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Abstract Renal cell carcinoma (RCC) ranks as a prevalent malignant neoplasm, with clear cell renal cell carcinoma (ccRCC, also known as KIRC) accounting for approximately 75% of all RCC cases. The farnesoid X receptor (FXR, encoded by NR1H4), functioning as a nuclear receptor, plays a crucial role in regulating gene transcription. Although the involvement of FXR in tumors of the digestive system and in acute kidney injury has been extensively studied, its specific role in the pathogenesis of ccRCC has yet to be thoroughly investigated. Consequently, the objective of our current investigation is to uncover the functional roles of FXR in ccRCC. In this study, plasmids for the overexpression of FXR were constructed, and small interfering RNA (siRNA) constructs were designed. Dual-luciferase reporter assays confirmed a direct binding interaction between FXR and the promoter of the matrix metalloproteinase 7 (MMP-7) gene. Additionally, a mouse xenograft model elucidated the regulatory effect of FXR on MMP-7 in the context of tumor growth. This study elucidates how FXR regulates the promotion of ccRCC through the MMP-7-mediated EMT pathway. Interestingly, FXR is typically regarded as a tumor suppressor gene that affects gastrointestinal tumors, providing a potential new therapeutic direction for ccRCC.

The TC4 titanium alloy is extensively utilized in marine engineering due to its exceptional comprehensive performance. However, when subjected to harsh marine environments, the TC4 titanium alloy is susceptible to tribocorrosion, which can shorten the service life of components. This paper employs an electrochemical anodic oxidation treatment of the TC4 titanium alloy and a ceramic adhesive to fabricate a TC4 anodic oxidation/carbon fiber composite (CFCM) to address this challenge. Hence, A systematic study has been conducted on the friction and wear behavior of TC4 titanium alloy in artificial marine and air environments, focusing on exploring the tribocorrosion behavior and their intrinsic mechanisms in marine environments. The corrosion behavior of the TC4 titanium alloy was determined through kinetic potential polarization analysis. The results indicate that the anodized/carbon fiber composite can significantly enhance the tribocorrosion resistance of the material. Two orders of magnitude reduce the passivation corrosion density, and the corrosion potential increases to −0.136 V compared to the TC4 substrate. Furthermore, the wear mechanism is predominantly characterized by abrasive wear. This study offers novel insights for optimizing the selection of anticorrosive materials and designing coatings in marine engineering.

High-temperature-resistant adhesives are critical materials in the aerospace field. The zirconium-modified aluminum phosphate-based adhesives developed in this work had the advantage of adjustable thermal expansibility, achieving a high matching of coefficient of thermal expansion (CTE) with alumina. The introduction of zirconium can significantly improve the thermal stability of the adhesive matrix, and the Zr/Al ratio substantially affects the various reaction processes inside the adhesive, especially the types of zirconium-containing compounds. Most of the zirconium-containing compounds in the A7Z3 adhesive were ZrO2 only when the mass ratio of zirconium hydroxide to aluminum hydroxide was 3 : 7, which was the key reason why it had the highest CTE. The room-temperature bonding strength of A7Z3 after heat treatment at 1500 °C reached 67.2 MPa. After pretreatment at 1500 °C, the high-temperature bonding strength of A7Z3 was greater than 50 MPa in the range of (room temperature) RT–1000 °C. After 40 thermal cycles between RT and 1500 °C, the bonding strength still reached 10 MPa. Physical bonding occurred at temperatures below 1000 °C, while chemical bonding dominated above 1000 °C based on the generation of Al5BO9 and mullite at the interfaces.

In order to investigate the mechanism of aspartic acid, glutamic acid and their glycine dipeptides on calcium ion uptake, the isothermal titration calorimetry technique, electrochemistry, and Caco-2 cell model combined with quantum mechanical calculation (density functional theory) were used to investigate the interactions between aspartic acid and glutamic acid, as well as their glycine dipeptides. The results showed that aspartic acid and glutamic acid form complexes with calcium ions through exothermic reactions driven by enthalpy and entropy, while their dipeptides interacted with calcium ions by entropy-driven endothermic reactions. In addition, dipeptides exhibited stronger calcium binding capacity than the single amino acids. Quantum chemical calculations showed that the carboxyl groups in the amino acid/dipeptide were the main binding site of calcium ions, while under alkaline conditions, the amino group could also participate in calcium binding, leading to a calcium binding site shift. Caco-2 cell uptake experiments showed that aspartic acid, glutamic acid and their dipeptides could promote calcium absorption. Among them, Gly-Glu dipeptide had the best promotion effect, and the calcium absorption rate was 1.33±0.115. Furthermore, there was no clear correlation between the ability to promote calcium absorption and the ability to bind calcium ions. However, it was more closely related to its electron affinity. The results elucidated the interactions between aspartic acid, glutamic acid and their glycine dipeptides and calcium ions, providing scientific basis for further development of calcium supplements

It is well known that the grain size of high-entropy ceramics is quite small owing to the sluggish diffusion effect. However, abnormal grain growth often occurs in high-entropy pseudobrookite ceramics, ultimately resulting in the formation of many abnormally grown grains with a grain size as large as 50 μm. To study this phenomenon, the grain growth behavior of high-entropy pseudobrookite ceramics was systematically investigated in this paper. The results demonstrate that the starting material powders first react with each other to form a high-entropy intermediate phase and calcined TiO2 powders (TiO2-1100 °C), and then as the sintering temperature increases, the formed high-entropy intermediate phase further reacts with TiO2-1100 °C to form high-entropy pseudobrookite ceramics. Thus, in this system, in addition to the sluggish diffusion effect, the grain sizes of the high-entropy intermediate phase and TiO2-1100 °C also affect the morphology of high-entropy pseudobrookite. Compared to nanosized TiO2, micron-sized TiO2 has a lower sintering activity. Therefore, the high-entropy intermediate phases (Mg,Co,Ni,Zn)TiO3 and TiO2-1100 °C prepared with micron-sized starting materials exhibit lower grain sizes, finally resulting in the formation of high-entropy (Mg,Co,Ni,Zn)Ti2O5 with small grain sizes. Moreover, nano-indentation and thermal conductivity tests were carried out on high-entropy (Mg,Co,Ni,Zn)Ti2O5 with different morphologies. The results show that the hardness of high-entropy (Mg,Co,Ni,Zn)Ti2O5 increases from 6.05 to 9.95 GPa as the grain size increases, whereas the thermal conductivity decreases from 2.091±0.006 to 1.583±0.006 W·m−1·K−1. All these results indicate that high-entropy (Mg,Co,Ni,Zn)Ti2O5 with a small grain size is a potential material for thermal protection.

