Systematic Mendelian Randomization Exploring Druggable Genes for Hemorrhagic Strokes.

Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke. We sequentially performed summary-data-based MR analysis and two-sample MR analysis to assess the associations of all genes within the database with intracranial aneurysm, intracerebral hemorrhage, and their subtypes. Validated genes were further analyzed by colocalization. Only genes that were positive in all three analyses and were druggable were considered desirable genes. We also explored the mediators of genes affecting hemorrhagic stroke incidence. Finally, the associations of druggable genes with other cardiovascular diseases were analyzed to assess potential side effects. We identified 56 genes that significantly affected hemorrhagic stroke incidence. Moreover, TNFSF12, SLC22A4, SPARC, KL, RELT, and ADORA3 were found to be druggable. The inhibition of TNFSF12, SLC22A4, and SPARC can reduce the risk of intracranial aneurysm, subarachnoid hemorrhage, and intracerebral hemorrhage. Gene-induced hypertension may be a potential mechanism by which these genes cause hemorrhagic stroke. We also found that blocking these genes may cause side effects, such as ischemic stroke and its subtypes. Our study revealed that six druggable genes were associated with hemorrhagic stroke, and the inhibition of TNFSF12, SLC22A4, and SPARC had preventive effects against hemorrhagic strokes.

Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N-Arylquinazolinones.

Visible light-driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of deracemization of allenes have been established, where the activated energy of photosensitizer should surpass that of the substrates, representing an intrinsic requirement. Accordingly, this method is not applicable for axially chiral molecules with significantly high triplet energies. In this study, we present a photoredox catalytic deracemization approach that enables the efficient synthesis of valuable yet challenging-to-access axially chiral 2-azaarene-functionalized quinazolinones. The substrate scope is extensive, allowing for both 3-axis and unmet 1-axis assembly through facile oxidation of diverse central chiral 2,3-dihydroquinazolin-4(1H)-ones that can be easily prepared and achieve enantiomer enrichment via deracemization. Mechanistic studies reveal the importance of photosensitizer selection in attaining excellent chemoselectivity and highlight the indispensability of a chiral Brønsted acid in enabling highly enantioselective protonation to accomplish efficient deracemization.

Relationship between childhood trauma and non-suicidal self-injury in high school students: the mediating role of the stress perception and the moderating role of teacher-student relationship.

This study delves into the correlation between childhood trauma and non-suicidal self-injury (NSSI) behaviors among high school students. Additionally, it examines the mediating role of stress perception and the moderating role of the teacher-student relationship in this association. A questionnaire survey was administered to 1,329 high school students in Yunnan Province to assess childhood trauma, NSSI behaviors, and stress perception. Firstly, the survey revealed a 12% prevalence of NSSI, with girls exhibiting a higher occurrence compared to boys (OR = 0.413, 95% CI: 0.280-0.609). Secondly, childhood trauma emerged as a significant predictor of NSSI behavior, irrespective of gender or whether the individual was an only child (r = 0.17, P < 0.01). Thirdly, stress perception functioned as a mediator in the relationship between childhood trauma and NSSI among high school students (t = 4.65, P < 0.01). The mediation effect occupies 26.56% of the total effect. Furthermore, the teacher-student relationship moderated the mediating effect of stress perception on the link between childhood trauma and NSSI (ß = 0.0736, P < 0.01). Notably, individuals with strong teacher-student relationships exhibited a significant elevation in stress perception upon exposure to childhood trauma. The findings of this study support a moderated mediation model in the association between childhood trauma and NSSI, suggesting profound implications for the development of targeted interventions and prevention strategies among high school students.

Polystyrene nanoplastics of different particle sizes regulate the polarization of pro-inflammatory macrophages.

