Neuraminidase-1 (NEU1): Biological Roles and Therapeutic Relevance in Human Disease.

Neuraminidases catalyze the desialylation of cell-surface glycoconjugates and play crucial roles in the development and function of tissues and organs. In both physiological and pathophysiological contexts, neuraminidases mediate diverse biological activities via the catalytic hydrolysis of terminal neuraminic, or sialic acid residues in glycolipid and glycoprotein substrates. The selective modulation of neuraminidase activity constitutes a promising strategy for treating a broad spectrum of human pathologies, including sialidosis and galactosialidosis, neurodegenerative disorders, cancer, cardiovascular diseases, diabetes, and pulmonary disorders. Structurally distinct as a large family of mammalian proteins, neuraminidases (NEU1 through NEU4) possess dissimilar yet overlapping profiles of tissue expression, cellular/subcellular localization, and substrate specificity. NEU1 is well characterized for its lysosomal catabolic functions, with ubiquitous and abundant expression across such tissues as the kidney, pancreas, skeletal muscle, liver, lungs, placenta, and brain. NEU1 also exhibits a broad substrate range on the cell surface, where it plays hitherto underappreciated roles in modulating the structure and function of cellular receptors, providing a basis for it to be a potential drug target in various human diseases. This review seeks to summarize the recent progress in the research on NEU1-associated diseases and highlight the mechanistic implications of NEU1 in disease pathogenesis. An improved understanding of NEU1-associated diseases should help accelerate translational initiatives to develop novel or better therapeutics.

Reductive Amination of Aldehyde and Ketone with Ammonia and H2 by an In Situ-Generated Cobalt Catalyst under Mild Conditions.

Herein, we present the simplest approach for the synthesis of primary amines via reductive amination using H2 as a reductant and aqueous ammonia as a nitrogen source, catalyzed by amorphous Co particles. The highly active Co particles were prepared in situ by simply mixing commercially available CoCl2 and NaBH4/NaHBEt3 without any ligand or support. This reaction system features mild conditions (80 °C, 1-10 bar), high selectivity (99%), a wide substrate scope, simple operation, and easy separation of the catalyst. The successful large-scale application of this reaction in the production of primary amines suggests its potential industrial interest.

Factors associated with concomitant prostate cancer in benign prostatic hyperplasia patients aged 60 years and above.

OBJECTIVE: Prostate hyperplasia and cancer are more prevalent in middle-aged and elderly men. Previous studies have linked both disorders to androgen receptors. Herein, efforts were made to identify factors associated with prostate cancer in patients ≥60 years, aiming to enhance their health management. METHODS: An analytical framework was established utilizing the "Prostate Cancer Early Warning Dataset" from the National Clinical Medical Science Data Center. Variables selection was conducted through LASSO regression, followed by multifactorial logistic stepwise regression to construct a predictive model. RESULTS: A total of 1,502 patients with BPH and 294 with combined PCa were hereby included. Multivariate regression delineated several independent predictors of PCa coexistence, including age (OR [95% CI]: 1.06 [1.04-1.09], p < 0.001), fPSA/tPSA ratio (OR [95% CI]: 0.01 [0.002-0.05], p < 0.001), serum inorganic phosphorus (OR [95% CI]: 5.85 [2.61-13.15], p < 0.001), globulin levels (OR [95% CI]: 1.06 [1.02-1.11], p = 0.005), serum potassium (OR [95% CI]: 0.58 [0.40-0.86], p = 0.006), low-density lipoprotein (LDL) cholesterol (OR [95% CI]: 1.28 [1.06-1.54], p = 0.009), among others. CONCLUSION: The analysis revealed connections between PCa occurrence in men aged over 60 and BPH, along with specific serum biomarkers such as inorganic phosphorus, globulin, LDL cholesterol, lower fPSA/tPSA ratios and serum potassium.

Exploring Causal Relationships Between Gut Microbiota and Alzheimer's Disease: A Bidirectional Mendelian Randomization Study.

