Search

Abstract Background Long-term, potentially lifelong therapy is needed to treat noninfectious uveitis (NIU) in children. Previous research has focused primarily on treatment approaches, but few studies have investigated the effect of children’s chronic illness on other family members. The aim of this study is to explore the experiences of burden and needs in caregivers of children with NIU, and to provide a reference for formulating targeted intervention strategies. Methods A total of 11 caregivers of children with NIU were recruited from a tertiary-level eye hospital in Wenzhou Province, China. For data collection, semi-structured interviews were conducted. Data analysis was conducted using Colaizzi’s seven-step analysis method. Themes were encoded and created with NVivo 14.0 for Mac software. Results Based on the Social Ecosystem Theory, three major themes and ten subthemes emerged from the analysis: (1) Micro system — Caregiver distress and growth coexist (subthemes: Affected physical health, difficulties in the child’s health management, emotional well-being, psychological Adjustment and Growth); (2) Mezzo system — Changes in family lifestyle (subthemes: Family financial challenges, family management dilemmas, weakened family socialization); (3) Macro system — Weak support system (subthemes: Insufficient information support, limited medical support conditions, lack of social understanding and support). Conclusions The social-ecological systems of caregivers for children with NIU present numerous difficulties impacting their caregiving experiences. It is imperative for healthcare providers to address the psychosocial issues faced by caregivers and to develop family-centered intervention strategies and support systems, enabling them to cope effectively and overcome challenges.

Seed germination is a crucial stage in plant development, intricately regulated by various environmental stimuli. Understanding these interactions is essential for optimizing planting and seedling management but remains challenging due to the trade-off effects of environmental factors on the germination process. We proposed a new conceptual model by viewing seed germination as a dynamic process in a physiological dimension, with the influence of environmental factors and seed heterogeneity characterized by a germination speed and a dispersion coefficient. To validate the model, we conducted field experiments by drilling wheat seeds at different dates to establish a temperature gradient and in different plots to create a soil water content gradient. Comparisons with our experimental data and literature results show the model accurately reproduces all germination patterns and the subsequent seedling tillering, with R2 > 0.95. Our results reveal that within suboptimal temperature range, the seed germination increases asymptotically with temperature, and that as soil water content increases, the germination speed increases initially before decreasing, illustrating the trade-off effect of soil water on bioavailability of water and oxygen. Introducing a physiological dimension enables seed germination and the subsequent tillering process to be modelled as a continuous physiological process, providing deeper insight into plant growth dynamics.

With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in MP sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019–2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.

Abstract To investigate the prognostic value of lymph node status in patients with cervical cancer (CC) patients who underwent neoadjuvant chemotherapy (NACT) and followed hysterectomy. Patients in two referral centers were retrospectively analyzed. The baseline tumor size and radiological lymph node status (LNr) were evaluated on pre-NACT MRI. Tumor histology, differentiation and pathological lymph node status (LNp) were obtained from post-operative specimen. The log-rank test was used to compare survival between patient groups. Cox proportional hazards regression models were employed to estimate the hazard ratio (HR) of various factors with progression-free survival (PFS) and overall survival (OS). A total of 266 patients were included. Patients with 2018 FIGO IIIC showed worse PFS compared to those with FIGO IB-IIB (p

BackgroundThis study aims to develop and validate a pretreatment MRI-based radiomics model to predict lymph node metastasis (LNM) following neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC).MethodsPatients with LACC who underwent NACT from two centers between 2013 and 2022 were enrolled retrospectively. Based on the lymph node (LN) status determined in the pathology reports after radical hysterectomy, patients were categorized as LN positive or negative. The patients from center 1 were assigned as the training set while those from center 2 formed the validation set. Radiomics features were extracted from pretreatment sagittal T2-weighted imaging (Sag-T2WI), axial diffusion-weighted imaging (Ax-DWI), and the delayed phase of dynamic contrast-enhanced sagittal T1-weighted imaging (Sag-T1C) for each patient. The K-best and least absolute shrinkage and selection operator (LASSO) methods were employed to reduce dimensionality, and the radiomics features strongly associated with LNM were selected and used to construct three single-sequence models. Furthermore, clinical variables were incorporated through multivariate regression analysis and fused with the selected radiomics features to construct the clinical-radiomics combined model. The diagnostic performance of the models was assessed using receiver operating characteristic (ROC) curve analysis. The clinical utility of the models was evaluated by the area under the ROC curve (AUC) and decision curve analysis (DCA).ResultsA total of 282 patients were included, comprising 171 patients in the training set, and 111 patients in the validation set. Compared to the Sag-T2WI model (AUC, 95%CI, training set, 0.797, 0.722-0.782; validation set, 0.648, 0.521-0.776) and the Sag-T1C model (AUC, 95%CI, training set, 0.802, 0.723-0.882; validation set, 0.630, 0.505-0.756), the Ax-DWI model exhibited the highest diagnostic performance with AUCs of 0.855 (95%CI, 0.791-0.919) in training set, and 0.753 (95%CI, 0.638-0.867) in validation set, respectively. The combined model, integrating selected features from three sequences and FIGO stage, surpassed predictive ability compared to the single-sequence models, with AUC of 0.889 (95%CI, 0.833-0.945) and 0.859 (95%CI, 0.781-0.936) in the training and validation sets, respectively.ConclusionsThe pretreatment MRI-based radiomics model, integrating radiomics features from three sequences and clinical variables, exhibited superior performance in predicting LNM following NACT in patients with LACC.

