FCRL3 expression is upregulated and closely correlates with TIGIT expression in regulatory T cells of patients with systemic lupus erythematosus.

Using data from single-cell RNA sequencing and flow cytometry, we initially examined the expression of FCRL3, finding it to be elevated and positively associated with TIGIT expression in the regulatory T cells of patients with systemic lupus erythematosus. This also suggests that the co-expression of FCRL3 and TIGIT warrants further attention.

Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress.

Running exercise has been shown to alleviate depressive symptoms. However, the mechanism underlying the antidepressant effects of running exercise is not fully understood. The imbalance of M1/M2 microglia phenotype/polarization and concomitant dysregulation of neuroinflammation play crucial roles in the pathogenesis of depression. Running exercise increases circulating levels of adiponectin which is known to cross the blood‒brain barrier and suppress inflammatory responses. AdipoR1 is an adiponectin receptor that is involved in regulating microglial phenotypes and activation states. However, whether running exercise regulates hippocampal microglial phenotypes and neuroinflammation through adiponectin/AdipoR1 to exert its antidepressant effects remains unclear. In the current study, 4 weeks of running exercise significantly alleviated the depressive-like behaviors of chronic unpredictable stress (CUS)-exposed mice. Moreover, running exercise decreased the microglial numbers and altered microglial morphology in three subregions of the hippocampus to restore the M1/M2 balance; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in CUS-exposed mice. These effects may involve elevation of peripheral tissue (adipose tissue and muscle) and plasma adiponectin levels, and hippocampal AdipoR1 levels as well as activation of the AMPK-NF-κB/STAT3 signaling pathway by running exercise. When an adeno-associated virus was used to knock down hippocampal AdipoR1, mice showed depressive-like behaviors and alterations in microglia and inflammatory factor expression in the hippocampus that were similar to those observed in CUS-exposed mice. Together, these results suggest that running exercise maintains the M1/M2 balance and inhibits neuroinflammation in the hippocampus of CUS-exposed mice. These effects might occur via adiponectin/AdipoR1-mediated activation of the AMPK-NF-κB/STAT3 signaling pathway.

Metal nanowire-based transparent electrode for flexible and stretchable optoelectronic devices.

High-quality transparent electrodes are indispensable components of flexible optoelectronic devices as they guarantee sufficient light transparency and electrical conductivity. Compared to commercial indium tin oxide, metal nanowires are considered ideal candidates as flexible transparent electrodes (FTEs) owing to their superior optoelectronic properties, excellent mechanical flexibility, solution treatability, and higher compatibility with semiconductors. However, certain key challenges associated with material preparation and device fabrication remain for the practical application of metal nanowire-based electrodes. In this review, we discuss state-of-the-art solution-processed metal nanowire-based FTEs and their applications in flexible and stretchable optoelectronic devices. Specifically, the important properties of FTEs and a cost-benefit analysis of existing technologies are introduced, followed by a summary of the synthesis strategy, key properties, and fabrication technologies of the nanowires. Subsequently, we explore the applications of metal-nanowire-based FTEs in different optoelectronic devices including solar cells, photodetectors, and light-emitting diodes. Finally, the current status, future challenges, and emerging strategies in this field are presented.

Hybrid Thin Film Encapsulation for Improving the Stability of PbS Quantum Dot Solar Cells.

The instability to moisture, heat, and ultraviolet (UV) light is the main problem in the application of quantum dot solar cells (QDSCs). Thin film encapsulation can effectively improve their operational stability. However, it is difficult to achieve multiple barrier effects with single layer of encapsulated film. Here, a hybrid thin-film encapsulation strategy is reported to encapsulate lead sulfide QDSCs, which can isolate moisture and partial thermal, and prevent the penetration of UV light, thus retarding the surface oxidation process of the quantum dots. After 60 h, the encapsulated device retains a normalized power conversion efficiency of 83.8% and 80.6% at 85% humidity and 75 °C, respectively, which is three and six times of the value obtained in unencapsulated devices. At continuous UV illumination, encapsulated device exhibits five times higher stability than the reference. This strategy provides the way for the overall improvement of the operating stability of lead sulfide QDSCs in harsh environments of high humidity, high temperature, and UV light.

