Effects of Phaffia rhodozyma on microbial community dynamics and tobacco quality during tobacco fermentation.

Introduction: Carotenoids are important precursors of various aroma components in tobacco and play an important role in the sensory quality of tobacco. Phaffia rhodozyma is a species of Xanthophyllomyces capable of synthesizing a highly valuable carotenoid-astaxanthin, but has not yet been used in improving tobacco quality. Methods: The dynamic changes of microbial community and metabolites during tobacco fermentation were analyzed in combination with microbiome and metabolome, and the quality of tobacco after fermentation was evaluated by sensory scores. Results: P. rhodozyma could grow and produce carotenoids in tobacco extract, with a maximum biomass of 6.50 g/L and a maximum carotenoid production of 36.13 mg/L at 100 g/L tobacco extract. Meanwhile, the correlation analysis combined with microbiome and metabolomics showed that P. rhodozyma was significantly positively correlated with 11 metabolites such as 6-hydroxyluteolin and quercetin. Furthermore, the contents of alcohols, ketones and esters, which were important aromatic components in fermented tobacco, reached 77.57 µg/g, 58.28 µg/g and 73.51 µg/g, increasing 37.39%, 265.39% and 266.27% compared to the control group, respectively. Therefore, the aroma and flavor, and taste scores of fermented tobacco increased by 0.5 and 1.0 points respectively. Discussion: This study confirmed that P. rhodozyma fermentation could effectively improve the sensory evaluation of tobacco, and provided a novel microbial fermentation method to improve tobacco quality.

Comparative network analysis reveals the regulatory mechanism of 1-methylcyclopropene on sugar and acid metabolisms in yellow peach stored at non-chilling temperatures.

Soluble carbohydrates and organic acids are critical determinants of fruit flavor and consumer preference, both of which are susceptible to postharvest treatments and storage conditions. While the individual effectiveness of 1-methylcyclopropene (1-MCP) and non-chilling temperature storage in delaying fruit ripening and influencing flavor development has been established, their combined effects on peach storage traits remain unexplored. This study investigated the impact of 1-MCP combined with non-chilling temperature storage on the quality and flavor attributes of yellow peach. Our results revealed that 1-MCP treatment reduced ethylene production during storage and delayed ripening and softening by down-regulating ethylene biosynthesis and signaling genes. Transcriptomic analysis indicated that 1-MCP maintained higher levels of soluble carbohydrates by up-regulating sucrose phosphate synthase (PpSPS1/2) and sorbitol dehydrogenase (PpSDH1) while down-regulating hexokinase (PpHXK1). Concurrently, 1-MCP preserved citric and malic acid levels by suppressing aconitate hydratase (PpACO1) and inducing malate dehydrogenase (PpMDH1), thereby delaying flavor degradation. Co-expression network analysis implicated ethylene response factors (PpERFs) as major regulators of sugar and acid metabolisms genes, with PpERF19 potentially functioning as a key transcriptional controller. Overall, this study verified the efficacy of combined 1-MCP and non-chilling storage for yellow peach preservation, identified key 1-MCP-modulated genes involved in sugar and acid metabolisms, and provided insights into regulating peach flavor development via postharvest approaches.

In Situ Inorganic/Organic Protective Layer on Carbon Paper as Advanced Current Collector for Robust Li Metal Anode.

Lithium (Li) metal is regarded as the most promising anode for next-generation batteries with high energy density. However, the uncontrolled dendrite growth and infinite volume expansion during cycling seriously hinder the application of Li metal batteries (LMBs). Herein, an inorganic/organic protective layer (labeled as BPH), composed of in situ formed inorganic constituents and PVDF-HFP, is designed on the 3D carbon paper (CP) surface by hot-dipping method. The BPH layer can effectively improve the mechanical strength and ionic conductivity of the SEI layer, which is beneficial to expedite the Li-ion transfer of the entire framework and achieve stable Li plating/stripping behavior. As a result, the modified 3D CP (BPH-CP) exhibits an ultrahigh average Coulombic efficiency (CE) of ≈99.7% over 400 cycles. Further, the Li||LiFePO4 (LFP) cell exhibits an extremely long-term cycle life of over 3000 cycles at 5 C. Importantly, the full cell with high mass loading LiFePO4 (20 mg cm-2) or LiNi0.8Co0.1Mn0.1O2 (NCM, 16 mg cm-2) cathode exhibits stable cycling for 100 or 150 cycles at 0.5 C with high-capacity retention of 86.5% or 82.0% even at extremely low N/P ratio of 0.88 or 0.94. believe that this work enlightens a simple and effective strategy for the application of high-energy-density and high-rate-C LMBs.

