Artemisia argyi extract exerts antioxidant properties and extends the lifespan of Drosophila melanogaster.

BACKGROUND: Chinese mugwort (Artemisia argyi) possesses extensive pharmacological activities associated with anti-tumour, antioxidative and anti-inflammatory effects. The present study aimed to investigate the antioxidant and anti-ageing effects of A. argyi extract (AAE) on the fruit fly (Drosophila melanogaster) ageing model by detecting antioxidant enzyme activities and the mRNA level of antioxidant genes. RESULTS: AAE could significantly lengthen the mean lifespan, 50% survival days, and maximum lifespan of D. melanogaster, especially when the amount of AAE added reached 6.68 mg mL-1, the mean lifespan of both female and male flies increased by 23.74% and 22.30%, respectively, indicating the effective life extension effect of AAE. At the same time, AAE could improve the climbing ability and tolerance to hydrogen peroxide in D. melanogaster. In addition, the addition of AAE effectively increased the activities of copper-zinc-containing superoxide dismutase, manganese-containing superoxide dismutase and catalase in D. melanogaster and reduced the contents of malondialdehyde. Moreover, when reared with diets containing AAE, the expression of antioxidant-related genes SOD1, SOD2 and CAT was up-regulated in D. melanogaster and down-regulated for MTH genes. CONCLUSION: The study indicates that AAE effectively enhances the antioxidant capacity of D. melanogaster and has potential applications as an antioxidant and anti-ageing agent in the nutraceutical industry. © 2024 Society of Chemical Industry.

A novel risk variant block across introns 36-45 of CACNA1C for schizophrenia: a cohort-wise replication and cerebral region-wide validation study.

OBJECTIVES: Numerous genome-wide association studies have identified CACNA1C as one of the top risk genes for schizophrenia. As a necessary post-genome-wide association study (GWAS) follow-up, here, we focused on this risk gene, carefully investigated its novel risk variants for schizophrenia, and explored their potential functions. METHODS: We analyzed four independent samples (including three European and one African-American) comprising 5648 cases and 6936 healthy subjects to identify replicable single nucleotide polymorphism-schizophrenia associations. The potential regulatory effects of schizophrenia-risk alleles on CACNA1C mRNA expression in 16 brain regions (n = 348), gray matter volumes (GMVs) of five subcortical structures (n = 34 431), and surface areas and thickness of 34 cortical regions (n = 36 936) were also examined. RESULTS: A novel 17-variant block across introns 36-45 of CACNA1C was significantly associated with schizophrenia in the same effect direction across at least two independent samples (1.8 × 10-4 ≤ P ≤ 0.049). Most risk variants within this block showed significant associations with CACNA1C mRNA expression (1.6 × 10-3 ≤ P ≤ 0.050), GMVs of subcortical structures (0.016 ≤ P ≤ 0.048), cortical surface areas (0.010 ≤ P ≤ 0.050), and thickness (0.004 ≤ P ≤ 0.050) in multiple brain regions. CONCLUSION: We have identified a novel and functional risk variant block at CACNA1C for schizophrenia, providing further evidence for the important role of this gene in the pathogenesis of schizophrenia.

Hypoconnectivity within the cingulo-opercular network in patients with mild cognitive impairment in Chinese communities.

INTRODUCTION: At rest, the brain's higher cognitive systems engage in correlated activity patterns, forming networks. With mild cognitive impairment (MCI), it is essential to understand how functional connectivity within and between resting-state networks changes. This study used resting-state functional connectivity to identify significant differences within and between the cingulo-opercular network (CON) and default mode network (DMN). METHODS: We assessed cognitive function in patients using the Chinese version of the Alzheimer's disease assessment scale-Cognitive subscale (ADAS-Cog). A group of MCI subjects (ages 60-83 years, n = 45) was compared to age-matched healthy controls (n = 70). Resting-state functional connectivity was used to determine functional connectivity strength within and between the CON and DMN. RESULTS: Compared to healthy controls, the MCI group showed significantly lower functional connectivity within the CON (F = 10.76, df = 1, p = 0.001, FDR adjusted p = 0.003). Additionally, the MCI group displayed no distinct differences in functional connectivity within DMN (F = 0.162, df = 1, p = 0.688, FDR adjusted p = 0.688) and between CON and DMN (F = 2.270, df = 1, p = 0.135, FDR adjusted p = 0.262). Moreover, we found no correlation between ADAS-Cog and within- or between-connectivity metrics among subjects with MCI. CONCLUSIONS: Our findings indicate that specific patterns of hypoconnectivity within CON circuitry may characterize MCI relative to healthy controls. This work improves our understanding of network dysfunction underlying MCI and could inform more targeted treatment.