Algal Extracellular Organic Matter Induced Photochemical Oxidation of Mn(II) to Solid Mn Oxide: Role of Mn(III)-EOM Complex and Its Ability to Remove 17α-Ethinylestradiol.

Photosensitizer-mediated abiotic oxidation of Mn(II) can yield soluble reactive Mn(III) and solid Mn oxides. In eutrophic water systems, the ubiquitous algal extracellular organic matter (EOM) is a potential photosensitizer and may have a substantial impact on the oxidation of Mn(II). Herein, we focused on investigating the photochemical oxidation process from Mn(II) to solid Mn oxide driven by EOM. The results of irradiation experiments demonstrated that the generation of Mn(III) intermediate was crucial for the successful photo oxidization of Mn(II) to solid Mn oxide mediated by EOM. EOM can serve as both a photosensitizer and a ligand, facilitating the formation of the Mn(III)-EOM complex. The complex exhibited excellent efficiency in removing 17α-ethinylestradiol. Furthermore, the complex underwent decomposition as a result of reactions with reactive intermediates, forming a solid Mn oxide. The presence of nitrate can enhance the photochemical oxidation process, facilitating the conversion of Mn(II) to Mn(III) and then to solid Mn oxide. This study deepens our grasp of Mn(II) geochemical processes in eutrophic water and its impact on organic micropollutant fate.

Relationship between socioeconomic status and hypertension incidence among adults in southwest China: a population-based cohort study.

PURPOSE: To investigate the correlation between socioeconomic status (SES) and the incidence of hypertension among adults aged 18 or above in southwest China. METHODS: A multistage proportional stratified cluster sampling method was employed to recruited 9280 adult residents from 12 counties in southwest China, with all participants in the cohort tracked from 2016 to 2020. The questionnaire survey gathered information on demographics, lifestyle habits, and household income. The physical exam recorded height, weight, and blood pressure. Biochemical tests measured cholesterol levels. The chi-square test was employed to assess the statistical differences among categorical variables, while the Cox proportional hazards regression model was applied to evaluate the association between socioeconomic status (SES) and the incidence of hypertension. RESULTS: The finally effective sample size for the cohort study was 3546 participants, after excluding 5734 people who met the exclusion criteria. Adults in the highest household income group had a significantly lower risk of hypertension compared to those in the lowest income group (HR = 0.636, 95% CI: 0.478-0.845). Besides, when compared to individuals in the illiterate population, the risk of hypertension among adults with elementary school, junior high school, senior high school and associate degree educational level decreased respectively by 34.4% (HR = 0.656, 95%CI: 0.533-0.807), 44.9% (HR = 0.551, 95%CI: 0.436-0.697), 44.9% (HR = 0.551, 95%CI: 0.405-0.750), 46.1% (HR = 0.539, 95%CI: 0. 340-0.854). After conducting a thorough analysis of socioeconomic status, compared with individuals with a score of 6 or less, the risk of hypertension in participants with scores of 8, 10, 11, 12, and greater than 12 decreased respectively by 23.9% (HR = 0.761, 95%CI: 0.598-0.969), 29.7% (HR = 0.703, 95%CI: 0.538-0.919), 34.0% (HR = 0.660, 95%CI: 0.492-0.885), 34.3% (HR = 0.657, 95%CI: 0.447-0.967), 43.9% (HR = 0.561, 95%CI: 0.409-0.769). CONCLUSION: The findings indicate a negative correlation between socioeconomic status and hypertension incidence among adults in southwest China, suggesting that individuals with higher socioeconomic status are less likely to develop hypertension.

