Disease-Associated Streptococcus pneumoniae Genetic Variation.

Streptococcus pneumoniae is an opportunistic pathogen that causes substantial illness and death among children worldwide. The genetic backgrounds of pneumococci that cause infection versus asymptomatic carriage vary substantially. To determine the evolutionary mechanisms of opportunistic pathogenicity, we conducted a genomic surveillance study in China. We collected 783 S. pneumoniae isolates from infected and asymptomatic children. By using a 2-stage genomewide association study process, we compared genomic differences between infection and carriage isolates to address genomic variation associated with pathogenicity. We identified 8 consensus k-mers associated with adherence, antimicrobial resistance, and immune modulation, which were unevenly distributed in the infection isolates. Classification accuracy of the best k-mer predictor for S. pneumoniae infection was good, giving a simple target for predicting pathogenic isolates. Our findings suggest that S. pneumoniae pathogenicity is complex and multifactorial, and we provide genetic evidence for precise targeted interventions.

CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response.

BACKGROUND: LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment. METHODS: Potential miRNAs binding to the 3'-untranslated region (3'-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo. RESULTS: LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth. CONCLUSIONS: MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

Chiral Effect on the Electrochemistry of Magnetic Ferrite Colloidal Nanocrystal Assembly Modified by Amino Acids.

Chirality on the molecular or nanometer scale is particularly significant in chemistry, materials science, and biomedicine. Chiral electrochemical reactions on solid surfaces are currently a hot research topic. Herein, a chiral solid surface is constructed in aqueous solutions by mixing chiral molecules, d- and l-glutamic, with γ-Fe2O3 and Fe3O4 nanoparticles (NPs) and MnFe2O4 colloidal nanocrystal assembly (CNA). Cyclic voltammetry and differential pulse voltammetry measurements are conducted in a phosphate buffer solution (PBS) containing ascorbic acid (AA) or isoascorbic acid (IAA), and a chiral effect appears on the electroreduction of ferric ions of amino acid-modified magnetic samples. A negative or positive potential shift is observed, respectively, for magnetic structures modified by l- and d-glutamic acid in aqueous AA electrolyte, while the opposite is observed for these samples in IAA electrolyte. The reduction peak current increases by 0.8-1.2 times for the electrodes modified with l- and d-glutamate molecules, improving the electron transport efficiency. The chiral effect is absent when the electrolytes contain achiral uric acid or dopamine, or even chiral l-/d-/ld-tartaric acid. The chiral recognition between d-/l-glutamic acid and AA/IAA at the electrochemical interface is suggested to be related to their spinal configurations. These observations will be helpful for the rational design of inorganic functional chiral micro/nanostructures.

A friend in need is a friend indeed: Acute tandem rope skipping enhances inter-brain synchrony of socially avoidant individuals.

Team-based physical activity (PA) can improve social cognition; however, few studies have investigated the neurobiological mechanism underlying this benefit. Accordingly, a hyper-scanning protocol aimed to determine whether the interbrain synchrony (IBS) is influenced by an acute bout of team-based PA (i.e., tandem rope skipping). Specifically, we had socially avoidant participants (SOA, N=15 dyads) and their age-matched controls (CO, N=16 dyads) performed a computer-based cooperative task while EEG was recorded before and after two different experimental conditions (i.e., 30-min of team-based PA versus sitting). Phase locking value (PLV) was used to measure IBS. Results showed improved frontal gamma band IBS after the team-based PA compared to sitting when participants received successful feedback in the task (Mskipping = 0.016, Msittting = -0.009, p = 0.082, ηp2 = 0.387). The CO group showed a larger change in frontal and central gamma band IBS when provided failure feedback in the task (Mskipping = 0.017, Msittting = -0.009, p = 0.075, ηp2 = 0.313). Thus, results suggest that socially avoidant individuals may benefit from team-based PA via improved interbrain synchrony. Moreover, our findings deepen our understanding of the neurobiological mechanism by which team-based PA may improve social cognition among individuals with or without social avoidance.