Perturbation walking effects on prefrontal cortical activation and walking performance in older women with and without osteoarthritis: a FNIRS study.

Introduction: Perturbation walking (PW) has been shown to improve gait, however its effect on the cortical control of gait might provide insights on neural mechanisms underlying falls in adults with osteoarthritis. The objective of this study is to investigate the effect of PW on prefrontal cortical (PFC) activation in older women with (OA) and without osteoarthritis (HOA). We hypothesized that there would be an increase in PFC activation during PW relative to comfortable walking (CW) and higher increase in PFC activation during PW in HOA compared to OA. Methods: Twenty community-dwelling older women (66.7 ± 5.41 years old) walked on an instrumented treadmill that provided perturbations at pseudo-random intervals between 5-25 s using a counterbalanced design. Functional Near Infrared Spectroscopy was used to quantify PFC oxygenated hemoglobin (HbO2) and deoxyhemoglobin (Hb) levels, while standing prior to the task as a baseline. A linear mixed effects model was conducted to investigate the effects of cohort (HOA vs OA), task (PW vs CW), and their interaction on HbO2 (µM) and Hb (µM) levels. Results: HbO2 and Hb levels differed significantly between CW and PW tasks for both cohorts (P < 0.001) and demonstrated significant task by cohort interaction (P < 0.05). In addition, we found changes in walking performance (stride time, stride length, stride width and stance time) during and after PW. Spearman correlation demonstrated a strong association between increased stance time, increased body mass index and decreased PFC activation during PW. No other significant results were found. Discussion: This study found increase in PFC activation during PW and gait adaptation after a short bout of PW in HOA and OA. This increase in PFC activation was higher in HOA compared to OA, particularly during PW tasks, and was consistent with theory of limitations in mobility affecting neural activation in older adults. Further work remains to examine how pain, obesity, and mobility impacts cortical control in older adults with and without osteoarthritis.

Practical feature filter strategy to machine learning for small datasets in chemistry.

Many potential use cases for machine learning in chemistry and materials science suffer from small dataset sizes, which demands special care for the model design in order to deliver reliable predictions. Hence, feature selection as the key determinant for dataset design is essential here. We propose a practical and efficient feature filter strategy to determine the best input feature candidates. We illustrate this strategy for the prediction of adsorption energies based on a public dataset and sublimation enthalpies using an in-house training dataset. The input of adsorption energies reduces the feature space from 12 dimensions to two and still delivers accurate results. For the sublimation enthalpies, three input configurations are filtered from 14 possible configurations with different dimensions for further productive predictions as being most relevant by using our feature filter strategy. The best extreme gradient boosting regression model possesses a good performance and is evaluated from statistical and theoretical perspectives, reaching a level of accuracy comparable to density functional theory computations and allowing for physical interpretations of the predictions. Overall, the results indicate that the feature filter strategy can help interdisciplinary scientists without rich professional AI knowledge and limited computational resources to establish a reliable small training dataset first, which may make the final machine learning model training easier and more accurate, avoiding time-consuming hyperparameter explorations and improper feature selection.

Lifetime physical activity influences Parkinson's disease progression.