Complete degradation of di-n-butyl phthalate by Glutamicibacter sp. strain 0426 with a novel pathway.

Di-n-butyl phthalate (DBP) is widely used as plasticizer that has potential carcinogenic, teratogenic, and endocrine effects. In the present study, an efficient DBP-degrading bacterial strain 0426 was isolated and identified as a Glutamicibacter sp. strain 0426. It can utilize DBP as the sole source of carbon and energy and completely degraded 300 mg/L of DBP within 12 h. The optimal conditions (pH 6.9 and 31.7 °C) for DBP degradation were determined by response surface methodology and DBP degradation well fitted with the first-order kinetics. Bioaugmentation of contaminated soil with strain 0426 enhanced DBP (1 mg/g soil) degradation, indicating the application potential of strain 0426 for environment DBP removal. Strain 0426 harbors a distinctive DBP hydrolysis mechanism with two parallel benzoate metabolic pathways, which may account for the remarkable performance of DBP degradation. Sequences alignment has shown that an alpha/beta fold hydrolase (WP_083586847.1) contained a conserved catalytic triad and pentapeptide motif (GX1SX2G), of which function is similar to phthalic acid ester (PAEs) hydrolases and lipases that can efficiently catalyze hydrolysis of water-insoluble substrates. Furthermore, phthalic acid was converted to benzoate by decarboxylation, which entered into two different pathways: one is the protocatechuic acid pathway under the role of pca cluster, and the other is the catechol pathway. This study demonstrates a novel DBP degradation pathway, which broadens our understanding of the mechanisms of PAE biodegradation.

Work-family conflict among primary health workers during the COVID-19 pandemic: Its mediating role in the relationship between workload and job burnout.

AIMS AND OBJECTIVES: This study explores the situation of workload, work-family conflict and job burnout among primary health workers in China in the context of COVID-19 and identifies the mediating effect of work-family conflict between workload and job burnout. BACKGROUND: Since the breakout of the COVID-19 pandemic, primary health workers have been working on the frontline of the epidemic and may experience increasing workload, work-family conflict and job burnout. It is important to focus on the issue of how to alleviate job burnout of primary health workers. DESIGN: A cross-sectional study (STROBE) was used. METHODS: Data were collected from 785 primary health workers in China. Multiple regression analysis was used to examine the mediating effect of work-family conflict between workload and job burnout. RESULTS: 18.7%, 10.4% and 39.5% of respondents had high job burnout in the dimensions of emotional exhaustion, depersonalization and personal accomplishment, respectively. 34.6% of the respondents had high or very high workload, and 12.8% of the respondents had high or very high work-family conflict. Results of multiple regression analysis indicated that work-family conflict mediated the relationship between workload and job burnout. Workload (ß = .163, CI = .207-.549) and work-family conflict (ß = .211, CI = .311-.640) positively influenced job burnout, and workload (ß = .428, CI = .375-.508) positively influenced work-family conflict. CONCLUSION: The study indicated that primary health workers experienced a high level of job burnout, especially in the personal accomplishment dimension. Furthermore, this study verified the mediating effect of work-family conflict between workload and job burnout. RELEVANCE TO CLINICAL PRACTICE: Some interventions for alleviating workload, work-family conflict and job burnout should be taken, including workplace assistance programmes, family-friendly policies and a well-integrated healthcare system. NO PATIENT OR PUBLIC CONTRIBUTION: This study does not involve patient or public contribution in any part. IMPACT STATEMENT: Nurses and other primary health workers are health gatekeepers of residents and play a vital role in the healthcare system. Due to the breakout of COVID-19, they have taken more work and are more vulnerable to work overload, work-family conflict and the consequent job burnout. Some interventions should be taken to effectively alleviate their job burnout and improve their health and performance.

Exploring the Roles of Key Mediators IKBKE and HSPA1A in Alzheimer's Disease and Hepatocellular Carcinoma through Bioinformatics Analysis.

