migration and epithelial-mesenchymal transition via regulating FGF7 and PI3K/AKT pathway.

BACKGROUND: Diabetic cataract (DC) is a common complication of diabetes and its etiology and progression are multi-factorial. In this study, the roles of specific protein 1 (SP1) and fibroblast growth factor 7 (FGF7) in DC development were explored. METHODS: DC cell model was established by treating SRA01/04 cells with high glucose (HG). MTT assay was conducted to evaluate cell viability. Transwell assay and wound-healing assay were performed to assess cell migration and invasion. Western blot assay and qRT-PCR assay were conducted to measure the expression of N-cadherin, E-cadherin, Collagen I, Fibronectin, SP1 and FGF7 expression. CHIP assay and dual-luciferase reporter assay were conducted to analyze the combination between FGF7 and SP1. RESULTS: FGF7 was upregulated in DC patients and HG-induced SRA01/04 cells. HG treatment promoted SRA01/04 cell viability, migration, invasion and epithelial-mesenchymal transition (EMT), while FGF7 knockdown abated the effects. Transcription factor SP1 activated the transcription level of FGF7 and SP1 overexpression aggravated HG-induced SRA01/04 cell injury. SP1 silencing repressed HG-induced SRA01/04 cell viability, migration, invasion and EMT, but these effects were ameliorated by upregulating FGF7. Additionally, SP1 knockdown inhibited the PI3K/AKT pathway by regulating the transcription level of FGF7. CONCLUSION: Transcription factor SP1 activated the transcription level of FGF7 and the PI3K/AKT pathway to regulate HG-induced SRA01/04 cell viability, migration, invasion and EMT.

Organofluorosilicon Modified Polyacrylate with the Unidirectional Migration Promotion of Disperse Dyes toward Polyester Fabric for Wash-Free Digital Inkjet Dyeing.

The printing and dyeing industry is currently accelerating toward a direction of high efficiency, energy conservation, environmental protection, and integration with digitalization. Disperse dye wash-free digital inkjet dyeing is a revolutionary breakthrough for cleaning and coloring polyester fabric. Based on the solubility parameters and the hot-melt dyeing characteristics of disperse dyes, soft, hard, and functional monomers of acrylate were used as the main body. Moreover, single-vinyl fluorinated polysiloxane and divinyl polysiloxane with low solubility parameters were used as modified monomers. A modified polyacrylate (PFSMA) adhesive containing silicon in the main chain and fluorine silicon in the side chain was prepared via miniemulsion polymerization. Using disperse digital inkjet dyeing of polyester fabric without washing can realize energy saving, emission reduction, and carbon reduction. Results showed that the optimum preparation conditions of PFSMA were as follows: DVFS molecular weight of 957 g/mol and DVFS content of 2.5 wt %. Compared with that of polyacrylate (PA), the glass-transition temperature of PFSMA film decreased, and its water resistance, toughness, and adhesion enhanced. When the PFSMA content in the wash-free disperse red ink was 8 wt %, the color yields of the front and back of the PFSMA jet-dyed polyester fabric were 18.86 and 13.28, respectively. Moreover, the color yield of the front of PFSMA jet-dyed polyester fabric was 39.9% higher than that of the pure liquid disperse red jet-dyed fabric. The simulated fixation rate was 87.9%, approximately 2.9 times higher than that of the PA wash-free jet-dyed fabric. The color fastness to dry rubbing reached level 4 and the color fastness to wet rubbing reached level 3-4, which was one level higher than that of pure liquid disperse red jet-dyed fabrics. The color fastness to soaping reached grade 5 and the color fastness to heat compression reached grades 4-5 and above. The fabric was a little firmer but smoother. The color properties, color fastness, and hand feeling of the PFSMA wash-free jet-dyed polyester fabric exceeded the levels of commercially available adhesives.

Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Inhomogeneous Strain Behaviors of the High Strength Pipeline Girth Weld under Longitudinal Loading.

