The effect of drugs and guns on life expectancy in the United States, 2000-2020.

OBJECTIVES: This study estimated the effect of changing trends in drug- and firearm-related mortality on life expectancy in the U.S. over the last two decades. STUDY DESIGN: Retrospective cross-sectional study. METHODS: We used national vital registration data from CDC WONDER, stratified by sex, to estimate the mortality rate due to accidental and intentional poisoning (ICD Codes X40-X49, X60-X69, Y10-Y19 and X85), and firearm deaths (ICD codes W32-W34, X72-X74, X93-X95, Y22-Y24) for the period 2000-2020. We applied standard life table methods to all cause mortality rates with and without these mortality causes to estimate the life expectancy at each age over this period. RESULTS: In 2020, mortality due to drugs and firearms combined reduced male life expectancy by1.67 years compared to 0.67 years in 2000, and without the effect of these two causes of death, male life expectancy in 2019 would have been 78.02 years. For women, drugs and firearm-related mortality reduced life expectancy by 0.20 years in 2000 and 0.63 years in 2020, and female life expectancy would have been 82.25 years in 2019 without the retarding effect of these two preventable causes. CONCLUSIONS: Drug- and firearm-related deaths have increased so rapidly, especially among younger populations, that life expectancy at birth is significantly reduced by these causes of death. Without urgent action to tackle these preventable causes of death, US life expectancy will continue to stagnate and may even decline, even without the effect of COVID-19.

Dynamic Changes and Potential Correlations between Microbial Diversity and Volatile Flavor Compounds in Chinese Medium-Temperature Daqu during Manufacturing.

To investigate the dynamic changes and potential correlations between microbial diversity and volatile organic compounds (VOCs) during Chinese medium-temperature Daqu (MTD) manufacturing at different key stages, in this study, high-throughput sequencing (HTS) and gas chromatography-ion mobility spectrometry (GC-IMS) were employed to analyze the microbial diversity and VOCs of MTD, respectively. The results showed that Weissella, Staphylococcus, Thermoactinomyces, Kroppenstedtia, and Lactobacillus were the dominant bacterial genera, while Aspergillus, Alternaria, Thermoascus, Thermomyces, Wickerhamomyces, and Saccharomyces were the dominant fungal genera. A total of 61 VOCs were detected by GC-IMS, among which, 13 differential VOCs (VIP > 1) were identified, that could be used as potential biomarkers to judge the fermentation stage of MTD. Kroppenstedtia and Saccharopolyspora were positively correlated with 3-methyl-2-butenal and 2,2,4,6,6-pentamethylheptane-D, respectively, and both of these were positively correlated with butanal-D. Acetobacter, Streptomyces, and lactic acid bacteria (LAB) including Leuconostoc, Pediococcus, Weissella, and Lactobacillus were negatively correlated with their associated VOCs, while fungi were generally positively correlated with VOCs. Wickerhamomyces, Saccharomyces, and Candida were positively correlated with butan-2-one-M. This study provides a theoretical basis for explaining the mechanisms of MTD flavor formation and screening functional microorganisms to improve the quality of MTD.

Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition.

BACKGROUND: Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechanism between ceftazidime-avibactam (CAZ-AVI) resistance and bacterial hypermucoviscosity in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp). RESULTS: The proportion of CAZ-AVI-sensitive clinical isolates exhibiting the hypermucoviscous phenotype was significantly lower than that of the resistant strains (5.6% vs. 46.7%, P < 0.001). To further verify the correlation and molecular mechanism between CAZ-AVI resistance and hypermucoviscosity, 10 CAZ-AVI-resistant isolates were generated through in vitro resistance selection from CAZ-AVI-sensitive KPC-Kp. The results showed the same association as it showed in the clinical isolates, with four out of ten induced CAZ-AVI-resistant isolates transitioning from negative to positive in the string tests. Comparative genomic analysis identified diverse mutations in the wzc gene, crucial for capsule polysaccharide (CPS) synthesis, in all four CAZ-AVI-resistant hypermucoviscous KPC-Kp strains compared to the parent strains. However, these mutations were absent in the other six KPC-Kp strains that did not exhibit induced hypermucoviscosity. Cloning of the wzc gene variants and their expression in wild-type strains confirmed that mutations in the wzc gene can induce bacterial hypermucoviscosity and heightened virulence, however, they do not confer resistance to CAZ-AVI. CONCLUSIONS: These results indicated that resistance to CAZ-AVI in KPC-Kp isolates may be accompanied by the acquisition of hypermucoviscosity, with mutations in the wzc gene often involving in this process.

