Multicopper Oxidase from Lactobacillus hilgardii: Mechanism of Degradation of Tyramine and Phenylethylamine in Fermented Food.

Elevated levels of biogenic amines (BAs) in fermented food can have negative effects on both the flavor and health. Mining enzymes that degrade BAs is an effective strategy for controlling their content. The study screened a strain of Lactobacillus hilgardii 1614 from fermented food system that can degrade BAs. The multiple copper oxidase genes LHMCO1614 were successfully mined after the whole genome protein sequences of homologous strains were clustered and followed by homology modeling. The enzyme molecules can interact with BAs to stabilize composite structures for catalytic degradation, as shown by molecular docking results. Ingeniously, the kinetic data showed that purified LHMCO1614 was less sensitive to the substrate inhibition of tyramine and phenylethylamine. The degradation rates of tyramine and phenylethylamine in huangjiu (18% vol) after adding LHMCO1614 were 41.35 and 40.21%, respectively. Furthermore, LHMCO1614 demonstrated universality in degrading tyramine and phenylethylamine present in other fermented foods as well. HS-SPME-GC-MS analysis revealed that, except for aldehydes, the addition of enzyme treatment did not significantly alter the levels of major flavor compounds in enzymatically treated fermented foods (p > 0.05). This study presents an enzymatic approach for regulating tyramine and phenylethylamine levels in fermented foods with potential applications both targeted and universal.

The extremotolerant desert moss Syntrichia caninervis is a promising pioneer plant for colonizing extraterrestrial environments.

Many plans to establish human settlements on other planets focus on adapting crops to growth in controlled environments. However, these settlements will also require pioneer plants that can grow in the soils and harsh conditions found in extraterrestrial environments, such as those on Mars. Here, we report the extraordinary environmental resilience of Syntrichia caninervis, a desert moss that thrives in various extreme environments. S. caninervis has remarkable desiccation tolerance; even after losing >98% of its cellular water content, it can recover photosynthetic and physiological activities within seconds after rehydration. Intact plants can tolerate ultra-low temperatures and regenerate even after being stored in a freezer at -80°C for 5 years or in liquid nitrogen for 1 month. S. caninervis also has super-resistance to gamma irradiation and can survive and maintain vitality in simulated Mars conditions; i.e., when simultaneously exposed to an anoxic atmosphere, extreme desiccation, low temperatures, and intense UV radiation. Our study shows that S. caninervis is among the most stress tolerant organisms. This work provides fundamental insights into the multi-stress tolerance of the desert moss S. caninervis, a promising candidate pioneer plant for colonizing extraterrestrial environments, laying the foundation for building biologically sustainable human habitats beyond Earth.

ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated (ECMO-RESCUE): study protocol for a prospective, multicentre, non-randomised cohort study.

INTRODUCTION: Severe septic cardiomyopathy (SCM) is one of the main causes of refractory septic shock (RSS), with a high mortality. The application of venoarterial extracorporeal membrane oxygenation (ECMO) to support the impaired cardiac function in patients with septic shock remains controversial. Moreover, no prospective studies have been taken to address whether venoarterial ECMO treatment could improve the outcome of patients with sepsis-induced cardiogenic shock. The objective of this study is to assess whether venoarterial ECMO treatment can improve the 30-day survival rate of patients with sepsis-induced refractory cardiogenic shock. METHODS AND ANALYSIS: ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated is a prospective, multicentre, non-randomised, cohort study on the application of ECMO in SCM. At least 64 patients with SCM and RSS will be enrolled in an estimated ratio of 1:1.5. Participants taking venoarterial ECMO during the period of study are referred to as cohort 1, and patients receiving only conventional therapy without ECMO belong to cohort 2. The primary outcome is survival in a 30-day follow-up period. Other end points include survival to intensive care unit (ICU) discharge, hospital survival, 6-month survival, quality of life for long-term survival (EQ-5D score), successful rate of ECMO weaning, long-term survivors' cardiac function, the number of days alive without continuous renal replacement therapy, mechanical ventilation and vasopressor, ICU and hospital length of stay, the rate of complications potentially related to ECMO treatment. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2020-hs-51). Participants will be screened and enrolled from ICU patients with septic shock by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION NUMBER: NCT05184296.

