Lipopeptides from Bacillus velezensis ZLP-101 and their mode of action against bean aphids Acyrthosiphon pisum Harris.

BACKGROUND: Natural products are important sources for the discovery of new biopesticides to control the worldwide destructive pests Acyrthosiphon pisum Harris. Here, insecticidal substances were discovered and characterized from the secondary metabolites of the bio-control microorganism Bacillus velezensis strain ZLP-101, as informed by whole-genome sequencing and analysis. RESULTS: The genome was annotated, revealing the presence of four potentially novel gene clusters and eight known secondary metabolite synthetic gene clusters. Crude extracts, prepared through ammonium sulfate precipitation, were used to evaluate the effects of strain ZLP-101 on Acyrthosiphon pisum Harris aphid pests via exposure experiments. The half lethal concentration (LC50) of the crude extract from strain ZLP-101 against aphids was 411.535 mg/L. Preliminary exploration of the insecticidal mechanism revealed that the crude extract affected aphids to a greater extent through gastric poisoning than through contact. Further, the extracts affected enzymatic activities, causing holes to form in internal organs along with deformation, such that normal physiological activities could not be maintained, eventually leading to death. Isolation and purification of extracellular secondary metabolites were conducted in combination with mass spectrometry analysis to further identify the insecticidal components of the crude extracts. A total of 15 insecticidal active compounds were identified including iturins, fengycins, surfactins, and spergualins. Further insecticidal experimentation revealed that surfactin, iturin, and fengycin all exhibited certain aphidicidal activities, and the three exerted synergistic lethal effects. CONCLUSIONS: This study improved the available genomic resources for B. velezensis and serves as a foundation for comprehensive studies of the insecticidal mechanism by Bacillus velezensis ZLP-101 in addition to the active components within biological control strains.

Acceleration index predicts efficacy of orthostatic training on postural orthostatic tachycardia syndrome in children.

The objective of this study was to examine the utility of the acceleration index observed in an electrocardiogram (ECG) for the prediction of the effectiveness of orthostatic training in pediatric patients diagnosed with postural orthostatic tachycardia syndrome (POTS). This investigation focused on children diagnosed with POTS and undergoing orthostatic training at the Department of Pediatrics of Peking University First Hospital from January 2012 to October 2022. Specifically, patients hospitalized from January 2012 to December 2019 were included in the training set (54 cases), while those hospitalized from January 2020 to October 2022 were included in the external validation set (37 cases). All children received a 3-month orthostatic training, and the baseline symptom score (SS) was calculated in agreement with the pretreatment orthostatic intolerance symptom frequency. Additionally, we determined post-treatment SS during follow-up via telephone after the 3-month treatment. Children with a decrease in post-treatment SS by ≥ 50% of the baseline were considered as responders; otherwise, they were considered as non-responders. Demographic data (age, sex, and body mass index), hemodynamic parameters (supine blood pressure, time to achieve a positive standing test, maximum increase in heart rate during the standing test, maximal heart rate reached during the standing test, and blood pressure at the point of maximal heart rate during the standing test), and electrocardiographic parameters (RR interval in the supine position, shortest RR interval in the upright position, and acceleration index) were collected from all the children prior to treatment. Univariate and multivariate regression analysis were conducted to investigate factors associated with the efficacy of orthostatic training. The predictive value of these indicators for the therapeutic effectiveness of orthostatic training in children with POTS was evaluated using receiver operating characteristic (ROC) analysis, and the indicators were validated using the validation set. Among the 54 children in the training set, 28 responded to orthostatic training, and 26 were nonresponsive. Compared with the non-responders, the responders demonstrated a significant reduction in acceleration index (P < 0.01). The ROC curve for the predictive value of the acceleration index exhibited an area under the curve = 0.81 (95% confidence interval: 0.685-0.926). With the acceleration index threshold < 27.93%, the sensitivity and specificity in the prediction of orthostatic training efficacy among children with POTS were 85.7% and 69.2%, respectively. The external validation results demonstrated that using acceleration index < 27.93% as the threshold, the sensitivity, specificity, and accuracy of predicting orthostatic training efficacy among children with POTS were 89.5%, 77.8%, and 83.8%, respectively. CONCLUSIONS: Electrocardiographic acceleration index can be used to predict the effectiveness of orthostatic training in treating children with POTS. WHAT IS KNOWN: • Postural orthostatic tachycardia syndrome (POTS) is a chronic orthostatic intolerance involving multiple mechanisms. Autonomic dysfunction is one of the main mechanisms of POTS in children and could be treated with orthostatic training. • In order to improve the efficacy of orthostatic training in children with POTS, it is particularly important to identify the patients with autonomic dysfunction as the main mechanism before the treatment. WHAT IS NEW: • We found acceleration index of the electrocardiogram (ECG) can be used as a satisfactory index to predict the efficacy of orthostatic training in the treatment of POTS in children. • Using the acceleration index to predict the efficacy of orthostatic training on POTS in children is easy to be popularized in hospitals at all levels because it is non-invasive, convenient, and not expensive.