Unforeseen failures in girth welds present a significant challenge for the pipeline industry. This study utilizes 3D Digital Image Correlation (DIC) assisted cross-weld tensile testing to analyze the strain response of high-strength thick-walled pipelines, providing essential insights into the strain migration and fracture mechanisms specific to girth welds. The results reveal that the welding process significantly affects the mechanical distribution within the girth weld. The tested Shielded Metal Arc Welded (SMAW-ed) pipe exhibited undermatched girth welds due to high heat input, while Gas Metal Arc Welding (GMAW) introduced a narrower weld and Heat-Affected Zone (HAZ) with higher hardness than the base metal, indicative of overmatched girth welds. Strain migration, resulting from a combination of metallurgical heterogeneous materials and geometrical reinforcement strengthening, progressed from the softer HAZ to the base metal in the SMAW-ed sample with reinforcement, ultimately leading to fracture in the base metal. In contrast, the GMAW-ed sample shows no strain migration. Reinforcement significantly improves the tensile strength of girth welds and effectively prevents failure in the weld region. Sufficient reinforcement is crucial for minimizing the risk of failure in critical areas such as the weld metal and HAZ, particularly in SMAW-ed pipes.

Identification of antidepressant constituents from Xiangfu-chuanxiong herbal medicine pair via spectrum-effect relationship analyses, molecular docking and corticosterone-induced PC12 cells.

Herbal medicine pair, composed of two single herbs, is a relatively fixed minimum prescription unit in the traditional Chinese medicine's formula and has special significance in clinic. The combination of Xiangfu (the rhizoma of Cyperus rotundus L, XF) and Chuanxiong (the rhizoma of Ligusticum chuanxiong Hort, CX) has been recoded as an herbal medicine pair XF-CX in the Yuan Dynasty (1347 CE) of China and widely used in traditional Chinese medicine formula, including Chaihu Shugan San, which has been clinically used for treatment of depression. However, the optimal ratio of the XF-CX herbal medicine pair and its antidepressant constituents are still unclear. Herein, the antidepressive-like effects of XF-CX herbal medicine pairs with different ratios of XF and CX (2:1, 1:1, 1:2) were evaluated using behavioral despair animal models in mice, and then its potential antidepressant constituents were recognized by spectrum-effect relationship analyses. Finally, the potential antidepressant constituents of the XF-CX herbal medicine pair were validated by molecular docking with glucocorticoid receptor and corticosterone (CORT)-induced PC12 cell injury model. The results indicated that different ratios of XF-CX pairs had antidepressive-like effects, and the XF-CX (2:1) exhibited a more significant effect. Thirty-two potential antidepressant constituents in the XF-CX herbal medicine pair were screened out from the spectrum-effect relationship combined molecular docking analyses. Among them, senkyunolide A, cyperotundone, Z-ligustilide, and levistilide A were validated to have protective effects against CORT-induced injury in PC12 cells. Our findings not only obtained the optimal ratio of XF-CX in the herbal medicine pair for the treatment of depression but also its potential antidepressant constituents, which will benefit in elucidating the mechanism of action and promoting the application of the herbal medicine pair in the clinic.

Ecofriendly dual-function cotton fabric with antibacterial and anti-adhesion properties based on modified natural materials.

Ecofriendly fabrics with antibacterial and anti-adhesion properties have been attracted an increasing attention in recent years. Herein, natural menthol modified polyacrylate (PMCA) antibacterial adhesion agent was synthesized by esterification and polymerisation while natural pterostilbene-grafted-chitosan (PGC) antibacterial agent was prepared through Mannich reaction. The antibacterial and anti-adhesion cotton fabric was fabricated through durable PMCA dip finishing and then layer-by-layer self-assembly of PGC. The results showed that the antibacterial adhesion rates and antibacterial rates of the dual-function cotton fabric against Staphylococcus aureus and Escherichia coli reached up to 99.9 %. Its antibacterial adhesion rates improved by 36.1 % and 40.1 % in comparison with those of cotton fabric treated by menthol alone. Meanwhile against S. aureus, the dual-function cotton fabrics improved the antibacterial rates by 56.7 % and 36.4 %, respectively, from those of chitosan- and pterostilbene-treated fabrics. Against E. coli, the improvements were 89.4 % and 24.8 %, respectively. After 20 household washings, the dual-function cotton fabric maintained >80 % of its original anti-adhesion and antibacterial rates against both species. The dual-function cotton fabric also possessed safe and excellent wearability.

Pitfalls in Developing Machine Learning Models for Predicting Cardiovascular Diseases: Challenge and Solutions.

In recent years, there has been explosive development in artificial intelligence (AI), which has been widely applied in the health care field. As a typical AI technology, machine learning models have emerged with great potential in predicting cardiovascular diseases by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of cardiovascular diseases. Although the field has become a research hot spot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, and reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of a comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, data set characteristics, model design, and statistical methods, as well as clinical implications, and provide possible solutions to these problems, such as gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, using specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, and enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.

TRAF6-mediated ubiquitination of AKT1 in the nucleus occurs in a ß-arrestin2-dependent manner upon insulin stimulation.