The key to managing urban heat island (UHI) is identifying and cooling the core areas of UHI. Studies have shown that spatial differences in urban green space (UGS) indicators have a significant impact on spatial differences in land surface temperature (LST). However, previous studies have mainly explored UGS and LST in the entire region, with few focusing on the urban core area. In this study, we extracted the urban core area based on the Point of Interest (POI) and kernel density methods. Correlation and regression analyses were then used to investigate the correlation between UGS indicators and seasonal LST in the urban core area. Our results confirm the significant cooling effect of UGS at the urban core scale. The effects of UGS landscape composition and configuration on LST varied across seasons and across urban green space ratio (UGSR) gradients. In the warm season, increasing the UGSR proved to be the most effective way to mitigate the urban thermal environment. In urban core areas where expanding UGS is not possible or in cores with high UGSR, designing UGS with complex shapes and clusters can better achieve the cooling effect. These results suggest that the influence of UGS landscape features on the urban surface thermal environment at the urban core area scale is very complex. Therefore, implementing urban greening to mitigate the UHI problem requires considering the premise of multifactorial analysis.

Abstract Objective Early diagnosis of osteoporosis is crucial to prevent osteoporotic vertebral fracture and complications of spine surgery. We aimed to conduct a hybrid transformer convolutional neural network (HTCNN)-based radiomics model for osteoporosis screening in routine CT. Methods To investigate the HTCNN algorithm for vertebrae and trabecular segmentation, 92 training subjects and 45 test subjects were employed. Furthermore, we included 283 vertebral bodies and randomly divided them into the training cohort (n = 204) and test cohort (n = 79) for radiomics analysis. Area receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were applied to compare the performance and clinical value between radiomics models and Hounsfield Unit (HU) values to detect dual-energy X-ray absorptiometry (DXA) based osteoporosis. Results HTCNN algorithm revealed high precision for the segmentation of the vertebral body and trabecular compartment. In test sets, the mean dice scores reach 0.968 and 0.961. 12 features from the trabecular compartment and 15 features from the entire vertebral body were used to calculate the radiomics score (rad score). Compared with HU values and trabecular rad-score, the vertebrae rad-score suggested the best efficacy for osteoporosis and non-osteoporosis discrimination (training group: AUC = 0.95, 95%CI 0.91–0.99; test group: AUC = 0.97, 95%CI 0.93–1.00) and the differences were significant in test group according to the DeLong test (p

Abstract To evaluate the diagnostic accuracy of a new modified MR dual precision positioning of thin-slice oblique sagittal fat suppression proton density-weighted imaging (DPP-TSO-Sag-FS-PDWI) sequence in detecting ACL injuries and its grades compared to standard sequences using arthroscopy as the standard reference. 42 patients enrolled in this retrospective study received the 1.5-T MRI with standard sequences and the new modified DPP-TSO-Sag-FS-PDWI sequence, and their arthroscopy results was recorded. The Mc Nemer-Bowker and weighted Kappa was performed to compare the consistency of MRI diagnosis with arthroscopic results. Finally, the diagnostic accuracy was calculated based on the true positive, true negative, false negative and false positive values. The diagnostic consistency of the DPP-TSO-Sag-FS-PDWI were higher than standard sequences for both reader 1 (K = 0.876 vs. 0.620) and reader 2 (K = 0.833 vs. 0.683) with good diagnostic repeatability (K = 0.794 vs. 0.598). Furthermore, the DPP-TSO-Sag-FS-PDWI can classify and diagnose three grades of ACL injury [the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value were more than 84%], especially for grade II injury as the PPV was superior for reader 1 (92.3% vs. 53.9%) and reader 2 (84.6% vs. 69.2%). The new modified DPP-TSO-Sag-FS-PDWI sequence can display the ACL injury on one or continuous levels by maximizing the acquisition of complete ligament shape and true anatomical images, and excluding the influence of anatomical differences between individuals. It can improve the diagnostic accuracy with good repeatability and classify three grades of the ACL injury.

The development of automation and intelligence in geological core drilling is not yet mature. The selection and improvement of drilling parameters rely mainly on experience, and adjustments are often made after drilling by evaluating the core, which introduces a lag and reduces the drilling efficiency. Therefore, this study first establishes a geological core drilling experiment platform to collect drilling data. Through the constructed geological core drilling experimental platform, the practical data at the drill bit can be directly obtained, solving the problem of the data from the surface equipment in the practical drilling differing from the practical data. Second, the back propagation (BP) algorithm is used to perform the ROP prediction, with weight on bit (WOB), torque (TOR), flow rate (Q), and rotation speed (RPM) as input parameters, and rate of penetration (ROP) as the output. Subsequently, correlation analysis is used to perform the feature parameter optimization, and the effects of bit wear and bit cutting depth on the experiment are considered. Finally, comparison with algorithms such as ridge regression, SVM and KNN shows that the ROP prediction model using the BP neural network has the highest prediction accuracy of 94.1%. The results provide a reference for ROP prediction and the automation of geological core drilling rigs.

Single-Pilot Operations (SPO) mode is set to reshape the decision-making process between human-machine and air-ground operations. However, the limited on-board computing resources impose greater demands on the organization of performance parameters and the optimization of process efficiency in SPO mode. To address this challenge, this paper first investigates the flexible requirements of avionics systems arising from changes in SPO operational scenarios, then analyzes the architecture of Reconfigurable Integrated Modular Avionics (RIMA) and its resource allocation framework in the context of scarcity and configurability. A “mission-function-resource” mapping relationship is established between the reconfiguration service elements of SPO mode and avionics resources. Subsequently, the Proximal Policy Optimization (PPO) algorithm is introduced to simulate the resource allocation process of IMA reconfiguration in SPO mode. The objective optimization process is transformed into a sequential decision-making problem by considering constraints and optimization criteria such as load, latency, and power consumption within the feasible domain of avionics system resources. Finally, the resource allocation scheme for avionics system reconfiguration is determined by controlling the probability of action selection during the interaction between the agent and the environment. The experimental results show that the resource allocation scheme based on the PPO algorithm can effectively reduce power consumption and latency, and the DRL model has strong anti-interference and generalization. This enables avionics resources to respond dynamically to the capabilities required in SPO mode and enhances their ability to support the aircraft mission at all stages.