Recent studies have hinted at a potential link between Alzheimer's Disease (AD) and cancer. Thus, our study focused on finding genes common to AD and Liver Hepatocellular Carcinoma (LIHC), assessing their promise as diagnostic indicators and guiding future treatment approaches for both conditions. Our research utilized a broad methodology, including differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), gene enrichment analysis, Receiver Operating Characteristic (ROC) curves, and Kaplan-Meier plots, supplemented with immunohistochemistry data from the Human Protein Atlas (HPA) and machine learning techniques, to identify critical genes and significant pathways shared between AD and LIHC. Through differential gene expression analysis, WGCNA, and machine learning methods, we identified nine key genes associated with AD, which served as entry points for LIHC analysis. Subsequent analyses revealed IKBKE and HSPA1A as shared pivotal genes in patients with AD and LIHC, suggesting these genes as potential targets for intervention in both conditions. Our study indicates that IKBKE and HSPA1A could influence the onset and progression of AD and LIHC by modulating the infiltration levels of immune cells. This lays a foundation for future research into targeted therapies based on their shared mechanisms.

Hypertriglyceridemic hyperapoB and the development and resolution of nonalcoholic fatty liver disease: a cohort study.

Hypertriglyceridemic hyperapoB is an adverse lipoprotein phenotype characterized by low high density lipoprotein (HDL) cholesterol, high triglycerides, high apolipoprotein B (ApoB), and low low density lipoprotein (LDL) cholesterol to ApoB ratio. We investigated whether and to what extent hypertriglyceridemic hyperapoB associates with the incidence and resolution of nonalcoholic fatty liver disease (NAFLD). This prospective cohort study included 9,019 Chinese participants 40 years or older, from 2010 to 2015. Logistic regression models were used to examine the odds ratios (ORs) for the incidence and resolution of NAFLD associated with the hypertriglyceridemic hyperapoB lipoprotein phenotype and individual lipid and lipoprotein parameters. During a median 4.3 years of follow-up, compared with participants with optimal phenotype, the fully adjusted ORs (95% CIs) for participants with hypertriglyceridemic hyperapoB were 2.75 (1.91, 3.95) and 0.57 (0.33, 1.00) for incidence and resolution of NAFLD, respectively. These associations were consistent across subgroup participants with varied demographic, lifestyle, and metabolic status. Individually, each unit increase in HDL cholesterol (OR: 0.98; 95% CI: 0.97, 0.99), natural logarithm-transformed triglycerides (1.89; 1.52, 2.36), and ApoB (1.006; 1.002, 1.011) was independently associated with NAFLD incidence, and only triglycerides (0.77; 0.60, 0.99) was independently associated with NAFLD resolution. Our findings suggest that Chinese adults with hypertriglyceridemic hyperapoB have a higher risk of NAFLD incidence and a lower likelihood of NAFLD resolution. These associations were stable among adults with different demographic, lifestyle, and metabolic status, supporting hypertriglyceridemic hyperapoB as a valuable clinical marker for the prevention and control of NAFLD.

Transcriptome analysis reveals core lncRNA-mRNA networks regulating melanization and biomineralization in Patinopecten yessoensis shell-infested by Polydora.

