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Abstract Background Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with the tumor microenvironment (TME) playing a crucial role in its progression. Aggregated autophagy (AA) has been recognized as a factor that exacerbates CRC progression. This study aims to study the relationship between aggregated autophagy and CRC using single-cell sequencing techniques. Our goal is to explain the heterogeneity of the TME and to explore the potential for targeted personalized therapies. Objective To study the role of AA in CRC, we employed single-cell sequencing to discern distinct subpopulations within the TME. These subpopulations were characterized by their autophagy levels and further analyzed to identify specific biological processes and marker genes. Results Our study revealed significant correlations between immune factors and both clinical and biological characteristics of the tumor microenvironment (TME), particularly in cells expressing TUBA1B and HSP90AA1. These immune factors were associated with T cell depletion, a reduction in protective factors, diminished efficacy of immune checkpoint blockade (ICB), and enhanced migration of cancer-associated fibroblasts (CAFs), resulting in pronounced inflammation. In vitro experiments showd that silencing TUBA1B and HSP90AA1 using siRNA (Si-TUBA1B and Si-HSP90AA1) significantly reduced the expression of IL-6, IL-7, CXCL1, and CXCL2 and inhibition of tumor cell growth in Caco-2 and Colo-205 cell lines. This reduction led to a substantial alleviation of chronic inflammation and highlighted the heterogeneous nature of the TME. Conclusion This study marks an initial foray into understanding how AA-associated processes may potentiate the TME and weaken immune function. Our findings provide insights into the complex dynamics of the TME and highlight potential targets for therapeutic intervention, suggesting a key role for AA in the advancement of colorectal cancer.

BackgroundThe Objective Structured Clinical Examination (OSCE) is a pivotal tool for assessing health care professionals and plays an integral role in medical education. ObjectiveThis study aims to map the bibliometric landscape of OSCE research, highlighting trends and key influencers. MethodsA comprehensive literature search was conducted for materials related to OSCE from January 2004 to December 2023, using the Web of Science Core Collection database. Bibliometric analysis and visualization were performed with VOSviewer and CiteSpace software tools. ResultsOur analysis indicates a consistent increase in OSCE-related publications over the study period, with a notable surge after 2019, culminating in a peak of activity in 2021. The United States emerged as a significant contributor, responsible for 30.86% (1626/5268) of total publications and amassing 44,051 citations. Coauthorship network analysis highlighted robust collaborations, particularly between the United States and the United Kingdom. Leading journals in this domain—BMC Medical Education, Medical Education, Academic Medicine, and Medical Teacher—featured the highest volume of papers, while The Lancet garnered substantial citations, reflecting its high impact factor (to be verified for accuracy). Prominent authors in the field include Sondra Zabar, Debra Pugh, Timothy J Wood, and Susan Humphrey-Murto, with Ronaldo M Harden, Brian D Hodges, and George E Miller being the most cited. The analysis of key research terms revealed a focus on “education,” “performance,” “competence,” and “skills,” indicating these are central themes in OSCE research. ConclusionsThe study underscores a dynamic expansion in OSCE research and international collaboration, spotlighting influential countries, institutions, authors, and journals. These elements are instrumental in steering the evolution of medical education assessment practices and suggest a trajectory for future research endeavors. Future work should consider the implications of these findings for medical education and the potential areas for further investigation, particularly in underrepresented regions or emerging competencies in health care training.

IntroductionThe hair follicle (HF) is a micro-organ capable of regeneration. A HF cycle consists of an anagen, catagen and telogen. Abnormalities in the HF cycle can lead to many hair disorders such as hair loss. The pig is a good biomedical model, but there are few data on their HF cycle. The aim of this study was to classify the pig HF cycle and determine the feasibility of the pig as an animal model for human HF cycle.MethodsSkin samples from 10 different postnatal (P) days Yorkshire pigs was collected to determine the key time points of the first HF cycle in pig by H&E staining, immunofluorescence staining, q-PCR and western-blot.ResultsBy morphological observation and detection of markers at different stages, pig HF cycle was classified into three main periods - the first anagen until P45, catagen (P45–P85), telogen (P85–P100), and next anagen (>P100). In addition, we examined the expression of important genes AE15, CD34, Versican, Ki67 et al. related to the HF cycle at different stages of pig HF, indicating that pig and human share similarities in morphology and marker gene expression patterns of HF cycle.DiscussionOur findings will facilitate the study of HF cycle and offer researchers a suitable model for human hair research.

Abstract Background Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. Methods A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question ‘Do you feel you have more problems with memory than most?’ in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient’s age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People’s Hospital during the morning of the survey. Results The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). Conclusions This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.

Anti-human thymocyte globulin-Fresenius (ATG-F) is frequently utilized to achieve successful induction for kidney transplantation recipients. This study aimed to examine the association between the ATG-F dose-to-recipient-weight ratio (ADR) and the risk of developing urinary tract infections (UTIs) following kidney transplantation. Data of kidney transplant recipients who underwent ATG-F-induction peri-operatively in a medical center were retrospectively collected, and the incidence of UTIs during the first postoperative year was also recorded. The risk of UTI associated with ADR was analyzed, and receiver operating characteristic curves were drawn to determine the optimal ADR, followed by Cox regression models. In total, 131 recipients were included, with an UTI incidence of 19.08% and a mean interval of 3.08 months. The optimal ADR was 6.34, involving 41 and 90 patients in the low ADR and high ADR groups, respectively. The UTI-free rate in the low ADR group was significantly higher than that in the high ADR group (p = 0.007). Cox regression analysis indicated that a high ADR independently increased the risk of UTI following kidney transplantation (hazard ratio: 5.306, 95% confidence interval: 1.243–22.660, p = 0.024). There was no significant difference in rejection rate between the high ADR and low ADR groups. In conclusion, a high ADR increased the incidence of early postoperative UTI among kidney transplant recipients.

ABSTRACTUrinary tract infections (UTIs) are among the most common late-onset infections in preterm infants, characterized by nonspecific symptoms and a pathogenic spectrum that diverges from that of term infants and older children, which present unique diagnostic and therapeutic challenges. Existing data on the role of gut microbiota in UTI pathogenesis in this demographic are limited. This study aims to investigate alterations in gut microbiota and fecal calprotectin levels and their association with the development of UTIs in hospitalized preterm infants. A longitudinal case-control study was conducted involving preterm infants admitted between January 2018 and October 2020. Fecal samples were collected weekly and analyzed for microbial profiles and calprotectin levels. Propensity score matching, accounting for key perinatal factors including age and antibiotic use, was utilized to match samples from UTI-diagnosed infants to those from non-UTI counterparts. Among the 151 preterm infants studied, 53 were diagnosed with a UTI, predominantly caused by Enterobacteriaceae (79.3%) and Enterococcaceae (19.0%). Infants with UTIs showed a significantly higher abundance of these families compared to non-UTI infants, for both Gram-negative and positive pathogens, respectively. Notably, there was a significant pre-UTI increase in the abundance of pathogen-specific taxa in infants later diagnosed with UTIs, offering high predictive value for early detection. Shotgun metagenomic sequencing further confirmed the dominance of specific pathogenic species pre-UTI and revealed altered virulence factor profiles associated with Klebsiella aerogenes and Escherichia coli infections. Additionally, a decline in fecal calprotectin levels was observed preceding UTI onset, particularly in cases involving Enterobacteriaceae. The observed pathogen-specific alterations in the gut microbiota preceding UTI onset offer novel insight into the UTI pathogenesis and promising early biomarkers for UTIs in preterm infants, potentially enhancing the timely management of this common infection. However, further validation in larger cohorts is essential to confirm these findings.

