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Abstract Regulatory T cells (Tregs), an essential component of the human immune system, are a heterogeneous group of T lymphocytes with the ability to suppress immune responses and maintain immune homeostasis. Recent evidence indicates that Tregs may impair antitumor immunity and facilitate cancer progression by weakening functions of effector T cells (Teffs). Consequently, targeting Tregs to eliminate them from tumor microenvironments to improve Teffs’ activity could emerge as an effective strategy for cancer immunotherapy. This review outlines the biology of Tregs, detailing their origins, classification, and crucial markers. Our focus lies on the complex role of Tregs in cancer’s development, progression and treatment, particularly on their suppressive role upon antitumor responses via multiple mechanisms. We delve into Tregs’ involvement in immune checkpoint blockade (ICB) therapy, their dual effect on cancer immunotherapy and their potential biomarkers for ICB therapy effectiveness. We also summarize advances in the therapies that adjust Tregs to optimize ICB therapy, which may be crucial for devising innovative cancer treatment strategies.

Abstract The occurrence of multiple primary lung cancer (MPLC) has witnessed a significant surge in recent years within the Chinese population. MPLC is distinguished by its potential genetic susceptibility and notable genetic heterogeneity. Investigating the etiology of MPLC holds substantial clinical importance.The whole genome sequencing (WGS) and genome-wide linkage analysis were performed in a family affected by a dominant form of lung abnormalities. Specifically, five family members were diagnosed with MPLC, while nine members had pulmonary nodules and one normal member. To confirm the potential pathogenic germline mutations sites, Sanger sequencing was performed in an additional 162 MPLC family patients. Furthermore, molecular biology experiments were conducted to investigate the function and the mechanism of the identified pathogenic mutation site in lung cancer A549 and H322, both in vitro and in vivo. Linkage analysis revealed the presence of shared genomic regions among affected family members. Subsequent exome sequencing identified a deleterious variant within these linkage intervals, specifically a heterozygous mutation in ETS-oncogene transcription factors 4 (ETV4). This particular variant was found in affected family members at a rate of 13 out of 15 individuals. Furthermore, ETV4 P433L mutation could be detected in an additional MPLC family patients and mutation frequency was 3.7% (6 out of 162). The ETV4 P433L mutations site was introduced into lung cancer cell lines, resulting in altered migration and stem-like properties of the cancer cells. Further investigation revealed that the activation of the Wnt/β-catenin signaling pathway, which is associated with stemness, could be attributed to the presence of the ETV4 P433L mutation, suggesting its involvement in tumor promotion. A novel pathogenic germline mutation, ETV4 P433L, was identified in a dominant MPLC family, with a mutation rate of 3.7% among MPLC family patients. The ETV4 P433L mutation was found to impact the stem-like properties and migration of tumors through Wnt/β-catenin signaling pathway.

Abstract Magnesium (Mg) plays a pivotal role as an essential component of plant chlorophyll and functions as a critical coenzyme. However, research exploring the regulatory mechanisms of magnesium ions on the synthesis of secondary metabolites is still in its early stages. Sophora tonkinensis is a widely utilized medicinal plant in China, recognized for its diverse secondary metabolites with active properties. This study investigates variations in these ingredients in tissue-cultured seedlings under varying magnesium concentrations. Simultaneously, an omics data analysis was conducted on tissue-cultured seedlings subjected to treatments with magnesium and low magnesium. These comprehensive omics analyses aimed to elucidate the mechanisms through which magnesium influences active components, growth, and development. Magnesium exerts a pervasive influence on various metabolic pathways, forming an intricate network. Research findings indicate that magnesium impacts diverse metabolic processes, including the absorption of potassium and calcium, as well as photosynthetic activity. Consequently, these influences lead to discernible changes in the levels of pharmacologically active compounds and the growth and developmental status.This study is the first to employ a multi-omics data analysis in S. tonkinensis. This methodology allows us to uncover the overarching impact of metabolic networks on the levels of various active ingredients and specific phenotypes.

Abstract Background Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn’s disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences. Methods ROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab. Results In patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004–2.320; P

Abstract Background Congenital craniovertebral deformity, including basilar invagination (BI) and atlantoaxial instability (AAI), are often associated with three-dimensional (3D) deformity, such as C1-2 rotational deformity, craniocervical kyphosis, C1 lateral inclination, among other abnormalities. Effective management of these conditions requires the restoration of the 3D alignment to achieve optimal reduction. Recently, 3D printing technology has emerged as a valuable tool in spine surgery, offering the significant advantage of allowing surgeons to customize the prosthesis design. This innovation provides an ideal solution for precise 3D reduction in the treatment of craniovertebral deformities. Objective This study aims to describe our approach to individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cages for the quantitative correction of craniovertebral junction deformities. Methods A retrospective analysis was conducted on patients with craniovertebral deformities treated at our institution using individualized 3D-printed porous titanium alloy cages. Preoperative CT data were used to construct models for 3D realignment simulations. Cage designs were tailored to the simulated joint morphology following computer-assisted realignment. Preoperative and postoperative parameters were statistically analyzed. Results Fourteen patients were included in the study, with a total of 28 3D-printed porous titanium alloy cages implanted. There were no cases of C2 nerve root resection or vertebral artery injury. All patients experienced symptom relief and stable implant fixation achieved in all cases. No implant-related complications were reported. Conclusion The use of individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cage facilitates precise 3D realignment in patients with craniovertebral deformities, demonstrating effectiveness in symptom relief and stability.

Abstract In this study, SiO2 coating was electrodeposited on Ti45Al8.5Nb alloy to enhance its oxidation resistance at 900 °C. The focus was on the interaction between SiO2 coating and the alloy substrate, and specifically, the role of the Nb element in this context. The formation of a SiO2/(Ti, Nb)O2/Ti5Si3 + Al2O3 three-layer oxide scale significantly inhibits the inward diffusion of oxygen. Beyond the characteristic Ti5Si3 + Al2O3 layer at the interface, the Nb2Al phase embedded within Ti5Si3 was observed. Concurrently, the presence of a (Ti, Nb)O2 layer was confirmed. The relationship between the coating thickness and oxidation resistance was also investigated. It was found that the thickness of the SiO2 coating affects the density of the oxide scale and the inward diffusion rate of oxygen. Moreover, due to the good adhesion to the substrate, the derived oxide scale exhibited good anti-peeling performance when subjected to a cyclic oxidation test.

