Individualized, dynamic, and full-course vancomycin dosing prediction: a study on the customized dose model.

Purpose: The single-point trough-based therapeutic drug monitoring (TDM) and Bayesian forecasting approaches are still limited in individualized and dynamic vancomycin delivery. Until recently, there has not yet been enough focus on the direct integration of pharmacokinetic/pharmacodynamic (PK/PD) and TDM to construct a customized dose model (CDM) for vancomycin to achieve individualized, dynamic, and full-course dose prediction from empirical to follow-up treatment. This study sought to establish CDM for vancomycin, test its performance and superiority in clinical efficacy prediction, formulate a CDM-driven full-course dosage prediction strategy to overcome the above challenge, and predict the empirical vancomycin dosages for six Staphylococci populations and four strains in patients with various creatinine clearance rates (CLcr). Methods: The PK/PD and concentration models derived from our earlier research were used to establish CDM. The receiver operating characteristic (ROC) curve, with the area under ROC curve (AUCR) as the primary endpoint, for 21 retrospective cases was applied to test the performance and superiority of CDM in clinical efficacy prediction by comparison to the current frequently-used dose model (FDM). A model with an AUCR of at least 0.8 was considered acceptable. Based on the availability of TDM, the strategy of CDM-driven individualized, dynamic, and full-course dose prediction for vancomycin therapy was formulated. Based on the CDM, Monte Carlo simulation was used to predict the empirical vancomycin dosages for the target populations and bacteria. Results: Four CDMs and the strategy of CDM-driven individualized, dynamic, and full-course dose prediction for vancomycin therapy from empirical to follow-up treatment were constructed. Compared with FDM, CDM showed a greater AUCR value (0.807 vs. 0.688) in clinical efficacy prediction. The empirical vancomycin dosages for six Staphylococci populations and four strains in patients with various CLcr were predicted. Conclusion: CDM is a competitive individualized dose model. It compensates for the drawbacks of the existing TDM technology and Bayesian forecasting and offers a straightforward and useful supplemental approach for individualized and dynamic vancomycin delivery. Through mathematical modeling of the vancomycin dosage, this study achieved the goal of predicting doses individually, dynamically, and throughout, thus promoting "mathematical knowledge transfer and application" and also providing reference for quantitative and personalized research on similar drugs.

Queen bee acid pretreatment attenuates myocardial ischemia/reperfusion injury by enhancing autophagic flux.

Queen bee acid (QBA), which is exclusively found in royal jelly, has anti-inflammatory, antihypercholesterolemic, and antiangiogenic effects. A recent study demonstrated that QBA enhances autophagic flux in the heart. Considering the significant role of autophagy in the development of myocardial ischemia/reperfusion (I/R) injury, we investigated the effect of pretreatment with QBA on myocardial damage. In an in vivo model, left coronary artery blockage for 30 min and reperfusion for 2 h were used to induce myocardial I/R. In an in vitro model, neonatal rat cardiomyocytes (NRCs) were exposed to 3 h of hypoxia and 3 h of reoxygenation (H/R). Our results showed that pretreatment with QBA increased the cell viability of cardiomyocytes exposed to H/R in a dose-dependent manner, and the best protective concentration of QBA was 100 µM. Next, we noted that QBA pretreatment (24h before H/R) enhanced autophagic flux and attenuated mitochondrial damage, cardiac oxidative stress and apoptosis in NRCs exposed to H/R injury, and these effects were weakened by cotreatment with the autophagy inhibitor bafilomycin A1 (Baf). In addition, similar results were observed when QBA (10 mg/kg) was injected intraperitoneally into I/R mice 30 min before ischemia. Compared to mice subjected to I/R alone, those treated with QBA had decreased myocardial infarct area and increased cardiac function, whereas, these effects were partly reversed by Baf. Notably, in NRCs exposed to H/R, tandem fluorescent mRFP-GFP-LC3 assays indicated increased autophagosome degradation due to the increase in autophagic flux upon QBA treatment, but coinjection of Baf blocked autophagic flux. In this investigation, no notable adverse effects of QBA were detected in either cellular or animal models. Our findings suggest that QBA pretreatment mitigates myocardial I/R injury by eliminating dysfunctional mitochondria and reducing reactive oxygen species via promoting autophagic flux.