Microplastics (MPs) are defined as plastic particles smaller than 5 mm in size, and nanoplastics (NPs) are those MPs with a particle size of less than 1000 nm or 100 nm. The prevalence of MPs in the environment and human tissues has raised concerns about their potential negative effects on human health. Macrophages are the major defence against foreign substances in the intestine, and can be polarized into two types: the M1 phenotype and the M2 phenotype. However, the effect of NPs on the polarization of macrophages remains unclear. Herein, we selected polystyrene, one of the most plastics in the environment and controlled the particle sizes at 50 nm and 500 nm respectively to study the effects on the polarization of macrophages. We used mouse RAW264.7 cell line models in this macrophage-associated study. Experiments on cell absorption showed that macrophages could quickly ingest polystyrene nanoplastics of both diameters with time-dependent uptake. Compared to the untreated group and 10 µg/mL treatment group, macrophages exposed to 50 µg/mL groups (50 nm and 500 nm) had considerably higher levels of CD86, iNOS, and TNF-α, but decreased levels of aCD206, IL-10, and Arg-1. According to these findings, macrophage M1 and M2 polarization can both be induced and inhibited by 50 µg/mL 50 nm and 500 nm polystyrene nanoplastics. This work provided the first evidence of a possible MPs mode of action with appropriate concentration and size through the production of polarized M1, providing dietary and environmental recommendations for people, particularly those with autoimmune and autoinflammatory illnesses.

Electrochemical deoxygenative amination of stabilized alkyl radicals from activated alcohols.

Alkylamine structures represent one of the most functional and widely used in organic synthesis and drug design. However, the general methods for the functionalization of the shielded and deshielded alkyl radicals remain elusive. Here, we report a general deoxygenative amination protocol using alcohol-derived carbazates and nitrobenzene under electrochemical conditions. A range of primary, secondary, and tertiary alkylamines are obtained. This practical procedure can be scaled up through electrochemical continuous flow technique.

The relationship between structure and ecosystem services of forest and grassland based on pattern analysis method: A case study of the Mongolian Plateau.

Global warming has led to severe land desertification on the Mongolian plateau. It puts great environmental pressure on vegetation communities. This pressure leads to fragmentation of land use and landscape patterns, thus triggering changes in the spatial distribution patterns of vegetation. The spatial distribution pattern of vegetation is crucial for the performance of its ecosystem services. However, there is not enough research on the relationship between large-scale spatial distribution patterns of vegetation and ecosystem services. Therefore, this study is to construct an ecological spatial network on the Mongolian Plateau based on landscape ecology and complex network theory. Combining pattern analysis methods to analyze the network, we obtained the spatial and temporal trends of forest and grass spatial distribution patterns from 2000 to 2100, and explored the relationship between the topological properties of source patches and ecosystem services in different patterns. It was found that there are four basic patterns of spatial distribution of forest and grass in the Mongolian Plateau. The Core-Linked Ring pattern accounts for 40.74 % and exhibits the highest stability. Under the SSP5-RCP8.5 scenario, source patches are reduced by 22.76 % in 2100. Topological indicators of source patches showed significant correlations with ecosystem services. For example, the CUE of grassland patches in the Centralized Star pattern was positively correlated with betweeness centrality. The most significant improvement in WUE after optimization is 19.90 % compared to pre-optimization. The conclusion of the study shows that the spatial distribution pattern of vegetation can be used to enhance the stability of ecological spatial network and improve ecosystem services at a larger scale. It can provide a certain reference for the study of spatial patterns of vegetation distribution in arid and semi-arid areas.

Combining blood pressure variability and heart rate variability to analyze the autonomic nervous function of rotenone induced Parkinson's rat model.

