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Abstract Background Mesenchymal stromal cell (MSC)-derived exosomes (MSC-Exo) have been recognized for their significant role in regulating macrophage polarization, a process crucial to the pathogenesis of abdominal aortic aneurysm (AAA). However, the therapeutic effects of MSC-Exo on AAA remain largely unexplored. Therefore, this study aimed to investigate the functional and mechanistic aspects of MSC-Exo in the progression of AAA. Methods The MSC-derived exosomes were characterized using Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Western blotting. An experimental mouse model of AAA was established through the administration of angiotensin II (Ang II) in male apoe−/− mice and calcium chloride (CaCl2) in male C57/B6 mice, with subsequent tail vein injection of exosomes to evaluate their efficacy against AAA. Macrophage polarization was assessed using immunofluorescence staining and WB analysis. Mechanistic analysis was performed using 4D Label-free Proteomics analysis. Results We found that intravenous administration of MSC-Exo induced M2 polarization of macrophages within an inflammatory environment, effectively impeding AAA development in Ang II or CaCl2-induced AAA model. The therapeutic efficacy of MSC-Exo treatment was dependent on the presence of macrophages. Mechanistically, MSC-Exo suppressed the levels of cluster of differentiation 74 (CD74), modulating macrophage polarization through the TSC2-mTOR-AKT pathway. These findings highlight the potential of MSC-Exo as a therapeutic strategy for AAA by modulating macrophage polarization.

Abstract Aims Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. Results According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. Conclusions This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future.

Abstract In order to cope with the grid fluctuation caused by large‐scale wind power connected to the grid, the wind thermal power generation system has been proposed and extensively studied. The wind thermal power generation system uses a wind turbine to drive a heat generation device to heat the heat storage medium, which is further exchanged to drive a turbine to generate electricity. A superconducting magnetic eddy current heater (SMH) is proposed for the characteristics of wind thermal power generation system, which uses non‐resistive, large current‐carrying superconducting coils for excitation, and has high output efficiency and power density. The working principle of magnetic eddy current heating is analysed, and the structure of SMH with no ferromagnetic material and two heating screens inside and outside is proposed according to the characteristics of SMH. An analytical model of the SMH is established, and the influence of the structure and materials of the SMH on the magnetic field distribution is analysed. Based on this, a 22‐pole SMH was designed and analysed for output power at 10–20 rpm. A three‐dimensional magnetism‐stress combined analysis model of SMH is established, and the strain and stress characteristics of SMH are simulated under the condition of maximum output power, which verifies the feasibility of the mechanical properties of existing superconducting materials for application in SMH.

Abstract Background The link between diabetes and dementia risk is not well understood. This study evaluates the factors linking diabetes to dementia onset, providing guidance for preventing dementia in diabetic patients. Methods This analysis utilized databases such as PubMed, Embase, Web of Science, and the Cochrane Library to review literature from January 31, 2012, to March 5, 2023. Articles were rigorously assessed using specific inclusion and exclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. Data analysis was performed with STATA 15.0. Results The study analyzed 15 articles, covering 10,103,868 patients, with 8,821,516 diagnosed with diabetes. The meta-analysis reveals a substantial association between diabetes and an increased risk of dementia [RR: 1.59, 95%CI (1.40–1.80), P

Background/Objectives: Due to the character of the taekwondo, the adenosine triphosphate–phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated execution of kicks, and the aerobic system promotes recovery between these movements and the bout. Therefore, taekwondo athletes require high explosive power and anaerobic capacity in order to carry out sustained and powerful attacks. So, the purpose of this study is to compare the effects of APRE and VBRT on lower-limb explosive power and anaerobic capacity in college taekwondo players. Methods: A total of 30 taekwondo players completed an 8-week training intervention with autoregulatory progressive resistance exercise (APRE; n = 15) and velocity-based resistance training (VBRT; n = 15). Testing included the one-repetition maximum squat, countermovement jump (CMJ), taekwondo anaerobic intermittent kick test (TAIKT), and 30-s Wingate anaerobic test (WAnT). Results: (1) Intragroup comparisons revealed significant effects for one-repetition maximum squat, peak power of CMJ (CMJPP), relative peak power of CMJ (CMJRPP), and total number of TAIKT (TAIKTTN) in both the APRE and VBRT groups. The VBRT group exhibited small effect sizes for time at peak power of WAnT (WAnTPPT) and moderate effect sizes for peak power of WAnT (WAnTPP), relative peak power of WAnT (WAnTRPP), and fatigue index of TAIKT (TAIKTFI), whereas the APRE group exhibited small effect sizes for TAIKTFI. (2) Intergroup comparisons revealed no significant effects in any of the results. However, VBRT demonstrated a moderate advantage in WAnTPP and WAnTRPP, whereas APRE had a small advantage in CMJPP and CMJRPP. Conclusions: These findings suggest that APRE improved explosive power (CMJPP and CMJRPP) more, whereas VBRT improved anaerobic power output (WAnTPP and WAnTRPP) more. Both methods were found to have similar effects in improving the anaerobic endurance (WAnTPPT and TAIKTTN) and fatigue index (power drop of WAnT and TAIKTFI).

During tumor development, the tumor itself must continuously generate new blood vessels to meet their growth needs while also allowing for tumor invasion and metastasis. One of the most common features of tumors is hypoxia, which drives the process of tumor angiogenesis by regulating the tumor microenvironment, thus adversely affecting the prognosis of patients. In addition, to overcome unsuitable environments for growth, such as hypoxia, nutrient deficiency, hyperacidity, and immunosuppression, the tumor microenvironment (TME) coordinates angiogenesis in several ways to restore the supply of oxygen and nutrients and to remove metabolic wastes. A growing body of research suggests that tumor angiogenesis and hypoxia interact through a complex interplay of crosstalk, which is inextricably linked to the TME. Here, we review the TME's positive contribution to angiogenesis from an angiogenesis-centric perspective while considering the objective impact of hypoxic phenotypes and the status and limitations of current angiogenic therapies.

ObjectiveThis study investigates the efficacy of training methodologies aimed at mitigating asymmetries in lower limb strength and explosiveness among basketball players.MethodsThirty male university basketball athletes were enrolled in this research. Initial assessments were made regarding their physical attributes, strength, and explosiveness. Subsequently, the participants were randomly allocated into two groups: an experimental group (EG, n = 15) and a control group (CG, n = 15). Over 10 weeks, the EG engaged in a unilateral compound training regimen, incorporating resistance training exercises such as split squats, Bulgarian split squats, box step-ups, and single-leg calf raises (non-dominant leg: three sets of six repetitions; dominant leg: one set of six repetitions) and plyometric drills including lunge jumps, single-leg hops with back foot raise, single-leg lateral jumps, and single-leg continuous hopping (non-dominant leg: three sets of 12 repetitions; dominant leg: one set of 12 repetitions). The CG continued with their standard training routine. Assessments of limb asymmetry and athletic performance were conducted before and after the intervention to evaluate changes.Results1) Body morphology assessments showed limb length and circumference discrepancies of less than 3 cm. The initial average asymmetry percentages in the single-leg countermovement jump (SLCMJ) for jump height, power, and impulse were 15.56%, 12.4%, and 4.48%, respectively. 2) Post-intervention, the EG demonstrated a significant reduction in the asymmetry percentages of SLCMJ height and power (p < 0.01), along with improvements in the isometric mid-thigh pull (IMTP) test metrics (p < 0.05). 3) The EG also showed marked enhancements in the double-leg countermovement jump (CMJ) and standing long jump (SLJ) outcomes compared to the CG (p < 0.01), as well as in squat performance (p < 0.05).ConclusionThe 10-week unilateral compound training program effectively reduced the asymmetry in lower limb strength and explosiveness among elite male university basketball players, contributing to increased maximal strength and explosiveness.

