Differences in the prevalence of allergy and asthma among US children and adolescents during and before the COVID-19 pandemic.

BACKGROUND: The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It's unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents. METHODS: This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata. RESULTS: In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018-2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020-2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables. CONCLUSION: Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection.

Dietary patterns interfere with gut microbiota to combat obesity.

Obesity and obesity-related metabolic disorders are global epidemics that occur when there is chronic energy intake exceeding energy expenditure. Growing evidence suggests that healthy dietary patterns not only decrease the risk of obesity but also influence the composition and function of the gut microbiota. Numerous studies manifest that the development of obesity is associated with gut microbiota. One promising supplementation strategy is modulating gut microbiota composition by dietary patterns to combat obesity. In this review, we discuss the changes of gut microbiota in obesity and obesity-related metabolic disorders, with a particular emphasis on the impact of dietary components on gut microbiota and how common food patterns can intervene in gut microbiota to prevent obesity. While there is promise in intervening with the gut microbiota to combat obesity through the regulation of dietary patterns, numerous key questions remain unanswered. In this review, we critically review the associations between dietary patterns, gut microbes, and obesity, aiming to contribute to the further development and application of dietary patterns against obesity in humans.

Matricellular proteins: Potential biomarkers in head and neck cancer.

The extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly contribute to the mechanical properties of tissues. Matricellular proteins (MCPs), as a family of non-structural proteins, play a crucial role in regulating various ECM functions. They exert their biological effects by interacting with matrix proteins, cell surface receptors, cytokines, and proteases. These interactions govern essential cellular processes such as differentiation, proliferation, adhesion, migration as well as multiple signal transduction pathways. Consequently, MCPs are pivotal in maintaining tissue homeostasis while orchestrating intricate molecular mechanisms within the ECM framework. The expression level of MCPs in adult steady-state tissues is significantly low; however, under pathological conditions such as inflammation and cancer, there is a substantial increase in their expression. In recent years, an increasing number of studies have focused on elucidating the role and significance of MCPs in the development and progression of head and neck cancer (HNC). During HNC progression, there is a remarkable upregulation in MCP expression. Through their distinctive structure and function, they actively promote tumor growth, invasion, epithelial-mesenchymal transition, and lymphatic metastasis of HNC cells. Moreover, by binding to integrins and modulating various signaling pathways, they effectively execute their biological functions. Furthermore, MCPs also hold potential as prognostic indicators. Although the star proteins of various MCPs have been extensively investigated, there remains a plethora of MCP family members that necessitate further scrutiny. This article comprehensively examines the functionalities of each MCP and highlights the research advancements in the context of HNC, with an aim to identify novel biomarkers for HNC and propose promising avenues for future investigations.

Blade-Coating (100)-Oriented α-FAPbI3 Perovskite Films via Crystal Surface Energy Regulation for Efficient and Stable Inverted Perovskite Photovoltaics.

Photoactive formamidinium lead triiodide (α-FAPbI3) perovskite has dominated the prevailing high-performance perovskite solar cells (PSCs), normally for those spin-coated, conventional n-i-p structured devices. Unfortunately, α-FAPbI3 has not been made full use of its advantages in inverted p-i-n structured PSCs fabricated via blade-coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5 mol% of N-aminoethylpiperazine hydroiodide (NAPI) additive into α-FAPbI3 crystal-derived perovskite ink, which enabled the formation of phase-pure, highly-oriented α-FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade-coated α-FAPbI3 perovskite films via combining a series of in-situ characterizations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb-I framework help to reduce the surface energy of (100) crystal plane by 42%, retard the crystallization rate and lower the formation energy of α-FAPbI3. The resultant blade-coated inverted PSCs based on (100)-oriented α-FAPbI3 perovskite films realized promising efficiencies up to 24.16% (~26.5% higher than that of the randomly-oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3-based inverted PSCs fabricated via scalable deposition methods.

Real-time detection of aging status of methylammonium lead iodide perovskite thin films by using terahertz time-domain spectroscopy.