BACKGROUND: Parkinson's patients have significant autonomic dysfunction, early detect the disorder is a major challenge. To assess the autonomic function in the rat model of rotenone induced Parkinson's disease (PD), Blood pressure and ECG signal acquisition are very important. NEW METHOD: We used telemetry to record the electrocardiogram and blood pressure signals from awake rats, with linear and nonlinear analysis techniques calculate the heart rate variability (HRV) and blood pressure variability (BPV). we applied nonlinear analysis methods like sample entropy and detrended fluctuation analysis to analyze blood pressure signals. Particularly, this is the first attempt to apply nonlinear analysis to the blood pressure evaluate in rotenone induced PD model rat. RESULTS: HRV in the time and frequency domains indicated sympathetic-parasympathetic imbalance in PD model rats. Linear BPV analysis didn't reflect changes in vascular function and blood pressure regulation in PD model rats. Nonlinear analysis revealed differences in BPV, with lower sample entropy results and increased detrended fluctuation analysis results in the PD group rats. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: our experiments demonstrate the ability to evaluate autonomic dysfunction in models of Parkinson's disease by combining the analysis of BPV with HRV, consistent with autonomic impairment in PD patients. Nonlinear analysis by blood pressure signal may help in early detection of the PD. It indicates that the fluctuation of blood pressure in the rats in the rotenone model group tends to be regular and predictable, contributes to understand the PD pathophysiological mechanisms and to find strategies for early diagnosis.

Preparation of Ultra-High Temperature Resistant Cyclodextrin-Based Filtration Loss Reducer for Water-Based Drilling Fluids.

In the development of ultra-deep wells, extremely high temperatures can lead to inefficiency of additives in drilling fluids. Hence, there is a need to prepare additives with a simple preparation process and good effects at ultra-high temperatures to ensure stable drilling fluid performance. In this study, a high temperature resistant filtration loss polymer (LY-2) was prepared using γ-methacryloyloxypropyltrimethoxysilane (KH570), N,N-dimethylallyl ammonium chloride (DMDAAC), sodium p-styrenesulfonate (SSS), and ß-cyclodextrin (ß-CD). The impact of the different monomer ratios on particle size, rheology, and filtration performance was systematically investigated. Infrared spectroscopy afforded the structural features. Thermogravimetric Analysis detected the temperature stability, and scanning electron microscopy characterized the polymer micromorphology. LY-2 was completely decomposed at a temperature above 600 °C. Experiments showed FLAPI of the drilling fluid containing 3% LY-2 aged at 260 °C/16 h was only 5.1 mL, which is 85.4% lower compared to the base fluid. This is attributed to the synergistic effect of the polymer adsorption through chemical action at high temperatures and the blocking effect of carbon nanoparticles on the filter cake released by cyclodextrin carbonization at high temperatures. Comparing LY-2 with commercial filter loss reducers shows that LY-2 has excellent temperature resistance, which exhibited five times higher filtration performance and relatively low cost, making it possible to be applied to ultra-high temperature drilling operations in an industrial scale-up.

Heme pocket modulates protein conformation and diguanylate cyclase activity of a tetrameric globin coupled sensor.

Bacteria use the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) to control biofilm formation and other key phenotypes in response to environmental signals. Changes in oxygen levels can alter c-di-GMP signaling through a family of proteins termed globin coupled sensors (GCS) that contain diguanylate cyclase domains. Previous studies have found that GCS diguanylate cyclase activity is controlled by ligand binding to the heme within the globin domain, with oxygen binding resulting in the greatest increase in catalytic activity. Herein, we present evidence that heme-edge residues control O2-dependent signaling in PccGCS, a GCS protein from Pectobacterium carotovorum, by modulating heme distortion. Using enzyme kinetics, resonance Raman spectroscopy, small angle X-ray scattering, and multi-wavelength analytical ultracentrifugation, we have developed an integrated model of the full-length PccGCS tetramer and have identified conformational changes associated with ligand binding, heme conformation, and cyclase activity. Taken together, these studies provide new insights into the mechanism by which O2 binding modulates activity of diguanylate cyclase-containing GCS proteins.

