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1.
Pediatr Neonatol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38991861

ABSTRACT

BACKGROUND: The objective was to evaluate the efficacy of introducing less invasive surfactant administration (LISA) for management of preterm neonates with respiratory distress syndrome (RDS). METHODS: This was a retrospective cohort study identifying preterm neonates with RDS born between 2017 and 2022 in a tertiary neonatal unit, where LISA was introduced in January 2020. Time trend analysis comparing cohort of neonates born before (2017-2020) and after LISA introduction (2020-2022) was performed. The primary outcomes were incidence and severity of bronchopulmonary dysplasia (BPD). Multivariable regression models were used to estimate the association between introducing LISA to RDS management and health and safety outcomes. RESULTS: In total, 261 neonates with RDS were included (114 born after LISA was introduced). Neonates receiving invasive surfactant administration had lower gestational age, birth weight, lower Apgar scores, and higher oxygen requirement, compared to those receiving LISA. In the time trend analysis, introduction of LISA was associated with lower incidence of BPD (odds ratio (95% confidence interval) 0.34 (0.16, 0.72)), and lower severity of BPD (0.31 (0.16, 0.59)). Pre- and post-LISA period showed similar treatment safety profiles. CONCLUSION: Introduction of LISA was associated with improved prognosis in neonates with RDS in Hong Kong.

2.
J Anim Sci Biotechnol ; 15(1): 92, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38965570

ABSTRACT

BACKGROUND: Environmental heat stress (HS) can have detrimental effects on milk production by compromising the mammary function. Mammary plasma flow (MPF) plays a crucial role in nutrient supply and uptake in the mammary gland. In this experiment, we investigated the physiological and metabolic changes in high-yielding cows exposed to different degrees of HS: no HS with thermal-humidity index (THI) below 68 (No-HS), mild HS (Mild-HS, 68 ≤ THI ≤ 79), and moderate HS (Mod-HS, 79 < THI ≤ 88) in their natural environment. Our study focused on the changes in blood oxygen supply and mammary glucose uptake and utilization. RESULTS: Compared with No-HS, the MPF of dairy cows was greater (P < 0.01) under Mild-HS, but was lower (P < 0.01) in cows under Mod-HS. Oxygen supply and consumption exhibited similar changes to the MPF under different HS, with no difference in ratio of oxygen consumption to supply (P = 0.46). The mammary arterio-vein differences in glucose concentration were lower (P < 0.05) under Mild- and Mod-HS than under no HS. Glucose supply and flow were significantly increased (P < 0.01) under Mild-HS but significantly decreased (P < 0.01) under Mod-HS compared to No-HS. Glucose uptake (P < 0.01) and clearance rates (P < 0.01) were significantly reduced under Mod-HS compared to those under No-HS and Mild-HS. Under Mild-HS, there was a significant decrease (P < 0.01) in the ratio of lactose yield to mammary glucose supply compared to that under No-HS and Mod-HS, with no difference (P = 0.53) in the ratio of lactose yield to uptaken glucose among different HS situations. CONCLUSIONS: Degrees of HS exert different influences on mammary metabolism, mainly by altering MPF in dairy cows. The output from this study may help us to develop strategies to mitigate the impact of different degrees of HS on milk production.

