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Highlights The constructions under internal and external driving forces were introduced and compared with each other. The physicochemical properties were analyzed for the assessment of crystalline quality and photoelectric characteristics. The photocatalytic applications, mechanisms, and developments of the core-shell semiconductor-graphene nanoarchitectures were illustrated in detail.

Introduction Frailty significantly influences the prognosis of elderly patients diagnosed with heart failure. The assessment of frailty is a critical initial step in the management of these patients, as a systematic and precise evaluation facilitates the identification of individuals at high risk. This identification enables timely and targeted interventions, which can subsequently reduce the likelihood of adverse cardiovascular events and improve the quality of life for elderly patients with heart failure. Nevertheless, there exists a notable deficiency in research regarding the most effective frailty assessment tools specifically for elderly patients with heart failure in China. The objective of this study is to identify the frailty assessment tool that demonstrates the highest predictive value for outcomes in this population.Methods and analysis This study is a multicentre, prospective cohort investigation that commenced in October 2023 across three tertiary hospitals in Beijing, China. Employing a continuous enrolment strategy, the study encompasses all elderly patients diagnosed with heart failure who are undergoing either outpatient or inpatient treatment, continuing until an adequate sample size is achieved. Follow-up evaluations are scheduled every 3 months from the point of patient enrolment, extending until the 12th month post-enrolment. Comprehensive data collection, which includes demographic information, heart failure-related metrics, frailty assessments and significant biochemical test results, is conducted through face-to-face interviews at baseline.Ethics and dissemination Participant inclusion will depend on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Central Ethics Committee of Beijing Hospital. The approval letter number is 2023BJYYEC-356-01. Outcomes of the study will be published in a peer-reviewed scientific journal.

This study was a randomized, parallel-controlled of homologous vaccines with different immune procedure research to evaluate the immunogenicity and immune persistence of Zagreb 2-1-1 regimen of rabies vaccine in Chinese healthy individuals. 240 subjects aged ≤ 20、21-50、≥51 y were randomly divided into 2 groups (1:1), Zagreb 2-1-1 regimen receivers as experimental group and Essen 5 regimen receivers as controlled group. Researchers collected venous blood of each subject before vaccine injection and on the day 7, 14, 42, 180, 365 after first dose. The immunogenicity and immune persistence was assessed by neutralizing antibody. The positive rate of neutralizing antibody in experimental group was 14.53% on the 7th day, and raised to 100% on the 14th day. It showed no significant difference between experimental and controlled group (P>0.05). Either in experimental or controlled group, GMC of neutralizing antibody was up to the peak on the 14th day, and it showed no significant difference between two groups (P>0.05). On the 42nd day, the antibody positive rate remained 100% with both Zagreb 2-1-1 and Essen 5 regimens, and the GMC of antibodies also remained high level. Then, on the 180th and 365th day with both regimens, the GMC of antibodies dropped dramatically, although it remained above the protective level of 0.5 IU/ml, the positive rates dropped to 84.40% and 84.11% (on the 180th day), and 61.29% and 58.62% (on the 365th day). Rabies vaccine injected by Zagreb 2-1-1 regimen can produce neutralizing antibody fastly and perdurably.Registration: ClinicalTrials.gov #NCT01821911and NCT01827917

Drainage modeling that accurately captures urban storm inundation serves as the foundation for flood warning and drainage scheduling. In this paper, we proposed a novel coupling ideology that, by integrating 2D-1D and 1D-2D unidirectional processes, overcomes the drawback of the conventional unidirectional coupling approach that fails to properly represent the rainfall surface catchment dynamics, and provides more coherent hydrological implications compared to the bidirectional coupling concept. This paper first referred to a laboratory experimental case from the literature, applied and analyzed the coupling scheme proposed in this paper and the bidirectional coupling scheme that has been widely studied in recent years, compared the two coupling solutions in terms of the resulting accuracy and applicability, and discussed their respective strengths and weaknesses to validate the reliability of the proposed method. The verified proposed coupling scheme was then applied to the modeling of a real drainage system in a region of Nanjing, China, and the results proved that the coupling mechanism proposed in this study is of practical application value. HIGHLIGHTS A novel coupling approach by combining two unidirectional processes.; Comparison with bidirectional tight coupling scheme in terms of simulation accuracy and applicability.; The proposed coupling idea provides reliable outcomes with enhanced applicability.;