Cross-Modal Remote Sensing Image-Text Retrieval via Context and Uncertainty-Aware Prompt.

The cross-modal remote sensing image-text retrieval (CMRSITR) is a lively research topic in the remote sensing (RS) community. Benefiting from the large pretrained image-text models, many successful CMRSITR methods have been proposed in recent years. Although their performance is attractive, there are still some challenges. First, fine-tuning large pretrained models requires a significant amount of computational resources. Second, most large models are pretrained by natural images, which reduces their effectiveness in processing RS images. To tackle these challenges, we propose a new CMRSITR network named context and uncertainty-aware prompt (CUP). First, prompt tuning theory is introduced into CUP to eliminate the burden of optimization resources. By training the prompt tokens rather than all parameters, the large model's knowledge can be transferred to CMRSITR tasks with small trainable parameters. Second, considering the differences between natural-image-based prior clues and RS images, apart from adopting the free-prompt tokens, we develop a prompt generation module (PGM) to produce the RS-oriented prompt tokens. The specific prompt tokens are rich in object-level messages of RS images, which help CUP narrow the gaps between natural large models and RS images. Third, we further design an uncertainty estimation module (UEM) to whittle down the uncertainties caused by the model and data. This way, can not only the semantic misalignment and intraclass diversity imbalance problems be mitigated but also the RS clues can be deeply explored. Competitive experimental results counted on three public benchmark datasets demonstrate that our CUP can achieve competitive performance in the CMRSITR task compared with many existing methods. Our source codes are available at: https://github.com/TangXu-Group/Cross-modal-remote-sensing-image-and-text-retrieval-models/tree/main/CUP.

Discovery of lignans and curcuminoids as the effective inhibitors of pancreatic lipase: structure-activity relationship and inhibitory mechanism.

Pancreatic lipase (PL) is the main enzyme in the digestive system that breaks down triglyceride and promotes its absorption. In this paper, we found that lignans 2, 3 and 21, curcuminoids 24-26 exhibited significant inhibitory potential against PL. The structure-activity relationship (SAR) indicated that benzo-1, 3-dioxole group in the construction of lignans is essential to inhibitory effects against PL, while double bonds at C-7/C-2 position and 4-hydroxyphenyl moiety in the structure of curcuminoids are beneficial for PL inhibition. The kinetic studies and molecular docking were also conducted, the results showed that the three curcuminoids with the strongest inhibition effect above were all mixed inhibitors of PL. Furthermore, curcuminoids 24-26 displayed a preferential selectivity towards, in contrast to other serine hydrolases. The above results indicate that lignans and curcuminoids are natural functional components for PL inhibition, providing new ideas for finding and developing novel lead compounds for the treatment of obesity.

Comparison of Hypervirulent and Non-Hypervirulent Carbapenem-Resistant Acinetobacter baumannii Isolated from Bloodstream Infections: Mortality, Potential Virulence Factors, and Combination Therapy In Vitro.

Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR, and all ST1486 non-hv-CRAB-BSI lacked adeG. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.

The I7L protein of African swine fever virus is involved in viral pathogenicity by antagonizing the IFN-γ-triggered JAK-STAT signaling pathway through inhibiting the phosphorylation of STAT1.