Background: For adolescent soccer players, good sprinting and jumping abilities are crucial for their athletic performance. The application of plyometric training on boosting explosive strength in adolescent soccer players is contingent upon the maturation phase, which can mediate the training-induced adaptations. Purpose: This systematic review and meta-analysis aim to explore the maturation effect of plyometric training on the lower limb explosive power of adolescent soccer players, with vertical countermovement jump (CMJ) and 20-m sprint as the main outcome indicators. Methods: An extensive search of the literature was carried out on various databases including PubMed, Web of Science, Scopus, ProQuest, and the China National Knowledge Infrastructure (CNKI), covering the time period from the establishment of each database to February 6, 2023. The search was conducted using English keywords such as ‘Plyometric,’ ‘Adolescent,’ ‘football,’ and ‘Explosive strength.’ This study utilized the Cochrane risk of bias assessment tool to conduct a standardized quality evaluation of all the included literature. Additionally, the Review Manager 5.4 software was employed to perform data analysis on all the extracted data. Results: A total of 17 studies involving 681 adolescent soccer players aged 10 to 19 were included. Plyometric training significantly improved CMJ performance across different maturation stages, especially in the post-peak height velocity stage (POST-PHV) [MD = 4.35, 95 % CI (2.11, 6.59), P

With the efficiency of storage and retrieval speed, the hashing methods have attracted a lot of attention for cross-modal retrieval applications. In contrast to traditional cross-modal hashing by using handcrafted features, deep cross-modal hashing integrates the advantages of deep learning and hashing methods to encode raw multimodal data into compact binary codes with semantic information preserved. Generally speaking, most of the existing deep cross-modal hashing methods simply define the semantic similarity between heterogeneous modalities by counting the number of shared semantic labels (such as, two samples share at least one label, they are similar, otherwise they are dissimilar), which fails to represent the accurate multi-label semantic relations between heterogeneous data. In this paper, we propose a new Deep Self-supervised Hashing with Fine-grained Similarity Mining (DSH-FSM) framework to efficiently preserve the fine-grained multi-label semantic similarity, learning a highly separable embedding space. Specifically, by employing an asymmetric guidance strategy, a novel Semantic-Network is introduced into cross-modal hashing to learn two semantic dictionaries, including the semantic feature dictionary and the semantic code dictionary, which guides the Image-Network and the Text-Network to capture multi-label semantic relevance across different modalities. Based on the obtained semantic dictionary, an asymmetric margin-scalable loss is proposed to obtain fine-grained pair-wise similarity information, which could contribute to the production of similarity-preserving and discriminative binary codes. Besides, two feature extractors with transformer encoders are designed to achieve the Image-Network and Text-Network, which could extract the representative semantic characteristics from raw heterogeneous samples. Extensive experimental results on various benchmark datasets show that our proposed DSH-FSM framework achieves state-of-the-art cross-modal similarity search performance. Compared to the state-of-the-art methods, the results of mAP are significantly improved by 1.9%, 9.1%, and 9.8%, respectively, on the three widely used datasets.

In recent years, both convolutional neural networks (CNN) and transformers have demonstrated impressive feature extraction capabilities in the field of medical image segmentation. A common approach is to utilize a combination of CNN and transformer encoders to efficiently learn both local and global features, making them widely adopted techniques in semantic segmentation of medical images. However, challenges remain due to the limited sample size of medical image datasets and the intricate foreground edge information in these images. These challenges make it difficult for models to capture key structures and information related to foreground edge details, especially when trained on smaller datasets. To address these issues, we propose a U-Net-based model called “Rotate U-Net” (RotU-Net). Our model design is inspired by the successful U-Net architecture, which is characterized by direct connections between encoders and decoders, and skipping connections at multiple resolutions. Meanwhile, we propose weight rotator as a feature extraction module, which enhances network to discriminate edge information in the foreground region by computing partial element correlations to improve the network to focus on the foreground region while reducing redundant information in the features. Finally, we have validated RotU-Net on the Synapse Multi-Organ Segmentation Dataset (Synapse) and the Segmentation of Multiple Myeloma Plasma Cells in Microscopic Images (SegPC). The experimental results show that RotU-Net with a very small number of parameters achieves impressive performance, which demonstrates the effectiveness and efficiency of RotU-Net.

Soft magnetic composite (SMC) material is an ideal soft magnetic material employed for developing 3D magnetic flux electromagnetic equipment, due to its advantages of 3D magnetic isotropy characteristic, low eddy current loss, and simple manufacturing process. The permanent magnet claw pole machine (PMCPM) with SMC cores is a good case that the SMC to be adopted for developing 3D flux electrical machines. In this paper, a novel axial-radial flux permanent magnet claw pole machine (ARPMCPM) with SMC cores and ferrite magnets is proposed. Compared with the traditional PMCPM, the proposed ARPMCPM is designed with only one spoke PM rotor and its whole structure is quite compact. For the performance prediction, the 3D finite element method (FEM) is used. Meanwhile, for the performance evaluation, a previously developed axial flux claw pole permanent magnet machine (AFCPM) is employed as the benchmark machine and all these machines are optimized by using the combined multilevel robust Taguchi method. It can be seen that the proposed ARPMCPM is with higher torque/weight density and operation efficiency.

Abstract This study aims to reconstruct signals that are sparse with a tight frame from undersampled data by using the ℓ q $\ell _{q}$ -minimization method. This problem can be cast as a ℓ q $\ell _{q}$ -minimization problem with a tight frame subjected to an undersampled measurement with a known noise bound. We proved that if the measurement matrix satisfies the restricted isometry property with δ 2 s ≤ 1 / 2 $\delta _{2s}\leq 1/2$ , there exists a value q 0 $q_{0}$ such that for any q ∈ ( 0 , q 0 ] $q\in (0,q_{0}]$ , any signal that is s-sparse with a tight frame can be robustly recovered to the true signal. We estimated q 0 $q_{0}$ as q 0 = 2 / 3 $q_{0} = 2/3$ in the case of δ 2 s ≤ 1 / 2 $\delta _{2s}\leq 1/2$ and discussed that the value of q 0 $q_{0}$ can be much higher. We also showed that when δ 2 s ≤ 0.3317 $\delta _{2s}\leq 0.3317$ , for any q ∈ ( 0 , 1 ] $q\in (0,1]$ , robust recovery for signals via ℓ q $\ell _{q}$ -minimization holds, which is consistent with the case of ℓ q $\ell _{q}$ -minimization without a tight frame.

Maritime accidents frequently lead to severe property damage and casualties, and an accurate and reliable risk prediction model is necessary to help maritime stakeholders assess the current risk situation. Therefore, the present study proposes a hybrid methodology to develop an explainable prediction model for maritime accident types. Based on the advantages of selective ensemble learning method, this study pioneers to introduce a two-stage model selection method, aiming to enhance the predictive accuracy and stability of the model. Then, SHAP (Shapley Additive Explanations) method is integrated to identify effective mapping associations of seafarers’ unsafe acts and their risk factors with the prediction results. The results demonstrate that the model developed achieves good prediction performance with an accuracy of 87.50 % and an F1-score of 84.98 %, which benefits stakeholders in assessing the type of maritime accident in advance, so as to make proactive intervention measures.