As large amounts of distributed renewable energy generation (DREG) replace conventional generating units on the grid, the tension between the supply lack of flexible resources and the increased demand for flexible resources on the grid intensifies. To address this issue, this paper focuses on distributed renewable energy generation aggregation (DREGA) applications based on energy storage systems (ESS). Considering the interconnection and supply–demand coupling between generation and consumption in the grid, ESS is used to flexibly regulate the flow of electrical energy between producers and consumers in DREGA. A pricing methodology that takes into account aggregation differences and real-time changes based on supply and demand is developed. This method mobilizes resources within the aggregator to help the network operator balance supply and demand through price incentives. Electricity is shared directly between producers and consumers within the aggregation, in addition to indirectly shared through ESS. It improves the self-consumption of renewable energy and the self-supply rate of users from the perspective of aggregators. The validity of the proposed method is proven by case study results.

Abstract To determine the dietary structure and its associated factors of tuberculosis (TB) patients in the community. This cross-sectional study analysed the dietary intake of 300 TB patients in two impoverished counties in China. Food intake was collected by using food frequency and two consecutive 24-h dietary review (24hdr) methods. The dietary composition and dietary structure of TB patients were compared with China’s 2022 Dietary Reference Intake (DRIs) and the average reference value of dietary composition (ARC) in China in 2013. Binary logistic regression models were used to explore the factors associated with inadequate intake of animal food, insufficient protein and fat energy supply in patients with TB. The daily intake of various foods in TB patients was measured and the results were as follows: staple foods—median 372.12 g (interquartile range [IQR] 315.87 g); vegetables—median 200.00 g (IQR 205.55 g); fruits—median 20.22 g (IQR 36.82 g); animal foods—median 100.82 g (IQR 180.74 g); dairy products—median 0.00 g (IQR 0.00 g); nuts—median 17.10 g (IQR 29.75 g). The average daily intakes of vegetables, fruits, animal food, dairy products, soy and nuts were lower than those recommended by the DRIs (P

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Abstract The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin‐related diseases in humans. Here, single‐cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The cross‐species comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis. Moreover, Phenome‐wide association study analysis revealed that the conserved genes between pigs and humans are strongly associated with human skin‐related diseases. In the epidermis, two lineage differentiation trajectories describe hair follicle (HF) morphogenesis and epidermal development. By comparing normal and hairless fetal pigs, it is found that the hair placode (Pc), the most characteristic initial structure in HFs, arises from progenitor‐like OGN+/UCHL1+ cells. These progenitors appear earlier in development than the previously described early Pc cells and exhibit abnormal proliferation and migration during differentiation in hairless pigs. The study provides a valuable resource for in‐depth insights into HF development, which may serve as a key reference atlas for studying human skin disease etiology using porcine models.

To solve the problem of safe and stable grid operation caused by the uncontrollability of renewable energy power generation with a high proportion, this paper focuses on the method of energy storage participation in grid supply and demand balance regulation based on differentiated electricity prices. From the perspective of demand-side and regulable resources, the paper investigates the method of using differentiated electricity prices to improve demand-side responsiveness and expand energy storage operation revenue, so as to explore and activate the potential of regulable resources in the grid. Firstly, the necessity and feasibility of considering differentiated electricity prices are analyzed. Secondly, a demand-side response and energy storage regulation model based on differentiated electricity prices is established, and the supply–demand balance regulation method considering differentiated electricity prices is proposed. Then, the supply–demand balance regulation process under two conditions before and after the implementation of differentiated electricity prices is compared and analyzed through case simulation. Finally, via the practical example, the effectiveness of the method is verified, and the proposed method is able to reduce the demand for energy storage by half in rated power and reduce the rated capacity of the energy storage to 8.66%.

This study addresses the challenges of accurately analyzing the reliability of aviation power systems (APS) using traditional models by introducing the Aviation Power System Reliability Probability Network Model (APS-RPNM). The model directly transforms the system architecture into an equivalent probability network, aiming to develop a precise reliability model that captures system functions and fault logic. By classifying APS components into five distinct structural patterns and mapping them to corresponding nodes in the APS-RPNM, the model is successfully constructed. Specifically, None-Input-to-Multiple-Output components are transformed into two-state nodes, while Multiple-Input-to-None-Output, Single-Input-to-Multiple-Output, and Multiple-Input-to-Single-Output components are mapped to three-state nodes. For Multiple-Input-to-Multiple-Output components, a novel approach employing multiple two-state sub-nodes is adopted to capture their complex functional logic. A case study comparing the performance of the APS-RPNM with the traditional minimal path set method in reliability analysis was conducted. The results demonstrate that the APS-RPNM not only simplifies the model construction process and eliminates errors stemming from subjective engineering judgments but also enables the efficient computation of power supply reliability for all load points in a single inference by integrating all of the components. This significantly improves computational efficiency and system dependency analysis capabilities, highlighting the APS-RPNM’s tremendous potential in optimizing the reliability design of APS.

BackgroundPeer interactions are critical to young children’s social development, and proximal-system has a direct influence on personal growth. The study aims to analyze the relationship between parental psychological control and young children’s peer interactions, as well as the moderating role of teachers’ emotional support in this association.MethodsA total of 241 children aged 3–6 years, alongside their parents, and 27 teachers, participated in the study. Teachers reported children’s peer interactions whilst parents reported their psychological control. The level of teachers’ emotional support was co-coded by two researchers.ResultsThe results of the study indicated that parental psychological control was significantly and negatively related to young children’s peer interactions; teachers’ emotional support was significantly and positively related to young children’s peer interactions; the cross-level moderating effect validates our hypothesis that teachers’ emotional support has a moderating effect between parental psychological control and young children’s peer interactions, buffering the impact of parental psychological control on young children’s peer interactions.ConclusionThese findings expand our comprehension of the association between parental psychological control, teachers’ emotional support, and young children’s peer interactions, and provide guidance for integrating the components of the proximal system and devising interventions to establish a home-school harmony environment that fosters children’s social development.

