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Abstract Hypertrophic scar (HS), which results from prolonged inflammation and excessive fibrosis in re‐epithelialized wounds, is one of the most common clinical challenges. Consequently, sophisticated transdermal transfersome nanogels (TA/Fu‐TS) are prepared to control HS formation by synergistically inhibiting inflammation and suppressing fibrosis. TA/Fu‐TSs have unique structures comprising hydrophobic triamcinolone acetonide (TA) in lipid multilayers and hydrophilic 5‐fluorouracil in aqueous cores, and perform satisfactorily with regard to transdermal co‐delivery to macrophages and HS fibroblasts in emerging HS tissues. According to the in vitro/vivo results, TA/Fu‐TSs not only promote macrophage phenotype‐switching to inhibit inflammation by interleukin‐related pathways, but also suppress fibrosis to remodel extracellular matrix by collagen‐related pathways. Therefore, TA/Fu‐TSs overcome prolonged inflammation and excessive fibrosis in emerging HS tissues, and provide an effective therapeutic strategy for controlling HS formation via their synergy of macrophage phenotype‐switching and anti‐fibrosis effect.

Abstract This article presents a closed‐form synthesis method for wideband bandpass filters with suppressed harmonics, where stepped‐impedance resonators (SIRs), scaled lines, and vertically installed planar (VIP) structures are introduced to improve the in‐band and out‐of‐band performances. By combining SIRs and scaled lines, the rejection level of the filter is greatly improved and a more compact size is achieved. And the VIP structures help to bring wide passband as well as suppressed harmonics. Then, a 3rd‐order filter is designed to verify the validity of the proposed method and topology. The simulated and measured results demonstrate that the proposed design has a wide passband (FBW = 52.9%), low insertion loss (

Abstract Background and aims Diagnosis of leptomeningeal metastasis (LM) is challenging. In our previous study, CEACAM6 mRNA was found to be highly expressed in the circulating tumor cells of cerebrospinal fluid (CSF) from patients with lung adenocarcinoma with LM (LUAD‐LM). The aim of this study was to identify whether CEACAM6 could be used as a biomarker for LUAD‐LM. Materials and methods The level of CEACAM6 was determined by enzyme‐linked immunosorbent assay (ELISA) in CSF from 40 LUAD‐LM and 44 normal controls, and additional serum samples from 138 LUAD patients, including 12 LUAD‐LM patients, and 30 healthy controls. Carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21‐1) and neuron‐specific enolase (NSE) levels in the CSF and sera were detected by chemiluminescent immunoassay. Receiver operating characteristic curve was plotted to evaluate the diagnostic performance for LUAD‐LM. Results CSF CEACAM6 level was higher in LUAD‐LM than that in normal controls. In serum, LUAD patients had a higher level of CAECAM6 than healthy controls, and LM patients had the highest level among them. Serum CEACAM6 had a higher AUC than CEA in differentiating LM from non‐LM in LUAD patients (0.95 vs. 0.64, p

Abstract Blood pressure and pulse pressure (PP) had their own characteristics in the elderly population. This cross‐sectional study including 5030 elderly participants was conducted to describe the distribution of blood pressure and wide PP in the elderly population and find influencing factors of wide PP. Wide PP was defined as PP equal to or more than 65 mmHg, and was classified three types as low systolic blood pressure (SBP) and low diastolic blood pressure (DBP) (LSLD), high SBP and low DBP (HSLD), and high SBP and high DBP (HSHD). Using multivariate logistic regression models to analyze the associations of demographic factors, health‐related factors and lifestyle factors with different wide PP types. The associations of lifestyles with wide PP by gender were estimated by subgroup analyses. Among 5030 elderly participants, 2727 (54.2%) participants had wide PP. Logistic regression models showed older age (OR = 2.48, 95%CI: 2.14‐2.88), female (OR = 1.31, 95%CI: 1.07‐1.60), not married (OR = 1.26, 95%CI: 1.07‐1.49), having chronic diseases (OR = 1.28, 95%CI: 1.09‐1.50), current alcohol drinker (OR = 1.29, 95%CI: 1.11‐1.50) were positively associated, and higher body height (OR = .78, 95%CI: .62‐.99), higher education level (OR = .60, 95%CI: .43‐.82), current smoker (OR = .79, 95%CI: .64‐.97) were negatively associated with wide PP. Among three different types of wide PP including LSLD, HSLD, HSHD, these factors had different effects. Subgroup analyses found that only among male, current smoker was negatively associated and current alcohol drinker was positively associated with wide PP.