An efficient visible-light photoelectrochemical photodetector based on a compact In-rich n-InGaN layer activated by p-Cu2O microcrystals operating as photoanode in the self-powered mode is demonstrated. The photocurrent density of 80 µA/cm2 under one-sun illumination is more than 10 times larger than that of a bare InGaN layer. Moreover, the photocurrent density, responsivity of 0.8 mA/W, specific detectivity of 4 × 109 Jones, and response times of 5–8 ms are more than five times better compared to those of our previously reported nanowire counterpart. The excellent performance is attributed to maximized photocarrier separation in the built-in electric field of the internal p–n junction for fully depleted Cu2O microcrystals with maximized height and the planar geometry, guaranteeing unhindered diffusion of the electrolyte to and from the photoanode surface.

Abstract Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell population in breast tumors. A functionally diverse population of CAFs increases the dynamic complexity of the tumor microenvironment (TME). The intertwined network of the TME facilitates the interaction between activated CAFs and breast cancer cells, which can lead to the proliferation and invasion of breast cells. Considering the special transmission function of CAFs, the aim of this review is to summarize and highlight the crosstalk between CAFs and breast cancer cells in the TME as well as the relationship between CAFs and extracellular matrix (ECM), soluble cytokines, and other stromal cells in the metastatic state. The crosstalk between cancer-associated fibroblasts and tumor microenvironment also provides a plastic therapeutic target for breast cancer metastasis. In the course of the study, the inhibitory effects of different natural compounds on targeting CAFs and the advantages of different drug combinations were summarized. CAFs are also widely used in the diagnosis and treatment of breast cancer. The cumulative research on this phenomenon supports the establishment of a targeted immune microenvironment as a possible breakthrough in the prevention of invasive metastasis of breast cancer. Graphical Abstract

With the development of offshore wind power generation, there is an urgent demand for high-power wind turbines. Superconducting machines with high power density and efficiency are one of the solutions for wind turbines of 10 MW and above. This paper summarizes the existing superconducting synchronous generators in several structural forms and features, and considers that the coreless machine can avoid the impact of core oversaturation on the power density increase of the machine, which is the development direction of the superconducting machine. In this paper, the structural topology of a coreless superconducting machine is established and the similarities and differences between its structure and that of a conventional one are analyzed. Since the conventional magnetic circuit method is no longer applicable, a designing model based on the analytical method is established for the designing of coreless machines, which considers the effects of slotless armature, the superconducting excitation winding thickness and the nonlinearity of the ferromagnetic material. Based on this method, the magnetic field distribution is solved and verified with the finite element method. Further, the effect of the superconducting excitation winding opening angle on the magnetic field in the air gap of the machine is investigated, and the machine structure is optimized based on this. The steady-state and transient performance analysis of the machine is carried out to illustrate the operating characteristics of the coreless superconducting machine. The design method and analysis results of this paper can provide a reference for building higher power density coreless superconducting wind turbines.

Galectin-9 (Gal-9) is a vital member of the galectin family, functioning as a multi-subtype galactose lectin with diverse biological roles. Recent research has revealed that Gal-9’s interaction with tumors is an independent factor that influences tumor progression. Furthermore, Gal-9 in the immune microenvironment cross-talks with tumor-associated immune cells, informing the clarification of Gal-9’s identity as an immune checkpoint. A thorough investigation into Gal-9’s role in various cancer types and its interaction with the immune microenvironment could yield novel strategies for subsequent targeted immunotherapy. This review focuses on the latest advances in understanding the direct and indirect cross-talk between Gal-9 and hematologic malignancies, in addition to solid tumors. In addition, we discuss the prospects of Gal-9 in tumor immunotherapy, including its cross-talk with the ligand TIM-3 and its potential in immune-combination therapy.

To reveal the dynamic response characteristic and damage-fracture evolution laws of concrete under pulse water jet impact, the numerical simulations on pulse water jets impinging concrete for different operating parameters were established based on SPH-FEM coupling algorithm and verified in this paper. The concrete-breaking effects of pulse water jet and continuous water jet were compared, and the effects of key jet parameters and concrete strength on the damage-fracture characteristics of concrete were investigated. And the damage and stress evolution laws inner concrete were revealed. The results show that there is a better concrete-breaking effect for pulse water jet by repeatedly utilizing the extremely high water-hammer pressure and effectively weakening the water-cushion effect, compared with continuous water jet. The broken pit area and the total length of main cracks decrease with the increase of pulse length, and there is an optimal pulse spacing for pulse water jet to improve the concrete-breaking effect. The broken pit area and the total length of main cracks both linearly increase with the increasing jet velocity and exponentially increase with the increasing jet diameter. As the concrete strength increases, the broken pit area shows an S-shaped curve decreasing trend and the total length of main cracks exponentially decreases. The broken pit width first rapidly increases and tends to stabilize with the increase of jet velocity and concrete strength, and changes linearly with jet diameter and is less affected by pulse length and spacing. The farther away from the jet impact center, the longer the damage cumulative period of concrete due to the jet impact energy attenuation. In horizontal direction, concrete breakage range is approximately 4–5 times of jet diameter; in vertical direction, the previous pulses will cause concrete to be destroyed or damaged, and the subsequent pulses will make the damaged concrete suffer greater stress, causing more serve damage. And the induced stress peak decreases in form of Power function with the increasing distance. The research results could provide theoretical guidance for the parameters selection of pulse water jet efficiently breaking concrete.

Abstract Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, lacks effective treatment options. Sophora flavescens Aiton, a Chinese medicinal plant, is often used in traditional Chinese medicine to treat cancer. Matrine (MAT) is an alkaloid extracted from Sophora flavescens. It has good anticancer effects, and thus can be explored as a new therapeutic agent in TNBC research. We performed bioinformatics analysis to analyze the differentially expressed genes between normal breast tissues and TNBC tissues, and comprehensive network pharmacology analyses. The activity and invasion ability of TNBC cells treated with MAT were analyzed. Apoptosis and cell cycle progression were determined using cytometry. We used Monodansylcadaverine (MDC) staining to determine the condition of autophagosomes. Finally, the expression levels of the key target proteins of the PI3K/AKT pathway were determined using western blotting. The proliferation and invasion ability of MDA-MB-231 and MDA-MB-468 can be effectively inhibited by MAT. The results of flow cytometry indicated that MAT arrested the TNBC cell cycle and induced apoptosis. In addition, we confirmed that MAT inhibited the expression of BCL-2 while up-regulating the expression of cleaved caspase-3. Moreover, enhanced intensity of MDC staining and high LC3-II expression were observed, which confirmed that MAT induced autophagy in TNBC cells. Western blotting showed that MAT inhibited the PI3K/AKT pathway and downregulated the expressions of PI3K, AKT, p-AKT, and PGK1. This study provides feasible methods, which include bioinformatics analysis and in vitro experiments, for the identification of compounds with anti-TNBC properties. MAT inhibited the PI3K/AKT signaling pathway, arrested cell cycle, as well as promoted cell apoptosis and autophagy. These experiments provide evidence for the anti-TNBC effect of MAT and identified potential targets against TNBC.