Cloning and functional validation of DsWRKY6 gene from Desmodium styracifolium.

The purpose of this study was to analyze the role of transcription factor in Desmodium styracifolium, proving that the DsWRKY6 transcription factor was related to the plant phenotypes of Desmodium styracifolium - cv. 'GuangYaoDa1' and it could be used in molecular-assisted breeding. 'GuangYaoDa1' was used as the material and its DNA was the template to clone DsWRKY6, the transgenic Arabidopsis thaliana line was constructed by agrobacterium tumefaciens­mediated transformation. Transgenic Arabidopsis thaliana was cultivated to study phenotype and physiological and biochemical indexes. Phenotypic observation showed that DsWRKY6 transgenic Arabidopsis thaliana had a faster growth rate while compared with the control group, they had longer lengths of main stem, lateral branches of cauline leaves, and root, but a lower number of cauline leaves and lateral branches of cauline leaves. And it also showed that their flowering and fruiting periods were advanced. The results of physiological and biochemical indexes showed that the relative expressions of DsWRKY6 increased and the abscisic acid content significantly increased in DsWRKY6 transgenic Arabidopsis thaliana compared with the control group. According to the above results, DsWRKY6 could regulate the advancing of flowering and fruiting periods caused by the improvement of abscisic acid content, and expression of the DsWRKY6 transcription factor might be the cause of the upright growth of 'GuangYaoDa1'.

Association between septic shock and tracheal injury score in intensive care unit patients with invasive ventilation: a prospective single-centre cohort study in China.

OBJECTIVES: There was no evidence regarding the relationship between septic shock and tracheal injury scores. Investigate whether septic shock was independently associated with tracheal injury scores in intensive care unit (ICU) patients with invasive ventilation. DESIGN: Prospective observational cohort study. SETTING: Our study was conducted in a Class III hospital in Hebei province, China. PARTICIPANTS: Patients over 18 years of age admitted to the ICU between 31 May 2020 and 3 May 2022 with a tracheal tube and expected to be on the tube for more than 24 hours. PRIMARY AND SECONDARY OUTCOME MEASURES: Tracheal injuries were evaluated by examining hyperaemia, ischaemia, ulcers and tracheal perforation by fiberoptic bronchoscope. Depending on the number of lesions, the lesions were further classified as moderate, severe or confluent. RESULTS: Among the 97 selected participants, the average age was 56.6±16.5 years, with approximately 64.9% being men. The results of adjusted linear regression showed that septic shock was associated with tracheal injury scores (ß: 2.99; 95% CI 0.70 to 5.29). Subgroup analysis revealed a stronger association with a duration of intubation ≥8 days (p=0.013). CONCLUSION: Patients with septic shock exhibit significantly higher tracheal injury scores compared with those without septic shock, suggesting that septic shock may serve as an independent risk factor for tracheal injury. TRIAL REGISTRATION NUMBER: ChiCTR2000037842, registered 03 September 2020. Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=57011&htm=4.

Association Between Serum Anion Gap and Mortality in Critically Ill Patients with COPD in ICU: Data from the MIMIC IV Database.