Abstract In a high proportion of new energy grids or a 100% new energy source of power grid, the dynamic performance of PMSG under fault conditions is very important. However, the current small signal model lacks detailed and deep analysis of a permanent‐magnet synchronous generator (PMSG)‐based wind power generation under LVRT control. Here, a small signal model of a PMSG under pre‐fault, fault and after fault failure recovery stages are established. This paper employs linear analyses to characterize the dynamic performance of a PMSG‐based wind power generation system under LVRT control and practical generator characteristics. In particular, the conflict between frequency regulation and LVRT is discussed based on the constructed model. On this basis, the impact of dc‐link bandwidth on the system performance during failure recovery stage is discussed, and the active damping method is analysed to improve the performance of PMSG during failure and failure recovery stages. Finally, time‐domain simulations are utilized to verify the analyses and models discussed. The research results in this paper are helpful to promote and improve the performance of PMSG during LVRT conditions.

Abstract With millions of years of evolution, owls have developed many excellent characteristics in terms of their flight. The speed of an owl in flight is similar to the relative speed of the blade of a small wind turbine with respect to air. Therefore, the owl wing airfoil is selected as the design airfoil of the wind turbine blade to reduce the flow separation under low Reynolds number. In this study, we analyze an owl wing‐section airfoil and the non‐smooth leading‐edge shape of an owl's wing, and implement an orthogonal optimum design to optimize the wavelength and amplitude of the non‐smooth leading edge. We extract the cross‐sectional features of the airfoil and the non‐smooth leading‐edge shape of the wing. Based on the orthogonal optimum design results, we determine the optimal combination of the wavelength, amplitude, and airfoil, and then design a horizontal‐axis wind turbine blade through bionic coupling. The flow field at different tip speed ratios (TSRs) is simulated using the k‐ωSST turbulence model at the rated wind speed. The results show that the power coefficient (CP) of the bionic wind turbine at a high tip speed ratio is 17.7% higher than that of the standard type. Furthermore, we analyze the operation of the turbine at TSRs of 2 and 5. At a high TSR, the leading edge bulge of the bionic wind turbine blade can change the flow direction distribution of the airflow on the blade surface, make the airflow to adhere to the suction surface, and then reduce the stall area on the suction surface of the blade. Thus, the wind turbine produces higher torque, thereby generating higher power.

Abstract Background Numerous studies have suggested that fasting plasma glucose (FPG) was associated with the risk of mortality. However, relationship on longitudinal changes of FPG with the risk of mortality remained inconsistent. Methods We examined the association of FPG at baseline and its longitudinal changes with risk of mortality based on a cohort study in Yinzhou, China, during 2010–2018. Cox regression models and competing risk models were separately used to examine the association of FPG levels and long‐term fluctuation with risk of total and cause‐specific mortality. Results Subjects who had an impaired fasting glucose or diabetes suffered a higher risk of total mortality than subjects who had a normal fasting glucose (HRs and 95% CIs: 1.17 [1.01–1.35], 1.30 [1.10–1.53], respectively). The HR for total mortality was 1.54 (95% CI: 1.29–1.84) and for cancer mortality was 1.41 (95% CI: 1.04–1.92) in the highest quartile of coefficient of variation of FPG. Trajectory analysis indicated that subjects with a significantly changed FPG suffered a higher risk of total mortality. Conclusion According to this cohort study, we found that long‐term fluctuation of FPG was significantly associated with the risk of total and cancer mortality. Our findings suggest that long‐term fluctuation of FPG could be used as an efficient indicator for predicting the subsequent risk of mortality.

Abstract Purpose Ischemia is one of the most familiar complications in the different procedures for moyamoya disease (MMD), but the optimal surgical approaches for MMD remain unknown. We aimed to evaluate the efficiency of various surgical treatments. Methods A literature search word was performed through four databases such as Cochrane Library, Web of Science, PubMed, and EMBASE for the literature published until May 2021. The I2 statistic was used to assess heterogeneity. A random/fixed‐effects model was used to pool. Results There are a total of 18 studies including three surgical treatments such as including indirect, direct, and combined bypass in this study. The result revealed that indirect bypass was related to a higher incidence of recurrence stroke compared to the direct and combined bypass treatment (p = .001). Furthermore, the cases undergoing direct bypass were associated with a better angiographic change than the indirect bypass (OR = 3.254, p = .013). Conclusion This meta‐analysis demonstrated a positive effect of using the direct and combined bypass to treat MMD compared to indirect bypass due to their lower rates of recurrence stroke.