Background: Many observational studies have investigated the link between the gut microbiota and Alzheimer's disease (AD), but the causality remains uncertain. Objective: This study aimed to evaluate the causal impact of gut microbiota on AD. Methods: A two-sample Mendelian randomization (MR) study was conducted employing summary data. Summary statistics for AD were from the latest genome-wide association study (cases and proxy cases: 85,934; controls: 401,577). Summary data for gut microbiota were acquired from MiBioGen consortium. Causal effect estimations primarily relied on the inverse variance weighting method along with the sensitivity analyses for testing for pleiotropy and heterogeneity. Additionally, reverse MR analyses were performed to examine potential reverse causality. Results: Seven gut microbiota were identified as associated with AD risk. Order Selenomonadales (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.03-1.24, p = 0.01), Family Pasteurellaceae (OR 1.07, 95% CI 1.01-1.13, p = 0.01), and Genus Methanobrevibacter (OR 1.07, 95% CI 1.00-1.13, p = 0.04) were correlated with an elevated likelihood of AD, while Class Mollicutes (OR 0.87, 95% CI 0.79-0.95, p = 0.00), Genus Ruminiclostridium9 (OR 0.87, 95% CI 0.78-0.97, p = 0.01), Genus Clostridiuminnocuumgroup (OR 0.94, 95% CI 0.89-0.99, p = 0.03), and Genus Eggerthella (OR 0.94, 95% CI 0.89-1.00, p = 0.04) exerted beneficial impact in mitigating AD. No statistically significant reverse causality was found between AD and each of these seven specific gut microbiota species. Conclusions: This study unveiled a causal link between certain gut microbiota and AD, offering new insights for advancing clinical treatments.

Integrated metabolomics and transcriptomics analysis reveals the mechanism of Tangbi capsule for diabetic lower extremities arterial disease.

Objective: Tangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD). Methods: The mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction. Results: Mass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-ß, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD. Conclusion: TBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD.

Additional Hepatic Arterial Infusion Chemotherapy to Sorafenib Was Cost-Effective for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis.

Purpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers. Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results. Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters. Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.

The Impact of Low Workplace Support During Pregnancy on Surgeon Distress and Career Dissatisfaction.

OBJECTIVE: To describe the impact of lack of workplace support (LOWS) for obstetric health on surgeon distress and career satisfaction. BACKGROUND: Although most pregnant surgeons desire clinical duty reductions to mitigate obstetric risk, few modify their schedules due to low workplace support. METHODS: US surgeons with at least one live birth completed an electronic survey. LOWS during pregnancy was defined as (1) disagreeing that colleagues/leadership were supportive of obstetric-mandated bedrest; (2) feeling unable to reduce clinical duties despite health concerns due to risk of financial penalties, requirement to make up missed call shifts, being perceived as "weak", burdening colleagues, or accommodations being denied by the workplace. Multivariate logistic regression determined the association between LOWS and burnout, low quality of life, plans to leave clinical practice or to reduce work hours, and likelihood of recommending a surgical career to one's child. RESULTS: Of 557 surgeons, the 360 (64.6%) who reported LOWS during pregnancy were more likely to report burnout (OR:2.57; 95%CI:1.60-4.13), low quality of life (OR:1.57; 95%CI:1.02-2.41), a desire to leave their practice (OR:2.74; 95%CI: 1.36-5.49), plans to reduce clinical hours in the next year (OR:4.25; 95%CI:1.82-9.90), and were less likely to recommend their career to their child (OR:0.44; 95%CI:0.28-0.70). CONCLUSIONS: LOWS for maternal-fetal health concerns is associated with burnout, low quality of life, and career dissatisfaction. The work environment is a modifiable factor requiring system-level interventions to limit clinical work during pregnancy and provide fair compensation for covering surgeons. Supporting surgeons during pregnancy is a short-term investment with long-term implications for improving longevity and diversity of the workforce.

Efficacy, safety, and tolerability of adjunctive Lacosamide therapy for focal seizures in young children aged ≥1 month to ≤4 years: A real-world study.