Ultrasound-Assisted Sagittal View for Retrograde Puncture of the P2 Segment of Popliteal Artery for Recanalization of Femoropopliteal Lesions.

BACKGROUND: To assess the safety and efficacy of ultrasound-assisted sagittal view for retrograde puncture of the P2 segment of popliteal artery (PA) for treating femoropopliteal lesions. METHODS: A retrospective study was conducted on consecutive patients who underwent retrograde puncture of the PA for the recanalization of femoropopliteal lesions. A retrograde access was made to either the P2 or P3 segment of the PA in 23 cases. In 10 cases (8 men; mean age 68 ± 9 years), ultrasound-guided retrograde PA (P2 segment) puncture using the long-axis in-the-plane approach was performed, and in 13 cases (11 men; mean age 69 ± 5 years), angiography-guided retrograde PA (P3 segment) puncture was performed. Clinical data was compared preintraoperatively and postoperatively in the 2 groups. RESULTS: All occluded lesions were successfully recanalized via dual channel intervention. Puncture success were 100% (10/10) in the P2 group compared with 92.3% (12/13) in the P3 group (P > 0.05). The mean puncture time in the P2 group was significantly shorter when compared to the P3 group (4.70 ± 0.95 mins vs 11.33 ± 6.37 mins; P < 0.05). There was no difference in mean hemostasis time between the 2 groups (6.11 ± 2.20 mins vs 8.46 ± 3.76 mins; P > 0.05). There were no in-hospital deaths in all patients. The occurrence of puncture-related complications in the P2 group was 10% compared with 15% in the P3 group (P > 0.05). A low-flow arteriovenous fistula was observed in one case in the P3 group. None of the patients reported any access-related complication at a mean follow-up of 11.3 ± 5.5 months. CONCLUSIONS: Ultrasound-assisted sagittal view for retrograde puncture of the P2 segment of PA is at least as safe as angiography-guided retrograde puncture of the P3 segment for femoropopliteal lesions. Furthermore, this technique appears to be more suitable for patients with tandem iliofemoral artery occlusion, as it allows for the creation of a retrograde access.

Association between temperature and mortality: a multi-city time series study in Sichuan Basin, southwest China.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS: Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.

Anion Chemistry towards On-Site Construction of Solid-Electrolyte Interface for Highly Stable Metallic Zn Anode.

Reversibility of metallic Zn anode serves as the corner stone for the development of aqueous Zn metal battery, which motivates scrutinizing the electrolyte-Zn interface. As the representative organic zinc salt, zinc trifluorosulfonate (Zn(OTf)2) facilitates a broad class of aqueous electrolytes, however, the stability issue of Zn anode remains crucial. The great challenge lies in the lack of Zn anode protection by the pristinely formed surface structure in aqueous Zn(OTf)2 electrolytes. Accordingly, an electrochemical route was developed to grow a uniform zinc trifluorosulfonate hydroxide (ZTH) layer on Zn anode as an artificial SEI, via regulation on metal dissolution and strong coordination ability of zinc ions. Co-precipitation was proposed to be the formation mechanism for the artificial SEI, where the reduction stability of OTf‾ anion and the low-symmetry layer structure of ZTH was unmasked. This artificial SEI favors interfacial kinetics, depresses side reactions, and well maintains its integrity during cycling, leading to a prolonged lifespan of Zn stripping/plating with a high DOD of ~85%, and an improved cycling stability of ~92% retention rate for V2O5/Zn cell at 1 A g-1. The unveiled role of anion on Zn anode drives the contemplation on the surface chemistry for the blooming aqueous rechargeable battery.

Converting Commercial Zn Foils into Single (002)-Textured Zn with Millimeter-Sized Grains for Highly Reversible Aqueous Zinc Batteries.