The inadequate stability of organic-inorganic hybrid perovskites remains a significant barrier to their widespread commercial application in optoelectronic devices. Aging phenomena profoundly affect the optoelectronic performance of perovskite-based devices. In addition to enhancing perovskite stability, the real-time detection of aging status, aimed at monitoring the aging progression, holds paramount importance for both fundamental research and the commercialization of organic-inorganic hybrid perovskites. In this study, the aging status of perovskite was real-time investigated by using terahertz time-domain spectroscopy. Our analysis consistently revealed a gradual decline in the intensity of the absorption peak at 0.968 THz with increasing perovskite aging. Furthermore, a systematic discussion was conducted on the variations in intensity and position of the terahertz absorption peaks as the perovskite aged. These findings facilitate the real-time assessment of perovskite aging, providing a promising method to expedite the commercialization of perovskite-based optoelectronic devices.

The educational resource management based on image data visualization and deep learning.

In order to address issues such as inaccurate education resource positioning and inefficient resource utilization, this study optimizes the Educational Resource Management System (ERMS) by combining image data visualization techniques with convolutional neural networks (CNNs) technology in deep learning. Firstly, the crucial role of ERMS in education and teaching is analyzed. Secondly, the application of image data visualization techniques and CNNs in the system is explained, along with the associated challenges. Finally, by optimizing the CNNs model and system architecture and validating with experimental data, the rationality of the proposed model is confirmed. Experimental results indicate a significant improvement in various performance metrics compared to traditional models. The recognition accuracy on the Mnist dataset reaches 98.1 %, and notably, on the cifar-10 dataset, the optimized model achieves an accuracy close to 98.3 % with improved runtime reduced to only 640.4 s. Additionally, through systematic simulation experiments, the designed system is shown to fully meet the earlier requirements for system functionality, validating the feasibility and rationality of the model and system in this study. Therefore, this study holds high practical value for optimizing ERMS and provides meaningful insights into image data visualization techniques and CNNs optimization.

Treatment outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumors.

Background: The incidence rate of duodenal neuroendocrine tumors has been increasing in recent years. Endoscopic resection [ER; endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD)] is recommended for nonampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in diameter that are confined to the submucosal layer and without lymph node or distant metastasis. However, the efficacy and safety of and indications for EMR/ESD remain unclear. Methods: Between November 2011 and April 2021, 12 NAD-NETs in 12 patients who underwent either EMR or ESD were analyzed retrospectively. The rates of en bloc resection, complete resection, pathologic complete resection, margin involvement, lymphovascular invasion, perineural invasion, complications and prognosis were determined during follow-up (median observation period 53.0 months). Results: EMR was performed for two tumors, and ESD was performed for ten tumors. En bloc resection was performed for both tumors (100%) in the EMR group, and complete resection was achieved in one case (50%). Pathological complete resection was achieved in one case (50%), while in the ESD group, these three rates were 90% (9/10), 80% (8/10), and 80% (8/10), respectively. Intraoperative perforation occurred in one patient (10%) during ESD treatment, with no intraoperative or delayed bleeding in either group. Recurrence and distant metastasis were not observed during the mean follow-up period of 53.0 months (range, 18-131 months). Conclusions: For NAD-NETs that measure ≤10 mm in size, are confined to the submucosal layer and have neither suspicious lymph nodes nor distant metastasis, ER (EMR and ESD) may be a safe, effective, and feasible endoscopic technique for removing them.

Effects of PCSK9 Inhibitors on Early Neurologic Deterioration in Patients with Acute Non-Cardioembolism without Hemorrhagic Transformation After Intravenous Thrombolysis.

