Substrate entering and product leaving trajectories predict an engulfing dynamic for the major conformational change of the β-lactam acylase

It is still a major challenge to acquire insight into the conformational changes between the ground state and the transition state of an enzyme, although conformational fluctuation within interconverting conformers has been widely investigated (1-4). Here, we utilize different enzymatic reactions in b-lactam acylase to figure out the substrate/product trajectories in the enzyme, thereby probing the overall conformational changes in transition state. First, an auto-proteolytic intermediate of cephalosporin acylase (EC 3.5.1.11) with partial spacer segment was identified. As a final proteolytic step, the deletion of this spacer segment was revealed to be a first-order reaction, suggesting an intramolecular Ntn mechanism for the auto-proteolysis. Accordingly, the different proteolytic sites in the acylase precursor indicate a substrate entering pathway along the spacer peptide. Second, bromoacyl-7ACA can interact with penicillin G acylase (EC 3.5.1.11) in two distinguish aspects, to be hydrolyzed as a substrate analogue and to affinity alkylate the conserved Trpb4 as a product analogue. The kinetic correlation between these two reactions suggests a channel opening from Serb1 to Trpb4, responsible for the main product leaving. These two reaction trajectories relaying at the active centre, together with the crystal structures (5-10), predict an engulfing dynamic involving pocket constriction and channel opening

Foaming behaviour of primary, secondary and tertiary aqueous solution of amine for the removal of carbon dioxide

This study is focusing on the effect by the usage of different amine in order to remove acid gases that is foaming. Foam is made up of thousands of gas filled bubbles. Bubbles are formed when a liquid film encapsulates gas. This research is to investigate the foaming behaviour on the different cases for the primary (monoethanolamine, MEA), secondary (diethanolamine, DEA) and tertiary (methyldiethanolamine, MDEA) amine on the effect of concentration, temperature and impurities. Effect of all this parameters will be evaluated based on height of foam and collapse time of foam. Nitrogen gas (N2) will be used in this experiments as bubble gas. For this work several hypothesis has been set according to respectively cases. The hypothesis of this study is a higher solution concentration of MEA will reduce the foaminess. Other hypothesis is a higher solution temperature of MEA and DEA will reduce the foaminess also. Effects of impurities toward foaming formation are classified as following: iron sulphide, for MDEA solution foaming decrease; sodium chloride, for MDEA solution tendency for formation of foam decrease; methanol, foaming decrease in MDEA solution. It is apparently iron sulphide meet the most influential contaminants to the foam formation at the same concentrations of all impurities studie

Patients Infected with CRF07_BC Have Significantly Lower Viral Loads than Patients with HIV-1 Subtype B: Mechanism and Impact on Disease Progression

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag

ProbRadarM3F: mmWave Radar based Human Skeletal Pose Estimation with Probability Map Guided Multi-Format Feature Fusion

Millimeter wave (mmWave) radar is a non-intrusive privacy and relatively convenient and inexpensive device, which has been demonstrated to be applicable in place of RGB cameras in human indoor pose estimation tasks. However, mmWave radar relies on the collection of reflected signals from the target, and the radar signals containing information is difficult to be fully applied. This has been a long-standing hindrance to the improvement of pose estimation accuracy. To address this major challenge, this paper introduces a probability map guided multi-format feature fusion model, ProbRadarM3F. This is a novel radar feature extraction framework using a traditional FFT method in parallel with a probability map based positional encoding method. ProbRadarM3F fuses the traditional heatmap features and the positional features, then effectively achieves the estimation of 14 keypoints of the human body. Experimental evaluation on the HuPR dataset proves the effectiveness of the model proposed in this paper, outperforming other methods experimented on this dataset with an AP of 69.9 %. The emphasis of our study is focusing on the position information that is not exploited before in radar singal. This provides direction to investigate other potential non-redundant information from mmWave rader

Catalytic trajectory of a dimeric nonribosomal peptide synthetase subunit with an inserted epimerase domain.

Nonribosomal peptide synthetases (NRPSs) are modular assembly-line megaenzymes that synthesize diverse metabolites with wide-ranging biological activities. The structural dynamics of synthetic elongation has remained unclear. Here, we present cryo-EM structures of PchE, an NRPS elongation module, in distinct conformations. The domain organization reveals a unique "H"-shaped head-to-tail dimeric architecture. The capture of both aryl and peptidyl carrier protein-tethered substrates and intermediates inside the heterocyclization domain and L-cysteinyl adenylate in the adenylation domain illustrates the catalytic and recognition residues. The multilevel structural transitions guided by the adenylation C-terminal subdomain in combination with the inserted epimerase and the conformational changes of the heterocyclization tunnel are controlled by two residues. Moreover, we visualized the direct structural dynamics of the full catalytic cycle from thiolation to epimerization. This study establishes the catalytic trajectory of PchE and sheds light on the rational re-engineering of domain-inserted dimeric NRPSs for the production of novel pharmaceutical agents

