Cobalt germanium hydroxides with asymmetric electron distribution and surface hydroxyl groups for superb catalytic degradation performances.

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) are attractive approaches for solving the global problem of water pollution, due to the generation of highly-active reactive oxygen species (ROS). Therefore, highly-efficient PMS activation is crucial for promoting the catalytic degradation of environmental pollutants. Here, bimetallic CoGeO2(OH)2 nanosheets with abundant surface hydroxyl groups (CGH) were synthesized via a simple hydrothermal route for PMS activation and degradation of various organic contaminants for the first time. The abundant surface hydroxyl groups (≡Co-OH/≡Ge-OH) could promptly initiate PMS to generate highly-active species: singlet oxygen (1O2), sulfate radicals (SO4·-) and hydroxyl radicals (HO•), while the asymmetric electron distribution among Co-O-Ge bonds derived from the higher electronegativity of Ge than Co further enhances the quick electron transfer to promote the redox cycle of Co2+/Co3+ and Ge2+/Ge4+, thereby achieving an outstanding catalytic capability. The optimal catalyst exhibits nearly 100 % catalytic degradation performance of dyes (Methylene blue, Rhodamine B, Methyl orange, Orange II, Methyl green) and antibiotics (Norfloxacin, Bisphenol A, Tetracycline) over a wide pH range of 3-11 and under different coexisting anion conditions (Cl-, HCO3-, NO3-, HA), suggesting the excellent adaptability for practical usage. This study could potentially lead to novel perspectives on the remediation of water areas such as groundwater and deep-water areas.

A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia.

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Confronting the Mysteries of Oxidative Reactive Species in Advanced Oxidation Processes: An Elephant in the Room.

Advanced oxidation processes (AOPs) are rapidly evolving but still lack well-established protocols for reliably identifying oxidative reactive species (ORSs). This Perspective presents both the radical and nonradical ORSs that have been identified or proposed, along with the extensive controversies surrounding oxidative mechanisms. Conventional identification tools, such as quenchers, probes, and spin trappers, might be inadequate for the analytical demands of systems in which multiple ORSs coexist, often yielding misleading results. Therefore, the challenges of identifying these complex, short-lived, and transient ORSs must be fully acknowledged. Refining analytical methods for ORSs is necessary, supported by rigorous experiments and innovative paradigms, particularly through kinetic analysis based on in situ spectroscopic techniques and multiple-probe strategies. To demystify these complex ORSs, future efforts should be made to develop advanced tools and strategies to enhance the mechanism understanding. In addition, integrating real-world conditions into experimental designs will establish a reliable framework in fundamental studies, providing more accurate insights and effectively guiding the design of AOPs.

A single-nucleotide polymorphism in PvPW1 encoding ß-1,3-glucanase 9 is associated with pod width in Phaseolus vulgaris L.

Pod width influences pod size, shape, yield, and consumer preference in snap beans (Phaseolus vulgaris L.). In this study, we map PvPW1, a quantitative trait locus associated with pod width in snap beans, through genotyping and phenotyping of recombinant plants. We identify Phvul.006G072800, encoding the ß-1,3-glucanase 9 protein, as the causal gene for PvPW1. The PvPW1G3555 allele is found to positively regulate pod width, as revealed by an association analysis between pod width phenotype and the PvPW1G3555C genotype across 17 bi-parental F2 populations. 97.7% of the 133 wide pod accessions carry PvPW1G3555, while 82.1% of the 78 narrow pod accessions carry PvPW1C3555, indicating strong selection pressure on PvPW1 during common bean breeding. Re-sequencing data from 59 common bean cultivars identify an 8-bp deletion in the intron linked to PvPW1C3555, leading to the development of the InDel marker of PvM436. Genotyping 317 common bean accessions with PvM436 demonstrated that accessions with PvM436247 and PvM436227 alleles have wider pods compared to those with PvM436219 allele, establishing PvM436 as a reliable marker for molecular breeding in snap beans. These findings highlight PvPW1 as a critical gene regulating pod width and underscore the utility of PvM436 in marker-assisted selection for snap bean breeding.

Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition criteria in nutritional diagnosis of hepatocellular carcinoma.

