Inhibition of the cGAS-STING pathway: contributing to the treatment of cerebral ischemia-reperfusion injury.

The cGAS-STING pathway plays an important role in ischemia-reperfusion injury in the heart, liver, brain, and kidney, but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed. Here, we outline the components of the cGAS-STING pathway and then analyze its role in autophagy, ferroptosis, cellular pyroptosis, disequilibrium of calcium homeostasis, inflammatory responses, disruption of the blood-brain barrier, microglia transformation, and complement system activation following cerebral ischemia-reperfusion injury. We further analyze the value of cGAS-STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms. Inhibition of the cGAS-STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.

The Synthesis of Needle-Like Monocrystalline Diamonds with a High Aspect Ratio up to 14.

Diamond exhibits nontrivial hardness and abrasion, ultra-high thermal conductivity, and light transmission over a wide wavelength range. All these properties are anisotropic. There is considerable literature on the synthesis of large-sized monocrystalline diamonds but the synthesis of highly oriented monocrystalline diamonds is limited. Here, [100] oriented monocrystalline needle-like diamonds are successfully synthesized with an aspect ratio of up to 14 by controlling the temperature gradient and carbon concentration gradient using FeCo alloy as the catalyst at ≈5.8 GPa and 1473 K. The distinctive morphology and microstructure of needle-like diamonds are characterized using Scanning Electron Microscopy, X-ray diffraction, and Focused Ion Beam-Transmission Electron Microscopy. A four-stage growth model is established to elucidate the growth mechanism along the [100], which sheds light on the synthesis of diamonds with predetermines crystal orientations. Increasing the aspect ratio of needle-like diamonds further may enable the development of diamond fibers and assist in the fabrication of laser diamonds with specific orientation requirements.

Mechano-triggered eradication of dentinal tubule biofilm via in situ generation of nanoscale sonosensitizer by the tailored irrigation formulation.

The efficient elimination of bacteria within the dentinal tubules has been hindered by the poor deposition and short residence of disinfecting agents. Meanwhile, the current irrigant (e.g., NaClO, 5.25 %) shows severe adverse effects on the surrounding soft tissues because of its inherent high irritancy. To address this issue, this work reports an in situ generated sonosensitizer to handle the biofilm in dentinal tubules with minimal adverse effects. The production of nanoscale sonosensitizer involves the concurrent delivery of H2O2 (0.01 %), ferrocene derivative (Fc), and indocyanine green (ICG). With ultrasound treatment, the reaction between H2O2 and Fc liberated Fe3+ that was further complexed with ICG to generate the nanoscale sonosensitizer in situ, followed by singlet oxygen production for potent disinfecting action. Because the above cascade reactions occur within the confined dentinal tubules, the generated ICG-Fe3+ nanosensitizer would show prolonged retention therein. The anti-bacterial potency of nanosensitizer was demonstrated in petrodish and ex vivo biofilm models. Meanwhile, the transmission electron microscope imaging of biofilm and cytotoxicity assay in L929 fibroblast cells proved the superiority of nanosensitizer against NaClO regarding adverse effects. The current work opens new avenues of biofilm elimination in dentinal tubules, showing a high translation potential.

Global, regional, and national epidemiology of ischemic stroke from 1990 to 2021.

BACKGROUND AND PURPOSE: This study aims to examine the global, regional, and national burden of ischemic stroke from 1990 to 2021. METHOD: We used data from the Global Burden of Disease (GBD) 2021 database to comprehensively assess ischemic stroke indicators globally, regionally, and in 204 countries, including incidence, deaths, disability-adjusted life years (DALYs), estimated annual percentage change (EAPC), and Joinpoint regression analysis. RESULTS: In 2021, there were a total of 7,804,449 cases of ischemic stroke globally (95% uncertainty interval = 6,719,760-8,943,692), with an age-standardized incidence rate (ASIR) of 92.39. This represents a declining trend compared to 1990, with an EAPC of -0.67 (95% confidence interval [CI] = -0.76 to -0.58). Mortality and DALY rates also showed a downward trend (EAPC in age-standardized mortality rate: -1.83, 95% CI = -1.92 to -1.74; EAPC in age-standardized DALY rate = -1.59, 95% CI = -1.68 to -1.50). The burden of ischemic stroke was inversely correlated with gross domestic product. Regionally, from 2014 to 2021, the Caribbean experienced the fastest increase in ASIR (annual percent change = 0.15, 95% CI = 0.13 to 0.18). Among 204 countries, North Macedonia had the highest incidence, mortality, and DALY rates. In addition to metabolic risks, particulate matter pollution and low temperatures were significant environmental and occupational risk factors for ischemic stroke. Smoking and a diet high in sodium were identified as key behavioral risk factors. CONCLUSIONS: Ischemic stroke remains a serious global health challenge, and our results from this cross-sectional study suggest that the burden of disease remains high in Eastern Europe, East Asia, Central Asia, and Sub-Saharan Africa.