Rechargeable aqueous zinc batteries are promising but hindered by unfavorable dendrite growth and side reactions on zinc anodes. In this study, we demonstrate a fast melting-solidification approach for effectively converting commercial Zn foils into single (002)-textured Zn featuring millimeter-sized grains. The melting process eliminates initial texture, residual stress, and grain size variations in diverse commercial Zn foils, guaranteeing the uniformity of commercial Zn foils into single (002)-textured Zn. The single (002)-texture ensures large-scale epitaxial and dense Zn deposition, while the reduction in grain boundaries significantly minimizes intergranular reactions. These features enable large grain single (002)-textured Zn shows planar and dense Zn deposition under harsh conditions (100 mA cm-2, 100 mAh cm-2), impressive reversibility in Zn||Zn symmetric cell (3280 h under 1 mA cm-2, 830 h under 10 mAh cm-2), and long cycling stability over 180 h with a high depth of discharge value of 75 %. This study successfully addresses the issue of uncontrollable texture formation in Zn foils following routine annealing treatments with temperatures below the Zn melting point. The findings of this study establish a highly efficient strategy for fabricating highly reversible single (002)-textured Zn anodes.

A Ni-MOF derived graphene oxide combined Ni3S2-Ni/C composite and its use in the separator coating for lithium sulfur batteries.

Lithium-sulfur batteries (LSBs) are widely regarded as reliable novel secondary batteries due to their low price and high capacity. Nevertheless, the notorious "shuttle effect" limits the commercialization of LSBs. In order to solve this problem, we fabricated a Ni3S2-Ni/C composite through carbonization, vulcanization and hydrothermal reactions by using a Ni-MOF precursor and applied it as a separator modification layer to enhance the electrochemical properties of LSBs. To further increase the conductivity of the material, a small amount of GO was added during the experiment. The prepared material was also used as separator modified coating material to optimize the electrochemical performance of LSBs. The as prepared Ni3S2-Ni/C(GO) composite shows good conductivity and has a superior porous structure and abundant active sites. Lithium polysulfides (LPs) can be physically confined and chemically adsorbed, what is more, the Ni and Ni3S2 active sites enable fast conversion of LPs which further optimizes the rate performance. From the cycle performance measurement, the initial discharge specific capacity of the Ni3S2-Ni/C(GO) modified separator battery is found to be 1263.4, 1181.5, 1090.6, and 840.3 mA h g-1 at 0.05, 0.1, 0.3 and 0.5C, respectively. After 400 charge/discharge cycles at 0.5C, the capacity remains at 483.6mA h g-1 with a capacity retention ratio of 57.56%.

Effects of ambient temperature on mortality among elderly residents of Chengdu city in Southwest China, 2016-2020: a distributed-lag non-linear time series analysis.

BACKGROUND: With complex changes in the global climate, it is critical to understand how ambient temperature affects health, especially in China. We aimed to assess the effects of temperature on daily mortality, including total non-accidental, cardiovascular disease (CVD), respiratory disease, cerebrovascular disease, and ischemic heart disease (IHD) mortality between 2016 and 2020 in Chengdu, China. METHODS: We obtained daily temperature and mortality data for the period 2016-2020. A Poisson regression model combined with a distributed-lag nonlinear model was used to examine the association between temperature and daily mortality. We investigated the effects of individual characteristics by sex, age, education level, and marital status. RESULTS: We found significant non-linear effects of temperature on total non-accidental, CVD, respiratory, cerebrovascular, and IHD mortality. Heat effects were immediate and lasted for 0-3 days, whereas cold effects persisted for 7-10 days. The relative risks associated with extreme high temperatures (99th percentile of temperature, 28 °C) over lags of 0-3 days were 1.22 (95% confidence interval [CI]: 1.17, 1.28) for total non-accidental mortality, 1.40 (95% CI: 1.30, 1.50) for CVD morality, 1.34 (95% CI: 1.24, 1.46) for respiratory morality, 1.33 (95% CI: 1.20, 1.47) for cerebrovascular mortality, and 1.38 (95% CI: 1.20, 1.58) for IHD mortality. The relative risks associated with extreme cold temperature (1st percentile of temperature, 3.0 °C) over lags of 0-14 days were 1.32 (95% CI: 1.19, 1.46) for total mortality, 1.45 (95% CI: 1.24, 1.68) for CVD morality, 1.28 (95% CI: 1.09, 1.50) for respiratory morality, 1.36 (95% CI: 1.09, 1.70) for cerebrovascular mortality, and 1.26 (95% CI: 0.95, 1.68) for IHD morality. We found that hot and cold affects were greater in those over 85 years of age, and that women, individuals with low education levels, and those who were widowed, divorced, or never married, were more vulnerable. CONCLUSIONS: This study showed that exposure to hot and cold temperatures in Chengdu was associated with increased mortality, with people over 85 years old, women, those with low education levels, and unmarried individuals being more affected by hot and cold temperatures.