Abstract Background Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. Methods A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). Results In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg

Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p

Abstract Background Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. Methods We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. Results In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. Conclusions miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs.

Abstract Background The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. Methods Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA

Abstract Background Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem. Methods This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score. Discussion Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function. Trial registration Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 .

BackgroundThis study aimed to examine the evolving trends in the global burden of low back pain (LBP) from 1990 to 2021 and predicted disease burden until 2035.Materials and methodsLBP-related data were obtained from the Global Health Data Exchange (GHDx) query tool. All estimates and their 95% uncertainty intervals (UIs) were generated using DisMod-MR 2.1, a Bayesian meta-regression tool in Global Burden of Disease, Injury, and Risk Factor Study (GBD) 2021. Data processing and visualization were conducted using The R Programming Language software version 4.3.2 and Joinpoint 4.7.ResultsIn 2021, approximately 628.8 million people worldwide were affected by LBP, with approximately 266.9 million new incident cases and age-standardized incidence rate (ASIR) of 3176.6 per 100,000. Compared with 1990, although the ASIR and age-standardized disability-adjusted life years rate (ASDALYsR) decreased, absolute numbers increased significantly. Projections for 2035 reveal a continued decline in ASIR and ASDALYsR for LBP. The LBP burden varied by the sociodemographic index quintile and GBD region, with the highest ASIR and ASDALYsR observed in Central Europe and the greatest decrease in East Asia. Globally, women bear a higher burden of LBP than men, with middle-aged populations experiencing the heaviest burden. Occupational ergonomic factors, high body mass index, and smoking remain the primary risk factors for LBP, with occupational ergonomic factors contributing the most to the overall burden.ConclusionDespite a projected decline in incidence, the global burden of LBP persists, exhibiting significant regional and gender disparities. To mitigate its future burden, precise and effective prevention and control strategies targeting high-risk factors are imperative.

To determine the effect of ignition height on indoor flame spread behavior and overpressure development, a comprehensive full-scale deflagration testing facility was established. Extensive experimental research was conducted within this facility. The findings indicate that indoor flame reignition and the occurrence of secondary explosions are most pronounced with intermediate ignition. Furthermore, the explosion overpressure generated during the reverse turn of shock wave propagation is greater than that produced by the forward turn. In comparison to the peak overpressure Pext in the master bedroom for top, middle, and bottom ignition, the peak overpressure Pext in the second bedroom increased by approximately 14.48 %, 15.04 %, and 19.20 %, respectively. When comparing middle ignition to top ignition, the propagation speed of shock waves in the kitchen balcony, restroom, second bedroom, and master bedroom was enhanced by 34.21 %, 40.85 %, 40.70 %, and 34.65 %, respectively. Furthermore, when comparing middle ignition to bottom ignition, the propagation speed of shock waves in these areas experienced a significant increase of 126.32 %, 124.39 %, 123.26 %, and 113.86 %, respectively. These research findings provide a theoretical foundation and empirical data to support the investigation and analysis of the causes of indoor gas explosion incidents.

BackgroundHypertension (HT) is a common chronic disease in older adults. It not only leads to dizziness and other symptoms affecting balance in older adults with HT but also affects the hemodynamics of the cerebral cortex. At present, potential neural mechanisms of balance control in older adults with HT are still unclear. Therefore, this study aimed to explore the differences in the center of pressure (COP) and cerebral cortex activation between older adults with HT and normotension (NT) during standing balance tasks. This study May provide guidance for the early detection of the risk of falls among older adults with HT and the development of clinical rehabilitation strategies.MethodsIn this cross-sectional study, 30 older adults with NT (NT group) and 27 older adults with HT (HT group) were subjected to three conditions: task 1, standing with eyes open on a stable surface; task 2, standing with eyes closed on a stable surface; and task 3, standing with eyes open on the surface of the foam pad. Cortical hemodynamic reactions were measured using functional near-infrared spectroscopy, and COP parameters were measured using a force plate.ResultsThe mean velocity of the COP in the medial–lateral direction in the NT group was significantly higher than that in the HT group (F = 5.955, p = 0.018) during task 3. When proprioception was disturbed, the activation of the left premotor cortex and supplementary motor cortex in the HT group was significantly lower than that in the NT group (F = 14.381, p

Abstract Background Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues. Methods To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids. Results The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation. Conclusions These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.

Silicon carbide (SiC) power modules play an essential role in the electric vehicle drive system. To improve their performance, reduce their size, and increase production efficiency, this paper proposes a multiple staked direct bonded copper (DBC) unit based power module packaging method to parallel more chips. This method utilizes mutual inductance cancellation effect to reduce parasitic inductance. Because the conduction area in the new package is doubled, the overall area of power module can be reduced. Entire power module is divided into smaller units to enhance manufacture yield, and improve design freedom. This paper provides a detailed design, analysis and fabrication procedure for the proposed package structure. Additionally, this paper offers several feasible solutions for the connection between power terminals and DBC untis. With the structure, 18 dies were paralleled for each phase-leg in a econodual size power module. Both simulation and double pulse test results demonstrate that, compared to conventional layouts, the proposed package method has 74.8% smaller parasitic inductance and 34.9% lower footprint.

High-performance Cu/Graphene composite wire synergistically strengthened by nano Cr 3 C 2 phase was directly synthesized via hot press sintering followed by severe cold plastic deformation, using liquid paraffin and CuCr alloy powder as the raw materials. Since graphene is in situ formed under the catalysis of copper powder during the sintering process, the problem that graphene is easy to agglomerate and difficult to disperse uniformly in the copper matrix has been solved. The nano Cr 3 C 2 -particles nailed at the interface favor to improve the interface bonding. The Cu/Graphene composite possesses high electrical conductivity, hardness, and plasticity. The composite wire exhibits high electrical conductivity of 96.93% IACS, great tensile strength of 488 MPa, and excellent resistance to softening. Even after annealing at 400°C for 1 h, the tensile strength can still reach 268 MPa with a conductivity of about 99.14% IACS. The wire's temperature coefficient of resistance (TCR) is largely reduced to 0.0035/°C due to the complex structure, which leads the wire to present low resistivity at higher temperatures. Such Cu/Graphene composite wire with excellent comprehensive performance has a good application prospect in high-power density motors.