Summary: Background: The optimal treatment strategy for patent ductus arteriosus (PDA) in extremely preterm infants is currently highly controversial. This study aimed to evaluate the association between PDA treatment and short-term outcomes among extremely preterm infants. Methods: This cohort study included all extremely preterm infants (≤27 and 6/7 weeks) who were admitted to hospitals participating in the Chinese Neonatal Network from January 2019 to December 2021, and were diagnosed to have PDA by echocardiogram. PDA treatment was defined as medical treatment and/or surgical ligation of PDA during hospitalization. Short-term outcomes included death, bronchopulmonary dysplasia (BPD), death/BPD, retinopathy of prematurity, necrotizing enterocolitis, and severe brain injury. Multivariate logistic regression was used to evaluate the association between PDA treatment and outcomes. Subgroup analysis were performed among infants with different respiratory support on 3 and 7 days of life. Findings: A total of 2494 extremely preterm infants with the diagnosis of PDA were enrolled, of which 1299 (52.1%) received PDA treatment. PDA treatment was significantly associated with lower risk of death (adjusted odds ratio, 0.48; 95% confidence interval, 0.38–0.60). The decreased risk of death was accompanied by increased risk of BPD and death/BPD. In subgroup analysis according to respiratory support, PDA treatment was associated with lower risk of death among infants who required invasive ventilation. However, the beneficial effect on death was not significant among infants who did not require invasive ventilation. Interpretation: PDA treatment was associated with reduced mortality in extremely preterm infants, but this beneficial effect was mainly present among infants who required invasive ventilation. Funding: This study was funded by the Shanghai Science and Technology Commission's Scientific and Technological Innovation Action Plan (21Y21900800) and the Canadian Institutes of Health Research (CTP87518).

Background China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases.Methods We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee.Results This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management.Conclusions This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

In industry, forecast prediction and health management (PHM) is used to improve system reliability and efficiency. In PHM, remaining useful life (RUL) prediction plays a key role in preventing machine failures and reducing operating costs, especially for reliability requirements such as critical components in aviation as well as for costly equipment. With the development of deep learning techniques, many RUL prediction methods employ convolutional neural network (CNN) and long short-term memory (LSTM) networks and demonstrate superior performance. In this paper, a novel two-stream network based on a bidirectional long short-term memory neural network (BiLSTM) is proposed to establish a two-stage residual life prediction model for mechanical devices using CNN as the feature extractor and BiLSTM as the timing processor, and finally, a particle swarm optimization (PSO) algorithm is used to adjust and optimize the network structural parameters for the initial data. Under the condition of lack of professional knowledge, the adaptive extraction of the features of the data accumulated by the enterprise and the effective processing of a large amount of timing data are achieved. Comparing the prediction results with other models through examples, it shows that the model established in this paper significantly improves the accuracy and efficiency of equipment remaining life prediction.

Fixed-diamond abrasive wire saw cutting is one of the most common methods for cutting hard and brittle materials. This process has unique advantages including a narrow kerf and the ability to use a relatively small cutting force. In the cutting process, controlling the main process parameters can improve the processing efficiency, obtaining a better processing surface roughness. This work designs the PI controller (Proportional–Integral controller) based on the reciprocating wire saw cutting process. The control objects are the workpiece feed rate and wire saw velocity, and the control objective is the normal cutting force. For the control trials, several reference values of various normal cutting forces were chosen. The effects of feed rate and saw velocity on the cutting surface finish and cutting time were investigated in this work using wire saw cutting analysis on a square monocrystalline silicon specimen. The results of this study showed that under a constant applied force of 2.5 N, the optimal feed rate of the diamond wire through the specimen could reduce cutting time by 42% while achieving a 60% improvement in the measured surface finish. Likewise, optimal control of the wire saw velocity could reduce cycle time by 18% with a 45% improvement in the surface finish. Consequently, the feed speed control is more effective than the wire saw velocity.

The gecko can achieve flexible climbing on various vertical walls and even ceilings, which is closely related to its unique foot adhesion system. In the past two decades, the mechanism of the gecko adhesion system has been studied in-depth, and a verity of gecko-inspired adhesives have been proposed. In addition to its strong adhesion, its easy detachment is also the key to achieving efficient climbing locomotion for geckos. A similar controllable adhesion characteristic is also key to the research into artificial gecko-inspired adhesives. In this paper, the structures, fabrication methods, and applications of gecko-inspired controllable adhesives are summarized for future reference in adhesive development. Firstly, the controllable adhesion mechanism of geckos is introduced. Then, the control mechanism, adhesion performance, and preparation methods of gecko-inspired controllable adhesives are described. Subsequently, various successful applications of gecko-inspired controllable adhesives are presented. Finally, future challenges and opportunities to develop gecko-inspired controllable adhesive are presented.

This study aimed to describe the prevalence of comorbid hypertension and hyperuricemia (HH) and detected the dietary factors for HH in Chinese adults aged 18 to 64 years. All of the data were collected from the China Nutrition and Health Surveillance 2015–2017, with a stratified, multistage, random sampling method on a national scale. A total of 52,627 adult participants aged 18~64 years from the CNHS 2015–2017 were included in this study. HH was identified as SUA level cut-offs for males and females of 420 μmol/L and 360 μmol/L, respectively, with mean systolic blood pressure ≥140 mmHg and/or mean diastolic blood pressure ≥ 90 mmHg and/or received antihypertensive treatment within two weeks. The differences in HH prevalence between or among the subgroups were compared by the Rao–Scott chi-square test. The correlations between HH and covariates or metabolic factors were detected by a weighted two-level multivariate survey logistic regression. The total weighted sufficient intake ratios of beans and nuts, vegetables, and red meat were 59.1%, 46.6%, and 64.8%, respectively. The weighted prevalence of HH in the total participants was 4.7% (95% CI: 4.3–5.0%). The positive effects of bean and nut on HH were observed. The participants who had sufficient bean and nut intake showed lower risk for HH (for the total participants: OR = 0.734, 95% CI = 0.611–0.881). The prevalence of HH might have been a public health problem, and bean and nut intake might be a protective factor for HH in the Chinese population.

Abstract Background Chronic kidney disease (CKD) is prevalent in older adults. In the aging CKD population, cognitive frailty is more common, but its prevalence and associated risk factors need to be further investigated. Methods This is a cross-sectional study that enrolled patients aged ≥ 60 years with a diagnosis of CKD from January 2018 to February 2021. Patients were assessed for frailty and cognition with the FRAIL and the Mini-Mental State Examination (MMSE) scales and were divided into the cognitive frailty and non-cognitive frailty groups. Risk factors for cognitive frailty were identified by univariate and multivariate logistic regression analyses. A prediction model for cognitive frailty was built and a nomogram was plotted. The performance of the nomogram was evaluated by using a concordance index (C-index) and calibration plots. Results A total of 1015 older patients with CKD were enrolled, among whom 607 (59.8%) were males and 408 (40.2%) were females, with an age ranging from 60 to 98 years, and an cognitive frailty prevalence of 15.2%. The prevalence of cognitive frailty varied among the CKD stages 1–5, with rates of 4.7%, 7.5%, 13.8%, 18.5%, and 21.4%, respectively. Multivariate logistic regression analysis showed that age (OR = 1.11, 95%CI 1.08–1.14, p