Metabolic labeling of peptidoglycan enabled optical analysis of probiotic vitality.

The growing awareness of the health benefits associated with probiotics has led to an increasing interest in probiotic products. To develop probiotic functional foods that deliver health benefits, it is essential to characterize both probiotic viability (the ability to survive) and vitality (the ability to remain active and effective). However, traditional probiotic assays only provide limited information about their survival state. To gain a comprehensive understanding of probiotic states, a D-amino-acid-based metabolic labeling strategy was applied to quantitatively depict probiotic vitality. In this approach, probiotics were first metabolically incorporated with azido-modified D-lysine and then labeled with dibenzocyclooctyne-sulfo-Cy5 through click chemistry. This two-step labeling process provides a visual representation of the metabolic levels of probiotics as well as the bacterial membrane integrity. Besides, this method is capable of characterizing the influence of various environmental conditions, from manufacturing to oral administration, on probiotic vitality. With its rapid detection process and general applicability, this strategy has the potential to be widely implemented in the food industry for probiotic vitality evaluation.

Combining No-Tillage with Hairy Vetch Return Improves Production and Nitrogen Utilization in Silage Maize.

The combination of no-till farming and green manure is key to nourishing the soil and increasing crop yields. However, it remains unclear how to enhance the efficiency of green manure under no-till conditions. We conducted a two-factor field trial of silage maize rotated with hairy vetch to test the effects of tillage methods and returning. Factor 1 is the type of tillage, which is divided into conventional ploughing and no-tillage; factor 2 is the different ways of returning hairy vetch as green manure, which were also compared: no return (NM), stubble return (H), mulching (HM), turnover (HR, for CT only), and live coverage (LM, for NT only). Our findings indicate that different methods of returning hairy vetch to the field will improve maize yield and quality. The best results were obtained in CT and NT in HM and LM, respectively. Specifically, HM resulted in the highest dry matter quality and yield, with improvements of 35.4% and 31.9% over NM under CT, respectively. It also demonstrated the best economic and net energy performance. However, other treatments had no significant effect on the beneficial utilization and return of nutrients. The LM improved yields under NT by boosting soil enzyme activity, promoting nitrogen transformation and accumulation, and increasing nitrogen use efficiency for better kernel development. Overall, NTLM is best at utilizing and distributing soil nutrients and increasing silage maize yield. This finding supports the eco-efficient cultivation approach in silage maize production in the region.

1,25-D3 ameliorates ischemic brain injury by alleviating endoplasmic reticulum stress and ferroptosis: Involvement of vitamin D receptor and p53 signaling.

Endoplasmic reticulum stress (ERS) and ferroptosis are linked to cerebral ischemia reperfusion injury (CIRI). The neuroprotective properties of 1α, 25-dihydroxyvitamin D3 (VitD3 or 1,25-D3) have been well established; however, the mechanism by which VitD3 treats CIRI through ERS and ferroptosis has not been examined. Hence, we developed middle cerebral artery occlusion/reperfusion (MCAO/R) model in SD rats to ascertain if VitD3 preconditioning mediates ERS and ferroptosis involving of p53 signaling. In this study, we observed that VitD3 can reduce infarction volume and cerebral edema, which leads to the improvement of nerve function. HE, Nissl and Tunel staining showed that VitD3 treatment significantly improved the morphology of neuronal cells and reduced their death. The expression and activation of Vitamin D receptor (VDR), PKR-like ER kinase (PERK), C/EBP-homologous protein (CHOP), p53, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and reactive oxygen species (ROS) in the ischemic penumbral area were detected by real-time qPCR, Western-blotting and Elisa. The results showed that after VitD3 treatment, VDR increased, ERS-related indices (PERK, CHOP) significantly decreased and ferroptosis-related indices (Nrf2, GPX4) increased. As a VDRs antagonist, pyridoxal-5-phosphate (P5P) can partially block the neuroprotective effects of VitD3. Therefore, CIRI can induce ERS and ferroptosis in the ischemic penumbra area and VitD3 may ameliorate nerve damage in CIRI rats by up-regulating VDR, alleviating p53-associated ERS and ferroptosis.