In the context of accelerated urbanization, assessing the quality of the existing built environment plays a crucial role in urban renewal. In the existing research and use of deep learning models, most categories are urban construction areas, forest land, farmland, and other categories. These categories are not conducive to a more accurate analysis of the spatial distribution characteristics of urban green space, parking space, blue space, and square. A small sample of refined land use classification data for urban built-up areas was produced using remote sensing images. The large-scale remote sensing images were classified using deep learning models, with the objective of inferring the fine land category of each tile image. In this study, satellite remote sensing images of four cities, Handan, Shijiazhuang, Xingtai, and Tangshan, were acquired by Google Class 19 RGB three-channel satellite remote sensing images to establish a data set containing fourteen urban land use classifications. The convolutional neural network model EfficientNetV2 is used to train and validate the network framework that performs well on computer vision tasks and enables intelligent image classification of urban remote sensing images. The model classification effect is compared and analyzed through accuracy, precision, recall, and F1-score. The results show that the EfficientNetV2 model has a classification recognition accuracy of 84.56% on the constructed data set. The testing set accuracy increases sequentially after transfer learning. This paper verifies that the proposed research framework has good practicality and that the results of the land use classification are conducive to the fine-grained quantitative analysis of built-up environmental quality.

Abstract Background Anxiety may stay with nursing students throughout their internship and even persist afterwards. Although many studies have explored the effects of perceived stress on anxiety, the relationship between pre-internship perceived stress and post-internship anxiety levels has not been clarified. In addition, none had focused on the moderating roles of career adaptability and professional commitment between perceived stress and anxiety. This study aims to investigate the influence of pre-internship perceived stress on the post-internship anxiety level of nursing college students, and to analyze the moderating effects of career adaptability and professional commitment on their relationships. Methods A longitudinal study design was employed. Full-time nursing college students from a Chinese medical university were recruited by convenient sampling. All surveys were conducted via Wen Juan Xing ( www.wjx.cn ), a widely used web-based survey platform in China. Two waves of surveys were collected in the pre-internship and post-internship periods, with an interval of one year. Among 823 nursing students recruited, 692 students completed all two waves of the survey (response rate: 84.08%). Participants completed a series of questionnaires examining general demographic characteristics, perceived stress, anxiety, career adaptability, and professional commitment both before and after the internship. The bias-corrected bootstrap technique of the Hayes PROCESS macro (Model 2) was used to test the moderation effect. Results Pre-internship perceived stress was positively associated with post-internship anxiety (β = 0.474, p

Abstract Background The error-proneness in the preanalytical and postanalytical stages is higher than that in the analytical stage of the total testing process. However, preanalytical and postanalytical quality management has not received enough attention in medical laboratory education and tests in clinical biochemistry courses. Methods/approach Clinical biochemistry teaching program aim to improve students’ awareness and ability of quality management according to international organization for standardization 15,189 requirements. We designed a student-centred laboratory training program, according to case-based learning that included 4 stages: “establish an overall testing process based on the patient’s clinical indicator, clarify principles, improve operational skills, and review process and continuous improvement”. The program was implemented in our college during the winter semesters of 2019 and 2020. A total of 185 undergraduate students majoring in medical laboratory science participated in the program as a test group, and the other 172 students were set up as the control group and adopted the conventional method. The participants were asked to finish an online survey to evaluate the class at the end. Results/outcomes The test group had significantly better examination scores not only in experimental operational skills (89.27 ± 7.16 vs. 77.51 ± 4.72, p

Genetic mitochondrial cardiomyopathy (MCM) is a myocardial condition characterized by abnormal cardiac structure and function secondary to genetic defects. Severity can vary from asymptomatic to severe with manifestations that include heart failure, arrhythmias, and sudden cardiac death. The heterogeneity of gene mutation-provoked mitochondrial dysfunction and a variety of manifestations hamper the development of effective therapeutics. In this review, we present the common pathogenesis of mitochondrial cardiomyopathies, and the most recent promising novel therapeutic strategies for cardiac repair including use of cells or stem cells, adeno-associated virus (AAV)-based gene therapies, mitochondrial-based therapy, pharmaceutical compounds, dietary supplementation, and exercise. We discuss their respective advantages and limitations that may aid their broader clinical application. Some novel treatments remain a long way from achieving safe and effective clinical therapeutic effects.