BACKGROUND: The Global Leadership Initiative on Malnutrition criteria (GLIM) was established to build a global consensus on the diagnostic criteria for malnutrition. The study aimed to assess the prevalence of the malnutrition diagnosed by GLIM criteria for patients with hepatocellular carcinoma (HCC), and to determine the role of the reduced muscle mass defined by CT scans in the GLIM criteria. METHODS: This cohort research was conducted on adult cirrhotic patients with HCC. The risk of malnutrition was screened by Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. The third lumbar vertebrae (L3-SMI) were used to represent the muscle mass in GLIM criteria. The variables associated with overall mortality were assessed by multivariate Cox regression analyses. RESULTS: The incidence of malnutrition diagnosed by GLIM criteria was 49.7% (179/360) in patients with HCC. If reduced muscle mass was not included in GLIM criteria, the prevalence of malnutrition was 31.7% (114/360). GLIM-defined malnutrition (HR = 1.979, 95%CI 1.019-3.841, P = 0.044) was independently associated with overall mortality in patients with HCC. However, the GLIM-defined malnutrition (without muscle mass) was not associated with overall mortality (HR = 0.863, 95%CI 0.399-1.867, P = 0.709). CONCLUSIONS: Skeletal muscle mass is an integral component of the GLIM criteria for patients with HCC. The malnutrition is common in patients with HCC, and malnourishment is associated with higher overall mortality. GLIM criteria are recommended to assess the nutritional status of hospitalized patients with HCC, which is recommended and can be used as the basis for nutritional interventions.

Contamination of liposomal bupivacaine during multi-dose usage in a clinical setting evaluated by culture and PCR.

Introduction: Liposomal bupivacaine, a long-acting local anesthetic, is sold in single-dose vials at a cost of approximately $200/20 mL vial. As many veterinary patients are not dosed an entire vial, the vials have been used for multiple doses at our institution to provide cost savings. Multiple punctures of a vial can lead to increased opportunity for contamination of the contents. This study aims to describe our institutional procedure for multi-dose use of single-dose liposomal bupivacaine vials and to evaluate clinically utilized liposomal bupivacaine for bacterial and fungal contamination using molecular and bacteriological methods. Methods: The first (Control) and last (Sample B) 0.5 mL from each vial were collected and submitted for bacterial and fungal PCR, anaerobic and aerobic bacterial culture, and opportunistic fungal culture. Results: All 40 bacterial cultures yielded no growth; Bacterial or fungal DNA was identified in 19 samples (50%). Of the 19 samples in which bacterial or fungal DNA was identified, 10 (52.6%) were from Control, and 9 (47.4%) were from Sample B. PCR does not appear to be useful in detecting bacterial or fungal contamination from liposomal bupivacaine. Discussion: Results support the aseptic handling protocol described in this article is successful in preventing detectable bacterial and fungal contamination of liposomal bupivacaine vials for up to 7 individual punctures and vials open for up to 5 days.

Brain Functional Alterations in Patients With Benign Paroxysmal Positional Vertigo Demonstrate the Visual-Vestibular Interaction and Integration.

OBJECTIVE: This study aimed to analyze the features of resting-state functional magnetic resonance imaging (rs-fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. METHODS: A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed-based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. RESULTS: Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed-based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. CONCLUSION: The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.

The diagnostic value and validation of IL-22 combimed with sCD40L in tuberculosis pleural effusion.

BACKGROUND: There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy. METHODS: A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1ß (IL-1ß), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort. RESULTS: The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort. CONCLUSION: We demonstrated that the levels of IL-1ß, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy.

Mycobacterium tuberculosis Suppresses Inflammatory Responses in Host through Its Cholesterol Metabolites.

Cholesterol is a key carbon source for Mycobacterium tuberculosis (Mtb) survival and persistence within macrophages. However, little is known about the role of cholesterol metabolism by Mtb in host-Mtb interplay. Here, we report the immune suppression mediated by Mtb's cholesterol metabolites. Conducting the cholesterol metabolic profiling and loss-of-function experiments, we show that the cholesterol oxidation products catalyzed by a thiolase FadA5 from Mtb H37Ra, 4-androstenedione (AD), and its derivant 1,4-androstenedione (ADD) inhibit the expression of pro-inflammatory cytokines and thus promote bacterial survival in bone marrow-derived macrophages (BMDMs). Our time-resolved fluorescence resonance energy transfer (TR-FRET)-based screening further identifies the nuclear receptor LXRα as the target of ADD. Activation of LXRα via ADD impedes the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling and reduces cholesterol accumulation in lipid rafts upon TLR4 simulation, thereby compromising the inflammatory responses. Our findings provide the evidence that Mtb could suppress the host immunity through its cholesterol metabolic enzyme and products, which are potential targets for screening novel anti-tuberculosis (TB) agents.