3.
Clin Nutr ESPEN ; 63: 214-225, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38970786

ABSTRACT

BACKGROUND: Bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) serves as common modalities for body composition assessment. This study was aimed to evaluate the agreement between BIA and DXA measures in UK Biobank. METHODS: UK Biobank participants with body fat mass (FM) and fat-free mass (FFM) estimates obtained through BIA (Tanita BC418MA) and DXA concurrently were included. Correlation between BIA and DXA-derived estimates were assessed with Lin's concordance correlation coefficients. Bland-Altman and Passing-Boblok analyses were performed to quantify the difference and agreement between BIA and DXA. Multivariable linear regression was used to identify predictors influencing the differences. Finally, prediction models were developed to calibrate BIA measures against DXA. RESULTS: The analysis included 34437 participants (female 51.4%, mean age 64.1 years at imaging assessment). BIA and DXA measurements were highly correlated (Lin's concordance correlation coefficient 0.94 for FM and 0.94 for FFM). BIA (Tanita BC418MA) underestimates FM overall by 1.84 kg (23.77 vs. 25.61, p < 0.01), and overestimated FFM overall by 2.56 kg (52.49 vs. 49.93, p < 0.01). The BIA-DXA differences were associated with FM, FFM, BMI and waist circumference. The developed prediction models showed overall good performance in calibrating BIA data. CONCLUSION: Our analysis exhibited strong correlation between BIA (Tanita BC418MA)- and DXA-derived body composition measures at a population level in UK Biobank. However, the BIA-DXA differences were observed at individual level and associated with individual anthropometric measures. Future studies may explore the use of prediction models to enhance the calibration of BIA measures for more accurate assessments in UK Biobank.

4.
iScience ; 27(6): 110130, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38952687

ABSTRACT

The development of osteoarthritis (OA) involves subchondral bone lesions, but the role of osteoblastic autophagy-related genes (ARGs) in osteoarthritis is unclear. Through integrated analysis of single-cell dataset, Bulk RNA dataset, and 367 ARGs extracted from GeneCards, 40 ARGs were found. By employing multiple machine learning algorithms and PPI networks, three key genes (DDIT3, JUN, and VEGFA) were identified. Then the RF model constructed from these genes indicated great potential as a diagnostic tool. Furthermore, the model's effectiveness in predicting OA has been confirmed through external validation datasets. Moreover, the expression of ARGs was examined in osteoblasts subject to excessive mechanical stress, human and mouse tissues. Finally, the role of ARGs in OA was confirmed through co-culturing explants and osteoblasts. Thus, osteoblastic ARGs could be crucial in OA development, providing potential diagnostic and treatment strategies.

5.
Heliyon ; 10(12): e32839, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975213

ABSTRACT

This study examines the atmospheric water cycle dynamics in the China-Mongolia Arid Region (CMAR), a region significantly affected by aridity. By employing a combination of Empirical Orthogonal Function (EOF) analysis, ERA5 reanalysis data, and the Dynamic Recycling Model (DRM), we investigate the spatial and temporal variations in the Precipitation Recycling Ratio (PRR) and Precipitable Water Conversion Rate (PWCR) over a forty-year period (1979-2021). Our findings reveal that both PRR and PWCR are generally higher but decreasing in most subregions of CMAR, suggesting a notable contribution of local moisture to precipitation. We also identify an increasing trend in PRR across the northwestern subregions and a decreasing trend in other areas. Similarly, PWCR exhibits an increasing trend in the northwestern and southern subregions, while decreasing elsewhere, implying a decline in water vapor conversion and recycling efficiency. Furthermore, our EOF analysis uncovers distinct spatial patterns, with dominant modes accounting for significant variances in PRR and PWCR, correlating with local variations in atmospheric moisture and advective changes. These results underscore the complex interplay between regional topography, atmospheric dynamics, and the hydrological cycle in CMAR. The insights from this study are vital for formulating effective water management strategies and adapting to climate change impacts in arid regions, holding broad implications for environmental science, climate studies, and sustainable resource management. Our findings reveal distinct spatial patterns and contrasting trends in precipitation recycling and water vapor conversion across the subregions of CMAR. This heterogeneity underscores the importance of conducting analyses at finer spatial scales to avoid contradictory conclusions that can arise from topographic influences when treating CMAR as a single unit. Future studies should focus on smaller subregions to accurately capture the intricacies of the water cycle in this topographically complex arid region.

6.
Front Immunol ; 15: 1391848, 2024.
Article in English | MEDLINE | ID: mdl-38983856

ABSTRACT

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.