AKT, also known as protein kinase B (PKB), serves as a crucial regulator of numerous biological functions, including cell growth, metabolism, and tumorigenesis. Increasing evidence suggests that the kinase activity of AKT is regulated via ubiquitination by various E3 ligase enzymes in response to different stimuli. However, the molecular mechanisms underlying insulin-induced AKT ubiquitination are not yet fully understood. Here, we show that activation of the insulin receptor (IR) leads to enhanced ubiquitination of AKT1 at K8 and K14 residues, facilitated by the cytosolic E3 ubiquitin ligase enzyme, TRAF6. Further investigation using AKT1 mutants with modified nucleocytoplasmic shuttling properties reveals that TRAF6-mediated AKT1 ubiquitination occurs within the nucleus in a ß-Arr2-dependent manner. The nuclear entry of TRAF6 depends on importin ß1, while ß-Arr2 regulates this process by facilitating the interaction between TRAF6 and importin ß1. Additionally, the ubiquitination of AKT1 is essential for its translocation to the activated IR on the plasma membrane, where it plays a functional role in recruiting Glut4 and facilitating glucose uptake. This study uncovers the cellular components and processes involved in insulin-induced ubiquitination and activation of AKT1, providing insights and detailed strategies for manipulating AKT1.

Integrated multilevel investigation of photosynthesis revealed the algal response distinction to differentially charged nanoplastics.

Nanoplastics (NPs), especially those with different charges, as one of emerging contaminants pose a threat to aquatic ecosystems. Although differentially charged NPs could induce distinct biological effects, mechanistic understanding of the critical physiological processes of aquatic organisms from an integrated multilevel perspective on aquatic organisms is still uncertain. Herein, multi-effects of differentially charged nanosized polystyrene (nPS) including neutral nPS, nPS-COOH, and nPS-NH2 on the photosynthesis-related physiological processes of algae were explored at the population, individual, subcellular, protein, and transcriptional levels. Results demonstrated that both nPS and nPS-COOH exhibited hormesis to algal photosynthesis but nPS-NH2 triggered severe inhibition. As for nPS-NH2, the integrity of algal subcellular structure, chlorophyll biosynthesis, and expression of photosynthesis-related proteins and genes were interfered. Intracellular NPs' content in nPS treatment was 25.64 % higher than in nPS-COOH treatment, and the content of chloroplasts in PS and nPS-COOH treatment were 3.09 % and 4.56 % higher than control, respectively. Furthermore, at the molecular levels, more photosynthesis-related proteins and genes were regulated under nPS-COOH exposure than those exposed to nPS. Light-harvesting complex II could be recognized as an underlying explanation for different effects between nPS and nPS-COOH. This study first provides a novel approach to assess the ecological risks of NPs at an integrated multilevel.

Short-term exposure to air pollution on peripheral white blood cells and inflammation biomarkers: a cross-sectional study on rural residents.

Effects of short-term exposure to ambient air pollution on systemic immunological and inflammatory biomarkers in rural population have not been adequately characterized. From May to July 2021, 5816 participants in rural villages of northern Henan Province, China, participated in this cross-sectional study. Blood biomarkers of systemic inflammation were determined including peripheral white blood cells (WBC), eosinophils (EOS), basophils (BAS), monocytes (MON), lymphocytes (LYM), neutrophils (NEU), neutrophil-lymphocyte ratio (NLR), and serum high-sensitivity C-reactive protein (hs-CRP). The concentrations of ambient fine particulate matter (PM2.5), PM10, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were assessed up to 7 days prior to the blood draw. A generalized linear model was used to analyze the associations between air pollution exposure and the above-mentioned blood biomarkers. Significantly positive associations were revealed between PM2.5, CO and WBC; CO, O3 and LYM; PM2.5, PM10, SO2, CO and NEU; PM2.5, PM10, SO2, CO and NLR; PM2.5, PM10, SO2, NO2, CO, O3 and hs-CRP. Meanwhile, negative associations were found between SO2 and WBC; PM2.5, PM10, NO2, CO, or O3 and EOS; PM2.5, SO2, or CO and BAS; SO2, NO2 or O3 and MON; PM2.5, PM10, SO2, or NO2 and LYM. Moreover, men, individuals with normal body mass index (BMI), current smokers, and those older than 60 years were found vulnerable to air pollution effects. Taken together, short-term exposure to air pollution was associated with systemic inflammatory responses, providing insight into the potential mechanisms for air pollution-induced detrimental systemic effects in rural residents.