Impacts of exposure to humidex on cardiovascular mortality: a multi-city study in Southwest China.

BACKGROUND: Many studies have reported the association between ambient temperature and mortality from cardiovascular disease (CVD). However, the health effects of humidity are still unclear, much less the combined effects of temperature and humidity. In this study, we used humidex to quantify the effect of temperature and humidity combined on CVD mortality. METHODS: Daily meteorological, air pollution, and CVD mortality data were collected in four cities in southwest China. We used a distributed lag non-linear model (DLNM) in the first stage to assess the exposure-response association between humidex and city-specific CVD mortality. A multivariate meta-analysis was conducted in the second stage to pool these effects at the overall level. To evaluate the mortality burden of high and low humidex, we determined the attributable fraction (AF). According to the abovementioned processes, stratified analyses were conducted based on various demographic factors. RESULTS: Humidex and the CVD exposure-response curve showed an inverted "J" shape, the minimum mortality humidex (MMH) was 31.7 (77th percentile), and the cumulative relative risk (CRR) was 2.27 (95% confidence interval [CI], 1.76-2.91). At extremely high and low humidex, CRRs were 1.19 (95% CI, 0.98-1.44) and 2.52 (95% CI, 1.88-3.38), respectively. The burden of CVD mortality attributed to non-optimal humidex was 21.59% (95% empirical CI [eCI], 18.12-24.59%), most of which was due to low humidex, with an AF of 20.16% (95% eCI, 16.72-23.23%). CONCLUSIONS: Low humidex could significantly increase the risk of CVD mortality, and vulnerability to humidex differed across populations with different demographic characteristics. The elderly (> 64 years old), unmarried people, and those with a limited level of education (1-9 years) were especially susceptible to low humidex. Therefore, humidex is appropriate as a predictor in a CVD early-warning system.

Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3.

Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti-tumor, anti-oxidant, anti-viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM-induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING-finger containing protein-1 (MuRF1) and muscle atrophy Fbox protein (Atrogin-1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia.

Lightweight Model for Pavement Defect Detection Based on Improved YOLOv7.

Existing pavement defect detection models face challenges in balancing detection accuracy and speed while being constrained by large parameter sizes, hindering deployment on edge terminal devices with limited computing resources. To address these issues, this paper proposes a lightweight pavement defect detection model based on an improved YOLOv7 architecture. The model introduces four key enhancements: first, the incorporation of the SPPCSPC_Group grouped space pyramid pooling module to reduce the parameter load and computational complexity; second, the utilization of the K-means clustering algorithm for generating anchors, accelerating model convergence; third, the integration of the Ghost Conv module, enhancing feature extraction while minimizing the parameters and calculations; fourth, introduction of the CBAM convolution module to enrich the semantic information in the last layer of the backbone network. The experimental results demonstrate that the improved model achieved an average accuracy of 91%, and the accuracy in detecting broken plates and repaired models increased by 9% and 8%, respectively, compared to the original model. Moreover, the improved model exhibited reductions of 14.4% and 29.3% in the calculations and parameters, respectively, and a 29.1% decrease in the model size, resulting in an impressive 80 FPS (frames per second). The enhanced YOLOv7 successfully balances parameter reduction and computation while maintaining high accuracy, making it a more suitable choice for pavement defect detection compared with other algorithms.