BackgroundCompared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes. ObjectiveWe aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes. MethodsWe evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results. ResultsAt baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a widespread zoonotic disease seriously threatening Chinese residents' health. HFRS of Weihe Basin remains highly prevalent in recent years and attracts wide attention. With the acceleration of urbanization and related environmental changes, the interaction among anthropogenic activities, environmental factors, and host animals becomes more complicated in this area, which posed increasingly complex challenges for implementing effective prevention measures. Identifying the potential influencing factors of continuous HFRS epidemics in this typical area is critical to make targeted prevention and control strategies.MethodsSpatiotemporal characteristics of HFRS epidemic were analyzed based on HFRS case point data in Weihe Basin from 2005 to 2020. MaxEnt models were constructed to explore the main influencing factors of HFRS epidemic based on HFRS data, natural environment factors and socioeconomic factors.ResultsResults showed that the HFRS epidemics in Weihe Basin were temporally divided into three periods (the relatively stable period, the rapid rising period, and the fluctuating rising period) and were spatially featured by relatively concentrated in the plains alongside the Weihe River. Landscape played controlling effect in this area while land use, vegetation and population in the area interacted with each other and drove the change of HFRS epidemic. The potential high-risk area for HFRS epidemic was 419 km2, where the HFRS case density reached 12.48 cases/km2, especially in the northern plains of Xi'an City.ConclusionWe suggested that the temporal and spatial variations in the HFRS epidemics, as well as their dominant influencing factors should be adequately considered for making and/or adjusting the targeted prevention and control strategies on this disease in Weihe Basin.

BackgroundThe aim of this study was to explore the clinical relevance of linear measures of Wilson's disease (WD).MethodsRelative values of brain atrophy in 30 patients with WD and 30 healthy volunteers were measured and compared using a manual measurement method. Linear measurement indicators of brain atrophy in patients with and without mental disorders were also compared. In addition, correlations of patients' age, disease duration, and Unified Wilson's Disease Rating Scale (UWDRS) scores with brain atrophy indicators were determined.ResultsThe results showed that the e-value, Huckman number, Evans index, and lateral ventricular body index were higher in the WD group compared with the control group. The age of patients with WD was negatively correlated with the k-value and significantly positively correlated with the brainstem index. WD duration was prominently positively correlated with the d-value and negatively correlated with the j-value. In addition, neurological function scores were significantly positively correlated with the c-value, e-value, caudate nucleus index, Huckman number, Evans index, and lateral ventricular body index. By contrast, patients with psychiatric symptoms had a higher a-value and fourth ventricular index than those without psychiatric symptoms.ConclusionTherefore, it can be concluded that patients with WD and those with psychiatric symptoms have more severe brain atrophy compared to normal subjects. The patient's age, disease duration, and neurological function scores were positively correlated with the severity of brain atrophy.

Abstract Background Aging metrics incorporating cognitive and physical function are not fully understood, hampering their utility in research and clinical practice. This study aimed to determine the proportions of vulnerable persons identified by three existing aging metrics that incorporate cognitive and physical function and the associations of the three metrics with mortality. Methods We considered three existing aging metrics including the combined presence of cognitive impairment and physical frailty (CI-PF), the frailty index (FI), and the motoric cognitive risk syndrome (MCR). We operationalized them using data from the China Health and Retirement Longitudinal Study (CHARLS) and the US National Health and Nutrition Examination Survey (NHANES). Logistic regression models or Cox proportional hazards regression models, and receiver operating characteristic curves were used to examine the associations of the three metrics with mortality. Results In CHARLS, the proportions of vulnerable persons identified by CI-PF, FI, and MCR were 2.2, 16.6, and 19.6%, respectively. Each metric predicted mortality after adjustment for age and sex, with some variations in the strength of the associations (CI-PF, odds ratio (OR) (95% confidence interval (CI)) 2.87 (1.74–4.74); FI, OR (95% CI) 1.94 (1.50–2.50); MCR, OR (95% CI) 1.27 (1.00–1.62)). CI-PF and FI had additional predictive utility beyond age and sex, as demonstrated by integrated discrimination improvement and continuous net reclassification improvement (all P

Background: Feeding intolerance (FI) is a significant concern in the care of preterm infants, impacting their growth and development. We previously reported that FI is linked to lower fecal calprotectin (FC) levels. This study aims to explore the postnatal dynamics and interplay between microbiota, metabolic profiles, and host immunity in preterm infants with and without FI. Methods: Infants with gestational age

Their unique layered structure, large specific surface area, good stability, high negative charge density between layers, and customizable composition give layered double hydroxides (LDHs) excellent adsorption and detection performance for heavy metal ions (HMIs). However, their easy aggregation and low electrical conductivity limit the practical application of untreated LDHs. In this work, a ternary MgZnFe-LDHs engineered porous biochar (MgZnFe-LDHs/PBC) heterojunction was proposed as a sensing and adsorption material for the effective detection and removal of Cd2+ from wastewater. The growth of MgZnFe-LDHs in the PBC pores not only reduces the accumulation of MgZnFe-LDHs, but also improves the electrical conductivity of the composite. The synergistic effect between MgZnFe-LDHs and PBC enables the composite to achieve a maximum adsorption capacity of up to 293.4 mg/g for Cd2+ in wastewater. Meanwhile, the MgZnFe-LDHs/PBC-based electrochemical sensor shows excellent detection performance for Cd2+, presenting a wide linear range (0.01 ng/L–1 mg/L), low detection limit (3.0 pg/L), good selectivity, and stability. The results indicate that MgZnFe-LDHs/PBC would be a potential material for detecting and removing Cd2+ from wastewater.

Hard and brittle materials have excellent physical and mechanical properties and are widely used in the fields of microelectronics and optoelectronics. However, due to their high hardness and brittleness, the machining quality of a workpiece struggles to meet the requirements of practical applications. In order to improve the surface quality of deep-hole machining of hard and brittle materials, this article analyzes the formation mechanism of surface roughness and the exit-chipping width during the drilling machining of hard and brittle materials and establishes a mathematical prediction model for the surface roughness and the exit-chipping width of hard and brittle materials using a trepanning cutter. The experimental study on K9 optical glass machining shows that the surface roughness of the workpiece and the exit-chipping width increase with the increase in feed rate, and decrease with the increase in rotational speed. Through comparison and verification between theoretical and experimental values, the average errors of workpiece surface roughness and the exit-chipping width are 13.15% and 6.73%, respectively. This article analyzes the reasons for the errors. The results indicate that the theoretical model proposed in this article can be used to predict the surface roughness and the exit-chipping width of hard and brittle materials processed under the same conditions, providing a theoretical basis to optimize process parameters to improve the surface quality of the workpiece.