Cell-passage-adapted strains of African swine fever virus (ASFV) typically exhibit substantial genomic alterations and attenuated virulence in pigs. We have indicated that the human embryonic kidney (HEK293T) cells-adapted ASFV strain underwent genetic alterations and the I7L gene in the right variable region was deleted compared with the ASFV HLJ/2018 strain (ASFV-WT). A recent study has revealed that the deletion of the I7L-I11L genes results in attenuation of virulent ASFV in vivo, but the underlying mechanism remains largely unknown. Therefore, we hypothesized that the deletion of the I7L gene may be related to the pathogenicity of ASFV in pigs. We generated the I7L gene-deleted ASFV mutant (ASFV-ΔI7L) and found that the I7L gene deletion does not influence the replication of ASFV in primary porcine alveolar macrophages (PAMs). Using transcriptome sequencing analysis, we identified that the differentially expressed genes in the PAMs infected with ASFV-ΔI7L were mainly involved in antiviral immune responses induced by interferon gamma (IFN-γ) compared with those in the ASFV-WT-infected PAMs. Meanwhile, we further confirmed that the I7L protein (pI7L) suppressed the IFN-γ-triggered JAK-STAT signaling pathway. Mechanistically, pI7L interacts with STAT1 and inhibits its phosphorylation and homodimerization, which depends on the tyrosine at position 98 (Y98) of pI7L, thereby preventing the nuclear translocation of STAT1 and leading to the decreased production of IFN-γ-stimulated genes. Importantly, ASFV-ΔI7L exhibited reduced replication and virulence compared with ASFV-WT in pigs, likely due to the increased production of IFN-γ-stimulated genes, indicating that pI7L is involved in the virulence of ASFV. Taken together, our findings demonstrate that pI7L is associated with pathogenicity and antagonizes the IFN-γ-triggered JAK-STAT signaling pathway via inhibiting the phosphorylation and homodimerization of STAT1 depending on the Y98 residue of pI7L and the Src homology 2 domain of STAT1, which provides more information for understanding the immunoevasion strategies and designing the live attenuated vaccines against ASFV infection.

A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank.

The metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate "biomarker - disease" causal pairs at the nominal significance level. We develop a metabolomic aging score that outperforms other aging metrics in predicting short-term mortality risk and exhibits strong potential for discriminating aging-accelerated populations and improving disease risk prediction. A longitudinal analysis of 13,263 individuals enables us to calculate a metabolomic aging rate which provides more refined aging assessments and to identify candidate anti-aging and pro-aging NMR biomarkers. Taken together, our study has presented a comprehensive aging-related metabolomic profile and highlighted its potential for personalized aging monitoring and early disease intervention.

Association of the modified creatinine index with quality of life in haemodialysis patients.

Aims/Background The evaluation of health-related quality of life in patients undergoing maintenance haemodialysis has garnered increasing attention. The modified creatinine index, a surrogate marker for muscle mass, has been linked to various clinical outcomes. However, the relationship between modified creatinine index and health-related quality of life in maintenance haemodialysis patients remains unclear. This study aims to elucidate the association between modified creatinine index and health-related quality of life in individuals receiving maintenance haemodialysis. Methods This cross-sectional study included 217 maintenance haemodialysis patients. Health-related quality of life was assessed using the Kidney Disease Quality of Life Instrument. Collected data included general patient information, laboratory results, and haemodialysis-related parameters. The modified creatinine index was calculated based on gender, age, single-pool Kt/V (spKt/V), and pre-dialysis serum creatinine levels. Multiple linear regression models and smooth curve fitting were used to investigate the relationship between modified creatinine index and health-related quality of life. Subgroup analyses and interaction tests were performed to identify potential effect modifiers. Results The 217 maintenance haemodialysis patients had a mean age of 53.66±13.15 years and a median dialysis vintage of 39 (25-84) months; 120 (55.30%) were male. The mean health-related quality of life score was 55.76±10.33, and the mean modified creatinine index was 22.72±2.95 mg/kg/day. After adjusting for confounding factors, an increase in modified creatinine index was associated with an improvement in health-related quality of life (ß=0.55, 95% CI: 0.04, 1.06, p = 0.033). No nonlinear relationship was identified between modified creatinine index and health-related quality of life by smooth curve fitting. Subgroup and interaction analyses indicated that the relationship between modified creatinine index and health-related quality of life was stable and not significantly influenced by age, gender, dialysis vintage, diabetes status, or body mass index (p > 0.05). Conclusion Modified creatinine index is positively correlated with health-related quality of life in maintenance haemodialysis patients, suggesting its potential utility in evaluating patient quality of life. Modified creatinine index could be clinically useful to improve the predictability of health-related quality of life in maintenance haemodialysis patients.

Cilia-Inspired Magnetic Flexible Shear Force Sensors for Tactile and Fluid Monitoring.

Recently, there has been a burgeoning interest in flexible shear force sensors capable of precisely detecting both magnitude and direction. Despite considerable efforts, the challenge of achieving accurate direction recognition persists, primarily due to the inherent structural characteristics and sensing mechanisms. Here, we present a shear force sensor constructed by a magnetically induced assembled Ni/PDMS composite membrane, which is magnetized and integrated with a three-axis Hall sensor, facilitating its ability to simultaneously monitor both shear force magnitude (0.7-87 mN) and direction (0-360°). The cilia-inspired shear force magnetic sensor (CISFMS) exhibits admirable attributes, including exceptional flexibility, high sensitivity (0.76 mN-1), an exceedingly low detection limit (1° and 0.7 mN), and remarkable durability (over 10,000 bending cycles). Further, our results demonstrate the capacity of the CISFMS in detecting tactile properties, fluid velocity, and direction, offering substantial potential for future developments in wearable electronics.