BackgroundDiabetes poses a significant public health challenge in China and globally, with the number of patients expected to reach 592 million by 2035, notably in Asia. In China alone, an estimated 140 million individuals are living with diabetes, and a significant portion is nonadherent to medications, underscoring the urgency of effective management strategies. Recognizing the necessity of early and comprehensive management for newly diagnosed patients with type 2 diabetes, this study leverages an online teach-back method and “Internet + Nursing” platform based on King’s Theory of Goal Attainment. The approach aims to enhance glycemic control and reduce fear and misconceptions about the disease, addressing both the educational and emotional needs of the patients. ObjectiveThe primary aim of this study was to assess the effectiveness of King’s Goal Attainment Theory in the management of newly diagnosed patients with type 2 diabetes. This research sought to develop a collaborative model for blood glucose management, integrating the expertise and roles of physicians, nurses, and patients. The model is designed to enhance the synergy in health care provision, ensuring a comprehensive approach to diabetes management. MethodsIn this study conducted at Changzhou Traditional Chinese Medicine Hospital between January 2022 and February 2023, eligible patients were randomized into a control group or an online feedback group. The control group received standard care, while the online feedback group participated in a King’s Theory of Goal Attainment–based online teach-back program, enhanced by “Internet + Nursing” strategies. This included an interactive platform for goal planning, video content sharing, comprehension assessment, misconception correction, and patient-driven recaps of disease information. Health monitoring was facilitated through the “Internet + Nursing” platform. The study focused on comparing changes in glucose metabolism and emotional disorder symptoms between the groups to evaluate the intervention’s effectiveness. ResultsFollowing a 24-week intervention, we observed significant differences in key metrics between the online feedback group and the control group, each comprising 60 participants. The online feedback group demonstrated significant reductions in fasting plasma glucose, 2-hour postprandial glucose, and hemoglobin A1c (P

Cisplatin-induced acute kidney injury (AKI) increases the patient mortality dramatically and results in an unfavorable prognosis. A strong correlation between AKI and ferroptosis, which is a notable type of programmed cell death, was found in recent studies. Myricitrin is a natural flavonoid compound with diverse pharmacological properties. To investigate the protective effect of myricitrin against cisplatin induced human tubular epithelium (HK-2) cell injury and the underlying anti-ferroptic mechanism by this study. Firstly, a pharmacology network analysis was proposed to explore the myricitrin’s effect. HK-2 cells were employed for in vitro experiments. Ferroptosis was detected by cell viability, quantification of iron, malondialdehyde, glutathione, lipid peroxidation fluorescence, and glutathione peroxidase (GPX4) expression. Ferritinophagy was detected by related protein expression (NCOA4, FTH, LC3II/I, and SQSTM1). In our study, GO enrichment presented that myricitrin might be effective in eliminating ferroptosis. The phenomenon of ferroptosis regulated by ferritinophagy was observed in cisplatin-activated HK-2 cells. Meanwhile, pretreatment with myricitrin significantly rescued HK-2 cells from cell death, reduced iron overload and lipid peroxidation biomarkers, and improved GPX4 expression. In addition, myricitrin downregulated the expression of LC3II/LC3I and NCOA4 and elevated the expression of FTH and SQTM. Furthermore, myricitrin inhibited ROS production and preserved mitochondrial function with a lower percentage of green JC-1 monomers. However, the protection could be reserved by the inducer of ferritinophagy rapamycin. Mechanically, the Hub genes analysis reveals that AKT and NF-κB are indispensable mediators in the anti-ferroptic process. In conclusion, myricitrin ameliorates cisplatin induced HK-2 cells damage by attenuating ferritinophagy mediated ferroptosis.

Abstract Sepsis is a common acute and severe medical condition with a high mortality rate. Anoikis, an emerging form of cell death, plays a significant role in various diseases. However, the role of anoikis in sepsis remains poorly understood. Based on the datasets from Gene Expression Omnibus and anoikis-related genes from GeneCards, the differentially expressed anoikis-related genes (DEARGs) were identified. Based on hub genes of DEARGs, a novel prognostic risk model was constructed, and the pattern of immune infiltration was investigated by CIBERSORT algorithm. And small molecule compounds targeting anoikis in sepsis were analyzed using Autodock. Of 23 DEARGs, CXCL8, CFLAR, FASLG and TP53 were significantly associated with the prognosis of sepsis (P

Abstract Magnetically coupled rodless cylinders are widely used in the coordinate positioning of mechanical arms, electrostatic paintings, and other industrial applications. However, they exhibit strong nonlinear characteristics, which lead to low servo control accuracy. In this study, a mass-flow equation through the valve port was derived to improve the control performance, considering the characteristics of the dynamics and throttle-hole flow. Subsequently, a friction model combining static, viscous, and Coulomb friction with a zero-velocity interval was proposed. In addition, energy and dynamic models were set for the experimental investigation of the magnetically coupled rodless cylinder. A nonlinear mathematical model for the position of the magnetically coupled rodless cylinder was proposed. An incremental PID controller was designed for the magnetically coupled rodless cylinder to control this system, and the PID parameters were adjusted online using RBF neural network. The response results of the PID parameters based on the RBF neural network were compared with those of the traditional incremental PID control, which proved the superiority of the optimization control algorithm of the incremental PID parameters based on the RBF neural network servo control system. The experimental results of this model were compared with the simulation results. The average error between the established model and the actual system was 0.005175054 (m), which was approximately 2.588% of the total travel length, demonstrating the accuracy of the theoretical model.