Achieving the target of carbon neutrality has been an important approach for China to mitigate global climate change. Enterprises are major carbon emitters, and a well-designed early warning system is needed to ensure that their emissions align with carbon neutrality goals. Therefore, this study utilized electricity big data to construct an early warning model for enterprise carbon emissions based on carbon quota allocation. Taking key carbon-emitting enterprises in Guangxi as a case study, we aim to provide insights to support China’s dual carbon goals. Firstly, we established the Carbon Quota Allocation System, enabling carbon quota allocation at the enterprise levels. Secondly, we developed the Enterprise Carbon Neutrality Index, facilitating dynamic warnings for carbon emissions among enterprises. The main conclusions are as follows: (1) In 2020, Guangdong received the highest carbon quota of 606 million tons, representing 5.72% of the national total, while Guangxi only received 2.63 billion tons. (2) Only 39.34% of enterprises in Guangxi are able to meet the carbon neutrality target, indicating significant emission reduction pressure faced by enterprises in the region. (3) Over 90% of enterprises in Guangxi receive Commendation and Encouragement warning levels, suggesting that enterprises in Guangxi are demonstrating a promising trend in emission reduction efforts.

After a major debt crisis occurs in a listed company, the stock prices of related enterprises may also fluctuate sharply, resulting in the spread of debt risk to more enterprises. Taking the stocks of listed companies as network nodes, we constructed a complex stock market network over three periods of time through the logarithmic return rate of stocks for the three periods of prophase, metaphase, and anaphase of the debt crisis. We studied the topological characteristics of the network and destructiveness over the three periods. Finally, the minimum spanning tree was used to construct a network and the community structure of the network. The empirical analysis took the debt crisis of the China Evergrande Company as an example to analyze the impact of its major debt crisis on the Chinese stock market. The research findings were as follows: First, the debt crisis increased the inter-industry connections within the network, that is, the correlations between enterprises in different industries was enhanced. Second, the closeness of the cross-industry connections increased the connectivity efficiency of the network, but compared with the other two periods, the debt crisis in the metaphase was less stable. Third, community research showed that in the metaphase of the debt crisis, the enterprises became the core nodes of the network.

Leaf morphology is a crucial aspect of plant architecture, yet the molecular mechanisms underlying leaf development remain incompletely understood. In this study, a narrow leaf mutant, m625, was identified in rice (Oryza sativa L.), exhibiting pleiotropic developmental defects. Pigment measurement revealed reduced levels of photochromic pigments in m625. Cytological analysis demonstrated that the m625 gene affected vascular patterns and cell division. Specifically, the narrowing of the leaf was attributed to a decrease in small vein number, shorter vein spacing, and an abnormal V-shaped arrangement of bulliform cells, while the thickening was caused by longer leaf veins, thicker mesophyll cells, and an increased number of parenchyma cell layers. The dwarf stature and thickened internode were primarily due to shortened internodes and an increase in cell layers, respectively. Positional cloning and complementation assays indicated that the m625 gene is a novel allele of NAL1. In the m625 mutant, a nucleotide deletion at position 1103 in the coding sequence of NAL1 led to premature termination of protein translation. Further RNA-Seq and qRT-PCR analyses revealed that the m625 gene significantly impacted regulatory pathways related to IAA and ABA signal transduction, photosynthesis, and lignin biosynthesis. Moreover, the m625 mutant displayed thinner sclerenchyma and cell walls in both the leaf and stem, particularly showing reduced lignified cell walls in the midrib of the leaf. In conclusion, our study suggests that NAL1, in addition to its known roles in IAA transport and leaf photosynthesis, may also participate in ABA signal transduction, as well as regulate secondary cell wall formation and sclerenchyma thickness through lignification.

In the traditional control scheme of a 12/8-pole bearingless switched reluctance motor (BSRM), radial force and torque are usually controlled as a compromise due to the conflict between their effective output areas. Additionally, each phase requires individual power circuits and is excited in turn to produce a continuous levitation force, resulting in high power device requirements and high controller costs. This paper discusses a 12/8-pole single-winding hybrid-rotor bearingless switched reluctance motor (HBSRM) with a hybrid rotor consisting of cylindrical and salient-pole lamination segments. The asymmetric rotor of the HBSRM slightly increases the complexity of its structure and magnetic circuit, but makes it possible to generate the desired radial force at any rotor angular position. A control scheme for the HBSRM is developed to utilize the independent excitation of the four windings in one phase to generate the desired levitation force at any rotor angular position, and it requires only half the number of power circuits used in the conventional control scheme of a 12/8-pole single-winding BSRM. Different from the average torque chosen to be controlled in traditional methods, this scheme directly regulates the instantaneous total torque produced by all excited phases together and presents a current algorithm to optimize the torque contribution of each phase so as to reduce torque pulsation, and the improved performance of this bearingless motor is finally validated by simulation analysis.

Abstract In perovskite solar cells (PSCs), the light‐soaking effect, which means device performance changes obviously under continuous light illumination, is potentially harmful to loaded devices as well as accurately assessing their efficiency. Herein, chemically stable tungsten trioxide (WO3) with high electron mobility is used as electron transport material in methylamine (MA)‐free PSCs. However, the light‐soaking effect is observed apparently in our devices. A fullerene derivative, C60 pyrrolidine Tris‐acid (CPTA), is introduced to modify the interface between WO3 and perovskite (PVK) layers, which can bond with WO3 and PVK simultaneously, leading to the passivation of the defect and the suppression of trap‐assisted nonradiative recombination. What is more, the introduction of CPTA can enhance the built‐in electric field between WO3 and PVK layers, thereby facilitating the electron extraction and inhibiting the carrier accumulation at the interface. Consequently, the light‐soaking effect of WO3‐based PSCs has been eliminated, and the power conversion efficiency has been boosted from 17.4% for control device to 20.5% for WO3/CPTA‐based PSC with enhanced stability. This study gives guidance for the design of interfacial molecules to eliminate the light‐soaking effect.

With the improvement of high temperature superconducting (HTS) materials, HTS machines have shown better competitive advantages in wind power generation and other fields. However, the conventional structure of superconducting machines has led to low reliability of the machines due to the complex structures such as brush and rotating dewar. Based on the analysis of the properties of second-generation high-temperature superconducting strips — YBCO strips, a kind of rotating pole shoe superconducting machine (RPHTSM) with dual HTS coils is proposed in this paper, which avoids the use of brush and rotating dewar used in the conventional HTS machine. The three-dimensional model for magnetic field analysis of the RPHTSM is established and the structure of the RPHTSM is optimized according to the calculation. A two-dimensional simplified model was developed and based on which the output performance of the machine was calculated. By comparing with the conventional HTS machine, it is concluded that the dual-coil RPHTSM has great advantage in reducing the consumption of superconducting strips and the inertia of the rotor.

The tumor microenvironment (TME), the ''soil'' on which tumor cells grow, has an important role in regulating the proliferation and metastasis of tumor cells as well as their response to treatment. Cancer-associated fibroblasts (CAFs), as the most abundant stromal cells of the TME, can not only directly alter the immunosuppressive effect of the TME through their own metabolism, but also influence the aggregation and function of immune cells by secreting a large number of cytokines and chemokines, reducing the body’s immune surveillance of tumor cells and making them more prone to immune escape. Our study provides a comprehensive review of fibroblast chemotaxis, malignant transformation, metabolic characteristics, and interactions with immune cells. In addition, the current small molecule drugs targeting CAFs have been summarized, including both natural small molecules and targeted drugs for current clinical therapeutic applications. A complete review of the role of fibroblasts in TME from an immune perspective is presented, which has important implications in improving the efficiency of immunotherapy by targeting fibroblasts.