Abstract The roles of oncogenic KRAS in tumor immune evasion remain poorly understood. Here, mutant KRAS is identified as a key driver of tumor immune evasion in colorectal cancer (CRC). In human CRC specimens, a significant reduction in cytotoxic CD8+ T‐cell tumor infiltration is found in patients with mutant versus wild type KRAS. This phenomenon is confirmed by preclinical models of CRC, and further study showed KRAS mutant tumors exhibited poor response to anti‐PD‐1 and adoptive T‐cell therapies. Mechanistic analysis revealed lactic acid derived from mutant KRAS‐expressing tumor cells sensitized tumor‐specific cytotoxic CD8+ T‐cells to activation‐induced cell death via NF‐κB inactivation; this may underlie the inverse association between intratumoral cytotoxic CD8+ T‐cells and KRAS mutation. Importantly, KRAS mutated tumor resistance to immunotherapies can be overcome by inhibiting KRAS or blocking lactic acid production. Together, this work suggests the KRAS‐mediated immune program is an exploitable therapeutic approach for the treatment of patients with KRAS mutant CRC.

Background. Kawasaki disease (KD) is characterized by a disordered inflammation response of unknown etiology. Immune cells are closely associated with its onset, although the immune-related genes’ expression and possibly involved immune regulatory mechanisms are little known. This study aims to identify KD-implicated significant immune- and inflammation-related biomarkers and pathways and their association with immune cell infiltration. Patients and Methods. Gene microarray data were collected from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to find KD hub markers. GSEA was used to assess the infiltration by 28 immune cell types and their connections to essential gene markers. Receiver operating characteristic (ROC) curves were used to examine hub markers’ diagnostic effectiveness. Finally, hub genes’ expressions were validated in Chinese KD patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results. One hundred and fifty-one unique genes were found. Among 10 coexpression modules at WGCNA, one hub module exhibited the strongest association with KD. Thirty-six overlapping genes were identified. Six hub genes were potential biomarkers according to LASSO analysis. Immune infiltration revealed connections among activated and effector memory CD4+ T cells, neutrophils, activated dendritic cells, and macrophages. The six hub genes’ diagnostic value was shown by ROC curve analysis. Hub genes were enriched in immunological and inflammatory pathways. RT-qPCR verification results of FCGR1B (P

BackgroundTurner syndrome is a rare systemic disease and a significant proportion of these patients experience aortic coarctation. Selection of optimal therapy for aortic coarctation in patients with Turner syndrome is difficult due to the pathologic change of the systemic vessel.Case presentationWe report one successful case of covered stent implantation for the treatment of severe native coarctation of the aorta in a 15-year-old patient with Turner syndrome weighing 36 kg. A covered stent was implanted in this patient. After the stent implantation, the peak systolic pressure gradient immediately decreased from 48 mmHg to 14 mmHg. The aortic diameter at the coarctation site increased from 3 mm to 10 mm after stenting. A femoral arterial complication occurred in this case, and we stabilized the situation finally.ResultsDuring a follow-up of 3 years, no restenosis of aortic coarctation was observed and the patient no longer experienced hypertension. The dissection of the right femoral artery remained stable.ConclusionA covered stent implantation for severe aortic coarctation in patients with Turner syndrome could be safe and effective. However, caution should be taken when using the technique to prevent complications.

Case PresentationA 3-year-and-6-month-old child was reported to have recurrent high fever with generalized lymph node enlargement and significant elevation of inflammatory markers such as C-reactive protein and procalcitonin in tests. Later, whole exome sequencing determined that the child's disease was haploinsufficiency of A20 (HA20).ResultsAfter immunosuppressive therapy, the child's symptoms improved significantly, and the inflammatory markers dropped to the normal range.ConclusionBecause of the characteristics of HA20, this disease is often underdiagnosed and misdiagnosed in clinical practice. By reporting this case of HA20 in a child, we hope to increase the awareness of this disease in the clinic.

Objectives To examine the association between housing types and COVID-19 infection (or mental health) during the early stages of the pandemic by using the large-scale individual-level All of Us Research Program COVID-19 Participant Experience (COPE) survey data. We hypothesise that housing types with a shared component are associated with elevated COVID-19 infection and subsequent mental health conditions.Design A retrospective case–control study.Setting Secondary analysis of online surveys conducted in the USA.Participants 62 664 participant responses to COPE from May to July 2020.Primary and secondary outcome measures Primary outcome measure is the self-reported COVID-19 status, and the secondary outcome measures are anxiety or stress. Both measures were applied for matched cases and controls of the same race, sex, age group and survey version.Results A multiple logistic regression analysis revealed that housing types with a shared component are significantly associated with COVID-19 infection (OR=1.19, 95% CI 1.1 to 1.3; p=2×10−4), anxiety (OR=1.26, 95% CI 1.1 to 1.4; p=1.1×10−6) and stress (OR=1.29, 95% CI 1.2 to 1.4; p=4.3×10−10) as compared with free-standing houses, after adjusting for confounding factors. Further, frequent optional shopping or outing trips, another indicator of the built environment, are also associated with COVID-19 infection (OR=1.36, 95% CI 1.1 to 1.8; p=0.02), but not associated with elevated mental health conditions. Confounding factors are controlled in the analysis such as ethnicity, age, social distancing behaviour and house occupancy.Conclusion Our study demonstrates that houses with a shared component tend to have an increased risk of COVID-19 transmission, which consequently leads to high levels of anxiety and stress for their dwellers. The study also suggests the necessity to improve the quality of the built environment such as residential housing and its surroundings through planning, design and management, ensuring a more resilient society that can cope with future pandemics.

The extreme precipitation threshold is fundamental to extreme precipitation research, directly affecting the cognition of extreme characteristics. Based on the daily precipitation data of 62 meteorological stations from 1985 to 2005, this study uses parametric and non-parametric approaches to determine the extreme precipitation threshold in Central Asia, analyzes the statistics and spatial distribution of different threshold criteria, and discusses the trend of extreme precipitation. The capability of the grid dataset of APHRODITE and GPCC in the extreme precipitation analysis in Central Asia is evaluated from the threshold perspective. The results are as follows: 1) Contrary to the parametric approach, the threshold determined by the percentile indices in the warm season is slightly higher than in the cold season. The mean threshold of the warm (cold) season in Central Asia is defined by the 95th percentile index and the 10-year return period, which are 14.0 mm (13.5 mm) and 24.2 mm (25.7 mm), respectively. 2) The spatial distribution of extreme precipitation threshold in Central Asia is higher in the southeast and lower in the north during the cold season; In the warm season, it is high in the north and southwest and low in the center. 3) Although both APHRODITE and GPCC datasets can basically reproduce the spatial distribution of extreme precipitation threshold, they underestimate the magnitude of the threshold, especially APHRODITE. 4) There is no obvious extreme precipitation trend in Central Asia during the study period. Furthermore, the trend in characteristics of extreme precipitation based on different thresholds shows a consistent trend in time but not spatially. We suggest that the threshold selection should adjust the balance between sufficient samples and extreme values according to actual conditions. The results of this study can provide a reference for extreme precipitation threshold criteria under specific application conditions in Central Asia.

