Tea's Characteristic Components Eliminate Acrylamide in the Maillard Model System.

This study investigated the effects of various characteristic components of tea-theaflavins, catechins, thearubigins, theasinensins, theanine, catechin (C), catechin gallate (CG), epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), epigallocatechin gallate (EGCG), gallocatechin (GC), and gallocatechin gallate (GCG)-on acrylamide formation. The results revealed that most of tea's characteristic components could significantly eliminate acrylamide, ranked from highest to lowest as follows: GC (55.73%) > EC (46.31%) > theaflavins (44.91%) > CG (40.73%) > thearubigins (37.36%) > ECG (37.03%) > EGCG (27.37%) > theabrownine (22.54%) > GCG (16.21%) > catechins (10.14%) > C (7.48%). Synergistic elimination effects were observed with thearubigins + EC + GC + CG, thearubigins + EC + CG, thearubigins + EC + GC, theaflavins + GC + CG, and thearubigins + theaflavins, with the reduction rates being 73.99%, 72.67%, 67.62%, 71.03%, and 65.74%, respectively. Tea's components reduced the numbers of persistent free radicals to prevent acrylamide formation in the model system. The results provide a theoretical basis for the development of low-acrylamide foods and the application of tea resources in the food industry.

A flexible strategy to fabricate trumpet-shaped porous PDMS membranes for organ-on-chip application.

Porous polydimethylsiloxane (PDMS) membrane is a crucial element in organs-on-chips fabrication, supplying a unique substrate that can be used for the generation of tissue-tissue interfaces, separate co-culture, biomimetic stretch application, etc. However, the existing methods of through-hole PDMS membrane production are largely limited by labor-consuming processes and/or expensive equipment. Here, we propose an accessible and low-cost strategy to fabricate through-hole PDMS membranes with good controllability, which is performed via combining wet-etching and spin-coating processes. The porous membrane is obtained by spin-coating OS-20 diluted PDMS on an etched glass template with a columnar array structure. The pore size and thickness of the PDMS membrane can be adjusted flexibly via optimizing the template structure and spinning speed. In particular, compared to the traditional vertical through-hole structure of porous membranes, the membranes prepared by this method feature a trumpet-shaped structure, which allows for the generation of some unique bionic structures on organs-on-chips. When the trumpet-shape faces upward, the endothelium spreads at the bottom of the porous membrane, and intestinal cells form a villous structure, achieving the same effect as traditional methods. Conversely, when the trumpet-shape faces downward, intestinal cells spontaneously form a crypt-like structure, which is challenging to achieve with other methods. The proposed approach is simple, flexible with good reproducibility, and low-cost, which provides a new way to facilitate the building of multifunctional organ-on-chip systems and accelerate their translational applications.

Causal relationships of grey matter structures in multiple sclerosis and neuromyelitis optica spectrum disorder: insights from Mendelian randomization.

Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus (ß = 0.018, P = 2.383 × 10-4) and negatively associated with the volumes of the bilateral caudate (left: ß = -0.020, P = 7.203 × 10-5; right: ß = -0.021, P = 3.274 × 10-5) and putamen nuclei (left: ß = -0.030, P = 2.175 × 10-8; right: ß = -0.024, P = 1.047 × 10-5). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus (ß = 0.023, P = 1.025 × 10-4). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Shared Genetic Architecture Among Gastrointestinal Diseases, Schizophrenia, and Brain Subcortical Volumes.

BACKGROUND AND HYPOTHESIS: The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. STUDY DESIGN: Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. STUDY RESULTS: The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. CONCLUSIONS: These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases.

Functional magnetic resonance imaging alternations in suicide attempts individuals and their association with gene expression.

BACKGROUND: Functional Magnetic Resonance Imaging (fMRI) has shown brain activity alterations in individuals with a history of attempted suicide (SA) who are diagnosed with depression disorder (DD) or bipolar disorder (BD). However, patterns of spontaneous brain activity and their genetic correlations need further investigation. METHODS: A voxel-based meta-analysis of 19 studies including 26 datasets, involving 742 patients with a history of SA and 978 controls (both nonsuicidal patients and healthy controls) was conducted. We examined fMRI changes in SA patients and analyzed the association between these changes and gene expression profiles using data from the Allen Human Brain Atlas by partial least squares regression analysis. RESULTS: SA patients demonstrated increased spontaneous brain activity in several brain regions including the bilateral inferior temporal gyrus, hippocampus, fusiform gyrus, and right insula, and decreased activity in areas like the bilateral paracentral lobule and inferior frontal gyrus. Additionally, 5,077 genes were identified, exhibiting expression patterns associated with SA-related fMRI alterations. Functional enrichment analyses demonstrated that these SA-related genes were enriched for biological functions including glutamatergic synapse and mitochondrial structure. Concurrently, specific expression analyses showed that these genes were specifically expressed in the brain tissue, in neurons cells, and during early developmental periods. CONCLUSION: Our findings suggest a neurobiological basis for fMRI abnormalities in SA patients with DD or BD, potentially guiding future genetic and therapeutic research.