BACKGROUND: Patinopecten yessoensis, a large and old molluscan group, has been one of the most important aquaculture shellfish in Asian countries because of its high economic value. However, the aquaculture of the species has recently been seriously affected by the frequent outbreaks of Polydora disease, causing great economic losses. Long non-coding RNAs (lncRNAs) exhibit exhibit crucial effects on diverse biological processes, but still remain poorly studied in scallops, limiting our understanding of the molecular regulatory mechanism of P. yessoensis in response to Polydora infestation. RESULTS: In this study, a high-throughput transcriptome analysis was conducted in the mantles of healthy and Polydora-infected P. yessoensis by RNA sequencing. A total of 19,133 lncRNAs with 2,203 known and 16,930 novel were identified. The genomic characterizations of lncRNAs showed shorter sequence and open reading frame (ORF) length, fewer number of exons and lower expression levels in comparison with mRNAs. There were separately 2280 and 1636 differentially expressed mRNAs and lncRNAs (DEGs and DELs) detected in diseased individuals. The target genes of DELs were determined by both co-location and co-expression analyses. Functional enrichment analysis revealed that DEGs involved in melanization and biomineralization were significantly upregulated; further, obviously increased melanin granules were observed in epithelial cells of the edge mantle in diseased scallops by histological and TEM study, indicating the crucial role of melanizaiton and biomineralization in P. yessoensis to resist against Polydora infestation. Moreover, many key genes, such as Tyrs, Frizzled, Wnts, calmodulins, Pifs, perlucin, laccase, shell matrix protein, mucins and chitins, were targeted by DELs. Finally, a core lncRNA-mRNA interactive network involved in melanization and biomineralization was constructed and validated by qRT-PCR. CONCLUSIONS: This work provides valuable resources for studies of lncRNAs in scallops, and adds a new insight into the molecular regulatory mechanisms of P. yessoensis defending against Polydora infestation, which will contribute to Polydora disease control and breeding of disease-resistant varieties in molluscs.

Opposite causal effects of birthweight on myocardial infarction and atrial fibrillation and the distinct mediating pathways: a Mendelian randomization study.

BACKGROUND: Previous observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways. METHODS: We performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight. RESULTS: Genetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22-1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16-1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association. CONCLUSIONS: Cardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.

Causal impacts of educational attainment on chronic liver diseases and the mediating pathways: Mendelian randomization study.

BACKGROUND AND AIMS: Educational attainment is an essential socio-economic indicator with broad implications for lifestyle behaviour and metabolic health. We aimed to investigate the causal effect of education on chronic liver diseases and the potential mediating pathways. METHODS: We applied univariable Mendelian randomization (MR) to assess the causal associations between educational attainment and non-alcoholic fatty liver disease (NAFLD) (cases/controls: 1578/307 576 in FinnGen; 1664/400 055 in UK Biobank), viral hepatitis (1772/307 382; 1215/403 316), hepatomegaly (199/222 728; 297/400 055), chronic hepatitis (699/301 014; 277/403 316), cirrhosis (1362/301 014; 114/400 055) and liver cancer (518/308 636; 344/393 372) using summary statistics of genome-wide association studies from the FinnGen Study and the UK Biobank, respectively. We used two-step MR to evaluate potential mediators and their mediation proportions in the association. RESULTS: Meta-analysis of inverse variance weighted MR estimates from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was causally associated with decreased risks of NAFLD (OR: 0.48; 95%CI: 0.37-0.62), viral hepatitis (0.54; 0.42-0.69) and chronic hepatitis (0.50; 0.32-0.79), but not hepatomegaly, cirrhosis and liver cancer. Nine, two and three out of 34 modifiable factors were identified as causal mediators in the associations of education with NAFLD, viral hepatitis and chronic hepatitis, respectively, including six adiposity traits (mediation proportion: 16.5%-32.0%), major depression (16.9%), two glucose metabolism-related traits (2.2%-15.8%) and two lipids (9.9%-12.1%). CONCLUSIONS: Our findings supported the causal protective effects of education on chronic liver diseases and outlined mediating pathways to inform prevention and intervention strategies to reduce the burden of liver diseases, especially for individuals with lower education.

Causal effect of lower birthweight on non-alcoholic fatty liver disease and mediating roles of insulin resistance and metabolites.