A novel framework for predicting glacial lake outburst debris flows in the Himalayas amidst climate change.

The retreat of Himalayan glaciers and the expansion of glacial lakes due to global warming have increased the occurrence of glacial lake outburst debris flow (GLODF), posing a serious threat to downstream communities. However, there are gaps in understanding the changes in GLODF occurrence driven by climate change, which challenges disaster management and cross-border cooperation in the Himalayas. To consider this issue, our study presents a novel framework integrating environmental evolution, a process-driven indicator system, and a hybrid machine learning model to predict Himalayan GLODF occurrence in the 21st century. Our findings indicate ongoing temperature (0.27-0.60 °C/10a) and precipitation (1.30-5.00 %/10a) increases under both SSP245 and SSP585 scenarios. Meanwhile, Himalayan glaciers are projected to lose between 70 % and 86 % of their mass by 2100 compared to 2020. Additionally, 2722 ± 207 new glacial lakes are expected to emerge by 2100. GLODF occurrence probability index is anticipated to rise to 1.27-1.30 times the current levels, with the Western Himalayas and Indus basin as high-incidence areas. Currently and in the future, the China-Nepal border remains a hotspot for cross-border GLODF. Our framework offers valuable long-term insights into Himalayan GLODF occurrence trends in response to climate change.

Precision control and parameter optimization in screw extrusion 3D printing of polypropylene materials.

Fused Deposition Modeling (FDM), a widely-utilized additive manufacturing (AM) technology, has found significant favor among automotive manufacturers. Polypropylene (PP) compound is extensively employed in the production of automotive parts due to its superior mechanical properties and formability. However, aiming at the problem of poor dimensional accuracy of pure PP parts, the quality of products can be enhanced by optimizing the combination of processing parameters. In this paper, the dimensional accuracy of 3D-printed components made from pure PP material is investigated. Key influencing factors such as infill percentage, infill pattern, layer thickness, and extrusion temperature are considered. To gain a deeper understanding, fluid simulation is conducted, and mathematical models are established to correlate processing parameters with dimensional accuracy. Furthermore, the Taguchi's experiments are designed and the experimental data are subjected to rigorous Signal-to-Noise ratio and ANOVA analyses. Within the experimental range, the lower extrusion temperature, infill percentage and layer thickness yield the best dimensional accuracy. Considering the influence factors of X, Y and Z directions, the optimal processing parameters for PP prints using screw extrusion 3D printers are determined as follows: an extrusion temperature of 210 °C, an infill percentage of 40 %, a layer thickness of 0.3 mm, and a concentric circle infill pattern. This study provides reference value for the subsequent improvement of the dimensional accuracy of the printed parts.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Elucidating the mechanisms of Buyang Huanwu Decoction in treating chronic cerebral ischemia: A combined approach using network pharmacology, molecular docking, and in vivo validation.