Abstract Transforming growth factor (TGF)-β is a multifunctional cytokine expressed by almost every tissue and cell type. The signal transduction of TGF-β can stimulate diverse cellular responses and is particularly critical to embryonic development, wound healing, tissue homeostasis, and immune homeostasis in health. The dysfunction of TGF-β can play key roles in many diseases, and numerous targeted therapies have been developed to rectify its pathogenic activity. In the past decades, a large number of studies on TGF-β signaling have been carried out, covering a broad spectrum of topics in health, disease, and therapeutics. Thus, a comprehensive overview of TGF-β signaling is required for a general picture of the studies in this field. In this review, we retrace the research history of TGF-β and introduce the molecular mechanisms regarding its biosynthesis, activation, and signal transduction. We also provide deep insights into the functions of TGF-β signaling in physiological conditions as well as in pathological processes. TGF-β-targeting therapies which have brought fresh hope to the treatment of relevant diseases are highlighted. Through the summary of previous knowledge and recent updates, this review aims to provide a systematic understanding of TGF-β signaling and to attract more attention and interest to this research area.

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.

Adaptive compliance control is critical for rehabilitation robots to cope with the varying rehabilitation needs and enhance training safety. This article presents a trajectory deformation-based multi-modal adaptive compliance control strategy (TD-MACCS) for a wearable lower limb rehabilitation robot (WLLRR), which includes a high-level trajectory planner and a low-level position controller. Dynamic motion primitives (DMPs) and a trajectory deformation algorithm (TDA) are integrated into the high-level trajectory planner, generating multi-joint synchronized desired trajectories through physical human-robot interaction (pHRI). In particular, the amplitude modulation factor of DMPs and the deformation factor of TDA are adapted by a multi-modal adaptive regulator, achieving smooth switching of human-dominant mode, robot-dominant mode, and soft-stop mode. Besides, a linear active disturbance rejection controller is designed as the low-level position controller. Four healthy participants and two stroke survivors are recruited to conduct robot-assisted walking experiments using the TD-MACCS. The results show that the TD-MACCS can smoothly switch three control modes while guaranteeing trajectory tracking accuracy. Moreover, we find that appropriately increasing the upper bound of the deformation factor can enhance the average walking speed (AWS) and root mean square of trajectory deviation (RMSTD).

Abstract Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients’ poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.

To realize the effective reuse of the existing model measurement process planning and to improve the efficiency of the preparation of the measurement program, this paper proposes an on-machine measurement model partial retrieval method based on geometric features. First, the B-Rep information and measurement procedures of the model are extracted, and combined with the analysis of the geometric features of the on-machine measurement, the model is transformed into an attribute adjacency labeling graph; next, the index tree is constructed by using hash coding, and the result set is obtained through the filtering-verification framework to realize the synthesis similarity evaluation of the geometrical level of the on-machine measurement model; lastly, different reuse methods of the measurement process planning are selected based on the model’s similarity value. Fast programming based on partial retrieval of on-machine measurement models is realized by directly selecting programs, calling macros, and assigning values to variables. The experimental results show that the method can realize the effective reuse of the existing model measurement process planning, which can improve the efficiency of the preparation of the measurement program and meet the actual needs of on-machine measurement.

Objective To evaluate the impact of H3K27M mutation in the prognosis of histological high-grade intramedullary astrocytoma. Methods A total of 78 patients who were diagnosed with high-grade spinal cord astrocytoma were included. Clinical data consisting demographic, radiological, molecular features and treatment data were recorded. Univariate and multivariate Cox analysis were performed to investigate variables associated with survival outcome of histological high-grade spinal cord astrocytoma. Results Median survival time was 21 months. Overall survival (OS) at 1 and 3 years was 65.7% and 40.7%, respectively. Sex, location, and tumor span did not present significant association with OS. Patients with H3K27M mutation showed significant shorter duration of symptom than patients with H3K27 wild-type. As respect to adjuvant treatment, adjuvant radiotherapy and chemotherapy were associated with favorable OS (both p = 0.01). Younger patients (age ≤ 18 years) had shorter OS (p = 0.008) than adult patients (age > 18 years). Of note, H3K27M mutation did not show significant impact on the survival outcome, regardless of histology grade 3 or grade 4 (p = 0.3). Conclusion Histological high-grade spinal cord astrocytoma has dismal prognosis. Our study demonstrated that H3K27M mutation did not show significant impact on survival outcome of histological high-grade spinal cord astrocytoma.

Abstract Histone H3 lysine 4 trimethylation (H3K4me3) is a canonical chromatin modification associated with active gene transcription, playing a pivotal role in regulating various cellular functions. Components of the H3K4me3 methyltransferase complex, known as the proteins associated with SET1 (COMPASS), have been implicated in exerting cancer-protective or cancer-inhibitory effects through inducive H3K4me3 modification. However, the role of the indispensable non-catalytic component of COMPASS CXXC-type zinc finger protein 1 (CFP1) in malignant progression remains unclear. We have unveiled that CFP1 promote lung adenocarcinoma (LUAD) cell proliferation, migration, and invasion while impairing cell apoptosis through in vitro and in vivo models. In addition, high CFP1 expression was identified as emerged as an adverse prognostic indicator across multiple public and in-house LUAD datasets. Notably, CFP1 deficiency led to dual effects on cancer cell transcriptome including extensive inactivation of cancer-promoting as well as activation of cancer repressors. Combining this with the chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we showed that CFP1 ablation reshaped the genomic H3K4me3 distribution signature, with prominent effects on TGF-β and WNT signaling pathways. Collectively, our study proposes that CFP1 mediates tumorigenesis by genomic histone methylation reprogramming, offering insights for future investigations into epigenetic modifications in cancer progression and potential therapeutic advancements.