The electrochemical production of hydrogen peroxide (H2O2) by the two-electron oxygen reduction (2e−-ORR) process has the advantages of high safety, low energy consumption, and environmental friendliness. For 2e−-ORR, the catalyst/electrode is the key component as it strongly affects catalytic performance and cost. Carbon materials have the advantages of high electronic conductivity, good structural stability, easy control of nanostructures, and low cost. Therefore, it has been regarded as a promising catalyst/electrode material for the electrosynthesis of H2O2 via 2e−-ORR. In addition, studies have also considered the optimization of the liquid/gas interface by tuning the electrode surface, electrolyte pH, and reactor configurations for further improving the activity and selectivity of catalysts. In this review, we provide an in-depth discussion of the recent research on the carbon-based electrocatalysts for 2e−-ORR, especially in terms of microenvironment tuning, catalyst/electrode interface engineering, and reactor design for achieving stable and efficient production of H2O2. The challenges that we are still facing and the future development prospects will then be concluded, which we believe should help the future development in this field.

Treatment of multiple myeloma (MM) has evolved remarkably over the past few decades. Autologous stem cell transplantation, as well as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has substantially improved the prognosis of patients with MM. Novel therapies, including chimeric antigen receptor-T cells, bispecific T-cell engagers, antibody-drug conjugates, histone deacetylase inhibitors, and nuclear export inhibitors, have provided more options. However, MM remains incurable. T cells are the principal weapons of antitumor immunity, but T cells display a broad spectrum of dysfunctional states during MM. The promising clinical results of T-cell-directed immunotherapies emphasize the significance of enhancing T-cell function in antimyeloma treatment. This review summarizes the potential effects of these antimyeloma agents on T-cell function and discusses possible optimized strategies for MM management by boosting T-cell immunity.

Calcium is an essential nutrient for human health and plays a crucial role in various physiological processes such as bone formation, muscle contraction, nerve transmission, and blood clotting. Calcium absorption mainly occurs in the small intestine where the calcium enters the enterocytes through active transport or passive diffusion. However, the free calcium ions dissolved in gastric acid may form insoluble precipitates with other dietary components (such as phytate, oxalate, fiber) in the slightly alkaline intestinal environment, leading to decreased calcium absorption and bioavailability. Decreased calcium absorption can result in a range of bone metabolic diseases, such as rickets and osteoporosis. Therefore, it is important to choose foods or supplements that can provide highly soluble and bioavailable forms of calcium. Some organic calcium salts such as calcium gluconate and calcium citrate have been shown to form supersaturated solutions in the intestinal tract, which can enhance calcium absorption by increasing the concentration gradient across the intestinal epithelium. Furthermore, calcium-peptide complexes are proven to be very effective for improving calcium absorption without causing any side effects. Calcium-peptide complexes can serve as a novel calcium supplement. In this paper, the effects of food components on calcium absorption and bioavailability are reviewd, and the mechanisms underlying the enhancement of calcium absorption by some organic salts (such as calcium gluconate and calcium citrate) and peptides are summarized. And the potential applications of calcium-peptide complexes in human nutrition are also discussed, aiming to provide new insights that can aid in the development of safe and effective calcium supplements

The inertial measurement method of pipelines utilizes a Micro-Electro-Mechanical Systems Inertial Measurement Unit (MIMU) to get the three-dimensional trajectory of underground pipelines. The initial attitude is significant for the inertial measurement method of pipelines. The traditional method to obtain the initial attitude uses three-axis magnetometers to measure the Earth’s magnetic field. However, the magnetic field in urban underground pipelines is intricate, which leads to the initial attitude being inaccurate. To overcome this challenge, a novel multi-position initial alignment method based on data backtracking for a single-axis FOG and a three-axis Micro-Electro-Mechanical Inertial Measurement Unit (MIMU) is proposed. Firstly, the configuration of the sensors is determined. Secondly, according to the three-point support structure of the pipeline measuring instrument, a three-position alignment scheme is designed. Additionally, an initial alignment algorithm using the data backtracking method is developed. In this algorithm, a rough initial alignment is conducted by the data from single-axis FOG, and a fine initial alignment is conducted by the data from FOG/MIMU. Finally, an experiment was conducted to validate this method. The experiment results indicate that the pitch and roll angle errors are less than 0.05°, and the azimuth angle errors are less than 0.2°. This improved the precision of the 3-D trajectory of underground pipelines.

As the synthesis, modularization, and integration of avionics systems increase, the interconnections between systems and equipment within subsystems become increasingly complex, posing risks to the safety and reliability of the integrated avionics system. To address the risk of fault propagation due to functional cascade failures in integrated avionics systems, this paper proposes a discrete dynamic fault propagation analysis method, which was applied to an all-electric braking system to assess its feasibility. First, the architectural features of the Distributed Integrated Modular Avionics system are summarized. Subsequently, the constructed system layer model is described, establishing the function–resource hierarchical architecture. Subsequently, the behavior of cascading failure propagation in discrete dynamic systems is analyzed by integrating the cascading failure analysis method from SAE ARP 4761A and considering the coupling characteristics between system properties and functions comprehensively. This approach facilitates the development of a cascading failure propagation model for DIMA based on discrete dynamic systems. Finally, by using the all-electric braking system under DIMA architecture as a case study, key Core Processing Modules and failure-prone functions are identified. The findings reveal that within this system, CPM2 and CPM6 are particularly susceptible to failure propagation, and the automatic brake function is notably vulnerable. Data show that the system’s failure rate escalates markedly after 2×104 h of operation. Performing maintenance before reaching this threshold can further mitigate risks. This practice aligns with current international aircraft maintenance time regulations. The method proposed in this paper can be applied early in the allocation of DIMA resources to enhance security and support DIMA design.