Post-marketing safety concerns with rimegepant based on a pharmacovigilance study.

PURPOSE: This study aimed to comprehensively assess the safety of rimegepant administration in real-world clinical settings. METHODS: Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) spanning the second quarter of 2020 through the first quarter of 2023 were retrospectively analyzed in this pharmacovigilance investigation. This study focuses on employing subgroup analysis to monitor rimegepant drug safety. Descriptive analysis was employed to examine clinical characteristics and concomitant medication of adverse event reports associated with rimegepant, including report season, reporter country, sex, age, weight, dose, and frequency, onset time, et al. Correlation analysis, including techniques such as violin plots, was utilized to explore relationships between clinical characteristics in greater detail. Additionally, four disproportionality analysis methods were applied to assess adverse event signals associated with rimegepant. RESULTS: A total of 5,416,969 adverse event reports extracted from the FAERS database, 10, 194 adverse events were identified as the "primary suspect" (PS) drug attributed to rimegepant. Rimegepant-associated adverse events involved 27 System Organ Classes (SOCs), and the significant SOC meeting all four detection criteria was "general disorders and administration site conditions" (SOC: 10018065). Additionally, new significant adverse events were discovered, including "vomiting projectile" (PT: 10047708), "eructation" (PT: 10015137), "motion sickness" (PT: 10027990), "feeling drunk" (PT: 10016330), "reaction to food additive" (PT: 10037977), etc. Descriptive analysis indicated that the majority of reporters were consumers (88.1%), with most reports involving female patients. Significant differences were observed between female and male patients across age categories, and the concomitant use of rimegepant with other medications was complex. CONCLUSION: This study has preliminarily identified potential new adverse events associated with rimegepant, such as those involving the gastrointestinal system, nervous system, and immune system, which warrant further research to determine their exact mechanisms and risk factors. Additionally, significant differences in rimegepant-related adverse events were observed across different age groups and sexes, and the complexity of concomitant medication use should be given special attention in clinical practice.

Efficacy of graphene nanocomposites for air disinfection in dental clinics: A randomized controlled study.

BACKGROUND: Aerosols containing disease-causing microorganisms are produced during oral diagnosis and treatment can cause secondary contamination. AIM: To investigate the use of graphene material for air disinfection in dental clinics by leveraging its adsorption and antibacterial properties. METHODS: Patients who received ultrasonic cleaning at our hospital from April 2023 to April 2024. They were randomly assigned to three groups (n = 20 each): Graphene nanocomposite material suction group (Group A), ordinary filter suction group (Group B), and no air suction device group (Group C). The air quality and air colony count in the clinic rooms were assessed before, during, and after the procedure. Additionally, bacterial colony counts were obtained from the air outlets of the suction devices and the filter screens in Groups A and B. RESULTS: Before ultrasonic cleaning, no significant differences in air quality PM2.5 and colony counts were observed among the three groups. However, significant differences in air quality PM2.5 and colony counts were noted among the three groups during ultrasonic cleaning and after ultrasonic treatment. Additionally, the number of colonies on the exhaust port of the suction device and the surface of the filter were significantly lower in Group A than in Group B (P = 0.000 and P = 0.000, respectively). CONCLUSION: Graphene nanocomposites can effectively sterilize the air in dental clinics by exerting their antimicrobial effects and may be used to reduce secondary pollution.

Multi-omics integration analysis reveals the role of N6-methyladenosine in lncRNA translation during glioma stem cell differentiation.

Glioblastoma is one of the most lethal brain diseases in humans. Although recent studies have shown reciprocal interactions between N6-methyladenosine (m6A) modifications and long noncoding RNAs (lncRNAs) in gliomagenesis and malignant progression, the mechanism of m6A-mediated lncRNA translational regulation in glioblastoma remains unclear. Herein, we profiled the transcriptomes, translatomes, and epitranscriptomics of glioma stem cells and differentiated glioma cells to investigate the role of m6A in lncRNA translation comprehensively. We found that lncRNAs with numerous m6A peaks exhibit reduced translation efficiency. Transcript-level expression analysis demonstrates an enrichment of m6A around short open reading frames (sORFs) of translatable lncRNA transcripts. Further comparison analysis of m6A modifications in different RNA regions indicates that m6A peaks downstream of sORFs inhibit lncRNA translation more than those upstream. Observations in glioma-associated lncRNAs H19, LINC00467, and GAS5 further confirm the negative effect of m6A methylation on lncRNA translation. Overall, these findings elucidate the dynamic profiles of the m6A methylome and enhance the understanding of the complexity of lncRNA translational regulation.