Feature selection and risk prediction for diabetic patients with ketoacidosis based on MIMIC-IV

BackgroundDiabetic ketoacidosis (DKA) is a frequent acute complication of diabetes mellitus (DM). It develops quickly, produces severe symptoms, and greatly affects the lives and health of individuals with DM.This article utilizes machine learning methods to examine the baseline characteristics that significantly contribute to the development of DKA. Its goal is to identify and prevent DKA in a targeted and early manner.MethodsThis study selected 2382 eligible diabetic patients from the MIMIC-IV dataset, including 1193 DM patients with ketoacidosis and 1186 DM patients without ketoacidosis. A total of 42 baseline characteristics were included in this research. The research process was as follows: Firstly, important features were selected through Pearson correlation analysis and random forest to identify the relevant physiological indicators associated with DKA. Next, logistic regression was used to individually predict DKA based on the 42 baseline characteristics, analyzing the impact of different physiological indicators on the experimental results. Finally, the prediction of ketoacidosis was performed by combining feature selection with machine learning models include logistic regression, XGBoost, decision tree, random forest, support vector machine, and k-nearest neighbors classifier.ResultsBased on the importance analysis conducted using different feature selection methods, the top five features in terms of importance were identified as mean hematocrit (haematocrit_mean), mean hemoglobin (haemoglobin_mean), mean anion gap (aniongap_mean), age, and Charlson comorbidity index (charlson_comorbidity_index). These features were found to have significant relevance in predicting DKA. In the individual prediction using logistic regression, these five features have been proven to be effective, with F1 scores of 1.000 for hematocrit mean, 0.978 for haemoglobin_mean, 0.747 for age, 0.692 for aniongap_mean and 0.666 for charlson_comorbidity_index. These F1 scores indicate the effectiveness of each feature in predicting DKA, with the highest score achieved by mean hematocrit. In the prediction of DKA using machine learning models, including logistic regression, XGBoost, decision tree, and random forest demonstrated excellent results, achieving an F1 score of 1.000. Additionally, by applying feature selection techniques, noticeable improvements were observed in the experimental performance of the support vector machine and k-nearest neighbors classifier.ConclusionThe study found that hematocrit, hemoglobin, anion gap, age, and Charlson comorbidity index are closely associated with ketoacidosis. In clinical practice, these five baseline characteristics should be given with the special attention to achieve early detection and treatment, thus reducing the incidence of the disease

Analysis of gas composition and nitrogen sources of shale gas reservoir under strong tectonic events:Evidence from the complex tectonic area in the yangtze plate

Strong tectonic movement brings great risk to exploration of shale gas in southern China, especially in Lower Cambrian shale with complex tectonic backgrounds, which has good hydrocarbon-generation matter but low or no gas content. In this paper, the Lower Cambrian shale from the southeast Chongqing region, located in the Upper Yangtze Platform, and the Xiuwu Basin, located in the Lower Yangtze Platform, were selected as the research objects. First, the gas components in shale gas samples were measured, then analysis of nitrogen isotopic was used to reveal the nitrogen sources. Using regional geological backgrounds, core description, and seismic interpretation, combined with the perpendicular and parallel permeability test and focused ion beam–helium ion microscopy (FIB–HIM) observation, the reasons for high content of nitrogen in the Lower Cambrian shale from the Xiuwu Basin and the Southeast Chongqing region were clarified. The results indicate that the main sources of nitrogen in the Lower Cambrian shale gas at the Southeast Chongqing region is the thermal evolution of organic matter and atmosphere. Nitrogen in the atmosphere is filled into the shale reservoir through migration channels formed by detachment layers at the bottom of the Lower Cambrian, shale stratification planes, and widespread thrust faults. Nitrogen was also produced during the thermal evolution of organic matter. Both are responsible for the low content of hydrocarbon and high content of nitrogen of shale gas in the Southeast Chongqing region. Further, the main sources of nitrogen in the Lower Cambrian shale gas at the Xiuwu Basin is the upper mantle, superdeep crust, and atmosphere. Nitrogen in the atmosphere is also filled into the shale reservoir through migration channels formed by detachment layers at the bottom of the Lower Cambrian, shale stratification planes, and widespread thrust faults. Nitrogen was also produced by volcanism during the Jurassic. Both are the causes of the low content of hydrocarbon and high content of nitrogen in shale gas in the Xiuwu Basin. Finally, destruction models for shale gas reservoirs with complex tectonic backgrounds were summarized. This research aimed to provide a theoretical guidance for shale gas exploration and development in areas with complex tectonic backgrounds