BACKGROUND: END (Early Neurologic Deterioration) significantly elevates the risk of morbidity and mortality. While numerous studies have investigated END following hemorrhagic transformation post-thrombolysis in acute cerebral infarction research on END without hemorrhagic transformations in patients with acute cerebral infarction due to non-cardiogenic embolism remains scarce. AIM: This study aimed to elucidate the impact of PCSK9 inhibitors on early neurological deterioration (END) in patients with acute non-cardioembolism cerebral infarction without hemorrhagic transformation post-intravenous thrombolysis. Additionally it aimed to identify risk factors associated with END in patients suffering from this type of stroke. OBJECTIVE: The objective of this study is to investigate the effect of PCSK9 inhibitors on early neurologic deterioration (END) in patients with acute non-cardiogenic cerebral infarction without hemorrhagic transformation after intravenous thrombolysis and identify associated risk factors for END in this patient population. METHODS: In this retrospective case-control study the data of consecutive patients who underwent intravenous thrombolysis after AIS (acute ischemic stroke) without hemorrhagic transformation during hospitalization at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 to February 2023 were retrieved and assessed. An increase of >2 in the National Institutes of Health Stroke Scale (NIHSS) within 7 days after admission was defined as END. RESULTS: This study included 250 patients (56 males 22.4%) they were 63.34±12.901 years old. There were 41 patients in the END group and 209 in the non-END group. The usage rate of PCSK9 inhibitors was significantly different between the END group and non-END group (29.268% vs 58.852% P<0.001). The White blood cell count (WBC) and homocysteine levels showed a significant difference between the two groups (all P<0.05). Patients not using PCSK9 inhibitors (OR=0.282 95%CI: 0.127-0.593) and white blood cell count (OR=1.197, 95%CI: 1.085-1.325) were independently associated with END. Receiver-operating characteristic curve analysis suggested that the sensitivity specificity and area under the curve for PCSK9 inhibitors used for END were 88.9%, 80.7% and 0.648 respectively. CONCLUSION: The use of PCSK9 inhibitors can reduce the incidence of early neurological deterioration in patients with acute non-cardioembolism and non-hemorrhagic transformation after intravenous thrombolysis.

Theoretical insights into enantioselective [2 + 1] cyclopropanation reactions of diazo compounds with electron-deficient olefins.

CONTEXT: The cyclopropane skeleton plays a significant role in bioactive  molecules due to its distinctive structural properties. This has sparked keen interest and in-depth exploration in the field of stereoselective synthesis of cyclopropane derivatives. In the present study, the mechanism and the origin of stereoselectivity of diastereodivergent synthesis of cyclopropane derivatives via the catalyst-free [2 + 1]-cyclopropanation reactions of 3-diazo-N-methylindole (R1) with two types of electron-deficient olefins (R2 and R3) in both aqueous and toluene media have been studied using the DFT calculations. The findings indicate that these [2 + 1] cycloaddition reactions proceed in two stages, where the first step is not only the rate-determining step but also critically dictates the stereoselectivity of the product. The calculated diastereomeric ratios are in agreement with the experimental results. Furthermore, by utilizing non-covalent interaction (NCI) analysis and energy decomposition analysis based on molecular force fields (EDA-FF), we elucidated that the electrostatic interactions between reactant fragments in the transition state TS1s for the first step are the predominant factors determining the stereoselectivity, as opposed to the experimentally hypothesized steric hindrance and π-π stacking interactions. METHODS: The geometrical structures of all minima and transition states on the potential energy surface (PES) in solvents water and toluene were fully optimized using the DFT method at the M06-2X(D3)/SMD/6-31 + G(d,p) level of theory. Single-point energy calculations were carried out based on the optimized geometries in the solution at the M06-2X(D3)/6-311 + G(d,p) level. All the DFT calculations were performed using the Gaussian 09 software. The optimized molecular structures were visualized using CYLview software. NCI analysis was performed using the Multiwfn and VMD softwares. The Multiwfn program was also used for CDFT and EDA-FF analyses.

Electric Field Generated at the Millisecond Pulse-Polarized Interface Facilitates the Electrolytic Conversion of SO2 into H2S.

Interfacial electric field holds significant importance in determining both the polar molecular configuration and surface coverage during electrocatalysis. This study introduces a methodology leveraging the varying electric dipole moment of SO2 under distinct interfacial electric field strengths to enhance the selectivity of the SO2 electroreduction process. This approach presented the first attempt to utilize pulsed voltage application to the Au/PTFE membrane electrode for the control of the molecular configuration and coverage of SO2 on the electrode surface. Remarkably, the modulation of pulse duration resulted in a substantial inhibition of the hydrogen evolution reaction (HER) (FEH2 < 3%) under millisecond pulse conditions (ta = 10 ms, tc = 300 ms, Ea = -0.8 V (vs Hg/Hg2SO4), Ec = -1.8 V (vs Hg/Hg2SO4)), concomitant with a noteworthy enhancement in H2S selectivity (FEH2S > 97%). A comprehensive analysis, incorporating in situ Raman spectroscopy, electrochemical quartz crystal microbalance, COMSOL simulations, and DFT calculations, corroborated the increased selectivity of H2S products was primarily associated with the inherently large dipole moment of the SO2 molecule. The enhancement of the interfacial electric field induced by millisecond pulses was instrumental in amplifying SO2 coverage, activating SO2, facilitating the formation of the pivotal intermediate product *SOH, and effectively reducing the reaction energy barrier in the SO2 reduction process. These findings provide novel insights into the influences of ion and molecular transport dynamics, as well as the temporal intricacies of competitive pathways during the SO2 electroreduction process. Moreover, it underscores the intrinsic correlation between the electric dipole moment and surface-molecule interaction of the catalyst.

