Analysis of Metabolite Differences in Different Tea Liquors Based on Broadly Targeted Metabolomics.

To expand the development of characteristic extension products of Yunnan tea and improve the utilization rate of Yunnan tea resources, in this study, we compared the metabolite composition among raw Pu-erh tea, ripe Pu-erh tea prepared with glutinous rice (according to tea to glutinous rice ratio of 1:3), and ripe Pu-erh tea prepared with a mixture of sorghum, rice, glutinous rice, wheat, and corn as raw materials (according to a tea to glutinous rice ratio of 1:3). Rice flavor liquor prepared with 100% glutinous rice served as a control. The raw Pu-erh tea liquor (RAWJ), ripe Pu-erh tea liquor (RIPEJ), ripe Pu-erh tea mixed grain liquor (HHLSJ), and rice-flavor liquor (MJ) were all brewed by semi-solid fermentation. The non-volatile components of the liquor samples were analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry as a broadly targeted metabolomics technique. A total of 691 metabolites were identified from the four samples. Among them, 674, 671, 633, and 667 species were detected in RAWJ, RIPEJ, HHLSJ, and MJ samples, respectively. Venn diagram analysis demonstrated 19, 21, and 14 unique metabolites in RAWJ, RIPEJ, and HHLSJ, respectively, compared with the metabolite composition of MJ. Flavonoids are the most important differential metabolite between tea liquor and rice-flavor liquor. This study provides a theoretical basis for the development of tea liquor products and offers insight into the difference in non-volatile components between tea liquor and rice-flavor liquor.

H3PO4-Impregnated Covalent Organic Framework Membrane on Separators to Prevent Lithium Metal Anode Dendrite Growth.

Inhibiting the growth of lithium dendrites is crucial for battery safety. For separators, their favorable electrolyte wettability, uniform current density, and high ionic conductivity are beneficial for avoiding Li dendrite growth. In this work, we propose a separator (PA@COF/PP) by modifying a polypropylene separator with H3PO4-functionalized covalent organic frameworks. The uniform channels of the covalent organic frameworks and H3PO4 can homogenize the current and act as ionic conductors for efficient Li+ migration. The synthesized separator effectively suppresses the growth of lithium dendrites and improves the stability of the batteries. A symmetric cell with the PA@COF/PP separator exhibits a stable life span over 4000 hours at a high current density of 5 mA cm-2, compared to the commercial PP separator, which lasts only 159 hours. This work provides an efficient method and novel inspiration for the construction of dendrite-free lithium metal batteries.

Multispectral bioactivity studies of N-terminal fatty acid modified antimicrobial peptide Andricin B.

A series of Andricin B derivatives were designed and synthesized using fatty acid modification at N-terminus of the antimicrobial peptides. The hydrophobicity of Andricin B was altered through fatty acid modification, and the bioactivity was investigated. The interaction between Andricin B and its derivatives with DNA was measured using multi-spectroscopy. Spectroscopic analysis revealed that Andricin B and its derivatives can interact with ct-DNA and G-quadruplexes DNA, and the interaction related with the length of fatty acid chain. Antimicrobial activity tests showed a significant increase using peptides with 8-10 carbons fatty acid chain. C10-Andricin B exhibited the highest antimicrobial activity, with up to a 16-fold enhancement compared to the original peptide Andricin B. Meanwhile, the protease hydrolysis stability test showed that fatty acid modification improved the stability of Andricin B against protease. Scanning electron microscopy results distinctly showed that C8-Andricin B could rupture the cell wall of bacteria. All results indicated that fatty acid modification peptides are an effective strategy for enhancing activity and stability of antimicrobial peptides. This research provides valuable insights for further research on antimicrobial peptides.

The effect of long-term care insurance on women's health outcomes in China: evidence from a disability inclusion action.