Abstract Background Mid‐rectal cancer treatment traditionally involves conventional laparoscopic‐assisted resection (CLAR). This study aimed to assess the clinical and therapeutic advantages of Natural Orifice Specimen Extraction Surgery (NOSES) over CLAR. Aims To compare the clinical outcomes, intraoperative metrics, postoperative recovery, complications, and long‐term prognosis between NOSES and CLAR groups. Materials & Methods A total of 136 patients were analyzed, with 92 undergoing CLAR and 44 undergoing NOSES. Clinical outcomes were evaluated, and propensity score matching (PSM) was employed to control potential biases. Results The NOSES group exhibited significant improvements in postoperative recovery, including lower pain scores on days 1, 3, and 5 (p < .001), reduced need for additional analgesics (p = .02), shorter hospital stays (10.8 ± 2.3 vs. 14.2 ± 5.3 days; p < .001), and decreased intraoperative blood loss (48.1 ± 52.7 mL vs. 71.0 ± 55.0 mL; p = .03). Patients undergoing NOSES also reported enhanced satisfaction with postoperative abdominal appearance and better quality of life. Additionally, the NOSES approach resulted in fewer postoperative complications. Conclusion While long‐term outcomes (overall survival, disease‐free survival, and local recurrence rates) were comparable between the two methods, NOSES demonstrated superior postoperative outcomes compared to CLAR in mid‐rectal cancer treatment, while maintaining similar long‐term oncological safety. These findings suggest that NOSES could serve as an effective alternative to CLAR without compromising long‐term results.

Oil field-associated gas is typically a mixture of light alkanes. To ensure production safety, it is essential to investigate the combustion characteristics and the reaction mechanism of light alkane gas mixtures to uncover the underlying mechanisms of the combustion reaction. This paper investigates the equilibrium gas component concentrations resulting from the reaction of a gas mixture of methane, ethane, and propane at specific ratios through experimental tests. The study's results demonstrate that the equilibrium concentrations of methane, ethane, and propane initially decrease and then increase with the rise of the equivalence ratio under the same initial pressure conditions. In oxygen-poor conditions, the equilibrium concentration ratio of methane gradually increases in proportion to the equilibrium ratio, confirming that ethane and propane are the preferred participants in the reaction. Furthermore, a study of the equilibrium concentration of the critical intermediate product, ethylene, revealed that it does not completely oxidize in the combustion reaction. It can persist under both oxygen-rich and oxygen-poor conditions, with an equilibrium concentration of approximately 0.02%. The findings of this paper can serve as a theoretical supplement to the research on explosive gas combustion and explosions.

Abstract Infectious diseases pose significant threats to public health and the global economy, necessitating rapid and accurate detection of the causative microorganisms to prevent their transmission. Nanomaterials, with their unique size‐dependent physical and chemical attributes, present innovative solutions for the detection of infectious diseases, thereby playing a crucial role in the development of advanced detection technologies. This review describes the application of inorganic nanomaterials in the detection of infectious diseases, focusing on the potential uses of nanomaterials, including carbon nanoallotropes, quantum dots, gold and silver nanoparticles, magnetic nanoparticles and upconversion nanoparticles.

Abstract Background Xylo-oligomers are a kind of high value-added products in biomass fractionation. Although there are several chemical methods to obtain xylo-oligomers from biomass, the reports about the deep eutectic solvents (DESs)-mediated co-production of xylo-oligomers and fermentable sugars and the related kinetic mechanism are limited. Results In this work, glycolic acid-based DESs were used to obtain xylo-oligomers from corncob. The highest xylo-oligomers yield of 65.9% was achieved at 120 °C for 20 min, of which the functional xylo-oligosaccharides (XOSs, DP 2–5) accounted for up to 31.8%. Meanwhile, the enzymatic digestion of cellulose and xylan in residues reached 81.0% and 95.5%, respectively. Moreover, the addition of metal inorganic salts significantly accelerated the hydrolysis of xylan and even the degradation of xylo-oligomers in DES, thus resulting in higher selectivity of xylan removal. AlCl3 showed the strongest synergistic effect with DES on accelerating the processes, while FeCl2 is best one for xylo-oligomers accumulation, affording the highest xylo-oligomers yield of 66.1% for only 10 min. Furthermore, the kinetic study indicates that the ‘potential hydrolysis degree’ model could well describe the xylan hydrolysis processes and glycolic acid/lactic acid (3:1) is a promising solvent for xylo-oligomers production, in particular, it worked well with FeCl2 for the excellent accumulation of xylo-oligomers. Conclusions Glycolic acid-based deep eutectic solvents can be successfully applied in corncob fractionation with excellent xylo-oligomers and fermentable sugars yields on mild conditions, and the large amount of xylo-oligosaccharides accumulation could be achieved by specific process controlling. The strategies established here can be useful for developing high-valued products from biomass.

Ducted fan motors play a crucial role in promoting various applications of flying electric vehicles. In ducted fan motor systems, motor performance affects the speed of the fan, the flow field of the fan affects the thermal field of the motor, and the thermal field influences the performance of the motor. The coupling model between fan static thrust, motor power, and motor temperature rise is established in this paper. After confirming the external dimensions of the motor, three cooling schemes of the motor casing are designed. The casing forms are as follows: model 1 with smooth surface, model 2 with circular fins, and model 3 with longitudinal fins. The optimization work was carried out on the geometric dimensions of two types of fins for model 2 and model 3, and the static thrust and heat transfer performance of the motors were calculated. This study proposes that the ratio of thrust-to-temperature rise is an indicator for future optimization design of ducted fan motors. Model 3 with longitudinal fins has a higher thrust-to-temperature rise ratio. The thrust temperature rise in model 3 has increased by 24.77% compared to model 1.