Pleiotropic Association of CACNA1C Variants With Neuropsychiatric Disorders.

BACKGROUND: Neuropsychiatric disorders are highly heritable and have overlapping genetic underpinnings. Single nucleotide polymorphisms (SNPs) in the gene CACNA1C have been associated with several neuropsychiatric disorders, across multiple genome-wide association studies. METHOD: A total of 70,711 subjects from 37 independent cohorts with 13 different neuropsychiatric disorders were meta-analyzed to identify overlap of disorder-associated SNPs within CACNA1C. The differential expression of CACNA1C mRNA in five independent postmortem brain cohorts was examined. Finally, the associations of disease-sharing risk alleles with total intracranial volume (ICV), gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA), and average cortical thickness (TH) were tested. RESULTS: Eighteen SNPs within CACNA1C were nominally associated with more than one neuropsychiatric disorder (P < .05); the associations shared among schizophrenia, bipolar disorder, and alcohol use disorder survived false discovery rate correction (five SNPs with P < 7.3 × 10-4 and q < 0.05). CACNA1C mRNA was differentially expressed in brains from individuals with schizophrenia, bipolar disorder, and Parkinson's disease, relative to controls (three SNPs with P < .01). Risk alleles shared by schizophrenia, bipolar disorder, substance dependence, and Parkinson's disease were significantly associated with ICV, GMVs, SA, or TH (one SNP with P ≤ 7.1 × 10-3 and q < 0.05). CONCLUSION: Integrating multiple levels of analyses, we identified CACNA1C variants associated with multiple psychiatric disorders, and schizophrenia and bipolar disorder were most strongly implicated. CACNA1C variants may contribute to shared risk and pathophysiology in these conditions.

Covalent organic framework-MnO2 nanoparticle composites for shape-selective sensing of bithiols.

Covalent organic frameworks (COFs) for detecting biological macromolecules in water or biological environments are generally challenging. In this work, a composite material IEP-MnO2 is obtained by combining manganese dioxide (MnO2) nanocrystals and a fluorescent COF (IEP), which is synthesized by using 2,4,6-tris(4-aminophenyl)-s-triazine and 2,5-dimethoxyterephthalaldehyde. By the addition of biothiols, such as glutathione, cysteine or homocysteine with different sizes, the fluorescence emission spectra of IEP-MnO2 changed ("turn-on" or "turn-off") via different mechanisms. The fluorescence emission of IEP-MnO2 increased in the presence of GSH by the elimination of the FRET (Förster resonance energy transfer) effect between MnO2 and IEP. Surprisingly, due to the formation of a hydrogen bond between Cys/Hcy and IEP, the fluorescence quenching for IEP-MnO2 + Cys/Hcy may be explained via the photoelectron transfer (PET) process, which endows IEP-MnO2 with specificity in distinguishing the detection of GSH and Cys/Hcy compared to other MnO2 complex materials. Therefore, IEP-MnO2 was used to detect GSH and Cys in human whole blood and serum, respectively. The limit of detection for GSH in whole blood and Cys in human serum was calculated to be 25.58 µM and 4.43 µM, which indicates that IEP-MnO2 can be used to investigate some diseases related to GSH and Cys concentration. Moreover, the research expands the application of covalent organic frameworks in the fluorescence sensing field.

Secular trends and sociodemographic determinants of thinness, overweight and obesity among Chinese children and adolescents aged 7-18 years from 2010 to 2018.