A Phase II Clinical Study on Apatinib Plus Vinorelbine in Refractory HER2-Negative Breast Cancer and its Metabolic Implications of Drug Resistance.

BACKGROUND: Apatinib, a tyrosine-kinase inhibitor that targets the vascular endothelial growth factor receptor 2, contributes to the inhibition of angiogenesis. Vinorelbine, a semisyn-thetic vinca alkaloid, primarily inhibits metaphase mitosis of cancer cells through its interactions with tubulin. This study aimed to evaluate whether apatinib combined with vinorelbine was ef-fective and safe for refractory human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who failed taxanes and/or anthracycline and analyze the possible mechanism of drug resistance through metabolomic analysis. METHODS: Eligible patients were HER2-negative, inoperable, locally advanced, or metastatic breast cancer patients who progressed after at least one chemotherapy regimen in this present prospective phase II study. Patients took oral apatinib (250-500 mg/day) plus intravenous infusion of vinorelbine (25 mg/m2 on day 1, day 8 at 3-week intervals). Objective response rate (ORR) was our primary endpoint, while disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity were our secondary endpoints. The exploratory purpose was to identify biomarkers or drug resistance mechanisms through metabolomics changes before and after the combination therapy. RESULTS: Between September, 2019 and June, 2022, a total of 34 patients were included. ORR and DCR were 32.4% (11/34) and 85.3% (29/34), respectively. The median PFS was 5.0 months (95% CI, 3.766-6.234), while the median OS was 13.0 months (95% CI, 8.714-17.286). Side effects included hematologic toxicity, gastrointestinal reaction, and sinus tachycardia, which were mild to moderate. The mainly disturbed metabolic pathways were the cAMP signaling pathway, the alanine/aspartate/glutamate metabolism, the central carbon metabolism in cancer, the beta-alanine metabolism, the butanoate metabolism, and the glyoxylate and dicarboxylate metabolism, which may lead to the resistance of patients to this combination therapy. CONCLUSION: Apatinib combined with vinorelbine is effective and safe in patients with locally advanced or metastatic refractory HER2-negative breast cancer. The findings of this study con-tribute to a better understanding of the metabolic effect of apatinib and vinorelbine therapy.

Exposure to submicron particulate matter and long-term survival: Cross-cohort analysis of 3 Chinese national surveys.

BACKGROUND: Cohort evidence linking increased mortality with airborne fine particulate matter (PM2.5, particulate matter [PM] with aerodynamic diameter ≤2.5 µm) exposure was extensively validated worldwide. Nevertheless, long-term survival associated with submicron particulate matter (PM1, PM with aerodynamic diameter ≤1 µm) exposure remained largely unstudied, particularly in highly exposed populations. METHODS: We performed a population-based investigation involving 86844 adults aged 16+ years from 3 national dynamic cohorts spanning from 2005 to 2018. Residential annual exposure to PM1 and PM2.5 was assigned for each follow-up year using satellite-derived spatiotemporal estimates at a 1-km2 resolution. The concentration of PM1-2.5 (PM with aerodynamic diameter between 1 and 2.5 µm) was calculated by subtracting PM1 from PM2.5. Time-independent Cox proportional hazards regression models were applied to assess the associations of all-cause mortality with long-term exposure to size-specific particles. To investigate the effect of PM1 on PM2.5-mortality associations, we categorized participants into low, medium, and high groups based on PM1/PM2.5 ratio and examined the risk of PM2.5-associated mortality in each stratum. Effect modifications were checked via subgroup analyses. RESULTS: A total of 18722 deaths occurred during 497069.2 person-years of follow-up (median 5.7 years). Participants were exposed to an average annual concentration of 31.8 µg/m³ (range: 7.6-66.8 µg/m³) for PM1, 56.3 µg/m³ (range: 19.8-127.2 µg/m³) for PM2.5, and 24.5 µg/m³ (range: 7.3-60.3 µg/m³) for PM1-2.5. PM1, PM2.5, and PM1-2.5 were consistently associated with elevated mortality risks, with a hazard ratio (HR) of 1.029 (95% confidence interval [CI]: 1.013-1.046), 1.014 (95% CI: 1.005-1.023), and 1.019 (95% CI: 1.001-1.038) for each 10-µg/m3 increase in exposure, respectively. Compared with low (HR = 0.986, 95% CI: 0.967-1.004) and medium (HR = 1.015, 95% CI: 1.002-1.029) PM1/PM2.5 ratio groups, PM2.5-related risk of mortality was more pronounced in high PM1/PM2.5 ratio stratum (HR = 1.041, 95% CI: 1.019-1.064). Greater risks of mortality associated with size-specific particles were found among the elderly (>80 years old), southeastern participants, and those living in warmer areas. CONCLUSIONS: This study demonstrated that long-term exposure to PM1, PM2.5, and PM1-2.5 was associated with heightened mortality, and PM1 may play a predominant role in PM2.5-induced risk. Our results emphasized the population health implications of establishing ambient PM1 air quality guidelines to mitigate the burden of premature mortality stemming from particulate air pollution.