Objective Long-level intramedullary spinal cord tumors (LIMSCTs) cause complex treatment issues. However, LIMSCTs have rarely been analyzed separately. The authors reported a large case series of LIMSCTs and analyzed the clinical characteristics and treatment outcomes. Methods The medical data of patients with LIMSCTs at our institution between January 2015 and December 2019 were retrospectively reviewed. Demographics, tumor size and location, pathology, extent of resection, and neurological functional status were collected. Results A total of 43 consecutive cases were included. Twenty-three cases (53.5%) of LIMSCTs were ependymal tumors. All patients with ependymal tumors achieved gross total resection (GTR). In ependymal tumor cases, 3 cases (13%) of ependymal tumors experienced postoperative neurological deterioration, and 66% of them showed an improvement at follow-up; 25.6% were low-grade astrocytic tumors. The rates of GTR, subtotal resection (STR) and partial resection (PR) were 63.6%, 27.3%, and 9.1%, respectively. Twenty-seven percent cases showed postoperative neurological worsening, and 33% of them had an improvement at follow-up; 20.9% were high-grade astrocytic tumors. The excision rates were 44.4% for GTR, 44.4% for STR, and 11% for PR, respectively. Fifty-five percent cases showed postoperative neurological worsening, and none of them had an improvement at follow-up. Conclusion In this series, all LIMSCTs were gliomas. Aggressive tumor resection did not increase the risk of long-term functional deterioration in ependymal tumors and low-grade astrocytic tumors, but in high-grade astrocytic tumors, patients had a higher risk of neurological deterioration and difficulty in recovery. In ependymal tumors and low-grade astrocytic tumors, patients can achieve long-time survival after performing aggressive tumor resection.

Background Second-line anti-tuberculosis drugs are widely used in clinic for multi-drug resistant tuberculosis (MDR-TB) . At present, there are several reticulated meta-analyses investigating them, but the effect is not very satisfactory. Objective To systematically evaluate the efficacy and safety of five anti-tuberculosis chemotherapy regimens in the treatment of MDR-TB. Methods Randomized controlled trials (RCTs) on anti-tuberculosis drug for MDR-TB were retrieved from PubMed, Medline, Web of Science, VIP, and Wanfang data from January 2010 to March 2022. The experimental group was treated with individualized treatment combined with moxifloxacin (Mfx) , levofloxacin (Lfx) , linezolid (Lzd) , clofazimine (Cfz) and bedaquiline (Bdq) . The control group was treated with individualized treatment combined with placebo or Lfx. After literature screening and data extraction, quality assessment was performed using the risk of bias assessment tool provided by the Cochrane system evaluator handbook 5.1.0. Bayesian network Meta-analysis on the rate of sputum culture conversion, clinical efficacy rate and incidence of adverse reactions was conducted using GeMTC 0.14.3 software and Stata SE 15.0 software. Results A total of 39 RCTs and 3 860 patients were included. Results of Meta-analysis showed that the rate of sputum culture conversion of Bdq, Cfz, Lfx, Lzd, Mfx, were higher than those of placebo〔OR=3.49, 95%CI (2.11, 5.73) ; OR=2.85, 95%CI (1.93, 4.23) ; OR=2.93, 95%CI (1.45, 6.94) ; OR=6.37, 95%CI (3.67, 11.31) ; OR=8.15, 95%CI (3.97, 18.47) 〕 (PLzd (82.1%) >Bdq (50.2%) >Lfx (37.5%) >Cfz (35.9%) >placebo (0.1%) . The clinical response rates for Bdq, Cfz, Lfx, Lzd and Mfx were all higher than that of placebo〔OR=2.80, 95%CI (1.74, 4.46) ; OR=2.02, 95%CI (1.33, 3.08) ; OR=4. 93, 95%CI (2.13, 11.50) ; OR=5.72, 95%CI (3.44, 10.08) ; OR=3.20, 95%CI (1.16, 9.21) 〕 (PLzd (86.2%) >Lfx (54.6%) >Bdq (47.3%) >Cfz (24.3%) >placebo (0.1%) . There were no significant differences both in the incidence of adverse reactions among the 5 anti-tuberculosis drugs and placebo (P>0.05) and in the incidence of adverse reactions of each anti-tuberculosis drugs between groups (P>0.05) . Conclusion Current evidence suggests that Mfx and Lzd are more effective than other drugs in the treatment of MDR-TB. The results of the study need to be further verified due to the small number clinical studies and sample size.

Background and Aims: This study compared disease burden, experiences, and health-related quality of life (HRQoL) between patients with Crohn’s perianal fistulas (CPFs) and those with Crohn’s disease (CD) without perianal fistulas (PFs; non-PF CD). Methods: This cross-sectional, observational study was conducted in 3 cohorts of US patients aged 18–89 years with self-reported, physician-diagnosed CD: (1) non-PF CD; (2) CPF without PF-related surgery; and (3) CPF with PF-related surgery. Data on medical and surgical interventions, CD-specific symptoms, HRQoL (assessed using the Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaires), and fecal incontinence (assessed using Revised Faecal Incontinence Scale and Fecal Incontinence Quality of Life questionnaires) were collected via a web-enabled questionnaire. Results: In total, 403 patients with CD completed the questionnaire (non-PF CD, n = 300; CPF without surgery, n = 51; CPF with surgery, n = 52). A high symptom burden was seen across cohorts. More patients with CPF underwent ≥1 CD-related surgery and experienced ≥1 failure of CD-related surgery (79% and 20%) vs non-PF CD (53% and 9%; P < .001). Overall HRQoL outcomes were worse for patients with CPF vs non-PF CD, with significantly worse Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaire scores for those without PF-related surgery (P < .01). Across all cohorts, 58% of patients reported experiencing fecal incontinence, which had a greater negative impact (higher Revised Faecal Incontinence Scale scores; lower Fecal Incontinence Quality of Life scores) in patients with CPF vs non-PF CD. Conclusion: Patients with CPF experience substantial HRQoL burden, reflecting the impact of symptoms and medical/surgical interventions. These results may help to inform comprehensive care strategies to improve patient HRQoL.