Digestive system malignancies, including cancers of the esophagus, pancreas, stomach, liver, and colorectum, are the leading causes of cancer-related deaths worldwide due to their high morbidity and poor prognosis. The lack of effective early diagnosis methods is a significant factor contributing to the poor prognosis for these malignancies. Tetraspanins (Tspans) are a superfamily of 4-transmembrane proteins (TM4SF), classified as low-molecular-weight glycoproteins, with 33 Tspan family members identified in humans to date. They interact with other membrane proteins or TM4SF members to form a functional platform on the cytoplasmic membrane called Tspan-enriched microdomain and serve multiple functions including cell adhesion, migration, propagation and signal transduction. In this review, we summarize the various roles of Tspans in the progression of digestive system tumors and the underlying molecular mechanisms in recent years. Generally, the expression of CD9, CD151, Tspan1, Tspan5, Tspan8, Tspan12, Tspan15, and Tspan31 are upregulated, facilitating the migration and invasion of digestive system cancer cells. Conversely, Tspan7, CD82, CD63, Tspan7, and Tspan9 are downregulated, suppressing digestive system tumor cell metastasis. Furthermore, the connection between Tspans and the metastasis of malignant bone tumors is reviewed. We also summarize the potential role of Tspans as novel immunotherapy targets and as an approach to overcome drug resistance. Finally, we discuss the potential clinical value and therapeutic targets of Tspans in the treatments of digestive system malignancies and provide some guidance for future research.

ObjectiveIn this research, we investigated the current status, hotspots, frontiers, and trends of research in the field of bone-tendon interface (BTI) from 2000 to 2023, based on bibliometrics and visualization and analysis in CiteSpace, VOSviewer, and a bibliometric package in R software.MethodsWe collected and organized the papers in the Web of Science core collection (WoSCC) for the past 23 years (2000–2023), and extracted and analyzed the papers related to BTI. The extracted papers were bibliometrically analyzed using CiteSpace for overall publication trends, authors, countries/regions, journals, keywords, research hotspots, and frontiers.ResultsA total of 1,995 papers met the inclusion criteria. The number of papers published and the number of citations in the field of BTI have continued to grow steadily over the past 23 years. In terms of research contribution, the United States leads in terms of the number and quality of publications, number of citations, and collaborations with other countries, while the United Kingdom and the Netherlands lead in terms of the average number of citations. The University of Leeds publishes the largest number of papers, and among the institutions hosting the 100 most cited papers Hospital for Special Surgery takes the top spot. MCGONAGLE D has published the highest number of papers (73) in the last 10 years. The top three clusters include #0 “psoriatic arthritis”, #1 “rotator cuff repair”, and #2 “tissue engineering”. The structure and function of the BTI and its key mechanisms in the healing process are the key to research, while new therapies such as mechanical stimulation, platelet-rich plasma, mesenchymal stem cells, and biological scaffolds are hot topics and trends in research.ConclusionOver the past 23 years, global research on the BTI has expanded in both breadth and depth. The focus of research has shifted from studies concentrating on the structure of the BTI and the disease itself to new therapies such as biomaterial-based alternative treatments, mechanical stimulation, platelet-rich plasma, etc.

As a highly pathogenic large DNA virus, African swine fever virus (ASFV) has huge particles and numerous encoded proteins. At present, few of the existing studies on ASFV proteins have investigated the function of p17. Specific antibodies against p17 to promote the development of prevention techniques against African swine fever (ASF) are urgently needed. Herein, we successfully expressed ASFV p17 in CHO cells using a suspension culture system and generated a monoclonal antibody (mAb) against p17. The mAb recognized a novel linear epitope (8LLSHNLSTREGIK20) and exhibited specific reactivity, which was conducive to the identification of ectopically expressed p17, the recombinant porcine reproductive and respiratory syndrome virus expressing p17, and the ASFV-SY18. The epitope was conservative among genotype I and genotype II ASFV strains. Overall, the mAb against p17 revealed efficient detection and promising application prospects, making it a useful tool for future vaccine research on ASF. Determination of the conserved linear epitope of p17 would contribute to the in-depth exploration of the biological function of ASFV antigen protein.

The wide pillars are generally popular due to the high productivity and efficiency in Northwest China. The distribution of lateral abutment pressure in coal pillars is important for mining safety. To reveal the effect of the first mining on the lateral abutment pressure distribution and evolution in wide pillars, an in-situ experiment, theoretical analysis and numerical simulation were performed. First, the field monitoring of lateral abutment pressure was conducted from the perspective of time and space in the Chahasu Coal Mine, Huangling No. 2 Coal Mine and Lingdong Coal Mine during the first mining. Based on the field monitoring stress, a theoretical model was proposed to reveal the lateral abutment pressure distribution. The methodology was demonstrated through a case study. Aiming at the distribution mechanism, a numerical experiment was conducted through the finite-discrete element method (FDEM). Last, field observations of borehole fractures were performed to further study the damage distribution. In addition, two types of lateral abutment pressure evolution with mining advance were discussed. Suggestions on the stress monitoring layout were proposed as well. The results could provide foundations for strata control and disaster prevention in wide pillars in underground coal mines.

Abstract Endometrial cancer (EC) is one of the most common gynecologic cancers and its incidence is rising globally. Although advanced EC has a poor prognosis; diagnosing EC at an earlier stage could improve long-term patient outcomes. However, there is no consensus on the early detection strategies for EC and the current diagnostic practices such as transvaginal ultrasound, hysteroscopy and endometrial biopsy are invasive, costly and low in specificity. Thus, accurate and less invasive screening tests that detect EC in women with early stages of the disease are needed. Current research has revolutionized novel EC early detection methodologies in many aspects. This review aims to comprehensively characterizes minimally invasive screening techniques that can be applied to EC in the future, and fully demonstrate their potential in the early detection of EC.

Abstract Background Type 2 diabetes (T2D) onset is a complex, organized biological process with multilevel regulation, and its physiopathological mechanisms are yet to be elucidated. This study aims to find out the key drivers and pathways involved in the pathogenesis of T2D through multi-omics analysis. Methods The datasets used in the experiments comprise three groups: (1) genomic (2) transcriptomic, and (3) epigenomic categories. Then, a series of bioinformatics technologies including Marker set enrichment analysis (MSEA), weighted key driver analysis (wKDA) was performed to identify key drivers. The hub genes were further verified by the Receiver Operator Characteristic (ROC) Curve analysis, proteomic analysis, and Real-time quantitative polymerase chain reaction (RT-qPCR). The multi-omics network was applied to the Pharmomics pipeline in Mergeomics to identify drug candidates for T2D treatment. Then, we used the drug-gene interaction network to conduct network pharmacological analysis. Besides, molecular docking was performed using AutoDock/Vina, a computational docking program. Results Module-gene interaction network was constructed using MSEA, which revealed a significant enrichment of immune-related activities and glucose metabolism. Top 10 key drivers (PSMB9, COL1A1, COL4A1, HLA-DQB1, COL3A1, IRF7, COL5A1, CD74, HLA-DQA1, and HLA-DRB1) were selected by wKDA analysis. Among these, COL5A1, IRF7, CD74, and HLA-DRB1 were verified to have the capability to diagnose T2D, and expression levels of PSMB9 and CD74 had significantly higher in T2D patients. We further predict the co-expression network and transcription factor (TF) binding specificity of the key driver. Besides, based on module interaction networks and key driver networks, 17 compounds are considered to possess T2D-control potential, such as sunitinib. Conclusions We identified signature genes, biomolecular processes, and pathways using multi-omics networks. Moreover, our computational network analysis revealed potential novel strategies for pharmacologic interventions of T2D.