Tumor-associated macrophages (TAMs) are the most critical effector cells of innate immunity and the most abundant tumor-infiltrating immune cells. They play a key role in the clearance of apoptotic bodies, regulation of inflammation, and tissue repair to maintain homeostasis in vivo. With the progression of triple-negative breast cancer（TNBC）, TAMs are ''subverted'' from tumor-promoting immune cells to tumor-promoting immune suppressor cells, which play a significant role in tumor development and are considered potential targets for cancer therapy. Here, we explored how macrophages, as the most important part of the TNBC ecosystem, are ''subverted'' to drive cancer evolution and the uniqueness of TAMs in TNBC progression and metastasis. Similarly, we discuss the rationale and available evidence for TAMs as potential targets for TNBC therapy.

Abstract This study aims at the problem of reconstruction the unknown links in debt networks among enterprises. We use the topological matrix of the enterprise debt network as the object of reconstruction and use the time series data of accounts receivable and payable as input and output information in the debt network to establish an underdetermined linear system about the topological matrix of the debt network. We establish an iteratively reweighted least-squares algorithm, which is an algorithm in compressed sensing. This algorithm uses reweighted $$\ell _2$$ ℓ 2 -minimization to approximate $$\ell _1$$ ℓ 1 -norm of the target vectors. We solve the $$\ell _1$$ ℓ 1 -minimization problem of the underdetermined linear system using the iteratively reweighted least-squares algorithm and obtain the reconstructed topological matrix of the debt network. Simulation experiments show that the topology matrix reconstruction method of enterprise debt networks based on compressed sensing can reconstruct over 70% of the unknown network links, and the error is controlled within 2%.

Objectives Jumping ability has been identified as a key factor that influences the performance of badminton athletes. Autoregulatory progressive resistance exercise (APRE) and velocity-based resistance training (VBRT) are commonly used approaches to enhance muscle strength and have been shown to accurately monitor the development of explosive power to improve jumping ability. This study aims to investigate the effects of APRE and VBRT on badminton athletes’ jumping ability and to provide practical insights into improving their jumping performance during competitions. Methods Upon completing familiarization and pretesting, 18 badminton athletes were included and completed the training intervention (age, 21.4 ± 1.4 years; stature, 170.1 ± 7.3 cm; body mass, 65.9 ± 12 kg); they were randomly divided into the APRE group (n = 9) and VBRT group (n = 9). Jumping performance was assessed during the countermovement jump (CMJ), squat jump (SJ), and drop jump (DJ) via SmartJump, with CMJ ’s and SJ’s jump height, eccentric utilization ratio (EUR), and reactive strength index (RSI). All participants then completed a 4-week in-season resistance training intervention. Results (1) The results of the within-group indicated that only the CMJ (pre: 41.56 ± 7.84 vs post: 43.57 ± 7.85, p < 0.05) of the APRE group had significant differences, whereas the SJ, EUR, and RSI were not significantly different (p > 0.05). (2) The results of the intergroups revealed that all indicators had no significant differences (p > 0.05), but APRE had a moderate effect size on the improvement of the CMJ (η2 = 0.244) and EUR (η2 = 0.068) when compared with VBRT. Conclusions The results showed that, compared to VBRT, APRE can effectively improve the performance of the reactive athletes’ lower limb explosive power in the CMJ in a shorter period of time. The findings indicate that APRE may be useful for coaches seeking to improve the CMJ performance of athletes in the short term.

ABSTRACT The genus Megalocytivirus of the family Iridoviridae is composed of two distinct species, namely, infectious spleen and kidney necrosis virus (ISKNV) and scale drop disease virus (SDDV), and both are important causative agents in a variety of bony fish worldwide. Of them, the ISKNV species is subdivided into three genotypes, namely, red seabream iridovirus (RSIV), ISKNV, and turbot reddish body iridovirus (TRBIV), and a further six subgenotypes, RSIV-I, RSIV-II, ISKNV-I, ISKNV-II, TRBIV-I, and TRBIV-II. Commercial vaccines derived from RSIV-I , RSIV-II and ISKNV-I have been available to several fish species. However, studies regarding the cross-protection effect among different genotype or subgenotype isolates have not been fully elucidated. In this study, RSIV-I and RSIV-II were demonstrated as the causative agents in cultured spotted seabass, Lateolabrax maculatus, through serial robust evidence, including cell culture-based viral isolation, whole-genome determination and phylogeny analysis, artificial challenge, histopathology, immunohistochemistry, and immunofluorescence as well as transmission electron microscope observation. Thereafter, a formalin-killed cell (FKC) vaccine generated from an ISKNV-I isolate was prepared to evaluate the protective effects against two spotted seabass original RSIV-I and RSIV-II. The result showed that the ISKNV-I-based FKC vaccine conferred almost complete cross-protection against RSIV-I and RSIV-II as well as ISKNV-I itself. No serotype difference was observed among RSIV-I, RSIV-II, and ISKNV-I. Additionally, the mandarin fish Siniperca chuatsi is proposed as an ideal infection and vaccination fish species for the study of various megalocytiviral isolates. IMPORTANCE Red seabream iridovirus (RSIV) infects a wide mariculture bony fish and has resulted in significant annual economic loss worldwide. Previous studies showed that the phenotypic diversity of infectious RSIV isolates would lead to different virulence characteristics, viral antigenicity, and vaccine efficacy as well as host range. Importantly, it is still doubted whether a universal vaccine could confer the same highly protective effect against various genotypic isolates. Our study here presented enough experimental evidence that a water in oil (w/o) formation of inactivated ISKNV-I vaccine could confer almost complete protection against RSIV-I and RSIV-II as well as ISKNV-I itself. Our study provides valuable data for better understanding the differential infection and immunity among different genotypes of ISKNV and RSIV isolates in the genus Megalocytivirus.

With the rapid development of next-generation sequencing technology, several studies have shown that ncRNAs can act as competitive endogenous RNAs (ceRNAs) and are involved in various biological processes, such as proliferation, differentiation, apoptosis, and migration of breast cancer (BC) cells, and plays an important role in BC progression as a molecular target for its diagnosis, treatment, prognosis, and differentiation of subtypes and age groups of BC patients. Based on the description of ceRNA-related biological functions, this study screened and sorted the sequencing analysis and experimental verification conclusions of BC-related ceRNAs and found that the ncRNAs mediated ceRNA networks can promote the development of BC by promoting the expression of genes related to BC proliferation, drug resistance, and apoptosis, inducing the production of epithelial-mesenchymal transition (EMT) to promote metastasis and activating cancer-related signaling pathways.

In isotropic two dimensional systems, long range ferromagnetic order is supressed by thermal fluctuations, and it is due to magnetic anisotropy that van der Waals magnetic materials can have ferromagnetic ordering at finite temperatures. Usually this magnetic anisotropy is relatively small, but in this manuscript Zhang et al make a two dimensional van der Waals material with exceptionally large perpendicular magnetic anisotropy and ferromagnetic ordering that exits up to 350 K.