A prospective study on maternal periodontal diseases and neonatal adverse outcomes.

OBJECTIVE: It is evident that periodontitis is linked to various adverse pregnancy outcomes. This prospective study explored the potential link of maternal periodontal diseases to neonatal adverse outcomes. MATERIALS AND METHODS: A total of 193 generally healthy females in their third trimester (34-36 weeks) of pregnancy were enrolled. All subjects received full-mouth periodontal assessment, and the periodontal inflamed surface area (PISA) was calculated. Demographic data, lifestyles and anthropometric measurements of the neonates (e.g., body length and head circumference) were recorded. Herein, small-for-gestational age (SGA) referred to gender- and age-adjusted birth weight below the 10th percentile in line with the standard reference. Multivariable logistic regression analysis and restricted cubic spline were performed for examining the association of periodontal parameters with SGA.  Results: There were 8.3% (16/193) of neonates with SGA. Significantly positive correlation existed between the percentage of tooth sites with increased probing depth and an elevated risk of SGA (OR: 1.052; P < 0.05). Yet, the PISA was positively associated with the risk of SGA (OR: 1.002; P < 0.05) as well. No significant link occurred between maternal periodontal status and other neonatal outcome measures. CONCLUSION: Within the limitations of this study, the findings suggest that there could be a link between maternal periodontal diseases and neonatal adverse outcomes like SGA. Further investigation is required to clarify the current findings and potential implications for promoting maternal oral/periodontal health and newborn health.

Prevalence of Depression and Anxiety Disorders in Patients with Glaucoma: A Systematic Review and Meta-Analysis Based on Cross-Sectional Surveys.

OBJECTIVE: Glaucoma is a chronic disease with an insidious onset that often brings severe psychological burden to patients. Therefore, based on a systematic review and meta-analysis, we explore the prevalence and severity of depression and anxiety in glaucoma patients, and provide clinically valuable information for medical staff. METHODS: Computer searches were conducted for relevant studies in PubMed, Embase, ProQuest PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, The Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure, Wanfang Database, and China VIP Database. The search date range was from the establishment of the database to December 2023. Literature was screened and data were extracted. The Cochrane risk of bias assessment tool was used to evaluate the quality of the literature, and RevMan5.4 was used for meta-analysis. RESULTS: The total sample size of the 15 included studies was 24,334 cases. All included studies were of high quality. The results of the meta-analysis revealed that, compared with control patients without glaucoma, patients with glaucoma were more likely to experience depression and to have more severe depressive symptoms [RR (Relative Risk) = 5.92, 95% CI (Confidence Interva) (3.29, 10.66), p < 0.01]; they were also more likely to experience anxiety and to have more severe anxiety symptoms [RR = 2.99, 95% CI (1.93, 4.64), p < 0.01]. The results of the sensitivity analysis showed that the two studies by Cumurcu E. 2005 and Yochim 2012 were the sources of heterogeneity in the meta-analysis of depression; and the three studies by Mabuchi 2012, Otori 2017, and Yochim 2012 were the sources of heterogeneity in the meta-analysis of anxiety disorders. CONCLUSION: People with glaucoma are more likely to experience depression and anxiety than people without glaucoma. Medical staff should pay greater attention to patients' emotional problems and help patients improve their quality of life.

The relationship between perceived family support and subclinical positive symptoms of psychosis among Black college students.

AIM: Black individuals in the Unites States endure compounded and unique experiences of discrimination and structural racism that may not be as overtly evident in other countries. These distinctive forms of discrimination and racism can impact the mental health of Black individuals in the Unites States, in this case, their risk for psychosis. Adolescence and early adulthood are vulnerable periods in life where mental illness typically begins to manifest. Understanding the factors contributing to an increased likelihood of specific mental illnesses, such as psychosis, among youth in these vulnerable periods can inform intervention development. This is particularly important for those from minoritized backgrounds Unites States; this group is especially important to study given that Black American youth tend to experience higher psychosis rates and different symptom presentations than non-Black groups. METHODS: This study examined the associations between perceived family support, a critical environmental factor known to be associated with full-psychosis, and attenuated positive symptoms and distress levels in a sample of 155 Black students from a Historically Black College and University (HBCU). Participants completed the Prodromal Questionnaire-Brief that assessed psychosis risk and the Family Environment Scale that assessed three dimensions of family support (family cohesion, expressiveness, and conflict). RESULTS AND CONCLUSION: Positive symptom intensity (r = .30, p < .001) and distress (r = .34, p < .001) were significantly associated with higher family conflict for Black individuals in the Unites States. The findings inform novel intervention targets for psychoeducation and family therapy that have potential to reduce psychosis risk.

