Investigating the mechanism of Fuling-Banxia-Dafupi in the treatment of diabetic kidney disease using network pharmacology and molecular docking.

Go deeply into the molecular mechanism of Fuling-Banxia-Dafupi in the treatment of diabetic kidney disease (DKD) by network pharmacology and molecular docking. Fuling-Banxia-Dafupi is a pair of traditional Chinese medicine for diabetic kidney disease, which can slow down the development of diabetic kidney disease. Screening active components and targets of Fuling-Banxia-Dafupi using the TCMSP database. The Uniprot database was also used to identify effective drug targets. DKD-related Targets were retrieved from the Gene Cards database, and the overlap between these targets and Fuling-Banxia-Dafupi was obtained. GO and KEGG pathway concentration analyses were showed using Metascape, and the results were presented by the microcredit platform. A total of 616 active ingredients and targets were confrimed and intersected with 3,951 diabetic neuropathy-related targets, resulting in 306 common targets. Baicalein and cerevisterol are the core components of Fuling-Banxia-Dafupi, and the key targets are TP53, SRC, and STAT 3. PI3K-Akt signalling pathway is an important pathway. The molecular docking indicated that its main active components and target proteins have good binding activity.

Case report: a cataract induced by bleomycin in a patient with testicular cancer.

Background: Bleomycin is a glycopeptide antibiotic with outstanding anti-tumor effects. A major adverse effect of bleomycin is lung fibrosis. However, the development of cataracts as a severe adverse effect has not been reported. Case summary: Herein, we describe the first case of cataract induced by bleomycin therapy in a 22-year-old male with testicular cancer. After surgical intervention and following five successive chemotherapy cycles of the BEP regimen, including bleomycin, etoposide and cisplatin, the patient reported a gradual painless loss of vision, with substantial decline in visual ability, especially in the right eye. Following comprehensive eye examinations, a cataract was diagnosed. Eventually, the patient underwent phacoemulsification and received replacement of the intraocular lenses. Conclusion: Bleomycin can cause cataracts, which induces a significant loss of vision. Therefore, clinicians should observe early symptoms and properly adjust treatment to prevent aggravation of symptoms.

Farmland's silent threat: Comprehensive multimedia assessment of micropollutants through non-targeted screening and targeted analysis in agricultural systems.

Intricate agricultural ecosystems markedly influence the dynamics of organic micropollutants, posing substantial threats to aquatic organisms and human health. This study examined the occurrence and distribution of organic micropollutants across soils, ditch sediment, and water within highly intensified farming setups. Using a non-targeted screening method, we identified 405 micropollutants across 10 sampling sites, which mainly included pesticides, pharmaceuticals, industrial chemicals, and personal care products. This inventory comprised emerging contaminants, banned pesticides, and controlled pharmaceuticals that had eluded detection via conventional monitoring. Targeted analysis showed concentrations of 3.99-1021 ng/g in soils, 4.67-2488 ng/g in sediment, and 12.5-9373 ng/L in water, respectively, for Σ40pesticides, Σ8pharmaceuticals, and Σ3industrial chemicals, indicating notable spatial variability. Soil organic carbon content and wastewater discharge were likely responsible for their spatial distribution. Principal component analysis and correlation analysis revealed a potential transfer of micropollutants across the three media. Particularly, a heightened correlation was decerned between soil and sediment micropollutant levels, highlighting the role of sorption processes. Risk quotients surpassed the threshold of 1 for 13-23 micropollutants across the three media, indicating high environmental risks. This study highlights the importance of employing non-targeted and targeted screening in assessing and managing environmental risks associated with micropollutants.

High-yield synthesis of hydroxylated boron nitride nanosheets and their utilization in thermally conductive polymeric nanocomposites.