Subject(s)
Arthritis, Rheumatoid , Gene Expression Profiling , Transcriptome , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/diagnosis , Humans , Antirheumatic Agents/therapeutic use , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Biomarkers , CD8-Positive T-Lymphocytes/immunology
8.
Molecules ; 29(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38893464

ABSTRACT

Acrylamide polymers with a high degree of polymerization are widely used in petroleum production. It is of great significance to study the oil displacement mechanism of acrylamide polymers with a high degree of polymerization from the micro level. In recent years, the rapid development of computer molecular simulation technology has filed the gaps in macroscopic experiments and theories. This technology has been highly valued in the study of the molecular behaviour of polymer systems. In this paper, the research progress of molecular simulation applied to high-polymerization-degree acrylamide polymer is summarized. The application status of acrylamide polymer flooding, the analysis of polymer flooding mechanisms, and the research progress of molecular simulation in acrylamide linear and crosslinked polymers are expounded. Finally, the development prospect of acrylamide polymer research is given, and suggestions are put forward in terms of simulation direction and simulation tools.

9.
Sci Total Environ ; 943: 173748, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38857793

ABSTRACT

In many coastal cities around the world, continuing water degradation threatens the living environment of humans and aquatic organisms. To assess and control the water pollution situation, this study estimated the Biochemical Oxygen Demand (BOD) concentration of Hong Kong's marine waters using remote sensing and an improved machine learning (ML) method. The scheme was derived from four ML algorithms (RBF, SVR, RF, XGB) and calibrated using a large amount (N > 1000) of in-situ BOD5 data. Based on labeled datasets with different preprocessing, i.e., the original BOD5, the log10(BOD5), and label distribution smoothing (LDS), three types of models were trained and evaluated. The results highlight the superior potential of the LDS-based model to improve BOD5 estimate by dealing with imbalanced training dataset. Additionally, XGB and RF outperformed RBF and SVR when the model was developed using log10(BOD5) or LDS(BOD5). Over two decades, the BOD5 concentration of Hong Kong marine waters in the autumn (Sep. to Nov.) shows a downward trend, with significant decreases in Deep Bay, Western Buffer, Victoria Harbour, Eastern Buffer, Junk Bay, Port Shelter, and the Tolo Harbour and Channel. Principal component analysis revealed that nutrient levels emerged as the predominant factor in Victoria Harbour and the interior of Deep Bay, while chlorophyll-related and physical parameters were dominant in Southern, Mirs Bay, Northwestern, and the outlet of Deep Bay. LDS provides a new perspective to improve ML-based water quality estimation by alleviating the imbalance in the labeled dataset. Overall, the remotely sensed BOD5 can offer insight into the spatial-temporal distribution of organic matter in Hong Kong coastal waters and valuable guidance for the pollution control.


Subject(s)
Environmental Monitoring , Machine Learning , Seawater , Hong Kong , Environmental Monitoring/methods , Seawater/chemistry , Remote Sensing Technology , Biological Oxygen Demand Analysis , Water Pollution/statistics & numerical data , Water Pollution/analysis , Water Pollutants, Chemical/analysis
10.
Article in English | MEDLINE | ID: mdl-38913036

ABSTRACT

A novel chemoheterotrophic iron-reducing micro-organism, designated as strain LSZ-M11000T, was isolated from sediment of the Marianas Trench. Phylogenetic analysis based on the 16S rRNA gene revealed that strain LSZ-M11000T belonged to genus Tepidibacillus, with 97 % identity to that of Tepidibacillus fermentans STGHT, a mesophilic bacterium isolated from the Severo-Stavropolskoye underground gas storage facility in Russia. The polar lipid profile of strain LSZ-M11000T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, as well as other unidentified phospholipids and lipids. The major fatty acids were C16 : 0 (28.4 %), C18 : 0 (15.8 %), iso-C15 : 0 (12.9 %), and anteiso-C15 : 0 (12.0 %). Strain LSZ-M11000T had no menaquinone. Genome sequencing revealed that the genome size of strain LSZ-M11000T was 2.97 Mb and the DNA G+C content was 37.9 mol%. The average nucleotide identity values between strain LSZ-M11000T and its close phylogenetic relatives, Tepidibacillus fermentans STGHT and Tepidibacillus decaturensis Z9T, were 76.4 and 72.6 %, respectively. The corresponding DNA-DNA hybridization estimates were 20.9 and 23.4 %, respectively. Cells of strain LSZ-M11000T were rod-shaped (1.0-1.5×0.3-0.5 µm). Using pyruvate as an electron donor, it was capable of reducing KMnO4, MnO2, As(V), NaNO3, NaNO2, Na2SO4, Na2S2O3, and K2Cr2O7. Based on phenotypic, genotypic, and phylogenetic evidence, strain LSZ-M11000T is proposed to be a novel strain of the genus Tepidibacillus, for which the name Tepdibacillus marianensis is proposed. The type strain is LSZ-M11000T (=CCAM 1008T=JCM 39431T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Iron , Phospholipids , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , RNA, Ribosomal, 16S/genetics , Geologic Sediments/microbiology , DNA, Bacterial/genetics , Russia , Iron/metabolism , Heterotrophic Processes , Nucleic Acid Hybridization , Bacillaceae/classification , Bacillaceae/genetics , Bacillaceae/isolation & purification , Whole Genome Sequencing , Oxidation-Reduction
11.
BMJ Paediatr Open ; 8(1)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38897621