Horizontal wells within the roof are an effective method to develop gas in broken and soft coal seams, and layer-penetrating fracturing is a key engineering method for the stimulating of horizontal wells within the roof of a coal seam. To understand the propagation law of fracture in the composite roof of coal seams, this study conducted research using numerical simulation and physical similarity simulation methods. Furthermore, engineering experiments were carried out at the Panxie coal mine in the Huainan Mining Area and the Luling coal mine in Huaibei Mining Area, to further validate this technology. The numerical simulation results indicated that fracture within the coal seam roof can propagate from the roof to the target coal seam, effectively fracturing the coal seam. Due to the coal seam’s plasticity being greater than that of the roof mudstone, the coal seam forms a broader fracture than the roof. With the increase in pseudo roof mudstone thickness and being under constant fracturing displacement, the energy consumed by the pseudo roof mudstone during fracturing causes a decrease in pore pressure when fracture extends to the coal seam, resulting in a reduction in fracture width. Therefore, the pseudo roof mudstone is an adverse factor for the expansion of hydraulic fracturing. Physical similarity simulation results demonstrated that when horizontal boreholes were arranged within the siltstone of the coal seam roof, were under reasonable vertical distance and high flow rate fracturing via fluid injection conditions, and if the coal seam had a thin pseudo roof mudstone, the fracture could propagate through the direct roof-pseudo roof interface and the pseudo roof-coal seam interface, extending to the lower coal seam. The fracture form was curved and had irregular vertical fractures, indicating that hydraulic fracturing can achieve production enhancement and the transformation of soft and hard coal seams. However, when the coal seam had a thick pseudo roof mudstone, the mudstone posed strong resistance to hydraulic fracturing, making it difficult for the fracture to propagate to the lower coal seam. Therefore, the pseudo roof mudstone plays a detrimental role in hydraulic fracturing and the production enhancement of coal seams. The engineering verification conducted at Panxie coal mine and Luling coal mine showed that by utilizing a construction drainage rate of 7.5 cubic meters per minute at Panxie coal mine, the maximum fracture length reached 218.3 m, with a maximum fracture height of 36.8 m. The maximum daily gas production of a single well reached 1450 cubic meters per day, with a total gas extraction volume of 43.62 × 104 cubic meters across 671 days. At Luling coal mine, utilizing a construction drainage rate of 10 cubic meters per minute, the maximum fracture length reached 169.1 m, with a maximum fracture height of 20.5 m. The maximum daily gas production of a single well reached 10,775 cubic meters per day, with a total gas extraction volume of 590 × 104 cubic meters for 1090 days. This indicated that the fracture within the roof of coal seams can penetrate the composite roof of coal seams and extend to the interior of the coal seams, achieving the purpose of transforming fractured and low-permeability coal seams and providing an effective mode of gas extraction.

We sorted the waste from mechanical processing to form recycled steel fibers. In order to study the flexural mechanical properties of reinforced concrete beams after the addition of recycled steel fibers, four recycled steel fiber concrete beams (RSFCBs) and one normal concrete beam (NCB) were designed and poured using the volume fraction of steel fibers (0%, 0.5%, 1%, 1.5%, 2%) as the variables. Normal section bending tests were conducted on them under a concentrated load. We obtained experimental data such as the cracking load, ultimate load, mid-span deflection, and steel and concrete strain of the beam by gradually loading the test beam, and we observed and recorded the development of cracks. The results indicate that the NCB exhibits crushing failure, while the RSFCBs exhibit equilibrium failure. The addition of recycled steel fibers effectively controls the extension of cracks, resulting in a better bending toughness of the beam. The bending performance of RSFCBs with different volume additions shows a trend of first increasing and then decreasing with the increase in steel fiber content. The peak value was reached when the steel fiber content was 1.5%, which increased the bending bearing capacity by 54.72% compared with the NCB. With the increase in steel fiber content, the required load value for tensile steel bars to yield also increases, reaching a peak at a content of 1.5%, which increases the bending bearing capacity by 44.64% compared with the NCB. The addition of recycled steel fibers enables the beam to improve its bearing capacity while limiting the development of longitudinal reinforcement strain, allowing the longitudinal reinforcement to yield under higher loads and improving the overall bending performance of the beam.

In this paper, a new type of assembled RC beam–column joint with a beam-end steel cover-plate connection is proposed to achieve seismic toughness and damage control of the joint. Energy-dissipation plates with different structural forms are proposed, and a series of seismic performance indexes of the joints are calculated and analyzed by using the finite element method. The energy-dissipation plate with an arc notch can reach the yield condition faster, and the ultimate bearing capacity of the joint reaches the maximum. The bending design of energy-dissipation plates is carried out by calculating the demand bending moment, and energy-dissipation plates of different structural forms are simulated and verified. The results show that the proposed design formula can ensure that the bending moment at the beam end still maintains elastic deformation when the energy-dissipation plate yields. The important parameters affecting the bending moment of the weakened part in the middle of the energy-dissipation plate are analyzed. Finally, this paper also analyzes the important parameters affecting the seismic performance of the joints. The results show that the seismic performance of the newly assembled RC beam–column joints proposed in this paper is better than that of cast-in-place joints. Increasing the longitudinal reinforcement ratio appropriately can greatly improve the ultimate bearing capacity and ductility of the joints. Increasing the thickness of the energy-dissipation plate, increasing the strength of the energy-dissipation plate, increasing the axial compression ratio of the column, increasing the strength of the concrete, and increasing the strength of the shear web can improve the ultimate bearing capacity of the joints but also reduce their ductility. Under different axial compression ratios, the strain in the core area of the joints is low, and the compressive damage of the concrete is zero, which verifies the effectiveness of the damage-control design of the proposed model.

Earthquakes frequently cause serious casualties and property loss in China. Building smart communities is an effective means of preventing damage and reducing disastrous outcomes from earthquakes. This article reports on the Chinese experience of building a smart community and the concept of smart service for preventing damage and mitigating disasters from earthquakes in Hubei province. The case study examined the Xinheyuan Smart Community, which is the first such community constructed in Hubei province, including its background development, system design and system functions. The disaster mitigation function was tested when a magnitude 4.9 earthquake occurred in Yingcheng earthquake.