COVID-19 vaccination and long COVID among 50 years older and above European: The role of chronic multimorbidity.

BACKGROUND AND AIMS: We aimed to explore the association between coronavirus disease-19 (COVID-19) vaccination and long COVID according to the status of chronic multimobidity. METHODS: A total of 1913 participants were recruited in the cross-sectional study on the basis of the Survey of Health and Retirement in Europe. COVID-19 vaccination was defined as vaccination within the last 12 months. Chronic multimorbidity was defined as history of 2 + chronic disease. The study outcome was long COVID during the 12-month follow-up. Multivariable logistic models were performed to estimate the influence of chronic multimorbidity on the association of vaccination with long COVID. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. RESULTS: Chronic multimorbidity significantly modified the association of COVID-19 vaccination with long COVID (Pinteraction = 0.024). The rates of study outcome were significantly lower among vaccinated participants in the chronic multimorbidity subgroup, but not in the other subgroup. Multivariable odds ratios (95 % confidence intervals) of study outcome for unvaccination vs. vaccination were 1.494 (1.013-2.203) in those with multimorbidity and 0.915 (0.654-1.280) in those without multimorbidity, respectively. Adding COVID-19 vaccination to a model containing conventional risk factors significantly improved risk reclassification for study outcome among those with chronic multimobidity (continuous NRI was 25.39 % [P = 0.002] and IDI was 0.42 % [P = 0.075]) CONCLUSION: An inverse association of COVID-19 vaccination with long COVID was found among participants with chronic multimorbidity, but not among those without chronic multimorbidity. Chronic multimorbidity might expand the influence of unvaccination on developing long COVID among European aged ≥50 years.

Research on Component Variation and Factors Affecting Minimum Miscible Pressure in Low Viscosity Oil Miscibility Process.

Miscible gas flooding is an important approach for enhancing the recovery of unconventional oil reservoirs. The injected gas and crude oil components has a significant impact on the minimum miscible pressure. In order to clarify the miscibility characteristics and factors influencing the minimum miscibility pressure, combining PVT and slim tube experiments, the minimum miscibility pressure between Tuha low viscosity oil and different injected gas was measured. Additionally, chromatography experiments were conducted to study the composition changes of produced oil. The results indicate that when the injection pressure is higher than the minimum miscible pressure, the extraction effect of injected gas on heavy fraction (C16+) in crude oil is enhanced and the extraction effect on light alkanes (C1-C6) is reduced. The increase in the content of light alkanes (C1-C6) and middle distillates (C7-C15) in crude oil reduces the minimum miscibility pressure between crude oil and injected gas. Pipeline gas can effectively extract heavy fraction from crude oil, but its breakthrough time is early. Under the same pressure, earlier breakthrough time of injected gas makes it more difficult for the crude oil and injected gas to miscible. Through the analysis of experimental results, the following main conclusions are drawn: Immiscible flooding causes heavy fraction (C16+) in crude oil to remain, which might affect the physical properties of the reservoir, increasing the difficulty of subsequent development. Gas fingering phenomenon significantly influences the miscibility of injected gas and crude oil, and the viscosity ratio of injected gas and crude oil under high-pressure conditions can be used as an important criterion for screening injected gas.