OBJECTIVE: This study aimed to explore the potential mechanisms of Buyang Huanwu Decoction (BHD) in regulating the AKT/TP53 pathway and reducing inflammatory responses for the treatment of chronic cerebral ischemia (CCI) using UHPLC-QE-MS combined with network pharmacology, molecular docking techniques, and animal experiment validation. METHODS: Targets of seven herbal components in BHD, such as Astragalus membranaceus, Paeoniae Rubra Radix, and Ligusticum chuanxiong, were identified through TCMSP and HERB databases. CCI-related targets were obtained from DisGeNET and Genecards, with an intersection analysis conducted to determine shared targets between the disease and the herbal components. Functional enrichment analysis of these intersecting targets was performed. Networks of gene ontology and pathway associations with these targets were constructed and visualized. A pharmacological network involving intersecting genes and active components was delineated. A protein-protein interaction network was established for these intersecting targets and visualized using Cytoscape 3.9.1. The top five genes from the PPI network and their corresponding active components underwent molecular docking. Finally, the 2-vessel occlusion (2-VO) induced CCI rat model was treated with BHD, and the network pharmacology findings were validated using Western blot, RT-PCR, behavioral tests, laser speckle imaging, ELISA, HE staining, Nissl staining, LFB staining, and immunohistochemistry and immunofluorescence. RESULTS: After filtration and deduplication, 150 intersecting genes were obtained, with the top five active components by Degree value identified as Quercetin, Beta-Sitosterol, Oleic Acid, Kaempferol, and Succinic Acid. KEGG pathway enrichment analysis linked key target genes significantly with Lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. The PPI network highlighted ALB, IL-6, AKT1, TP53, and IL-1ß as key protein targets. Molecular docking results showed the strongest binding affinity between ALB and Beta-Sitosterol. Behavioral tests using the Morris water maze indicated that both medium and high doses of BHD could enhance spatial memory in 2-VO model rats, with high-dose BHD being more effective. Laser speckle results showed that BHD at medium and high doses could facilitate CBF recovery in CCI rats, demonstrating a dose-response relationship. HE staining indicated that all doses of BHD could reduce neuronal damage in the cortex and hippocampal CA1 region to varying extents, with the highest dose being the most efficacious. Nissl staining showed that nimodipine and medium and high doses of BHD could alleviate Nissl body damage. LFB staining indicated that nimodipine and medium and high doses of BHD could reduce the pathological damage to fiber bundles and myelin sheaths in the internal capsule and corpus callosum of CCI rats. ELISA results showed that nimodipine and BHD at medium and high doses could decrease the levels of TNF-α, IL-6, IL-17, and IL-1ß in the serum of CCI rats (p < 0.05). Immunohistochemistry and immunofluorescence demonstrated that BHD could activate the AKT signaling pathway and inhibit TP53 in treating CCI. Western blot and RT-PCR results indicated that nimodipine and all doses of BHD could upregulate Akt1 expression and downregulate Alb, Tp53, Il-1ß, and Il-6 expression in the hippocampus of CCI rats to varying degrees (p < 0.05). CONCLUSION: BHD exerts therapeutic effects in the treatment of CCI by regulating targets, such as AKT1, ALB, TP53, IL-1ß, and IL-6, and reducing inflammatory responses.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

CONTEXT: Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. OBJECTIVE: To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. METHODS: We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. RESULTS: In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003). CONCLUSIONS: These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

ISODISTROTLaMTeO6 (M = Ga3+ and Mn3+): the critical role of electronic configuration and cation ordering in crystal structures.

In this work, PbSb2O6-type oxides LaMTeO6 (M = Ga3+ and Mn3+) were synthesized and structurally characterized by Rietveld refinements against high-resolution X-ray powder diffraction data. The Ga3+/Te6+ partial ordering within the honeycomb-like two-dimensional [GaTeO6]3- anionic layer leads to the loss of the inversion center between Ga3+ and Te6+; however the inversion center on the 3̄-roto-inversion axis is preserved, thereby resulting in a 2-fold PbSb2O6-type superstructure by doubling the c-axis associated with a structural symmetry descending from the original P3̄1m to P3̄1c symmetry. In contrast, LaMnTeO6 (P21/c) adopts a monoclinically distorted 4-fold superstructure with lattice dimensions of a ≈ aH, b ≈ √3aH, c ≈ 2cH, where aH and cH represent the lattice parameters of trigonal PbSb2O6. The formation of this P21/c-superstructure is attributed to the combination of complete Mn3+/Te6+ ordering and the first-order Jahn-Teller distortion of Mn3+ with the electronic configuration of d4. Such a monoclinic distortion can effectively lift the Mn3+ spin moments arranged on the triangular sublattice, resulting in a sharp peak for antiferromagnetic transition, which is in stark contrast to subtle magnetic transitions for PbSb2O6-type tellurates AMn(VI)TeO6 (A = alkaline earth and Pb2+) and LnCrTeO6 (Ln = rare earth) with higher structural symmetry. Our findings highlight that the electronic configuration effects of M-cations play a critical role in controlling the structure symmetry of LaMTeO6, providing a strategy to fine-tune the crystal structures and physical properties.

Ct-based diagnosis of sarcopenia as a prognostic factor for postoperative mortality after elective open-heart surgery in older patients: a cohort-based systematic review and meta-analysis.

Background: Cardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis. Methods: We conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Results: A total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke. Conclusion: Sarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate.