Prioritizing drug targets in systemic lupus erythematosus from a genetic perspective: a druggable genome-wide Mendelian randomization study.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with an unsatisfactory state of treatment. We aim to explore novel targets for SLE from a genetic standpoint. METHODS: Cis-expression quantitative trait loci (eQTLs) for whole blood from 31,684 samples provided by the eQTLGen Consortium as well as two large SLE cohorts were utilized for screening and validating genes causally associated with SLE. Colocalization analysis was employed to further investigate whether changes in the expression of risk genes, as indicated by GWAS signals, influence the occurrence and development of SLE. Targets identified for drug development were evaluated for potential side effects using a phenome-wide association study (PheWAS). Based on the multiple databases, we explored the interactions between drugs and genes for drug prediction and the assessment of current medications. RESULTS: The analysis comprised 5427 druggable genes in total. The two-sample Mendelian randomization (MR) in the discovery phase identified 20 genes causally associated with SLE and validated 8 genes in the replication phase. Colocalization analysis ultimately identified five genes (BLK, HIST1H3H, HSPA1A, IL12A, NEU1) with PPH4 > 0.8. PheWAS further indicated that drugs acting on BLK and IL12A are less likely to have potential side effects, while HSPA1A and NEU1 were associated with other traits. Four genes (BLK, HSPA1A, IL12A, NEU1) have been targeted for drug development in autoimmune diseases and other conditions. CONCLUSIONS: .This study identified five genes as therapeutic targets for SLE. Repurposing and developing drugs targeting these genes is anticipated to improve the existing treatment state for SLE. Key Points • We identified five gene targets of priority for the treatment of SLE, with BLK and IL12A indicating fewer side effects. • Among the existing drugs that target these candidate genes, Ustekinumab, Ebdarokimab, and Briakinumab (targeting the IL12 gene) and CD24FC (targeting HSPA1A) may potentially be repurposed for the treatment of SLE.

Exploring the correlation between childhood trauma experiences, inflammation, and brain activity in first-episode, drug-naive major depressive disorder.

BACKGROUND: Childhood trauma experiences and inflammation are pivotal factors in the onset and perpetuation of major depressive disorder (MDD). However, research on brain mechanisms linking childhood trauma experiences and inflammation to depression remains insufficient and inconclusive. METHODS: Resting-state fMRI scans were performed on fifty-six first-episode, drug-naive MDD patients and sixty healthy controls (HCs). A whole-brain functional network was constructed by thresholding 246 brain regions, and connectivity and network properties were calculated. Plasma interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assays in MDD patients, and childhood trauma experiences were evaluated through the Childhood Trauma Questionnaire (CTQ). RESULTS: Negative correlations were observed between CTQ total (r = -0.28, p = 0.047), emotional neglect (r = -0.286, p = 0.042) scores, as well as plasma IL-6 levels (r = -0.294, p = 0.036), with mean decreased functional connectivity (FC) in MDD patients. Additionally, physical abuse exhibited a positive correlation with the nodal clustering coefficient of the left thalamus in patients (r = 0.306, p = 0.029). Exploratory analysis indicated negative correlations between CTQ total and emotional neglect scores and mean decreased FC in MDD patients with lower plasma IL-6 levels (n = 28), while these correlations were nonsignificant in MDD patients with higher plasma IL-6 levels (n = 28). CONCLUSIONS: This finding enhances our understanding of the correlation between childhood trauma experiences, inflammation, and brain activity in MDD, suggesting potential variations in their underlying pathophysiological mechanisms.

Voxel-based texture similarity networks reveal individual variability and correlate with biological ontologies.