Thyroid stimulating receptor autoantibodies.

Thyroid-stimulating hormone receptor autoantibodies (TRAbs) play a crucial role as pathogenic antibodies in both the diagnosis and management of Graves' disease (GD). GD, an autoimmune disease resulting from a combination of genetic and environmental factors, is the most common cause of hyperthyroidism. With advancements in technology for TRAb detection and the availability of automated commercial kits, TRAb has become an essential clinical laboratory marker for the diagnosis of GD, as well as extra-thyroidal manifestations like Graves' ophthalmopathy (GO). This article provides a comprehensive review of TRAb, encompassing its clinical assays along with its significance in the clinical setting.

Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

Coumarin-furo[2,3-d]pyrimidone hybrid molecules targeting human liver cancer cells: synthesis, anticancer effect, EGFR inhibition and molecular docking studies.

The design, synthesis and investigation of antitumor activities of some coumarin-furo[2,3-d]pyrimidone hybrid molecules are reported. In vitro, HepG2 cells were used to investigate the cytotoxicity of 6a-n and 10a-n. The results demonstrated that coupling a furopyrimidone scaffold with coumarin through a hydrazide linker can effectively improve their synergistic anticancer activity. The coumarin-furo[2,3-d]pyrimidone combination 10a exhibited significant inhibitory activity against HepG2 cells with IC50 = 7.72 ± 1.56 µM, which is better than those of gefitinib and sorafenib. It is worth mentioning that the coumarin-furo[2,3-d]pyrimidone combination 10a showed excellent inhibition of the EGFR enzymatic activity with IC50 = 1.53 µM and 90% inhibition at 10 µM concentration. In silico investigation predicts the possibility of direct binding between the new coumarin-furo[2,3-d]pyrimidone hybrid molecules and the EGFR. The results suggest that coumarin-furo[2,3-d]pyrimidone hybrid molecules are potential antitumor agents targeting human liver cancer cells.

Plasma Steroid Profiling Combined With Machine Learning for the Differential Diagnosis in Mild Autonomous Cortisol Secretion From Nonfunctioning Adenoma in Patients With Adrenal Incidentalomas.

OBJECTIVE: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. RESULTS: Seventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11ß-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection.

Virtues of impact financing: Do financial institutions benefit from considering the environmental impact on financing decisions?

The impact investing literature largely focuses on private equity investing and overlooks the investments made through debt financing that actually dominate the market. To address this research gap, this paper investigates whether impact financing is associated with financial benefits. By using COVID-19 as an exogenous shock to China's stock market, this paper applies fixed effects panel data analysis with a difference-in-differences research design to provide robust empirical outcomes. The results reveal those financial institutions that better integrated environmental impacts into their financing process experienced positive stock return changes in response to the shock. This study answers the question of how well an impact scales. The findings suggest that impact financing is an effective model, as the impacts incorporated in the debt can be scaled up compared to impact investing funds with low volumes. Impact financing has enormous potential for financial institutions to engage in the green transition since they can derive pecuniary utility while delivering environmental impacts. The revelation of financial benefits also contributes to overcoming the lack of knowledge about impact financing and helps to remove the barriers that advance industry growth.

Prevalence, Clinical Features, and Genotypes of Norovirus-Associated Diarrhea in Wuxi, China, 2013-2020.