Hexagonal boron nitride nanosheets (BNNSs) possess remarkable potential for various applications due to their unprecedented properties. However, the scalable production of BNNSs with both expansive surface and high solubility continues to present a significant challenge. Herein, we propose an innovative and efficient two-step method for manufacturing hydroxyl-functionalized BNNSs (OH-BNNSs). Initially, hydroxyl groups are covalently attached to bulk hexagonal boron nitride (h-BN) surfaces through H2O2 treatment. Then, the hydroxyl-functionalized h-BN undergoes exfoliation on account of a sudden increase in interlayer gas pressure generated by the vigorous decomposition of H2O2 in alkali solutions, resulting in the creation of OH-BNNSs. This approach produces relatively large flakes with an average dimension of 1.65 µm and a high yield of 45.2%. The resultant OH-BNNSs exhibit remarkable stability and dispersibility in a range of solvents. Their integration into thermoplastic polyurethane (TPU) significantly enhances both thermal conductivity and stability, attributed to the excellent compatibility with the resin matrix. This study represents a significant advancement in the functionalization and exfoliation of h-BN, opening new avenues for its promising applications in polymer composites.

Volatile Compounds for Discrimination between Beef, Pork, and Their Admixture Using Solid-Phase-Microextraction-Gas Chromatography-Mass Spectrometry (SPME-GC-MS) and Chemometrics Analysis.

This study addresses the prevalent issue of meat species authentication and adulteration through a chemometrics-based approach, crucial for upholding public health and ensuring a fair marketplace. Volatile compounds were extracted and analyzed using headspace-solid-phase-microextraction-gas chromatography-mass spectrometry. Adulterated meat samples were effectively identified through principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). Through variable importance in projection scores and a Random Forest test, 11 key compounds, including nonanal, octanal, hexadecanal, benzaldehyde, 1-octanol, hexanoic acid, heptanoic acid, octanoic acid, and 2-acetylpyrrole for beef, and hexanal and 1-octen-3-ol for pork, were robustly identified as biomarkers. These compounds exhibited a discernible trend in adulterated samples based on adulteration ratios, evident in a heatmap. Notably, lipid degradation compounds strongly influenced meat discrimination. PCA and PLS-DA yielded significant sample separation, with the first two components capturing 80% and 72.1% of total variance, respectively. This technique could be a reliable method for detecting meat adulteration in cooked meat.

The growth-promoting and disease-suppressing mechanisms of Trichoderma inoculation on peanut seedlings.

Trichoderma spp. is known for its ability to enhance plant growth and suppress disease, but the mechanisms for its interaction with host plants and pathogens remain unclear. This study investigated the transcriptomics and metabolomics of peanut plants (Arachis hypogaea L.) inoculated with Trichoderma harzianum QT20045, in the absence and presence of the stem rot pathogen Sclerotium rolfsii JN3011. Under the condition without pathogen stress, the peanut seedlings inoculated with QT20045 showed improved root length and plant weight, increased indole acetic acid (IAA) production, and reduced ethylene level, with more active 1-aminocyclopropane-1-carboxylate acid (ACC) synthase (ACS) and ACC oxidase (ACO), compared with the non-inoculated control. Under the pathogen stress, the biocontrol efficacy of QT20045 against S. rolfsii was 78.51%, with a similar effect on plant growth, and IAA and ethylene metabolisms to the condition with no biotic stress. Transcriptomic analysis of peanut root revealed that Trichoderma inoculation upregulated the expression of certain genes in the IAA family but downregulated the genes in the ACO family (AhACO1 and AhACO) and ACS family (AhACS3 and AhACS1) consistently in the absence and presence of pathogens. During pathogen stress, QT20045 inoculation leads to the downregulation of the genes in the pectinesterase family to keep the host plant's cell wall stable, along with upregulation of the AhSUMM2 gene to activate plant defense responses. In vitro antagonistic test confirmed that QT20045 suppressed S. rolfsii growth through mechanisms of mycelial entanglement, papillary protrusions, and decomposition. Our findings highlight that Trichoderma inoculation is a promising tool for sustainable agriculture, offering multiple benefits from pathogen control to enhanced plant growth and soil health.

Artificial intelligence-driven multiomics predictive model for abdominal aortic aneurysm subtypes to identify heterogeneous immune cell infiltration and predict disease progression.