The roles of cell wall polysaccharides in response to waterlogging stress in Brassica napus L. root.

BACKGROUND: Brassica napus L. (B. napus) is susceptible to waterlogging stress during different cultivation periods. Therefore, it is crucial to enhance the resistance to waterlogging stress to achieve a high and stable yield of B. napus. RESULTS: Here we observed significant differences in the responses of two B. napus varieties in root under waterlogging stress. The sensitive variety (23651) exhibited a more pronounced and rapid reduction in cell wall thickness and root integrity compared with the tolerant variety (Santana) under waterlogging stress. By module clustering analysis based on transcriptome data, we identified that cell wall polysaccharide metabolism responded to waterlogging stress in root. It was found that pectin content was significantly reduced in the sensitive variety compared with the tolerant variety. Furthermore, transcriptome analysis revealed that the expression of two homologous genes encoding polygalacturonase-inhibiting protein 2 (PGIP2), involved in polysaccharide metabolic pathways, was highly upregulated in root of the tolerant variety under waterlogging stress. BnaPGIP2s probably confer waterlogging resistance by inhibiting the activity of polygalacturonases (PGs), which in turn reduces the degradation of the pectin backbone polygalacturonic acid. CONCLUSIONS: Our findings demonstrate that cell wall polysaccharides in root plays a vital role in response to the waterlogging stress and provide a theoretical foundation for breeding waterlogging resistance in B. napus varieties.

Enhanced Nanoparticle Recognition via Deep Learning-Accelerated Plasmonic Sensing.

Surface plasmon microscopy proves to be a potent tool for capturing interferometric scattering imaging data of individual particles at both micro and nanoscales, offering considerable potential for label-free analysis of bio-particles and bio-molecules such as exosomes, viruses, and bacteria. However, the manual analysis of acquired images remains a challenge, particularly when dealing with dense samples or strong background noise, common in practical measurements. Manual analysis is not only prone to errors but is also time-consuming, especially when handling a large volume of experimental images. Currently, automated methods for sensing and analysis of such data are lacking. In this paper, we develop an accelerated approach for surface plasmon microscopy imaging of individual particles based on combining the interference scattering model of single particle and deep learning processing. We create hybrid datasets by combining the theoretical simulation of particle images with the actual measurements. Subsequently, we construct a neural network utilizing the EfficientNet architecture. Our results demonstrate the effectiveness of this novel deep learning technique in classifying interferometric scattering images and identifying multiple particles under noisy conditions. This advancement paves the way for practical bio-applications through efficient automated particle analysis.

Pyraclostrobin induces developmental toxicity and cardiotoxicity through oxidative stress and inflammation in zebrafish embryos.

Pyraclostrobin, a typical representative of strobilurin fungicides, is extensively used in agriculture to control fungi and is often detected in water bodies and food. However, the comprehensive toxicological molecular mechanism of pyraclostrobin requires further study. To assess the toxic effects and underlying mechanisms of pyraclostrobin on aquatic organisms, zebrafish embryos were exposed to pyraclostrobin (20, 40, and 60 µg/L) until 96 h post fertilization (hpf). These results indicated that exposure to pyraclostrobin induces morphological alterations, including spinal curvature, shortened body length, and smaller eyes. Furthermore, heart developmental malformations, such as pericardial edema and bradycardia, were observed. This indicated severe cardiotoxicity induced by pyraclostrobin in zebrafish embryos, which was confirmed by the dysregulation of genes related to heart development. Besides, our findings also demonstrated that pyraclostrobin enhanced the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), up-regulated catalase (CAT) activity, but inhibited superoxide dismutase (SOD) activity. Subsequently, the NF-κb signaling pathway was further studied, and the results indicated that the up-regulation of tnf-α, tlr-4, and myd88 activated the NF-κb signaling pathway and up-regulated the relative expression level of pro-inflammatory cytokines, such as cc-chemokine, ifn-γ, and cxcl-clc. Collectively, this study revealed that pyraclostrobin exposure induces developmental toxicity and cardiotoxicity, which may result from a combination of oxidative stress and inflammatory responses. These findings provide a basis for continued evaluation of the effects and ecological risks of pyraclostrobin on the early development of aquatic organisms.