Norovirus (NoV) is a common pathogen that can cause infectious diarrhea. This study aimed to determine the prevalence, clinical features, and genotypes of NoV-associated diarrhea in Wuxi, China. A total of 4,416 stool samples were collected from patients with diarrhea at enteric disease clinics of sentinel hospitals in Wuxi from February 1, 2013 to December 31, 2020. Univariate and Akaike information criterion stepwise logistic regression were used to identify differences as integrated within a clinical setting (NoV positive [+] versus NoV negative [-], NoV+ versus rotavirus [RV]+, NoV+ versus bacteria+, genogroup [G] I and GII genotypes). Norovirus was detected in 9.85% of stool samples, which was greater than other tested pathogens. Excluding coinfection of NoV and other viruses or bacteria, patients infected with NoV had a lower chance of acquiring the virus in summer (P < 0.001; odds ratio [OR], 0.257; 95% CI, 0.189-0.36) when compared with patients without NoV. Patients with diarrhea infected with NoV featured nausea and vomiting (P < 0.001; OR, 2.297, 95% CI, 1.85-2.86) and loose stools (P = 0.006; OR, 2.247; 95% CI, 1.30-4.10), but less abdominal cramping (P = 0.001; OR, 0.676; 95% CI, 0.54-0.84). Patients infected with RV (P < 0.001; OR, 0.413; 95% CI, 0.25-0.68) or bacteria (P < 0.001; OR, 0.422; 95% CI, 0.26-0.67) were more vulnerable to fever than those infected with NoV. A total of 379 GII strains were detected concomitant with 48 GI strains, and there was a seasonal difference between the GI and GII genotypes. Strengthening pathogen detection for infectious diarrhea was helpful for understanding the epidemiological characteristics of infections with NoV and, potentially, for preventing disease outbreaks.

Establishment and validation of a multivariate predictive model for the efficacy of oral rehydration salts in children with postural tachycardia syndrome.

BACKGROUND: The therapeutic effectiveness of the empirical and unselected use of oral rehydration salts (ORS) on postural tachycardia syndrome (POTS) is not satisfactory in children. Therefore, looking for suitable predictors of the therapeutic effects of ORS before treatment is extremely necessary to implement individualised treatment for paediatric patients with POTS. METHODS: A retrospective case-control analysis of 130 patients (aged 5-18 years) who suffered from POTS with a 3-month treatment of ORS was conducted. A nomogram model was developed in the training set (n = 87) to predict the therapeutic response to ORS. Univariate analysis and logistic regression were applied to select the most useful predictors. ROC curves were applied to evaluate the discriminative performance of the nomogram model. The nomogram was then evaluated by calibration curves and the Hosmer-Lemeshow (H-L) test. The results were further validated using 1000 bootstrap resamples. External validation was performed in an independent validation set (n = 43). FINDINGS: Among the ten variables with significant differences between the responders and non-responders in univariate analysis, five variables were found to be independently associated factors for ORS therapeutic efficacy among POTS children in the further logistic regression, including mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean arterial pressure (MAP) at the first minute of the upright position, urine specific gravity (SG), and P-wave voltage peaking ratio (PWP). The nomogram model was established in the training set (AUC 0.926 [95% CI: 0.865-0.988], yielding a sensitivity of 87.8% and a specificity of 86.8%). The calibration curves showed good agreement between the prediction of the nomogram and actual observation in both the training and validation sets. The nomogram also effectively predicted the external validation set (sensitivity 82.1%, specificity 73.3%, and accuracy 79.1%). INTERPRETATION: We established a feasible and high-precision nomogram model to predict the efficacy of ORS, which would help implement individualised treatment for children with POTS. FUNDING: This study was supported by National High-Level Hospital Clinical Research Funding (Multi-centre Clinical Research Project of Peking University First Hospital) (2022CR59).

Chitosan modified magnetic nanocomposite for biofilm destruction and precise photothermal/photodynamic therapy.

Getting rid of the biofilms is a major challenge when treating skin and soft tissue infections (SSTI), an inflammatory illness brought on by bacteria. Traditional magnetic materials have a limited dispersibility and a biofilm permeable property, making it challenging to remove biofilms and causing infection to linger. To solve these problems, we developed a kind of magnetic composite nanoplatform coated with indocyanine green carbon dots and modified with chitosan modification (Fe-ICGCDs@CS). Fe-ICGCDs@CS has high dispersibility and improves the conductivity of biofilms under magnetic action. Fe-ICGCDs@CS can adsorb bacteria via the positive charge and achieve precise photothermal sterilization and photodynamic therapy (PDT). Moreover, by catalyzing hydrogen peroxide (2 mM), Fe-ICGCDs@CS can produce oxygen to relieve the anoxic state in the deep layer of biofilms and activate dormant bacteria to make them sensitive to external stimuli. All in all, unlike the common "just kill" sterilization model, Fe-ICGCDs@CS can accurately kill bacteria and be recovered by an external magnetic field at the end of treatment, thus reducing the potential biological toxicity of nanomaterials. Therefore, the proposed Fe-ICGCDs@CS provides a new antibacterial method with low biotoxicity for clinical application in the treatment of biofilm infections.