Non-destructive phenotyping of roots and measurement of root water uptake from different soil layers in the field are vital for improving water management and facilitating the development of drought-resistant crop varieties, but difficult because of their opaqueness. As a result, indirect methods using easy-to-measure variables such as soil water content have been used as alternatives. However, the inherent measurement errors could undermine the robustness and reliability of these methods. This paper proposes a new method to bridge this knowledge gap by using soil water content profiles measured at two time points to calculate root uptake and root-length density. It is based on the Richards' equation by treating root uptake from different soil layers between the two time points as random unknown numbers; their distributions are calculated using the Bayesian framework, solved by the Markov Chain Monte Carlo method. We applied the method to 39 winter wheat lines grown in a silt-clay loam field. Soil water content profile measured at the first time point from each plot served as the initial condition, and water content measured at the second time point was the target to match the model for calculating average root water uptake and root-length density between the two time points. The results show that the measured soil water contents fall within the 95% confidence interval of the calculated soil water contents. The inherent soil water measurement errors lead to uncertainties in the calculated root water uptake for all lines, but such uncertainties decrease with soil depth. Although the soil types and agronomic management were the same for all 39 lines, their root water uptake from different soil layers varies considerably, with some lines more capable of using subsoil water than others. Generally, the calculated and measured root-length densities agree well, albeit the degree of the agreement varies with lines. While this paper focuses on methodology and applies the method to one growth stage spanning one month only, the consistent results for all 39 lines indicates the method is robust and can be applied to other crops cultivated in different conditions. Given the growing interest in improving root traits to enhance water use efficiency, the proposed method has important implications as phenotyping roots and understanding their water uptake from different soil layers in the field is a prerequisite to achieve this crucial target.

From quantum communications to quantum computing, single-photon emitters (SPEs) are essential components of numerous quantum technologies. Two-dimensional (2D) materials have especially been found to be highly attractive for the research into nanoscale light–matter interactions. In particular, localized photonic states at their surfaces have attracted great attention due to their enormous potential applications in quantum optics. Recently, SPEs have been achieved in various 2D materials, while the challenges still remain. This paper reviews the recent research progress on these SPEs based on various 2D materials, such as transition metal dichalcogenides (TMDs), hexagonal boron nitride (hBN), and twisted-angle 2D materials. Additionally, we summarized the strategies to create, position, enhance, and tune the emission wavelength of these emitters by introducing external fields into these 2D system. For example, pronounced enhancement of the SPEs’ properties can be achieved by coupling with external fields, such as the plasmonic field, and by locating in optical microcavities. Finally, this paper also discusses current challenges and offers perspectives that could further stimulate scientific research in this field. These emitters, due to their unique physical properties and integration potential, are highly appealing for applications in quantum information and communication, as well as other physical and technological fields.

Abstract Background Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus that contributes to 85% of nontraumatic lower extremity amputations in diabetic patients. Preliminary clinical benefits have been shown in treatments based on mesenchymal stem cells for patients with DFU or peripheral arterial disease (PAD). However, the long-term safety and benefits are unclear for patients with both DFU and PAD who are not amenable to surgical revascularization. Methods In this phase I pilot study, 14 patients with PAD and incurable DFU were enrolled to assess the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) administration based on conservative treatments. All patients received topical and intravenous administrations of hUC-MSCs at a dosage of 2 × 105 cells/kg with an upper limit of 1 × 107 cells for each dose. The adverse events during treatment and follow-up were documented for safety assessments. The therapeutic efficacy was assessed by ulcer healing status, recurrence rate, and 3-year amputation-free rate in the follow-up phase. Results The safety profiles were favorable. Only 2 cases of transient fever were observed within 3 days after transfusion and considered possibly related to hUC-MSC administration intravenously. Ulcer disclosure was achieved for more than 95% of the lesion area for all patients within 1.5 months after treatment. The symptoms of chronic limb ischaemia were alleviated along with a decrease in Wagner scores, Rutherford grades, and visual analogue scale scores. No direct evidence was observed to indicate the alleviation of the obstruction in the main vessels of target limbs based on computed tomography angiography. The duration of rehospitalization for DFU was 2.0 ± 0.6 years. All of the patients survived without amputation due to the recurrence of DFU within 3 years after treatments. Conclusions Based on the current pilot study, the preliminary clinical benefits of hUC-MSCs on DFU healing were shown, including good tolerance, a shortened healing time to 1.5 months and a favorable 3-year amputation-free survival rate. The clinical evidence in the current study suggested a further phase I/II study with a larger patient population and a more rigorous design to explore the efficacy and mechanism of hUC-MSCs on DFU healing. Trial registration: The current study was registered retrospectively on 22 Jan 2022 with the Chinese Clinical Trial Registry (ChiCTR2200055885), http://www.chictr.org.cn/showproj.aspx?proj=135888 Graphical Abstract

Abstract Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.