Association of oxidative balance score with epilepsy and moderate to severe depression: Insights from the NHANES study.

BACKGROUND: Depression is a significant public health issue, closely associated with epilepsy and oxidative stress (OS). This study aims to explore the level of OS in patients with epilepsy and its relationship with moderate to severe depression (MSD). METHODS: This cross-sectional study includes 10,819 participants aged 20-80 from the National Health and Nutrition Examination Survey (NHANES) database (2013-2020 pre-pandemic). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and epilepsy was diagnosed based on antiepileptic drug use in the past 30 days. The oxidative balance score (OBS) was calculated from dietary recall and lifestyle habits over the previous 24 h. RESULTS: Compared to non-epileptic subjects, epileptic patients have a significantly higher prevalence of depression. Epileptic patients exhibit lower OBS and Dietary Oxidative Balance Scores (DOBS), while there is no significant difference in Lifestyle Oxidative Balance Scores (LOBS). Depressed patients show lower OBS, DOBS, and LOBS. The mediation model indicates that DOBS mediates 3.44 % of epilepsy-related MSD. CONCLUSIONS: Epileptic patients exhibit significantly higher levels of OS and consume more pro-oxidant foods compared to the general population. However, their lifestyle habits do not differ significantly from those of the control group. Additionally, epileptic patients are at a higher risk of developing MSD. Although a pro-oxidant diet may be associated with epilepsy-mediated MSD, its mediating effect is relatively weak.

Treatment of Atrophic Acne Scarring with Fractional Microplasma Radiofrequency: A Multicentric Experience.

Background: Atrophic scarring is a severe form-disfiguring sequela of acne, which can lead to negative effect on patients' life. Fractional microplasma radiofrequency (RF) has emerged as a promising modality, leveraging dermal fibroblast remodeling to enhance aesthetic results for scars and hyperpigmentation. This study evaluates the efficacy and safety of high-power fractional microplasma RF for atrophic acne scars, considering patient tolerance to procedural discomfort. Methods: In this prospective study, 95 Chinese patients with atrophic facial acne scars underwent three sessions of fractional microplasma RF treatment, with assessments at 1, 3, and 6 months post-treatment. Patients were categorized based on treatment power: Group A (50-70 W) and Group B (70-85 W). Efficacy was determined by three independent dermatologists using digital photographs and Echelle d'Evaluation Clinique des Cicatrices d'Acné (ECCA) scores, and patient-reported outcomes gauged satisfaction levels. Results: Eighty-six patients completed the study. Significant improvements were observed, with a reduction in ECCA scores from 107.21 to 42.27 (P<0.05), demonstrating notable scar amelioration across both groups, albeit with a superior outcome in Group B. All patients experienced transient side effects such as pain, erythema, and edema, deemed tolerable with no long-term adverse effects reported. The treatment was well-received, with high satisfaction rates, underscoring its efficacy and acceptable safety profile. Conclusion: Fractional microplasma RF therapy, particularly at higher power settings, is an effective and safe option for treating atrophic acne scars, offering significant aesthetic improvement with manageable discomfort. This modality presents a valuable addition to acne scar management strategies, especially for patients with darker skin tones seeking minimal downtime and reduced risk of hyperpigmentation.

Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy. METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy. RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 âˆ¼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy. CONCLUSION: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.

Exploration of the causal associations between circulating inflammatory proteins, immune cells, and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study and mediation analysis.