Candida vulturna belongs to the Candida haemulonii species complex and is phylogenetically related to C. auris. We report a C. vulturna outbreak among persons in Shanxi Province, China, during 2019–2022. Isolates were resistant to multiple antifungal drugs and exhibited enhanced adhesion and biofilm formation properties.

Abstract The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.

BK7 glass, with its outstanding mechanical strength and optical performance, plays a crucial role in many cutting-edge technological fields and has become an indispensable and important material. These fields have extremely high requirements for the surface quality of BK7 glass, and any small defects or losses may affect its optical performance and stability. However, as a hard and brittle material, the processing of BK7 glass is extremely challenging, requiring precise control of machining parameters to avoid material fracture or excessive defects. Therefore, how to obtain the required surface quality with lower cost machining techniques has always been the focus of researchers. This article introduces the properties, application background, machining methods, material removal mechanism, and surface and subsurface damage of optical glass BK7 material. Finally, scientific predictions and prospects are made for future development trends and directions for improvement of BK7 glass machining.

This paper presents the design of a symmetric variable stiffness joint that employs worm gear and sliding helical transmissions to adjust the effective length of the leaf springs. Firstly, the design concept and working principle of the variable stiffness joint are presented, along with two different assembly methods. Secondly, the stiffness equations and characteristics of the variable stiffness joint are then derived and analyzed. Next, the dynamics of the variable stiffness joint are modeled and simulated visually using Simulink. Finally, a prototype of the variable stiffness joint is constructed and its stiffness characteristics are experimentally verified. The experimental results demonstrate that both assembly methods are capable of adjusting the stiffness and position of the joint within a certain range. This study contributes to the understanding and development of symmetric variable stiffness joints by presenting a comprehensive design, analysis, simulation, and experimental evaluation. The proposed joint has potential applications in various fields that require adaptability, adjustability, and safety.

ABSTRACTSmoothed Particle Hydrodynamics (SPH) method is used to solve water hammer equations for pipeline systems due to its potential advantages of easily capturing column separation and slug impact. Currently, the SPH-based water hammer model has been only developed to simulate single pipe flow with simple boundary conditions. It is still a challenge to apply the SPH-based water hammer model to practical water distribution systems (WDSs). To address this issue, this study develops a complete SPH-based Water Hammer model for Water Distribution System (SPH-WHWDS). Within the proposed method, the complex internal and external boundary condition treatment models of the multi-pipe joint junction and different hydraulic components are developed. Buffer and mirror particles are designed for boundary treatment coupling with the method of characteristics (MOC). Two benchmark test cases, including an unsteady pipe flow experiment and a complex WDS, are used to validate the proposed model, with the data from the experimental test in the literature and the simulation results by the classical MOC. The results show the proposed SPH-WHWDS model is capable to simulate transient flows with accurate and robust results for pipeline systems, which may provide further insights and an alternative tool to study water hammer phenomena in complex WDSs.

This case report describes a rare case of cervical necrotizing fasciitis (CNF) of the nasopharynx. The patient presented with intractable chronic suppurative otitis media and underwent radiological examination including CT, MRI, and PET/CT. All of the images misdiagnosed this condition as nasopharyngeal carcinoma. Finally, the patient underwent a nasopharyngeal mass biopsy and CNF was diagnosed. A retrospective analysis of the radiological scans was performed and the causes of the misdiagnosis were evaluated. The CT, MRI, and PET/CT characteristics and key features for the early diagnosis of CNF were summarized. Our findings may contribute to current knowledge of the precise diagnosis of CNF.

Abstract Background Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up. Methods Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses. Results The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Conclusion The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.

Abstract Objective Although the tumor mutation burden (TMB) was reported as a biomarker for immunotherapy of various cancers, whether it can effectively predict the survival prognosis in breast cancer patients remains unclear. In this study, the prognostic value of TMB and its correlation with immune infiltration were explored by using multigroup studies. Methods The somatic mutation data of 986 breast cancer patients were obtained from TCGA database. Breast cancer patients were divided into a low-TMB group and a high-TMB group according to the quartile of TMB scores. The differentially expressed genes (DEGs) were identified by the “limma” R program. The CIBERSORT algorithm was utilized to estimate the immune cell fraction of each sample. The TIMER database was utilized to evaluate the association between CNVs of immune genes and tumor immune cell infiltration and the prognostic value of the immune cells in breast cancer. Results In breast cancer, TP53, PIK3CA, TTN, CDH1 and other genes were the most important mutated genes. Higher survival rate of patients was found in the low-TMB group. Among the top 10 DEGs, three of them belong to the KRT gene family. GSEA enrichment analysis showed that MAPK, Hedgehog, mTOR, TGF-bate and GnRH signaling pathways were enriched in the low-TMB group. The infiltration levels of the most of immune cells were higher in the low-TMB group (P