Flexible micro-supercapacitor (MSC) with in-plane electrodes has attracted significant attention as microscale energy storage device. Especially, flexible MSCs with adhesion properties are of great interest for wearable electronics. Here, we demonstrate a facile and cost-effective mask-assisted drop-casting method to fabricate adhesive MSC on medical tape using dimethyl sulfoxide (DMSO) doped poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) aqueous solution. The fabricated MSC with poly (vinyl alcohol)/H3PO4 gel electrolyte exhibits an areal specific capacitance of 10.96 mF cm−2 at a current density of 0.1 mA cm−2 with excellent mechanical flexibility. The MSC can be attached on various substrates due to the stickiness of the medical tape. For practical application, the MSC can be coupled with a solar cell to achieve a stand-alone power supply system for a flex senor in monitoring finger movements. Therefore, we believe that the mask-assisted drop-casting method paves a new way to develop flexible and adhesive MSCs for self-powered integrated wearable electronics.

Abstract Background Severe asthma is difficult to control. Therapeutic patient education enables patients to better understand their disease and cope with treatment, but the effect of therapeutic patient education in severe uncontrolled asthma is unclear. We evaluated whether therapeutic patient education is effective in improving asthma control and decreasing the frequency of exacerbations in severe uncontrolled asthma. Methods This was a prospective, observational, and self-controlled study that enrolled 40 subjects with severe uncontrolled asthma. Patients were seen at a clinic four times (on day 1 and after 3, 6, and 12 months). After baseline data collection, the subjects completed a therapeutic patient education program and were also followed-up via telephone after 1, 2, 4, 5, 7, 8, 9, 10, and 11 months to monitor asthma medication adherence and collect asthma-related information. Results Within the 1-year study period, a total of 23 exacerbations were recorded in 14 patients, seven of whom required emergency treatment and two of whom were hospitalized. Twelve months after the standardized therapeutic patient education program, pulmonary function and fractional exhaled nitric oxide levels improved significantly in all 40 patients. Moreover, the scores from three standardized asthma questionnaires and indices suggested improved quality of life in these patients with severe uncontrolled asthma. Serum levels of biomarkers reflecting asthma immune responses did not change between baseline and the 1-year follow-up time point. Conclusions Therapeutic patient education is effective in improving asthma control and decreasing exacerbations in patients with severe uncontrolled asthma.

Children with prosopagnosia, also known as face blindness, struggle to recognize the faces of acquaintances, which can have a negative impact on their social interactions and overall functioning. This paper reviews existing research on interventions for children with prosopagnosia, including compensatory and remedial strategies, and provides a summary and comparison of their effectiveness. However, despite the availability of these interventions, their effectiveness remains limited and constrained by various factors. The lack of a widely accepted treatment for children with prosopagnosia emphasizes the need for further research to improve intervention strategies. Last, three future research directions were proposed to improve interventions for prosopagnosia, including ecological approaches, the social challenges faced by children, and new potential intervention methods.

College students' motivation and engagement are regarded as essential factors to promote their academic development and wellbeing. However, motivation and engagement among college students appear to decline after they enter the university. Guided by the framework of self-determination theory, this study attempted to explore a motivational model of how three dimensions of perceived teacher support (autonomy, structure, and involvement) related to student motivation and class engagement, using need satisfaction as a mediator. Drew on a survey of the perceptions of 705 Chinese university students, the results showed that besides structure, both autonomy support and involvement positively related to students' need satisfaction. Further, need satisfaction was positively associated with autonomous motivation, controlled motivation, and class engagement and negatively linked with amotivation. Yet, only autonomous motivation was positively predicted for class engagement. Need satisfaction and the chain from need satisfaction to autonomous motivation were found to be the significant mediators. The practical implications of educational practices are discussed.

RNA, one of the major building blocks of the cell, participates in many essential life processes. RNA stability is well-established to be closely related to various RNA modifications. To date, hundreds of different RNA modifications have been identified. N6-methyladenosine (m6A) is one of the most important RNA modifications in mammalian cells. An increasing body of evidence from recently published studies suggests that m6A modification is a novel immune system regulator of the generation and differentiation of hematopoietic stem cells (HSCs) and immune cells. In this review, we introduce the process and relevant regulatory mechanisms of m6A modification; summarize recent findings of m6A in controlling HSC generation and self-renewal, and the development and differentiation of T and B lymphocytes from HSCs; and discuss the potential mechanisms involved.