BACKGROUND: Long-term care insurance (LTCI) in China provides financial and care security for persons with disabilities and includes caregivers in the paid labour workforce. However, it is unclear how the LTCI affects health outcomes in female recipients, female caregivers, and female non-recipients and female non-caregivers. METHODS: Using the China Health and Retirement Longitudinal Study data and staggered difference-in-differences method, we evaluated the effect of LTCI on health outcomes in women with different roles, including female recipients, female caregivers, and female non-recipients and female non-caregivers, and discussed the heterogeneity of the effect on women's health outcomes. RESULTS: LTCI statistically significant increased self-rated health and reduced depression in women and improved the health in women with different roles by increasing self-rated health in female recipients, reducing chronic diseases in female caregivers, and reducing depression in female non-recipients and female non-caregivers. There was a more pronounced improvement in health outcomes among women in the west and northeast and women in rural village. CONCLUSIONS: After the implementation of LTCI, health outcomes in female recipients, female caregivers, and female non-recipients and female non-caregivers were improved. LTCI' improvement on women's health outcomes was heterogeneous geographically and socially. Our findings highlight the importance of delivering differentiated health interventions for women with different roles in the implementation process of LTCI and minimizing women's health inequalities in geography and society.

Efficacy and safety of BaitouWeng decoction for ulcerative colitis: A meta-analysis of randomized and controlled trials.

BACKGROUND: To systematically evaluate the therapeutic effect of BaitouWeng Decoction in patients with ulcerative colitis (UC), evaluate its safety and effectiveness, and provide a reference for clinical medication. METHODS: The research literature on the treatment of UC with BaitouWeng Decoction was searched in databases such as China National Knowledge Infrastructure, Wanfang Data, VIP database for Chinese Technical Periodicals, Chinese BioMedical Literature Database, and PubMed. The literature was screened by setting inclusion and exclusion criteria, strictly following the inclusion and exclusion criteria, and following the search strategy for literature screening, data extraction, and methodological quality evaluation. According to the Cochrane System Evaluation Manual, methodological quality evaluation was conducted on the included studies using the bias risk assessment tool for randomized controlled trials. For meta-analysis, Review Manager software was used. RESULTS: A total of 24 articles were included, including 2131 patients. Meta-analysis showed that compared with conventional Western medicine, BaitouWeng Decoction can significantly improve the effective rate (odds ratio = 5.10, 95% confidence interval [CI] [3.74-6.96], P < .00001), reduce the traditional Chinese medicine syndrome score (mean difference [MD] = -4.23, 95% CI [-5.17--3.30], P < .00001), Baron endoscopic score (MD = -0.68, 95% CI [-0.78--0.58], P < .00001), and intestinal lesion activity score (MD = -2.29, 95% CI [-1.15--1.03], P < .00001); improve serum factors and reduce serum tumor necrosis factor α levels (MD = -16.84, 95% CI [-19.92--13.76], P < .00001), serum interleukin-8 levels (MD = -10.41, 95% CI [-10.87--9.95], P < .00001), and increased serum interleukin-10 levels (MD = 4.96, 95% CI [2.76-7.16], P < .00001). CONCLUSION: BaitouWeng Decoction has good efficacy and safety in treating UC. BaitouWeng Decoction improved the symptoms of colitis injury and inhibited inflammatory response. However, more rigorously designed randomized controlled trials with blinding, concealment, and placebo controls should be conducted on Baitouweng decoction to generate higher quality evidence and longer-term studies on sustained benefits are needed.

Machine learning aided design of single-atom alloy catalysts for methane cracking.

The process of CH4 cracking into H2 and carbon has gained wide attention for hydrogen production. However, traditional catalysis methods suffer rapid deactivation due to severe carbon deposition. In this study, we discover that effective CH4 cracking can be achieved at 450 °C over a Re/Ni single-atom alloy via ball milling. To explore single-atom alloy catalysis, we construct a library of 10,950 transition metal single-atom alloy surfaces and screen candidates based on C-H dissociation energy barriers predicted by a machine learning model. Experimental validation identifies Ir/Ni and Re/Ni as top performers. Notably, the non-noble metal Re/Ni achieves a hydrogen yield of 10.7 gH2 gcat-1 h-1 with 99.9% selectivity and 7.75% CH4 conversion at 450 °C, 1 atm. Here, we show the mechanical energy boosts CH4 conversion clearly and sustained CH4 cracking over 240 h is achieved, significantly surpassing other approaches in the literature.

Bioactive sulfur-containing amides from the leaves of Glycosmis lucida.

Two new sulphur-containing amides, glylucidamides C-D (1-2), along with twelve known analogues (3-14) were isolated and characterised from the leaves of Glycosmis lucida. The chemical structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons their data with those reported in the literatures. All new compounds were evaluated for their anti-inflammatory activities via examining the inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro.