Traditional antibody-drug conjugates (ADCs) mainly suppress tumor growth through either chemotherapy with cytotoxic payloads or immunotherapy with immuno-modulators. However, a single therapeutic modality may limit their exploration. Herein, we developed a new type of drug conjugate termed CAR-EDC (CAR-M-derived exosome-drug conjugate) by using CAR-exosomes from CAR-M cells as the targeting drug carrier that contains a high level of CXCL10. CAR-exosomes could significantly enhance the immunological activation and migratory capacity of T lymphocytes and promote their differentiation into CD8+ T cells. It also increased the proportion of M1 macrophages. The CAR-EDC, covalently loaded with SN-38, was internalized into Raji cells through endocytosis mediated by the CAR molecules. It exerted excellent antitumor activity in vivo by virtue of not only chemotherapy by SN38 but also immunotherapy by CXCL10-mediated antitumor immunity. Generally, this study provides an exosome-drug conjugate system with enhanced antitumor effects over traditional ADCs through the synergism of chemotherapy and immunotherapy.

Role of reactive manganese and oxygen species in the KMnO4/Na2SO3 process for purification of algal-rich water and membrane fouling alleviation.

Ultrafiltration (UF) is a highly efficient technique for algal-rich water purification, but it is heavily contaminated due to the complex water characteristics. To solve this problem, potassium permanganate (KMnO4) oxidation enhanced with sodium sulfite (Na2SO3) was proposed as a pretreatment means. The results showed that the end-normalized flux was elevated from 0.10 to 0.91, and the reversible fouling resistance was reduced by 99.95%. The membrane fouling mechanism also changed obviously, without the generation of cake filtration. Regarding the properties of algal-rich water, the zeta potential was decreased from -29.50 to -5.87 mV after KMnO4/Na2SO3 pretreatment, suggesting that the electrostatic repulsion was significantly reduced. Meanwhile, the fluorescent components in algal-rich water were significantly eliminated, and the removal of dissolved organic carbon was increased to 67.46%. In the KMnO4/Na2SO3 process, reactive manganese species (i.e., Mn(V), Mn(III) and MnO2) and reactive oxygen species (i.e., SO4•- and •OH) played major roles in purifying algal-rich water. Specifically, SO4•-, •OH, Mn(V) and Mn(III) could effectively oxidize algal pollutants. Simultaneously, the in-situ adsorption and coagulation of MnO2 could accelerate the formation of flocs by decreasing the electrostatic repulsion between cells, and protect the algal cells from being excessive oxidized. Overall, the KMnO4/Na2SO3 process showed significant potential for membrane fouling alleviation in purifying algal-rich water.

The learning curve of laparoscopic splenectomy and esophagogastric devascularization for portal hypertension with 10-year follow-up.

INTRODUCTION AND OBJECTIVES: Laparoscopic splenectomy and esophagogastric devascularization (LSED) are minimally invasive, effective, and safe in treating esophageal-fundic variceal bleeding with portal hypertension (PHT). The study aimed to assess the learning curve of LSED by cumulative summation (CUSUM) analysis. The 10-year follow-up data for LSED and open surgery were also examined. PATIENTS AND METHODS: Five hundred and ninety-four patients were retrospectively analyzed. Operation time, intraoperative blood loss, open operation conversion, and postoperative complications were selected as the evaluation indicators of surgical ability. The learning curve of LESD was assessed by the CUSUM approach. Patient features, perioperative indices, and 10-year follow-up data were examined. RESULTS: Totally 236 patients underwent open surgery, and 358 underwent LSED. Patient characteristics were similar between groups. The LSED patients experienced less intraoperative blood loss, fewer complications, and faster recovery compared to the open surgery cohort. The learning curve of LESD was maximal for a case number of 50. Preoperative general characteristics were comparable for both stages. But the skilled stage had decreased operation time, reduced blood loss, less postoperative complications, and better recovery compared to the learning stage. The LSED group had higher recurrent hemorrhage-free survival rate and increased overall survival in comparison with cases administered open surgery in the 10-year follow-up. Free-liver cancer rates were similar between two groups. CONCLUSIONS: About 50 cases are needed to master the LSED procedure. Compared to open surgery, LSED is a safer, feasible, and safe procedure for PHT patients, correlating with decreased rebleeding rate and better overall survival.