Abstract Structure has been considered to play an important role in photocatalytic performance of the semiconductors, but the intrinsic factors were rarely revealed. Herein, ZnO nanomaterials in the structures of thin film, nanowire array and nanosheet array were synthesized, and their structural characteristics, optical properties, photocurrent response and photocatalytic efficiency were compared with each other for illustrating the issue. The photoluminescence intensity decreased in the order of nanosheets, thin film and nanowires for improved lifetime of the photoexcited charges. The absorption of the nanosheets and nanowires improved obviously in the visible range with a redshift of the absorption edge than that of the thin film. The nanowires possessed the highest response current of 82.65 μA at a response time of 2.0 ms in a sensitivity of 87.93 at the light frequency of 1 Hz, and gained the largest catalytic efficiency of 2.45 μg/cm2 h for the methylene blue degradation in UV light. Nevertheless, the improvement of catalytic efficiency of the nanosheets (up to 42.4%) was much larger than that of nanowires (5.7%) and thin film (2.6%) for the Au coating. The analysis revealed that the photocatalytic efficiency of the ZnO nanomaterials was modulated by the structure as it contained different surface area, roughness, defect and doping states, vacancies, polar and non-polar crystalline faces, which would provide structural design of semiconductor nanomaterials for the photoelectric and photocatalytic applications.

Surface defect detection of strip steel is an important guarantee for improving the production quality of strip steel. However, due to the diverse types, scales, and texture structures of surface defects on strip steel, as well as the irregular distribution of defects, it is difficult to achieve rapid and accurate detection of strip steel surface defects with existing methods. This article proposes a real-time and high-precision surface defect detection algorithm for strip steel based on YOLOv7. Firstly, Partial Conv is used to replace the conventional convolution blocks of the backbone network to reduce the size of the network model and improve the speed of detection; Secondly, The CA attention mechanism module is added to the ELAN module to enhance the ability of the network to extract detect features and improve the effectiveness of detect detection in complex environments; Finally, The SPD convolution module is introduced at the output end to improve the detection performance of small targets with surface defects on steel. The experimental results on the NEU-DET dataset indicate that the mean average accuracy (mAP@IoU = 0.5) is 80.4%, which is 4.0% higher than the baseline network. The number of parameters is reduced by 8.9%, and the computational load is reduced by 21.9% (GFLOPs). The detection speed reaches 90.9 FPS, which can well meet the requirements of real-time detection.

The research on biomimetic robots, especially soft robots with flexible materials as the main structure, is constantly being explored. It integrates multi-disciplinary content, such as bionics, material science, mechatronics engineering, and control theory, and belongs to the cross-disciplinary field related to mechanical bionics and biological manufacturing. With the continuous development of various related disciplines, this area has become a hot research field. Particularly with the development of practical technologies such as 3D printing technology, shape memory alloy, piezoelectric materials, and hydrogels at the present stage, the functions and forms of soft robots are constantly being further developed, and a variety of new soft robots keep emerging. Soft robots, combined with their own materials or structural characteristics of large deformation, have almost unlimited degrees of freedom (DoF) compared with rigid robots, which also provide a more reliable structural basis for soft robots to adapt to the natural environment. Therefore, soft robots will have extremely strong adaptability in some special conditions. As a type of robot made of flexible materials, the changeable pose structure of soft robots is especially suitable for the large application environment of the ocean. Soft robots working underwater can better mimic the movement characteristics of marine life in the hope of achieving more complex underwater tasks. The main focus of this paper is to classify different types of underwater organisms according to their common motion modes, focusing on the achievements of some bionic mechanisms in different functional fields that have imitated various motion modes underwater in recent years (e.g., the underwater sucking glove, the underwater Gripper, and the self-powered soft robot). The development of various task types (e.g., grasping, adhesive, driving or swimming, and sensing functions) and mechanism realization forms of the underwater soft robot are described based on this article.

The use of electrochemical energy storage systems based on alkali metal electrodes is hindered by the dendrites’ growth and volume changes upon cycling. Here, the authors propose nitrogen and zinc co-doped porous carbon nanofibers as potassium metal hosting material for reversible metal deposition.

In this paper, a two-patch SIS model with saturating contact rate and one-directing population dispersal is proposed. In the model, individuals can only migrate from patch 1 to patch 2. The basic reproduction number $ R_0^1 $ of patch 1 and the basic reproduction number $ R_0^2 $ of patch 2 is identified. The global dynamics are completely determined by the two reproduction numbers. It is shown that if $ R_0^1 < 1 $ and $ R_0^2 < 1 $, the disease-free equilibrium is globally asymptotically stable; if $ R_0^1 < 1 $ and $ R_0^2 > 1 $, there is a boundary equilibrium which is globally asymptotically stable; if $ R_0^1 > 1 $, there is a unique endemic equilibrium which is globally asymptotically stable. Finally, numerical simulations are performed to validate the theoretical results and reveal the influence of saturating contact rate and migration rate on basic reproduction number and the transmission scale.