Effect of different implant angulations on the biomechanical performance of prosthetic screws in two implant-supported, screw-retained prostheses: A numerical and experimental study.

STATEMENT OF PROBLEM: A mesiodistal angle frequently forms between 2 splinted implant-supported, screw-retained fixed dental prostheses (TIS-FDPs). Mechanical complications commonly occur in prosthetic screws. Studies regarding the effect of the degree of implant angulation on the biomechanical performance of prosthetic screws in TIS-FDPs are sparse. PURPOSE: The purpose of this numerical and experimental study was to investigate the effects of different implant angulations on the biomechanical performance, including stress distribution, stability of the screw joint, and surface morphology change of the prosthetic screws in TIS-FDPs. MATERIAL AND METHODS: TIS-FDPs were classified into 4 groups: 0, 10, 20, and 30 degrees based on the degree of mesiodistal angle between the long axes of the 2 implants. In the finite element analysis (FEA), 4 series of 3D models were constructed and loaded with simulated occlusal forces. The von Mises stresses and rotational angles of the prosthetic screws were then calculated. In the mechanical test, each group of 5 TIS-FDPs with 10 prosthetic screws was tested under 1 million loading cycles by using a universal testing machine. The removal torque values (RTVs) and the surface roughness of the prosthetic screws were measured after cyclic loading. The normality of the outcome variables was assessed by the Shapiro-Wilk test. Analysis of variance and the Kruskal-Wallis test were used for further analysis (α=.05). RESULTS: The FEA results showed that the von Mises stresses of the prosthetic screws were concentrated in the first screw thread crest engaged with the abutment, and the maximum values of the threads and the rotation angles of the prosthetic screws increased in the 2-implant mesiodistal angulation from 0 to 30 degrees. The mechanical tests showed that the RTVs of the prosthetic screws in each group were not significantly different after 1 million loading cycles (P=.107). The surface roughness of the crest of the first 2 threads of the prosthetic screws in the 30-degree group changed significantly compared with those in the other groups. CONCLUSIONS: When TIS-FDPs were delivered, larger angulations of the 2 splinted implants seemed to increase the stress concentrated on the crest of the first engaged thread and the rotation angles of the prosthetic screws. After 1 million loading cycles, significant surface adhesive wear was identified on the crest of the first 2 threads of the prosthetic screws in the 30-degree group compared with groups with a smaller angulation.

Independent and combined associations of multiple-heavy-metal exposure with lung function: a population-based study in US children.

Previous research has found relationships between some single metals and lung function parameters. However, the role of simultaneous multi-metal exposure is poorly understood. The crucial period throughout childhood, when people are most susceptible to environmental dangers, has also been largely ignored. The study aimed to evaluate the joint and individual associations of 12 selected urinary metals with pediatric lung function measures using multi-pollutant approaches. A total of 1227 children aged 6-17 years from the National Health and Nutrition Examination Survey database of the 2007-2012 cycles were used. The metal exposure indicators were 12 urine metals adjusted for urine creatinine, including arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), cobalt (Co), mercury (Hg), molybdenum (Mo), lead (Pb), antimony (Sb), thallium (Tl), tungsten (Tu), and uranium (Ur). The outcomes of interest were lung function indices, including the 1st second of a forceful exhalation (FEV1), forced vital capacity (FVC), forced expiratory flow between 25 and 7% of vital capacity (FEF25-75%), and peak expiratory flow (PEF). Multivariate linear regression, quantile g-computation (QG-C), and Bayesian kernel machine regression models (BKMR) were adopted. A significantly negative overall effect of metal mixtures on FEV1 (ß = - 161.70, 95% CI - 218.12, - 105.27; p < 0.001), FVC (ß = - 182.69, 95% CI - 246.33, - 119.06; p < 0.001), FEF25-75% (ß = - 178.86 (95% CI - 274.47, - 83.26; p < 0.001), and PEF (ß = - 424.17, 95% CI - 556.55, - 291.80; p < 0.001) was observed. Pb had the largest negative contribution to the negative associations, with posterior inclusion probabilities (PIPs) of 1 for FEV1, FVC, and FEF25-75%, and 0.9966 for PEF. And Pb's relationship with lung function metrics showed to be nonlinear, with an approximate "L" shape. Potential interactions between Pb and Cd in lung function decline were observed. Ba was positively associated with lung function metrics. Metal mixtures were negatively associated with pediatric lung function. Pb might be a crucial element. Our findings highlight the need for prioritizing children's environmental health to protect them from later respiratory disorders and to guide future research into the toxic mechanisms of metal-mediated lung function injury in the pediatric population.