Background: An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells. Results: A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators. Conclusion: Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors.

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 µg/mL that was superior to that of the agricultural fungicide boscalid (2.2 µg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 µM that was superior to that of boscalid (7.9 µM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.

[Analysis of rare mutations associated with Thalassemia and their hematological characteristics in Chenzhou region of Hunan Province].

OBJECTIVE: To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention. METHODS: A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing. RESULTS: A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-I-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+(Aγδß)0 had typical microcytic hypochromic and ß-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50（G>A）heterozygotes of ß-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2. CONCLUSION: Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

Densification and Surface Carbon Transformation of Diamond Powders under High Pressure and High Temperature.

A new type of poly-diamond plate without a catalyst was produced via the high-pressure high-temperature (HPHT) compression of diamond powders. The densification of diamond powders and sp3 to sp2 carbon on the surface under HPHT compression was investigated through the characterization of the microstructure, Raman spectroscopy analysis and electrical resistance measurement. The densification and sp3-sp2 transformation on the surface are mainly affected by the pressure, temperature and particle size. The quantitative analysis of the diamond sp3 and sp2 carbon amount was performed through the peak fitting of Raman spectra. It was found that finer diamond particles under a higher temperature and a lower pressure tend to produce more sp2 carbon; otherwise, they produce less. In addition, it is interesting to note that the local residual stresses measured using Raman spectra increase with the diamond particle size. The suspected reason is that the increased particle size reduces the number of contact points, resulting in a higher localized pressure at each contact point. The hypothesis was supported by finite element calculation. This study provides detailed and quantitative data about the densification of diamond powders and sp3 to sp2 transformation on the surface under HPHT treatment, which is valuable for the sintering of polycrystalline diamonds (PCDs) and the HPHT treatment of diamonds.

Design, synthesis and herbicidal activity of novel cyclohexanedione derivations containing pyrazole and pyridine groups as potential HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

Assessing tobacco-related ischemic stroke in Pakistan (1990-2019): Insights from the Global Burden of Disease Study.

INTRODUCTION: This study analyzes the impact of active smoking and secondhand smoke on the ischemic stroke burden of Pakistan, 1990-2019. METHODS: We used data from the Global Burden of Disease (GBD) database to conduct a comprehensive evaluation of ischemic stroke-related indicators in Pakistan, including the number of deaths, mortality rates, disability-adjusted life years (DALYs), DALY rates, and the estimated annual percentage change (EAPC). Joinpoint analysis was applied to assess sex-specific temporal trends in the burden of active smoking and secondhand smoke in Pakistan and regions of Pakistan. These assessments incorporated the Socio-Demographic Index (SDI) and we have made comparative analyses of epidemiological differences between active smoking and secondhand smoke exposure. RESULTS: The burden of ischemic stroke related to tobacco use is presented in terms of the age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) per 100000 population. The results (ASMR/ASDR) for Pakistan were 6.04/130.81, in the middle SDI region 7.69/176.54, and low-middle SDI region 5.64/124.22. Pakistan's ASMR is higher than the global average of 5.85, while ASDR is lower than the global average of 140.23. From 1990 to 2019, a downward trend in both ASMR and ASDR was observed, indicating progress in controlling tobacco-related stroke burdens. Individuals aged ≥70 years experienced the highest rates of stroke (ASMR: 66.31; ASDR: 1091.20). Gender disparities were evident: men were more affected by active smoking (ASMR: 3.08; ASDR: 78.47) than women (ASMR: 0.79; ASDR: 20.76), while women faced a higher burden from secondhand smoke (ASMR: 0.66; ASDR: 16.33) compared to men (ASMR: 0.79; ASDR: 9.93). Regional differences within Pakistan show fluctuating death and DALY rates. Notably, an increasing trend in female ASDR due to secondhand smoke in the Khyber Pakhtunkhwa Region (annual percentage change, APC=0.17 from 2010 to 2019) calls for focused health interventions. CONCLUSIONS: The study finds ASMR for tobacco-related ischemic stroke in Pakistan exceeds global averages, with significant gender and age disparities in exposure to smoke, highlighting the need for targeted health interventions.