Cerebral Ischemic Coma Model Induced by Modified Four-Vessel Occlusion.

Coma caused by cerebral ischemia is the most serious complication of cerebral ischemia. Four-vessel occlusion can establish a cerebral ischemic coma model for disease research and drug development. However, the commonly used four-vessel occlusion method mainly involves inserting an electrocoagulation pen into the bilateral pterygoid foramen of the first cervical vertebra behind the neck to electrocoagulate the vertebral arteries. This process carries the risk of incomplete electrocoagulation, bleeding, and damage to the brainstem and spinal cord. Twenty-four hours after surgery, re-anesthetized rats undergo carotid artery ligation in front of the neck. Two surgeries expose the rats to a higher risk of infection and increase the experimental period. In this study, during a single surgical procedure, an anterior cervical incision was used to locate the key site where the vertebral artery penetrates the first cervical vertebra. The bilateral vertebral arteries were electrocauterized under visual conditions, while the bilateral common carotid arteries were separated to place loose knots. When the rats showed consciousness of the inversion reaction, the bilateral common carotid arteries were quickly ligated to induce ischemic coma. This method can avoid the risk of infection caused by two surgical operations and is easy to perform with a high success rate, providing a useful reference for relevant practitioners.

A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion.

The middle cerebral artery occlusion reperfusion (MCAO/R) model is crucial for understanding the pathological mechanisms of stroke and for drug development.However, among the commonly used modeling methods, the Koizumi method often faces scrutiny due to its ligation of the common carotid artery (CCA) and its inability to achieve adequate reperfusion. Similarly, the Longa method has been criticized for disconnecting and ligating the external carotid artery (ECA). This study aims to introduce a modified model preparation method that preserves the integrity of the ECA, involves inserting a monofilament nylon suture through the CCA, repairing the ligated CCA incision, and maintaining reperfusion from the CCA. Reperfusion of blood flow was confirmed using laser speckle flow imaging. Evaluation methods such as the Longa scale, Modified Neurological Severity Score, triphenyltetrazolium chloride (TTC) staining, and immunofluorescence labeling of neurons demonstrated that this approach could induce stable ischemic nerve damage. This modified MCAO/R model protocol is simple and stable, providing valuable guidance for practitioners in the field of cerebral ischemia.

Transcriptome Analysis Reveals the Venom Genes of the Ectoparasitoid Habrobracon hebetor (Hymenoptera: Braconidae).

The ectoparasitoid Habrobracon hebetor (Hymenoptera: Braconidae) exhibits a broad parasitic capability towards various lepidopteran pests, with venom serving as a crucial virulent factor ensuring successful parasitization and subsequent host mortality. Analyzing the constituents of its venom is essential for elucidating the mechanisms underlying efficient host killing by this parasitoid and for exploring potentially functional venom proteins. Through a transcriptomic analysis, a total of 34 venom proteins were identified within the venom of H. hebetor, encompassing known components such as serine protease, metalloproteinase, esterase, and serine protease inhibitors commonly present in parasitoid venoms. Unique components like paralytic protein and ion transport peptide-like were identified, possibly specific to certain parasitoids, along with novel proteins with uncharacterized functions. Spatial gene expression profiling of the identified venom proteins using transcriptomic data, corroborated by quantitative PCR validation for 13 randomly selected proteins, revealed abundant expression levels in the venom apparatus, affirming them as genuine venom components. Notably, the paralytic protein exhibited prominent expression, with the highest FPKM (fragments per kilobase of transcript per million fragments mapped) value of 24,704.87 in the venom apparatus, indicative of its significant role in successful parasitism by H. hebetor. The identification of these venom proteins establishes a foundation for the further exploration of bioactive agents for pest management strategies.

Recent Advances in Fluorescent Probes for G-quadruplex DNAs / RNAs.