LESM-YOLO: An Improved Aircraft Ducts Defect Detection Model.

Aircraft ducts play an indispensable role in various systems of an aircraft. The regular inspection and maintenance of aircraft ducts are of great significance for preventing potential failures and ensuring the normal operation of the aircraft. Traditional manual inspection methods are costly and inefficient, especially under low-light conditions. To address these issues, we propose a new defect detection model called LESM-YOLO. In this study, we integrate a lighting enhancement module to improve the accuracy and recognition of the model under low-light conditions. Additionally, to reduce the model's parameter count, we employ space-to-depth convolution, making the model more lightweight and suitable for deployment on edge detection devices. Furthermore, we introduce Mixed Local Channel Attention (MLCA), which balances complexity and accuracy by combining local channel and spatial attention mechanisms, enhancing the overall performance of the model and improving the accuracy and robustness of defect detection. Finally, we compare the proposed model with other existing models to validate the effectiveness of LESM-YOLO. The test results show that our proposed model achieves an mAP of 96.3%, a 5.4% improvement over the original model, while maintaining a detection speed of 138.7, meeting real-time monitoring requirements. The model proposed in this paper provides valuable technical support for the detection of dark defects in aircraft ducts.

KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.

Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Preadsorbed Chymotrypsin Modulated the Composition of Protein Corona and Immunological Response.

It is well-known that proteins after administration into biological environments adsorb on the surface of nanoparticles (NPs). The biological identity could be determined by protein corona, but whether and how the preadsorbed molecules impact the composition of the corona and immunological response have rarely been reported. Here, the effects of preadsorbed chymotrypsin (Chy) on forming protein corona and subsequent immunological response are reported. We find that preadsorbed Chy on the surface of AuNPs results in a protein corona with enriched immunoglobulins and reduced human serum albumin protein, which further affect the polarization of macrophages into specific phenotypes. Our study suggests that the protein surrounding the nanoparticles could affect the protein corona and immunological response, which may direct the preparation of multifunctional nanomedicine for future studies.

[Estimation of soil moisture and organic matter content in saline alkali farmland by using CARS algorithm combined with covariates]. / 利用CARS算法联合协变量估算盐碱农田土壤水分和有机质含量.

Rapid acquisition of the data of soil moisture content (SMC) and soil organic matter (SOM) content is crucial for the improvement and utilization of saline alkali farmland soil. Based on field measurements of hyperspectral reflectance and soil properties of farmland soil in the Hetao Plain, we used a competitive adaptive reweighted sampling algorithm (CARS) to screen sensitive bands after transforming the original spectral reflectance (Ref) into a standard normal variable (SNV). Strategies Ⅰ, Ⅱ, and Ⅲ were used to model the input variables of Ref, Ref SNV, Ref-SNV+ soil covariate (SC), and digital elevation model (DEM). We constructed SMC and SOM estimation models based on random forest (RF) and light gradient boosting machine (LightGBM), and then verified and compared the accuracy of the models. The results showed that after CARS screening, the sensitive bands of SMC and SOM were compressed to below 3.3% of the entire band, which effectively optimized band selection and reduced redundant spectral information. Compared with the LightGBM model, the RF model had higher accuracy in SMC and SOM estimation, and the input variable strategy Ⅲ was better than Ⅱ and Ⅰ. The introduction of auxiliary variables effectively improved the estimation ability of the model. Based on comprehensive analysis, the coefficient of determination (Rp2), root mean square error (RMSE), and relative analysis error (RPD) of the SMC estimation model validation based on strategy Ⅲ-RF were 0.63, 3.16, and 2.01, respectively. The SOM estimation models based on strategy Ⅲ-RF had Rp2, RMSE, and RPD of 0.93, 1.15, and 3.52, respectively. The strategy Ⅲ-RF model was an effective method for estimating SMC and SOM. Our results could provide a new method for the rapid estimation of soil moisture and organic matter content in saline alkali farmland.

Practice of standardization of CLSI M45 A3 antimicrobial susceptibility testing of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in Guangdong Province 2017-2021.