BACKGROUND: Abdominal aortic aneurysm (AAA) poses a significant health risk and is influenced by various compositional features. This study aimed to develop an artificial intelligence-driven multiomics predictive model for AAA subtypes to identify heterogeneous immune cell infiltration and predict disease progression. Additionally, we investigated neutrophil heterogeneity in patients with different AAA subtypes to elucidate the relationship between the immune microenvironment and AAA pathogenesis. METHODS: This study enrolled 517 patients with AAA, who were clustered using k-means algorithm to identify AAA subtypes and stratify the risk. We utilized residual convolutional neural network 200 to annotate and extract contrast-enhanced computed tomography angiography images of AAA. A precise predictive model for AAA subtypes was established using clinical, imaging, and immunological data. We performed a comparative analysis of neutrophil levels in the different subgroups and immune cell infiltration analysis to explore the associations between neutrophil levels and AAA. Quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay were performed to elucidate the interplay between CXCL1, neutrophil activation, and the nuclear factor (NF)-κB pathway in AAA pathogenesis. Furthermore, the effect of CXCL1 silencing with small interfering RNA was investigated. RESULTS: Two distinct AAA subtypes were identified, one clinically more severe and more likely to require surgical intervention. The CNN effectively detected AAA-associated lesion regions on computed tomography angiography, and the predictive model demonstrated excellent ability to discriminate between patients with the two identified AAA subtypes (area under the curve, 0.927). Neutrophil activation, AAA pathology, CXCL1 expression, and the NF-κB pathway were significantly correlated. CXCL1, NF-κB, IL-1ß, and IL-8 were upregulated in AAA. CXCL1 silencing downregulated NF-κB, interleukin-1ß, and interleukin-8. CONCLUSION: The predictive model for AAA subtypes demonstrated accurate and reliable risk stratification and clinical management. CXCL1 overexpression activated neutrophils through the NF-κB pathway, contributing to AAA development. This pathway may, therefore, be a therapeutic target in AAA.

Distinctive phenotypic and microenvironmental characteristics of neuroendocrine carcinoma and adenocarcinoma component in gastric mixed adenoneuroendocrine carcinoma.

This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N=32) or NEC (N=23) were analysed using digital spatial profiling (GeoMx® DSP). Representative regions of interest (ROIs) were selected from the adenocarcinoma portion (ADC-MANEC) and neuroendocrine carcinoma portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All ROIs were separated into epithelial components and stromal components by the masking procedure in GeoMx® platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including PEG10, MAP1B, STMN3, and AKT3) and stromal (FN1, COL1A1, SPARC, and BGN) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, while fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histological component of MANEC according to its tumour versus stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation dataset for future studies.

Two-dimensional and high-order directional information modulations for secure communications based on programmable metasurface.

Conventional wireless communication schemes indiscriminately transmit information into the whole space and pose inherent security risks. Recently, directional information modulation (DIM) has attracted enormous attention as a promising technology. DIM generates correct constellation symbols in the desired directions and distorts them in undesired directions, thus ensuring the security of the transmitted information. Although several DIM schemes have been reported, they suffer from defects of bulkiness, energy consumption, high cost, and inability to support two-dimensional (2D) and high-order modulations. Here, we propose a DIM scheme based on a 2-bit programmable metasurface (PM) that overcomes these defects. A fast and efficient discrete optimization algorithm is developed to optimize the digital coding sequences, and the correct constellation symbols can be generated and transmitted in multi-directional beams. As a proof-of-concept, three sets of constellation diagrams (8 phase shift keying (PSK), 16 quadrature amplitude modulation (QAM), and 64QAM) are realized in the multi-channel modes. This work provides an important route of employing DIM for ensuring physical-layer security and serves as a stepping stone toward endogenous secure communications.

An artificial intelligence system for comprehensive pathologic outcome prediction in early gastric cancer through endoscopic image analysis (with video).

