The relationship between dietary total flavonoids and thyroid function in U.S.adults, NHANES 2007-2010.

BACKGROUND: Although small studies have shown that flavonoids can affect thyroid disease, few epidemiological studies have explored the relationship between dietary total flavonoids (TFs) intake and serum thyroid function. The aim of this research was to evaluate the relationship between TFs and serum thyroid function. METHODS: Our study included 4,949 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Multivariable linear regression, subgroup analyses, and interaction terms were used to explore the relationships between TFs and thyroid function. And we also used restricted cubic splines (RCS) to investigate possible nonlinear relationships. RESULTS: After adjusting for covariates, we found that log10-transformated dietary total flavonoids intake (LgTFs) was negatively associated with total thyroxine (TT4) (ß = -0.153, 95% CI = -0.222 to -0.084, P<0.001). Subgroup analyses revealed a stronger and statistically supported association in subjects with high annual family income (ß = -0.367, P<0.001, P for interaction = 0.026) and subjects with high poverty to income ratio (PIR) (ß = -0.622, P<0.001, P for interaction = 0.042). And we found a U-shaped curve association between LgTFs and free triiodothyronine (FT3) (inflection point for LgTFs: 2.063). CONCLUSION: The results of our study demonstrated that a higher intake of total flavonoids in the diet was negatively associated with a lower TT4. Furthermore, the associations were more pronounced in high annual family income and high PIR adults. And we found a U-shaped relationship between LgTFs and FT3. These findings provided guidance for future thyroid dysfunction diet guidelines.

Better clinical outcomes and return to sport rates with additional medial meniscus root tear repair in high tibial osteotomy for medial compartmental knee osteoarthritis.

PURPOSE: This retrospective study aimed to investigate whether the repair of medial meniscus posterior root tears (MMPRTs) is effective for improving clinical outcomes and return to sports rates in young patients (50 years old or younger) with medial compartment knee osteoarthritis (KOA) and MMPRTs. METHODS: Between 2016 and 2019, 153 patients with KOA and MMPRTs who underwent open-wedge high tibial osteotomy (OWHTO) were retrospectively included. The patients were divided into OWHTO combined with MMPRT repair (n = 73) and isolated OWHTO (n = 80) groups. Lysholm scores, Hospital for Special Surgery (HHS) scores, Tegner scores, flexion contracture, range of knee flexion, return to sports rates and postoperative complications were compared. Radiological outcomes, including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA) and Kellgren-Lawrence (K-L) grade, were compared between the two groups. RESULTS: After a mean follow-up of 30.1 ± 3.0 months, the OWHTO + Repair group observed better clinical outcomes compared with the OWHTO group (Lysholm score: 86.7 ± 7.4 vs. 81.6 ± 6.9, p = 0.023. HHS score: 85.4 ± 8.20 vs. 80.5 ± 7.1, p = 0.039). The OWHTO + Repair group had higher Tegner scores and return to sports rates than the OWHTO group (Tegner score: 6 vs. 5, p = 0.020; return to sports rates: 38% vs. 15%, p = 0.001). No fracture or major complications occurred. Radiological outcomes showed no significant differences between the two groups (HKA: 181.1 ± 2.7 vs. 180.1 ± 1.5 n.s; MPTA: 90.1 ± 1.8 vs. 89.2 ± 1.4, n.s; JLCA:1.9 ± 0.7 vs. 2.1 ± 0.7, n.s). CONCLUSIONS: Additional MMPRT repair during OWHTO was associated with better clinical outcomes and higher rates of return to sports in young patients with medial compartment KOA and MMPRTs. LEVEL OF EVIDENCE: Level III.

Microbaculum marinisediminis sp. nov., isolated from marine sediment.