The One-Stop Integrated Nanoagent Based on Photothermal Therapy for Deep Infection Healing and Inflammation Inhibition.

Chronic wounds caused by bacterial infections are a major challenge in medical fields. The hypoxia condition extremely induces reactive oxygen species (ROS) generation and upregulates the expression of hypoxia-inducible factor, both of which can increase the pro-inflammatory M1 subtype macrophages production while reducing the anti-inflammatory M2 subtype macrophages. Besides, bacteria-formed biofilms can hinder the penetration of therapeutic agents. Encouraged by natural motors automatically executing tasks, hypothesized that supplying sufficient oxygen (O2 ) would simultaneously drive therapeutic agent movement, rescue the hypoxic microenvironment, and disrupt the vicious cycle of inflammation. Here, small organic molecule-based nanoparticles (2TT-mC6B@Cu5.4 O NPs) that possess high photothermal conversion efficiency and enzymatic activities are developed, including superoxide dismutase-, catalase-, and glutathione peroxidase-like activity. 2TT-mC6B@Cu5.4 O NPs exhibit superior ROS-scavenging and O2 production abilities that synergistically relieve inflammation, alleviate hypoxia conditions, and promote their deep penetration in chronic wound tissues. Transcriptome analysis further demonstrates that 2TT-mC6B@Cu5.4O NPs inhibit biological activities inside bacteria. Furthermore, in vivo experiments prove that 2TT-mC6B@Cu5.4 O NPs-based hyperthermia can effectively eliminate bacteria in biofilms to promote wound healing.

Study on the correlation between the dominant microflora and the main flavor substances in the fermentation process of cigar tobacco leaves.

The flavor of cigar tobacco leaf determines the quality of finished cigar tobacco, and the enhancement of flavor generally relies on microbial fermentation. In this paper, the correlation between the dominant microorganisms and the main flavor substances of cigar tobacco leaves during fermentation and the correlation between the two were investigated to reveal the correlation between microorganisms and flavor and the metabolic pathways of microorganisms affecting the flavor substances. During the fermentation process, the main flavors of cigar tobacco leaves were sweet, light and grassy, with hexanal, 2,6-dimethylpyridine, nonanal, phenylacetaldehyde, naphthalene, and methyl benzoate as the main constituents, and the key microorganisms Haloferax mediterranei, Haloterrigena limicola, Candidatus Thorarchaeota archaeon SMTZ-45, the genera Methyloversatilis, Sphingomonas, Thauera, Pseudomonas, Penicillium, and Aspergillus. Correlation analysis revealed that fungi were negatively correlated with the main aroma and inhibited the main flavor substances, while bacteria were positively correlated with Benzoic acid, methyl ester in the main flavor substances, which was conducive to the accumulation of green aroma. Functional analysis revealed that the dominant bacterial population was producing aroma by metabolizing glycoside hydrolases and glycosyltransferases, performing amino acid metabolism, carbohydrate metabolism and film transport metabolism. The present study showed that the bacterial and fungal dominant microorganisms during the fermentation of cigar tobacco were influencing the production and degradation of the main flavor substances through the enzyme metabolism by the occurrence of the Merad reaction.

A well-dispersed OV-NiCo2O4 nanosphere modified separator for Li-S batteries.

The commercialization of lithium-sulfur batteries is facing great challenges, such as the "shuttle effect" and the poor conductivity of sulfur and Li2S2/Li2S, so it is extremely important to design new separator-modified materials with fast charge transfer capability and effective immobilization of polysulfides (LiPSs) to facilitate their conversion to address these challenges. In this paper, we propose a simple way to synthesize NiCo2O4 nanospheres containing oxygen vacancies (OV-NiCo2O4 NSs) and thus modify the separator. The synthesized OV-NiCo2O4 NSs accelerated the conversion of LiPSs through strong chemical interactions. In addition, the introduction of oxygen vacancies provided more active sites for LiPSs, which improved the electron conduction rate and accelerated the ion transport. Based on the above advantages, the battery with an OV-NiCo2O4 modified separator showed excellent electrochemical performance (the initial capacity of the battery was 801 mA h g-1 at 0.5 C, the specific capacity of discharge was maintained at 695 mA h g-1 after 500 cycles, and the capacity retention rate was as high as 87%).