Abstract As a type of titanate, the pseudobrookite (MTi2O5/M2TiO5) exhibits a low thermal expansion coefficient and thermal conductivity, as well as excellent dielectric and solar spectrum absorption properties. However, the pseudobrookite is unstable and prone to decomposing below 1200 °C, which limits the practical application of the pseudobrookite. In this paper, the high-entropy pseudobrookite ceramic is synthesized for the first time. The pure high-entropy (Mg,Co,Ni,Zn)Ti2O5 with the pseudobrookite structure and the biphasic high-entropy ceramic composed of the high-entropy pseudobrookite (Cr,Mn,Fe,Al,Ga)2TiO5 and the high-entropy spinel (Cr,Mn,Fe,Al,Ga,Ti)3O4 are successfully prepared by the in-situ solid-phase reaction method. The comparison between the theoretical crystal structure of the pseudobrookite and the aberration-corrected scanning transmission electron microscopy (AC-STEM) images of high-entropy (Mg,Co,Ni,Zn)Ti2O5 shows that the metal ions (M and Ti ions) are disorderly distributed at the A site and the B site in high-entropy (Mg,Co,Ni,Zn)Ti2O5, leading to an unprecedentedly high configurational entropy of high-entropy (Mg,Co,Ni,Zn)Ti2O5. The bulk high-entropy (Mg,Co,Ni,Zn)Ti2O5 ceramics exhibit a low thermal expansion coefficient of 6.35×10−6 K−1 in the temperature range of 25–1400 °C and thermal conductivity of 1.840 W·m−1·K−1 at room temperature, as well as the excellent thermal stability at 200, 600, and 1400 °C. Owing to these outstanding properties, high-entropy (Mg,Co,Ni,Zn)Ti2O5 is expected to be the promising candidate for high-temperature thermal insulation. This work has further extended the family of different crystal structures of high-entropy ceramics reported to date.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high mortality rate and unclarified aetiology. Immune response is elaborately regulated during the progression of IPF, but immune cells subsets are complicated which has not been detailed described during IPF progression. Therefore, in the current study, we sought to investigate the role of immune regulation by elaborately characterize the heterogeneous of immune cells during the progression of IPF. To this end, we performed single-cell profiling of lung immune cells isolated from four stages of bleomycin-induced pulmonary fibrosis—a classical mouse model that mimics human IPF. The results revealed distinct components of immune cells in different phases of pulmonary fibrosis and close communication between macrophages and other immune cells along with pulmonary fibrosis progression. Enriched signals of SPP1, CCL5 and CXCL2 were found between macrophages and other immune cells. The more detailed definition of the subpopulations of macrophages defined alveolar macrophages (AMs) and monocyte-derived macrophages (mo-Macs)—the two major types of primary lung macrophages—exhibited the highest heterogeneity and dynamic changes in expression of profibrotic genes during disease progression. Our analysis suggested that Gpnmb and Trem2 were both upregulated in macrophages and may play important roles in pulmonary fibrosis progression. Additionally, the metabolic status of AMs and mo-Macs varied with disease progression. In line with the published data on human IPF, macrophages in the mouse model shared some features regarding gene expression and metabolic status with that of macrophages in IPF patients. Our study provides new insights into the pathological features of profibrotic macrophages in the lung that will facilitate the identification of new targets for disease intervention and treatment of IPF.

Cisplatin is one of the major causes of acute kidney injury (AKI) in clinical practice, and ferroptosis is an essential form of cell death in cisplatin-induced AKI (CP-AKI). WW domain binding protein-2 (WBP2), a molecular chaperon, is involved in the progression of various malignancies, but its role in renal injuries has not been investigated. Our present study employed bioinformatics analysis to identify WBP2 as a potential modulator of AKI and ferroptosis. Preliminary laboratory investigations showed that WBP2, highly expressed in renal proximal tubular cells, was downregulated in CP-AKI. Further studies demonstrated that WBP2 decelerated ferroptosis to alleviate CP-AKI. Mechanistically, WBP2 interacted with glutathione peroxidase 4 (GPX4, a key detoxicating enzyme for ferroptosis) via its PPXY1 motif to inhibit ferroptosis. Furthermore, the in-depth investigations revealed that WBP2 competed with heat shock cognate protein 70 (HSC70) for the binding with the KEFRQ-like motifs of GPX4, leading to the deceleration of chaperon-mediated autophagy of GPX4. All in all, this study indicated the beneficial effect of WBP2 in CP-AKI and its relevance with ferroptosis, thus providing a novel insight into the modulation of ferroptosis in cisplatin-related nephropathy.

Abstract Extracellular microRNAs (miRNAs) play a critical role in horizontal gene regulation. Uptake of extracellular miRNAs by recipient cells and their intracellular transport, however, remains elusive. Here RNA phase separation is shown as a novel pathway of miRNA uptake. In the presence of serum, synthetic miRNAs rapidly self‐assembly into ≈110 nm discrete nanoparticles, which enable miRNAs’ entry into different cells. Depleting serum cationic proteins prevents the formation of such nanoparticles and thus blocks miRNA uptake. Different from lipofectamine‐mediated miRNA transfection in which majority of miRNAs are accumulated in lysosomes of transfected cells, nanoparticles‐mediated miRNA uptake predominantly delivers miRNAs into mitochondria in a polyribonucleotide nucleotidyltransferase 1(PNPT1)‐dependent manner. Functional assays further show that the internalized miR‐21 via miRNA phase separation enhances mitochondrial translation of cytochrome b (CYB), leading to increase in adenosine triphosphate (ATP) and reactive oxygen species (ROS) reduction in HEK293T cells. The findings thus reveal a previously unrecognized mechanism for uptake and delivery functional extracellular miRNAs into mitochondria.