Background: Serum anion gap (AG) has been proven to be associated with prognosis in critically ill patients. However, few studies have investigated the association between AG and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Objective: We hypothesized that the initial AG level would predict the mortality risk in critically ill patients with COPD. Methods: This retrospective cohort study was based on the Medical Information Mart for Intensive Care (MIMIC) IV database. We extracted demographics, vital signs, laboratory tests, comorbidity, and scoring systems from the first 24 hours after patient ICU admission. Multivariable logistic regression analysis models were used to explore the association between serum AG levels and mortality. Interaction and stratified analyses were conducted including age, gender and comorbidity. Results: A total of 5531 critically ill patients with COPD were enrolled, composed of 53.6% male and 46.4% female with a median age of 73 years. The all-cause mortality of these patients during ICU hospitalization was 13.7%. The risk of all-cause mortality increased as the AG level increased in the univariate logistic regression analysis (OR=1.13, 95% CI: 1.11-1.15, p<0.01). After adjusting for all the covariates in multivariate logistic regression analysis, the odds ratio was 1.06 (95% CI: 1.04-1.09, p<0.01). Compared with the lowest AG group Q1 (≤11mmol/L), the adjusted OR value for AG and mortality in Q2 (12-13mmol/L) was 0.89 (95% CI: 0.63-1.25, p=0.502), Q3 (14-15mmol/L) was 0.95 (95% CI: 0.68-1.34, p=0.788), and Q4 (≥16mmol/L) was 1.49 (95% CI: 1.10-2.02, p=0.009) respectively. In addition, the results of the subgroup and stratified analyses were robust. Conclusion: AG is positively related to all-cause mortality in critically ill patients with COPD.

Donor-recipient intermicrobial interactions impact transfer of subspecies and fecal microbiota transplantation outcome.

Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.

Isoflavonoid metabolism in leguminous plants: an update and perspectives.

Isoflavonoids constitute a well-investigated category of phenylpropanoid-derived specialized metabolites primarily found in leguminous plants. They play a crucial role in legume development and interactions with the environment. Isoflavonoids usually function as phytoalexins, acting against pathogenic microbes in nature. Additionally, they serve as signaling molecules in rhizobial symbiosis. Notably, owing to their molecular structure resembling human estrogen, they are recognized as phytoestrogens, imparting positive effects on human health. This review comprehensively outlines recent advancements in research pertaining to isoflavonoid biosynthesis, transcriptional regulation, transport, and physiological functions, with a particular emphasis on soybean plants. Additionally, we pose several questions to encourage exploration into novel contributors to isoflavonoid metabolism and their potential roles in plant-microbe interactions.

Association of early dietary fiber intake and mortality in septic patients with mechanical ventilation based on MIMIC IV 2.1 database: a cohort study.

BACKGROUND: Whether early dietary fiber intake in septic patients is associated with a better clinical prognosis remains unclear, especially the time and the amount. Therefore, we assessed the association between early dietary fiber intake and clinical outcomes in septic patients by examining an extensive database. METHODS: We conducted a retrospective cohort study using data from the MIMIC IV 2.1 database, focusing on consecutive septic patients requiring mechanical ventilation in medical or mixed medical-surgical ICUs. We collected patient demographics and nutritional data. Dietary fiber amounts were calculated according to enteral nutrition instructions from manufacturers within the first 72 h after admission. After adjusting for covariates, we employed restricted cubic spline (RCS) regression to investigate the relationship between fiber intake (FI) and 28-day mortality. Patients were categorized into three groups based on their fiber index (FI) within 72 h of admission: low fiber index (LFI) group when FI was < 3 g/(%), medium fiber index (MFI) group when FI ranged from 3 to 35 g(%), and high fiber index (HFI) group when FI ≥ 35 g(%). Univariate and multivariate Cox proportional hazards regression models were utilized to assess the association between early FI and 28-day mortality. We ultimately employed Kaplan-Meier (KM) curves and log-rank test visually represent the association between FI and 90-day mortality. The second outcomes include ICU-acquired infections and the hospital and ICU death, length of hospital and ICU stay, and length of mechanical ventilation. RESULTS: Among 1057 subjects, 562 (53.2%) were male, with a median age of 64.8 years (IQR 53.4-75.2). We observed a J-shaped relationship between FI and 28-day mortality. The MFI group exhibited the lowest 28-day mortality [adjusted HR 0.64 (0.45-0.91), p = 0.013] and the lowest rate of hospital mortality [adjusted OR 0.60 (0.39-0.93), p = 0.022], with no statistically significant differences noted in the HFI group when compared to the LFI group. Similar patterns were observed for 60-day and 90-day mortality. However, no statistically significant differences were observed in other secondary outcomes after adjusting for covariates. CONCLUSION: Early medium fiber index intake improved 28-day mortality and lower hospital mortality in septic M/SICU patients on mechanical ventilation.