AIMS: To evaluate the efficacy, safety, and tolerability of adjunctive lacosamide therapy against focal seizures in young children (1 month - 4 years). METHODS: This non-randomized, open-label, and self-controlled real-world study included 105 children (1 month-4 years) with focal seizures treated with adjunctive lacosamide therapy at Children's Hospital of Chongqing Medical University. RESULTS: (1) The 50% response rates at 3, 6, 9, and 12 months of follow-up were 58.1%, 61.0%, 57.1%, and 56.2%, while the seizure-free rates were 27.6%, 34.3%, 32.4%, and 37.1%, respectively. The 50% response rate of the first addition of lacosamide for focal seizures was much higher than the second and later added treatment at 3 months (p = 0.038). After 1 year of follow-up, these children showed an improvement in neurodevelopmental levels (p < 0.05). (2) Lacosamide retention rate was 72.7% (64/88) after 1 year of follow-up. Lack of efficacy and serious adverse events were independent risk factors for the lacosamide retention rate. (3) During adjunctive lacosamide therapy, 13 (12.4%) patients reported adverse events and five (4.7%) patients withdrew due to adverse events, including vomiting drowsiness, ataxia (0.94%), neck itching with eczema (0.94%), irritability (1.88%), and gastrointestinal discomfort (0.94%). CONCLUSION: Adjunctive lacosamide therapy was effective, safe, and well-tolerated in young Chinese children with focal seizures in this study.

Successful percutaneous coronary intervention in a congenital single right coronary artery with acute myocardial infarction: A case report and literature review.

RATIONALE: Single coronary artery (SCA) is a rare coronary artery malformation. SCA combined with atherosclerotic plaques can cause severe and widespread myocardial ischemia and infarction, leading to hemodynamic instability and even sudden death. PATIENT CONCERNS: A 48-year-old Chinese man was admitted for treatment of persistent chest tightness and panic for 5 hours. The patient was a lorry driver with high work intensity and mental stress, with body mass index of 33.78, history of smoking and alcohol consumption, but no history of hypertension and diabetes. DIAGNOSES: Admission examination showed Troponin was 183.083 µg/L and CK-MB value was >300 µg/L. The patient was diagnosed with a congenital single right coronary artery (RCA) with acute myocardial infarction (AMI) by coronary angiography (CAG). Due to atherosclerotic plaques rupture, a complete occlusion of the proximal RCA with thrombolysis in myocardial infarction grade 0 of distal blood flow were found. INTERVENTIONS AND OUTCOMES: The patient was treated with thrombus aspiration and thrombolytic therapy by percutaneous coronary intervention under the support of intra-aortic balloon pump. Postoperative the chest tightness and panic were relieved, and CAG revealed that the proximal thrombus of the RCA was reduced, and distal blood flow was restored to thrombolysis in myocardial infarction grade 3. After 2 weeks of intensive antithrombotic and lipid-regulating drug therapy, the patient was successfully discharged. Follow-up for 6 months, the patient was able to live and work normally without experiencing chest tightness and chest pain. Computed tomography angiography (CTA) confirmed a congenital single RCA with patent lumen and no severe stenosis. LESSONS: The congenital single RCA is very rare, and it is fatal in conjunction with acute coronary syndrome. Early detection and appropriate treatment is critical for AMI patient with single RCA. CAG is the gold standard for diagnosis of single RCA, and CTA is a necessary to describe the anatomical course of abnormal coronary arteries.

Clinical characteristics and detection of MYB-QKI fusions in patients with angiocentric glioma.