Stapled hemorrhoidopexy for hemorrhoids: A overview of systematic reviews and meta-analysis.

Stapled hemorrhoidopexy has been used for years to treat hemorrhoids. Despite numerous systematic reviews and meta-analyses on the topic, inconsistent conclusions have left people uncertain about its effectiveness and raised doubts about the quality of these reviews.In order to provide reliable evidence for clinical practice, it is crucial to conduct an overview to assess the quality of MAs/SRs regarding the efficacy and complications of SH.A comprehensive search was performed across seven databases to identify MAs/SRs on the efficacy and complications of SH from inception to October 2023. The selected MAs/SRs were then assessed using three well-established tools: AMSTAR-2, PRISMA 2020and GRADE. These assessments provide a robust evaluation of the quality and reliability of the included MAs/SRs.We removed overlapping randomized controlled trials (RCTs) and conducted a new meta-analysis of the outcomes. The overview included 23 meta-analyses.In AMSTAR-2, three reviews were deemed moderate quality, nine reviews were classified as low quality, and eleven reviews were evaluated as critically low quality.In PRISMA 2020,certain deficiencies were exhibited, such as abstracts (0/23:0 %),final retrieval date (0/23:0 %), sensitivity analysis (6/23:26.09 %),publication bias assessment (11/23:47.83 %), the quality of evidence (2/23:8.70 %) and so on.In GRADE,twenty-six items were rated as moderate quality (27.96 %),forty-one items were rated as low quality (44.09 %) and twenty-six items were rated as critically low quality (27.96 %).SH has been found to be an effective intervention for reducing postoperative pain, shortening procedure time, and promoting wound healing. The re-analysis indicated that SH can reduce postoperative pain in hemorrhoid patients (odds ratio = 0.28, 95 % confidence interval [0.15,0.55], p = 0.0002; I2 = 74 %, p < 0.00001). But SH is associated with a higher risk of postoperative bleeding and recurrence of prolapse.Given that the reviews included in this overview were rated as low quality, caution should be exercised when interpreting the findings.

Changing Benzoxazole Ring into Nonring Imine Linkages on Covalent Organic Frameworks with Tuning H2O2 Photosynthesis Performance.

Two π-conjugated covalent organic frameworks (COFs) with nonring imine or benzoxazole ring linkages were prepared by reacting 3,3'-dihydrooxybenzidine (BDOH) with 3,5-triformylbenzene (Tb) in the presence or absence of benzimidazole (BDOH-Tb-IM and BDOH-Tb-BO). Although two COFs indicated similar composition, crystalline structures, and morphologies, imine-based BDOH-Tb-IM exhibited a photocatalytic H2O2 production rate of 2490 µmol·g-1·h-1 in sacrificial reagent-free pure water, higher than that of benzoxazole-based BDOH-Tb-BO-a (1168 µmol·g-1·h-1). The higher photocatalytic activity of BDOH-Tb-IM was attributed to its more efficient photoinduced charge separation and utilization efficiency and different 2e- ORR active sites over the two COFs. This study demonstrated an available ring effect to adjust photocatalytic performance between π-conjugated COFs.

Physiological Mechanisms by Which the Functional Ingredients in Beer Impact Human Health.

Nutritional therapy, for example through beer, is the best solution to human chronic diseases. In this article, we demonstrate the physiological mechanisms of the functional ingredients in beer with health-promoting effects, based on the PubMed, Google, CNKI, and ISI Web of Science databases, published from 1997 to 2024. Beer, a complex of barley malt and hops, is rich in functional ingredients. The health effects of beer against 26 chronic diseases are highly similar to those of barley due to the physiological mechanisms of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. Functional beer with low purine and high active ingredients made from pure barley malt, as well as an additional functional food, represents an important development direction, specifically, ginger beer, ginseng beer, and coix-lily beer, as consumed by our ancestors ca. 9000 years ago. Low-purine beer can be produced via enzymatic and biological degradation and adsorption of purines, as well as dandelion addition. Therefore, this review paper not only reveals the physiological mechanisms of beer in overcoming chronic human diseases, but also provides a scientific basis for the development of functional beer with health-promoting effects.

Stable cyclic ether as an electrolyte additive for high-performance lithium metal batteries.