Guanine-quadruplexes (G4s) are high-level structures formed by the folding of guaninerich nucleic acid sequences. G4s play important roles in various physiological processes, such as gene transcription, replication, recombination, and maintenance of chromosomal stability. Specific and sensitive monitoring of G4s lays the foundation for further understanding the structure, content, distribution, and function of G4s in organisms, which is important for the treatment and diagnosis of diseases. Moreover, visualization of G4s will provide new ideas for developing antitumor strategies targeting G4s. The design and development of G4-specific ligands are challenging due to the subtle differences in the structure of G4s. This review focuses on the progress of research on G4 fluorescent probes and their binding mechanisms to G4s. Finally, the challenges and future prospects for better detection and targeting of G4s in different organisms are discussed. This paper provides ideas for the development of novel G4 fluorescent probes.

Network pharmacology and experimental verification of the mechanism of licochalcone A against Staphylococcus aureus pneumonia.

Staphylococcus aureus strains cause the majority of pneumonia cases and are resistant to various antibiotics. Given this background, it is very important to discover novel host-targeted therapies. Licochalcone A (LAA), a natural plant product, has various biological activities, but its primary targets in S. aureus pneumonia remain unclear. Therefore, the purpose of this study was to identify its molecular target against S. aureus pneumonia. Network pharmacology analysis, histological assessment, enzyme-linked immunosorbent assays, and Western blotting were used to confirm the pharmacological effects. Network pharmacology revealed 33 potential targets of LAA and S. aureus pneumonia. Enrichment analysis revealed that these potential genes were enriched in the Toll-like receptor and NOD-like receptor signaling pathways. The results were further verified by experiments in which LAA alleviated histopathological changes, inflammatory infiltrating cells and inflammatory cytokines (TNF, IL-6, and IL-1ß) in the serum and bronchoalveolar lavage fluid in vivo. Moreover, LAA treatment effectively reduced the expression levels of NF-κB, p-JNK, p-p38, NLRP3, ASC, caspase 1, IL-1ß, and IL-18 in lung tissue. The in vitro experimental results were consistent with the in vivo results. Thus, our findings demonstrated that LAA exerts anti-infective effects on S. aureus-induced lung injury via suppression of the Toll-like receptor and NOD-like receptor signaling pathways, which provides a theoretical basis for understanding the function of LAA against S. aureus pneumonia and implies its potential clinical application.

Aspergillus oryzae ß-D-galactosidase immobilization on glutaraldehyde pre-activated amino-functionalized magnetic mesoporous silica: Performance, characteristics, and application in the preparation of sesaminol.

Aspergillus oryzae ß-D-galactosidase (ß-Gal) efficiently hydrolyzes sesaminol triglucoside into sesaminol, which has higher biological activity. However, ß-Gal is difficult to be separate from the reaction mixture and limited by stability. To resolve these problems, ß-Gal was immobilized on amino-functionalized magnetic nanoparticles mesoporous silica pre-activated with glutaraldehyde (Fe3O4@mSiO2-ß-Gal), which was used for the first time to prepare sesaminol. Under the optimal conditions, the immobilization yield and recovered activity of ß-Gal were 57.9 ± 0.3 % and 46.5 ± 0.9 %, and the enzymatic loading was 843 ± 21 Uenzyme/gsupport. The construction of Fe3O4@mSiO2-ß-Gal was confirmed by various characterization methods, and the results indicated it was suitable for heterogeneous enzyme-catalyzed reactions. Fe3O4@mSiO2-ß-Gal was readily separable under magnetic action and displayed improved activity in extreme pH and temperature conditions. After 45 days of storage at 4 °C, the activity of Fe3O4@mSiO2-ß-Gal remained at 92.3 ± 2.8 %, which was 1.29 times than that of free enzyme, and its activity remained above 85 % after 10 cycles. Fe3O4@mSiO2-ß-Gal displayed higher affinity and catalytic efficiency. The half-life was 1.41 longer than free enzymes at 55.0 °C. Fe3O4@mSiO2-ß-Gal was employed as a catalyst to prepare sesaminol, achieving a 96.7 % conversion yield of sesaminol. The excellent stability and catalytic efficiency provide broad benefits and potential for biocatalytic industry applications.

Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice.