Genetic association of serum lipids and lipid-modifying targets with endometriosis: Trans-ethnic Mendelian-randomization and mediation analysis.

BACKGROUND: Prior observational research identified dyslipidemia as a risk factor for endometriosis (EMS) but the causal relationship remains unestablished due to inherent study limitations. METHODS: Genome-wide association study data for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) from European (EUR) and East Asian (EAS) ancestries were sourced from the Global Lipids Genetics Consortium. Multi-ancestry EMS data came from various datasets. Univariable Mendelian randomization (MR) examined causal links between serum lipids and EMS. Multivariable and mediation MR explored the influence of seven confounding factors and mediators. Drug-target MR investigates the association between lipid-lowering target genes identified in positive results and EMS. The primary method was inverse-variance weighted (IVW), with replication datasets and meta-analyses reinforcing causal associations. Sensitivity analyses included false discovery rate (FDR) correction, causal analysis using summary effect estimates (CAUSE), and colocalization analysis. RESULTS: IVW analysis in EUR ancestry showed a significant causal association between TG and increased EMS risk (OR = 1.112, 95% CI 1.033-1.198, P = 5.03×10-3, PFDR = 0.03), supported by replication and meta-analyses. CAUSE analysis confirmed unbiased results (P < 0.05). Multivariable and mediation MR revealed that systolic blood pressure (Mediation effect: 7.52%, P = 0.02) and total testosterone (Mediation effect: 10.79%, P = 0.01) partly mediated this relationship. No causal links were found between other lipid traits and EMS (P > 0.05 & PFDR > 0.05). In EAS ancestry, no causal relationships with EMS were detected (P > 0.05 & PFDR > 0.05). Drug-target MR indicated suggestive evidence for the influence of ANGPTL3 on EMS mediated through TG (OR = 0.798, 95% CI 0.670-0.951, P = 0.01, PFDR = 0.04, PP.H4 = 0.85%). CONCLUSIONS: This MR study in EUR ancestry indicated an increased EMS risk with higher serum TG levels.

In-depth characterization of cycloartane triterpenoids and discovery of species-specific markers from three Cimicifuga species guided by a strategy that integrates in-source fragment elimination, diagnostic ion recognition, and feature-based molecular networking.

Characterization studies of the plant metabolome are crucial for revealing plant physiology, developing functional foods, and controlling quality. Mass spectrometry-based metabolite profiling allows unprecedented qualitative coverage of complex biological extract composition. However, the electrospray ionization used in metabolite profiling generates multiple artifactual signals for a single analyte, which makes it challenging to filter out redundant signals and organize the signals corresponding to abundant constituents. This study proposed a strategy integrating in-source fragments elimination, diagnostic ions recognition, and feature-based molecular networking (ISFE-DIR-FBMN) to simultaneously characterize cycloartane triterpenoids (CTs) from three medicinal Cimicifuga species. The results showed that 63.1 % of the measured ions were redundant. A total of 184 CTs were annotated, with 27.1 % being reported for the first time. It presents a promising approach to assess the composition of natural extracts, thus facilitating new ingredient registrations or natural-extracts-based drug discovery campaigns. Besides, chemometrics analysis of the three Cimicifuga species identified 32 species-specific markers, highlighting significant differences among them. The valuable information can enhance the sustainable utilization and further development of Cimicifuga resources. The codes involved in ISFE-DIR-FBMN are freely available on GitHub (https://github.com/LHJ-Group/ISFE-DIR-FBMN.git).

The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis.