It is not clear how the distribution of retained fracturing fluids and its effect on the permeability and wettability in tight oil reservoirs interact. Especially, there are more qualitative studies and less quantitative studies on this issue. Under laboratory experimental conditions, this paper clarifies the distribution of retained fracturing fluids in the core and reveals the influence rule of retained fracturing fluids on tight reservoir permeability and wettability. It is found that the main retention space of retained fracturing fluids in a tight reservoir is a microporous interval, and the residual oil after oil displacement by retained fracturing fluids mainly exists in the core in the form of dots or porphyries. The smaller permeability and porosity of the core will lead to more retained fracturing fluids. The permeability of different cores after fracturing fluid retention has decreased to varying degrees compared with that before fracturing fluid retention. The wettability of core slices before and after fracturing fluid retention was tested, and the effect of retained fracturing fluids on reservoir wettability was not significant. This study has important significance for improving the recovery of tight oil reservoirs and enhancing the understanding of postfracturing fluid retention.

This paper investigates the mechanical properties of a traditional welded rigid joint with a weakened panel zone under seismic load. The created finite element model is calibrated by the high-strength steel joint test, carried out by the team in the early stage, and the effectiveness of the finite element method was verified. The finite element software ABAQUS is used to investigate the influence of different joint web thicknesses on the mechanical properties of middle column joints under a low-cyclic-loading test. Supported by a validated numerical model, the ductility, energy dissipation, and other properties of different thicknesses of panel zone column webs are carefully analyzed. The results indicate that the thickness of the web plate in the panel zone significantly affects the location of the joint plastic hinge. The ultimate loading capacity of the joints increased significantly with an increase in the thickness of the webs in the panel zones. Compared with the joint with a weakened panel zone, the hysteresis curve of the strengthened joint is fuller; meanwhile, it cannot alleviate the stress concentration at the weld holes of the web. When the thickness of the joint domain web is too weak, excessive deformation in the joint domain will lead to a decrease in the bearing capacity of the joint, causing damage. The stiffness degradation coefficient of the web-thickened specimen was found to be dominated and controlled by the stiffness of the beam; however, with an increase in the thickness of the web, the stiffness degradation coefficient remained basically unchanged. Finally, a recommendation for weakened beam–column interior joints based on the steel frame panel zone is made, which will lay a foundation for the simulation and analysis of the seismic performance of this structure.

This paper deals with the Dual-Function Radar and Communication (DFRC) signal design for a Multiple-Input–Multiple-Output (MIMO) system, considering the presence of signal-dependent clutter. A modulation methodology called Spectral Position Index and Amplitude (SPIA) modulation is proposed, which involves selecting passband and stopband positions and applying amplitude modulation. Signal to Interference plus Noise Ratio (SINR) is maximized to enhance radar detectability. Meanwhile, variable modulus and communication modulation constraints are enforced to ensure compatibility with the current hardware techniques and communication demand, respectively. In addition, the mainlobe width and sidelobe level constraints used to concentrate energy in a specific area of space are enforced. To tackle the resulting nonconvex and NP-hard optimization problem, an Iterative Block Enhancement (IBE) framework that alternately updates each signal in each emitting antenna is exploited to monotonically increase SINR. Each block involves the Dinkelbach’s Iterative Procedure (DIP), Sequential Convex Approximation (SCA) and Alternating Direction Method of Multipliers (ADMM) to obtain a single signal. The computational complexity and convergence of the algorithm are analyzed. Finally, the numerical results highlight the effectiveness of the proposed dual-function scheme in sidelobe signal-dependent clutter.

Thickness nonuniformity is a bottleneck in the micro electroforming process of micro-metal devices. In this paper, a new method of fabricating a layered auxiliary cathode is proposed to improve the thickness uniformity of a micro-electroforming layer. In order to analyze the general applicability of the proposed method, four basic microstructures, namely circular, square, regular triangular, and regular hexagonal were used to study the effect of a layered auxiliary cathode on thickness uniformity through simulation and experimentation. The simulation results showed that with the help of the proposed auxiliary cathode, the thickness nonuniformity of four microstructures should decrease due to the reduced edge effect of the current density. The experimental results showed that the thickness uniformity of four microstructures fabricated via the proposed method was improved by 190.63%, 116.74%, 80.43%, and 164.30% compared to that fabricated via the traditional method, respectively. Meanwhile, the micro-gear was fabricated and the nonuniformity was reduced by 101.15% using the proposed method.

The thickness nonuniformity of an electroformed layer is a bottleneck problem for electroformed micro metal devices. In this paper, a new fabrication method is proposed to improve the thickness uniformity of micro gear, which is the key element of various microdevices. The effect of the thickness of the photoresist on the uniformity was studied by simulation analysis, which showed that as the thickness of the photoresist increased, the thickness nonuniformity of the electroformed gear should decrease due to the reduced edge effect of the current density. Differently from the traditional method performed by one-step front lithography and electroforming, multi-step, self-aligned lithography and electroforming are used to fabricate micro gear structures in proposed method, which intermittently keeps the thickness of photoresist from decreasing during processes of alternate lithography and electroforming. The experimental results show that the thickness uniformity of micro gear fabricated by the proposed method was improved by 45.7% compared with that fabricated by the traditional method. Meanwhile, the roughness of the middle region of the gear structure was reduced by 17.4%.

In ocean voyages, cabin indoor localization plays a considerably important role in ship safety management. Due to the special structure of ships and the influence of internal and external environment, the mainstream indoor positioning technology nowadays is not ideal for positioning inside the cabin. In order to improve the positioning accuracy, this article proposes an adaptive K -value-based cabin indoor positioning algorithm. The algorithm constructs a fingerprint library by collecting Received Signal Strength Indication data and carries out filtering; matches fingerprint information by adaptive K -values during the localization process, while using double K -nearest neighbor to reduce the influence of outlier points on the final localization; and finally uses the multi-point mass center method to determine the final localization results. The experimental results in the automated cabin laboratory show that the average positioning error of the algorithm is 1.74 m, which can well meet the cabin indoor positioning requirements.