Background: Most studies have focused on overweight/obesity and its secular trend, with insufficient studies on the factors influencing thinness and trends recently. To examine the trends of prevalence and sociodemographic determinants of thinness, overweight, and obesity among Chinese children and adolescents aged 7 to 18 years from 2010 to 2018. Methods: This study was based on cross-sectional data of 11,234 children and adolescents aged 7 to 18 years from the Chinese Family Panel Studies (CFPS) in 2010, 2014, and 2018, including anthropometric and sociodemographic characteristics variables. The nutritional status of each individual was determined according to China and WHO criteria. The demographic characteristics of different subgroups were tested by chi-square, and log-binomial regression was used to analyze the trend of prevalence and the relationship between sociodemographic characteristics and different nutritional statuses. Results: After adjusting for age, from 2010 to 2018, the overall prevalence of thinness decreased, and the prevalence of overweight increased in Chinese children and adolescents. The overall prevalence of obesity declined in boys and increased in girls, but in adolescents aged 16-18 years, it increased significantly. Log-binomial regression analysis showed that among all subjects, time (years), 16-18 years were negatively associated with thinness, while 13-15 years, walking to school, large family size, and paternal age at childbirth older than 30 years old were positively associated with thinness; 10-12/13-15/16-18 years, boarding at school, medium and large family sizes, and mother's education at junior middle school/junior high school and above were negatively associated with overweight/obesity, while time (years), boys were positively associated with overweight/obesity in the multivariate model by adjusting for the statistically significant factors (all p < 0.05). Conclusion: Chinese children and adolescents are facing a double burden of malnutrition. Future public health policies and interventions should prioritize high-risk groups specifically young age groups, boys, larger family sizes and so on.

A significant, functional and replicable risk KTN1 variant block for schizophrenia.

Cortical and subcortical structural alteration has been extensively reported in schizophrenia, including the unusual expansion of gray matter volumes (GMVs) of basal ganglia (BG), especially putamen. Previous genome-wide association studies pinpointed kinectin 1 gene (KTN1) as the most significant gene regulating the GMV of putamen. In this study, the role of KTN1 variants in risk and pathogenesis of schizophrenia was explored. A dense set of SNPs (n = 849) covering entire KTN1 was analyzed in three independent European- or African-American samples (n = 6704) and one mixed European and Asian Psychiatric Genomics Consortium sample (n = 56,418 cases vs. 78,818 controls), to identify replicable SNP-schizophrenia associations. The regulatory effects of schizophrenia-associated variants on the KTN1 mRNA expression in 16 cortical or subcortical regions in two European cohorts (n = 138 and 210, respectively), the total intracranial volume (ICV) in 46 European cohorts (n = 18,713), the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258), and the surface areas (SA) and thickness (TH) of whole cortex and 34 cortical regions in 50 European cohorts (n = 33,992) and eight non-European cohorts (n = 2944) were carefully explored. We found that across entire KTN1, only 26 SNPs within the same block (r2 > 0.85) were associated with schizophrenia across ≥ 2 independent samples (7.5 × 10-5 ≤ p ≤ 0.048). The schizophrenia-risk alleles, which increased significantly risk for schizophrenia in Europeans (q < 0.05), were all minor alleles (f < 0.5), consistently increased (1) the KTN1 mRNA expression in 12 brain regions significantly (5.9 × 10-12 ≤ p ≤ 0.050; q < 0.05), (2) the ICV significantly (6.1 × 10-4 ≤ p ≤ 0.008; q < 0.05), (3) the SA of whole (9.6 × 10-3 ≤ p ≤ 0.047) and two regional cortices potentially (2.5 × 10-3 ≤ p ≤ 0.042; q > 0.05), and (4) the TH of eight regional cortices potentially (0.006 ≤ p ≤ 0.050; q > 0.05), and consistently decreased (1) the BG GMVs significantly (1.8 × 10-19 ≤ p ≤ 0.050; q < 0.05), especially putamen GMV (1.8 × 10-19 ≤ p ≤ 1.0 × 10-4; q < 0.05, (2) the SA of four regional cortices potentially (0.010 ≤ p ≤ 0.048), and (3) the TH of four regional cortices potentially (0.015 ≤ p ≤ 0.049) in Europeans. We concluded that we identified a significant, functional, and robust risk variant block covering entire KTN1 that might play a critical role in the risk and pathogenesis of schizophrenia.