Photoreceptors in the retina are highly specialized neurons with photosensitive molecules in the outer segment that transform light into chemical and electrical signals, and these signals are ultimately relayed to the visual cortex in the brain to form vision. Photoreceptors are composed of rods and cones. Rods are responsible for dim light vision, whereas cones are responsible for bright light, color vision, and visual acuity. Photoreceptors undergo progressive degeneration over time in many hereditary and age-related retinal diseases. Despite the remarkable heterogeneity of disease-causing genes, environmental factors, and pathogenesis, the progressive death of rod and cone photoreceptors ultimately leads to loss of vision/blindness. There are currently no treatments available for retinal degeneration. Cyclic guanosine 3′, 5′-monophosphate (cGMP) plays a pivotal role in phototransduction. cGMP governs the cyclic nucleotide-gated (CNG) channels on the plasma membrane of the photoreceptor outer segments, thereby regulating membrane potential and signal transmission. By gating the CNG channels, cGMP regulates cellular Ca2+ homeostasis and signal transduction. As a second messenger, cGMP activates the cGMP-dependent protein kinase G (PKG), which regulates numerous targets/cellular events. The dysregulation of cGMP signaling is observed in varieties of photoreceptor/retinal degenerative diseases. Abnormally elevated cGMP signaling interferes with various cellular events, which ultimately leads to photoreceptor degeneration. In line with this, strategies to reduce cellular cGMP signaling result in photoreceptor protection in mouse models of retinal degeneration. The potential mechanisms underlying cGMP signaling-induced photoreceptor degeneration involve the activation of PKG and impaired Ca2+ homeostasis/Ca2+ overload, resulting from overactivation of the CNG channels, as well as the subsequent activation of the downstream cellular stress/death pathways. Thus, targeting the cellular cGMP/PKG signaling and the Ca2+-regulating pathways represents a significant strategy for photoreceptor protection in retinal degenerative diseases.

4H-SiC (silicon carbide) is widely used in semiconductor devices due to its superior characteristics. However, processing techniques such as cutting, grinding, and polishing generally have problems such as low processing efficiency, high cost, difficulties guaranteeing processing quality, and serious material waste. The in-depth research on the mechanical behavior, material removal, and damage mechanism of SiC single crystals at the micro/nano scale is the foundation for solving these problems. This paper establishes a molecular dynamics simulation model for 4H-SiC single-crystal nano scratches, using three different directions of a Berkovich indenter to scratch the surface of the workpiece, studying the surface morphology, scratching force, and material removal during the scratching process. The results indicate that scratching directions of the tool varies, and the surface morphology also varies. After the scratching depth exceeds 1.6 nm, complete dislocations with a Burges vector of 1/32¯10> appear on the crystal subsurface, leading to the plastic removal of the material. During the process of material removal, a smaller tool rake angle removes a larger amount of material chips. By analyzing the damage layer of the workpiece, the difference in the damage layer is smaller when the scratching direction is different, but the damage layer generated by the smaller rake angle of the scratching tool is thinner. It shows that the scratching force and workpiece temperature are relatively small when the rake angle of the scratching tool is small. Therefore, when scratching 4H-SiC single crystals, choosing a tool with a smaller rake angle is more beneficial for the process.

Rhododendron aureum is identified as a vulnerable species in China. The establishment of an in vitro regeneration system assists significantly in species protection. Here, an in vitro regeneration system was developed using both direct and indirect organogenesis pathways. The role of thidiazuron (TDZ) in different developmental stages was also investigated. The leaves of wild-harvested R. aureum plants were used for callus induction after hydroponic cultivation. The optimal formula was found to be woody plant basal medium (WPM) supplemented with 0.5 mg·L−1 TDZ and 0.5 mg·L−1 3-indolebutyric acid (IBA), while the optimal formula for the subculture and induction of adventitious buds was WPM containing 0.1 mg·L−1 TDZ and 0.5 mg·L−1 IBA. The leaves from tissue-cultured seedlings were then used for the induction of bud clusters. An association was observed between the differentiation of bud clusters and the ratio of auxin and cytokinin. The optimal formula for the induction of bud clusters was WPM containing 0.5 mg·L−1 TDZ and 0.1 mg·L−1 IBA, yielding a 50% induction rate and the maximum number of buds. Higher concentrations of TDZ were found to be beneficial for bud proliferation, while a lower concentration was conducive to stem elongation. The optimal formula for subculture was WPM containing 0.1 mg·L−1 TDZ and 0.5 mg·L−1 IBA, while that for stem elongation was WPM supplemented with 0.002 mg·L−1 TDZ and 0.5 mg·L−1 IBA. Only IBA was found to be necessary for rooting, with increased IBA concentrations leading to an increased number of roots and earlier root formation, with larger callus areas; thus, an IBA concentration of 1.0 mg·L−1 was found to be optimal for the rooting of R. aureum. After hardening the seedlings for two days, a substrate composed of vermiculite and peat soil in a 10:1 ratio was identified as a transplantation formula. This system provides directions both for the protection of endangered species and the promotion of industrial development.

Monocrystalline silicon is widely used in the semiconductor market, but its hard and brittle physical properties make processing difficult. Fixed-diamond abrasive wire-saw (FAW) cutting is currently the most commonly used cutting method for hard and brittle materials due to advantages such as narrow cutting seams, low pollution, low cutting force and simple cutting process. During the process of cutting a wafer, the contact between the part and the wire is curved, and the arc length changes during the cutting process. This paper establishes a model of contact arc length by analyzing the cutting system. At the same time, a model of the random distribution of abrasive particles is established to solve the cutting force during the cutting process, using iterative algorithms to calculate cutting forces and chip surface saw marks. The error between the experiment and simulation of the average cutting force in the stable stage is less than 6%, and the errors with respect to the central angle and curvature of the saw arc on the wafer surface are less than 5% between the experiment and simulation. The relationship between the bow angle, contact arc length and cutting parameters is studied using simulations. The results show that the variation trend of the bow angle and contact arc length is consistent, increasing with an increase in the part feed rate and decreasing with an increase in the wire velocity.

Hard and brittle materials have excellent physical and mechanical performance, which are widely applied in the fields of microelectronics and optoelectronics. However, deep-hole machining of hard and brittle materials is very difficult and inefficient due to the high hardness and brittleness of these materials. To improve the quality and efficiency of deep-hole machining of hard and brittle materials, according to the brittle crack fracture removal mechanism of hard and brittle materials and the cutting model of the trepanning cutter, an analytical cutting force prediction model of hard and brittle materials processed using a trepanning cutter is established. This experimental study of K9 optical glass machining shows that as the feeding rate increase, the cutting force increase, and as the spindle speed increase, the cutting force decrease. By comparing and verifying the theoretical and experimental values, the average errors of axial force and torque are 5.0% and 6.7%, respectively, and the maximum error is 14.9%. This paper analyzes the reasons for the errors. The results indicate that the cutting force theoretical model can be used to predict the axial force and torque of machining hard and brittle materials under the same conditions, which provides a theory for optimizing machining process parameters.