Herbal medicines for SOD1G93A mice of amyotrophic lateral sclerosis: preclinical evidence and possible immunologic mechanism.

Currently, there is no cure or effective treatment for Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying ALS remain unclear, with immunological factors potentially playing a significant role. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a systematic review of preclinical studies was conducted, searching seven databases including PubMed, covering literature from the inception of the databases to April 10, 2024. Methodological quality of the included literature was assessed using CAMARADES, while the risk of bias in the included studies was evaluated using SYRCLE's ROB tool. Review Manager 5.4.1 statistical software was used for meta-analysis of the outcomes. The scoping review followed the Joanna Briggs Institute Methodological Guidelines and reporting of this review followed the PRISMA-extension for Scoping Reviews (PRISMA -ScR) checklist to explore the immunological mechanisms of Herbal Medicine (HM) in treating ALS. This systematic review and meta-analysis involved 18 studies with a total of 443 animals. The studies scored between 4 to 8 for methodological quality and 3 to 7 for risk of bias, both summing up to 10.A remarkable effects of HM in ALS mice, including onset time(Standardized Mean Difference(SMD): 1.75, 95% Confidence Interval(CI) (1.14 ~ 2.36), Z = 5.60, P < 0.01), survival time(SMD = 1.42, 95% CI (0.79 ~ 2.04), Z = 4.44, P < 0.01), stride length(SMD=1.90, 95% CI (1.21 to 2.59), Z = 5.39, P < 0.01) and duration time (Mean Difference(MD)=6.79, 95% CI [-0.28, 13.87], Z=1.88, P =0.06), showing HM's certain efficiency in treating ALS mice. The scoping review ultimately included 35 articles for review. HMs may treat ALS through mechanisms such as combating oxidative stress, excitatory amino acid toxicity, and calcium cytotoxicity, understanding and exploring the mechanisms will bring hope to patients. Individual herbs and their formulations within HM address ALS through a variety of immune pathways, including safeguarding the blood-brain barrier, countering neuroinflammation, impeding complement system activation, mitigating natural killer cell toxicity, and regulating T cell-mediated immune pathways. The preclinical evidence supports the utilization of HM as a conventional treatment for ALS mice. Growing evidence indicates that HM may potentially delay neurological degeneration in ALS by activating diverse signaling pathways, especially immune pathways.

Review of key issues and potential strategies in bio-degradation of polyolefins.

Polyolefins are the most widely used plastic product and a major contributor to white pollution. Currently, studies on polyolefin degradation systems are mainly focused on microorganisms and some redox enzymes, and there is a serious black-box phenomenon. The use of polyolefin-degrading enzymes is limited because of the small number of enzymes; in addition, the catalytic efficiency of these enzymes is poor and their catalytic mechanism is unclear, which leads to the incomplete degradation of polyolefins to produce microplastics. In this review three questions are addressed: the generation and degradation of action targets that promote the degradation of polyolefins, the different modes by which enzymes bind substrates and their application scenarios, and possible multienzyme systems in a unified system. This review will be valuable for mining or modifying polyolefin degradation enzymes and constructing polyolefins degradation systems and may provide novel ideas and opportunities for polyolefin degradation.

Associations of metabolic syndrome with cognitive function and dementia risk: Evidence from the UK Biobank cohort.