PURPOSE: Angiocentric glioma (AG), a benign tumor identified within the last two decades, was officially included in the 2007 WHO Classification of Tumors of the Central Nervous System, WHO grade I. The tumor is relatively rare, with only approximately 100 cases reported. We aim to complement the characteristics and long-term prognosis of AG, as well as to detect MYB-QKI fusions. METHODS: The characteristics of all cases collected between 1 March 2009 and 1 March 2023 at the Beijing Sanbo Brain Hospital, Capital Medical University, were summarized and analyzed. Additionally, all fourteen patients were tested for MYB-QKI fusions. RESULTS: AG more predominantly occurs in adolescents (median age 16.5-year-old), and commonly presents with drug-resistant epilepsy. AG is frequently localized in the supratentorial regions and only one patient is in the brainstem. Brain parenchyma atrophy, and stalk-like signs can observe in imaging. Pathologically, tumor cells are perivascular pseudorosettes, presenting immunoreactivity for GFAP, S-100, Vimentin, "dot-like" staining for EMA, and low proliferative activity. Focal cortex dysplasia was observed in four patients. Twelve of fourteen (85.7%) patients were found with MYB-QKI fusions. Completely surgical resection typically has a satisfactory prognosis with long-term follow-up. CONCLUSION: AG is a rare benign tumor with a favorable prognosis after complete resection, characterized by refractory epilepsy, frequently occurring in adolescents. MYB-QKI fusions were detected in most AG patients, as a good defining genetic alteration pathologically. The potential presence of focal cortical dysplasia (FCD) may affect the prognosis of epilepsy.

Edwardsiella tarda induces airways inflammation and production of autoantibodies against lung tissues through regulation of the IL-33-ST2 axis.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease characterised by irreversible airways obstruction associated with chronic airways inflammation and remodelling, while the pathogenesis and the mechanistic differences between patients remain to be fully elucidated. We previously reported that alarmin cytokine IL-33 may contribute to the production of autoantibodies against respiratory epithelial cells. Here we expand the hypothesis that pulmonary autoimmune responses induced by airway microbiota also contribute to the progression of COPD. We focused on Edwardsiella tarda which we detected uniquely in the induced sputum of patients with acute exacerbations of COPD. Pernasal challenge of the airways of WT mice with supernatants of cultured E. tarda induced marked, elevated expression of IL-33 in the lung tissues. Immunisation of animals with supernatants of cultured E. tarda resulted in significantly elevated airways inflammation, the formation of tertiary lymphatic structures and significantly elevated proportions of T follicular helper T cells in the lung tissue and mediastinal lymph nodes. Interestingly, such challenge also induced production of IgG autoantibodies directed against lung tissue lysate, alveolar epithelial cell proteins and elastin fragment, while putrescine, one of metabolites generated by the bacterium, might play an important role in the autoantibody production. Furthermore, all of these effects were partly but significantly abrogated in mice with deletion of the IL-33 receptor ST2. Collectively, these data support the hypothesis that COPD is progressed at least partly by airways microbiota such as E. tarda initiating autoimmune attack of the airways epithelium mediated at least partly through the IL-33-ST2 axis.

Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in HBV-related acute-on-chronic liver failure patients with cirrhosis.

Background & aims: HBV infection initiates autoimmune responses, leading to autoantibody generation. This research explores the role of autoantibodies in HBV-related Acute-on-Chronic Liver Failure (ACLF), offering novel perspectives for clinical management. Method: We applied immunoprecipitation and iTRAQ techniques to screen for autoantibodies in serum from HBV-related cirrhosis patients and conducted detection with conformation- stabilizing ELISA in a cohort of 238 HBV-infected individuals and 49 health controls. Our results were validated in a retrospective cohort comprising 106 ACLF patients and further assessed through immunohistochemical analysis in liver tissues from an additional 10 ACLF cases. Results: Utilizing iTRAQ, we identified Argonaute1-3 autoantibodies (AGO-Abs) in this research. AGO2-Abs notably increased in cirrhosis, decompensation, and further in ACLF, unlike AGO1-Abs and AGO3-Abs. This reflects disease severity correlation. Logistic regression and COX models confirmed AGO2-Abs as independent prognostic indicators for decompensated liver cirrhosis (DLC) and ACLF. In the ROC analysis, AGO2-Abs showed significant diagnostic value for predicting 28- and 90-day mortality (AUROC = 0.853 and 0.854, respectively). Furthermore, combining AGO2-Abs with the Child-Pugh, MELD, and AARC scores significantly improved their predictive accuracy (P < 0.05). Kaplan-Meier analysis showed poorer survival for AGO2-Abs levels above 99.14µg/ml. These findings were supported by a retrospective validation cohort. Additionally, immunohistochemistry revealed band-like AGO2 expression in periportal liver areas, with AGO2-Abs levels correlating with total bilirubin, indicating a potential role in exacerbating liver damage through periportal functions. Conclusions: AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.

