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Abstract 5-Methylcytosine (m5C) is closely associated with cancer. However, the role of m5C in breast cancer(BC)remains unclear. This study combined single-cell RNA sequencing (scRNA-Seq) and transcriptomics datasets to screen m5C regulators associated with BC progression and analyze their clinical values. Firstly, This study elucidates the mechanisms of the m5C landscape and the specific roles of m5C regulators in BC patients. we found that the dysregulation of m5C regulators with m5Cscore play the essential role of the carcinogenesis and progression in epithelial cells and myeloid cells of BC at single cell level. External validation was conducted using an independent scRNA-Seq datasets. Then, three distinct m5C modification patterns were identified by transcriptomics datasets. Based on the m5C differentially expressed regulators, the m5Cscore was constructed, and used to divide patients with BC into high and low m5Cscore groups. Patients with a high m5Cscore had more abundant immune cell infiltration, stronger antitumor immunity, and better prognoses. Finally, Quantitative real-time (PCR) and immunohistochemistry were used for the in vitro experimental validation, which had extensive prognostic value. In this study, we aimed to assess the expression of m5C regulators involved in BC and investigate their correlation with the tumor microenvironment, clinicopathological characteristics, and prognosis of BC. The m5C regulators could be used to effectively assess the cell specific regulation prognosis of patients with BC and develop more effective immunotherapy strategies.

Abstract Introduction Coaching is commonly used to facilitate leadership development among healthcare managers. However, there is limited knowledge of the components of coaching interventions and their impacts on healthcare managers’ leadership development. This mixed-methods systematic review aimed to synthesize evidence of coaching to develop leadership among healthcare managers. Methods The authors conducted a mixed-methods systematic review using a convergent synthesis design where quantitative and qualitative evidence was collected and analyzed concurrently using a matrix synthesis method. They reviewed studies published in English or Chinese by searching databases including MEDLINE (Ovid), CINAHL, Embase, Cochrane Library, Nursing & Allied Health Premium, Scopus, Wanfang, CNKI, SinoMed, and VIP databases from their inception to August 10, 2023, and updated the search again on July 9, 2024. Articles were screened and assessed for eligibility. First, from eligible studies, the qualitative data were extracted to describe intervention components, the perceived impact of coaching, and participants’ perceptions of being involved in coaching intervention. Second, quantitative data analysis was conducted to describe the impact of coaching interventions and the frequency of each theme evolved in the data. Third, qualitative and quantitative data were synthesized using the matrix synthesis method. Results A total of 13 studies were included in the analysis. Three qualitative studies were assessed as having ‘no or few limitations’, three case series studies were scored between five and eight out of 10 points, two quasi-experimental studies showed ‘moderate’ overall bias, and the five mixed-methods studies scored from 40 to 60% (out of 100%). For Objective 1, which covers the component of coaching (aims, ingredients, mechanism, and delivery), the typical aim of coaching interventions was to develop the leadership skills of middle management managers. The ingredients of coaching encompassed three distinct coaching categories and seven specific procedures. The mechanisms of most coaching interventions were based on theory and empirical evidence. The average delivery time was approximately four months. Overall, coaching positively impacts outcomes for managers, organizations, and staff (Objective 2). Perceptions of the participants toward coaching interventions were divided into six categories: barriers, facilitators, effective components, attitudes, satisfactory aspects, and suggestions for designing high-quality coaching interventions to improve leadership (Objective 3). Conclusions The components of coaching interventions varied across different studies. The impact of coaching on leadership development was positive across three levels (manager, organization, and staff). Therefore, we recommend coaching as an intervention for healthcare managers aiming to enhance their leadership level. Future coaching interventions may achieve greater effectiveness if they are specifically aligned with the participants’ perceptions identified in our study.

Periodontal disease is the most common type of oral disease. Periodontal bone defect is the clinical outcome of advanced periodontal disease, which seriously affects the quality of life of patients. Promoting periodontal tissue regeneration and repairing periodontal bone defects is the ultimate treatment goal for periodontal disease, but the means and methods are very limited. Hydrogels are a class of highly hydrophilic polymer networks, and their good biocompatibility has made them a popular research material in the field of oral medicine in recent years. This paper reviews the current mainstream types and characteristics of hydrogels, and summarizes the relevant basic research on hydrogels in promoting periodontal tissue regeneration and bone defect repair in recent years. The possible mechanisms of action and efficacy evaluation are discussed in depth, and the application prospects are also discussed.