Abstract Renal cell carcinoma (RCC) is a common malignant tumor in the world. Histologically, most of RCC is classified as clear cell renal cell carcinoma (ccRCC), which is the most prevalent subtype. The overall survival of patients with ccRCC is poor, thus it is urgent to further explore its mechanism and target. S-phase kinase-associated protein 2 (SKP2) is overexpressed in a variety of human cancers and is associated with poor prognosis by enhancing tumor progression. However, it is unclear whether or how SKP2 is involved in ccRCC progression. Here, we reported that overexpression of SKP2 enhanced cell proliferation of ccRCC, while SKP2 depletion exhibited the opposite effect. Bioinformatic analyses found that SKP2 was positively correlated with Aurora-A (Aur-A) in ccRCC. The protein and mRNA levels of SKP2 were elevated or reduced by Aur-A overexpression or silencing, respectively. It was further found that Aur-A caused an increase phosphorylation of FOXO3A, which is a negatively transcription factor for SKP2. Interestingly, SKP2 mediated ubiquitylation and degradation of FOXO3A depend on the kinase activity of Aur-A. The combination of Aur-A inhibitor MLN8237 and SKP2 inhibitor SZL P1-41 showed a synergistic tumor growth inhibition in vivo and in vitro of ccRCC models. Thus, our data reveal that Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in ccRCC, and the double inhibition of SKP2 and Aur-A shows significant synergistic effect, which indicates a potential new therapeutic strategy for ccRCC.

Background: In Unilateral (UNI) exercises are more effective than bilateral (BI) exercises in improving athletic performance is debatable.Objectives: this meta-analysis investigated the effects of UNI and BI exercises on different effect indicators of jump ability, sprint ability, maximal force, change of direction ability, and balance ability.Data Sources: PubMed, Google Scholar, Web of science, CNKI, Proquest, Wan Fang Data.Study Eligibility Criteria: To be eligible for inclusion in the meta-analysis, the study had to be: 1) athletes; 2) UNI training and BI training; 3) the intervention period had to be more than 6 weeks and the intervention frequency had to be more than 2 times/week; 4) the outcome indicators were jumping ability, sprinting ability, maximum strength, and change of direction and balance.Study Appraisal and Synthesis Method: We used the random-effects model for meta-analyses. Effect sizes (standardized mean difference), calculated from measures of horizontally oriented performance, were represented by the standardized mean difference and presented alongside 95% confidence intervals (CI).Results: A total of 28 papers met the inclusion criteria, and Meta-analysis showed that UNI training was more effective than BI training in improving jumping ability (ES = 0.61.0.23 to 0.09; Z = 3.12, p = 0.002 < 0.01), sprinting ability (ES = −0.02, −0.03 to −0.01; Z = 2.73, p = 0.006 < 0.01), maximum strength (ES = 8.95,2.30 to 15.61; Z = 2.64, p = 0.008 > 0.05), change of direction ability (ES = −0.03, −0.06 to 0.00; Z = 1.90, p = 0.06 > 0.01) and balance ability (ES = 1.41,-0.62 to 3.44; Z = 1.36, p = 0.17 > 0.01). The results of the analysis of moderating variables showed that intervention period, intervention frequency and intervention types all had different indicators of effect on exercise performance.Conclusion: UNI training has a more significant effect on jumping and strength quality for unilateral power patterns, and BI training has a more significant effect on jumping and strength quality for bilateral power patterns.

With designing stator teeth by using grain oriented silicon sheets (GO) and other parts still with non-grain oriented silicon sheets (NGO), the electromagnetic performance of interior permanent magnet synchronous machine (GO-IPMSM) can be improved greatly, however its torque ripple will be increased as well. For reducing its torque ripple, optimizing its rotor barrier shape is an effective way. In this paper, the polynomial method is proposed to establish the rotor barrier shape, and the genetic algorithm (GA) method is employed for the optimization process. In case the optimized GO-IPMSM can work normally, its anti irreversible demagnetization ability is analyzed as well. As shown, with the GO is adopted for designing the stator teeth and its rotor barrier shape is optimized, though its torque ability and efficiency have been increased, its anti irreversible demagnetization risk ability is reduced, however the proposed machine can still operate safely.

Automaticidentification and prevention of leaf diseases and insect pests on fruit crops represent a key trend in the development of smart agriculture. In order to address the limitations of existing models with low identification rates of apple leaf diseases and insect pests, a novel identification model based on an improved ResNet-50 architecture was proposed, which incorporated the coordinate attention (CA) module and weight-adaptive multi-scale feature fusion (WAMFF) to enhance the ResNet-50’s image feature extraction capabilities. Transfer learning and online data enhancement are employed to boost the model’s generalization ability. The proposed model achieved a top-1 accuracy rate of 98.32% on the basis of AppleLeaf9 datasets, which is 4.58% higher than the value from the original model, and the improved model can effectively improve the localization of lesion features. Furthermore, compared with mainstream deep networks, such as AlexNet, VGG16, DenseNet, MNASNet, and GoogLeNet on the same dataset, the top-1 accuracy rate increased by 7.3%, 3.19%, 4.98%, 6.04% and 3.87%, respectively. The experimental results demonstrate that the improved model is effective in improving the identification accuracy of apple leaf diseases and insect pests and enhancing the model’s effective feature extraction capabilities.

With the increasing demand for person re-identification (Re-ID) tasks, the need for all-day retrieval has become an inevitable trend. Nevertheless, single-modal Re-ID is no longer sufficient to meet this requirement, making Multi-Modal Data crucial in Re-ID. Consequently, a Visible-Infrared Person Re-Identification (VI Re-ID) task is proposed, which aims to match pairs of person images from the visible and infrared modalities. The significant modality discrepancy between the modalities poses a major challenge. Existing VI Re-ID methods focus on cross-modal feature learning and modal transformation to alleviate the discrepancy but overlook the impact of person contour information. Contours exhibit modality invariance, which is vital for learning effective identity representations and cross-modal matching. In addition, due to the low intra-modal diversity in the visible modality, it is difficult to distinguish the boundaries between some hard samples. To address these issues, we propose the Graph Sampling-based Multi-stream Enhancement Network (GSMEN). Firstly, the Contour Expansion Module (CEM) incorporates the contour information of a person into the original samples, further reducing the modality discrepancy and leading to improved matching stability between image pairs of different modalities. Additionally, to better distinguish cross-modal hard sample pairs during the training process, an innovative Cross-modality Graph Sampler (CGS) is designed for sample selection before training. The CGS calculates the feature distance between samples from different modalities and groups similar samples into the same batch during the training process, effectively exploring the boundary relationships between hard classes in the cross-modal setting. Some experiments conducted on the SYSU-MM01 and RegDB datasets demonstrate the superiority of our proposed method. Specifically, in the VIS→IR task, the experimental results on the RegDB dataset achieve 93.69% for Rank-1 and 92.56% for mAP.

Yield estimation can provide critical information for high-value crop growers. It helps them to plan and coordinate the logistics of harvesting operations. Most existing yield estimation techniques are based on manual sampling and statistical approaches, which are complex, labor-intensive, and time-consuming. In recent years, advances in image processing and the ubiquitous use of autonomous platforms, such as unmanned aerial platforms, have provided an opportunity for faster and more accurate yield estimation techniques for different crops. A new rapid, efficient, and accurate image processing algorithm was proposed in this study. The image segmentation technique was able to separate mature citrus trees and natural background in CIE (Commission International Eclairage) L*a*b* (i.e., Lab) color space. The effect of camera distance to object, affected resolution, and detection accuracy were evaluated and discussed. The results showed that the distance between 1.524 meters (5 feet) and 2.134 meters (7 feet) could provide high detection accuracy. The number of correctly counted fruit reached 91.69% at the average processing time of 1.1 s per picture for 132 pictures. A correlation coefficient (R2) of 0.98 was obtained between the citrus counting algorithm and counting performed through human observation of 66 sample trees. The comparative analysis of the proposed method showed a higher accuracy rate and robustness compared to other similar studies.