Transcriptome Profiles Reveals ScDREB10 from Syntrichia caninervis Regulated Phenylpropanoid Biosynthesis and Starch/Sucrose Metabolism to Enhance Plant Stress Tolerance.

Desiccation is a kind of extreme form of drought stress and desiccation tolerance (DT) is an ancient trait of plants that allows them to survive tissue water potentials reaching -100 MPa or lower. ScDREB10 is a DREB A-5 transcription factor gene from a DT moss named Syntrichia caninervis, which has strong comprehensive tolerance to osmotic and salt stresses. This study delves further into the molecular mechanism of ScDREB10 stress tolerance based on the transcriptome data of the overexpression of ScDREB10 in Arabidopsis under control, osmotic and salt treatments. The transcriptional analysis of weight gene co-expression network analysis (WGCNA) showed that "phenylpropanoid biosynthesis" and "starch and sucrose metabolism" were key pathways in the network of cyan and yellow modules. Meanwhile, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) also showed that "phenylpropanoid biosynthesis" and "starch and sucrose metabolism" pathways demonstrate the highest enrichment in response to osmotic and salt stress, respectively. Quantitative real-time PCR (qRT-PCR) results confirmed that most genes related to phenylpropanoid biosynthesis" and "starch and sucrose metabolism" pathways in overexpressing ScDREB10 Arabidopsis were up-regulated in response to osmotic and salt stresses, respectively. In line with the results, the corresponding lignin, sucrose, and trehalose contents and sucrose phosphate synthase activities were also increased in overexpressing ScDREB10 Arabidopsis under osmotic and salt stress treatments. Additionally, cis-acting promoter element analyses and yeast one-hybrid experiments showed that ScDREB10 was not only able to bind with classical cis-elements, such as DRE and TATCCC (MYBST1), but also bind with unknown element CGTCCA. All of these findings suggest that ScDREB10 may regulate plant stress tolerance by effecting phenylpropanoid biosynthesis, and starch and sucrose metabolism pathways. This research provides insights into the molecular mechanisms underpinning ScDREB10-mediated stress tolerance and contributes to deeply understanding the A-5 DREB regulatory mechanism.

Elimination of Pharmaceutical Compounds from Aqueous Solution through Novel Functionalized Pitch-Based Porous Adsorbents: Kinetic, Isotherm, Thermodynamic Studies and Mechanism Analysis.

The long-term presence of PPCPs in the aqueous environment poses a potentially significant threat to human life and physical health and the safety of the water environment. In our previous work, we investigated low-cost pitch-based HCP adsorbents with an excellent adsorption capacity and magnetic responsiveness through a simple one-step Friedel-Crafts reaction. In this work, we further investigated the adsorption behavior of the prepared pitch-based adsorbents onto three PPCP molecules (DFS, AMP, and antipyrine) in detail. The maximum adsorption capacity of P-MPHCP for DFS was 444.93 mg g-1. The adsorption equilibrium and kinetic processes were well described through the Langmuir model and the proposed secondary kinetic model. The negative changes in Gibbs free energy and enthalpy reflected that the adsorption of HCPs onto PPCPs was a spontaneous exothermic process. The recoverability results showed that the adsorption of MPHCP and P-MPHCP onto DFS remained above 95% after 10 adsorption-desorption cycles. The present work further demonstrates that these pitch-based adsorbents can be used for multiple applications, which have a very extensive practical application prospect.

α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice.