Biomimetic NO Scavenging Hyaluronic Acid Nanoparticles Enable Targeted Delivery of MTX and Integrated Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage, and bone damage. In the RA microenvironment, RA-involved cells, overproduced nitric oxide (NO), and pro-inflammatory cytokines are highly interplayed and mutually reinforced, which form a vicious circle and play crucial roles in the formation and progression of RA. To comprehensively break the vicious circle and obtain the maximum benefits, we have developed neutrophil membrane-camouflaged NO scavenging nanoparticles based on an NO-responsive hyaluronic acid derivative for delivery of MTX. These multifunctional nanoparticles (NNO-NPs/MTX), by inheriting the membrane functions of the source cells, possess prolonged circulation and specific localization at the inflamed sites when administrated in the body. Remarkably, NNO-NPs/MTX can neutralize the pro-inflammatory cytokines via the outer membrane receptors, scavenge NO, and be responsively disassociated to release MTX for RA-involved cell regulation and HA for lubrication in the RA sites. In a collagen-induced arthritis mouse model, NNO-NPs/MTX exhibits a significant anti-inflammation effect and effectively alleviates the characteristic RA symptoms such as synovial hyperplasia and cartilage destruction, realizing the synergistic and boosted therapeutic outcome against intractable RA. Thus, NNO-NPs/MTX provides a promising and potent platform to integrately treat RA.

Light-driven rGO/Cu2 + 1O tubular nanomotor with active targeted drug delivery for combination treatment of cancer cells.

The unprecedented navigation ability in micro/nanoscale and tailored functionality tunes micro/nanomotors as new target drug delivery systems, open up new horizons for biomedical applications. Herein, we designed a light-driven rGO/Cu2 + 1O tubular nanomotor for active targeting of cancer cells as a drug delivery system. The propulsion performance is greatly enhanced in real cell media (5% glucose cells isotonic solution), attributing to the introduction of oxygen vacancy and reduced graphene oxide (rGO) layer for separating photo-induced electron-hole pairs. The motion speed and direction can be readily modulated. Meanwhile, doxorubicin (DOX) can be loaded quickly on the rGO layer because of π-π bonding effect. The Cu2 + 1O matrix in the tiny robots not only serves as a photocatalyst to generate a chemical concentration gradient as the driving force but also acts as a nanomedicine to kill cancer cells as well. The strong propulsion of light-driven rGO/Cu2 + 1O nanomotors coupled with tiny size endow them with active transmembrane transport, assisting DOX and Cu2 + 1O breaking through the barrier of the cell membrane. Compared with non-powered nanocarrier and free DOX, light-propelled rGO/Cu2 + 1O nanomotors exhibit greater transmembrane transport efficiency and significant therapeutic efficacy. This proof-of-concept nanomotor design presents an innovative approach against tumor, enlarging the list of biomedical applications of light-driven micro/nanomotors to the superficial tissue treatment.

Impact of Topical 0.05% Cyclosporine A Eye Drops on Post-Femtosecond-Assisted Laser In Situ Keratomileusis Ocular Surface Recovery: A Randomized Clinical Trial.

OBJECTIVES: To investigate the effect of topical 0.05% cyclosporine A (CsA) eye drops as an adjunct to conventional therapy in maintaining post-femtosecond-assisted laser in situ keratomileusis (FS-LASIK) ocular surface stability. METHODS: Sixty-six patients (eyes) undergoing FS-LASIK were randomized into 2 groups: 33 patients (eyes) in group I (conventional treatment group) and 33 patients (eyes) in group II (CsA group). Conventional treatments include topical levofloxacin, fluorometholone, and artificial tears. Group II received topical 0.05% CsA eye drops twice daily for three months in addition to conventional treatment. Ocular Surface Disease Index (OSDI), numerical rating scale (NRS), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), conjunctival lissamine green (LG) staining, corneal sensitivity, and corneal nerve morphology were measured. In addition, tear inflammatory cytokine levels were measured using the Luminex assay. Follow-up was performed preoperatively and 1 and 3 months postoperatively. RESULTS: In the CsA group, OSDI, TBUT, LG, corneal sensitivity, and corneal nerve fiber total branch density recovered better than in the conventional treatment group. As for tear inflammatory cytokines, interferon (INF) -γ, interleukin (IL)-10, and IL-6 levels were significantly higher in the conventional treatment group as compared with the CsA group. In addition, no significant differences in NRS, SIt, and CFS scores were observed between the two groups. CONCLUSION: In conclusion, 0.05% CsA eye drops is a useful adjunct to conventional treatment for restoring the ocular surface stability after corneal refractive surgery and is more potent in sustaining anti-inflammatory effects.