We present a simulation-based study on a 3D heterogeneous photonic integration scheme based on a vertical microring coupler (VμRC). Our research introduces a more compact and efficient layout of photonic devices in the vertical direction, surpassing the limitations of traditional planar integration methods. This investigation focuses on optimizing the performance of the VμRC by analyzing critical parameters such as the dimensions of the microring and the waveguide and the refractive indices of surrounding materials, which serve as the guideline for future manufacturing of the device. The simulation results demonstrate that the careful selection and optimization of these parameters significantly impact the transmittance and coupling characteristics of the VμRC. To demonstrate the validity of this simulation model, we applied it to a few practical cases and achieved comparable results with our previous experiments.

(1) Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the second most common cause of cancer death. However, effective anti-CRC drugs are still lacking in clinical settings. This article investigated the anti-proliferative effect of involucrasin B on CRC Caco-2 cells. (2) Methods: This study employed a sulforhodamine B (SRB) method, colony formation experiments, flow cytometry, FastFUCCI assay, dual luciferase assay, and Western blot analysis for the investigation. (3) Results: The SRB method and colony formation experiments showed that involucrasin B exhibited an inhibitory effect on the Caco-2 cells cultured in vitro. Subsequently, the flow cytometry, FastFUCCI assay, and Western blotting results showed that involucrasin B induced cell cycle arrest in the G1 phase dose-dependently. Involucrasin B significantly enhanced the TGFβ RII protein level and SMAD3 phosphorylation, thus inhibiting the expression of CDK4 and cyclin D1 and causing G1 cell cycle arrest. (4) Conclusion: This study shows that involucrasin B exerts its anti-proliferative effect by regulating the TGFβ/SMAD2-3-4 pathway to cause G1 cycle arrest in Caco-2 cells.

Objectives DOT1L, a histone methylase, is overexpression in renal cell cancer. However, the role and detailed molecular mechanism of DOT1L involved in renal cancer development remain unknown. Methods The inhibition of DOT1L was used by SGC0946 and short hairpin RNA silencing. Monodansylcadaverine staining and transmission electron microscope were performed to detect autophagy changes as a result of the inhibition of DOT1L. MitoTracker Red assay was used to analyze mitochondrial morphology. The autophagy markers and mitochondria-related proteins were analyzed by Western blot, qPCR, or immunofluorescence. ChIP assay was performed to demonstrate H3K79me2 is involved in the direct regulation of Farnesoid X receptor transcription. Results DOT1L inhibition increased autophagy activity and promoted mito chondria fusion in cell lines of renal cancer. Inhibition of DOT1L upregulated levels of LC3α/β, P62, MFN1, and MFN2, which contributed to autophagy activity or mitochondria fusion. DOT1L knockdown showed a similar the above process. DOT1L inhibition or silencing resulted in AMP-activated protein kinase activation and mammalian target of rapamycin inhibition. Mechanistically, the DOT1L inhibitor and its short hairpin RNAs decreased the expression of Farnesoid X receptor in a histone methylase-dependent manner. Conclusion We revealed the essential role of Farnesoid X receptor in regulating DOT1L-induced autophagy and mitochondrial fission through the AMP-activated protein kinase/mammalian target of rapamycin pathway in cell lines of renal cancer, which may provide new insights into the pathogenesis of renal cell cancer.

The clearance function is essential for maintaining brain tissue homeostasis, and the glymphatic system is the main pathway for removing brain interstitial solutes. Aquaporin-4 (AQP4) is the most abundantly expressed aquaporin in the central nervous system (CNS) and is an integral component of the glymphatic system. In recent years, many studies have shown that AQP4 affects the morbidity and recovery process of CNS disorders through the glymphatic system, and AQP4 shows notable variability in CNS disorders and is part of the pathogenesis of these diseases. Therefore, there has been considerable interest in AQP4 as a potential and promising target for regulating and improving neurological impairment. This review aims to summarize the pathophysiological role that AQP4 plays in several CNS disorders by affecting the clearance function of the glymphatic system. The findings can contribute to a better understanding of the self-regulatory functions in CNS disorders that AQP4 were involved in and provide new therapeutic alternatives for incurable debilitating neurodegenerative disorders of CNS in the future.

African swine fever (ASF) is a contagious infectious disease with high lethality which continuously threatens the global pig industry causing huge economic losses. Currently, there are no commercially available vaccines or antiviral drugs that can effectively control ASF. The pathogen of ASF, ASF virus (ASFV) is a double-stranded DNA virus with a genome ranging from 170 to 193 kb and 151 to 167 open reading frames in various strains, which encodes 150–200 proteins. An effective method of monitoring ASFV antibodies, and specific antibodies against ASFV to promote the development of prevention techniques are urgently needed. In the present study, pK205R of ASFV was successfully expressed in mammalian cells using a suspension culture system. An indirect enzyme-linked immunosorbent assay (ELISA) based on the purified pK205R was established and optimized. The monoclonal antibody (mAb) against pK205R recognized a conservative linear epitope (2VEPREQFFQDLLSAV16) and exhibited specific reactivity, which was conducive to the identification of the recombinant porcine reproductive and respiratory syndrome virus (PRRSV) expressing pK205R. The ELISA method efficiently detected clinical ASFV infection and revealed good application prospects in monitoring the antibody level in vivo for recombinant PRRSV live vector virus expressing the ASFV antigen protein. The determination of the conserved linear epitope of pK205R would contribute to further research on the structural biology and function of pK205R. The indirect ELISA method and mAb against ASFV pK205R revealed efficient detection and promising application prospects, making them ideal for epidemiological surveillance and vaccine research on ASF.

Extracellular vesicles (EVs) play an important role in the communication between tissues and cells. However, it is difficult to screen and trace EVs secreted by specific tissues in vivo, which affects the functional study of EVs in certain tissues under pathophysiological conditions. In this study, a Cre-dependent CD63flag-EGFP co-expressed with mCherry protein system expressing mice was constructed, which can be used for the secretion, movement, and sorting of EVs from specific tissues in vivo. This mouse model is an ideal research tool for studying the secretion amount, target tissue, and functional molecule screening of EVs in specific tissues under different pathophysiological conditions. Moreover, it provides a new research method to clarify the mechanism of secreted EVs in the pathogenesis of the disease.