Exercise is usually regarded to have short-term beneficial effects on immune health. Here we show that early-life regular exercise exerts long-term beneficial effects on inflammatory immunity. Swimming training for 3 months in male mice starting from 1-month-old curbs cytokine response and mitigates sepsis when exposed to lipopolysaccharide challenge, even after an 11-month interval of detraining. Metabolomics analysis of serum and liver identifies pipecolic acid, a non-encoded amino acid, as a pivotal metabolite responding to early-life regular exercise. Importantly, pipecolic acid reduces inflammatory cytokines in bone marrow-derived macrophages and alleviates sepsis via inhibiting mTOR complex 1 signaling. Moreover, early-life exercise increases histone 3 lysine 4 trimethylation at the promoter of Crym in the liver, an enzyme responsible for catalyzing pipecolic acid production. Liver-specific knockdown of Crym in adult mice abolishes this early exercise-induced protective effects. Our findings demonstrate that early-life regular exercise enhances anti-inflammatory immunity during middle-aged phase in male mice via epigenetic immunometabolic modulation, in which hepatic pipecolic acid production has a pivotal function.

Effect of long-term care insurance policy on depression in non-disabled people: evidence from China.

BACKGROUND: Policy effect might be multidimensional and spill over to non-recipients. It is unclear how the implementation of Long-Term Care Insurance (LTCI) policy affects depression in non-disabled people and how this effect differs in different non-disabled groups. METHODS: Using time-varying differences-in-differences method and nationally representative health survey data in wave 2011, wave 2013, wave 2015 and wave 2018 from the China Health and Retirement Longitudinal Study, we assessed the effect of LTCI policy on depression in non-disabled people aged 45 years and older, and discussed the heterogeneity of effect across different population characteristics: retirement, financial support and social participation status. RESULTS: We found LTCI policy statistically significant reduced depression by 0.76 units in non-disabled people compared to non-pilot cities. Depression in non-disabled people who unretired, with financial support and without social participation was reduced by 0.8267, 0.7079 and 1.2161 units, respectively. CONCLUSIONS: Depression in non-disabled people was statistically significant reduced because of LTCI policy in China, and non-disabled people who unretired, with financial support and without social participation benefited more from LTCI policy. Our findings highlight the depression-reducing effect of LTCI policy in non-recipients and suggest that non-disabled people who unretired, with financial support and without social participation should be concerned during LTCI policy progress.

Exploration of YBX1 role in the prognostic value and immune characteristics by single-cell and bulk sequencing analysis for liver hepatocellular carcinoma.

BACKGROUND: Y-box binding protein 1 (YBX1) plays a variety of roles in progression of multiple tumors. However, the role of YBX1 in prognostic value and immune regulation for liver hepatocellular carcinoma (LIHC) remains unclear. The present study aimed to examine the effect of YBX1 on the regulation of tumor immunity and survival prediction in LIHC patients. METHODS: YBX1-related expression profiles and single-cell and bulk sequencing analysis were performed using online databases. YBX1 expression was validated by a quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. Univariate/multivariate Cox regression analysis was performed to determine independent predictors of overall survival (OS). The ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis were used to assess the relationships between YBX1 and LIHC immunity. RESULTS: YBX1 was over-expressed in LIHC tissues and cell lines. High YBX1 expression was significantly associated with poor OS. Univariate/multivariate Cox regression analysis revealed that YBX1 was an independent prognostic factor for LIHC. Gene set enrichment analysis revealed that YBX1 was associated with multiple signaling pathways correlated to LIHC. Additionally, YBX1 was expressed in multiple immune cells and was significantly correlated with immune cells, immune checkpoint markers and tumor immune microenvironment. The TIDE analysis demonstrated that LIHC patients with high YBX1 expression showed a higher T-cell dysfunction score and a higher exclusion score, as well as poorer immunotherapy response. CONCLUSIONS: YBX1 plays crucial oncogenic roles in LIHC and is closely associated with the immune defense system. YBX1 inhibition may serve as a potential treatment for LIHC.

Performance Degradation of a Double-Perovskite PrBaCo2O5+δ Cathode Operating under a CO2/H2O-Containing Atmosphere.