Abstract Background Ambiguous or atypical phenotypes can make a definite diagnosis of primary immunodeficiency diseases based on biochemical indices alone challenging. Further, mortality in early life because of infections in patients with these conditions supports the use of genetic tests to facilitate rapid and accurate diagnoses. Methods Genetic and clinical analyses of three unrelated Chinese children with clinical manifestations of recurrent infections, who were considered to have primary immunodeficiency diseases, were conducted. Patient clinical features and serum immunological indices were recorded. Next‐generation sequencing was used to screen for suspected pathogenic variants. Family co‐segregation and in silico analysis were conducted to evaluate the pathogenicity of identified variants, following the American College of Medical Genetics and Genomics guidance. Results All three patients were found to have predominant antibody defects. Sequencing analysis revealed that one had two compound heterozygous variants, c.255C>A and c.295C>T, in the autosomal gene, activation‐induced cytidine deaminase (AICDA). The other two patients were each hemizygous for the variants c.1185G>A and c.82C>T in the Bruton's tyrosine kinase (BTK) gene on the X chromosome. In silico analysis revealed that identified substituted amino acids were highly conserved and predicted to cause structural and functional damage to the proteins. Conclusion Four pathogenic variants in AICDA and BTK were confirmed to cause different forms of hyper‐IgM syndrome type 2 (HIGM2) and X‐linked agammaglobulinemia (XLA); two were novel mutations that have never been reported previously. This is the first report of HIGM2 caused by AICDA deficiency in a patient from the Chinese mainland.

Abstract Background Brain metastases explain the majority of mortality associated with lung cancer, which is the leading cause of cancer death. Cytology analysis of the cerebrospinal fluid (CSF) remains the diagnostic gold standard, however, the circulating tumor cells (CTCs) in CSF (CSF‐CTCs) are not well defined at the molecular and transcriptome levels. Methods We established an effective CSF‐CTCs collection procedure and isolated individual CSF cells from five lung adenocarcinoma leptomeningeal metastases (LUAD‐LM) patients and three controls. Three thousand seven hundred ninety‐two single‐cell transcriptomes were sequenced, and single‐cell RNA sequencing (scRNA‐seq) gene expression analysis was used to perform a comprehensive characterization of CSF cells. Results Through clustering and expression analysis, we defined CSF‐CTCs at the transcriptome level based on epithelial markers, proliferation markers, and genes with lung origin. The metastatic‐CTC signature genes are enriched for metabolic pathway and cell adhesion molecule categories, which are crucial for the survival and metastases of tumor cells. We discovered substantial heterogeneity in patient CSF‐CTCs. We quantified the degree of heterogeneity and found significantly greater among‐patient heterogeneity compared to among‐cell heterogeneity within a patient. This observation could be explained by spatial heterogeneity of metastatic sites, cell‐cycle gene, and cancer‐testis antigen (CTA) expression profiles as well as the proportion of CTCs displaying mesenchymal and cancer stem cell properties. In addition, our CSF‐CTCs transcriptome profiling allowed us to determine the biomarkers during the progression of an LM patient with cancer of unknown primary site (CUP). Conclusions Our results will provide candidate genes for an RNA‐based digital detection of CSF‐CTCs from LUAD‐LM and CUP‐LM cases, and shed light on the therapy and mechanism of LUAD‐LM.

Abstract RNA sequencing has greatly facilitated gene expression studies but is weak in studying temporal RNA dynamics; this issue can be addressed by analyzing nascent RNAs. A famous method for nascent RNA analysis is metabolic labeling with noncanonic nucleoside followed by affinity purification, however, purification processes can always introduce biases into data analysis. Here, a chemical method for nascent RNA sequencing that avoids affinity purification based on acrylonitrile‐mediated uridine‐to‐cytidine (U‐to‐C) conversion (AMUC‐seq) via 4‐thiouridine (s4U) cyanoethylation is presented. This method converts s4U base‐pairing with guanine through the nucleophilic addition of s4U to acrylonitrile. The high reaction efficiency permits AMUC‐seq directly and efficiently to recover nascent RNA information from total RNAs. AMUC‐seq is validated by being used to detect mRNA half‐lives and investigating the direct gene targets of a G‐quadruplex stabilizer, which can be regarded as potential anticancer drug, in human cells. Thousands of direct gene targets of this drug are verified (these genes are significantly enriched in cancer such as SRC and HRAS). AMUC‐seq also confirms G‐quadruplex stabilization that impacts RNA polyadenylation. These results show AMUC‐seq is qualified for the study of temporal RNA dynamics, and it can be a promising strategy to study the therapeutic mechanism of transcription‐modulating drugs.