BACKGROUND: Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos. METHODS: To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution. RESULTS: After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively. CONCLUSIONS: AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM.

Impact of Complete Revascularization for Acute Myocardial Infarction In Multivessel Coronary Artery Disease Patients With Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: The clinical benefits of complete revascularization (CR) in acute myocardial infarction (AMI) patients are unclear. Moreover, the benefit of CR is unknown in AMI with diabetes mellitus (DM) patients. We sought to compare the prognosis of CR and incomplete revascularization (IR) in patients with AMI and multivessel disease, according to the presence of DM. METHODS: A total of 2,150 AMI patients with multivessel coronary artery disease were analyzed. CR was defined based on the angiographic image. The primary endpoint of this study was the patient-oriented composite outcome (POCO) defined as a composite of all-cause death, any myocardial infarction, and any revascularization within 3 years. RESULTS: Overall, 3-year POCO was significantly lower in patients receiving angiographic CR (985 patients, 45.8%) compared with IR (1,165 patients, 54.2%). When divided into subgroups according to the presence of DM, CR reduced 3-year clinical outcomes in the non-DM group but not in the DM group (POCO: 11.7% vs. 23.2%, p<0.001, any revascularization: 7.2% vs. 10.8%, p=0.024 in the non-DM group, POCO: 24.3% vs. 27.8%, p=0.295, any revascularization: 13.3% vs. 11.3%, p=0.448 in the DM group, for CR vs. IR). Multivariate analysis showed that CR significantly reduced 3-year POCO (hazard ratio, 0.52; 95% confidence interval, 0.36-0.75) only in the non-DM group. CONCLUSIONS: In AMI patients with multivessel disease, CR may have less clinical benefit in DM patients than in non-DM patients.

Paeonol alleviates ox-LDL-induced endothelial cell injury by targeting the heme oxygenase-1/phosphoinositide 3-kinase/protein kinase B pathway.

Atherosclerosis is a leading cause of vascular disease worldwide. Paeonol has been reported to have therapeutical potential in atherosclerosis. The aim of this study is to explore the effect of paeonol on oxidized low-density lipoprotein (ox-LDL)-induced endothelial cells injury and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (100 µg/ml) to mimic atherosclerosis in vitro. The cell viability, proliferation, and apoptosis were assessed by cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry, respectively. The angiogenesis was detected by tube formation assay. The levels of inflammatory factor were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the levels of Fe2+, reactive oxygen species (ROS), and glutathione (GSH) were detected to assess ferroptosis. The western blot was used to detect the protein expression. Ox-LDL inhibited cell viability, proliferation, and angiogenesis, but induced apoptosis and inflammation in HUVECs, and paeonol (75 µM) relieves ox-LDL-induced HUVEC injury. Also, paeonol inhibited ox-LDL-induced ferroptosis of HUVECs. Interestingly, heme oxygenase-1 (HMOX1) knockdown alleviated ox-LDL-induced HUVECs injury and ferroptosis. Paeonol affected ox-LDL-induced HUVECs via regulating HMOX1. In addition, paeonol regulated PI3K/AKT pathway via HMOX1, and the inhibitor of phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway reversed the effects of HMOX1 knockdown on ox-LDL-induced HUVECs. Paeonol alleviated ox-LDL-induced HUVEC injury by regulating the PI3K/AKT pathway via targeting HMOX1.

Preparation, characterization, and liver targeting evaluation of a novel sustained-release brucine self-assembled micelle mediated by glycyrrhetinic acid.