The BCL-2 inhibitor venetoclax is currently approved for treatment of hematologic diseases and is widely used either as monotherapy or in combination strategies. It has produced promising results in the treatment of refractory or relapsed (R/R) and aged malignant hematologic diseases. However, with clinical use, resistance to venetoclax has emerged. We review the mechanism of reduced dependence on BCL-2 mediated by the upregulation of antiapoptotic proteins other than BCL-2, such as MCL-1 and BCL-XL, which is the primary mechanism of venetoclax resistance, and find that this mechanism is achieved through different pathways in different hematologic diseases. Additionally, this paper also summarizes the current investigations of the mechanisms of venetoclax resistance in terms of altered cellular metabolism, changes in the mitochondrial structure, altered or modified BCL-2 binding domains, and some other aspects; this article also reviews relevant strategies to address these resistance mechanisms.

Background: The relationship between CILP (1184T>C) and IL-1α(+889C/T) polymorphisms and intervertebral disc degeneration (IDD) have been explored in several studies but the results were conflicting. The aim of the study was to evaluate and synthesize the currently available data on the association between CILP (1184T>C) and IL-1α(+889C/T) polymorphisms and susceptibility of phenotype-dependent radiologic IDD (RIDD) and symptomatic intervertebral disk herniation (SIDH).Methods: A computerized literature search was in PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure database, and Web of Science. The pooled results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Moreover, the false-positive report probability (FPRP) test and trial sequential analysis (TSA) were applied to estimate the significant results.Results: Our evidence demonstrated that IL-1α(+889C/T) was significant associated with RIDD (allele model: OR = 1.34, 95%CI 1.03–1.74, p = 0.029) and SIDH (allele model: OR = 1.28, 95% CI 1.03–1.60, p = 0.028). However, the results were not noteworthy under the FPRP test and TSA analysis. Additionally, CILP (1184T>C) polymorphism was significantly associated with RIDD with adequate evidence (allele model: OR = 1.27, 95% CI 1.09–1.48, p = 0.002) instead of SIDH.Conclusion: The current meta-analysis illustrated firm evidence that CILP (1184T>C) polymorphism was significantly associated with the susceptibility of RIDD. However, the significant associations between IL-1α(+889C/T) and RIDD and SIDH were less credible. Thus, more multi-center studies with diverse populations were required to verify the results.

Background: Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are multifactor diseases characterized by progressively ectopic ossification in the spinal ligament. However, the shared ossification mechanism of OPLL and OLF remains to be elucidated. The study aims to investigate the common biomarkers related to ectopic ossification and the potential molecular regulatory mechanism.Methods: Microarray and RNA-seq datasets were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) from OPLL and OLF were identified to construct the protein-protein interaction (PPI) network. Furthermore, the hub intersection genes were screened and the diagnostic performance was assessed in the external OLF and OPLL cohorts. We also depicted the landscape of immune cell infiltration and m6A modification meanwhile further estimating the relationship with BMP4.Results: A total of nine up-regulated DEGs and 11 down-regulated DEGs were identified to construct the PPI networks. The integrative bioinformatic analysis defined five hub genes (BMP4, ADAMTS4, HBEGF, IL11, and HAS2) as the common risk biomarkers. Among them, BMP4 was the core target. ROC analysis demonstrated a high diagnostic value of the hub genes. Moreover, activated B cells were recognized as shared differential immune infiltrating cells and significantly associated with BMP4 in OPLL and OLF. Meanwhile, a strong correlation was detected between the expression pattern of the m6A regulator METTL3 and BMP4.Conclusion: This study first identified BMP4 as the shared core biomarker in the development of OPLL and OLF. Activated B cells and m6A writer METTL3 might be involved in the osteogenesis process mediated by BMP4. Our findings provide insights into the pathogenesis in the ossification of the spinal ligament and unveil the potential therapeutic targets.

Abstract Precipitation and its response to forcing is an important aspect of planetary climate system. In this study, we examine the strength of precipitation in the experiments with different atmospheric masses and their response to surface warming, using three global atmospheric general circulation models and one regional cloud‐resolving model. We find that precipitation is weaker when atmospheric mass is larger for a given surface temperature. Furthermore, the increasing rate of precipitation with increasing surface temperature under a larger atmospheric mass is smaller than that under a smaller atmospheric mass. These behaviors can be understood based on atmospheric or surface energy balance. Atmospheric mass influences Rayleigh scattering, multiple scattering in the atmosphere, pressure broadening, lapse rate, and thereby precipitation strength. These results have important implications on the climate and habitability of early Earth, early Mars, and exoplanets with oceans.

Elaborated in several forms before being formally defined, virtually coupled train sets (VCTS) have become an issue for capacity increase with obvious shorter train intervals. As the station organization strategy is still ambiguous due to the lack of literature, the receiving routing problem for VCTS is studied in particular. First, the existing concept of VCTS is explained, which refers to the virtual connection of trains through safe and reliable communication technology, allowing short-interval collaborative operations without the need for physical equipment. Subsequently, the operating characteristics and receiving requirements are analyzed. With a summary of factors affecting receiving operations, a mathematical model is proposed with the objectives of minimizing operation duration and maximizing effectiveness, which is solved by an improved genetic algorithm (GA) with an elitist and adaptive strategy. Numerical tests are carried out 250 times based on a practical station and EMU parameters. The macro results show the valid pursuit of designed objectives with an average duration of 204.95 s and an efficiency of 91.76%. Microevolution of an optimal scheme indicates that safety requirements are met while the process duration is only 35.83% of the original CTCS-3 mode.

The boom in online food delivery(OFD) platforms brings convenience to both consumers and restaurants but leads to pollution from nonbiodegradable plastic food containers. To reduce pollution, the Chinese government enacted a ban on using multiple single-use plastics, including nondegradable OFD food containers. There may be various interests involved in enforcing the ban, so careful analysis is required before implementing the ban. This study applied evolutionary game theory to examine the interaction mechanism of the problematic behaviors between OFD platforms and restaurants. By theoretical research and simulation, we analyzed the conditions under which the game can converge to the expected outcome. In addition, we discussed the measures that are most important to promote restaurants using degradable food packaging in their service.