Fibroblast growth factor receptor 4 deficiency in macrophages aggravates experimental colitis by promoting M1-polarization.

OBJECTIVE AND DESIGN: Compelling evidence indicates that dysregulated macrophages may play a key role in driving inflammation in inflammatory bowel disease (IBD). Fibroblast growth factor (FGF)-19, which is secreted by ileal enterocytes in response to bile acids, has been found to be significantly lower in IBD patients compared to healthy individuals, and is negatively correlated with the severity of diarrhea. This study aims to explore the potential impact of FGF19 signaling on macrophage polarization and its involvement in the pathogenesis of IBD. METHODS: The dextran sulfate sodium (DSS)-induced mouse colitis model was utilized to replicate the pathology of human IBD. Mice were created with a conditional knockout of FGFR4 (a specific receptor of FGF19) in myeloid cells, as well as mice that overexpressing FGF19 specifically in the liver. The severity of colitis was measured using the disease activity index (DAI) and histopathological staining. Various techniques such as Western Blotting, quantitative PCR, flow cytometry, and ELISA were employed to assess polarization and the expression of inflammatory genes. RESULTS: Myeloid-specific FGFR4 deficiency exacerbated colitis in the DSS mouse model. Deletion or inhibition of FGFR4 in bone marrow-derived macrophages (BMDMs) skewed macrophages towards M1 polarization. Analysis of transcriptome sequencing data revealed that FGFR4 deletion in macrophages significantly increased the activity of the complement pathway, leading to an enhanced inflammatory response triggered by LPS. Mechanistically, FGFR4-knockout in macrophages promoted complement activation and inflammatory response by upregulating the nuclear factor-κB (NF-κB)-pentraxin3 (PTX3) pathway. Additionally, FGF19 suppressed these pathways and reduced inflammatory response by activating FGFR4 in inflammatory macrophages. Liver-specific overexpression of FGF19 also mitigated inflammatory responses induced by DSS in vivo. CONCLUSION: Our study highlights the significance of FGF19-FGFR4 signaling in macrophage polarization and the pathogenesis of IBD, offering a potential new therapeutic target for IBD.

Leisure-time physical activity and the incidence of atrial fibrillation in senior adults: a prospective cohort study.

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Aggregation Behavior and Application Properties of Novel Glycosylamide Quaternary Ammonium Salts in Aqueous Solution.

Amidation of lactobionic acid with N,N-dimethylaminopropyltriamine was conducted to obtain N-(3'-dimethylaminopropyl)-lactamido-3-aminopropane (DDLPD), which was quaternized with bromoalkanes of different carbon chain lengths to synthesize double-stranded lactosylamide quaternary ammonium salt N-[N'[3-(lactosylamide)]propyl-N'-alkyl] propyl-N,N-dimethyl-N-alkylammonium bromide (CnDDLPB, n = 8, 10, 12, 14, 16). The surface activity and the adsorption and aggregation behaviors of the surfactants were investigated via equilibrium surface tension, dynamic light scattering, and cryo-electron microscopy measurements in an aqueous solution. The application properties of the products in terms of wettability, emulsification, foam properties, antistatic, salt resistance, and bacteriostatic properties were tested. CnDDLPB exhibited a low equilibrium surface tension of 27.82 mN/m. With an increase in the carbon chain length, the critical micellar concentration of CnDDLPBD decreased. Cryo-electron microscopy revealed that all products except C8DDLPB formed stable monolayer, multi-layer, and multi-compartmental vesicle structures in an aqueous solution. C14DDLPB has the best emulsification performance on soybean oil, with a time of 16.6 min; C14DDLPB has good wetting and spreading properties on polytetrafluoroethylene (PTFE) when the length of carbon chain is from 8 to 14, and the contact angle can be lowered to 33°~40°; CnDDLPB has low foam, which is typical of low-foaming products; C8DDLPB and C10DDLPB both show good antistatic properties. C8DDLPB and C14DDLPB have good salt resistance, and C12DDLPB has the best antimicrobial property, with the inhibition rate of 99.29% and 95.28% for E. coli and Gluconococcus aureus, respectively, at a concentration of 350 ppm.