Abstract Background Dilated cardiomyopathy (DCM) is one of the common causes of heart failure. Myocardial injury triggers an inflammatory response and recruits immune cells into the heart. High expression of Krüppel-like factor 2 (KLF2) in endothelial cells (ECs) potentially exerts an anti-inflammatory effect. However, the role of extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in DCM remains unclear. Methods and results EVs were separated from the supernatant of KLF2-overexpressing ECs by gradient centrifugation. Mice were repeatedly administered low-dose doxorubicin (DOX) and then received KLF2-EVs through an intravenous injection. Treatment with KLF2-EVs prevented doxorubicin-induced left ventricular dysfunction and reduced the recruitment of Ly6high Mo/Mø in the myocardium. We used flow cytometry to detect Ly6high monocytes in bone marrow and spleen tissues and to elucidate the mechanisms underlying this beneficial effect. KLF2-EVs increased the retention of Ly6Chigh monocytes in the bone marrow but not in the spleen tissue. KLF2-EVs also significantly downregulated C–C chemokine receptor 2 (CCR2) protein expression in cells from the bone marrow. Conclusions EVs derived from KLF2-overexpressing ECs reduced cardiac inflammation and ameliorated left ventricular dysfunction in DCM mice by targeting the CCR2 protein to inhibit Ly6Chigh monocyte mobilization from the bone marrow. Graphical Abstract

Most of the malignant melanomas are already in the middle and advanced stages when they are diagnosed, which is often accompanied by the metastasis and spread of other organs. Besides, the prognosis of patients is bleak. The characteristics of the local immune microenvironment in metastatic melanoma have important implications for both tumor progression and tumor treatment. In this study, data on patients with metastatic melanoma from the TCGA and GEO datasets were selected for immune, stromal, and estimate scores, and overlapping differentially expressed genes were screened. A nine-IRGs prognostic model (ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) was established by univariate COX regression, LASSO and multivariate COX regression. Receiver operating characteristic curves were used to test the predictive accuracy of the model. Immune infiltration was analyzed by using CIBERSORT and Xcell in high-risk and low-risk groups. The immune infiltration of the high-risk group was significantly lower than that of the low-risk group. Immune checkpoint analysis revealed that the expression of PDCD1, CTLA4, TIGIT, CD274, HAVR2 and LAG3 demonstrated the visible difference in groups with different levels of risk scores. WGCNA analysis found that the yellow-green module contained seven genes from the nine-IRG prognostic model, and the yellow-green module had the highest correlation with risk scores. The results of GO and KEGG suggested that the genes in the yellow-green module were mainly enriched in immune-related biological processes. Finally, the expression characteristics of ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22 were analyzed between metastatic melanoma and normal samples. Overall, a prognostic model for metastatic melanoma based on the tumor immune microenvironment characteristics was established, which left plenty of space for further studies. It could function well in helping people to understand characteristics of the immune microenvironment in metastatic melanoma.

Abstract Background A number of studies have indicated that Ubiquitin-conjugating enzyme E2T (UBE2T), as an oncogene, promotes progression and metastasis of lung cancer, including lung adenocarcinoma (LUAD), but it is completely unknown whether and how UBE2T is ubiquitylated and degraded, and by which E3 ligase. NEDD4L plays a critical role in the regulation of cellular processes of various cancers, most of which is attributed to its E3 ubiquitin ligase function. However, the relationship between NEDD4L and UBE2T in LUAD has not been elucidated. Methods The relationship between NEDD4L and UBE2T in LUAD tissues and cells was found by bioinformatic analyses and immunoblotting. Cell counting kit-8, colony formation assay, half-life analysis and the in vivo ubiquitylation assay, generation of xenograft model were performed to determine how NEDD4L regulates UBE2T and its downstream signaling pathway in vitro and in vivo. Results Bioinformatic analyses found that NEDD4L, as a potential correlation E3 ligase of UBE2T, was negatively correlated with UBE2T in LUAD. Consistently, UBE2T protein half-life was shortened or extended by NEDD4L overexpression or depletion, respectively. NEDD4L inhibited LUAD cell progression in vitro and in vivo via inducing the ubiquitination-mediated UBE2T degradation, which repressed PI3K-AKT signaling. Similarly, NEDD4L predicted a better patient survival, whereas UBE2T predicted a worse survival. Conclusions Collectively, our results reveal that NEDD4L is a novel E3 ligase of UBE2T, which can inhibit PI3K-AKT signaling by targeting for UBE2T ubiquitination and degradation, resulting in repression of LUAD cell progression.

Abstract Background There are differences in survival between high-and low-grade Upper Tract Urothelial Carcinoma (UTUC). Our study aimed to develop a nomogram to predict overall survival (OS) of patients with high- and low-grade UTUC after tumor resection, and to explore the difference between high- and low-grade patients. Methods Patients confirmed to have UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. The UTUCs were identified and classified as high- and low-grade, and 1-, 3- and 5-year nomograms were established. The nomogram was then validated using the Chinese multicenter dataset (patients diagnosed in Shandong, China between January 2010 and October 2020). Results In the high-grade UTUC patients, nine important factors related to survival after tumor resection were identified to construct nomogram. The C index of training dataset was 0.740 (95% confidence interval [CI]: 0.727–0.754), showing good calibration. The C index of internal validation dataset was 0.729(95% CI:0.707–0.750). On the other hand, Two independent predictors were identified to construct nomogram of low-grade UTUC. The C index was 0.714 (95% CI: 0.671–0.758) for the training set,0.731(95% CI:0.670–0.791) for the internal validation dataset. Encouragingly, the nomogram was clinically useful and had a good discriminative ability to identify patients at high risk. Conclusion We constructed a nomogram and a corresponding risk classification system predicting the OS of patients with an initial diagnosis of high-and low-grade UTUC.

Van der Waals crystals have recently been shown to exhibit ferromagnetism, however the Curie temperature is typically quite low. Herein, Wu et al succeed in producing mono and few layer crystals of CrTe, a non-van der Waals crystal, and demonstrate strong intrinsic room temperature ferromagnetism.

Coronary artery disease (CAD) is the most common cardiovascular disease worldwide. In this study, we investigated the pathogenesis of CAD. We downloaded the GSE98583 dataset, including 12 CAD samples and 6 normal samples, from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs) in CAD versus normal samples. Next, we performed functional enrichment analysis, protein-protein interaction (PPI) network, and functional module analyses to explore potential functions and regulatory functions of identified DEGs. Next, transcription factors (TFs) and microRNAs (miRNAs) targeting DEGs were predicted. In total, 456 DEGs were identified in CAD and normal samples, including 175 upregulated and 281 downregulated genes. These genes were enriched in the intestinal immune network for immunoglobulin A production and the mitogen-activated protein kinase signaling pathway (e.g., TGFBR2 and EGF). The PPI network contained 212 genes, and HIST1H2BJ, HIST1H2AC, EGF, and EP300 were hub genes with degrees higher than 10. Four significant modules were identified from the PPI network, with genes in the modules mainly enriched in the inflammatory response, protein ubiquitination involved in ubiquitin-dependent protein catabolic processes, protein transport, and mitochondrial translational elongation, respectively. Two TFs (E2F1 and FOXK1) and five miRNAs (miR-122A, miR-516-5P, miR-507, miR-342, and miR-520F) were predicted to target 112 DEGs. miR-122A reportedly targets both LRP10 and IQGAP1 in the TF-miRNA target regulatory network. The abnormal expression of TGFBR2, EGF, LRP10, and IQGAP1 may be implicated in CAD pathogenesis. Our study provides targets and potential regulators for investigating CAD pathogenesis.