The human brain is organized as a complex, hierarchical network. However, the structural covariance patterns among brain regions and the underlying biological substrates of such covariance networks remain to be clarified. The present study proposed a novel individualized structural covariance network termed voxel-based texture similarity networks (vTSNs) based on 76 refined voxel-based textural features derived from structural magnetic resonance images. Validated in three independent longitudinal healthy cohorts (40, 23, and 60 healthy participants, respectively) with two common brain atlases, we found that the vTSN could robustly resolve inter-subject variability with high test-retest reliability. In contrast to the regional-based texture similarity networks (rTSNs) that calculate radiomic features based on region-of-interest information, vTSNs had higher inter- and intra-subject variability ratios and test-retest reliability in connectivity strength and network topological properties. Moreover, the Spearman correlation indicated a stronger association of the gene expression similarity network (GESN) with vTSNs than with rTSNs (vTSN: r = 0.600, rTSN: r = 0.433, z = 39.784, P < 0.001). Hierarchical clustering identified 3 vTSN subnets with differential association patterns with 13 coexpression modules, 16 neurotransmitters, 7 electrophysiology, 4 metabolism, and 2 large-scale structural and 4 functional organization maps. Moreover, these subnets had unique biological hierarchical organization from the subcortex-limbic system to the ventral neocortex and then to the dorsal neocortex. Based on 424 unrelated, qualified healthy subjects from the Human Connectome Project, we found that vTSNs could sensitively represent sex differences, especially for connections in the subcortex-limbic system and between the subcortex-limbic system and the ventral neocortex. Moreover, a multivariate variance component model revealed that vTSNs could explain a significant proportion of inter-subject behavioral variance in cognition (80.0 %) and motor functions (63.4 %). Finally, using 494 healthy adults (aged 19-80 years old) from the Southwest University Adult Lifespan Dataset, the Spearman correlation identified a significant association between aging and vTSN strength, especially within the subcortex-limbic system and between the subcortex-limbic system and the dorsal neocortex. In summary, our proposed vTSN is robust in uncovering individual variability and neurobiological brain processes, which can serve as biologically plausible measures for linking biological processes and human behavior.

Treatment of landfill leachate by black soldier fly (Hermetia illucens L.) larvae and the changes of intestinal microbial community.

Black soldier fly larvae (BSFL) (Hermetia illucens) are commonly used to treat organic waste. This work aims to evaluate the transformation effect, heavy metal migration, and alterations in the gut microbiota of BSFL in addition to treating landfill leachate (LL) with BSFL. We found that BSFL may grow in various landfill leachate concentrations without obvious toxicity and growth inhibition. In addition, the results indicated a significant increase in the content of ammonia nitrogen and the activity of urease and ß-glucosidase (ß-GC) in LL, increased from 2570.17 mg/L to 5853.67 mg/L, 1859.17 mg/(g·d) to 517,177.98 mg/(g·d), 313.73 µg/(g·h) to 441.91 µg/(g·h) respectively. Conversely, the content of total nitrogen (TN) and total organic carbon (TOC) decreased in LL, decreasing by 31.24% and 29.45% respectively. Heavy metals are accumulated in the leachate by the BSFL to differing degrees, the descending sequence of accumulation is Cd > As > Cu > Cr. As dropped by 26.0%, Cd increased by 22.6%, Cu reduced by 5.23%, and Cr increased by 317.1% in the remaining matrix. The concentration of heavy metals satisfies the organic fertilizers' limit index (NY/T1978). The diversity of intestinal microorganisms in BSFL decreased, from 2819 OTUs to 2338 OTUs, with Providencia and Morganella emerging as the core flora. The gene abundance of nitrogen metabolism in the microbiota increased significantly. The TOC, ß-GC, and Copper (Cu) content in BSFL correlated significantly with the gut microbiota. In Summary, this study revealed the treatment effect of BSFL on LL, the migration of heavy metals, and changes in the intestinal microorganisms of BSFL. The content of heavy metals in BSFL was found to be much lower than the upper limit of feed protein raw materials, demonstrating that BSFL is a sustainable method to treat LL.

Arsenic redistribution associated with Fe(II)-induced jarosite transformation in the presence of polygalacturonic acid.