A novel Gram-stain-negative and facultatively anaerobic bacterium, designated A6E488T, was isolated from intertidal sediment collected from Xiaoshi Island, Weihai, PR China (122° 1' E 37° 31' N). Cells of strain A6E488T were rod-shaped with widths of 0.3-0.4 µm and lengths of 1.1-1.8 µm. The optimal growth conditions were determined to be in 1 % (w/v) NaCl, at 37 °C, and at pH 7.0. The predominant fatty acids (≥10 %) were C19 : 0 cyclo ω8c (59.7 %) and summed feature 8 (13.8 %, C18 : 1 ω7c and/or C18 : 1 ω6c). The sole isoprenoid quinone was Q-10. Oxidase activity was negative but catalase activity was positive. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid, one unidentified glycolipid, and one unidentified lipid. Based on phylogenetic analysis of 16S rRNA gene sequences, strain A6E488T showed the highest sequence similarity to Microbaculum marinum MCCC 1K03192T (97.6 %). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain A6E488T and M. marinum MCCC 1K03192T did not exceed 78 and 22 %, respectively. These values are below the recommended thresholds of 95 % (ANI) and 70 % (dDDH) for prokaryotic species delineation. On the basis of gene annotation, it was observed that strain A6E488T possesses the capability for thiosulphate oxidation, suggesting that this strain might be important in the sulphur cycle. Based on the results of phenotypic, genotypic, and chemical characterization, strain A6E488T is considered to represent a novel species of the genus Microbaculum, for which the name Microbaculum marinisediminis sp. nov. is proposed. The type strain is A6E488T (=KCTC 92197T=MCCC 1H00516T).

Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study.

Mosaic loss of chromosome Y (mLOY) is the most common somatic alteration as men aging and may reflect genome instability. PM exposure is a major health concern worldwide, but its effects with genetic factors on mLOY has never been investigated. Here we explored the associations of PM2.5 and PM10 exposure with mLOY of 10,158 males measured via signal intensity of 2186 probes in male-specific chromosome-Y region from Illumina array data. The interactive and joint effects of PM2.5 and PM10 with genetic factors and smoking on mLOY were further evaluated. Compared with the lowest tertiles of PM2.5 levels in each exposure window, the highest tertiles in the same day, 7-, 14-, 21-, and 28-day showed a 0.005, 0.006, 0.007, 0.007, and 0.006 decrease in mLRR-Y, respectively (all P < 0.05), with adjustment for age, BMI, smoking pack-years, alcohol drinking status, physical activity, education levels, season of blood draw, and experimental batch. Such adverse effects were also observed in PM10-mLOY associations. Moreover, the unweighted and weighted PRS presented significant negative associations with mLRR-Y (both P < 0.001). Participants with high PRS and high PM2.5 or PM10 exposure in the 28-day separately showed a 0.018 or 0.019 lower mLRR-Y level [ß (95 %CI) = -0.018 (-0.023, -0.012) and - 0.019 (-0.025, -0.014), respectively, both P < 0.001], when compared to those with low PRS and low PM2.5 or PM10 exposure. We also observed joint effects of PM with smoking on exacerbated mLOY. This large study is the first to elucidate the impacts of PM2.5 exposure on mLOY, and provides key evidence regarding the interactive and joint effects of PM with genetic factors on mLOY, which may promote understanding of mLOY development, further modifying and increasing healthy aging in males.

Effect of metacognitive therapy on depression in patients with chronic disease: a protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic diseases have a high prevalence worldwide, and patients with chronic diseases often suffer from depression, leading to a poor prognosis and a low quality of life. Metacognitive therapy is a transdiagnostic psychotherapy intervention focused on thinking patterns, with the advantages of reliable implementation effect, short intervention period and low cost. It can help patients change negative metacognition, alleviate depression symptoms, and has a higher implementation value compared with other cognitive interventions. Therefore, metacognitive therapy may be an effective way to improve the mental health of patients with chronic diseases. METHODS AND ANALYSIS: CNKI, Wanfang Database, VIP Database for Chinese Technical Periodicals, Sinomed, PubMed, SCOPUS, Embase, The Cochrane Library, Web of Science and PsycINFO will be used to select the eligible studies. As a supplement, websites (eg, the Chinese Clinical Registry, ClinicalTrials.gov) will be searched and grey literature will be included. The heterogeneity and methodological quality of the eligible studies will be independently screened and extracted by two experienced reviewers. All the data synthesis and analysis (drawing forest plots, subgroup analysis and sensitive analysis) will be conducted using RevMan 5.4.1. ETHICS AND DISSEMINATION: This article is a literature review that does not include patients' identifiable information. Therefore, ethical approval is not required in this protocol. The findings of this systematic review and meta-analysis will be published in a peer-reviewed journal as well as presentations at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42023411105.

Pathogenicity of Aeromonas veronii Isolated from Diseased Macrobrachium rosenbergii and Host Immune-Related Gene Expression Profiles.