RNase 4 is presented as a biomarker for prostate cancer, inducing AXL activation that promotes AKT/S6K activation and tumor cell proliferation, and its inhibition reduces the growth of xenograft human prostate tumors.

Aerosols can alter atmospheric stability through radiative forcing, thereby changing mean and daily extreme precipitation on regional scales. However, it is unclear how extreme sub-daily precipitation responds to aerosol radiative effects. In this study, we use the regional climate model (RCM) Consortium for Small-scale Modeling (COSMO) to perform convection-permitting climate simulations at a kilometer-scale (0.04°/~4.4 km) resolution for the period 2001–2010. By evaluating against the observed hourly precipitation-gauge data, the COSMO model with explicit deep convection can effectively reproduce sub-daily and daily extreme precipitation events, as well as diurnal cycles of summer mean precipitation and wet hour frequency. Moreover, aerosol sensitivity simulations are conducted with sulfate and black carbon aerosol perturbations to assess the direct and semi-direct aerosol effects on extreme sub-daily precipitation in the COSMO model. The destabilizing effects associated with decreased sulfate aerosols intensify extreme sub-daily precipitation, while increased sulfate aerosols tend to induce an opposite change. In contrast, the response of extreme sub-daily precipitation to black carbon aerosol perturbations exhibits a nonlinear behavior and potentially relies on geographical location. Overall, the scaling rates of extreme precipitation intensities decrease and approach the Clausius–Clapeyron rate from hourly to daily time scales, and the responses to sulfate and black carbon aerosols vary with precipitation durations. This study improves the understanding of aerosol radiative effects on sub-daily extreme precipitation events in RCMs.

Abstract Background Over 100 mutations in the SRD5A2 gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of SRD5A2 mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X/p.H232R mutation of the SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in this gene causes 46,XY DSD requires further exploration. Methods The two 46,XY DSD cases were identified and sequenced. In order to identify the source of the compound heterozygous p.Q6X/p.H232R mutation, the parents, maternal grandparents, and maternal uncle were sequenced. Since p.Q6X mutation is a nonsense mutation, p.H232R mutation was transfected into HEK293 cells and dihydrotestosterone (DHT) production were analyzed by liquid chromatography–mass spectrometry (LC–MS) for 5α-reductase 2 enzyme activities test. Apparent michaelis constant (Km) were measured of p.H232R mutation to analyze the binding ability change of 5α-reductase 2 enzyme with testosterone (T) or NADPH. Results The sequence results showed that the two 46,XY DSD cases were the compound heterozygous p.Q6X/p.H232R mutation, of which the heterozygous p.Q6X mutation originating from maternal family and heterozygous p.H232R mutation originating from the paternal family. The function analysis confirmed that p.H232R variant decreased the DHT production by LC–MS test. The Km analysis demonstrated that p.H232R mutation affected the binding of SRD5A2 with T or NADPH. Conclusions Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in the SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5α-reductase 2 enzyme.

BackgroundVitamin D deficiency (VDD) or vitamin D insufficiency is common in kidney transplant recipients (KTRs). The impact of VDD on clinical outcomes in KTRs remain poorly defined and the most suitable marker for assessing vitamin D nutritional status in KTRs is unknown so far.MethodsWe conducted a prospective study including 600 stable KTRs (367 men, 233 women) and a meta-analysis to pool existing evidence to determine whether 25(OH)D or 1,25(OH)2D predicted graft failure and all-cause mortality in stable KTRs.ResultsCompared with a higher 25(OH)D concentration, a low concentration of 25(OH)D was a risk factor for graft failure (HR 0.946, 95% CI 0.912−0.981, p = 0.003), whereas 1,25 (OH)2D was not associated with the study end-point graft loss (HR 0.993, 95% CI 0.977−1.009, p = 0.402). No association was found between either 25(OH)D or 1,25 (OH)2D and all-cause mortality. We furthermore conducted a meta-analysis including 8 studies regarding the association between 25(OH)D or 1,25(OH)2D and graft failure or mortality, including our study. The meta-analysis results were consistent with our study in finding that lower 25(OH)D levels were significantly associated with the risk of graft failure (OR = 1.04, 95% CI: 1.01−1.07), but not associated with mortality (OR = 1.00, 95% CI: 0.98−1.03). Lower 1,25(OH)2D levels were not associated with the risk of graft failure (OR = 1.01, 95% CI: 0.99−1.02) and mortality (OR = 1.01, 95% CI: 0.99−1.02).ConclusionBaseline 25(OH)D concentrations but not 1,25(OH)2D concentrations were independently and inversely associated with graft loss in adult KTRs.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) secreted by tumors was reported as a deleterious factor that led to the reduction of lymphocyte infiltration and the poorer efficacy of ICIs in vivo. This study aimed to explore whether PCSK9 expression in tumor tissue could predict the response of advanced non-small cell lung cancer (NSCLC) to anti-PD-1 immunotherapy and the synergistic antitumor effect of the combination of the PCSK9 inhibitor with the anti-CD137 agonist. One hundred fifteen advanced NSCLC patients who received anti-PD-1 immunotherapy were retrospectively studied with PCSK9 expression in baseline NSCLC tissues detected by immunohistochemistry (IHC). The mPFS of the PCSK9lo group was significantly longer than that of the PCSK9hi group [8.1 vs. 3.6 months, hazard ratio (HR): 3.450; 95% confidence interval (CI), 2.166-5.496]. A higher objective response rate (ORR) and a higher disease control rate (DCR) were observed in the PCSK9lo group than in the PCSK9hi group (54.4% vs. 34.5%, 94.7% vs. 65.5%). Reduction and marginal distribution of CD8+ T cells were observed in PCSK9hi NSCLC tissues. Tumor growth was retarded by the PCSK9 inhibitor and the anti-CD137 agonist alone in the Lewis lung carcinoma (LLC) mice model and further retarded by the PCSK9 inhibitor in combination with the CD137 agonist with long-term survival of the host mice with noticeable increases of CD8+ and GzmB+ CD8+ T cells and reduction of Tregs. Together, these results suggested that high PCSK9 expression in baseline tumor tissue was a deleterious factor for the efficacy of anti-PD-1 immunotherapy in advanced NSCLC patients. The PCSK9 inhibitor in combination with the anti-CD137 agonist could not only enhance the recruitment of CD8+ and GzmB+ CD8+ T cells but also deplete Tregs, which may be a novel therapeutic strategy for future research and clinical practice.