Male-specific, replicable and functional roles of genetic variants and cerebral gray matter volumes in ADHD: a gene-wide association study across KTN1 and a region-wide functional validation across brain.

Attention deficit hyperactivity disorder (ADHD) is associated with reduction of cortical and subcortical gray matter volumes (GMVs). The kinectin 1 gene (KTN1) has recently been reported to significantly regulate GMVs and ADHD risk. In this study, we aimed to identify sex-specific, replicable risk KTN1 alleles for ADHD and to explore their regulatory effects on mRNA expression and cortical and subcortical GMVs. We examined a total of 1020 KTN1 SNPs in one discovery sample (ABCD cohort: 5573 males and 5082 females) and three independent replication European samples (Samples #1 and #2 each with 802/122 and 472/141 male/female offspring with ADHD; and Sample #3 with 14,154/4945 ADHD and 17,948/16,246 healthy males/females) to identify replicable associations within each sex. We examined the regulatory effects of ADHD-risk alleles on the KTN1 mRNA expression in two European brain cohorts (n = 348), total intracranial volume (TIV) in 46 European cohorts (n = 18,713) and the ABCD cohort, as well as the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258) and of 118 cortical and subcortical regions in the ABCD cohort. We found that four KTN1 variants significantly regulated the risk of ADHD with the same direction of effect in males across discovery and replication samples (0.003 ≤ p ≤ 0.041), but none in females. All four ADHD-risk alleles significantly decreased KTN1 mRNA expression in all brain regions examined (1.2 × 10-5 ≤ p ≤ 0.039). The ADHD-risk alleles significantly increased basal ganglia (2.8 × 10-22 ≤ p ≤ 0.040) and hippocampus (p = 0.010) GMVs but reduced amygdala GMV (p = 0.030) and TIV (0.010 < p ≤ 0.013). The ADHD-risk alleles also significantly reduced some cortical (right superior temporal pole, right rectus) and cerebellar but increased other cortical (0.007 ≤ p ≤ 0.050) GMVs. To conclude, we identified a set of replicable and functional risk KTN1 alleles for ADHD, specifically in males. KTN1 may play a critical role in the pathogenesis of ADHD, and the reduction of specific cortical and subcortical, including amygdalar but not basal ganglia or hippocampal, GMVs may serve as a neural marker of the genetic effects.

Tracking objects outside the line of sight using laser Doppler coherent detection.

Based on the laser Doppler coherent detection method, a laser Doppler Non-Line-of Sight imaging technique (LD-NLOS) is proposed to obtain a series of effective information about the detected objects outside the line of sight. According to the analysis of the frequency and light intensity characteristics of the scattered signal, the information of the detected object hidden in the intermediate scattering surface is decoded. Without relying on complicated back-end algorithm processing and expensive experimental detection cost, the proposed LD-NLOS technique can detect the target vibration velocity and stably reconstruct its 2D shape.

Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe.

Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases.

The Effect of Exercise Motivation on Eating Disorders in Bodybuilders in Social Networks: The Mediating Role of State Anxiety.