[Screening of pathogenic molecular markers of Staphylococcus aureus in children based on whole genome sequencing technology]. / åŸºäºŽå ¨åŸºå› ç»„æµ‹åºæŠ€æœ¯ç­›é€‰å„¿ç«¥é‡‘é»„è‰²è‘¡è„çƒèŒçš„è‡´ç— ç›¸å ³åˆ†å­æ ‡å¿—ç‰©.

OBJECTIVES: To explore the molecular characteristics of Staphylococcus aureus (S. aureus) in children, and to compare the molecular characteristics of different types of strains (infection and colonization strains) so as to reveal pathogenic molecular markers of S. aureus. METHODS: A cross-sectional study design was used to conduct nasopharyngeal swab sampling from healthy children in the community and clinical samples from infected children in the hospital. Whole genome sequencing was used to detect antibiotic resistance genes and virulence genes. A random forest method to used to screen pathogenic markers. RESULTS: A total of 512 S. aureus strains were detected, including 272 infection strains and 240 colonization strains. For virulence genes, the carrying rates of enterotoxin genes (seb and sep), extracellular enzyme coding genes (splA, splB, splE and edinC), leukocytotoxin genes (lukD, lukE, lukF-PV and lukS-PV) and epidermal exfoliating genes (eta and etb) in infection strains were higher than those in colonization strains. But the carrying rates of enterotoxin genes (sec, sec3, seg, seh, sei, sel, sem, sen, seo and seu) were lower in infection strains than in colonization strains (P<0.05). For antibiotic resistance genes, the carrying rates of lnuA, lnuG, aadD, tetK and dfrG were significantly higher in infection strains than in colonization strains (P<0.05). The accuracy of cross-validation of the random forest model for screening pathogenic markers of S. aureus before and after screening was 69% and 68%, respectively, and the area under the curve was 0.75 and 0.70, respectively. The random forest model finally screened out 16 pathogenic markers (sem, etb, splE, sep, ser, mecA, lnuA, sea, blaZ, cat(pC233), blaTEm-1A, aph(3')-III, ermB, ermA, ant(9)-Ia and ant(6)-Ia). The top five variables in the variable importance ranking were sem (OR=0.40), etb (OR=3.95), splE (OR=1.68), sep (OR=3.97), and ser (OR=1.68). CONCLUSIONS: The random forest model can screen out pathogenic markers of S. aureus and exhibits a superior predictive performance, providing genetic evidence for tracing highly pathogenic S. aureus and conducting precise targeted interventions.

Hypermethylation of TMEM240 predicts poor hormone therapy response and disease progression in breast cancer.

BACKGROUND: Approximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression. METHODS: Circulating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and disease progression. The Cancer Genome Atlas (TCGA) data in Western countries and Illumina methylation arrays in Taiwanese breast cancer patients were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific PCR (QMSP), real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. TMEM240 gene manipulation, viability, migration assays, RNA-seq, and MetaCore were performed to determine its biological functions and relationship to hormone drug treatment response in breast cancer cells. RESULTS: Aberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240, which is localized to the cell membrane and cytoplasm, represses breast cancer cell proliferation and migration and regulates the expression levels of enzymes involved in estrone and estradiol metabolism. TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients, the methylation level of TMEM240 was at least twofold higher in tumor tissues than in matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response, especially hormone therapy response (p < 0.001). Circulating methylated TMEM240 dramatically and gradually decreased and then diminished in patients without disease progression, whereas it returned and its levels in plasma rose again in patients with disease progression. Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity, 93.1% specificity, and 90.2% accuracy. CONCLUSIONS: Hypermethylation of TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.