INTRODUCTION: Past studies suggested that Parkinson's disease (PD) patients who engage in physical activity (PA) after diagnosis have slower motor progression. Here, we examine the influence of lifetime PA prior to PD onset on motor, cognitive, and overall functional decline among PD patients. METHODS: For 495 participants in the Parkinson's Environment and Gene (PEG) studies, we collected PA-related measures through interviews and quantified these using metabolic equivalents (MET) scores. PD progression was defined as time to a Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) conversion to ≥ 35 points, Hoehn and Yahr (H&Y) ≥ 3, and a 4-point decline in Mini-Mental State Examination (MMSE). We used Cox frailty models to estimate hazard ratios and inverse probability weights to account for heterogeneity by enrollment wave and censoring. RESULTS: For PD patients reporting the highest lifetime strenuous MET-h/wk (highest quartile), we estimated a lower HR for time-to-UPDRS-III-conversion (Q4 vs. Q1: HR = 0.56, 95 % CI = [0.36, 0.87]). Additionally, having engaged in any competitive sport also reduced the risk of reaching a UPDRS-III ≥ 35 points (low vs. none: HR = 0.61, 95 % CI = [0.44, 0.86]; high vs. none: HR = 0.63; 95 % CI = [0.44,0.86]); high levels of sports activities also affected progression on the H&Y scale (high vs. none: HR = 0.73; 95 % CI = [0.46,1.00]). Lifetime PA measures did not affect time-to-MMSE decline. CONCLUSION: Our study suggests that PD patients who engaged in higher levels of lifetime strenuous PA and competitive sports prior to PD diagnosis experience slower motor and overall functional decline, suggesting that lifetime PA may contribute to a physical reserve advantageous for PD patients.

Palmatine as a potent immunomodulator: Enhancing resistance to Micropterus salmoides rhabdovirus in largemouth bass through innate immune activation and viral suppression.

Micropterus salmoides rhabdovirus (MSRV) poses a significant threat to aquaculture, causing substantial economic losses. In this study, we evaluated the antiviral efficacy and immunomodulatory potential of palmatine, a plant-derived monomer, against MSRV infection in largemouth bass. Our results demonstrated that palmatine significantly inhibited MSRV replication, with a reduction in viral nucleoprotein expression by 85 % at a safe concentration. Additionally, palmatine pre-treatment of EPC cells enhanced their antiviral capacity, with a maximum inhibition rate of 82 % following 24 h pre-incubation. Palmatine also effectively reduced MSRV-induced cytopathic effects, protecting cellular integrity and maintaining mitochondrial membrane potential. In vivo studies revealed that palmatine immersion at 80 mg/L was non-toxic and significantly suppressed MSRV replication in largemouth bass, increasing survival rates by 53 % over 15 d. Furthermore, palmatine pre-treatment enhanced the fish's resistance to MSRV, with a 78 % inhibition rate of viral replication and a 46 % increase in survival rate. Mechanistically, palmatine activated key immune genes, including IRF3, IRF7, and IFN, indicating its role in boosting innate immune responses. The compound also reduced horizontal transmission of MSRV in a cohabitation model, decreasing viral spread by up to 78 % over nine days. These findings highlight palmatine's potential as a small-molecule immunomodulator in aquaculture, offering a sustainable approach to disease management and enhancing fish health and welfare. Integrating palmatine into fish diets as an immunostimulant could provide a continuous, proactive defense against viral outbreaks, promoting more resilient and sustainable aquaculture practices.

Adaptor protein Src-homology 2 domain containing E (SH2E) deficiency induces heart defect in zebrafish.

Adaptor proteins play crucial roles in signal transduction across diverse signaling pathways. Src-homology 2 domain-containing E (SH2E) is the adaptor protein highly expressed in vascular endothelial cells and myocardium during zebrafish embryogenesis. In this study we investigated the function and mechanisms of SH2E in cardiogenesis. We first analyzed the spatiotemporal expression of SH2E and then constructed zebrafish lines with SH2E deficiency using the CRISPR-Cas9 system. We showed that homozygous mutants developed progressive pericardial edema (PCE), dilated atrium, abnormal atrioventricular looping and thickened atrioventricular wall from 3 days post fertilization (dpf) until death; inducible overexpression of SH2E was able to partially rescue the PCE phenotype. Using transcriptome sequencing analysis, we demonstrated that the MAPK/ERK and NF-κB signaling pathways might be involved in SH2E-deficiency-caused PCE. This study underscores the pivotal role of SH2E in cardiogenesis, and might help to identify innovative diagnostic techniques and therapeutic strategies for congenital heart disease.