The phase transformation behavior of nitrides-strengthened martensitic (NSM) heat resistant steel, showing excellent creep behavior under 500°C, was studied in this article. The results showed that during the heating procedure, the formation of austenite was composed successively by intermetallic compound formation in martensite, crystal structure shift from body-centered cubic (BCC) to face-centered cubic (FCC), martensite/ferrite grain boundary migration, austenite nucleation, and growing. The crystal structure switch from BCC to FCC was sensitive to temperature, while the switch from FCC to BCC was only done with phase transformations. During the continuous cooling procedure, the carbide-free bainite would form if the cooling rate was beneath the critical cooling rate. The critical cooling rate was defined as 0.5°C/s for single martensite in NSM steel, according to its inconsistent results of microstructure and continuous cooling transformation (CCT) expansion curve under this condition. Two phase transformation zones were detected in NSM steel: one was a nose-shaped bainite zone and the other was a stripe-shaped martensite zone.

The rise of cancer immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has significantly changed the clinical treatment paradigm for patients with cancer. The programmed death ligand 1 (PD-L1) protein in the tumor microenvironment (TME) binds to programmed cell death protein 1 (PD-1) on the surface of T cells and initiates the PD-1 / PD-L1 immunosuppressive program, which is currently one of the most promising target pathways for immunotherapy. However, problems such as low response rates, single targets, and high immunotoxicity have limited their clinical application. The upregulation or downregulation of PD-L1 expression in the TME can enhance the therapeutic efficacy of anti-PD-(L)1 inhibitors, and their combination with immunotherapy drugs may represent a novel anti-cancer treatment approach. The diverse immunomodulatory potential of polyphenolic compounds of plant origin offers a new direction for tumor immunotherapy. This review summarizes recent advances in research investigating the PD-L1 modulatory function of polyphenolic compounds and their combination with anti-PD-1/PD-L1 immunotherapy. In addition, we provide new insights into the advantages of polyphenolic compounds in macroscopic regulation in the tumor microenvironment and deeply explore the clinical application prospects and challenges of their immunotherapeutic potential. This study covers the most comprehensive understanding to date of polyphenolic compounds interfering with the PD-1/PD-L1 pathway in TME, intending to provide a comprehensive and valuable source of information regarding the development of polyphenolic phytochemicals as combinatorial adjuvant candidates for experimental studies, clinical applications, and their synergy with immune checkpoint blockade therapy.

Hypertension (HT) is the most common public-health challenge and shows a high incidence around the world. Cardiovascular diseases are the leading cause of mortality and morbidity among the elderly (age > 65 years) in the United States. Now, there is widespread acceptance of the causal link between HT and acute myocardial infarction (MI). This is the first data-mining study to identify co-expressed differentially expressed genes (co-DEGs) between HT and MI (relative to normal control) and to uncover potential biomarkers and therapeutic targets of HT-related MI. In this manuscript, HT-specific DEGs and MI-specific DEGs and differentially expressed microRNAs (DE-miRNAs) were identified in Gene Expression Omnibus (GEO) datasets GSE24752, GSE60993, GSE62646, and GSE24548 after data consolidation and batch correction. Subsequently, enrichment in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways as well as protein–protein interaction networks were identified, and single-gene gene set enrichment analysis was performed to determine the affected biological categories and networks. Cross-matching of the results on co-DE-miRNAs and predicted miRNAs targeting the co-DEGs was conducted and discussed as well. We found that MYC and HIST1H2BO may be associated with HT, whereas FCGR1A, FYN, KLRD1, KLRB1, and FOLR3 may be implicated in MI. Moreover, co-DEGs FOLR3 and NFE2 with predicted miRNAs and DE-miRNAs, especially miR-7 and miR-548, may be significantly associated and show huge potential as a new set of novel biomarkers and important molecular targets in the course of HT-related MI.

Abstract Background COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients. Methods Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients. Results Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4+ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). For severe patients, the counts of T cell, CD4+ T cell, CD8+ T cell gradually decreased with the increased delayed hospitalization (p = 0.001, 0.03, and

With the development in tumor immunology, people are gradually understanding the complexity and diversity of the tumor microenvironment immune status and its important effect on tumors. Tumor-associated macrophages (TAMs), an important part of the tumor immune microenvironment, have a double effect on tumor growth and metastasis. Many studies have focused on lung cancer, especially non-small cell lung cancer and other ''hot tumors'' with typical inflammatory characteristics. The polarization and infiltration of TAMs is an important mechanism in the occurrence and development of malignant tumors, such as lung cancer, and in the tumor immune microenvironment. Therapeutic drugs designed for these reasons are key to targeting TAMs in the treatment of lung cancer. A large number of reports have suggested that natural compounds have a strong potential of affecting immunity by targeting the polarization and infiltration of TAMs to improve the immune microenvironment of lung cancer and exert a natural antitumor effect. This paper discusses the infiltration and polarization effects of natural compounds on lung cancer TAMs, provides a detailed classification and systematic review of natural compounds, and summarizes the bias of different kinds of natural compounds by affecting their antitumor mechanism of TAMs, with the aim of providing new perspectives and potential therapeutic drugs for targeted macrophages in the treatment of lung cancer.

ABSTRACT Essential genus-specific genes have not been discovered for fowl adenovirus (FAdV), which hampers the development of FAdV-based vectors and attenuated FAdV vaccines. Reverse genetics approaches were employed to construct FAdV-4 mutants carrying deletions or frameshift mutations covering the whole left and right ends of the viral genome. The results of virus rescue and plaque forming experiments illustrated that all the 22 designated ORFs (open reading frames) were dispensable for the replication of FAdV-4 in chicken hepatoma Leghorn male hepatoma (LMH) cells and primary embryo hepatocytes. RNA-seq data demonstrated that ORF28 and ORF29 were not protein-encoding genes, and suggested a promoter (RP1) and an intron in these regions, respectively. The promoter activity of RP1 was further confirmed by reporter gene expression experiments. GAM-1-deleted FAdV-4 formed small plaques, while deletion of GAM-1 together with ORF22 resulted in even smaller ones in LMH cells. Simultaneous deletion of ORF28, ORF29, and GAM-1 led to growth defect of FAdV-4. These facts implied that genus-specific genes contributed to and synergistically affected viral replication, although no single one was essential. Notably, replication of FAdV-4 mutants could be different in vitro and in vivo. XGAM1-CX19A, a GAM-1-deleted FAdV-4 that replicated efficiently in LMH cells, did not kill chicken embryos because virus propagation took place at a very low level in vivo. This work laid a solid foundation for FAdV-4 vector construction as well as vaccine development, and would benefit viral gene function study. IMPORTANCE Identification of viral essential genes is important for adenoviral vector construction. Deletion of nonessential genes enlarges cloning capacity, deletion of essential genes makes a replication-defective vector, and expression of essential genes in trans generates a virus packaging cell line. However, the genus-specific essential genes in FAdV have not been identified. We constructed adenoviral plasmid carrying deletions covering all 22 genus-specific ORFs of FAdV-4, and found that all virus mutants could be rescued and amplified in chicken LMH cells except those that had defects in key promoter activity. These genus-specific genes affected virus growth, but no single one was indispensable. Dysfunction of several genus-specific genes at the same time could make FAdV-4 vectors replication-defective. In addition, the growth of FAdV-4 mutants could be different in LMH cells and in chicken embryos, suggesting the possibility of constructing attenuated FAdV-4 vaccines.