This study establishes a novel approach to investigate if accelerated aging tests can accurately model realistic cell aging in a short time while also maintaining the consistency of the involved aging mechanisms. As a trade-off between efficiency and consistent mechanism, the application of accelerated aging necessitates carefully selecting stress factors to identify the operational range and the significance of aging-related stress factors. Based on three levels of major stress factors designed for 43-month calendar aging tests and 10-month cyclic aging tests, this work aims at the stress ranking and indicating suitable operational intervals for commercial LFP/C batteries, taking two of the most popular lifetime distributions for batteries, namely log-normal and Weibull. Statistical distributions of lithium-ion batteries are attained from discharge capacity loss with nonlinear mixed-effects (NLME) models. Results prove that log-normal is the preferred model, and the right-skewed Weibull becomes more pronounced with deeper aging, especially in calendar aging. The evolution law of distribution parameters guided by the consistent acceleration factor was derived. The likelihood ratio parametric bootstrap approach based on the NLME model for life samples consistently yields that test conditions with the temperature above 47.5 °C and average state-of-charge (SOC) for cycling aging above 72.5% can result in different life behaviors. In contrast, the combination of SOC levels and higher temperatures does not lead to a change in the calendar aging mechanisms. The temperature is the most significant stress, followed by temperature-coupled cycle depth and SOC levels. This method can offer a reference to make reasonable test plans for detecting battery's performance to predict their life more accurately.

Hypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that skeletal stem and progenitor cells (SSPCs) localize to the surrounding periosteum and serve as a major source of marrow-associated SSPCs, osteoblasts, osteocytes, and adipocytes during skeletal development. To further understand the cell transition process by which hypertrophic chondrocytes contribute to osteoblasts or other marrow associated cells, we utilized inducible and constitutive hypertrophic chondrocyte lineage tracing and reporter mouse models (Col10a1CreERT2; Rosa26fs-tdTomato and Col10a1Cre; Rosa26fs-tdTomato) in combination with a PDGFRaH2B-GFP transgenic line, single-cell RNA-sequencing, bulk RNA-sequencing, immunofluorescence staining, and cell transplantation assays. Our data demonstrate that hypertrophic chondrocytes undergo a process of dedifferentiation to generate marrow-associated SSPCs that serve as a primary source of osteoblasts during skeletal development. These hypertrophic chondrocyte-derived SSPCs commit to a CXCL12-abundant reticular (CAR) cell phenotype during skeletal development and demonstrate unique abilities to recruit vasculature and promote bone marrow establishment, while also contributing to the adipogenic lineage.

There are currently no approved drugs to treat Zika virus (ZIKV) infection during pregnancy. Hyperimmune globulin products such as VARIZIG and WinRho are FDA-approved to treat conditions during pregnancy such as Varicella Zoster virus infection and Rh-incompatibility. We administered ZIKV-specific human immune globulin as a treatment in pregnant rhesus macaques one day after subcutaneous ZIKV infection. All animals controlled ZIKV viremia following the treatment and generated robust levels of anti-Zika virus antibodies in their blood. No adverse fetal or infant outcomes were identified in the treated animals, yet the placebo control treated animals also did not have signs related to congenital Zika syndrome (CZS). Human immune globulin may be a viable prophylaxis and treatment option for ZIKV infection during pregnancy, however, more studies are required to fully assess the impact of this treatment to prevent CZS.

Culture expanded bone marrow stromal cells (BMSCs) are easily isolated, can be grown rapidly en masse, and contain both skeletal stem cells (SSCs) and multipotent mesenchymal progenitors (MMPs). Despite this functional heterogeneity, BMSCs continue to be utilized for many applications due to the lack of definitive and universally accepted markers to prospectively identify and purify SSCs. Isolation is widely based on adherence to tissue culture plastic; however, high hematopoietic contamination is a significant impediment in murine models. Remarkably, when cultured at a physiological oxygen tension of 1% O2, a 10-fold reduction in CD45+ hematopoietic cells associated with a concomitant increase in PDGFRα+ stromal cells occur. This is due, in part, to a differential response of the two populations to hypoxia. In standard tissue culture conditions of 21% O2, CD45+ cells showed increased proliferation coupled with no changes in cell death compared to their counterparts grown at 1% O2. In contrast, PDGFR α+ stromal cells responded to hypoxia by increasing proliferation and exhibiting a 10-fold decrease in cell death. In summary, we describe a simple and reliable method exploiting the divergent biological response of hematopoietic and stromal cells to hypoxia to significantly increase the PDGFR α+ stromal cell population in murine BMSC cultures.

Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood–retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth.

The perirhinal cortex is known to support high-level perceptual abilities as well as familiarity judgments that may affect recognition memory. We tested whether poor perceptual abilities or a loss of familiarity judgment contributed to the recognition memory impairments reported earlier in monkeys with PRh lesions received in infancy (Neo-PRh) (Weiss and Bachevalier, 2016; Zeamer et al., 2015). Perceptual abilities were assessed using a version of the Visual Paired Comparison task with black&white (B&W) stimuli, and familiarity judgments were assessed using the Constant Negative task requiring repeated familiarization exposures. Adult monkeys with Neo-PRh lesions were able to recognize B&W stimuli after short delays, suggesting that their perceptual abilities were within the range of control animals. However, the same Neo-PRh monkeys were slower to acquire the Constant Negative task, requiring more exposures to objects before judging them as familiar compared to control animals. Taken together, the data help to account for the differential patterns of functional compensation on previously reported recognition tasks following neonatal versus adult-onset PRh lesions, and provide further support to the view that the PRh is involved in familiarity processes. Keywords: Recognition, Visual perception, Medial temporal lobe, Development, Monkey

With excellent economy and properties, pressureless sintered micron silver has been regarded as an environmentally friendly interconnection material. In order to promote its reliable application in deep space exploration considering the porous microstructural evolution and its effect on macroscopic performance, simulation analysis based on the reconstruction of pressureless sintered micron silver joints was carried out. In this paper, the deep space environment was achieved by a test of 250 extreme thermal shocks of −170 °C~125 °C, and the microstructural evolution was observed by using SEM. Taking advantage of the morphology autocorrelation function, three-dimensional models of the random-distribution medium consistent with SEM images were reconstructed, and utilized in further Finite Element Analysis (FEA) of material effective elastic modulus through a transfer procedure. Compared with test results and two analytical models, the good consistency of the prediction results proves that the proposed method is reliable. Through analyzing the change in autocorrelation functions, the microstructural evolution with increasing shocks was quantitively characterized. Mechanical response characteristics in FEA were discussed. Moreover, the elasticity degradation was noticed and the mechanism in this special environment was clarified.

Seasonal characteristics of PM2.5, organic carbon (OC) and elemental carbon (EC) were studied in Taiyuan from 2009 to 2010. PM2.5 samples were collected by pre-baked quartz filters with high-volume air sampler, and then OC and EC were analyzed by thermal/optical reflectance method. The annual average concentrations of PM2.5, OC and EC were 220.2, 37.4 and 19.6 µg/m3 respectively, which were higher than those in most regions in China. Total carbonaceous aerosol (TCA) accounted for more than one third of the total PM2.5 mass. The levels of PM2.5, OC and EC were the highest in winter, followed by spring, fall and summer. OC and EC were well correlated in summer compared with other seasons, indicating the presence of other additional sources such as biomass burning in fall, coal combustion for heating in winter and dust in spring. Higher OC/EC ratios in winter might be primarily attributed to the significant increase of direct emission of OC as a result of coal and biomass combustion, and also cooling effect of carbonaceous aerosols due to low temperature and stagnated atmospheric condition. These results showed that the pollution of carbonaceous particles in Taiyuan was serious, and might be an inducing factor of dust haze, especially in winter.

Seasonal characteristics of PM2.5, organic carbon (OC) and elemental carbon (EC) were studied in Taiyuan from 2009 to 2010. PM2.5 samples were collected by pre-baked quartz filters with high-volume air sampler, and then OC and EC were analyzed by thermal/optical reflectance method. The annual average concentrations of PM2.5, OC and EC were 220.2, 37.4 and 19.6 µg/m³ respectively, which were higher than those in most regions in China. Total carbonaceous aerosol (TCA) accounted for more than one third of the total PM2.5 mass. The levels of PM2.5, OC and EC were the highest in winter, followed by spring, fall and summer. OC and EC were well correlated in summer compared with other seasons, indicating the presence of other additional sources such as biomass burning in fall, coal combustion for heating in winter and dust in spring. Higher OC/EC ratios in winter might be primarily attributed to the significant increase of direct emission of OC as a result of coal and biomass combustion, and also cooling effect of carbonaceous aerosols due to low temperature and stagnated atmospheric condition. These results showed that the pollution of carbonaceous particles in Taiyuan was serious, and might be an inducing factor of dust haze, especially in winter. [ABSTRACT FROM AUTHOR]