BACKGROUND & AIMS: The causal association of lower birthweight with non-alcoholic fatty liver disease (NAFLD) and the mediating pathways remain unclear. We aimed to investigate the causal, independent association of lower birthweight with NAFLD and identify potential metabolic mediators and their mediation effects in this association. METHODS: We performed two-step, two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) summary statistics for birthweight from the Early Growth Genetics Consortium of 298 142 Europeans, NAFLD from a GWAS meta-analysis of 8434 NAFLD cases and 770 180 controls of Europeans, and 25 candidate mediators from corresponding reliable GWASs. RESULTS: Genetically determined each 1-SD lower birthweight was associated with a 45% (95% CI: 1.25-1.69) increased risk of NAFLD, and this causal association persisted after adjusting for childhood obesity or adult adiposity traits in multivariable MR. Two-step MR identified 6 of 25 candidate mediators partially mediate the effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.05%), leucine (17.29%), isoleucine (13.55%), valine (11.37%), alanine (10.01%) and monounsaturated fatty acids (MUFA; 7.23%). Bidirectional MR suggested a unidirectional effect of insulin resistance on isoleucine, leucine and valine and a unidirectional effect of alanine on insulin resistance. CONCLUSIONS: This MR study elucidated the causal impact of lower birthweight on subsequent risk of NAFLD, independently of later-life adiposity and identified mediators including insulin resistance, branched-chain amino acids, alanine and MUFA in this association pathway. Our findings shed light on the pathogenesis of NAFLD and imply additional targets for prevention and intervention of NAFLD attributed to low birthweight.

Elevated Layilin-Positive Monocyte Levels in the Peripheral Blood of Patients with Systemic Lupus Erythematosus Reflect Their Autoimmune Status.

OBJECTIVE: To investigate the expression of layilin (LAYN) in human circulating monocytes and lymphocytes and its clinical significance in systemic lupus erythematosus (SLE). METHODS: Blood samples were collected from 51 SLE patients and 50 healthy controls. Flow cytometry was used to analyze LAYN in lymphocytes and monocyte subsets. Functionally characterized molecules including human HLA, CD74 and CD62L were studied in LAYN+ monocytes. A correlation analysis was conducted between LAYN-related subsets and clinical indicators of SLE such as anti-double-stranded DNA and complements levels. ROC curves were used to explore the potential clinical diagnostic value of LAYN in SLE. RESULTS: LAYN was significantly higher in monocytes than in lymphocytes and higher in CD14+CD16+ monocytes than in CD14-CD16+ and CD14+CD16- monocytes. CD74 was upregulated and CD62L was downregulated in LAYN+ monocytes compared with LAYN- monocytes. The absolute number of LAYN+ monocytes was increased in SLE patients, and the median fluorescence intensity of HLA was decreased. LAYN+ monocytes were positively correlated with complement C4, while decreased CD62L+ percentages in LAYN+ monocytes were negatively correlated with C4. The ROC analysis revealed that the area under the curve (AUCs) for CD62L+ percentages in LAYN+ monocytes, LAYN+ lymphocyte numbers, and LAYN+ monocyte numbers to distinguish SLE from healthy individuals were 0.6245, 0.6196 and 0.6173, respectively. CONCLUSION: LAYN is differentially expressed in monocytes and their subpopulations and has corresponding functional differences. Changes in LAYN expression on monocytes are associated with complement C4 levels in SLE patients. These suggest that LAYN may be involved in the pathogenesis of SLE. ABBREVIATION: ANOVA: analysis of variance; anti-dsDNA: anti-double-stranded DNA; anti-ENA: anti-extractable nuclear antigen; anti-SSA: anti-Sjogren syndrome A; anti-SSB: anti-Sjogren syndrome B; anti-U1RNP: anti-U1 ribonucleoprotein; AUC: area under the ROC curve; CBC: complete blood count; CD62L: L-selectin; CD74/Ii: MHC class II invariant chain; CD44/HCAM: homing cell adhesion molecule; cMos: classical monocytes; CRP: C-reactive protein; CXCR2: C-X-C motif chemokine receptor 2; CXCR4: C-X-C motif chemokine receptor 4; ESR: erythrocyte sedimentation rate; HCs: healthy controls; HA: hyaluronan; HLA: human leukocyte antigen; Ig: immunoglobulin; iMos: intermediate monocytes; LAYN: layilin; MFI: median fluorescence intensity; MIF: migration inhibitory factor; ncMos: nonclassical monocytes; PBMCs: peripheral blood mononuclear cells; ROC: receiver operating characteristic curve; SLE: systemic lupus erythematosus; SLEDAI, SLE disease activity index; Treg: regulatory T cells; WBCs: white blood cells.