The aim of this study is to explore the relationship between exercise motivation and eating disorder and the mediating effect of anxiety in physical exercise. Athletes are in a social network, and the different human-machine relationships and situations generated in this may produce different sports motivations and anxiety states for athletes. The exercise motivation, status-trait anxiety, and eating disorder of 1076 fitness subjects were described and analyzed by questionnaire survey, and the survey data were statistically analyzed by means of correlation, regression, and structural equation model. The results showed that the overall detection rate of eating disorder was 56.3%. The overall detection rate of eating disorder was different between males and females. Exercise motivation has a significant positive correlation with state anxiety and eating disorder. Exercise motivation has a significant positive predictive effect on eating disorder, exercise motivation has a significant positive predictive effect on state anxiety, and state anxiety has a significant positive predictive effect on eating disorder. The mediating effect shows that state anxiety can partially mediate the relationship between exercise motivation and eating disorder, exercise motivation has a direct impact on eating disorder, and state anxiety has an indirect impact on eating disorder. In physical exercise, the exercisers' bad exercise motivation will produce too much anxiety. Poor exercise motivation and anxiety can lead to symptoms of eating disorders. In physical exercise, we should adopt reasonable value orientation and positive psychological suggestion and encourage healthy and reasonable eating behavior, which will help to prevent and treat eating disorders.

Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain.

Previous genome-wide association studies (GWAS) reported that the allele C of rs945270 of the kinectin 1 gene (KTN1) most significantly increased the gray matter volume (GMV) of the putamen and modestly regulated the risk for attention deficit hyperactivity disorder (ADHD). On the other hand, ADHD is known to be associated with a reduction in subcortical and cortical GMVs. Here, we examined the interrelationships of the GMVs, rs945270 alleles, and ADHD symptom scores in the same cohort of children. With data of rs945270 genotypes, GMVs of 118 brain regions, and ADHD symptom scores of 3372 boys and 3129 girls of the Adolescent Brain Cognition Development project, we employed linear regression analyses to examine the pairwise correlations adjusted for the third of the three traits and other relevant covariates, and examine their mediation effects. We found that the major allele C of rs945270 modestly increased risk for ADHD in males only when controlling for the confounding effects of the GMV of any one of the 118 cerebral regions (0.026 ≤ p ≤ 0.059: Top two: left and right putamen). This allele also significantly increased putamen GMV in males alone (left p = 2.8 × 10-5, and right p = 9.4 × 10-5; α = 2.1 × 10-4) and modestly increased other subcortical and cortical GMVs in both sexes (α < p < 0.05), whether or not adjusted for ADHD symptom scores. Both subcortical and cortical GMVs were significantly or suggestively reduced in ADHD when adjusted for rs945270 alleles, each more significantly in females (3.6 × 10-7 ≤ p < α; Top two: left pallidum and putamen) and males (3.5 × 10-6 ≤ p < α), respectively. Finally, the left and right putamen GMVs reduced 14.0% and 11.7% of the risk effects of allele C on ADHD, and allele C strengthened 4.5% (left) and 12.2% (right) of the protective effects of putamen GMVs on ADHD risk, respectively. We concluded that the rs945270-GMVs-ADHD relationships were sex-different. In males, the major allele C of rs945270 increased risk for ADHD, which was compromised by putamen GMVs; this allele also but only significantly increased putamen GMVs that then significantly protected against ADHD risk. In females, the top two GMVs significantly decreasing ADHD risk were left pallidum and putamen GMVs. Basal ganglia the left putamen in particular play the most critical role in the pathogenesis of ADHD.

A Novel Fluorescent Probe Strategy Activated by ß-Glucuronidase for Assisting Surgical Resection of Liver Cancer.

Liver cancer is a primary malignant tumor with a very high fatality rate, which has seriously threatened human health and life. In normal hepatocellular lesions, ß-glucuronidase (GLU) activity in liver cancer tissues is significantly increased. Therefore, GLU has become one of the important biomarkers of primary liver cancer. Here, a series of fluorescent probes (DCDH, DCDCH3, DCDOCH3, and DCDNO2) for early diagnosis of liver cancer and auxiliary surgical resection were successfully synthesized. Since the electron-withdrawing group -NO2 connected to the probe DCDNO2 accelerates the rapid cleavage of the glycosidic bond, DCDNO2 exhibits superior fluorescence properties that are more sensitive and rapid than the other three probes DCDH, DCDCH3, and DCDOCH3 when detecting GLU. DCDNO2 has been well-applied in real-time fluorescent visualization imaging for the detection of GLU activity in liver cancer cells and tumor tissues. In addition, DCDNO2 has also been successfully used in the early diagnosis of liver cancer and real-time imaging to guide the surgical resection of liver cancer tumors. Therefore, DCDNO2 has great potential for development in bioclinical medicine for the early detection and treatment of liver cancer.