Jarosite exists widely in acid-sulfate soil and acid mine drainage polluted areas and acts as an important host mineral for As(V). As a metastable Fe(III)-oxyhydoxysulfate mineral, its dissolution and transformation have a significant impact on the biogeochemical cycle of As. Under reducing conditions, the trajectory and degree of abiotic Fe(II)-induced jarosite transformation may be greatly influenced by coexisting dissolved organic matter (DOM), and in turn influencing the fate of As. Here, we explored the impact of polygalacturonic acid (PGA) (0-200 mg·L-1) on As(V)-coprecipitated jarosite transformation in the presence of Fe(II) (1 mM) at pH 5.5, and investigated the repartitioning of As between aqueous and solid phase. The results demonstrated that in the system without both PGA and Fe(II), jarosite gradually dissolved, and lepidocrocite was the main transformation product by 30 d; in Fe(II)-only system, lepidocrocite appeared by 1 d and also was the mainly final product; in PGA-only systems, PGA retarded jarosite dissolution and transformation, jarosite might be directly converted into goethite; in Fe(II)-PGA systems, the presence of PGA retarded Fe(II)-induced jarosite dissolution and transformation but did not alter the pathway of mineral transformation, the final product mainly still was lepidocrocite. The retarding effect on jarosite dissolution enhanced with the increase of PGA content. The impact of PGA on Fe(II)-induced jarosite transformation mainly was related to the complexation of carboxyl groups of PGA with Fe(II). The dissolution and transformation of jarosite drove pre-incorporated As transferred into the phosphate-extractable phase, the presence of PGA retarded jarosite dissolution and maintained pre-incorporated As stable in jarosite. The released As promoted by PGA was retarded again and almost no As was released into the solution by the end of reactions in all systems. In systems with Fe(II), no As(III) was detected and As(V) was still the dominant redox species.

Targeting autophagy in diabetic cardiomyopathy: From molecular mechanisms to pharmacotherapy.

Diabetic cardiomyopathy (DCM) is a cardiac microvascular complication caused by metabolic disorders. It is characterized by myocardial remodeling and dysfunction. The pathogenesis of DCM is associated with abnormal cellular metabolism and organelle accumulation. Autophagy is thought to play a key role in the diabetic heart, and a growing body of research suggests that modulating autophagy may be a potential therapeutic strategy for DCM. Here, we have summarized the major signaling pathways involved in the regulation of autophagy in DCM, including Adenosine 5'-monophosphate-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), Forkhead box subfamily O proteins (FOXOs), Sirtuins (SIRTs), and PTEN-inducible kinase 1 (PINK1)/Parkin. Given the significant role of autophagy in DCM, we further identified natural products and chemical drugs as regulators of autophagy in the treatment of DCM. This review may help to better understand the autophagy mechanism of drugs for DCM and promote their clinical application.

Characteristics of Citrate-Esterified Starch and Enzymatically Debranched Starch and Their Effects on Diabetic Mice.

Chickpea has significant benefits as an adjuvant treatment for type 2 diabetes mellitus (T2DM). The properties of chickpea resistant starches (RSs) and their abilities to reduce T2DM symptoms and control intestinal flora were investigated. The RS content in citrate-esterified starch (CCS; 74.18%) was greater than that in pullulanase-modified starch (enzymatically debranched starch (EDS); 38.87%). Compared with those of native chickpea starch, there were noticeable changes in the granular structure and morphology of the two modified starches. The CCS showed surface cracking and aggregation. The EDS particles exhibited irregular layered structures. The expansion force of the modified starches decreased. The CCS and EDS could successfully lower blood glucose, regulate lipid metabolism, lower the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduce the expressions of interleukin-6 (IL-6) and interleuki n-10 (IL-10), and decrease diabetes-related liver damage. Moreover, the CCS and EDS altered the intestinal flora makeup in mice with T2DM. The abundance of Bacteroidota increased. Both types of chickpea RSs exhibited significant hypoglycaemic and hypolipidaemic effects, contributing to the reduction in inflammatory levels and the improvement in gut microbiota balance.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

The global burden and risk factors of cardiovascular diseases in adolescent and young adults, 1990-2019.