[Application of modified grafted tubularized incised plate urethroplasty in hypospadias].

Objective: To investigate the clinical feasibility and effectiveness of the modified grafted tubularized incised plate urethroplasty (G-TIP), namely "glans G-TIP (GG-TIP) ", in treatment of hypospadias. Methods: A clinical data of 137 children with hypospadias qualified by the selection criteria between January 2021 and June 2023 was retrospectively analyzed. Among them, 75 children were treated with GG-TIP (GG-TIP group) and 62 with G-TIP (G-TIP group). There was no significant difference ( P>0.05) between the two groups in terms of age, hypospadias type, penile length, penile head width, penile head height, penile curvature, meatus-apex distance, urethral plate width, and distance from the distal endpoint of navicular groove to the dorsal or ventral midline point of the glans corona, and the difference between the two. The operation time, reconstructed urethral length, distance from meatus to ventral glans corona, postoperative complications, maximum urinary flow rate at 2 weeks after operation, and the hypospadias objective scoring evaluation (HOSE) score at 6 months after operation in the two groups were recorded and analyzed. Results: The operation time was significantly shorter in GG-TIP group than in G-TIP group ( P<0.05); but there was no significant difference ( P>0.05) between the two groups in terms of reconstructed urethral length and distance from meatus to ventral glans corona. All urinary meatus located at the tip of glans with vertical fissure shape. All children in the two groups were followed up 6-35 months (median, 26 months). During follow-up, there were 3 cases of urethral fistula, 2 cases of urethral stricture, and 1 case of glans separation in GG-TIP group, and 3, 3, and 1 cases in the G-TIP group, respectively. There was no significant difference in the incidence of complications between the two groups ( P>0.05). The maximum urinary flow rate at 2 weeks and the HOSE score at 6 months after operation were significantly higher in GG-TIP group than in G-TIP group ( P<0.05). Conclusion: GG-TIP is safe and effective for repairing hypospadias in children. Compared with G-TIP, it has the advantages of relatively simple operation, shortened operation time, significant improvement in urinary flow rate, and better cosmetic results.

Schisandrin A: A sustainable antiviral and immunomodulatory agent against spring viraemia of carp virus in aquaculture.

Spring viraemia of carp virus (SVCV) is a major threat to the aquaculture industry, causing severe economic losses and significantly impacting fish health. Despite this, no approved antiviral treatments are currently available for use in aquaculture, underscoring the urgent need for effective interventions. This study evaluated the antiviral and immunomodulatory potential of Schisandrin A (SA), a bioactive compound derived from the traditional Chinese medicinal herb Schisandra chinensis, against SVCV. Through a combination of in vitro and in vivo experiments, SA was found to significantly inhibit SVCV replication, lower the viral titer, and improve survival rates in infected juvenile carp. Mechanistically, SA enhanced the host's innate immune response, as demonstrated by the upregulation of key antiviral genes including interferon-alpha1 (ifna1), interferon-gamma (ifnγ), interferon-stimulated gene 15 (isg15), and myxovirus resistance 1 (mx1). Additionally, SA exhibited potent antioxidative properties, preserving mitochondrial integrity and reducing oxidative stress in SVCV-infected cells. These findings showed the dual role of SA in both directly suppressing viral replication and modulating the immune response, offering a multifaceted approach to managing SVCV infection. Given its low toxicity and biodegradability, SA emerges as a promising, sustainable antiviral agent for aquaculture. This study highlights the potential of SA to enhance biosecurity and promote sustainability in the industry, paving the way for the development of eco-friendly antivirals that could improve the management of viral diseases, ensuring healthier fish populations and greater economic stability.

Tai Chi Practice Buffers Aging Effects in Functional Brain Connectivity.