BACKGROUND: Toxic components frequently exhibit unique characteristics and activities, offering ample opportunities for the advancement of anti-cancer medications. As the main hepatotoxic component of Dioscorea bulbifera L. (DB), Diosbulbin B (DIOB) has been widely studied for its anti-tumor activity at nontoxic doses. However, the effectiveness and mechanism of DIOB against non-small cell lung cancer (NSCLC) remains unclear. PURPOSE: To evaluate the anti-NSCLC activity of DIOB and to elucidate the specific mechanism of action. METHOD: The effect of DIOB on NSCLCL in vitro was evaluated through CCK8, colony formation, and flow cytometry. The in vivo efficacy and safety of DIOB in treating NSCLC were assessed using various techniques, including HE staining, tunel staining, immunohistochemistry, and biochemical index detection. To understand the underlying mechanism, cell transfection, western blotting, molecular docking, cellular thermal shift assay (CESTA), and surface plasmon resonance (SPR) were employed for investigation. RESULTS: DIOB effectively hindered the progression of NSCLC both in vitro and in vivo settings at a no-observed-adverse-effect concentration (NOAEC) and a safe dosage. Specifically, DIOB induced significant G0/G1 phase arrest and apoptosis in A549, PC-9, and H1299 cells, while also notably inhibiting the growth of subcutaneous tumors in nude mice. Mechanistically, DIOB could directly interact with oncogene Yin Yang 1 (YY1) and inhibit its expression. The reduction in YY1 resulted in the triggering of the tumor suppressor P53, which induced cell cycle arrest and apoptosis in NSCLC cells by inhibiting the expression of Cyclin A2, B2, CDK1, CDK2, CDK4, BCL-2, and inducing the expression of BAX. In NSCLC cells, the induction of G0/G1 phase arrest and apoptosis by DIOB was effectively reversed when YY1 was overexpressed or P53 was knocked down. Importantly, we observed that DIOB exerted the same effect by directly influencing the expression of YY1-regulated c-Myc and BIM, particularly in the absence of P53. CONCLUSION: For the inaugural investigation, this research unveiled the anti-NSCLC impact of DIOB, alongside its fundamental mechanism. DIOB has demonstrated potential as a treatment agent for NSCLC due to its impressive efficacy in countering NSCLC.

Psoralen and Isopsoralen, Two Estrogen-Like Natural Products from Psoraleae Fructus, Induced Cholestasis via Activation of ERK1/2.

With the increasing use of oral contraceptives and estrogen replacement therapy, the incidence of estrogen-induced cholestasis (EC) has tended to rise. Psoralen (P) and isopsoralen (IP) are the major bioactive components in Psoraleae Fructus, and their estrogen-like activities have already been recognized. Recent studies have also reported that ERK1/2 plays a critical role in EC in mice. This study aimed to investigate whether P and IP induce EC and reveal specific mechanisms. It was found that P and IP increased the expression of esr1, cyp19a1b and the levels of E2 and VTG at 80 µM in zebrafish larvae. Exemestane (Exe), an aromatase antagonist, blocked estrogen-like activities of P and IP. At the same time, P and IP induced cholestatic hepatotoxicity in zebrafish larvae with increasing liver fluorescence areas and bile flow inhibition rates. Further mechanistic analysis revealed that P and IP significantly decreased the expression of bile acids (BAs) synthesis genes cyp7a1 and cyp8b1, BAs transport genes abcb11b and slc10a1, and BAs receptor genes nr1h4 and nr0b2a. In addition, P and IP caused EC by increasing the level of phosphorylation of ERK1/2. The ERK1/2 antagonists GDC0994 and Exe both showed significant rescue effects in terms of cholestatic liver injury. In conclusion, we comprehensively studied the specific mechanisms of P- and IP-induced EC and speculated that ERK1/2 may represent an important therapeutic target for EC induced by phytoestrogens.

Ultrasensitive upconverting nanoprobes for in situ imaging of drug-induced liver injury using miR-122 as the biomarker.

Drug-induced liver injury (DILI) is a frequent adverse drug reaction. The current clinical diagnostic methods are inadequate for accurate and early detection of DILI due to the lack of effective diagnostic biomarkers. Hepatocyte-specific miR-122 is released from injured hepatocytes promptly and its efflux is significantly correlated with the progression of DILI. Therefore, achieving precise in situ detection of miR-122 with high sensitivity is vital for early visualization of DILI. Herein, a new nanoprobe, consisting of miR-122 aptamer, upconversion nanoparticles (UCNPs) and Prussian blue nanoparticles (PBNPs) was introduced for the early and sensitive detection of DILI in situ. As the nanoprobes reached in the liver, miR-122 aptamer-based entropy-driven strand displacement (ESDR) signal amplification reaction was triggered and luminescence resonance energy transfer (LRET) between UCNPs and PBNPs was responded to achieve the high-fidelity detection of DILI. A negative correlation was observed between the intensity of upconversion luminescence (UCL) and the concentration of miR-122. UCL imaging conducted both in vivo and ex vivo indicated that a reduction in miR-122 concentration led to an increase in UCL intensity, revealing a precise state of DILI. The detection technique demonstrated a positive correlation between signal intensity and severity, offering a more straightforward and intuitive method of visualizing DILI.