Influence of the brain­gut axis on neuroinflammation in cerebral ischemia­reperfusion injury (Review).

Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut­brain­microbiota axis (GBMA) and cerebral ischemia­reperfusion has increasingly become a focal point of scientific exploration, emerging as a pivotal research avenue in stroke pathophysiology. In the present review, the authors delved into the nexus between the GBMA and neuroinflammation observed post­stroke. The analysis underscored the pivotal roles of histone deacetylase 3 and neutrophil extracellular traps subsequent to stroke incidents. The influence of gut microbial compositions and their metabolites, notably short­chain fatty acids and trimethylamine N­oxide, on neuroinflammatory processes, was further elucidated. The involvement of immune cells, especially regulatory T­cells, and the intricate signaling cascades including cyclic GMP­AMP synthase/stimulator of interferon genes/Toll­like receptor, further emphasized the complex regulatory mechanisms of GBMA in cerebral ischemia/reperfusion injury (CI/RI). Collectively, the present review offered a comprehensive perspective on the metabolic, immune and inflammatory modulations orchestrated by GBMA, augmenting the understanding of its role in neuroinflammation following CI/RI.

Genetic insights into the relationship between immune cell characteristics and ischemic stroke: A bidirectional Mendelian randomization study.

BACKGROUND AND PURPOSE: Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk. METHODS: By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk. RESULTS: Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T-cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87-0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90-0.97; p < 0.001), show notable neuroprotection against ischemic stroke. CONCLUSION: This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune-targeted therapies for stroke prevention and management.

Exploring causal correlations between systemic inflammatory cytokines and epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Inflammation plays a role in the development and advancement of epilepsy, but the relationship between inflammatory cytokines and epilepsy is still not well understood. Herein, we use two-sample Mendelian randomization (MR) to examine the causal association between systemic inflammatory cytokines and epilepsy. METHODS: We conducted a bidirectional two-sample MR analysis based on genome-wide association study data of 41 serum cytokines from 8293 Finnish individuals with various epilepsy subtypes from the International League against Epilepsy Consortium. RESULTS: Our study showed that three inflammatory cytokines were associated with epilepsy, five were associated with generalized epilepsy, four were associated with focal epilepsy, one was associated with focal epilepsy-documented lesion negative, three were associated with juvenile absence epilepsy, one was associated with childhood absence epilepsy, two were associated with focal epilepsy-documented lesion other than hippocampal sclerosis, and two were associated with juvenile myoclonic epilepsy. Furthermore, the expression of systemic inflammatory cytokines was unaffected by genetically predicted epilepsy. CONCLUSION: This study suggested that several inflammatory cytokines are probably the factors correlated with epilepsy. Additional research is required to ascertain if these biomarkers have therapeutic potential to prevent or manage epilepsy.

A Bio-Inspired Free-Standing Film with Versatility: From Heterogeneous CTCs Programed Isolating to Breast Cancer Molecular Typing.

Developing a robust strategy for profiling heterogeneous circular tumor cells specifically, distinguishing the phenotypes of which in blood sample of cancer patient precisely, and releasing them sequentially, is significant for cancer management by liquid biopsy. Herein, a bio-inspired free-standing and flexible film composed of TiO2 nanotube and silk fibroin, fabricated with multiply dynamic bioactive surface (TSF/MDBS) by a simple and eco-friendly way including using polydopamine chemistry and dual dynamic covalent chemistry, is reported. The as-prepared TSF/MDBS binds specific peptides toward cells with epithelial biomarker and human epithelial growth factor receptor 2 (HER2) biomarker, and antifouling agents bovine serum albumin for obviating platelets and proteins adhering of blood, can capture heterogeneous CTCs with enhanced capability due to the cytocompatible soft film and exquisite surface design, and further release the captured cells as program, by specifically breaking down the covalent bonds in sequence via the action of adding biocompatible molecules fructose and glutathione. By applying the TSF/MDBS, it can be tailored into desired pieces for identifying CTCs with different phenotypes (HER2-high and HER2-low) from the unprocessed blood samples of breast cancer patients, and finally profiling these heterogeneous CTCs, to discriminate HER2 positive or negative of breast cancer patients in clinical applications.