Abstract A systematic study was carried out for strain-induced microscale compositional pulling effect on the structural and optical properties of high Al content AlGaN multiple quantum wells (MQWs). Investigations reveal that a large tensile strain is introduced during the epitaxial growth of AlGaN MQWs, due to the grain boundary formation, coalescence and growth. The presence of this tensile strain results in the microscale inhomogeneous compositional pulling and Ga segregation, which is further confirmed by the lower formation enthalpy of Ga atom than Al atom on AlGaN slab using first principle simulations. The strain-induced microscale compositional pulling leads to an asymmetrical feature of emission spectra and local variation in emission energy of AlGaN MQWs. Because of a stronger three-dimensional carrier localization, the area of Ga segregation shows a higher emission efficiency compared with the intrinsic area of MQWs, which is benefit for fabricating efficient AlGaN-based deep-ultraviolet light-emitting diode.

BackgroundFms-like tyrosine kinase 3 (FLT3) gene mutations occur in approximately 30% of all patients with acute myeloid leukemia (AML). Internal tandem duplication (ITD) in the juxtamembrane domain and point mutations within the tyrosine kinase domain (TKD) are two distinct types of FLT3 mutations. FLT3-ITD has been determined as an independent poor prognostic factor, but the prognostic impact of potentially metabolically related FLT3-TKD remains controversial. Hence, we performed a meta-analysis to investigate the prognostic significance of FLT3-TKD in patients with AML.MethodsA systematic retrieval of studies on FLT3-TKD in patients with AML was performed in PubMed, Embase, and Chinese National Knowledge Infrastructure databases on 30 September 2020. Hazard ratio (HR) and its 95% confidence intervals (95% CIs) were used to determine the effect size. Meta-regression model and subgroup analysis were used for heterogeneity analysis. Begg’s and Egger’s tests were performed to detect potential publication bias. The sensitivity analysis was performed to evaluate the stability of findings in meta-analysis.ResultsTwenty prospective cohort studies (n = 10,970) on the prognostic effect of FLT3-TKD in AML were included: 9,744 subjects with FLT3-WT and 1,226 subjects with FLT3-TKD. We found that FLT3-TKD revealed no significant effect on disease-free survival (DFS) (HR = 1.12, 95% CI: 0.90–1.41) and overall survival (OS) (HR = 0.98, 95% CI: 0.76–1.27) in general. However, meta-regressions demonstrated that patient source contributed to the high heterogeneity observed in the prognosis of FLT3-TKD in AML. To be specific, FLT3-TKD represented a beneficial prognosis of DFS (HR = 0.56, 95% CI: 0.37–0.85) and OS (HR = 0.63, 95% CI: 0.42–0.95) for Asians, whereas it represented an adverse prognosis of DFS for Caucasians with AML (HR = 1.34, 95% CI: 1.07–1.67).ConclusionFLT3-TKD revealed no significant effects on DFS and OS of patients with AML, which is consistent with the controversial status nowadays. Patient source (Asians or Caucasians) can be partially explained the different effects of FLT3-TKD in the prognosis of patients with AML.