The concentration of antimicrobial agents in environments like water and food has increased rapidly, which led to a rapid increase in antimicrobial resistance levels in the environment. Monitoring of bacterial resistance levels is considered as a necessary means to control the bacterial resistance. Reference standards are critical for antimicrobial susceptibility testing. CLSI M45 A3 standard defines pathogenic microorganisms that cause infections less frequently than those covered by CLSI M02, M07, and M100 as Infrequently Isolated or Fastidious Bacteria and specifies antimicrobial susceptibility testing methods. Our study investigated the epidemiology and antimicrobial susceptibility testing data of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in 70 hospitals in Guangdong Province between 2017 and 2021. We defined testing methods other than those specified in CLSI M45 A3 as "Non-Standardized." The proportion of standardized antimicrobial susceptibility testing for penicillin increased significantly (Corynebacterium spp. 17.4% vs. 50.0% p < 0.05; Micrococcus spp. 50.0% vs. 77.8% p < 0.05; Abiotrophia spp. and Granulicatella spp. 21.4% vs. 90.9% p < 0.001), while for cefotaxime (Corynebacterium spp. 0.0% vs. 45.2% p < 0.05; Abiotrophia spp. and Granulicatella spp. 0.0% vs. 14.3% p = 0.515) and vancomycin increased finitely. Non-standardized methods were used for all other antimicrobials. Due to limitations in the economic and medical environment, some clinical laboratories are unable to fully comply with CLSI M45 A3 standard. We recommend that CLSI should add breakpoints for disk diffusion method to improve the standardization of antimicrobial susceptibility testing.

Diffusion tensor imaging combined with chemical shift-encoded sequence to quantify the adaptive changes of calf muscles in amateur marathoners.

PURPOSE: Calf muscles play an important role in marathon race, and the incidence of injury is high in this process. This study prospectively quantified diffusion tensor metrics, muscle fat fraction (MFF) and cross-sectional area (CSA) of calf muscles induced by endurance exercise in amateur marathoners, and the potential mechanisms underlying the changes in these parameters were analyzed. METHOD: In this prospective study, 35 marathoners (27 males, 8 females; mean age (standard deviation, SD), 38.92 (4.83) years) and 26 controls (18 males, 8 females; mean age (SD), 38.35 (6.75) years) underwent magnetic resonance imaging (MRI) from September 2022 to March 2023. The diffusion tensor eigenvalues (λ1, λ2, λ3), radial diffusivity (RD), fractional anisotropy (FA), MFF and CSA of calf muscles were compared between marathoners and controls. A binary logistic regression model with gender correction was performed analyze the relationship between marathon exercise and DTI parameters, CSA and MFF of calf muscles. RESULTS: Interobserver agreement was good (κ = 0.71). The results of binary logistic regression model with gender correction showed that the regression coefficients of FA values in anterior group of calf (AC), soleus (SOL), medial gastrocnemius (MG) and lateral gastrocnemius (LG) were negative, and the odds ratios (OR) were 0.33, 0.45, 0.35, 0.05, respectively (P < 0.05). The OR of RD in SOL and λ2 in external group of calf (EC) were relatively higher, 3.74 and 3.26, respectively (P < 0.05). CSA was greater in SOL of marathoners, with an OR value of 1.00(P < 0.05). The MFF in AC and LG was lower in marathoners and OR of two indexes were -0.69 and -0.59, respectively (P < 0.05). CONCLUSIONS: Diffusion tensor imaging (DTI) combined with chemical shift-encoded sequence can noninvasively detect and quantify the adaptive changes of calf muscle morphology, microstructure and tissue composition induced by long-term running training in amateur marathoners.

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants.

This study aimed to develop novel rapid-acting antidepressants with sustained efficacy and favorable safety profiles. We designed and synthesized a series of fluorine-containing scopolamine analogues and evaluated their antidepressant potential. In vitro cytotoxicity assays showed that most of these compounds exhibited minimal toxicity against neuronal and non-neuronal mammalian cell lines (IC50 > 100 µM). The antidepressant activities of the compounds were evaluated using the tail suspension test, and S-3a was identified as a lead compound with potent and sustained antidepressant effects. Behaviorally, S-3a alleviated depressive symptoms in mice and displayed a higher cognitive safety margin than scopolamine. Toxicological assessments confirmed S-3a's safety, while pharmacokinetics showed a rapid clearance (half-life: 16.6 min). Mechanistically, S-3a antagonized M1 receptors and elevated BDNF levels, suggesting its potential as an antidepressant for further exploration.