A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/angiogenesis and recruitment.

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.

Locally boosted Li2S nucleation on VO2 by loading carbon quantum dots for soft-packaged lithium-sulfur pouch cells.

VO2 affords ultrafast polysulfide adsorption on account of its oxidation potential, which matches the sulfur working window (1.7-2.8 V). Nevertheless, its nonconductive surface limits direct sulfur conversion. Herein, we gently load carbon quantum dots on VO2 to increase direct Li2S nucleation by enhanced electron conductivity. As a result, the soft-packaged lithium-sulfur pouch cell yields a capacity retention of 88.8% at 0.5C after 100 cycles and a decay rate of 0.17% per cycle over 200 cycles at 2C. The cell energy density of the multilayer cell is up to 386.1 W h kg-1.

Neural Network Mechanisms Underlying General Anesthesia: Cortical and Subcortical Nuclei.

General anesthesia plays a significant role in modern medicine. However, the precise mechanism of general anesthesia remains unclear, posing a key scientific challenge in anesthesiology. Advances in neuroscience techniques have enabled targeted manipulation of specific neural circuits and the capture of brain-wide neural activity at high resolution. These advances hold promise for elucidating the intricate mechanisms of action of general anesthetics. This review aims to summarize our current understanding of the role of cortical and subcortical nuclei in modulating general anesthesia, providing new evidence of cortico-cortical and thalamocortical networks in relation to anesthesia and consciousness. These insights contribute to a comprehensive understanding of the neural network mechanisms underlying general anesthesia.

Mutation of Pseudomonas aeruginosa lasI/rhlI diminishes its cytotoxicity, oxidative stress, inflammation, and apoptosis on THP-1 macrophages.

The management of Pseudomonas aeruginosa (P. aeruginosa) infections presents a substantial challenge to clinics and public health, emphasizing the urgent need for innovative strategies to address this issue. Quorum sensing (QS) is an intercellular communication mechanism that coordinates bacterial activities involved in various virulence mechanisms, such as acquiring host nutrients, facilitating biofilm formation, enhancing motility, secreting virulence factors, and evading host immune responses, all of which play a crucial role in the colonization and infection of P. aeruginosa. The LasI/R and RhlI/R sub-systems dominate in the QS system of P. aeruginosa. Macrophages play a pivotal role in the host's innate immune response to P. aeruginosa invasion, particularly through phagocytosis as the initial host defense mechanism. This study investigated the effects of P. aeruginosa's QS system on THP-1 macrophages. Mutants of PAO1 with lasI/rhlI deletion, as well as their corresponding complemented strains, were obtained, and significant downregulation of QS-related genes was observed in the mutants. Furthermore, the ΔlasI and ΔlasIΔrhlI mutants exhibited significantly attenuated virulence in terms of biofilm formation, extracellular polymeric substances synthesis, bacterial adhesion, motility, and virulence factors production. When infected with ΔlasI and ΔlasIΔrhlI mutants, THP-1 macrophages exhibited enhanced scavenging ability against the mutants and demonstrated resistance to cytotoxicity, oxidative stress, inflammatory response, and apoptosis induced by the culture supernatants of these mutant strains. These findings offer novel insights into the mechanisms underlying how the lasI/rhlI mutation attenuates cytotoxicity, oxidative stress, inflammation, and apoptosis in macrophages induced by P. aeruginosa.IMPORTANCEP. aeruginosa is classified as one of the ESKAPE pathogens and poses a global public health concern. The QS system of this versatile pathogen contributes to a broad spectrum of virulence, thereby constraining therapeutic options for serious infections. This study illustrated that the lasI/rhlI mutation of the QS system plays a prominent role in attenuating the virulence of P. aeruginosa by affecting bacterial adhesion, biofilm formation, extracellular polymeric substances synthesis, bacterial motility, and virulence factors' production. Notably, THP-1 macrophages infected with mutant strains exhibited increased phagocytic activity in eliminating intracellular bacteria and enhanced resistance to cytotoxicity, oxidative stress, inflammation, and apoptosis. These findings suggest that targeted intervention toward the QS system is anticipated to diminish the pathogenicity of P. aeruginosa to THP-1 macrophages.