BACKGROUND: In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. METHODS: In vivo, 2% AKG was added to the drinking water of mice undergoing transverse aortic constriction (TAC) surgery. Echocardiography and biopsy were performed to evaluate cardiac function and pathological changes. Myocardial metabolomics was analyzed by liquid chromatography‒mass spectrometry (LC‒MS/MS) at 8 weeks after surgery. In vitro, the expression of SIRT1 or PINK1 proteins was inhibited by selective inhibitors and siRNA in cardiomyocytes stimulated with angiotensin II (AngII) and AKG. NAD+ levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. RESULTS: AKG supplementation after TAC surgery could alleviate myocardial hypertrophy and fibrosis and improve cardiac function in mice. Metabolites of the malate-aspartate shuttle (MAS) were increased, but the TCA cycle and fatty acid metabolism pathway could be inhibited in the myocardium of TAC mice after AKG supplementation. Decreased NAD+ levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. CONCLUSION: Supplementation with AKG can improve myocardial hypertrophy, fibrosis and chronic cardiac insufficiency caused by pressure overload. By increasing the level of NAD+, the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage.

Dermal papilla cell-secreted biglycan regulates hair follicle phase transit and regeneration by activating Wnt/ß-catenin.

Alopecia is a prevalent problem of cutaneous appendages and lacks effective therapy. Recently, researchers have been focusing on mesenchymal components of the hair follicle, i.e. dermal papilla cells, and we previously identified biglycan secreted by dermal papilla cells as the key factor responsible for hair follicle-inducing ability. In this research, we hypothesized biglycan played an important role in hair follicle cycle and regeneration through regulating the Wnt signalling pathway. To characterize the hair follicle cycle and the expression pattern of biglycan, we observed hair follicle morphology in C57BL/6 mice on Days 0, 3, 5, 12 and 18 post-depilation and found that biglycan is highly expressed at both mRNA and protein levels throughout anagen in HFs. To explore the role of biglycan during the phase transit process and regeneration, local injections were administered in C57BL/6 and nude mice. Results showed that local injection of biglycan in anagen HFs delayed catagen progression and involve activating the Wnt/ß-catenin signalling pathway. Furthermore, local injection of biglycan induced HF regeneration and up-regulated expression of key Wnt factors in nude mice. In addition, cell analyses exhibited biglycan knockdown inactivated the Wnt signalling pathway in early-passage dermal papilla cell, whereas biglycan overexpression or incubation activated the Wnt signalling pathway in late-passage dermal papilla cells. These results indicate that biglycan plays a critical role in regulating HF cycle transit and regeneration in a paracrine and autocrine fashion by activating the Wnt/ß-catenin signalling pathway and could be a potential treatment target for hair loss diseases.

Association between the ß-blocker use and patients with sepsis: a cohort study.

Objective: This study aimed to assess whether ß-blockers are associated with mortality in patients with sepsis. Method: We conducted a retrospective cohort study of patients with sepsis using the Medical Information Market for Intensive Care (MIMIC)-IV and the emergency intensive care unit (eICU) databases. The primary outcome was the in-hospital mortality rate. The propensity score matching (PSM) method was adopted to reduce confounder bias. Subgroup and sensitivity analyses were performed to test the stability of the conclusions. Results: We included a total of 61,751 patients with sepsis, with an overall in-hospital mortality rate of 15.3% in MIMIC-IV and 13.6% in eICU. The inverse probability-weighting model showed that in-hospital mortality was significantly lower in the ß-blockers group than in the non-ß-blockers group [HR = 0.71, 95% CI: 0.66-0.75, p < 0.001 in MIMIC-IV, and HR = 0.48, 95% CI: 0.45-0.52, p < 0.001 in eICU]. In subgroups grouped according to sex, age, heart rate, APSIII, septic shock, and admission years, the results did not change. Conclusion: ß-blocker use is associated with lower in-hospital mortality in patients with sepsis, further randomized trials are required to confirm this association.

Metabolomic Analysis of the Desert Moss Syntrichia caninervis Provides Insights into Plant Dehydration and Rehydration Response.