ABSTRACT Soil nutrients and microbial community play a central role in determining crop productivity in agroecosystems. However, the relationship between microbial community structure and soil nutrients in various crop rotation-fallow systems remains unclear. Thus, we designed a 3-year crop rotation-fallow field with five cropping systems (one continuous cropping, three rotational cropping, and one fallow system). We conducted a comprehensive analysis by evaluating crop yield, soil physicochemical properties, and overall bacteria composition. Our results showed that rotation-fallow treatments markedly influenced the crop yield and soil physicochemical properties. Proteobacteria, Acidobacteriota, and Chloroflexi were the dominant phyla in all rotation-fallow treatments. pH, available-phosphorus, total nitrogen, and soil organic matter had considerable effects on the soil bacterial community structure in 2019; however, only available-phosphorus had an impact on soil bacterial community in each treatment in 2020. In summary, with the increase of tillage years, different rotational fallow systems can increase paddy yield by promoting soil nutrient uptake and increasing the relative abundances of bacteria in paddy fields. IMPORTANCE Soil nutrients and microbial community play a central role in determining crop productivity. Therefore, elucidating the microbial mechanisms associated with different cropping systems is indispensable for understanding the sustainability of agroecosystem. In the present study, we designed a 3-year field rotation experiment using five cropping systems, including one continuous cropping, three rotational cropping, and one fallow system, to indagate the outcomes of soil microbial community structures in the different tillage systems. Our results showed that the different rotational fallow systems had positive impacts on crop yield, soil physicochemical properties, and bacterial community structure and that available phosphorus might be a key determinant for the limited bacterial community structure in various rotation-fallow systems following a 3-year field experiment. This study suggests that crop rotation-fallow systems play critical roles in improving bacterial community structure.

BackgroundPompe disease is usually considered in children with elevated creatine kinase (CK) levels and decreased acidic α-glucosidase (GAA) enzyme activity. However, there are exceptions, such as GAA pseudo deficiency alleles, which result in lower GAA enzyme activity but do not cause Pompe disease. Here, we report two cases presenting with high CK levels and low GAA activity who were ultimately diagnosed with Duchenne muscular dystrophy (DMD).Case PresentationCase 1 patient was a 2-month-old boy who presented with an extremely high serum CK level (5,480∼11,880 U/L) and low GAA activity (2.72 nmol/1 h/mg). The whole-exome sequencing did not find the pathogenic GAA gene mutation, however, there was a DMD gene hemizygous variation (c. 7657C > T, p. Arg2553Ter) inherited from his mother, which was verified by the first-generation sequencing. Further genetic analysis of GAA identified two homozygous pseudo deficiency alleles (c.1726G > A, p. Gly576Ser and c.2065G > A, p. Glu689Lys), which were believed to induce the patient’s low GAA activity. Therefore, the boy was diagnosed with DMD, although he had extremely low GAA activity. Case 2 patient was also a 2-month-old boy presenting with a significant increase in CK level (12,408∼24,828 U/L). His blood GAA activity (colorimetric method) was 9.02 nmol/1 h/mg. Similarly, his whole-exome sequencing did not find the pathogenic mutation of the GAA gene, but a DMD gene hemizygous variation (c.5571del, p. Lys1857AsnfsTer8), hence he was diagnosed with DMD as well. Regarding GAA activity, the case 2 patient was not as low as the case 1 patient, mainly because his two GAA pseudo deficiency alleles were heterozygous.ConclusionPompe disease is usually screened in infants with high CK levels. We should be aware that pseudo deficiency alleles can cause low GAA activities but not Pompe disease. Genetic tests would be helpful to distinguish cases with GAA pseudo deficiency alleles from patients with some muscular disorder diseases such as DMD.

Fraxinus mandshurica is a widely used greening and ornamental tree species. However, its genetic transformation system has been hampered by problems such as low transformation efficiency, among others, which can hinder research related to molecular breeding and the analysis of functional genes. Thus, in this study, a novel genetic transformation method for efficient transformation of the embryonic callus of Fraxinus mandshurica was investigated. The method was optimized in terms of factors such as antibiotics, infection solution concentrations, co-culture time, and somatic embryo maturation. The results indicated that the optimal antibiotic concentration was 10 mg·L−1 of hygromycin (Hyg). At this point, the callus proliferation multiple was only 0.12. The highest transformation efficiency was found to be 93.93% when the absorbance of the infection solution concentration at OD600 was 0.4. Interestingly, transformation efficiency was found to be highest (77.9%) at 48 h of co-culture, with a GUS staining rate of 88.23%. The medium for somatic embryo maturation of transformed callus was half-strength MS medium (MS 1/2) containing 60 g·L−1 polyethylene glycol, 1 mg·L−1 abscisic acid, 400 mg·L−1 casein enzymatic hydrolysate (CH), 20 g·L−1 sucrose, 1 g·L−1 activated charcoal, and 5 g·L−1 gellan gum. The medium for somatic embryo germination was MS ½, containing 0.2 mg·L−1 of N-(Phenylmethyl)-9H-purin-6-amine(6-BA) and 5.0 mg·L−1 of gibberellin (GA). These results are of significance for the verification of the gene function and future genetic improvement of Fraxinus mandshurica.

Hard and brittle materials such as monocrystalline silicon still occupy an important position in the semiconductor industry, but hard and brittle materials are difficult to process because of their physical properties. Fixed-diamond abrasive wire-saw cutting is the most widely used method for slicing hard and brittle materials. The diamond abrasive particles on the wire saw wear to a certain extent, which affects the cutting force and wafer surface quality in the cutting process. In this experiment, keeping all the given parameters unchanged, a square silicon ingot is cut repeatedly with a consolidated diamond abrasive wire saw until the wire saw breaks. The experimental results show that the cutting force decreases with the increase in cutting times in the stable grinding stage. The wear of abrasive particles starts at the edges and corners, and the macro failure mode of the wire saw is fatigue fracture. The fluctuation of the wafer surface profile gradually decreases. The surface roughness of wafer is steady during the wear steady stage, and the large damage pits on the wafer surface are reduced in the whole process of cutting.

Abstract Robot deburring is an effective method for improving the surface quality of the high‐voltage copper contact. The first step of robot deburring is to acquire the burr images. We propose a new burr mathematical model and build a real burr image dataset for burr image denoising. In order to improve burr image denoising effects of the high‐voltage copper contact, this study proposes an online burr image denoising algorithm, that is, block cosparsity overcomplete learning transform algorithm (BCOLTA). The penalty term and the condition number are affected by the burr parameter. The clustering and transform alternate minimisation algorithms are adopted to achieve lower computational cost and better denoising effect. In addition, BCOLTA also has a good adaptibility to inherent noise images, especially in Gaussian noise. Compared with other traditional and deep learning algorithms by no reference and full reference image quality assessment methods, BCOLTA has state‐of‐the‐art denoising effects and computational complexity on dealing with burr images. This research will play an important role in the intelligent manufacturing field.