ABSTRACT

OBJECTIVES: To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI). METHODS: A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed. RESULTS: There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05). CONCLUSIONS: Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth. TRIAL REGISTRATION NUMBER: NCT06082414.


Subject(s)
Infant, Extremely Low Birth Weight , Infant, Extremely Premature , Weight Loss , Humans , Infant, Newborn , Female , Retrospective Studies , Male , Pregnancy , Weight Loss/drug effects , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/prevention & control , Bronchopulmonary Dysplasia/epidemiology , Bronchopulmonary Dysplasia/prevention & control , Bronchopulmonary Dysplasia/mortality , Dose-Response Relationship, Drug , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Gestational Age , Infant, Premature, Diseases/epidemiology , Infant, Premature, Diseases/prevention & control , Infant, Premature, Diseases/mortality
12.
Nat Commun ; 15(1): 5491, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38944656

ABSTRACT

Localized magnetic moments in non-magnetic materials, by interacting with the itinerary electrons, can profoundly change the metallic properties, developing various correlated phenomena such as the Kondo effect, heavy fermion, and unconventional superconductivity. In most Kondo systems, the localized moments are introduced through magnetic impurities. However, the intrinsic magnetic properties of materials can also be modulated by the dimensionality. Here, we report the observation of Kondo effect in a heterodimensional superlattice VS2-VS, in which arrays of the one-dimensional (1D) VS chains are encapsulated by two-dimensional VS2 layers. In such a heterodimensional Kondo superlattice, we observe the typical Kondo effect but with intriguing anisotropic field dependence. This unique anisotropy is determined to originate from the magnetic anisotropy which has the root in the unique 1D chains in the structure, as corroborated by the first-principles calculation. Our results open up a novel avenue of studying exotic correlated physics in heterodimensional materials.

14.
Pharmacol Res ; 205: 107263, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38876442

ABSTRACT

Pressure overload-induced pathological cardiac hypertrophy eventually leads to heart failure (HF). Unfortunately, lack of effective targeted therapies for HF remains a challenge in clinical management. Mixed-lineage leukemia 4 (MLL4) is a member of the SET family of histone methyltransferase enzymes, which possesses histone H3 lysine 4 (H3K4)-specific methyltransferase activity. However, whether and how MLL4 regulates cardiac function is not reported in adult HF. Here we report that MLL4 is required for endoplasmic reticulum (ER) stress homeostasis of cardiomyocytes and protective against pressure overload-induced cardiac hypertrophy and HF. We observed that MLL4 is increased in the heart tissue of HF mouse model and HF patients. The cardiomyocyte-specific deletion of Mll4 (Mll4-cKO) in mice leads to aggravated ER stress and cardiac dysfunction following pressure overloading. MLL4 knockdown neonatal rat cardiomyocytes (NRCMs) also display accelerated decompensated ER stress and hypertrophy induced by phenylephrine (PE). The combined analysis of Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and RNA sequencing (RNA-seq) data reveals that, silencing of Mll4 alters the chromatin landscape for H3K4me1 modification and gene expression patterns in NRCMs. Interestingly, the deficiency of MLL4 results in a marked reduction of H3K4me1 and H3K27ac occupations on Thrombospondin-4 (Thbs4) gene loci, as well as Thbs4 gene expression. Mechanistically, MLL4 acts as a transcriptional activator of Thbs4 through mono-methylation of H3K4 and further regulates THBS4-dependent ER stress response, ultimately plays a role in HF. Our study indicates that pharmacologically targeting MLL4 and ER stress might be a valid therapeutic approach to protect against cardiac hypertrophy and HF.