Background: Cancer is a serious threat to human life, health and social development. In recent years, nanomicelles, as an emerging drug carrier material, have gradually entered people's field of vision because of their advantages of improving bioavailability, maintaining drug levels, reducing systemic side effects and increasing drug accumulation at target sites. Methods: In this study, B-GPSG nano-micelles were prepared by film dispersion hydration method using brucine as model drug and glycyrrhetinic acid-polyethylene glycol-3-methylene glycol-dithiodipropionic acid-glycerol monostearate polymer as nano-carrier. The preparation process, characterization, drug release in vitro, pharmacokinetics and liver targeting were investigated. Results: The results showed that the range of particle size, polydispersion index and Zeta potential were 102.7 ± 1.09 nm, 0.201 ± 0.02 and -24.5 ± 0.19 mV respectively. The entrapment efficiency and drug loading were 83.79 ± 2.13% and 12.56 ± 0.09%, respectively. The drug release experiments in vitro and pharmacokinetic experiments showed that it had obvious sustained release effect. For pharmacokinetics study, it shows that both the B-GPSG solution group and the B-PSG solution group changed the metabolic kinetic parameters of brucine, but the B-GPSG solution group had a better effect. Compared with the B-PSG solution group, the drug was more prolonged in rats. The half-life in the body and the retention time in the body of B-GPSG are more helpful to improve the bioavailability of the drug and play a long-term effect. The tail vein injection results of mice indicate that B-GPSG can target and accumulate brucine in the liver without affecting other key organs. Cell uptake experiments and tissue distribution experiments in vivo show that glycyrrhetinic acid modified nano-micelles can increase the accumulation of brucine in hepatocytes, has a good liver targeting effect, and can be used as a new preparation for the treatment of liver cancer. Conclusion: The B-SPSG prepared in this experiment can provide a new treatment method and research idea for the treatment of liver cancer.

Associations between body mass index and all-cause and CVD mortality in agriculture, forestry, and fishing occupations: A prospective cohort study using NHANES data (1999-2014).

INTRODUCTION: Obesity, as indicated by elevated Body Mass Index (BMI), is a well-established global health concern associated with increased morbidity and mortality across diverse populations. However, the influence of BMI on individuals in Agriculture, Forestry, and Fishing (AFF) occupations, characterized by unique challenges and environmental factors, has received limited research attention. METHODS: Our study, a prospective cohort analysis, utilized National Health and Nutrition Examination Survey (NHANES) data from 1999-2014, targeting adults above 18 in AFF occupations with comprehensive BMI data, omitting individuals with a history of cancer. Mortality outcomes were extracted from the NHANES mortality file, and BMI was segmented into eight categories. Essential covariates such as age, sex, race, and various health factors were incorporated. The statistical analysis encompassed Cox regression, generalized additive models, smooth curve fitting, and stratified analyses. RESULTS: During 1,005 person-years with 201 all-cause and 57 CVD deaths, we observed L-shaped and U-shaped correlations of BMI with all-cause and CVD mortality, featuring a pivotal inflection at 26.69 and 27.40 kg/m2. Above this BMI threshold of 26.69 and 27.4 kg/m2, all-cause mortality association was not significant while CVD mortality was positive. CONCLUSIONS: This study highlights a unique BMI-mortality association in AFF occupations, diverging from standard patterns. The rigorous labor and environmental conditions in AFF jobs suggest that a certain range of higher BMI could reduce mortality risk. This highlights the necessity for tailored health guidelines in different occupations. Future research should concentrate on diverse health indicators and enhanced risk assessment for physically strenuous occupations.

Safety and feasibility of single-incision laparoscopic distal gastrectomy in overweight and obese gastric cancer patients: a propensity score-matched analysis.