Profiling Cystathionine ß/γ-Lyase in Complex Biosamples Using Novel Activatable Fluorogens.

Cystathionine lyase, the key enzyme in transsulfuration and reverse transsulfuration pathways, is involved in a wide array of physiological and pathophysiological processes in both mammals and nonmammals. Though the biological significance of the hydrogen sulfide/cystathionine lyase system in disease states is extensively discussed, the absence of molecular methods for direct monitoring of cystathionine lyase in complex biosamples renders the result unreliable and perplexing. Here, we present the first attempt at designing and developing effective activatable fluorescent probes for cystathionine lyase based on the naphthylamide scaffold. CBLP and CSEP were designed based on the catalytic preference of cystathionine ß-lyase (CBL) and cystathionine γ-lyase (CSE). Briefly, incorporation of cysteine/homocysteine as the recognition moiety and a carbamate ethyl sulfide group as a self-immolated linker proved to be an effective strategy for cystathionine lyase fluorescence reporting. CBLP exhibits high selectivity and sensitivity in vitro in semiquantifying CBL levels in roots of wild-type Arabidopsis thaliana and cbl mutants (cbl knockout: SALK_014740C, overexpressed: OE-CBL). Meanwhile, CSEP successfully detected CSE levels in HCC-LM3 cells, zebrafish models, and upregulated CSE in frozen section slides from the liver tissue of cecal ligation and puncture (CLP)-induced septic rats, which was also validated by Western blotting and immunohistochemical analysis. In summary, the practical design strategy facilitates profiling of cystathionine lyase activity in biological processes. It may pave the way for the development of accurate and efficient methods for the direct estimation of cystathionine lyase.

Dissection of transcriptome dysregulation and immune characterization in women with germline BRCA1 mutation at single-cell resolution.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most frequent and lethal type of ovarian cancer. It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial BRCA1/2 mutations. However, the molecular changes underlying malignant transformation remain unknown. METHOD: We performed single-cell RNA and T cell receptor sequencing of tubal fimbriated ends from 3 BRCA1 germline mutation carriers (BRCA1 carriers) and 3 normal controls with no high-risk history (non-BRCA1 carriers). RESULTS: Exploring the transcriptomes of 19,008 cells, predominantly from BRCA1+ samples, we identified 5 major cell populations in the fallopian tubal mucosae. The secretory cells of BRCA1+ samples had differentially expressed genes involved in tumor growth and regulation, chemokine signaling, and antigen presentation compared to the wild-type BRCA1 controls. There are several novel findings in this study. First, a subset of the fallopian tubal secretory cells from one BRCA1 carrier exhibited an epithelial-to-mesenchymal transition (EMT) phenotype, which was also present in the mucosal fibroblasts. Second, we identified a previously unreported phenotypic split of the EMT secretory cells with distinct evolutionary endpoints. Third, we observed increased clonal expansion among the CD8+ T cell population from BRCA1+ carriers. Among those clonally expanded CD8+ T cells, PD-1 was significantly increased in tubal mucosae of BRCA1+ patients compared with that of normal controls, indicating that T cell exhaustion may occur before the development of any premalignant or malignant lesions. CONCLUSION: These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with BRCA1 germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with BRCA1 germline mutation present with early development and rapid dissemination of HGSC.

Covalent organic framework modified carbon cloth for ratiometric electrochemical sensing of bisphenol A and S.