Tai Chi (TC) practice has been shown to improve both cognitive and physical function in older adults. However, the neural mechanisms underlying the benefits of TC remain unclear. Our primary aims are to explore whether distinct age-related and TC-practice-related relationships can be identified with respect to either temporal or spatial (within/between-network connectivity) differences. This cross-sectional study examined recurrent neural network dynamics, employing an adaptive, data-driven thresholding approach to source-localized resting-state EEG data in order to identify meaningful connections across time-varying graphs, using both temporal and spatial features derived from a hidden Markov model (HMM). Mann-Whitney U tests assessed between-group differences in temporal and spatial features by age and TC practice using either healthy younger adult controls (YACs, n = 15), healthy older adult controls (OACs, n = 15), or Tai Chi older adult practitioners (TCOAs, n = 15). Our results showed that aging is associated with decreased within-network and between-network functional connectivity (FC) across most brain networks. Conversely, TC practice appears to mitigate these age-related declines, showing increased FC within and between networks in older adults who practice TC compared to non-practicing older adults. These findings suggest that TC practice may abate age-related declines in neural network efficiency and stability, highlighting its potential as a non-pharmacological intervention for promoting healthy brain aging. This study furthers the triple-network model, showing that a balancing and reorientation of attention might be engaged not only through higher-order and top-down mechanisms (i.e., FPN/DAN) but also via the coupling of bottom-up, sensory-motor (i.e., SMN/VIN) networks.

Is therapeutic drug monitoring a dancing partner for TNF-α inhibitors in real-world practice? Answers from an updated systematic review and meta-analysis.

INTRODUCTION: This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria. METHODS: We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk. RESULTS: Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence. CONCLUSIONS: Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain. PROTOCOL REGISTRATION: www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.

Causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity.

The causative mechanisms underlying the genetic relationships of neurodegenerative diseases with epigenetic aging and human longevity remain obscure. We aimed to detect causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity. We obtained large-scale genome-wide association study summary statistics data for four measures of epigenetic age (GrimAge, PhenoAge, IEAA, and HannumAge) (N = 34,710), multivariate longevity (healthspan, lifespan, and exceptional longevity) (N = 1,349,462), and for multiple neurodegenerative diseases (N = 6618-482,730), including Lewy body dementia, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Main analyses were conducted using multiplicative random effects inverse-variance weighted Mendelian randomization (MR), and conditional/conjunctional false discovery rate (cond/conjFDR) approach. Shared genomic loci were functionally characterized to gain biological understanding. Evidence showed that AD patients had 0.309 year less in exceptional longevity (IVW beta = -0.309, 95% CI: -0.38 to -0.24, p = 1.51E-19). We also observed suggestively significant causal evidence between AD and GrimAge age acceleration (IVW beta = -0.10, 95% CI: -0.188 to -0.013, p = 0.02). Following the discovery of polygenic overlap, we identified rs78143120 as shared genomic locus between AD and GrimAge age acceleration, and rs12691088 between AD and exceptional longevity. Among these loci, rs78143120 was novel for AD. In conclusion, we observed that only AD had causal effects on epigenetic aging and human longevity, while other neurodegenerative diseases did not. The genetic overlap between them, with mixed effect directions, suggested complex shared genetic etiology and molecular mechanisms.

LncRNA-HMG incites colorectal cancer cells to chemoresistance via repressing p53-mediated ferroptosis.

Upon chemotherapy, excessive reactive oxygen species (ROS) often lead to the production of massive lipid peroxides in cancer cells and induce cell death, namely ferroptosis. The elimination of ROS is pivotal for tumor cells to escape from ferroptosis and acquire drug resistance. Nevertheless, the precise functions of long non-coding RNAs (lncRNAs) in ROS metabolism and tumor drug-resistance remain elusive. In this study, we identify LncRNA-HMG as a chemoresistance-related lncRNA in colorectal cancer (CRC) by high-throughput screening. Abnormally high expression of LncRNA-HMG predicts poorer prognosis in CRC patients. Concurrently, we found that LncRNA-HMG protects CRC cells from ferroptosis upon chemotherapy, thus enhancing drug resistance of CRC cells. LncRNA-HMG binds to p53 and facilitates MDM2-mediated degradation of p53. Decreased p53 induces upregulation of SLC7A11 and VKORC1L1, which contribute to increase the supply of reducing agents and eliminate excessive ROS. Consequently, CRC cells escape from ferroptosis and acquire chemoresistance. Importantly, inhibition of LncRNA-HMG by anti-sense oligo (ASO) dramatically sensitizes CRC cells to chemotherapy in patient-derived xenograft (PDX) model. LncRNA-HMG is also a transcriptional target of ß-catenin/TCF and activated Wnt signals trigger the marked upregulation of LncRNA-HMG. Collectively, these findings demonstrate that LncRNA-HMG promotes CRC chemoresistance and might be a prognostic or therapeutic target for CRC.