Abstract Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy to treat many degenerative diseases. Accumulating evidence shows that the function of MSCs declines with age, thus limiting their regenerative capacity. Nonetheless, the underlying mechanisms that control MSC ageing are not well understood. We show that compared with bone marrow-MSCs (BM-MSCs) isolated from young and aged samples, NADH dehydrogenase (ubiquinone) iron-sulfur protein 6 (Ndufs6) is depressed in aged MSCs. Similar to that of Ndufs6 knockout (Ndufs6−/−) mice, MSCs exhibited a reduced self-renewal and differentiation capacity with a tendency to senescence in the presence of an increased p53/p21 level. Downregulation of Ndufs6 by siRNA also accelerated progression of wild-type BM-MSCs to an aged state. In contrast, replenishment of Ndufs6 in Ndufs6−/−-BM-MSCs significantly rejuvenated senescent cells and restored their proliferative ability. Compared with BM-MSCs, Ndufs6−/−-BM-MSCs displayed increased intracellular and mitochondrial reactive oxygen species (ROS), and decreased mitochondrial membrane potential. Treatment of Ndufs6−/−-BM-MSCs with mitochondrial ROS inhibitor Mito-TEMPO notably reversed the cellular senescence and reduced the increased p53/p21 level. We provide direct evidence that impairment of mitochondrial Ndufs6 is a putative accelerator of adult stem cell ageing that is associated with excessive ROS accumulation and upregulation of p53/p21. It also indicates that manipulation of mitochondrial function is critical and can effectively protect adult stem cells against senescence.

Abstract Background Cough and airway eosinophilic inflammation has not been highlighted in hypereosinophilic syndrome (HES). Case presentation We report 2 further cases and reviewed the clinical features and treatment of HES present with cough from the literature. Both cases were middle age male, presenting with chronic cough, airway eosinophilic inflammation and hyper eosinophilia who have been previous misdiagnosed as cough-variant asthma and failed anti-asthma treatment. PDGFRA fusion gene was confirmed in one case, but not in the other case. Both had evidence of myeloproliferative features. The tyrosine kinase inhibitor, imatinib, resulted in complete resolution of eosinophilia and cough. By searching PubMed, we found 8 HES cohorts of 411 cases between 1975 and 2013, where the incidence of cough was 23.11%. Sixteen case reports of HES presented with cough as predominant or sole symptom, with nine male patients with positive PDGFRA fusion gene, who responded well to imatinib. Six of seven patients, who tested negative for the PDGFRA, responded to systemic glucocorticoids. Conclusions Cough and airway eosinophilic inflammation is common in some HES patients. PDGFRA+ HES patients present with chronic cough respond well to imatinib. Our case reports indicate that PDGFRA negative HES patients may respond to imatinib as well.

Modifying farming practices combined with breeding has the potential to improve water and nutrient use efficiency by regulating root growth, but achieving this goal requires phenotyping the roots, including their architecture and ability to take up water and nutrients from different soil layers. This is challenging due to the difficulty of in situ root measurement and opaqueness of the soil. Using stable isotopes and soil coring, we calculated the change in root water uptake of summer maize in response to planting density and nitrogen fertilization in a 2-year field experiment. We periodically measured root-length density, soil moisture content, and stable isotopes δ18O and δD in the plant stem, soil water, and precipitation concurrently and calculated the root water uptake based on the mass balance of the isotopes and the Bayesian inference method coupled with the Markov Chain Monte Carlo simulation. The results show that the root water uptake increased asymptotically with root-length density and that nitrogen application affected the locations in soil from which the roots acquired water more significantly than planting density. In particular, we find that reducing nitrogen application promoted root penetration to access subsoil nutrients and consequently enhanced their water uptake from the subsoil, while increasing planting density benefited water uptake of the roots in the topsoil. These findings reveal that it is possible to manipulate plant density and fertilization to improve water and nutrient use efficiency of the summer maize and the results thus have imperative implications for agricultural production.