Integrated Porous Cu Host Induced High-Stable Bidirectional Li Plating/Stripping Behavior for Practical Li Metal Batteries.

The double-sided electrodes with active materials are widely used for commercial lithium (Li) ion batteries with a higher energy density. Accordingly, developing an anode current collector that can accommodate the stable and homogeneous Li plating/stripping on both sides will be highly desired for practical Li metal batteries (LMBs). Herein, an integrated bidirectional porous Cu (IBP-Cu) film with a through-pore structure is fabricated as Li metal hosts using the powder sintering method. The resultant IBP-Cu current collector with tunable pore volume and size exhibits high mechanical flexibility and stability. The bidirectional and through-pore structure enables the IBP-Cu host to achieve homogeneous Li deposition and effectively suppresses the dendritic Li growth. Impressively, the as-fabricated Li/IBP-Cu anode exhibits a remarkable capacity of up to 7.0 mAh cm-2 for deep plating/stripping, outstanding rate performance, and ultralong cycling ability with high Coulombic efficiency of ≈100% for 1000 cycles. More practicably, a designed pouch cell coupled with one Li/IBP-Cu anode and two LiFePO4 cathodes exhibits a highly elevated energy density (≈187.5%) compared with a pouch cell with one anode and one cathode. Such design of a bidirectional porous Cu current collector with stable Li plating/stripping behaviors suggests its promising practical applications for next-generation Li metal batteries.

Unveiling the Synergistic Effects of Monodisperse Sea Urchin-like PdPb Alloy Nanodendrites as Stable Electrocatalysts for Ethylene Glycol and Glycerol Oxidation Reactions.

In recent times, the fabrication of noble metal-based catalysts with controllable morphologies has become a research hotspot. Electrocatalytic devices with excellent catalytic performance and enhanced durability for the ethylene glycol oxidation reaction (EGOR) and the glycerol oxidation reaction (GOR) are significant for commercial direct fuel cells. Herein, a series of PdPb sea urchin-like nanodendrite (ND) structures with controllable molar ratios were synthesized as EGOR and GOR electrocatalysts of high efficiency. The optimized structurally regular Pd3Pb NDs exhibit the best electrocatalytic activity and outstanding stability compared to other samples and commercial Pt/C. In addition, the integrated Pb on Pd3Pb NDs can mitigate the bond energy the intermediates generate and further boost the electrooxidation of the intermediates by supplying enough active sites without considering its intrinsic structure, which is beneficial to the enhanced EGOR and GOR activity and stability. With the assistance of electrochemical measurement, the mechanism of the enhanced alloy was further investigated. This paper presents a promising strategy to fabricate catalysts with stable structures, which will elucidate a very promising approach for developing Pd-based catalysts for further applications in fuel cells.

Phosphoproteomics of cold stress-responsive mechanisms in Rhododendron chrysanthum.

BACKGROUND: As an alpine plant, Rhododendron chrysanthum (R. chrysanthum) has evolved cold resistance mechanisms and become a valuable plant resource with the responsive mechanism of cold stress. METHODS AND RESULTS: We adopt the phosphoproteomic and proteomic analysis combining with physiological measurement to illustrate the responsive mechanism of R. chrysanthum seedling under cold (4 °C) stress. After chilling for 12 h, 350 significantly changed proteins and 274 significantly changed phosphoproteins were detected. Clusters of Orthologous Groups (COG) analysis showed that significantly changed phosphoproteins and proteins indicated cold changed energy production and conversion and signal transduction. CONCLUSIONS: The results indicated photosynthesis was inhibited under cold stress, but cold induced calcium-mediated signaling, reactive oxygen species (ROS) homeostasis and other transcription regulation factors could protect plants from the destruction caused by cold stress. These data provide the insight to the cold stress response and defense mechanisms of R. chrysanthum leaves at the phosphoproteome level.