Subject(s)
Endoplasmic Reticulum Stress , Heart Failure , Histone-Lysine N-Methyltransferase , Mice, Inbred C57BL , Myocytes, Cardiac , Animals , Heart Failure/metabolism , Heart Failure/genetics , Heart Failure/etiology , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/genetics , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , Endoplasmic Reticulum Stress/drug effects , Male , Humans , Mice, Knockout , Rats , Mice , Cells, Cultured , Cardiomegaly/metabolism , Cardiomegaly/genetics , Rats, Sprague-Dawley , Thrombospondins
15.
FEBS J ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38872483

ABSTRACT

Discoidin, CUB, LCCL domain-containing 2 (DCBLD2) is a type I transmembrane protein with a similar structure to neuropilin, which acts as a co-receptor for certain receptor tyrosine kinases (RTKs). The insulin receptor is an RTK and plays a critical role in endothelial cell function and glycolysis. However, how and whether DCBLD2 regulates insulin receptor activity in endothelial cells is poorly understood. Diabetes was induced through treatment of Dcbld2 global-genome knockout mice and endothelium-specific knockout mice with streptozotocin. Vascular ultrasound, vascular tension test, and hematoxylin and eosin staining were performed to assess endothelial function and aortic remodeling. Glycolytic rate assays, real-time PCR and western blotting were used to investigate the effects of DCBLD2 on glycolytic activity and insulin receptor (InsR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in endothelial cells. Co-immunoprecipitation was used to assess the effects of DCBLD2 on insulin receptor endocytosis and recycling. Membrane and cytoplasmic proteins were isolated to determine whether DCBLD2 could affect the localization of the insulin receptor. We found that Dcbld2 deletion exacerbated endothelial dysfunction and vascular remodeling in diabetic mice. Both Dcbld2 knockdown and Dcbld2 deletion inhibited glycolysis and the InsR/PI3K/Akt signaling pathway in endothelial cells. Furthermore, Dcbld2 deletion inhibited insulin receptor recycling. Taken together, Dcbld2 deficiency exacerbated diabetic endothelial dysfunction and vascular remodeling by inhibiting the InsR/PI3K/Akt pathway in endothelial cells through the inhibition of Rab11-dependent insulin receptor recycling. Our data suggest that DCBLD2 is a potential therapeutic target for diabetes and cardiovascular diseases.

16.
Am J Clin Nutr ; 119(6): 1386-1396, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38839194

ABSTRACT

BACKGROUND: The independent effect of waist-to-height ratio (WHtR) and body fat percentage (BF%) on ischemic cardiovascular disease (CVD) remains uncertain. OBJECTIVES: This study aimed to investigate the independent associations of WHtR and BF% with ischemic CVD. METHODS: This prospective cohort study used data from the UK Biobank. BF% was calculated as fat mass divided by body weight, measured by bioimpedance. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for overall and sex-specific associations of BF% and WHtR with risks of ischemic CVD and its main subtypes [myocardial infarction (MI) and ischemic stroke (IS)], adjusted for a range of potential confounders, including mutual adjustment for BF% and WHtR. RESULTS: In total, 468,333 participants without existing CVD were included in the analysis. During 12 y of follow-up, 20,151 ischemic CVD events, 13,604 MIs, and 6681 ISs were recorded. WHtR was linearly associated with ischemic CVD, MI, and IS, with an HR per 5% increase of 1.23 (95% CI: 1.20, 1.25), 1.24 (95% CI: 1.21, 1.27), and 1.22 (95% CI: 1.18, 1.26), respectively, independent of BF%. A stronger association between WHtR and MI was seen in females than in males. The association of BF% with these outcomes was substantially attenuated in both sexes after adjustment for WHtR. For example, in females, the HR (highest compared with lowest fifth) was reduced from 1.94 (95% CI: 1.76, 2.15) to 1.04 (95% CI: 0.90, 1.01) for ischemic CVD, from 2.04 (95% CI: 1.79, 2.32) to 0.97 (95% CI: 0.81, 1.16) for MI, and from 1.81 (95% CI: 1.54, 2.13) to 1.07 (95% CI: 0.85, 1.33) for IS. CONCLUSIONS: WHtR, when used as a proxy measure for central obesity, is linearly associated with ischemic CVD in both sexes, which is independent of BF%. In contrast, the relationship of BF% with these health outcomes is predominantly driven by its correlation with WHtR.