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is characterized by asthma-like attacks in its early stage, which is easily misdiagnosed as severe asthma. Therefore, new biomarkers for the early diagnosis of EGPA are needed, especially for differentiating the diagnosis of asthma.ObjectivesTo identify serum biomarkers that can be used for early diagnosis of EGPA and to distinguish EGPA from severe asthma.MethodData-independent acquisition (DIA) analysis was performed to identify 45 healthy controls (HC), severe asthma (S-A), and EGPA patients in a cohort to screen biomarkers for early diagnosis of EGPA and to differentiate asthma diagnosis. Subsequently, parallel reaction monitoring (PRM) analysis was applied to a validation cohort of 71 HC, S-A, and EGPA patients.ResultFour candidate biomarkers were identified from DIA and PRM analysis—i.e., serum amyloid A1 (SAA1), fibrinogen-α (FGA), and serum amyloid P component (SAP)—and were upregulated in the EGPA group, while cholesteryl ester transfer protein (CETP) was downregulated in the EGPA group compared with the S-A group. Receiver operating characteristics analysis shows that, as biomarkers for early diagnosis of EGPA, the combination of SAA1, FGA, and SAP has an area under the curve (AUC) of 0.947, a sensitivity of 82.35%, and a specificity of 100%. The combination of SAA1, FGA, SAP, and CETP as biomarkers for differential diagnosis of asthma had an AUC of 0.921, a sensitivity of 78.13%, and a specificity of 100%, which were all larger than single markers. Moreover, SAA1, FGA, and SAP were positively and CETP was negatively correlated with eosinophil count.ConclusionDIA-PRM combined analysis screened and validated four previously unexplored but potentially useful biomarkers for early diagnosis of EGPA and differential diagnosis of asthma.

The rapid development of intelligent connected vehicles has increased the attack surface of vehicles and made the complexity of vehicle systems unprecedented. Original equipment manufacturers (OEMs) need to accurately represent and identify threats and match corresponding security requirements. Meanwhile, the fast iteration cycle of modern vehicles requires development engineers to quickly obtain cybersecurity requirements for new features in their developed systems in order to develop system code that meets cybersecurity requirements. However, existing threat identification and cybersecurity requirement methods in the automotive domain cannot accurately describe and identify threats for a new feature while also quickly matching appropriate cybersecurity requirements. This article proposes a cybersecurity requirements management system (CRMS) framework to assist OEM security experts in conducting comprehensive automated threat analysis and risk assessment and to help development engineers identify security requirements prior to software development. The proposed CRMS framework enables development engineers to quickly model their systems using the UML-based (i.e., capable of describing systems using UML) Eclipse Modeling Framework and security experts to integrate their security experience into a threat library and security requirement library expressed in Alloy formal language. In order to ensure accurate matching between the two, a middleware communication framework called the component channel messaging and interface (CCMI) framework, specifically designed for the automotive domain, is proposed. The CCMI communication framework enables the fast model of development engineers to match with the formal model of security experts for threat and security requirement matching, achieving accurate and automated threat and risk identification and security requirement matching. To validate our work, we conducted experiments on the proposed framework and compared the results with the HEAVENS approach. The results showed that the proposed framework is superior in terms of threat detection rates and coverage rates of security requirements. Moreover, it also saves analysis time for large and complex systems, and the cost-saving effect becomes more pronounced with increasing system complexity.

Mitochondrial cardiomyopathy (MCM) is characterized by abnormal heart-muscle structure and function, caused by mutations in the nuclear genome or mitochondrial DNA. The heterogeneity of gene mutations and various clinical presentations in patients with cardiomyopathy make its diagnosis, molecular mechanism, and therapeutics great challenges. This review describes the molecular epidemiology of MCM and its clinical features, reviews the promising diagnostic tests applied for mitochondrial diseases and cardiomyopathies, and details the animal and cellular models used for modeling cardiomyopathy and to investigate disease pathogenesis in a controlled in vitro environment. It also discusses the emerging therapeutics tested in pre-clinical and clinical studies of cardiac regeneration.

Objective: Early identification of coronavirus disease 2019 (COVID-19) patients with worse outcomes may benefit clinical management of patients. We aimed to quantify pneumonia findings on CT at admission to predict progression to critical illness in COVID-19 patients.Methods: This retrospective study included laboratory-confirmed adult patients with COVID-19. All patients underwent a thin-section chest computed tomography (CT) scans showing evidence of pneumonia. CT images with severe moving artifacts were excluded from analysis. Patients' clinical and laboratory data were collected from medical records. Three quantitative CT features of pneumonia lesions were automatically calculated using a care.ai Intelligent Multi-disciplinary Imaging Diagnosis Platform Intelligent Evaluation System of Chest CT for COVID-19, denoting the percentage of pneumonia volume (PPV), ground-glass opacity volume (PGV), and consolidation volume (PCV). According to Chinese COVID-19 guidelines (trial version 7), patients were divided into noncritical and critical groups. Critical illness was defined as a composite of admission to the intensive care unit, respiratory failure requiring mechanical ventilation, shock, or death. The performance of PPV, PGV, and PCV in discrimination of critical illness was assessed. The correlations between PPV and laboratory variables were assessed by Pearson correlation analysis.Results: A total of 140 patients were included, with mean age of 58.6 years, and 85 (60.7%) were male. Thirty-two (22.9%) patients were critical. Using a cutoff value of 22.6%, the PPV had the highest performance in predicting critical illness, with an area under the curve of 0.868, sensitivity of 81.3%, and specificity of 80.6%. The PPV had moderately positive correlation with neutrophil (%) (r = 0.535, p < 0.001), erythrocyte sedimentation rate (r = 0.567, p < 0.001), d-Dimer (r = 0.444, p < 0.001), high-sensitivity C-reactive protein (r = 0.495, p < 0.001), aspartate aminotransferase (r = 0.410, p < 0.001), lactate dehydrogenase (r = 0.644, p < 0.001), and urea nitrogen (r = 0.439, p < 0.001), whereas the PPV had moderately negative correlation with lymphocyte (%) (r = −0.535, p < 0.001).Conclusions: Pneumonia volume quantified on initial CT can non-invasively predict the progression to critical illness in advance, which serve as a prognostic marker of COVID-19.