BACKGROUND: The technical challenges and safety concerns of single-incision laparoscopic gastrectomy for overweight and obese gastric cancer patients remain unclear. This study aimed to evaluate the safety and feasibility of single-incision laparoscopic distal gastrectomy (SIDG) compared to multiport laparoscopic distal gastrectomy (MLDG) in overweight and obese gastric cancer patients. METHODS: This study retrospectively analyzed overweight and obese patients (body mass index ≥ 25 kg/m2) and pathologic stage T1 primary gastric adenocarcinoma treated with either SIDG or MLDG. The SIDG and MLDG groups were propensity score matched at a 1:2 ratio using age, sex, height, body weight, American Society of Anesthesiologists classification, year of surgery, pathologic N stage, and anastomosis method as covariates. RESULTS: After 1:2 matching, the study included patients who underwent SIDG (n = 179) and MLDG (n = 358). No significant difference in the number of retrieved lymph nodes was found between the SIDG and MLDG groups (52.8 ± 19.3 vs. 53.9 ± 21.0, P = 0.56). Operation times were significantly shorter in the SIDG group (170.8 ± 60.0 min vs. 186.1 ± 52.6 min, P = 0.004). The postoperative hospital length of stay was comparable between the 2 groups (SIDG: 5.9 ± 3.4 days vs. MLDG: 6.3 ± 5.1 days, P = 0.23), as was postoperative complication rate (SIDG: 13.4% vs. MLDG: 12.8%, P = 0.89). CONCLUSIONS: SIDG was shown to be as safe and feasible as MLDG for overweight and obese gastric cancer patients, with comparable early postoperative complication rates without compromising operation time compared to MLDG.

Visible-Light-Promoted Cascade Carboxylation/Arylation of Unactivated Alkenes with CO2 for the Synthesis of Carboxylated Indole-Fused Heterocycles.

Described here is a visible-light-promoted cascade carboxylation/arylation of indole-tethered unactivated alkenes with CO2 to access various carboxylated indole-fused heterocycles. This reaction is initiated by the addition of a CO2 radical anion to the alkene motif toward an alkyl carbon radical, followed by its addition to the aromatic ring, and then rearomatization to afford the final products. This reaction provides a facile and sustainable protocol for the construction of carboxylated indole-fused heterocycles using CO2 as the carboxylic source.

Correlation between lipoprotein(a) and recurrent ischemic events post-cerebral vascular stent implantation.

BACKGROUND AND AIM: The association of Lipoprotein(a) (Lp[a]) with recurrent ischemic events in stented patients remains uncertain. So, this research aimed to investigate the impact of elevated Lp(a) levels on the occurrence of ischemic events in this specific patient population. METHODS: Totally 553 patients who underwent intracranial or extracranial artery stent implantation were included. Baseline data were collected and postoperative ischemic outcomes were followed up. Cox regression analysis was used to investigate the association between Lp(a) and outcomes, while accounting for confounding factors. Finally, we established prediction models based on nomogram. RESULTS: Of total 553 patients, a number of 107 (19.3%) experienced outcomes. These included 46 cases (34.7%) in group with elevated Lp(a) levels (>30 mg/dL) and 61 cases (18.4%) in non-elevated group (χ2=6.343, p=0.012). The group with elevated Lp(a) was 1.811 times more likely to experience ischemic events than the non-elevated group, each 1 mg/dL increase in Lp(a) resulted in a 1.008-fold increase in the recurrence rate of ischemic events. In addition, sex (male), previous history of coronary heart disease, decreased albumin, elevated very low density lipoprotein cholesterol and poorly controlled risk factors (including blood pressure and blood sugar) were also associated with a high risk of recurrent ischemic events after stent implantation. CONCLUSION: Lp(a) elevation was a significant risk factor for ischemic events in symptomatic patients who underwent intracranial or extracranial artery stenting.

Gut Microbiota, Human Blood Metabolites, and Esophageal Cancer: A Mendelian Randomization Study.

BACKGROUND: Unbalances in the gut microbiota have been proposed as a possible cause of esophageal cancer (ESCA), yet the exact causal relationship remains unclear. PURPOSE: To investigate the potential causal relationship between the gut microbiota and ESCA with Mendelian randomization (MR) analysis. METHODS: Genome-wide association studies (GWASs) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) and 205 gut microbiota metabolic pathways conducted by the Dutch Microbiome Project (DMP) and a FinnGen cohort GWAS of esophageal cancer specified the summary statistics. To investigate the possibility of a mediation effect between the gut microbiota and ESCA, mediation MR analyses were performed for 1091 blood metabolites and 309 metabolite ratios. RESULTS: MR analysis indicated that the relative abundance of 10 gut microbial taxa was associated with ESCA but all the 12 gut microbiota metabolic pathways with ESCA indicated no statistically significant association existing. Two blood metabolites and a metabolite ratio were discovered to be mediating factors in the pathway from gut microbiota to ESCA. CONCLUSION: This research indicated the potential mediating effects of blood metabolites and offered genetic evidence in favor of a causal correlation between gut microbiota and ESCA.