Aeromonas veronii is widespread in aquatic environments and is responsible for infecting various aquatic animals. In this study, a dominant strain was isolated from the hepatopancreas of diseased Macrobrachium rosenbergii and was named JDM1-1. According to its morphological, physiological, and biochemical characteristics and molecular identification, isolate JDM1-1 was identified as A. veronii. The results of artificial challenge showed isolate JDM1-1 had high pathogenicity to M. rosenbergii with an LD50 value of 8.35 × 105 CFU/mL during the challenge test. Histopathological analysis revealed severe damage in the hepatopancreas and gills of the diseased prawns, characterized by the enlargement of the hepatic tubule lumen and gaps between the tubules as well as clubbing and degeneration observed at the distal end of the gill filament. Eight virulence-related genes, namely aer, ompA, lip, tapA, hlyA, flgA, flgM, and flgN, were screened by PCR assay. In addition, virulence factor detection showed that the JDM1-1 isolate produced lipase, lecithinase, gelatinase, and hemolysin. Furthermore, the mRNA expression profiles of immune-related genes of M. rosenbergii following A. veronii infection, including ALF1, ALF2, Crustin, C-lectin, and Lysozyme, were assessed, and the results revealed a significant upregulation in the hepatopancreas and intestines at different hours post infection. This study demonstrates that A. veronii is a causative agent associated with massive die-offs of M. rosenbergii and contributes valuable insights into the pathogenesis and host defense mechanisms of A. veronii invasion.

Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers. METHODS: In this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments. RESULTS: Utilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model. CONCLUSION: The expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.

Development and application of Chinese medical ontology for diabetes mellitus.

OBJECTIVE: To develop a Chinese Diabetes Mellitus Ontology (CDMO) and explore methods for constructing high-quality Chinese biomedical ontologies. MATERIALS AND METHODS: We used various data sources, including Chinese clinical practice guidelines, expert consensus, literature, and hospital information system database schema, to build the CDMO. We combined top-down and bottom-up strategies and integrated text mining and cross-lingual ontology mapping. The ontology was validated by clinical experts and ontology development tools, and its application was validated through clinical decision support and Chinese natural language medical question answering. RESULTS: The current CDMO consists of 3,752 classes, 182 fine-grained object properties with hierarchical relationships, 108 annotation properties, and over 12,000 mappings to other well-known medical ontologies in English. Based on the CDMO and clinical practice guidelines, we developed 200 rules for diabetes diagnosis, treatment, diet, and medication recommendations using the Semantic Web Rule Language. By injecting ontology knowledge, CDMO enhances the performance of the T5 model on a real-world Chinese medical question answering dataset related to diabetes. CONCLUSION: CDMO has fine-grained semantic relationships and extensive annotation information, providing a foundation for medical artificial intelligence applications in Chinese contexts, including the construction of medical knowledge graphs, clinical decision support systems, and automated medical question answering. Furthermore, the development process incorporated natural language processing and cross-lingual ontology mapping to improve the quality of the ontology and improved development efficiency. This workflow offers a methodological reference for the efficient development of other high-quality Chinese as well as non-English medical ontologies.

Investigation of Phenolic Resin-Modified Asphalt and Its Mixtures.

This study comprehensively examines the influence of phenol-formaldehyde resin (PF) on the performance of base asphalt and its mixtures for road applications, emphasizing its innovative use in enhancing pavement quality. Optimal PF content was determined through the evaluation of standard indicators and rotational viscosity. In-depth analyses of PF-modified asphalt's high- and low-temperature rheological properties and viscoelastic behavior were conducted using dynamic shear rheometers and bending beam rheometers. Aging resistance was assessed through short-term aging and performance grade (PG) grading. Moreover, Marshall and water stability tests were performed on PF-modified asphalt mixtures. Findings indicate that the uniform dispersion of PF particles effectively inhibits asphalt flow at high temperatures, impedes oxygen penetration, and delays the transition from elasticity to viscosity. These unique properties enhance the high-temperature stability, rutting resistance, and aging resistance of PF-modified asphalt. However, under extremely low temperatures, PF's brittleness may impact asphalt flexibility. Nonetheless, the structural advantages of PF-modified asphalt, such as improved mixture density and stability, contribute to enhanced high-temperature performance, water stability, adhesion, and freeze-thaw cycle stability. This research demonstrates the feasibility and effectiveness of using PF to enhance the overall performance of base asphalt and asphalt mixtures for road construction.

Associations between plasma metal/metalloid mixtures and the risk of central obesity: A prospective cohort study of Chinese adults.