Covalent Organic Frameworks Doped with Different Ratios of OMe/OH as Fluorescent and Colorimetric Sensors.

Improving the luminescence properties of covalent organic frameworks (COFs) has always been an important issue. Here, a series of COFs (([OMe]x -TzDa (TzDa is composed only by monomerics Tz and Da, OMe represents the incorporation of monomeric Dm)) with different ratios of OMe and OH were designed and synthesized. The photochemical behavior of [OMe]x -TzDa changed significantly due to the synergistic effect of aggregation induced emission (AIE), intramolecular charge transfer (ICT), and excited-state intramolecular proton transfer (ESIPT) effects. [OMe]2 -TzDa, which contained a ratio of 2/1 of OMe/OH, showed the strongest fluorescence emission in water and the best linear relationship for the detection of pH. Furthermore, [OMe]2 -TzDa was used to monitor HCl and NH3 gases and showed a color change, visible to the naked eye. Therefore, a "confidential pigment" was successfully made. Moreover, [OMe]2 -TzDa was also applied to detect N2 H4 . The work indicates the [OMe]2 -TzDa can serve as the first fluorescence sensor to detect pH, HCl and NH3 gases, which also shows a good response to N2 H4 .

Comparison of the clinical efficacy of penicillin and ceftriaxone sodium in the treatment of neurosyphilis with psychiatric symptoms.

OBJECTIVE: To compare the clinical efficacy of penicillin and ceftriaxone sodium in the treatment of neurosyphilis with psychiatric symptoms. METHODS: 50 neurosyphilis with mental symptoms patients were randomly divided into penicillin group (4 million units, Q4h) and ceftriaxone sodium group (1 g, Q12h). The total treatment time was 14 and 15 days respectively.The activity of daily living scale (ADL), brief psychiatric rating scale (BPRS) and mini-mental state examination (MMSE) were scored as the measurement of efficiency in living ability, mental symptoms and cognitive function. RESULT: There were no significant differences in ADL, MMSE and BPRS between the penicillin group and the ceftriaxone sodium treatment group (p > 0.05). After treatment, the score of BPRS and ADL decreased from baseline, while MMSE scores increased from baseline, having a main time effect (F=31.098,F=26.342,F= 79.916; p < 0.05). CONCLUSION: Penicillin or ceftriaxone sodium are both effective in the aspect of mental symptoms, cognitive function and life ability among neurosyphilis with psychiatric symptoms patients.

Rosiglitazone Protects against Acetaminophen-Induced Acute Liver Injury by Inhibiting Multiple Endoplasmic Reticulum Stress Pathways.

Background: Excessive acetaminophen (APAP) use can lead to acute liver injury (ALI) by inducing endoplasmic reticulum stress (ERS). We previously found that pretreatment with the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand rosiglitazone (RSG) alleviated ALI in APAP-treated mice. Objective: To examine if RSG-mediated hepatoprotection is associated with ERS suppression. Methods: Forty-eight male CD-1 mice were randomly divided into control, RSG, APAP 4 h, APAP 24 h, RSG + APAP 4 h, and RSG + APAP 24 h groups. The RSG and RSG + APAP groups received RSG (20 mg/kg) by gavage 48, 24, and 1 h before intraperitoneal injection of 300 mg/kg APAP, while the APAP group received APAP alone and the control group received only normal saline. Animals were sacrificed immediately (RSG and control groups), 4 h (APAP 4 h and RSG + APAP 4 h), or 24 h (APAP 24 h and RSG + APAP 24 h) post-APAP injection. Liver tissues were collected for hematoxylin-eosin staining, TUNEL staining, and Western blotting for ERS-associated proteins. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also measured. A second cohort received APAP or RSG + APAP as described and were monitored for survival over one week. Results: At 4 and 24 h following APAP injection alone, serum ALT and AST levels were significantly elevated, and central lobular necrosis of the liver was observed. Necrosis area reached 21.7% at 4 h and 32.1% at 24 h post-APAP, while apoptotic fractions reached 25.6% and 32.4%. Further, 50% of mice in the survival analysis cohort died within one week post-APAP. At 4 h post-APAP, the ERS marker glucose-regulated protein-78 (GRP78) and ERS-associated proteins pJNK, GRP78, p-eIF2α, pPERK, and pIRE were all significantly upregulated. Pretreatment with RSG significantly reduced serum ALT and AST, liver necrosis area, apoptosis rate, and expression of ERS-associated proteins compared to APAP alone, while increasing survival to 80%. Conclusions: Rosiglitazone pretreatment can alleviate APAP-induced ALI by suppressing three branches of ERS signaling.