BackgroundThere were new points of interest in performing subsegmentectomy and segmentectomy for patients with early stage non-small cell lung cancer (NSCLC). However, whether patients who underwent subsegmentectomy could obtain satisfactory clinical outcomes remains unclear. The present study aimed to compare the clinical outcomes and security of surgical procedures between subsegmentectomy and segmentectomy.MethodsA systematic review and meta-analysis was performed through five online databases to identify the included literatures which presented intact clinical outcome data among different surgical procedures. The included studies were evaluated based on precise and predefined inclusion criteria.ResultsThere were 4 published studies identified in this meta-analysis. A total of 325 patients who underwent subsegmentectomy and 904 patients who underwent segmentectomy were involved in this analysis. The duration of drainage [MD −0.19; 95%CI (−0.36, −0.02), p = 0.03] and postoperative hospital stay [MD −0.30; 95%CI (−0.58, −0.02), p = 0.009] of subsegmentectomy were significantly less than that of segmentectomy. There was no statistically significant difference among recurrence rate [OR 0.85; 95%CI (0.21, 3.42), p = 0.82], operation time, blood loss, incidence of complications [OR 0.83; 95%CI (0.58, 1.20), p = 0.33] between subsegmentectomy and segmentectomy in patients with stage IA NSCLC.ConclusionThe meta-analysis was firstly performed to compare perioperative outcomes among surgical procedures. The perioperative outcomes were comparable between subsegmentectomy and segmentectomy. Subsegmentectomy might be an alternative treatment for the deep tumor with size less than 1.5 cm and mainly composed of Ground Glass Opacity (GGO).

Synoptic circulation patterns over the midlatitudes play a pivotal role in regional precipitation changes; however, the synoptic circulation patterns over eastern Asia (35°–60° N, 105°–145° E) and their effects on extreme precipitation events in the North China Plain (NCP) and northeastern China (NEC) remain unclear. The summer daily 500 hPa geopotential height anomaly fields for 1979–2021 are classified into six synoptic circulation patterns using self-organizing map (SOM) cluster analysis. The SOM1 pattern, characterized by a high-pressure ridge over the north of eastern Asia and a trough near the Korean Peninsula, yields decreased precipitation in NEC. The SOM2 pattern reveals a robust high ridge over eastern Asia, resulting in a higher incidence of regional extreme precipitation events (REPEs) of approximately 24% in the NCP. Under the SOM3 pattern, the anomalous cyclonic circulation over eastern Asia leads to above-average precipitation in the NCP. The SOM4 pattern yields the highest incidence of REPEs in NEC, with the lowest incidence of REPEs in the NCP, as the anomalous cyclonic circulation over eastern Asia moves southeastward compared to the SOM3 pattern. The SOM5 pattern presenting an anticyclone–cyclone dipole reduces precipitation in the NCP and NEC, and the anticyclonic circulation near eastern China associated with the SOM6 pattern causes above-average precipitation in the NCP. On interannual time scales, the SOM2 pattern occurrence with an increasing trend tends to induce an increasing summer precipitation trend in the NCP. The SOM3 pattern occurrence is negatively correlated with the summer precipitation in NEC. Overall, classifying the synoptic circulation patterns helps to improve precipitation forecasting and provides insights into the synoptic circulation patterns dominating the occurrences of REPEs.

A high-quality and granular probability of default (PD) model is on many practical dimensions far superior to any categorical credit rating system. Business adoption of a PD model, however, needs to factor in the long-established business/regulatory conventions built around letter-based credit ratings. A mapping methodology that converts granular PDs into letter ratings via referencing the historical default experience of some credit rating agency exists in the literature. This paper improves the PD implied rating (PDiR) methodology by targeting the historical credit migration matrix instead of simply default rates. This enhanced PDiR methodology makes it possible to bypass the reliance on arbitrarily extrapolated target default rates for the AAA and AA+ categories, a necessity due to the fact that the historical realized default rates on these two top rating grades are typically zero.

COVID-19 has affected China's financial markets; accordingly, we investigate the effect of COVID-19 on the risk spillover between fintech and traditional financial industries. Using data from April 25, 2012 to April 22, 2022, which we divide into two parts (before and during the COVID-19 periods), we model the dynamic risk spillover relationship following the DCC-GARCH-BEKK and MMV-MFDFA methods. The results show that: (1) The dynamic relationship between fintech and traditional finance is almost positive most of the time, and the dynamic correlations between fintech and realty (real estate development and operation) are the largest. The dynamic linkage between fintech and traditional finance declines after the COVID-19 outbreak. (2) There exists a risk spillover from fintech to every type of bank before and during the COVID-19 periods. Notably, the risk spillover effect of fintech to large state-owned banks and city commercial banks is the largest separately before and during the COVID-19 periods. Meanwhile, there exist a two-way risk spillover between fintech and almost all other traditional financial industries before and during the COVID-19 periods. (3) Owing to the COVID-19 pandemic, the risk spillover relationship, which is in pairs and in the system become more complex. (4) Regarding the whole system, the correlation in the system is anti-persistent most of the time. Moreover, there are large fluctuations and more complex characteristics during the COVID-19 outbreak. However, the whole system was smooth most of the time before the outbreak of the COVID-19 pandemic.