Enhancing the usability of pea protein in emulsion applications through modification by various approaches: A comparative study.

The extensive utilization in food industry of pea protein is often impeded by its low water solubility, resulting in poor functional properties. Various methods, including pH-shifting (PS), ultrasonication (US), high-pressure micro-fluidization (MF), pH-shifting combined with ultrasonication (PS-US), and pH-shifting with micro-fluidization (PS-MF), were utilized to modify pea protein isolate (PPI) in order to enhance its functionality in emulsion formulation. The physicochemical properties and structural changes of the protein were investigated by assessing solubility, particle size, surface charge, protein profile, surface hydrophobicity, free sulfhydryl groups, and secondary structure content. The extent of modification induced by each treatment method on PPI-stabilized emulsions was compared based on parameters such as adsorbed interfacial protein concentration, particle size, zeta potential, and microstructure of the prepared emulsions. All modification increased the solubility of pea protein in the sequence of PS (4-fold) < MF (7-fold) < US (11-fold) < PS-US (13-fold) < PS-MF (14-fold). For single treatments, proteins dissolved more readily under US, resulting in the most uniform emulsions with small particle. The combined processes of PS-US and PS-MF further improved solubility, decreased emulsions particle size, promoted uniformity of emulsions. PS-US-stabilized emulsions displayed more smaller droplet size, narrower size distribution, and slightly higher stability than those prepared by PS-MF. The relatively higher emulsifying capacity of PPI treated by PS-US than those by PS-MF may be attributed to its higher surface hydrophobicity.

Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: A systematic review and Meta-analysis.

BACKGROUND: The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC. METHODS: Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes we focus on. RESULTS: This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=-0.33; P=0.002 and SMD=-0.59; P<0.001, respectively) and a statistically significant ß-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that 4 genera were significantly increased in PDAC patients compared to HC (e.g., Escherichia-Shigella and Veillonella). CP patients had an increase in 4 genera (e.g., Escherichia-Shigella and Klebsiella) and a decrease in 8 genera (e.g., Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients. CONCLUSIONS: Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.

Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion.

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.

Tandem Four-Component Reaction to Access Fused Polycycles Exhibiting Aggregation-Enhanced Through-Space Charge Transfer Emission.

Rapid construction of new fluorescence emitters is essential in advancing synthetic luminescent materials. This study illustrated a piperidine-promoted reaction of chiral dialdehyde with benzoylacetonitrile and malonitrile, leading to the formation of the 6/6/7 fused cyclic product in good yield. The proposed reaction mechanism involves a dual condensation/cyclization process, achieving the formation of up to six bonds for fused polycycles. The single crystal structure analysis revealed that the fused cyclic skeleton contains face-to-face naphthyl and cyanoalkenyl motifs, which act as the electronic donor and acceptor, respectively, potentially resulting in through-space charge transfer (TSCT) emission. While the TSCT emissions were weak in solution, a notable increase in luminescence intensity was observed upon aggregation, indicating bright fluorescent light. A series of theoretical analyses further supported the possibility of spatial electronic communication based on frontier molecular orbitals, the distance of charge transfer, and reduced density gradient analysis. This work not only provides guidance for the one-step synthesis of complex polycycles, but also offers valuable insights into the design of aggregation-enhanced TSCT emission materials.

Environmental taxes, technological innovation and firm performance: Evidence from China's manufacturing firms.