An independent, replicable, functional and significant risk variant block at intron 3 of CACNA1C for schizophrenia.

OBJECTIVES: Genome-wide association studies have identified a significant risk gene, CACNA1C, for schizophrenia. In this study, we comprehensively investigated a large set of CACNA1C single-nucleotide polymorphisms (SNPs) to identify the replicable risk alleles for schizophrenia and explore their biological functions. METHODS: One Jewish (1044 cases vs 2052 controls), one European (1350 cases vs 1378 controls) and one exploratory African American samples (98 cases vs 20 controls) were analyzed to identify replicable single-nucleotide polymorphism-schizophrenia associations. The regulatory effects of risk alleles on CACNA1C messenger RNA expression were examined. The most robust risk tagSNP (rs1006737) was meta-analyzed on 17 studies (74,122 cases vs 109,062 controls), and associated with the gray matter volumes of seven subcortical structures in 38,258 Europeans, and the surface areas and thickness of 34 cortical regions in 33,992 Europeans and 2944 non-Europeans. RESULTS: Forty-seven replicable risk single-nucleotide polymorphisms, including a 20-single-nucleotide polymorphism haplotype block, were identified in our samples (1.8 × 10-4 ⩽ p ⩽ 0.049). This variant block was consistently associated with schizophrenia across four independent Psychiatric Genomics Consortium cohorts (79,645 cases vs 109,590 controls; 2.5 × 10-17 ⩽ p ⩽ 0.017). This block showed significant expression quantitative trait loci in three independent European brain cohorts (5.1 × 10-12 ⩽ p ⩽ 8.3 × 10-3) and could be tagged by the most significant risk single-nucleotide polymorphism rs1006737. The minor allele A of rs1006737 significantly increased risk for schizophrenia across the Jewish and European samples (p = 0.029 and 0.004, respectively), and this association was highly significant in the meta-analysis (p = 1.62 × 10-42). This allele also significantly altered the CACNA1C messenger RNA expression in five brain regions (5.1 × 10-12 ⩽ p ⩽ 0.05), decreased the gray matter volume of thalamus (p = 0.010), the surface area of isthmus cingulate cortex (p = 0.013) and the thickness of transverse temporal and superior temporal sulcus cortexes (0.005 ⩽ p ⩽ 0.043). CONCLUSION: We identified an independent, replicable, functional, and significant risk variant block at CACNA1C for schizophrenia, which could be tagged by the most robust risk marker rs1006737, suggesting an important role of CACNA1C in the pathogenesis of schizophrenia.

Structural Engineering of Covalent Organic Frameworks Comprising Two Electron Acceptors Improves Photocatalytic Performance.

Covalent organic frameworks (COFs) have recently attracted much attention as potential photocatalysts for hydrogen production. The effective separation of photogenerated charges is a key objective to improve the photocatalytic activity of COFs. Here, four COFs were synthesized through the Schiff-base reaction to investigate whether the presence (simultaneous or not) of triazine and ketone as acceptors in COFs improved electron-hole separation efficiency. Evidence indicated that charge separation was more efficient when triazine and ketone were simultaneously present in the COF. The COF comprising two acceptors displayed the highest photocatalytic hydrogen production rate (31.43 µmol h-1 ; 41.2 and 3.4 times as large as those of the COFs containing only triazine or ketone, respectively). Moreover, the effect of the distance between the two acceptors on the electron-hole separation was investigated by changing the length of a bridging biphenyl ring. It turned out that the transport distance of a single phenyl group was more favorable for the catalytic reaction. This work affords insight and support for the design of efficient COF photocatalysts.