Biological control is an effective measure in the green control of rice diseases. To search for biocontrol agents with broad-spectrum and high efficiency against rice diseases, in this study, a strain of antagonistic bacterium BR-01 with strong inhibitory effect against various rice diseases was isolated from Bolbostemmatis Rhizoma by plate confrontation method. The strain was identified as Bacillus velezensis by morphological observation, physiological and biochemical identification, and molecular characterization by 16S rDNA and gyrB gene sequencing analysis. The confrontation test (dual culture) and Oxford cup assays demonstrated that B. velezensis BR-01 had strong antagonistic effects on Magnaporthe oryzae, Ustilaginoidea virens, Fusarium fujikuroi, Xanthomonas oryzae pv. Oryzicola, and Xanthomonas oryzae pv. oryzae, the major rice pathogens. The genes encoding antimicrobial peptides (ituA, ituD, bmyB, bmyC, srfAA, fenB, fenD, bacA, and bacD) were found in B. velezensis BR-01 by PCR amplification with specific primers. B. velezensis BR-01 could produce protease, cellulase, β-1,3-glucanase, chitinase, indoleacetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase, and might produce three lipopeptide antibiotics, surfactin, iturin, and fengycin based on Liquid chromatography–mass spectrometry (LC-MS) results. Furthermore, the plant assays showed that B. velezensis BR-01 had significant control effects on rice bacterial blight and bacterial leaf streak by pot experiments in greenhouse. In conclusion, B. velezensis BR-01 is a broad-spectrum antagonistic bacterium and has the potential as the ideal biocontrol agent in controlling multiple rice diseases with high efficiency.

BackgroundSoluble programmed cell death-ligand 1 (sPD-L1) has been well documented to activate immunosuppression and is considered an essential predictor of negative clinical outcomes for several malignances and inflammatory conditions. However, the clinical significance of sPD-L1 in the peripheral blood of patients with coronary artery disease (CAD) remains unclear. The aim of this study was to assess the correlations of sPD-L1 with clinical features in CAD patients and evaluate the diagnostic value of this protein in CAD.MethodsA total of 111 CAD patients and 97 healthy volunteers who served as healthy controls (HCs) were consecutively enrolled. Plasma levels of sPD-L1 were measured with an amplified enzyme-linked immunosorbent assay (ELISA), and hs-CRP was measured with a C-reactive protein assay kit. The levels of other inflammatory cytokines were assessed in 88 CAD patients and 47 HCs by a multiparameter immunoluminescence flow cytometry detection technique. A logistic regression model was used to assess the independent association of sPD-L1 with acute coronary syndrome (ACS). The correlation between sPD-L1 and inflammatory cytokines in ACS was also assessed.ResultsPlasma levels of sPD-L1 were significantly increased in CAD patients, especially those with ACS. Univariate logistic regression analysis revealed that sPD-L1 (OR: 3.382, 95% CI: 2.249–5.084, p < 0.001), BMI, hypertension, diabetes, dyslipidemia, previous MI, and the levels of HDL-C, LDL-C and hs-CRP were significantly associated with ACS. sPD-L1 (OR: 3.336, 95% CI: 1.084–6.167, p = 0.001) was found to be independently and significantly associated with ACS in the subsequent multivariable logistic regression analysis. Additionally, elevated plasma sPD-L1 levels were associated with increased interleukin-6 and interleukin-8 levels in ACS patients. Receiver operating characteristic (ROC) analysis showed that the AUC of sPD-L1 for diagnosing ACS was 0.778, with a sensitivity of 73.9% and a specificity of 73.4%, which was comparable with that of the inflammatory biomarker hs-CRP.ConclusionThe plasma sPD-L1 level reflects the severity of CAD, is associated with inflammatory responses and is a potential new biomarker for the diagnosis of ACS.

Abstract Modern data center networks typically adopt multi-rooted tree topologies such leaf-spine and fat-tree to provide high bisection bandwidth. Load balancing is critical to achieve low latency and high throughput. Although the per-packet schemes such as Random Packet Spraying (RPS) can achieve high network utilization and near-optimal tail latency in symmetric topologies, they are prone to cause significant packet reordering and degrade the network performance. Moreover, some coding-based schemes are proposed to alleviate the problem of packet reordering and loss. Unfortunately, these schemes ignore the traffic characteristics of data center network and cannot achieve good network performance. In this paper, we propose a Heterogeneous Traffic-aware Partition Coding named HTPC to eliminate the impact of packet reordering and improve the performance of short and long flows. HTPC smoothly adjusts the number of redundant packets based on the multi-path congestion information and the traffic characteristics so that the tailing probability of short flows and the timeout probability of long flows can be reduced. Through a series of large-scale NS2 simulations, we demonstrate that HTPC reduces average flow completion time by up to 60% compared with the state-of-the-art mechanisms.

This paper review recent advances in ultraviolet LEDs and summarize that multiple physical fields could built a toolkit for effectively controlling and tailoring crucial properties of nitride quantum structures.