Central obesity has increased rapidly over the past decade and posed a substantial disease burden worldwide. Exposure to metals/metalloids has been acknowledged to be involved in the development of central obesity through regulation of cortisol, insulin resistance, and glucocorticoid receptor reduction. Despite the importance, it is lack of prospective study which comprehensively evaluate the relations between multiple metals exposure and central obesity. We explored the prospective associations of plasma metal concentrations with central obesity in a prospective study of the Dongfeng-Tongji cohort. The present study included 2127 participants with a 6.87-year mean follow-up duration. We measured 23 plasma metal/metalloid concentrations at baseline. The associations between metals and incident central obesity were examined utilizing the Cox proportional hazard regression in single and multiple metals models. Additionally, we applied elastic net (ENET), Bayesian kernel machine regression (BKMR), plasma metal score (PMS), and quantile-based g-computation (Qgcomp) models to explore the joint associations of metal mixtures with central obesity. After adjusting potential confounders, we found significant associations of plasma manganese (Mn) and thallium (Tl) concentrations with a higher risk of central obesity, whereas plasma rubidium (Rb) concentration was associated with a lower risk of central obesity both in single and multiple metals models (all FDR <0.05). The ENET and Qqcomp models verified similar metals (Mn, Rb, and Tl) as important predictors for central obesity. The results of both BKMR model and PMS suggested cumulative exposure to metal mixtures was associated with a higher risk of central obesity. Our findings suggested that co-exposure to metals was associated with a higher risk of central obesity. This study expands our knowledge that the management of metals/metalloids exposure may be beneficial for the prevention of new-onset central obesity, which may subsequently alleviate the disease burden of late-life health outcomes.

Research progress related to thermosensitive hydrogel dressings in wound healing: a review.

Wound healing is a dynamic and complex process in which the microenvironment at the wound site plays an important role. As a common material for wound healing, dressings accelerate wound healing and prevent external wound infections. Hydrogels have become a hot topic in wound-dressing research because of their high water content, good biocompatibility, and adjustable physical and chemical properties. Intelligent hydrogel dressings have attracted considerable attention because of their excellent environmental responsiveness. As smart polymer hydrogels, thermosensitive hydrogels can respond to small temperature changes in the environment, and their special properties make them superior to other hydrogels. This review mainly focuses on the research progress in thermosensitive intelligent hydrogel dressings for wound healing. Polymers suitable for hydrogel formation and the appropriate molecular design of the hydrogel network to achieve thermosensitive hydrogel properties are discussed, followed by the application of thermosensitive hydrogels as wound dressings. We also discuss the future perspectives of thermosensitive hydrogels as wound dressings and provide systematic theoretical support for wound healing.

Identification of pathogenic germline variants in a large Chinese lung cancer cohort by clinical sequencing.

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large-scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer-susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next-generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer-susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case-control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value < 0.05). P/LP variants in certain genes were associated with early onset of lung cancer. Our study indicates that Chinese lung cancer patients have a higher prevalence of P/LP variants than previously reported. P/LP variants are distributed in multiple pathways and dominated by DNA damage repair-associated pathways. The association between identified P/LP variants and lung cancer risk requires further studies for verification.

Predicting Atmospheric Particle Phase State Using an Explainable Machine Learning Approach Based on Particle Rebound Measurements.

The particle phase state plays a vital role in the gas-particle partitioning, multiphase reactions, ice nucleation activity, and particle growth in the atmosphere. However, the characterization of the atmospheric phase state remains challenging. Herein, based on measured aerosol chemical composition and ambient relative humidity (RH), a machine learning (ML) model with high accuracy (R2 = 0.952) and robustness (RMSE = 0.078) was developed to predict the particle rebound fraction, f, which is an indicator of the particle phase state. Using this ML model, the f of particles in the urban atmosphere was predicted based on seasonal average aerosol chemical composition and RH. Regardless of seasons, aerosols remain in the liquid state of mid-high latitude cities in the northern hemisphere and in the semisolid state over semiarid regions. In the East Asian megacities, the particles remain in the liquid state in spring and summer and in the semisolid state in other seasons. The effects of nitrate, which is becoming dominant in fine particles in several urban areas, on the particle phase state were evaluated. More nitrate led the particles to remain in the liquid state at an even lower RH. This study proposed a new approach to predict the particle phase state in the atmosphere based on RH and aerosol chemical composition.

A Pan-Ebolavirus Monoclonal Antibody Cocktail Provides Protection Against Ebola and Sudan Viruses.

Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as a promising strategy for the treatment of filovirus disease. Here, we describe 2 distinct cross-reactive monoclonal antibodies (mAbs) isolated from mice immunized with recombinant vesicular stomatitis virus-based filovirus vaccines. Both mAbs recognized the glycoproteins of multiple different ebolaviruses and exhibited broad but differential in vitro neutralization activities against these viruses. By themselves, each mAb provided partial to full protection against Ebola virus in mice, and in combination, the mAbs provided 100% protection against Sudan virus challenge in guinea pigs. This study identified novel mAbs that were elicited through immunization and able to provide protection from ebolavirus infection, thus enriching the pool of candidate therapeutics for treating Ebola disease.

Fluoride-Based Stable Quasi-Solid-State Zinc Metal Battery with Superior Rate Capability.

Aqueous zinc metal batteries are limited in practical applications due to their short lifespans. Herein, a LaF3-coated Zn anode (LF@Zn) is investigated to induce the uniform Zn deposition and successfully build a separator-free quasi-solid-state zinc metal battery. The LF@Zn enables smooth and dendrite-free Zn deposition, owing to the homogeneous Zn2+ flux regulated by the LaF3-based quasi-solid-state electrolyte. It can also suppress the corrosion side reactions by modulating the [Zn(H2O)6]2+ solvation sheath. The polarization of plating and stripping is relatively modest due to the reduced diffuse energy of desolvated Zn2+ in the quasi-solid-state electrolyte. In a separator-free symmetric cell, the LF@Zn anode shows a significantly prolonged lifespan of over 1300 h at 2 mA cm-2 and a superior rate performance with only 156 mV at an ultrahigh current density of 50 mA cm-2. A LF@Zn//VO2 quasi-solid-state full cell exhibits outperforming rate capability and a long cyclic performance for up to 3000 cycles at 6.0 A g-1. A stable Zn anode is established in this work with a fluoride-based quasi-solid-state electrolyte, opening up a new avenue for protecting metal anodes.

Improving the Performance of Aligned Carbon Nanotube-Based Transistors by Refreshing the Substrate Surface.

An aligned semiconducting carbon nanotube (A-CNT) array has been considered an excellent channel material to construct high-performance field-effect transistors (FETs) and integrated circuits (ICs). The purification and assembly processes to prepare a semiconducting A-CNT array require conjugated polymers, introducing stubborn residual polymers and stress at the interface between A-CNTs and substrate, which inevitably affects the fabrication and performance of the FETs. In this work, we develop a process to refresh the Si/SiO2 substrate surface underneath the A-CNT film by wet etching to clean the residual polymers and release the stress. Top-gated A-CNT FETs fabricated with this process show significant performance improvement especially in terms of saturation on-current, peak transconductance, hysteresis, and subthreshold swing. These improvements are attributed to the increase in carrier mobility from 1025 to 1374 cm2/Vs by 34% after the substrate surface refreshing process. Representative 200 nm gate-length A-CNT FETs exhibit an on-current of 1.42 mA/µm and a peak transconductance of 1.06 mS/µm at a drain-to-source bias of 1 V, subthreshold swing (SS) of 105 mV/dec, and negligible hysteresis and drain-induced barrier lowering (DIBL) of 5 mV/V.

Secondary organic aerosol formation in China from urban-lifestyle sources: Vehicle exhaust and cooking emission.

An increasing number of people tend to live in cities, where they suffer from serious air pollution from anthropogenic sources. Vehicle exhaust and cooking emission are closely related to daily life of urban residents, and could be defined as "urban-lifestyle sources". The primary emissions of urban-lifestyle sources tend to form abundant secondary organic aerosols (SOA) through complicated atmospheric chemistry processes. The newly formed SOA is a kind of complex mixture and causes considerable health effects with high uncertainty. Most studies focus on formation pathway, mass growth potential and chemical feature of urban-lifestyle SOA under simple laboratory conditions. Few studies have measured the urban-lifestyle SOA in ambient air, let alone verified laboratory findings under complicated atmospheric conditions. In this work, we established a new method that combined laboratory simulation and field observation, which quantified the urban-lifestyle SOA with high time resolution under the real atmospheric condition. The complex SOA was measured and resolved by a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). The multilinear engine model (ME-2) and multilinear correction methods were used to apply laboratory results into ambient SOA apportionment. It was found that the vehicle source dominated the SOA formation during the diurnal photochemical process, and the SOA:POA ratio of vehicle source was about 1.4 times larger than that of cooking source. The vehicle emission may undergo an alcohol/peroxide & carboxylic acid oxidation pathway and form higher oxidized SOA, while the cooking emission may undergo an alcohol/peroxide oxidation pathway and form relatively lower oxidized SOA. The vehicle SOA and cooking SOA contributed 45.6 % and 24.8 % of OA during a local episode in 2021 winter of downtown Beijing. Our findings could not only provide a new way to quantify urban SOA but also demonstrate some laboratory hypotheses, conducing to understand its ambient contributions, chemical features, and environmental effects.