In recent years, van der Waals heterostructures (vdWHs) of two-dimensional (2D) materials have attracted extensive research interest. By stacking various 2D materials together to form vdWHs, it is interesting to see that new and fascinating properties are formed beyond single 2D materials; thus, 2D heterostructures-based nanodevices, especially for potential optoelectronic applications, were successfully constructed in the past few decades. With the dramatically increased demand for well-controlled heterostructures for nanodevices with desired performance in recent years, various interfacial modulation methods have been carried out to regulate the interfacial coupling of such heterostructures. Here, the research progress in the study of interfacial coupling of vdWHs (investigated by Photoluminescence, Raman, and Pump–probe spectroscopies as well as other techniques), the modulation of interfacial coupling by applying various external fields (including electrical, optical, mechanical fields), as well as the related applications for future electrics and optoelectronics, have been briefly reviewed. By summarizing the recent progress, discussing the recent advances, and looking forward to future trends and existing challenges, this review is aimed at providing an overall picture of the importance of interfacial modulation in vdWHs for possible strategies to optimize the device’s performance.

Ion transport in solid-state materials is a fundamental process for many modern technologies. Utilizing electrostatic force microscopy, Yanget al. directly visualize ion motion and verify the oxygen ion dynamics within HfO2—a common metal-oxide based memristive material.

The geometrical structure and spatial arrangement of lumens, bordered pits, and scalariform perforation plates in xylem vessels modulate water flow from roots to leaves. Understanding their respective hydraulic functions is essential to unveil how plants regulate their hydraulic networks to facilitate the ascent of sap under biotic and abiotic stresses but is challenging because of the opaque nature of the vessel networks and water flow within them. We made the first-ever effort to discern the difference between lumens and scalariform perforation plates in cotton in impeding water flow in single vessels and vessel networks using X-ray tomography and pore-scale numerical simulation. Three-dimensional structures of xylem vessels in the stem of two cotton cultivars were acquired non-invasively using X-ray computed tomography (CT) at high spatial resolution, and a lattice Boltzmann model was developed to simulate water flow through the xylem networks at micrometer scale. The detailed water velocity and pressure simulated using the model were used to calculate the hydraulic resistance caused by the lumens and the scalariform perforation plates in individual vessels and the vessel networks of the two cotton cultivars. The results showed that the hydraulic resistance spiked whenever water flowed across a perforation plate and that the overall hydraulic resistance caused by the perforation plates in an individual vessel accounted for approximately 54% of the total resistance of the vessel. We also calculated the hydraulic conductance of individual vessels and vessel networks using the simulated water velocity and pressure at micrometer scale and compared it with those estimated from the Hagen Poiseuille (HP) equation as commonly used in the literature by approximating the xylem vessels in the cotton as isolated tubes. While it was found that the HP equation overestimated the hydraulic conductance by more than 200%, the overestimate was largely due to the incapability of the HP equation to represent the perforation plates rather than its approximation of the irregular vessels by circular tubes.

[This corrects the article DOI: 10.1371/journal.pone.0226400.].

Mathematical learning difficulties (MLD) refer to a variety of deficits in math skills, typically pertaining to the domains of arithmetic and problem solving. The present study examined the time course of attentional orienting in MLD children with a spatial cueing task, by parametrically manipulating the cue-target onset asynchrony (CTOA). The results of Experiment 1 revealed that, in contrast to typical developing children, the inhibitory aftereffect of attentional orienting – frequently referred to as inhibition of return (IOR) – was not observed in the MLD children, even at the longest CTOA tested (800 ms). However, robust early facilitation effects were observed in the MLD children, suggesting that they have difficulties in attentional disengagement rather than attentional engagement. In a second experiment, a secondary cue was introduced to the cueing task to encourage attentional disengagement and IOR effects were observed in the MLD children. Taken together, the present experiments indicate that MLD children are sluggish in disengaging spatial attention.