AIM: To investigate the associations of metabolic syndrome (MetS) with cognitive function, dementia and its subtypes. METHODS: Based on the participants recruited by UK Biobank, this study aims to investigate the associations of MetS with cognitive function, dementia and its subtypes. Generalized estimating equations, Cox proportional risk models, and multiple linear regression models were respectively used to assess associations between MetS and dementia-related outcomes. RESULTS: Among the 363,231 participants, 95,713 had MetS at baseline. The results showed that MetS was significantly associated with cognitive function related to fluid intelligence and prospective memory at follow-up. Among participants aged ≥60 years, MetS was correlated with elevated risk of all-cause dementia, particularly vascular dementia (VaD) [hazard ratio 1.115 (95% confidence interval: 1.047, 1.187), hazard ratio 1.393 (95% confidence interval: 1.233, 1.575), respectively]. With increasing MetS components, the risk of all-cause dementia and VaD tended to be elevated. MetS has also been associated with dementia-related structural changes in the brain, including alterations in overall brain volume, white matter volume, grey matter volume and white matter integrity. CONCLUSION: MetS was associated with poorer cognitive performance and might increase the risk of all-cause dementia as well as VaD, but the effect on Alzheimer's disease was not significant. Holistic control of the MetS may benefit the prevention and control of cognitive impairment and dementia.

The diagnostic value of combining preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging in preoperative resectability of pancreatic cancer.

OBJECTIVE: Pancreatic cancer is an increasing cause of cancer-related mortality, with persistently low survival rates. We investigated the clinical diagnostic value of the combination of preoperative serum carbohydrate antigen 19-9 (CA19-9), albumin-bilirubin (ALBI) score, and 18F-fluoro-2-deoxy-d-glucose PET integrated with computed tomography (18F-FDG PET/CT) imaging in pancreatic cancer preoperative resectability. METHODS: This study included 143 pancreatic cancer patients, including 68 preoperative resectable and 75 preoperative unresectable pancreatic cancer patients. Meanwhile, 67 patients with non-pancreatic cancer were included as the control group. The clinical data were collected. Serum CA19-9 level was measured by ELISA. The levels of total bilirubin and albumin were determined using a biochemical analyzer, with the ALBI score calculated. All patients underwent 18F-FDG PET/CT imaging. The consistency of the diagnosis was evaluated by the Kappa test. Logistic univariate and multivariate regression analyses were performed. The diagnostic efficacy of these parameters was evaluated using receiver operating characteristic (ROC) curves, and the optimal ROC curve thresholds were obtained using the Youden index. RESULTS: The preoperative serum CA19-9 and ALBI score of patients with preoperative resectable pancreatic cancer were increased, which helped diagnose preoperative resectable pancreatic cancer. 18F-FDG PET/CT imaging had diagnostic value for preoperative resectable pancreatic cancer. Preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging were independent influencing factors for pancreatic cancer preoperative resectability, and their combination had higher diagnostic value for preoperative resectable pancreatic cancer than any single of these indexes. CONCLUSION: The combination of preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging had high diagnostic value for pancreatic cancer preoperative resectability.

TarKG: A Comprehensive Biomedical Knowledge Graph for Target Discovery.

MOTIVATION: Target discovery is a crucial step in drug development, as it directly affects the success rate of clinical trials. Knowledge graphs (KGs) offer unique advantages in processing complex biological data and inferring new relationships. Existing biomedical KGs primarily focus on tasks such as drug repositioning and drug-target interactions, leaving a gap in the construction of KGs tailored for target discovery. RESULTS: We established a comprehensive biomedical KG focusing on target discovery, termed TarKG, by integrating seven existing biomedical KGs, nine public databases, and traditional Chinese medicine knowledge databases. TarKG consists of 1,143,313 entities and 32,806,467 relations across 15 entity categories and 171 relation types, all centered around three core entity types: Disease, Gene, Compound. TarKG provides specialized knowledges for the core entities including chemical structures, protein sequences or text descriptions. By using different KG embedding algorithms, we assessed the knowledge completion capabilities of TarKG, particularly for disease-target link prediction. In case studies, we further examined TarKG's ability to predict potential protein targets for Alzheimer's disease (AD) and to identify diseases potentially associated with the metallo-deubiquitinase CSN5, using literature analysis for validation. Furthermore, we provided a user-friendly web server (https://tarkg.ddtmlab.org) that enables users to perform knowledge retrieval and relation inference using TarKG. AVAILABILITY: TarKG is accessible at https://tarkg.ddtmlab.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.