Activation Mechanism of RhoA Caused by Constitutively Activating Mutations G14V and Q63L.

RhoA, a member of Rho GTPases, regulates myriad cellular processes. Abnormal expression of RhoA has been implicated in various diseases, including cancers, developmental disorders and bacterial infections. RhoA mutations G14V and Q63L have been reported to constitutively activate RhoA. To figure out the mechanisms, in total, 1.8 µs molecular dynamics (MD) simulations were performed here on RhoAWT and mutants G14V and Q63L in GTP-bound forms, followed by dynamic analysis. Both mutations were found to affect the conformational dynamics of RhoA switch regions, especially switch I, shifting the whole ensemble from the wild type's open inactive state to different active-like states, where T37 and Mg2+ played important roles. In RhoAG14V, both switches underwent thorough state transition, whereas in RhoAQ63L, only switch I was sustained in a much more closed conformation with additional hydrophobic interactions introduced by L63. Moreover, significantly decreased solvent exposure of the GTP-binding site was observed in both mutants with the surrounding hydrophobic regions expanded, which furnished access to water molecules required for hydrolysis more difficult and thereby impaired GTP hydrolysis. These structural and dynamic differences first suggested the potential activation mechanism of RhoAG14V and RhoAQ63L. Together, our findings complemented the understanding of RhoA activation at the atomic level and can be utilized in the development of novel therapies for RhoA-related diseases.

D1018 with higher stability and excellent lipopolysaccharide binding affinity has potent anti-bacterial and anti-inflammatory activity.

Escherichia coli (E. coli) infection and LPS-induced inflammation are still of severe threat to human health. With the increasing problem of antibiotic resistance, there is a desperate need to develop new approaches to solve the problem. Antimicrobial peptide (AMP) IDR-1018 exhibited potential antimicrobial and immunoregulation activity. However, moderate antimicrobial efficiency and susceptibility to protease cleavage limited its therapeutic application. Therefore, the derived 1018M which has better activity against MRSA and whole sequence D-amino acids substitution peptides (D1018 and D1018M) were synthesized in this study. The resistance of D1018 and D1018M against tested proteases increased (2-4 times), particularly in D1018. The antibacterial activity of D1018 was the same as that of the parent peptide IDR-1018, but the antimicrobial activity of D1018M was slightly increased (2-fold). Though the hemolysis of IDR-1018 and D1018 was about 2%, at the concentration of 8×MIC, the cytotoxicity of IDR-1018, D1018, and 1018M was negligible. The peptides could interact with E. coli cell wall and cytoplasmic membrane, penetrate the membrane, cause leakage of contents, and disrupt genomic DNA. Among them, D1018 is the most prominent one. In addition, IDR-1018 and D1018 showed potent binding ability to LPS, thus leading to excellent inhibition capacity to LPS-induced proinflammation response. Taken together, these data demonstrate that D1018 is a promising peptide candidate for the treatment of E. coli infection.

Simultaneous Improvement of Final Product-Tolerance and Thermostability of GH39 Xylosidase for Prebiotic Production by Directed Evolution.

Xylosidases are widely used for the production of prebiotics and the transformation of natural active substances in the food industry. However, xylosidases with excellent thermostability and product tolerance are required for industrial applications. In this study, the thermostability and final-product tolerance of the previously reported robust xylosidase Xyl21 were further improved via directed evolution. The triple mutant variant Xyl21-A16 (K16R, L94I, and K262N) showed significantly enhanced xylose tolerance, ethanol tolerance, and thermostability with no apparent changes in the specific activity, optimum pH, and temperature compared with the wild type. Single site mutations suggested that variant Xyl21-A16 is the cumulative result of three mutated sites, which indicated that K16 and L94 play important roles in enzyme characteristics. Moreover, a comparison of the predicted protein structures of Xyl21 and its variant indicated that additional molecular interactions formed by K16R and K262N might directly improve the rigidity of the protein structure, therefore contributing to the increased thermostability and product tolerance. The variant Xyl21-A16 developed in this study has great application potential in the production of prebiotics, and also provides a useful reference for the future engineering of other xylosidases.