BACKGROUND: To provide details of the burden and the trend of the cardiovascular disease (CVD) and its risk factors in adolescent and young adults. METHODS: Age-standardized rates (ASRs) of incidence, mortality and Disability-Adjusted Life Years (DALYs) were used to describe the burden of CVD in adolescents and young adults. Estimated Annual Percentage Changes (EAPCs) of ASRs were used to describe the trend from 1990 to 2019. Risk factors were calculated by Population Attributable Fractions (PAFs). RESULTS: In 2019, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) of CVD were 129.85 per 100 000 (95% Confidence interval (CI): 102.60, 160.31), 15.12 per 100 000 (95% CI: 13.89, 16.48) and 990.64 per 100 000 (95% CI: 911.06, 1076.46). The highest ASRs were seen in low sociodemographic index (SDI) and low-middle SDI regions. The burden was heavier in male and individuals aged 35-39. From 1990 to 2019, 72 (35.29%) countries showed an increasing trend of ASIR and more than 80% countries showed a downward trend in ASMR and ASDR. Rheumatic heart disease had the highest ASIR and Ischemic Heart Disease was the highest in both ASMR and ASDR. The main attributable risk factor for death and DALYs were high systolic blood pressure, high body-mass index and high LDL cholesterol. CONCLUSIONS: The burden of CVD in adolescent and young adults is a significant global health challenge. It is crucial to take into account the disparities in SDI levels among countries, gender and age characteristics of the population, primary types of CVD, and the attributable risk factors when formulating and implementing prevention strategies.

Divergent redistribution behavior of divalent metal cations associated with Fe(II)-mediated jarosite phase transformation.

The Fe(II)/Fe(III) cycle is an important driving force for dissolution and transformation of jarosite. Divalent heavy metals usually coexist with jarosite; however, their effects on Fe(II)-induced jarosite transformation and different repartitioning behavior during mineral dissolution-recrystallization are still unclear. Here, we investigated Fe(II)-induced (1 mM Fe(II)) jarosite conversion in the presence of Cd(II), Mn(II), Co(II), Ni(II) and Pb(II) (denoted as Me(II), 1 mM), respectively, under anaerobic condition at neutral pH. The results showed that all co-existing Me(II) retarded Fe(II)-induced jarosite dissolution. In the Fe(II)-only system, jarosite first rapidly transformed to lepidocrocite (an intermediate product) and then slowly to goethite; lepidocrocite was the main product. In Fe(II)-Cd(II), -Mn(II), and -Pb(II) systems, coexisting Cd(II), Mn(II) and Pb(II) retarded the above process and lepidocrocite was still the dominant conversion product. In Fe(II)-Co(II) system, coexisting Co(II) promoted lepidocrocite transformation into goethite. In Fe(II)-Ni(II) system, jarosite appeared to be directly converted into goethite, although small amounts of lepidocrocite were detected in the final product. In all treatments, the appearance or accumulation of lepidocrocite may be also related to the re-adsorption of released sulfate. By the end of reaction, 6.0 %, 4.0 %, 76.0 % 11.3 % and 19.2 % of total Cd(II), Mn(II), Pb(II) Co(II) and Ni(II) were adsorbed on the surface of solid products. Up to 49.6 %, 44.3 %, and 21.6 % of Co(II), Ni(II), and Pb(II) incorporated into solid product, with the reaction indicating that the dynamic process of Fe(II) interaction with goethite may promote the continuous incorporation of Co(II), Ni(II), and Pb(II).

Diagnosing schizophrenia using deep learning: Novel interpretation approaches and multi-site validation.

Schizophrenia is a profound and enduring mental disorder that imposes significant negative impacts on individuals, their families, and society at large. The development of more accurate and objective diagnostic tools for schizophrenia can be expedited through the employment of deep learning (DL), that excels at deciphering complex hierarchical non-linear patterns. However, the limited interpretability of deep learning has eroded confidence in the model and restricted its clinical utility. At the same time, if the data source is only derived from a single center, the model's generalizability is difficult to test. To enhance the model's reliability and applicability, leave-one-center-out validation with a large and diverse sample from multiple centers is crucial. In this study, we utilized Nine different global centers to train and test the 3D Resnet model's generalizability, resulting in an 82% classification performance (area under the curve) on all datasets sourced from different countries, employing a leave-one-center-out-validation approach. Per our approximation of the feature significance of each region on the atlas, we identified marked differences in the thalamus, pallidum, and inferior frontal gyrus between individuals with schizophrenia and healthy controls, lending credence to prior research findings. At the same time, in order to translate the model's output into clinically applicable insights, the SHapley Additive exPlanations (SHAP) permutation explainer method with an anatomical atlas have been refined, thereby offering precise neuroanatomical and functional interpretations of different brain regions.

MiR-2110 induced by chemically synthesized cinobufagin functions as a tumor-metastatic suppressor via targeting FGFR1 to reduce PTEN ubiquitination degradation in nasopharyngeal carcinoma.

Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.