Direct hydrogenation of natural oils to fatty alcohols enabled by an alcoholysis/hydrogenation relay strategy and two-phase solvent system.

Direct hydrogenation of natural oils to fatty alcohols was achieved via a relay strategy involving alcoholysis of natural oils followed by hydrogenation of fatty acid esters. A two-phase system was used to avoid catalyst poisoning by glycerol. This protocol is suitable for plant oils, animal fats and waste cooking oil.

Long noncoding RNA H19 knockdown promotes angiogenesis via IMP2 after ischemic stroke.

AIMS: This study aimed to explore the effects of long noncoding RNA (lncRNA) H19 knockdown on angiogenesis and blood-brain barrier (BBB) integrity following cerebral ischemia/reperfusion (I/R) and elucidate their underlying regulatory mechanisms. METHODS: A middle cerebral artery occlusion/reperfusion model was used to induce cerebral I/R injury. The cerebral infarct volume and neurological impairment were assessed using 2,3,5-triphenyl-tetrazolium chloride staining and neurobehavioral tests, respectively. Relevant proteins were evaluated using western blotting and immunofluorescence staining. Additionally, a bioinformatics website was used to predict the potential target genes of lncRNA H19. Finally, a rescue experiment was conducted to confirm the potential mechanism. RESULTS: Silencing of H19 significantly decreased the cerebral infarct volume, enhanced the recovery of neurological function, mitigated BBB damage, and stimulated endothelial cell proliferation following ischemic stroke. Insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) is predicted to be a potential target gene for lncRNA H19. H19 knockdown increased IMP2 protein expression and IMP2 inhibition reversed the protective effects of H19 inhibition. CONCLUSION: Downregulation of H19 enhances angiogenesis and mitigates BBB damage by regulating IMP2, thereby alleviating cerebral I/R injury.

Path-based reasoning for biomedical knowledge graphs with BioPathNet.

Understanding complex interactions in biomedical networks is crucial for advancements in biomedicine, but traditional link prediction (LP) methods are limited in capturing this complexity. Representation-based learning techniques improve prediction accuracy by mapping nodes to low-dimensional embeddings, yet they often struggle with interpretability and scalability. We present BioPathNet, a novel graph neural network framework based on the Neural Bellman-Ford Network (NBFNet), addressing these limitations through path-based reasoning for LP in biomedical knowledge graphs. Unlike node-embedding frameworks, BioPathNet learns representations between node pairs by considering all relations along paths, enhancing prediction accuracy and interpretability. This allows visualization of influential paths and facilitates biological validation. BioPathNet leverages a background regulatory graph (BRG) for enhanced message passing and uses stringent negative sampling to improve precision. In evaluations across various LP tasks, such as gene function annotation, drug-disease indication, synthetic lethality, and lncRNA-mRNA interaction prediction, BioPathNet consistently outperformed shallow node embedding methods, relational graph neural networks and task-specific state-of-the-art methods, demonstrating robust performance and versatility. Our study predicts novel drug indications for diseases like acute lymphoblastic leukemia (ALL) and Alzheimer's, validated by medical experts and clinical trials. We also identified new synthetic lethality gene pairs and regulatory interactions involving lncRNAs and target genes, confirmed through literature reviews. BioPathNet's interpretability will enable researchers to trace prediction paths and gain molecular insights, making it a valuable tool for drug discovery, personalized medicine and biology in general.