Desiccation-tolerant (DT) plants can survive extreme dehydration and tolerate the loss of up to 95% of their water content, making them ideal systems to determine the mechanism behind extreme drought stress and identify potential approaches for developing drought-tolerant crops. The desert moss Syntrichia caninervis is an emerging model for extreme desiccation tolerance that has benefited from high-throughput sequencing analyses, allowing identification of stress-tolerant genes; however, its metabolic response to desiccation is unknown. A liquid chromatography-mass spectrometry analysis of S. caninervis at six dehydration-rehydration stages revealed 912 differentially abundant compounds, belonging to 93 metabolic classes. Many (256) metabolites accumulated during rehydration in S. caninervis, whereas only 71 accumulated during the dehydration period, in contrast to the pattern observed in vascular DT plants. During dehydration, nitrogenous amino acids (l-glutamic acid and cysteinylglycine), alkaloids (vinleurosine) and steroids (physalin D) accumulated, whereas glucose 6-phosphate decreased. During rehydration, γ-aminobutyric acid, glucose 6-phosphate and flavonoids (karanjin and aromadendrin) accumulated, as did the plant hormones 12-oxo phytodienoic acid (12-OPDA) and trans-zeatin riboside. The contents ofl-arginine, maltose, turanose, lactulose and sucrose remained high throughout dehydration-rehydration. Syntrichia caninervis thus accumulates antioxidants to scavenge reactive oxygen species, accumulating nitrogenous amino acids and cytoprotective metabolites and decreasing energy metabolism to enter a protective state from dehydration-induced damage. During subsequent rehydration, many metabolites rapidly accumulated to prevent oxidative stress and restore physiological activities while repairing cells, representing a more elaborate rehydration repair mechanism than vascular DT plants, with a faster and greater accumulation of metabolites. This metabolic kinetics analysis in S. caninervis deepens our understanding of its dehydration mechanisms and provides new insights into the different strategies of plant responses to dehydration and rehydration.

Double Effects of Oxidative Aging on Carbon Nanotube-Asphalt Nanocomposite Interfaces: Enhancement and Deterioration.

Understanding the mechanisms of oxidative aging effects on the carbon nanotube (CNT)-asphalt nanocomposite interface has long been a challenge, as there are two opposing effects: enhancement and deterioration. In this study, a multiscale coupling method is proposed to analyze the dual effect of oxidative aging on the CNT-asphalt nanocomposite. The method is based on density functional theory (DFT) and molecular dynamics (MD) simulations, supported by microscopic interface observation and macroscopic property testing with a focus on the composite interface. The results show that oxidative aging has a resetting effect on benzene ring stacking at the interface and enhances the binding energy of CNT-asphalt. Meanwhile, oxidative aging enhanced the interfacial charge transfer, but no chemical reaction occurred between CNT-aged asphalt. This is also verified by Fourier Transform Infrared Spectroscopy (FTIR). Enhancement and degeneration effects of oxidative aging occur via distinct mechanisms. Oxidative aging enhanced the interfacial shear barrier by approximately 5% and the energy barrier by 44.87%, which increased the high-temperature deformation resistance of the CNT-asphalt nanocomposites. However, molecular oxidation was not responsible for the decline in the fatigue resistance. According to scanning electron microscopy (SEM) and atomic force microscopy (AFM) results, oxidative aging elevates the content of polar molecules, leading to an increase in the solid properties of asphalt and a 39.6% decrease in surface adhesion. This disrupts the three-dimensional network of the CNT and ultimately leads to a reduction in crack resistance. This study clarifies the mechanism underlying the dual effect of oxidative aging and provides fundamental support for understanding asphalt aging behavior and the interfacial behavior of composites.

Isolation and characterization of a novel Enterococcus phage Phi_Eg_SY1.

Enterococcus gallinarum, a gut pathobiont, is an opportunistic pathogen that carries the risk of antibiotic resistance in the clinic and has been proven to drive autoimmunity in both mice and humans. Screening for novel bacteriophages targeting Enterococcus gallinarum is expected to provide a promising strategy for controlling such infections or regulating related chronic diseases. In the present study, we isolated a novel lytic Enterococcus gallinarum phage, Phi_Eg_SY1, which presents favourable thermostability and pH stability. Further assays indicated that Phi_Eg_SY1 can efficiently adsorb and lyse the host bacteria in vitro. Genomic and phylogenetic analyses suggested that Phi_Eg_SY1 does not contain virulence or lysogeny genes and presents a novel unassigned evolutionary lineage among the related dsDNA phages. Phi_Eg_SY1 is therefore considered to be suitable for further applications.