Gut mycobiome in cardiometabolic disease progression: current evidence and future directions

Cardiometabolic diseases (CMD) are a cluster of complex syndromes characterized by cardiovascular damage resulting from metabolic dysregulation; however, their underlying mechanisms remain unclear. Recently, CMD research has paid considerable attention to the gut microbiota, though the emphasis has been on bacterial communities, and the gut mycobiome’s role is still not well understood. Hence, this review consolidates information on the correlation between the gut mycobiome and CMD and examines how the gut mycobiome may play a role in CMD progression. Accumulating evidence indicates that gut mycobiome dysbiosis, particularly the aberrant expansion of specific fungal genera such as Candida and Saccharomyces, is closely associated with the development and progression of cardiometabolic diseases. This association is primarily mediated through multiple mechanisms. For instance, fungal metabolites (enzymatic derivatives, alcohol) enhance intestinal lipid absorption, accelerate hepatic steatosis, and trigger systemic insulin resistance. Meanwhile, dysregulated cross-kingdom interactions disrupt intestinal barrier function, leading to endotoxemia and vascular inflammation, thereby promoting atherosclerosis. Additionally, fungal pathogen-associated molecular patterns activate the immune-metabolic axis, resulting in adipose tissue inflammation and glucose dysregulation. These pathways interact synergistically, collectively exacerbating metabolic dysfunction and cardiovascular damage. We also outline strategies targeting the gut mycobiome as a potential therapeutic approach for cardiometabolic diseases. By integrating current state-of-the-art insights, this review provides a critical reference for the development of novel mycobiome-based interventions in cardiometabolic disease management

Efficacy and safety of acupuncture as an adjuvant therapy for osteoporosis: a systematic review and meta-analysis of randomized controlled trials

ObjectiveTo systematically evaluate the efficacy and safety of acupuncture as an adjuvant therapy for osteoporosis (OP) through a comprehensive synthesis of recent randomized controlled trial (RCT) evidence.MethodsA systematic literature search was conducted across PubMed, Web of Science, CNKI, and Wanfang databases (2014 – 2024) to identify RCTs investigating acupuncture combined with conventional therapy for OP. Study quality was appraised using the Cochrane Risk of Bias tool, and meta-analyses were performed using RevMan 5.4 and Stata 15.0, with subgroup analyses stratified by intervention type, population characteristics, and treatment duration.Results28 RCTs (n=2,758) were included. Meta-analysis revealed acupuncture significantly enhanced bone mineral density (BMD) versus controls: total (SMD = 0.47, p = 0.03), femoral neck (MD = 0.05, p = 0.01), lumbar spine (SMD = 0.40, p < 0.001), Ward’s triangle (MD = 0.07, p = 0.02), and hip (SMD = 0.55, p < 0.001), with particularly marked improvements in the postmenopausal osteoporosis subgroup. Acupuncture demonstrated significant improvements in treatment efficacy, biochemical markers, pain scores, and symptom assessments, while reducing adverse events. Warm needle moxibustion outperformed controls in femoral neck (MD = 0.07, p = 0.002) and hip BMD (SMD = 0.87, p < 0.001), while electroacupuncture significantly elevated serum calcium (MD = 0.18, p = 0.02). Short-term interventions (≤ 3 months) demonstrated optimal efficacy.ConclusionAcupuncture demonstrates efficacy and safety as an OP adjuvant therapy. Current evidence is limited by regional bias and methodological heterogeneity. Multicenter, large-sample RCTs are needed to standardize protocols and validate long-term therapeutic efficacy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024499354

Effects of Exogenous Sugar Treatment on Enrichment of γ-Aminobutyric Acid in Peanut Sprouts

In order to explore the influence of sugar treatment on the enrichment of γ-aminobutyric acid (GABA) in peanut sprouts, this paper selected the optimal application concentration of different types of exogenous sugars (mannose, sucrose and glucose). The effects of GABA on the germination of peanut seeds and the related substances of GABA anabolic metabolism were investigated and the possible mechanism of action was studied. The results showed that mannose, sucrose and glucose treatment could significantly (P<0.05) increase the content of GABA in peanut sprouts, and the activity of glutamate decarboxylase (GAD), diamine oxidase (DAO), polyamine oxidase (PAO) and the contents of glutamic acid, putrescine, spermidine and spermidine were significantly changed in oxidase (P<0.05). At the same time, according to the test results, different exogenous sugar treatments could increase the contents of ascorbic acid, protein and resveratrol in peanut sprouts to different degrees. GABA in peanut sprouts can be enriched by exogenous sugar treatment, and its influence mechanism may be GABA branch and polyamine degradation pathway