The aim of our study was to elucidate the landscapes of genetic alterations of TSC1 and TSC2 as well as other possible non-TSC1/2 in Lymphangioleiomyomatosis (LAM) patients. Sixty-one Chinese LAM patients' clinical information was collected. Tumor biopsies and matched leukocytes from these patients were retrospectively analyzed by next generation sequencing (NGS), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA). Eighty-six TSC1/2 variants were identified in 46 of the 61 LAM patients (75.4%) in which TSC2 and TSC1 variants were 88.37% and 11.63% respectively. The 86 variants are composed of (i) 52 single nucleotide variants (SNVs) (including 30 novel variants), (ii) 23 indels (including 21deletions, and 2 insertions), (iii) a germline duplication of exon 31-42 of TSC2, (iv) a 2.68 Mb somatic duplication containing TSC2, and (v) 9 regions with copy-neutral loss of heterogeneity (CN-LOHs) present only in the LAM patients with single TSC1/2 mutations. Sixty-one non-TSC1/2 variants in 31 genes were identified in 37 LAM patients. Combined applications of different techniques are necessary to achieve maximal detection rate of TSC1/2 variants in LAM patients. Thirty novel TSC1/2 variants expands the spectrum of TSC1/2 in LAM patients. Identification of 61 non-TSC1/2 variants suggests that alternative genes might have contributed to the initiation and progression of LAM.

Constructing heterojunction is a promising method to enhance visible-light utility and promote photogenerated e ^− -h ^+ pairs separation of g-C _3 N _4 . Herein, the present work reported a g-C _3 N _4 /Cu _2 O heterojunction by a facile in situ synthetic strategy. The structure, morphology, optical, electrochemical and photocatalytic properties were investigated. The results showed the combination of g-C _3 N _4 nanosheets and Cu _2 O nanospheres resulted in the close contact interface and wide visible-light response range, and fast separation of the photo-generated e ^− -h ^+ pairs. The pristine g-C _3 N _4 showed weak photocatalytic performance towards methyl orange (MO) under visible-light irradiation, compared with pristine g-C _3 N _4 , the photocatalytic degradation rate of optimized g-C _3 N _4 /Cu _2 O composite demonstrates the substantially enhanced photocatalytic activity, which showed no obvious loss after five repeated use. The enhanced performance was ascribed to the synergistic effect of good visible-light harvesting and enhanced separation rate of the charge carriers.

Combining with the Crank-Nicolson/leapfrog scheme in time discretization, Chebyshev-Legendre spectral method is applied to space discretization for numerically solving the Benjamin-Bona-Mahony-Burgers (gBBM-B) equations. The proposed approach is based on Legendre Galerkin formulation while the Chebyshev-Gauss-Lobatto (CGL) nodes are used in the computation. By using the proposed method, the computational complexity is reduced and both accuracy and efficiency are achieved. The stability and convergence are rigorously set up. Optimal error estimate of the Chebyshev-Legendre method is proved for the problem with Dirichlet boundary condition. The convergence rate shows “spectral accuracy.” Numerical experiments are presented to demonstrate the effectiveness of the method and to confirm the theoretical results.

Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy and safety for tumor management, yet their self assembly typically relied on chemical modifications of drugs or the incorporation of surfactants, thereby compromising the drug's inherent pharmacological activity. To address this challenge, we proposed a triethylamine (TEA)-mediated protonation-deprotonation strategy that enabled the adjustable-proportion self assembly of dual drugs without chemical modification, achieving nearly 100% drug loading capacity. Molecular dynamic simulations, supported by experiment evidence, elucidated the underlying self-assembly mechanism. Specifically, TEA facilitated the deprotonation of Doxorubicin (Dox) and α-Tocopherol succinate (α-tos), causing Dox to transition from a hydrophilic to a hydrophobic state, while simultaneously increasing the hydrophilicity of α-tos. This allowed for a fine-tuned balance between the hydrophilic and hydrophobic properties of the two compounds, enabling their precise self assembly into a carrier-free nanomedicine (DT) with a tailored drug ratio. The engineered DT demonstrated the ability to accumulate at the tumor sites and release its therapeutic drugs in a controlled manner. The combination of Dox and α-tos synergistically generated reactive oxygen species and modulated the expression of tumor matrix metalloproteinase-9, leading to superior antitumor efficacy without significant metastasis, while maintaining excellent safety profiles. Our findings provided unique perspectives on the design of carrier-free nanomedicine for cancer therapy, thereby laying a solid foundation for its potential clinical translation. [ABSTRACT FROM AUTHOR]