Background. Heart failure (HF) is defined as the inability of the heart’s systolic and diastolic function to properly discharge blood flow from the veins to the heart. The goal of our research is to look into the possible mechanism that causes HF. Methods. The GSE5406 database was used for screening the differentially expressed genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) network were applied to analyze DEGs. Besides, cell counting Kit-8 (CCK-8) was conducted to observe the knockdown effect of hub genes on cell proliferation. Results. Finally, 377 upregulated and 461 downregulated DEGs came out, enriched in the extracellular matrix organization and gap junction. According to GSEA results, Hoft cd4 positive alpha beta memory t cell bcg vaccine age 18–45 yo id 7 dy top 100 deg ex vivo up, Sobolev t cell pandemrix age 18–64 yo 7 dy dn, and so on were significantly related to gene set GSE5406. 7 hub genes, such as COL1A1, UBB, COL3A1, HSP90AA1, MYC, STAT3 and MAPK1, were selected from PPI networks. CCK-8 indicated silencing of STAT3 promoted the proliferation of H9C2 cells and silencing of UBB inhibited the proliferation of H9C2 cells. Conclusion. Our analysis reveals that COL1A1, UBB, COL3A1, HSP90AA1, MYC, STAT3, and MAPK1 might promote the progression of HF and become the biomarkers for diagnosis and treatment of HF.

Objective. This study is to explore key immune markers and changes of immune microenvironment in neuropathic pain (NeuP). Method. The data sets of GSE145199 and GSE145226 in Gene Expression Omnibus (GEO) database was used to analyze, and the key immune markers were verified by GSE70006 and GSE91396, and the infiltration degree of immune cells in different samples were analyzed by CIBERSORT analysis package. Results. In this study, we found a key immune marker, namely, LANCL1. Regulatory axis closely related to LANCL1 has also been found, namely, miR-6325/LANCL1 axis. In the immune infiltration analysis, we also found that the LANCL1 is positively correlated with T cells CD4 naïve (r=0.880, p

Barley bran has potential bioactivities due to its high content of polyphenols and dietary fiber, etc. Fermentation has been considered as an effective way to promote the functional activity of food raw materials. In this study, polysaccharides from barley bran extract fermented by Lactiplantibacillus plantarum dy-1 (FBBE-PS) were analyzed, and its effects on lipid accumulation and oxidative stress in high-fat HepG2 cells induced by sodium oleate were evaluated. The results showed that the molecular weight decreased and monosaccharide composition of polysaccharides changed significantly after fermentation. In addition, 50 μg/mL FBBE-PS could reduce the triglyceride (TG) content and reaction oxygen species (ROS) level in high-fat HepG2 cells by 21.62% and 30.01%, respectively, while increasing the activities of superoxide dismutase (SOD) and catalase (CAT) represented by 64.87% and 22.93%, respectively. RT-qPCR analysis revealed that FBBE-PS could up-regulate the lipid metabolism-related genes such as ppar-α, acox-1 and cpt-1α, and oxidation-related genes such as nrf2, ho-1, nqo-1, sod1, cat, etc. The metabolomics analysis indicated that FBBE-PS could alleviate lipid deposition by inhibiting the biosynthesis of unsaturated fatty acids, which is consistent with the downregulation of scd-1 expression. It is demonstrated that fermentation can alter the properties and physiological activities of polysaccharides in barley bran, and FBBE-PS exhibited an alleviating effect on lipid deposition and oxidative stress in high-fat cells.

To improve the motor efficiency and expand the actual external characteristic region of electric vehicle permanent magnet synchronous motor (PMSM) drive systems, the optimal operation of mapping torque to d-q axis current is usually applied. Nevertheless, it is difficult to deal with the complex mechanism factors such as parameter saturation and temperature change for the traditional optimization method based on the basic voltage equation of PMSM. In this paper, a black-box-model-based torque–current optimization method is proposed, which does not rely on any information of the inner mechanism model, and the derivative-free, optimal, improved Nelder–Mead Simplex(NMS) method is used to minimize the copper loss and maximize the electromagnetic torque in the flux-weakening region. Moreover, a synchronous online compensation of the electromagnetic torque and optimal current angle is implemented, in view of the time variation of permanent magnet flux with temperature. Finally, through a comparison experiment with the nominal-parameters-based formula maximum torque per ampere (MTPA) method, the proposed method achieves higher torque accuracy and better efficiency performance in a wide temperature range with regard to a reasonable response speed.

Green manufacturing (especially the right production scale) and optimization of logistics transportation (especially logistics transportation to ensure economic benefits) have become challenging issues. This paper focuses on production planning and scheduling of dynamic supply chain via H∞ control scheme. This paper considers the production scale control and resource scheduling optimization of complex dynamic supply chain under the impact of the COVID-19 pandemic.Firstly, the information of green manufacturing production is collected, and a new mathematical model of complex dynamic supply chain including multi-level distributor/retailer, multi-delay inventory and multi-lead time is established. Secondly, the optimal resource scheduling scheme is designed based on the principle of H∞ cybernetics, which is called the hierarchical scheduling of complex dynamic supply chain in this paper. Finally, a numerical example shows the effectiveness and feasibility of the proposed scheme. Through this model, the production of manufacturers, the inventory of manufacturers and distributors, and the order quantity of distributors can be arranged in advance, which improves the robustness of the closed-loop dynamic supply chain.

In recent years, deep learning has been applied to the field of recommendation, which can learn complex user interaction features and make better recommendations. However, deep learning only focuses on the interaction of high-order features and neglects the low-order features. The DeepFM model combines the linear FM (Factorization Machines) model and the deep DNN (Deep Neural Network) model to realize the interactive learning of low-order and high-order features, but it does not take into account that user interests will change dynamically with time. When the data sparsity is high, it cannot be effectively recommended. Based on this, an improved DeepFM recommendation algorithm that combines depth feature extraction was proposed, named fDeepFM. Firstly, the word features are transformed into low-dimensional dense vectors through the Embedding layer. Then Doc2Vec is combined to mine item features with context, and the two are stitched together as the input to the FM model and DNN model. Subsequently, user features are input to the GRU (Gated Cyclic Unit) model according to different cycles to mine user features. Finally, the results of the FM model, DNN model, and GRU model are combined by linear stitching as the overall output of the fDeepFM model. Experiments were carried out on Movielens-20M and Amazon data sets. The experimental results showed that MAE, RMSE, F1-score, and AUC on the Movielens-20M data set were optimized by 1.69%, 2.4%, 1.67%, and 2.28%, respectively; On the Amazon dataset, MAE, RMSE, F1-score, and AUC are optimized by 3.2%, 3.86%, 1.63%, and 2.2% respectively compared with DeepFM.