The electrochemical activity and stability of the PBCO electrode are investigated under the annealing processes in an atmosphere containing CO2/H2O for solid oxide fuel cells (SOFCs). The electrochemical impedance spectrum results unequivocally confirm the significant deterioration in PBCO cathode performance upon annealing under ambient air conditions, particularly when exposed to CO2/H2O atmospheres. Microstructure and surface chemical state analyses reveal the segregation of BaO on the PBCO surface, and the formation of insulating BaCO3 degraded the electrochemical performance. CO2 and H2O exhibit a significant induced effect on the segregation of Ba in PBCO to the surfaces, thereby causing a rapid decline in electrode performance. Additionally, the analysis of volume relaxation reveals that the presence of oxygen in the electrode environment can also influence the deposition process occurring on the surface of the electrode. However, this phenomenon is not observed in N2. This study emphasizes the impact of various gases present in the working atmosphere on surface-separated BaO, which consequently plays a pivotal role in the activity and long-term stability of PBCO electrodes.

The relationship between dyslipidemia and menopausal symptoms in Chinese menopausal women: a cross-sectional study.

OBJECTIVE: To investigate the relationship of dyslipidemia and menopausal symptoms in Chinese menopausal women. MATERIAL AND METHODS: A total of 989 eligible participants with menopausal syndrome were recruited from outpatient clinics in several cities in China. Menopausal symptoms were assessed using the Chinese Menopause Rating Scale (CMRS), the Self-rating Depression Scale (SDS), and the Self-rating Anxiety Scale (SAS). Serum lipid profile was measured using enzyme colorimetry. The relationship between lipid profile and menopausal symptoms was assessed using Student's t test/nonparametric Mann-Whitney U test, Spearman's correlation test, and binary logistic regression analysis. RESULTS: Among the 989 patients, 527 had dyslipidemia while 462 did not. Patients with dyslipidemia had significantly higher Self-rating Anxiety Scale (SAS) scores than those without (p < 0.001), while there was no significant difference in Self-rating Depression Scale (SDS) scores. Patients without dyslipidemia had higher scores on the Chinese Menopause Rating Scale (CMRS) vascular dimension compared to those with dyslipidemia (p = 0.003). The correlation test revealed that variables associated with dyslipidemia included age (p = 0.031), CMRS hot flashes dimension score (P = 0.003), and SAS score (p < 0.001). Regression analysis demonstrated that BMI (OR: 1.08, 95% CI: 1.01-1.16, p = 0.027), SAS scores (OR = 1.10, 95% CI = 1.07-1.13), vasomotor dimension (OR = 0.89, 95% CI = 0.83-0.95), physical dimension (OR = 0.96, 95% CI = 0.93-1.00), and social dimension (OR = 0.84, 95% CI = 0.74-0.95) were independently associated with an increased risk of dyslipidemia. CONCLUSIONS: This study showed that anxiety was associated with an unfavorable lipid profile, and menopausal depression seemed to have no relationship with lipid profile, while vasomotor symptoms appeared to be a favorable factor for dyslipidemia in Chinese menopausal women.

Discovery of Melittin as Triple-Action Agent: Broad-Spectrum Antibacterial, Anti-Biofilm, and Potential Anti-Quorum Sensing Activities.

The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.

Long-term simulated microgravity fosters carotid aging-like changes via Piezo1.

AIMS: Elucidating the impacts of long-term spaceflight on cardiovascular health is urgently needed in face of the rapid development of human space exploration. Recent reports including the NASA Twins Study on vascular deconditioning and aging of astronauts in spaceflight are controversial. The aims of this study were to elucidate whether long-term microgravity promotes vascular aging and the underlying mechanisms. METHODS AND RESULTS: Hindlimb unloading (HU) by tail suspension was used to simulate microgravity in rats and mice. The dynamic changes of carotid stiffness in rats during 8 weeks of HU were determined. Simulated microgravity led to carotid artery aging-like changes as evidenced by increased stiffness, thickness, fibrosis, and elevated senescence biomarkers in the HU rats. Specific deletion of the mechanotransducer Piezo1 in vascular smooth muscles significantly blunted these aging-like changes in mice. Mechanistically, mechanical stretch-induced activation of Piezo1 elevated microRNA-582-5p in vascular smooth muscle cells, with resultant enhanced synthetic cell phenotype and increased collagen deposition via PTEN/PI3K/Akt signalling. Importantly, inhibition of miRNA-582-5p alleviated carotid fibrosis and stiffness not only in HU rats but also in aged rats. CONCLUSIONS: Long-term simulated microgravity induces carotid aging-like changes via the mechanotransducer Piezo1-initiated and miRNA-mediated mechanism.