Deterioration Effects of Oxidative Aging on Graphene-Asphalt Nanocomposite Interfaces: Multiscale Modeling.

The purpose of this study is to explore the mechanism of interfacial degradation of graphene-asphalt nanocomposites by oxidative aging and to explain the principle of reduced cracking resistance. In this study, density functional theory (DFT), molecular dynamics (MD) simulation, atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy, and linear amplitude scanning test (LAS) were used to quantify the effect of oxidative aging on the interfacial degradation of graphene-asphalt nanocomposites with different scales, and the coupling mechanism between scales was systematically analyzed. The results show that interfacial degradation is a complex multiscale coupling behavior. Oxidative aging reduced the fatigue life (Nf) of graphene-asphalt nanocomposites by 8.6% due to a 63.9% reduction in shear barriers and a 14.2% reduction in energy barriers at the molecular interface. Furthermore, oxidative aging enhanced the intermolecular interactions and compatibility of the graphene-asphalt molecules. The interfacial interaction of aged graphene-asphalt nanocomposites is mainly van der Waals force. Graphene-aged aromatics and graphene-aged saturates were the most compatible interfaces, and there was typical benzene ring stacking between graphene and aged aromatic 2. Aged aromatics and aged saturates are the main promoters of interfacial strength and stress transfer, while aged asphaltenes and aged resins sometimes play a weakening role, as verified by the AFM. In addition, DFT calculations show that there is no chemical reaction between graphene and aged asphalt molecules, which is consistent with the FTIR results. This study provides a theoretical basis for the development of targeted antiaging and anticracking technologies for asphalt-based materials.

Targeting VPS34 in autophagy: An update on pharmacological small-molecule compounds.

VPS34 is well-known to be the unique member of the class III phosphoinositide 3-kinase (PI3K) family, forming VPS34 complex 1 and complex 2, which are involved in several key physiological processes. Of note, VPS34 complex 1 is an important node of autophagosome generation, which controls T cell metabolism and maintains cellular homeostasis through the autophagic pathway. And, VPS34 complex 2 is involved in endocytosis as well as vesicular transport, and is closely related to neurotransmission, antigen presentation and brain development. Due to the two important biological functions of VPS34, its dysregulation can lead to the development of cardiovascular disease, cancer, neurological disorders, and many types of human diseases by altering normal human physiology. Thus, in this review, we not only summarize the molecular structure and function of VPS34, but demonstrate the relationships between VPS34 and human diseases. Moreover, we further discuss the current small molecule inhibitors targeting VPS34 based upon the structure and function of VPS34, which may provide an insight into the future targeted drug development.

Association between serum creatinine and type 2 diabetes in the Chinese population: a retrospective cohort study.

The relationship between serum creatinine and type 2 diabetes is limited. We aimed to investigate the association of baseline serum creatinine and new-onset type 2 diabetes in Chinese population. This retrospective cohort study was conducted using data from the health screening program in China. The population were divided into four groups based on serum creatinine levels, and the outcome of interest was the occurrence of a diabetic event. Cox proportional risk model was used to assess the independent effect of baseline serum creatinine level on future diabetes risk. Sensitivity and subgroup analysis were used to verify the reliability of the results. After an average follow-up of 3.12 years, among 201,298 individuals aged ≥ 20 years, 3389 patients developed diabetes. Compared with participants in quartile 2-4 (> 51.6umol/L for female, > 71.8umol/L for male,), a significantly higher risk of new-onset Type 2 Diabetes (OR, 1.15; 95%CI: 1.07-1.23) was found in those in quartile 1 (< 51.6umol/L for female, < 71.8umol/L for male). Moreover, Similar results were found in various subgroups stratified by age, BMI, TG, TC, FPG and family history group. Low serum creatinine is independently associated with increased risk of type 2 diabetes in Chinese adults. It was also stable in various subgroups stratified.