Anti-LSSDS pharmacological components identification of YuHuangLian based on the combination of spectrum-effect analysis and network pharmacology as well as molecular docking.

This research aimed to investigate the pharmacological components for liver stagnation and spleen deficiency syndrome (LSSDS) of Evodia rutaecarpa (also called Yu HuangLian [YHL]) by exploring the spectrum-effect relationship between fingerprints and pharmacological actions. The fingerprints of 17 batches of YHL with different preparation conditions according to Box-Behnken Design were generated and analyzed to identify the common peaks by HPLC and FT-IR. Vasoactive intestinal peptide (vip), substance P, and 5-HT levels in colon sample were measured by ELISA. Gray degree correlation and orthogonal partial least squares were employed to explore the correlation degree between components and pharmacologic activity. The presumed pharmacological components were further confirmed by network pharmacology, molecular docking, and qRT-PCR. The columbamine, jatrorrhizine, coptisine, berberine, rutecarpine, and evodiamine of the 14 common peaks in HPLC fingerprints were significantly correlated with the pharmacological indexes. Similarly, there was a strong correlation with -OH, δNC-H, and νC-O-C of the 10 common peaks in FT-IR fingerprints. PTGS2 and CHRM3 were the main targets intervening LSSDS, and the presumed pharmacological components could markedly increase the expression of CHRM3 and obviously reduce the expression of PTGS2 compared with the model group.

Anisomycin alleviates cognitive impairments and pathological features in 3xTg-AD mice.

Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus, which is an efficient anti-inflammatory agent that functions both in vivo and in vitro. However, it is not clear whether anisomycin can exert neuroprotective effect in AD. In the present study, anisomycin was intragastrically administrated to female triple-transgenic AD (3xTg-AD) model mice, then Morris water maze test was used to observe the long-term spatial memory of mice, the in vivo hippocampal field potential recording was performed to evaluate the synaptic plasticity, the Western blot and immunofluorescence were employed to detect pathological changes, and the bioinformatics analysis was used to predict the potential target of anisomycin exerting effects in AD. The results showed that anisomycin ameliorated the long-term spatial memory deficits, improved LTP depression and increased the expression of PSD-95, reduced the Aß and tau pathologies, and alleviated the activation of microglia and astrocytes in the brains of 3xTg-AD mice. In addition, the results from bioinformatics analysis showed that the potential target of anisomycin focused on inflammatory pathway. These results indicated that anisomycin exerts neuroprotective effects in 3xTg-AD mice by alleviating neuroinflammation, but the potential mechanism of anisomycin exerting neuroprotective effects needs to be further investigated.

Systemic lupus erythematosus and epilepsy: A Mendelian randomization study.