Mechanistic insights into tris(2-chloroisopropyl) phosphate biomineralization coupled with lead (II) biostabilization driven by denitrifying bacteria.

The ubiquity and persistence of organophosphate esters (OPEs) and heavy metal (HMs) pose global environmental risks. This study explored tris(2-chloroisopropyl)phosphate (TCPP) biomineralization coupled to lead (Pb2+) biostabilization driven by denitrifying bacteria (DNB). The domesticated DNB achieved synergistic bioremoval of TCPP and Pb2+ in the batch bioreactor (efficiency: 98 %).TCPP mineralized into PO43- and Cl-, and Pb2+ precipitated with PO43-. The TCPP-degrading/Pb2+-resistant DNB: Achromobacter, Pseudomonas, Citrobacter, and Stenotrophomonas, dominated the bacterial community, and synergized TCPP biomineralization and Pb2+ biostabilization. Metagenomics and metaproteomics revealed TCPP underwent dechlorination, hydrolysis, the TCA cycle-based dissimilation, and assimilation; Pb2+ was detoxified via bioprecipitation, bacterial membrane biosorption, EPS biocomplexation, and efflux out of cells. TCPP, as an initial donor, along with NO3-, as the terminal acceptor, formed a respiratory redox as the primary energy metabolism. Both TCPP and Pb2+ can stimulate phosphatase expression, which established the mutual enhancements between their bioconversions by catalyzing TCPP dephosphorylation and facilitating Pb2+ bioprecipitation. TCPP may alleviate the Pb2+-induced oxidative stress by aiding protein phosphorylation. 80 % of Pb2+ converted into crystalized pyromorphite. These results provide the mechanistic foundations and help develop greener strategies for synergistic bioremediation of OPEs and HMs.

Durable-polymer versus biodegradable-polymer drug-eluting stents in acute coronary syndromes: three-year outcomes of the HOST REDUCE POLYTECH RCT Trial.

BACKGROUND: Long-term follow-up is essential to evaluate the impact of polymer degradation in drug-eluting stents (DES). AIMS: We aimed to compare durable-polymer DES (DP-DES) and biodegradable-polymer DES (BP-DES) during a 3-year follow-up to evaluate the entire period of polymer resolution (before, during, and after degradation). METHODS: The HOST REDUCE POLYTECH RCT Trial was a randomised clinical trial enrolling patients with acute coronary syndrome (ACS) and comparing the efficacy and safety of DP-DES and BP-DES. The primary outcome was a patient-oriented composite outcome (POCO), and the key secondary outcome was a device-oriented composite outcome (DOCO). RESULTS: A total of 3,413 ACS patients were randomised to either the DP-DES (1,713 patients) or BP-DES (1,700 patients) group. During the 3-year follow-up, the risk of the POCO was similar between the DP-DES and BP-DES groups (14.8% vs 15.4%, hazard ratio [HR] 0.96, 95% confidence interval [CI]: 0.80-1.14; p=0.613). However, the risk of the DOCO was lower in the DP-DES group (6.0% vs 8.0%, HR 0.73, 95% CI: 0.57-0.95; p=0.020). In a landmark analysis, the lower risk of the DOCO for the DP-DES group was evident during the transition from the early to the late period after percutaneous coronary intervention (PCI) (from 8 to 16 months post-PCI; 1.8% vs 3.3%, HR 0.54, 95% CI: 0.34-0.84; p=0.007), which was mainly driven by a risk reduction of target lesion revascularisation. CONCLUSIONS: In ACS patients, DP-DES showed similar results to BP-DES regarding the POCO up to 3 years. For the DOCO, DP-DES were superior to BP-DES; this was due to the higher event rate during the period of polymer degradation.