Subject(s)
Adipose Tissue , Biological Specimen Banks , Waist-Height Ratio , Humans , Male , Female , Prospective Studies , United Kingdom/epidemiology , Middle Aged , Risk Factors , Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Adult , Cohort Studies , UK Biobank
17.
J Chem Inf Model ; 64(10): 3977-3991, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38727192

ABSTRACT

The worldwide spread of the metallo-ß-lactamases (MBL), especially New Delhi metallo-ß-lactamase-1 (NDM-1), is threatening the efficacy of ß-lactams, which are the most potent and prescribed class of antibiotics in the clinic. Currently, FDA-approved MBL inhibitors are lacking in the clinic even though many strategies have been used in inhibitor development, including quantitative high-throughput screening (qHTS), fragment-based drug discovery (FBDD), and molecular docking. Herein, a machine learning-based prediction tool is described, which was generated using results from HTS of a large chemical library and previously published inhibition data. The prediction tool was then used for virtual screening of the NIH Genesis library, which was subsequently screened using qHTS. A novel MBL inhibitor was identified and shown to lower minimum inhibitory concentrations (MICs) of Meropenem for a panel of E. coli and K. pneumoniae clinical isolates expressing NDM-1. The mechanism of inhibition of this novel scaffold was probed utilizing equilibrium dialyses with metal analyses, native state electrospray ionization mass spectrometry, UV-vis spectrophotometry, and molecular docking. The uncovered inhibitor, compound 72922413, was shown to be 9-hydroxy-3-[(5-hydroxy-1-oxa-9-azaspiro[5.5]undec-9-yl)carbonyl]-4H-pyrido[1,2-a]pyrimidin-4-one.


Subject(s)
Machine Learning , Microbial Sensitivity Tests , Molecular Docking Simulation , beta-Lactamase Inhibitors , beta-Lactamases , beta-Lactamases/metabolism , beta-Lactamases/chemistry , beta-Lactamase Inhibitors/pharmacology , beta-Lactamase Inhibitors/chemistry , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Escherichia coli/drug effects , Escherichia coli/enzymology , High-Throughput Screening Assays
18.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2402-2409, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812141

ABSTRACT

Due to the highly stable structure of keratin, the extraction and dissolution steps of animal medicines rich in keratin are complex, which seriously restricts the detection efficiency and flux. Therefore, this study simplified the pre-treatment steps of horn samples and optimized the detection methods of characteristic peptides to improve the efficiency of identifying the specificity of horn-derived animal medicines. For detection of the characteristic peptides in horn-derived animal medicines treated with/without iodoace-tamide(IAA), the ion pair conditions of the characteristic peptides were optimized, and the retention time, intensity and other data of the specific peptides were compared between the samples treated with/without IAA. Two pre-treatment methods, direct enzymatic hydrolysis and total protein extraction followed by enzymatic hydrolysis, were used to prepare horn-derived animal medicine samples. The effects of different methods on the detection of specific peptides in the samples of Saiga antelope horn, water buffalo horn, goat horn, and yak horn were compared regarding the retention time of specific peptides and ion intensity. The results indicated that after direct enzymatic hydrolysis, the specific peptides in the samples without IAA treatment can be detected. Compared with the characteristic peptides in the samples treated with IAA, their retention time shifted back and the mass spectrometry response slightly decreased. The specific peptides of the samples without IAA treatment had good specificity and did not affect the specificity identification of horn-derived animal medicines. Overall, the process of direct enzymatic hydrolysis can be used to treat horn samples, omitting the steps of protein extraction and dithiothreitol and IAA treatment, significantly improving the pre-treatment efficiency without affecting the specificity identification of horn-derived animal medicines. This study provides ideas for quality research and standard improvement of horn-derived animal medicines.