OBJECTIVE: Numerous observational studies have found a relationship between systemic lupus erythematosus (SLE) and epilepsy; however, their causal relationship remains unclear. This study aimed to investigate the causal role of SLE in epilepsy or any of its subtypes using a two-sample Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) linked to SLE were utilized as instrumental variables in MR analysis to assess their causal impact on epilepsy. The primary MR findings were derived using the inverse variance weighted (IVW) method, which was further supported by the weighted median and MR-Egger regression techniques. Additionally, sensitivity analyses, including Cochran's Q test and pleiotropy tests, were conducted to evaluate the influence of these SNPs on epilepsy, particularly looking for signs of horizontal pleiotropy and heterogeneity. RESULTS: We selected 43 SNPs that reached genome-wide significance from genome-wide association studies (GWASs) on SLE to serve as instrumental variables in this study. The IVW method showed no evidence to support a causal association between SLE and epilepsy (all epilepsy: odds ratio (OR) = 1.006, 95% confidence interval (CI) = 0.994-1.018; focal epilepsy: OR = 1.006, 95% CI = 0.994-1.019; generalized epilepsy: OR = 1.015, 95% CI = 0.996-1.035). Other MR complementary methods revealed consistent results. Furthermore, there was no evidence indicating heterogeneity or horizontal pleiotropy. SIGNIFICANCE: The findings of MR analysis did not support a genetically predicted causal relationship between SLE and epilepsy, but emphasized the need for further research on shared pathophysiological mechanisms, particularly the role of immune system abnormalities and potential influences such as chronic inflammation and therapeutic interventions. PLAIN LANGUAGE SUMMARY: The etiology of epilepsy is complex and diverse, including immune factors. Through a Mendelian randomization analysis, we did not find evidence of a genetic causal relationship between systemic lupus erythematosus and epilepsy. However, this does not invalidate epidemiological evidence, and further exploration is needed to investigate factors influencing the relationship between the two.

Therapeutic and Mechanistic Effects of Granulocyte Colony Stimulating Factor and Neurotrophin Receptor on Cerebral Ischemia-Reperfusion Injury: An Experimental Pilot Study.

OBJECTIVE: To study the therapeutic effect and protective mechanism of granulocyte colony stimulating factor (G-CSF) and neurotrophin receptor (NTR) on cerebral ischemia-reperfusion injury. METHODS: Rat models of permanent focal middle cerebral artery occlusion (MCAO) were constructed by using a modified suture method, and the rats were assigned into three groups such as treatment group (the rats were injected with mixed G-CSF and NTR once), sham operation group and PBS control group. The volume of the cerebral infarction was detected using Triphenyltetrazolium Chloride (TTC) staining method; the motor function in rats was evaluated; and qRT-PCR detection, double immunofluorescence histochemistry and immunohistochemistry were performed to observe various effects. RESULTS: After G-CSF and NTR treatment, the infarct volume induced by MCAO in the treatment group was significantly lower than that in the PBS control group (P<0.05). The motor function in the treatment group was significantly improved on day 7 and day 14 compared to the PBS control group (P<0.05). The levels of MCP-1, TNF-α, TGF-ß and IL-10 mRNA in the treatment group decreased by 22% compared with PBS control group, and the difference was statistically significant (P<0.05). The Bcl-2 protein level in the treatment group was greater than that in the PBS control group, while the Bax level in the treatment group was lower than in the control group; and both the differences were statistically significant (P<0.05). The number of BrdU + cells in the treatment group was significantly greater than that in the PBS control group (P<0.05). CONCLUSION: G-CSF can promote the regeneration of neurons, promote the formation of new blood vessels, promote the reconstruction of neural network in rat MCAO models through anti apoptosis, anti-inflammation and mobilization of bone marrow hematopoietic cells to exert its powerful protective effect on neurons, and contribute to the repair of neural function and improvement of prognosis.

Deconvoluting Surface and Bulk Charge Storage Processes in Redox-Active Oxides by Integrating Electrochemical and Optical Insights.

Redox-active transition metal oxides (TMOs) play crucial roles in diverse energy storage and conversion technologies, such as batteries and pseudocapacitors. These materials show intricate electrochemical charge storage processes, encompassing both bulk ion-intercalation, typical of battery electrodes, and pseudocapacitive-like behavior localized near the surfaces. However, understanding the underlying mechanisms of charge storage in redox-active TMOs is challenging due to the coexistence of these behaviors. In this study, we propose an integrated approach that combines operando electrochemical and optical techniques to disentangle the contributions of bulk and surface phenomena. Using birnessite δ-MnO2-x as a model system, we account for surface pseudocapacitive-like layers and employ a refined model that incorporates both surface reactions and bulk chemical diffusion. This methodology allows us to extract essential kinetic parameters, establishing a fundamental framework for unraveling surface and bulk electrochemical processes. This advancement provides a valuable tool for the rational design of energy storage devices, enhancing our ability to tailor these materials for specific applications.