Introducing a methyl group into 1,3-dioxolane (DOL) to obtain a stable cyclic ether, 4-methyl-1,3-dioxolane (4-Me DOL), allows it to be used as an additive in LiPF6-based carbonate electrolytes. The addition of 4-Me DOL can form a stable SEI with good Li+ transport ability, which can simultaneously improve the rate capability and cycling performance of lithium metal batteries.

Causal relationship between C-reactive protein and ischemic stroke caused by atherosclerosis: A Mendelian randomization study.

OBJECTIVES: This study investigates the association between C-reactive protein (CRP) and ischemic stroke caused by large artery atherosclerosis (LAA). METHODS: Five Mendelian Randomization (MR) methodologies were used for two-sample analyses: Inverse Variance Weighting (IVW), MR-Egger regression, Weighted Median (WM), Simple Mode, and Weighted Mode. CRP exposure data were obtained from aggregated summary statistics from a meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry (n = 343,524; UK Biobank). Stroke data were used as the outcome, with specific dataset details for relevant subtypes (cases = 40,585, controls = 406,111). RESULTS: In the CRP GWAS dataset, selected single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) showed genome-wide significance and a causal relationship with CRP, particularly in relation to LAA stroke. IVW indicated a robust causal connection between CRP and LAA stroke (Beta = 0.151, SE = 0.055, P = 0.006). The WM approach supported this relationship (Beta = 0.176, SE = 0.082, P = 0.033). However, MR-Egger regression suggested a potential absence of a causal link (Beta = 0.098, SE = 0.077, P = 0.206), with minimal influence from horizontal pleiotropy (Intercept = 0.0029; P = 0.317). The Simple mode found no significant association (Beta = 0.046, SE = 0.217, P = 0.834), while the Weighted mode revealed a significant causal association (Beta = 0.138, SE = 0.059, P = 0.020) between CRP and LAA stroke. CONCLUSIONS: MR analysis provides evidence for a potential causal relationship between CRP and an increased risk of LAA stroke.

Proteome-wide Ligand and Target Discovery by Using Strain-Enabled Cyclopropane Electrophiles.

The evolving use of covalent ligands as chemical probes and therapeutic agents could greatly benefit from an expanded array of cysteine-reactive electrophiles for efficient and versatile proteome profiling. Herein, to expand the current repertoire of cysteine-reactive electrophiles, we developed a new class of strain-enabled electrophiles based on cyclopropanes. Proteome profiling has unveiled that C163 of lactate dehydrogenase A (LDHA) and C88 of adhesion regulating molecule 1 (ADRM1) are ligandable residues to modulate the protein functions. Moreover, fragment-based ligand discovery (FBLD) has revealed that one fragment (Y-35) shows strong reactivity toward C66 of thioredoxin domain-containing protein 12 (TXD12), and its covalent binding has been demonstrated to impact its downstream signal pathways. TXD12 plays a pivotal role in enabling Y-35 to exhibit its antisurvival and antiproliferative effects. Finally, dicarbonitrile-cyclopropane has been demonstrated to be an electrophilic warhead in the development of GSTO1-involved dual covalent inhibitors, which is promising to alleviate drug resistance.

Formation of marine oil snow by soot particles generated from burning of oils.

This study aims to investigate the interactions between marine oil snow (MOS) formation and soot particles derived from two distinct oils: condensate and heavy oil. Experimental findings demonstrate that the properties of oil droplets and soot particles play a key role in MOS formation. Peak MOS formation is observed within the initial days for condensate, while for heavy oil, peak formation occurs at a later stage. Furthermore, the addition of oils and soot particles influences the final concentrations of polycyclic aromatic hydrocarbons (PAHs) in MOS. Remarkably, the ranking order of PAHs with different rings in various MOS samples remains consistent: 4- > 3- > 5- > 2- > 6-ring. Specific diagnostic ratios such as Phe/Ant, Ant/(Ant + Phe), BaA/(Chr + BaA), and LMW/HMW effectively differentiate petrogenic and pyrogenic sources of PAHs in MOS. And stable ratios like Flu/(Pyr + Flu), InP/(InP + BghiP), and BaF/BkF are identified for source analysis of soot MOS.