Subject(s)
Horns , Keratins , Peptides , Animals , Horns/chemistry , Peptides/chemistry , Keratins/chemistry , Cattle , Goats , Buffaloes , Chromatography, High Pressure Liquid
19.
Front Hum Neurosci ; 18: 1349186, 2024.
Article in English | MEDLINE | ID: mdl-38699563

ABSTRACT

Background: This study aimed to explore the risk factors and potential causes of unilateral classical or idiopathic trigeminal neuralgia (C-ITN) by comparing patients and healthy controls (HCs) with neurovascular compression (NVC) using machine learning (ML). Methods: A total of 84 C-ITN patients and 78 age- and sex-matched HCs were enrolled. We assessed the trigeminal pons angle and identified the compressing vessels and their location and severity. Machine learning was employed to analyze the cisternal segment of the trigeminal nerve (CN V). Results: Among the C-ITN patients, 53 had NVC on the unaffected side, while 25 HCs exhibited bilateral NVC, and 24 HCs showed unilateral NVC. By comparing the cisternal segment of CN V between C-ITN patients on the affected side and HCs with NVC, we identified the side of NVC, the compressing vessel, and certain texture features as risk factors for C-ITN. Additionally, four texture features differed in the structure of the cisternal segment of CN V between C-ITN patients on the unaffected side and HCs with NVC. Conclusion: Our findings suggest that the side of NVC, the compressing vessel, and the microstructure of the cisternal segment of CN V are associated with the risk of C-ITN. Furthermore, microstructural changes observed in the cisternal segment of CN V on the unaffected side of C-ITN patients with NVC indicate possible indirect effects on the CN V to some extent.

20.
Microorganisms ; 12(5)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38792684

ABSTRACT

To understand how the soil microbial community structure responds to vegetation restoration in alpine mining areas, this study specifically examines the grassland ecosystem in the Qianmalong mining area of the Qilian Mountains after five years of artificial restoration. High-throughput sequencing methods were employed to analyze soil bacteria and fungi microbial characteristics in diverse grassland communities. Combined with modifications in vegetation diversity as well as soil physicochemical properties, the impact of vegetation restoration on soil microbiome diversity in this alpine mining area was investigated. The findings indicated that the dominant plants were Cyperus rotundus, Carex spp., and Elymus nutans. As the extent of the grassland's restoration increased, the number of plant species, importance values, and plant community diversity showed an increasing trend. The plant functional groups were mainly dominated by Cyperaceae, followed by Poaceae. Plant height, density, plant cover, frequency, and aboveground biomass showed an increasing trend, and soil water content (SWC) increased. While soil pH and soil electrical conductivity (EC) exhibited a declining trend, available phosphorus (AP), total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (NO3-N), soil organic carbon (SOC), and soil water content (SWC) showed an increasing trend. The dominant bacterial communities were Actinobacteriota, Proteobacteria, Acidobacteriota, Chloroflexi, Firmicutes, and Gemmatimonadota, while the dominant fungal communities were Ascomycota, Mortierellomycota, Basidiomycota, unclassified_k_Fungi, and Glomeromycota. Significant differences were detected within soil microbial community composition among different degrees of restoration grasslands, with bacteria generally dominating over fungi. SWC, TP, and TN were found to be the main soil physicochemical factors affecting the distribution of soil bacterial communities' structure; however, SOC, TN, and NO3-N were the primary factors influencing the soil distribution of fungal communities. The results of this study indicate that different degrees of vegetation restoration in alpine mining areas can significantly affect soil bacterial and fungal communities, and the degree of restoration has varying effects on the soil bacteria and fungi community structure in alpine mining areas.

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