Based on panel data from 2011 to 2019 for heavily polluting listed firms in the manufacturing industry, this paper examines the impact of environmental taxes on technological innovation and firm performance using the propensity score matching (PSM) and differences-in-differences (DID) methods. The empirical results show the following: (i) Firm performance and innovation quantity are positively affected by environmental taxes. The average effects of environmental taxes on firm performance and innovation quantity are 1.28 and 0.219, respectively. However, environmental taxes have no significant impact on innovation quality. (ii) A mechanism analysis reveals that innovation quantity plays a significant partial mediating role in the positive effect of environmental taxes on firm performance. (iii) Heterogeneity analysis shows that different environmental tax rates lead to a variation in innovation quantity and firm performance across regions. The positive effect of environmental taxes on innovation quantity is only confirmed in high-tax and low-tax areas. Meanwhile, high environmental taxes are related to better firm performance. Based on the research, policy recommendations are put forward to optimise environmental taxes, such as improving the environmental tax system and coordinating environmental tax and innovation policies.

Gender differences in plasma S100B levels of patients with major depressive disorder.

BACKGROUND: Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders. METHODS: We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov-Smirnov test was used to test the normality of six groups of S100B samples. The Mann-Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis. RESULTS: All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation. CONCLUSIONS: In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells.

Distribution, migration patterns, and food chain human health risks of endocrine-disrupting chemicals in water, sediments, and fish in the Xiangjiang River.

Exposure to endocrine-disrupting chemicals (EDCs) in freshwater systems has garnered increasing attention. A comprehensive analysis of the migration patterns, bioaccumulation, and consumer health risk of EDCs along the Xiangjiang River due to fish consumption from the river ecosystem was provided. Twenty natural and synthetic target EDCs were detected and analyzed from the water, sediments, and fish samples collected along the Xiangjiang River. There were significant correlations between the EDC concentrations in fish and the sediments. This revealed that EDCs in sediments play a dominant role in the uptake of EDCs by fish. The bioaccumulation factor and biota-sediment accumulation factor were calculated, with the highest values observed for nonylphenol. Pearson's correlation analysis showed that bisphenol A is the most reliable biological indicator of EDC contamination in fish. Furthermore, based on the threshold of toxicological concerns and the health risk with dietary intake, crucian carp and catfish from the Xiangjiang River pose a certain risk for children and pregnant women compared to grass carp. The Monte Carlo simulation results indicated a certain risk of cumulative ∑EDC exposure for local residents due to fish consumption.

Adaptive Metabolic Responses Facilitate Blood-Brain Barrier Repair in Ischemic Stroke via BHB-Mediated Epigenetic Modification of ZO-1 Expression.

Adaptive metabolic responses and innate metabolites hold promising therapeutic potential for stroke, while targeted interventions require a thorough understanding of underlying mechanisms. Adiposity is a noted modifiable metabolic risk factor for stroke, and recent research suggests that it benefits neurological rehabilitation. During the early phase of experimental stroke, the lipidomic results showed that fat depots underwent pronounced lipolysis and released fatty acids (FAs) that feed into consequent hepatic FA oxidation and ketogenesis. Systemic supplementation with the predominant ketone beta-hydroxybutyrate (BHB) is found to exert discernible effects on preserving blood-brain barrier (BBB) integrity and facilitating neuroinflammation resolution. Meanwhile, blocking FAO-ketogenesis processes by administration of CPT1α antagonist or shRNA targeting HMGCS2 exacerbated endothelial damage and aggravated stroke severity, whereas BHB supplementation blunted these injuries. Mechanistically, it is unveiled that BHB infusion is taken up by monocarboxylic acid transporter 1 (MCT1) specifically expressed in cerebral endothelium and upregulated the expression of tight junction protein ZO-1 by enhancing local ß-hydroxybutyrylation of H3K9 at the promoter of TJP1 gene. Conclusively, an adaptive metabolic mechanism is elucidated by which acute lipolysis stimulates FAO-ketogenesis processes to restore BBB integrity after stroke. Ketogenesis functions as an early metabolic responder to restrain stroke progression, providing novel prospectives for clinical translation.