Effects of leisure activities and general health on the survival of older people: a cohort study in China.

Objective: This study aimed to examine the influence of physical and cognitive leisure activities on the survival of older adults in China, while also exploring the potential mediating and moderating effects of general health. Methods: This study utilized the China Longitudinal Healthy Longevity Survey (CLHLS) datasets spanning from 2008 to 2018, and 10,347 eligible participants were included. The primary study outcome was all-cause mortality, and independent variables included physical leisure activities (PLA), cognitive leisure activities (CLA), and self-rated general health. Three sets of covariates were adjusted, including socio-demographic characteristics, health behaviors, and health status. Results: The longest survival time was the older people participating in PLA & CLA (mean = 50.31 months), while those participating in neither exhibited the lowest (mean = 29.60 months). Significant differences in survival status were observed in different types of leisure activities participation (Log-rank test, Chi-square = 576.80, p < 0.001). Cox regression indicated that PLA (HR = 0.705, 95% CI: 0.651-0.764), CLA (HR = 0.872, 95% CI: 0.816-0.933), and the both PLA & CLA (HR = 0.700, 95% CI: 0.656-0.747) were protective factors for the survival. Additionally, general health significantly moderated the relationship between PLA and reduced mortality risk (Coefficient = -0.089, p = 0.042). While CLA indirectly influenced the survival through general health (Coefficient = -0.023, p < 0.001). For the older people participating in PLA and CLA, general health played mediating (Coefficient = -0.031, p < 0.001) and moderating (Coefficient = -0.026, p = 0.013) role in the relationship between leisure activities and survival. Conclusion: Leisure activities and self-rated general health were important predictors of survival of the older adults, and general health exhibited a mediator and moderator in the relationship between leisure activities and survival status.

Manganese-Iron Dual Single-Atom Catalyst with Enhanced Nanozyme Activity for Wound and Pustule Disinfection.

Even though great progress has been achieved in mimicking natural enzyme engineering, few artificial enzymes with efficient catalytic performance and multifunction have been reported. In this study, novel manganese-iron dual single-atom catalysts (Mn/Fe SACs) were synthesized via a hydrothermal/pyrolysis recipe. Iron atoms inside the Mn/Fe SACs adequately exerted the peroxidase (POD)-like activity, its Michaelis-Menten constant, and maximum initial velocity superior to the horseradish peroxidase. Manganese atoms sufficiently catalyzed the H2O2 to generate oxygen (O2), which alleviated the challenge of the continued lack of O2 in the infected wound. In addition, Mn/Fe SACs possess a glutathione oxidase-like activity that further enhanced POD-like activity in the therapeutic process. The antibacterial rates of Mn/Fe SACs were 95 and 94.5% for Escherichia coli and Staphylococcus aureus, respectively. In vitro anti-inflammatory experiments demonstrated that Mn/Fe SACs could regulate the polarization of macrophages into the anti-inflammatory M2 subtype. In vivo wound healing experiments suggested that the combination therapy of Mn/Fe SACs and chemodynamic therapy presented a great promotion of the recovery rate. Moreover, the O2 generated by the catalase-like process contributed to the catalysts permeating the interior of the infected wounds and achieved preferable abscess elimination ability. This work revealed the potential of Mn/Fe SACs as broad-spectrum antimicrobial materials, which provided a novel strategy for treating infected and abscess wounds.

Three-Pronged Flower-like Nanoplatforms for the Photothermal/Photodynamic/Quaternary Ammonium Salt Synergistic Antibacterial Method and Bioimaging.