In power systems, various types of disturbances can randomly affect the active power balance, which can result in unexpected frequency changes. A battery energy storage system (BESS) is an effective technique to assist power system primary frequency control. In this work, a comprehensive self-adaptive strategy considering load disturbance types is proposed that enables BESS participation in the primary frequency control of power grids. First, the different types of load disturbances in the power system are divided into two categories, namely, step disturbance and continuous small disturbance. Then, the advantages of virtual inertia control and virtual droop control are taken into full consideration. Model A and Model B are proposed to match the two load disturbance types. Model A is used to rapidly prevent sudden changes in frequency under step disturbance conditions without restricting the state of charge (SOC) of the BESS. Under the conditions of continuous small disturbances, we further propose Model B in which primary frequency control is realized while considering SOC recovery. Compared with the previous primary frequency control methods, the presented approach significantly improves the stability of complicated and changeable power systems. Meanwhile, it fulfills the frequency control requirements with superior frequency control performance.

Hair placode formation is an important stage of hair follicle morphogenesis and it is a complex process facilitated by non-coding RNAs. In this study, we conducted whole transcriptome sequencing analysis of skin, heart, liver, lung, and kidney tissues of day 41 (E41) normal and hairless pig embryos, and respectively detected 15, 8, and 515 skin-specific differentially expressed (DE) lncRNAs, miRNAs, and mRNAs. Furthermore, 18 competing endogenous RNA (ceRNA) networks were constructed. Following weighted gene co-expression network analysis (WGCNA) of stages E39, E41, E45, E52, and E60, between normal and hairless pig embryos, only two ceRNAs (lncRNA2162.1/miR-29a-5p/BMPR1b and lncRNA627.1/miR-29a-5p/EDAR) that showed period-specific differential expression in E41 skin were retained. Dual-luciferase reporter assays further indicated that EDAR was a direct, functioning target of miR-29a-5p and that no binding site was found in BMPR1b. Moreover, miR-29a-5p overexpression inhibited the mRNA and protein expression of EDAR while no significant differential expression of BMPR1b was detected. In addition, over-expressed lncRNA627.1 reduces the expression of miR-29a-5p and increase EDAR expression while inhibits lncRNA627.1 resulted in a opposite expression trend. Cell proliferation result demonstrated that lower expression of EDAR and lncRNA627.1 inhibited hair placode precursor cells (HPPCs) proliferation in a manner similar to that shown by over-expressed miR-29a-5p. This study identified that miR-29a-5p inhibited HPPCs proliferation via the suppression of EDAR expression in the EDA/EDAR signaling pathway, while lncRNA627.1 rescues EDAR expression. Our study provides a basis for a better understanding of the mechanisms underlying the ceRNA complex, miR29a-5p/EDAR/lncRNA627.1, that could regulate hair placode formation, which may help decipher diseases affecting human hair.

Heart failure is characterized by the inability of the heart to pump effectively and generate proper blood circulation to meet the body’s needs; it is a devastating condition that affects more than 100 million people globally. In spite of this, little is known about the mechanisms regulating the transition from cardiac hypertrophy to heart failure. Previously, we identified a cardiomyocyte-enriched gene, CIP, which regulates cardiac homeostasis under pathological stimulation. Here, we show that the cardiac transcriptional factor GATA4 binds the promotor of CIP gene and regulates its expression. We further determined that both CIP mRNA and protein decrease in diseased human hearts. In a mouse model, induced cardiac-specific overexpression of CIP after the establishment of cardiac hypertrophy protects the heart by inhibiting disease progression toward heart failure. Transcriptome analyses revealed that the IGF, mTORC2 and TGFβ signaling pathways mediate the inhibitory function of CIP on pathologic cardiac remodeling. Our study demonstrates GATA4 as an upstream regulator of CIP gene expression in cardiomyocytes, as well as the clinical significance of CIP expression in human heart disease. More importantly, our investigation suggests CIP is a key regulator of the transition from cardiac hypertrophy to heart failure. The ability of CIP to intervene in the onset of heart failure suggests a novel therapeutic avenue of investigation for the prevention of heart disease progression.

On-orbit periodic thermal loads degrade the reflector surface accuracy of AstroMesh antennas. To address this problem, a surface shape stability design method is proposed to passively pre-control the on-orbit thermal deformation of mesh reflectors, in which the structural parameters are properly designed to make the internal forces of the whole structure change coordinately and the surface shape of cable-mesh antennas insensitive to thermal loads. First, mathematical models of mechanical-thermal matching (MTM) are established for AstroMesh reflectors, in which an MTM model is developed for the cable net structure and the reflector membrane is equivalent to a cable net structure according to the force balance and thermal deformation coordination relationships. Then, based on the mathematical models, a surface shape stability design strategy is presented for AstroMesh antennas to properly design the cross-sectional dimensions of the cables. Finally, typical AstroMesh reflector structures are designed using the proposed method and simulation results show that the thermal deformations of the obtained AstroMesh reflectors are quite small under the whole temperature range.

Medication safety and efficacy-related pharmacogenomic research play a critical role in precision medicine. This study comprehensively analyzed the pharmacogenomic profiles of the central Han Chinese population in the context of medication safety and efficacy and compared them with other global populations. The ultimate goal is to improve medical treatment guidelines. We performed whole-genome sequencing in 487 Han Chinese individuals and investigated the allele frequencies of pharmacogenetic variants in 1,731 drug response-related genes. We identified 2,139 (81.18%) previously reported variants in our population with annotations in the PharmGKB database. The allele frequencies of these 2,139 clinical-related variants were similar to those in other East Asian populations but different from those in other global populations. We predicted the functional effects of nonsynonymous variants in the 1,731 pharmacogenes and identified 1,281 novel and 4,442 previously reported deleterious variants. Of the 1,281 novel deleterious variants, five are common variants with an allele frequency >5%, and the rest are rare variants with an allele frequency

BackgroundExisting aging metrics incorporating cognitive and physical function are often not feasible for application in research and clinical practice. Therefore, this study aimed to develop and validate a new simple functional score based on self-reported cognitive and physical function in the older Chinese population.MethodsThe development sample included 3,929 older adults aged 60–95 years from the China Health and Retirement Longitudinal Study (CHARLS). The validation sample included 1,345 older adults aged 60–87 years from the Rugao Longitudinal Aging study (RLAS). Logistic regression models and receiver operating characteristic curves were used to examine the associations of the new functional score with all-cause mortality risk.ResultsSix items were selected to construct the new functional score in CHARLS. This functional score was associated with all-cause mortality risk, with an adjusted odds ratio of 1.10 (95% confidence interval = 1.07, 1.13). This functional score presented additional predictive utility beyond age and sex, as demonstrated by the significantly increased C-statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (NRI) (all P < 0.001). Furthermore, this functional score was further validated in RLAS, such that adding the new functional score to a model of age and sex improved all-cause mortality risk discrimination (IDI = 0.036, P < 0.001; NRI = 0.485, P < 0.001). To facilitate the quick screening of the older population with deteriorations in cognitive and physical function, we introduced a publicly available online tool designed for this new functional score.ConclusionsA new functional score based on six self-reported items was developed and validated in the older Chinese population, and was demonstrated to be a simple and practical tool to assess functional deterioration, showing good feasibility, and performance.