A novel ratiometric electrochemical sensor was developed based on a carbon cloth electrodeposited with silver nanoparticles and drop-coated by covalent organic framework (COF-LZU1) for simultaneous determination of bisphenol A (BPA) and bisphenol S (BPS). Carbon cloth exhibited a significantly larger electrochemical active area than common glassy carbon electrodes (27.5 times). Silver nanoparticles not only provided a stable reference signal but also enhanced electroactivity for the oxidation of BPA and BPS. COF-LZU1 with good adsorption performance and large periodic π-arrays promoted the enrichment of BPA and BPS to further increase the current response. Compared with the traditional single-signal electrochemical sensor, the developed ratiometric sensor exhibited better reproducibility and a wider linear range for BPA and BPS from 0.5 to 100 µM with a limit of detection of 0.15 µM. Furthermore, the developed sensor showed excellent stability and superior anti-interference ability. The real sample analysis for BPA and BPS has been successfully carried out in mineral water, electrolyte drink, tea, juice, and beer with recoveries of 88.3-111.7%. The developed ratiometric sensor is expected to be a candidate for the preparation of other electrochemical sensors and the analysis of additional practical samples.

Research on Multi-Level Scheduling of Mine Water Reuse Based on Improved Whale Optimization Algorithm.

Aiming at the problem of the inefficiency of coal mine water reuse, a multi-level scheduling method for mine water reuse based on an improved whale optimization algorithm is proposed. Firstly, the optimization objects of mine water reuse time and reuse cost are used to establish the optimal scheduling model of mine water. Secondly, in order to overcome the defect that the whale optimization algorithm (WOA) is prone to local convergence, the opposition-based learning strategy is introduced to speed up the convergence speed, the Levy flight strategy is used to enhance the ability of the algorithm to jump out of the local optimization, the nonlinear convergence factor is used to balance the global and local search ability, and the adaptive inertia weight is used to improve the optimization accuracy of the algorithm. Finally, the improved whale optimization algorithm (IWOA) is applied to the mine water optimization scheduling model with multiple objects and constraints. The results show that the reuse efficiency of the multi-level scheduling method of mine water reuse is increased by 30.2% and 31.9%, respectively, in the heating and nonheating seasons, which can significantly improve the reuse efficiency of mine water and realize the efficient utilization of mine water reuse deployment. At the same time, experiments show that the improved whale optimization algorithm has higher convergence accuracy and speed, which proves the feasibility and superiority of its improvement strategies.

Optimal Reuse Design Scheduling of Mine Water Based on Improved Whale Algorithm.

The optimal scheduling of mine water is a multi-objective, multi-constraint, nonlinear, multi-stage combination of optimization problems, in view of the traditional solution methods with the increase in decision-making variable dimensions facing a large amount of computation, "dimensional disaster" and other problems, the introduction of a new intelligent simulation algorithm-the Whale Optimization Algorithm to solve the optimal scheduling problem of mine water. Aiming at the problem that the Whale Optimization Algorithm itself is prone to local optimization and slow convergence, it has been improved by improving its own parameters and introducing the inertia weight of the particle swarm and has achieved more obvious results. According to the actual situation of Nalinhe No. 2 Mine, the mathematical model of multi-target optimization of mine water is established based on the function of reuse time and reuse cost of mine water as the target function, and the balance of supply and demand of mine water, the water quality requirements of water use points at all levels, the water quantity requirements of reservoirs and the priority of water supply as the constraints. The improved Whale Optimization Algorithm was used to search optimal solution, and the results showed that the adaptability value of the improved Whale Optimization Algorithm was significantly improved compared with before, of which 8.65% and 7.69% were increased in the heating season and non-heating season, and the rate of cost reduction was 46.80% and 36.92%, and the iteration efficiency was also significantly improved, which improved the decision-making efficiency of optimal scheduling and became more suitable for the actual scheduling needs of Nalinhe No. 2 mine.