Bacterial infections caused by pathogenic bacteria are extremely threatening to human health. Currently, the treatment of bacterial infections relies heavily on antibiotics, leading to a high incidence of antibiotic abuse. Bacterial resistance appeared along with the misuse of antibiotics that produced growing harm to human beings. Therefore, a cutting-edge strategy for treating bacterial infections is indeed needed. Here we prepared QCuRCDs@BMoS2 nanocomposites (QBs) for an efficient bacterial trapping and triple quaternary ammonium salt/photothermal/photodynamic bactericidal method. Copper-doped carbon quantum dots were first prepared by using a solvothermal method, modified with quaternary ammonium salts, and then combined with grafted MoS2 nanoflowers. The long alkyl chains of QBs and the sharp surface of MoS2 facilitate the destruction of bacterial structures, while the electrostatic adsorption binds closely to bacteria, shortening the bactericidal distance of the reactive oxygen species (ROS). Moreover, the excellent photothermal performance under 808 nm irradiation in the near-infrared (NIR) region and deep penetrating heat can accelerate oxidative stress and achieve a multisynergistic bactericidal purpose. Consequently, QBs with ideal antibacterial properties and inherent brightness hold great promise in the biomedical field.

The association between long-term platelet count and disability-free survival among middle-aged and older Chinese: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND AND AIMS: We aimed to assess the associations of baseline and long-term platelet count (PLT) with disability-free survival (DFS) among middle-aged and older Chinese. METHODS AND RESULTS: A total of 7296 participants were recruited in the analysis. Updated mean PLT was defined as the mean of the two PLT measurements (4 years between wave 1-3). The long-term status of PLT was defined as persistent low, attenuated, increased and persistent high PLT according to the optimal cut points from the receiver operating characteristic curves of the two PLT measurements, respectively. The primary outcome was DFS, evaluated by the first occurrence of either disability or mortality. During 6-year visit, 1579 participants experienced disability or all-cause mortality. The rates of primary outcome were significantly higher among participants with elevated baseline PLT and updated mean PLT. Multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of primary outcome were 1.253 (1.049-1.496) for highest baseline PLT tertile and 1.532 (1.124-2.088) for highest updated mean PLT tertile, comparing to the lowest tertiles. Multivariable-adjusted spline regression models showed a linear association of baseline PLT (plinearity < 0.001) and updated mean PLT (plinearity = 0.005) with primary outcome. Moreover, participants with persistent high PLT and increased PLT had increased risk of primary outcome (ORs [95% CIs]: 1.825 [1.282-2.597] and 1.767 [1.046-2.985], respectively), compared with the reference of those with persistent low PLT. CONCLUSION: This study proved elevated baseline PLT, especially long-term persist high or increased PLT was associated with less likelihood of DFS among middle-aged and older Chinese.

Neutrophil-like Biomimic AIE Nanoparticles with High-Efficiency Inflammatory Cytokine Targeting Enable Precise Photothermal Therapy and Alleviation of Inflammation.

Although photothermal therapy (PTT) has thrived as a promising treatment for drug-resistant bacterial infections by avoiding the abuse of antibiotics, the remaining challenges that limit the treatment efficiency are the poor targeting properties of infected lesions and low penetration to the cell membrane of Gram-negative bacteria. Herein, we developed a biomimetic neutrophil-like aggregation-induced emission (AIE) nanorobot (CM@AIE NPs) for precise inflammatory site homing and efficient PTT effects. Due to their surface-loaded neutrophil membranes, CM@AIE NPs can mimic the source cell and thus interact with immunomodulatory molecules that would otherwise target endogenous neutrophils. Coupled with the secondary near-infrared region absorption and excellent photothermal properties of AIE luminogens (AIEgens), precise localization, and treatment in inflammatory sites can be achieved, thereby minimizing damage to surrounding normal tissues. Moreover, CM@AIE NP-mediated PTT was stimulated in vivo by a 980 nm laser irradiation, which contributed to the extent of the therapeutic depth and limited the damage to skin tissues. The good biocompatibility and excellent in vitro and in vivo antibacterial effects prove that CM@AIE NPs can provide a strategy for broad-spectrum antibacterial applications.