Measuring depression severity based on facial expression and body movement using deep convolutional neural network.

Introduction: Real-time evaluations of the severity of depressive symptoms are of great significance for the diagnosis and treatment of patients with major depressive disorder (MDD). In clinical practice, the evaluation approaches are mainly based on psychological scales and doctor-patient interviews, which are time-consuming and labor-intensive. Also, the accuracy of results mainly depends on the subjective judgment of the clinician. With the development of artificial intelligence (AI) technology, more and more machine learning methods are used to diagnose depression by appearance characteristics. Most of the previous research focused on the study of single-modal data; however, in recent years, many studies have shown that multi-modal data has better prediction performance than single-modal data. This study aimed to develop a measurement of depression severity from expression and action features and to assess its validity among the patients with MDD. Methods: We proposed a multi-modal deep convolutional neural network (CNN) to evaluate the severity of depressive symptoms in real-time, which was based on the detection of patients' facial expression and body movement from videos captured by ordinary cameras. We established behavioral depression degree (BDD) metrics, which combines expression entropy and action entropy to measure the depression severity of MDD patients. Results: We found that the information extracted from different modes, when integrated in appropriate proportions, can significantly improve the accuracy of the evaluation, which has not been reported in previous studies. This method presented an over 74% Pearson similarity between BDD and self-rating depression scale (SDS), self-rating anxiety scale (SAS), and Hamilton depression scale (HAMD). In addition, we tracked and evaluated the changes of BDD in patients at different stages of a course of treatment and the results obtained were in agreement with the evaluation from the scales. Discussion: The BDD can effectively measure the current state of patients' depression and its changing trend according to the patient's expression and action features. Our model may provide an automatic auxiliary tool for the diagnosis and treatment of MDD.

Efficacy and safety of bismuth quadruple regimens containing tetracycline or furazolidone for initial eradication of Helicobacter pylori.

ABSTRACT: Helicobacter pylori (H pylori) infection can cause chronic gastritis, peptic ulcer, and even gastric cancer, so effective eradication is critical.This study compared the efficacy and safety of bismuth quadruple regimens including either tetracycline or furazolidone for initial eradication.Patients newly diagnosed with H pylori infection from January 2020 to January 2021 were randomly assigned to receive either the tetracycline-containing regimen (n = 116) or furazolidone-containing regimen (n = 168). Both regimens included 1 proton pump inhibitor (rabeprazole 20 mg, or esomeprazole 20 mg, or eprazole 5 mg), colloidal pectin bismuth 300 mg, and amoxicillin 1000 mg in addition to tetracycline 1.0 g or furazolidone 0.1 g. All drugs were administered twice daily for 12 consecutive days. The 14C urea breath test was used for diagnosis, and re-test negativity at one-month follow-up was considered successful eradication. Adverse events were recorded during follow-up by telephone interview.In total, 109 patients in the tetracycline group and 157 in the furazolidone group were re-examined at 1 month. In the tetracycline group, 101 patients tested negative at follow-up, yielding an eradication rate of 92.7% according to per-protocol analysis and 87.1% by intention-to-treat analysis. In the furazolidone group, 141 patients tested negative, yielding eradication rates of 89.8% by PP and 83.9% by ITT. Eradication rates did not differ significantly between regimens (per-protocol: χ2 = 0.637, P = .517; intention-to-treat: χ2 = 0.537, P = .501). However, total adverse events incidence was significantly lower in the tetracycline group (20.2% vs 37.6%; χ2 = 9.193, P = .003).Both bismuth quadruple regimens produce high initial eradication, but the tetracycline regimen appears safer.