Fluorescent hyaluronic acid nanoprodrug: A tumor-activated autophagy inhibitor for synergistic cancer therapy.

Autophagy is a process that eliminates damaged cells and malfunctioning organelles via lysosomes, which is closely linked to cancer. Primaquine (PQ) was reported to impede autophagy flow by preventing autophagosomes from fusing with lysosomes at the late stage of autophagy. It will lead to cellular metabolic collapse and programmed cell death. Excessive or extended autophagy enhances the efficacy of chemotherapeutic drugs in cancer prevention. The utilization of autophagy inhibition in conjunction with chemotherapy has become a prevalent and reliable approach for the safe and efficient treatment of cancer. In this work, an acid-sensitive nanoprodrug (O@PD) targeting CD44 receptors was produced using Schiff-base linkages or electrostatic interactions from oxidized hyaluronic acid (OHA), PQ, and doxorubicin (DOX). The CD44-targeting prodrug system in triple-negative breast cancer (TNBC) cells was designed to selectively release DOX and PQ into the acidic tumor microenvironment and cellular endosomes. DOX was employed to investigate the cellular uptake and ex-vivo drug distribution of O@PD nanoprodrugs. PQ-induced autophagy suppression combined with DOX has a synergistic fatal impact in TNBC. O@PD nanoprodrugs demonstrated robust anticancer efficacy as well as excellent biological safety, making them suitable for clinical use.

Integrating gated recurrent unit in graph neural network to improve infectious disease prediction: an attempt.

Objective: This study focuses on enhancing the precision of epidemic time series data prediction by integrating Gated Recurrent Unit (GRU) into a Graph Neural Network (GNN), forming the GRGNN. The accuracy of the GNN (Graph Neural Network) network with introduced GRU (Gated Recurrent Units) is validated by comparing it with seven commonly used prediction methods. Method: The GRGNN methodology involves multivariate time series prediction using a GNN (Graph Neural Network) network improved by the integration of GRU (Gated Recurrent Units). Additionally, Graphical Fourier Transform (GFT) and Discrete Fourier Transform (DFT) are introduced. GFT captures inter-sequence correlations in the spectral domain, while DFT transforms data from the time domain to the frequency domain, revealing temporal node correlations. Following GFT and DFT, outbreak data are predicted through one-dimensional convolution and gated linear regression in the frequency domain, graph convolution in the spectral domain, and GRU (Gated Recurrent Units) in the time domain. The inverse transformation of GFT and DFT is employed, and final predictions are obtained after passing through a fully connected layer. Evaluation is conducted on three datasets: the COVID-19 datasets of 38 African countries and 42 European countries from worldometers, and the chickenpox dataset of 20 Hungarian regions from Kaggle. Metrics include Average Root Mean Square Error (ARMSE) and Average Mean Absolute Error (AMAE). Result: For African COVID-19 dataset and Hungarian Chickenpox dataset, GRGNN consistently outperforms other methods in ARMSE and AMAE across various prediction step lengths. Optimal results are achieved even at extended prediction steps, highlighting the model's robustness. Conclusion: GRGNN proves effective in predicting epidemic time series data with high accuracy, demonstrating its potential in epidemic surveillance and early warning applications. However, further discussions and studies are warranted to refine its application and judgment methods, emphasizing the ongoing need for exploration and research in this domain.

Genetic characteristics of chromosomally integrated carbapenemase gene (blaNDM-1) in isolates of Proteus mirabilis.

OBJECTIVE: This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. METHODS: The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain's sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. RESULTS: Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. CONCLUSION: This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as blaNDM-1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.

Isolation of potentially novel species expands the genomic and functional diversity of Lachnospiraceae.

The Lachnospiraceae family holds promise as a source of next-generation probiotics, yet a comprehensive delineation of its diversity is lacking, hampering the identification of suitable strains for future applications. To address this knowledge gap, we conducted an in-depth genomic and functional analysis of 1868 high-quality genomes, combining data from public databases with our new isolates. This data set represented 387 colonization-selective species-level clusters, of which eight genera represented multilineage clusters. Pan-genome analysis, single-nucleotide polymorphism (SNP) identification, and probiotic functional predictions revealed that species taxonomy, habitats, and geography together shape the functional diversity of Lachnospiraceae. Moreover, analyses of associations with atherosclerotic cardiovascular disease (ACVD) and inflammatory bowel disease (IBD) indicated that several strains of potentially novel Lachnospiraceae species possess the capacity to reduce the abundance of opportunistic pathogens, thereby imparting potential health benefits. Our findings shed light on the untapped potential of novel species enabling knowledge-based selection of strains for the development of next-generation probiotics holding promise for improving human health and disease management.

Nepetoidin B Alleviates Liver Ischemia/Reperfusion Injury via Regulating MKP5 and JNK/P38 Pathway.

Background: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear. Methods: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5). Results: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway. Conclusion: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.

Extracellular Vesicle-Contained Thrombospondin 1 Retards Age-Related Degenerative Tendinopathy by Rejuvenating Tendon Stem/Progenitor Cell Senescence.

Advanced age is a major risk factor for age-related degenerative tendinopathy. During aging, tendon stem/progenitor cell (TSPC) function declines owing to the transition from a normal quiescent state to a senescent state. Extracellular vesicles (EVs) from young stem cells are reported to possess anti-aging functions. However, it remains unclear whether EVs from young TSPCs (TSPC-EVs) can rejuvenate senescent TSPCs to delay age-related degeneration. Here, this study finds that TSPC-EVs can mitigate the aging phenotypes of senescent TSPCs and maintain their tenogenic capacity. In vitro studies reveal that TSPC-EVs can reinstall autophagy in senescent TSPCs to alleviate cellular senescence, and that the re-establishment of autophagy is mediated by the PI3K/AKT pathway. Mechanistically, this study finds that thrombospondin 1, a negative regulator of the PI3K/AKT pathway, is enriched in TSPC-EVs and can be transported to senescent TSPCs. Moreover, in vivo studies show that the local delivery of TSPC-EVs can rejuvenate senescent TSPCs and promote their tenogenic differentiation, thereby rescuing tendon regeneration in aged rats. Taken together, TSPC-EVs as a novel cell-free approach have promising therapeutic potential for aging-related degenerative tendinopathy.

Colossal Ferroelectric Photovoltaic Effect in Inequivalent Double-Perovskite Bi2FeMnO6 Thin Films.

Double perovskite films have been extensively studied for ferroelectric order, ferromagnetic order, and photovoltaic effects. The customized ion combinations and ordered ionic arrangements provide unique opportunities for bandgap engineering. Here, a synergistic strategy to induce chemical strain and charge compensation through inequivalent element substitution is proposed. A-site substitution of the barium ion is used to modify the chemical valence and defect density of the two B-site elements in Bi2FeMnO6 double perovskite epitaxial thin films. We dramatically increased the ferroelectric photovoltaic effect to ∼135.67 µA/cm2 from 30.62 µA/cm2, which is the highest in ferroelectric thin films with a thickness of less than 100 nm under white-light LED irradiation. More importantly, the ferroelectric polarization can effectively improve the photovoltaic efficiency of more than 5 times. High-resolution HAADF-STEM, synchrotron-based X-ray diffraction and absorption spectroscopy, and DFT calculations collectively demonstrate that inequivalent ion plays a dual role of chemical strain (+1.92 and -1.04 GPa) and charge balance, thereby introducing lattice distortion effects. The reduction of the oxygen vacancy density and the competing Jahn-Teller distortion of the oxygen octahedron are the main phenomena of the change in electron-orbital hybridization, which also leads to enhanced ferroelectric polarization values and optical absorption. The inequivalent strategy can be extended to other double perovskite systems and applied to other functional materials, such as photocatalysis for efficient defect control.