Metal-doped polymer derived ceramics (PDCs) exhibits multifunctional properties due to the introduction of special metal element; however as one of the cheapest metal element carriers, metal inorganic salts have rarely been reported for the fabrication of metal-doped PDCs. In this article, a novel hydrophilic photosensitive γ-methacryloxypropyl trimethoxy modified polyhydroxymethylsiloxane preceramic polymer was firstly synthesised and three different metal-doped SiOC ceramic lattices with a strut thickness of 200 μm were successfully fabricated using inorganic metal salts as the metal source by digital light processing. The photosensitive coefficient, initial photocuring coefficient and the corresponding working curves were employed to evaluate the photocurable ability of preceramic polymers with different recipes. Results showed that both the metal-containing polymer lattices and the metal-doped SiOC ceramic lattices exhibited high-resolution microstructure and homogeneous metal element distribution, indicating that the inorganic metal salt is an effective metal source for the fabrication of metal-doped PDCs.

Abstract The study of exploring the internal connection between rail transit and land use is of great significance for the coordinated development of urban space and rail transit construction, and it is also important for the intensive use of land affected by rail transit stations. The land use structure and population density surrounding the stations of Line 1.2.3 of Xi’an Rail Transit were clustered by SPSS for identifying the rail transit stations with high population density. Subsequently, We have established an indicator system of urban land use and rail transit operation capabilities based on multivariate data, and explored the coordinated relationship between rail transit and land use through data envelopment analysis (DEA) evaluation methods at high population density stations. Besides, the coupling degree of land use in rail transit stations with high population density was evaluated, and the key indicators affecting the coupling degree were further analyzed in Xi’an. In conclusion, this study finds that the relationship between rail transit capacity and land use of high population density rail transit stations is unbalanced. Hence, to promote the sustainable development of rail transit capacity and surrounding land, it is suggested that we should confine the development of land use intensity around the station, improve the service functions of small-scale living areas, and optimize the travel environment intended for short-distance travel. For residents, they are encouraged to choose the mode of rail transit for their long-distance travel. At the same time, the peak passenger flow at the stations should be evacuated accordingly.

The recombinant bivalent live vectored vaccine rPRRSV-E2 has been proved to be a favorable genetic engineering vaccine against classical swine fever (CSF) and highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS). NADC30-like strains have recently emerged in China and caused severe disease, and it is necessary to evaluate the vaccine candidate for the currently circulating viruses. This study established a good challenge model to evaluate the candidate rPRRSV-E2 vaccine in preventing infection with a representative NADC30-like strain (ZJqz21). It was shown that the challenge control piglets displayed clinical signs typical of PRRSV, including a persistent fever, dyspnea, moderate interstitial pneumonia, lymph node congestion, and viremia. In contrast, the rPRRSV-E2 vaccination significantly alleviated the clinical signs, yielded a high level of antibodies, provided adequate protection against challenge with ZJqz21, and inhibited viral shedding and the viral load in target tissues. Our results demonstrated that the recombinant bivalent live vectored vaccine strain rPRRSV-E2 can provide efficient protection against the challenge of heterologous circulating NADC30-like strain and could be a promising vaccine candidate for the swine industry.

As the most metabolically active organ in the body, there is a recognized need for pathways that remove waste proteins and neurotoxins from the brain. Previous research has indicated potential associations between the clearance system in the brain and the pathological conditions of the central nervous system (CNS), due to its importance, which has attracted considerable attention recently. In the last decade, studies of the clearance system have been restricted to the glymphatic system. However, removal of toxic and catabolic waste by-products cannot be completed independently by the glymphatic system, while no known research or article has focused on a comprehensive overview of the structure and function of the clearance system. This thesis addresses a neglected aspect of linkage between the structural composition and main components as well as the role of neural cells throughout the clearance system, which found evidence that the components of CNS including the glymphatic system and the meningeal lymphatic system interact with a neural cell, such as astrocytes and microglia, to carry out vital clearance functions. As a result of this evidence that can contribute to a better understanding of the clearance system, suggestions were identified for further clinical intervention development of severe conditions caused by the accumulation of metabolic waste products and neurotoxins in the brain, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD).

In this study, we employ a cloud-resolving model to investigate how gravity influences convection and clouds in a small-domain (96 × 96 km) radiative–convective equilibrium. Our experiments are performed with a horizontal grid spacing of 1 km, which can resolve large (>1 km ^2 ) convective cells. We find that under a given stellar flux, sea surface temperature increases with decreasing gravity. This is because a lower-gravity planet has larger water vapor content and more clouds, resulting in a larger clear-sky greenhouse effect and a stronger cloud warming effect in the small domain. By increasing stellar flux under different gravity values, we find that the convection shifts from a quasi-steady state to an oscillatory state. In the oscillatory state, there are convection cycles with a period of several days, comprised of a short wet phase with intense surface precipitation and a dry phase with no surface precipitation. When convection shifts to the oscillatory state, the water vapor content and high-level cloud fraction increase substantially, resulting in rapid warming. After the transition to the oscillatory state, the cloud net positive radiative effect decreases with increasing stellar flux, which indicates a stabilizing climate effect. In the quasi-steady state, the atmospheric absorption features of CO _2 are more detectable on lower-gravity planets because of their larger atmospheric heights. While in the oscillatory state, the high-level clouds mute almost all of the absorption features, making the atmospheric components hard to characterize.

High-power, broad-area, semiconductor lasers are attractive sources for material processing, aerospace, and laser pumping. The design of the active region is crucial to achieve the required high power and electro-optical conversion efficiency, since the temperature significantly affects the performance of the quantum well, including the internal quantum efficiency and mode gain. In this work, the temperature effects on the active region of a 808 nm high-power semiconductor laser were investigated theoretically and experimentally. The simulations were performed with a Quasi-3D model, which involved complete steady-state semiconductor and carrier confinement efficiency combined with a new mathematical method. The critical aluminum content of the quantum barrier was proposed and the relationship between temperature and various loss sources was disclosed in the temperature range of 213 to 333 K, which provides a reliable reference for the design of epitaxial structures of high-power semiconductor lasers in different operating conditions. Subsequently, the optimized epitaxial structure was determined and used to fabricate standard laser bar chips with a cavity length of 2 mm. The experimental electro-optical conversion efficiency of 71% was demonstrated with a slope efficiency of 1.34 W/A and an injection current of 600 A at the heatsink temperature of 223 K. A record high electro-optical conversion efficiency of 73.5% was reached at the injection current of 400 A, while the carrier confinement efficiency was as high as 98%.

ObjectiveIt is unclear whether the receptor status of breast malignancy or the proportion of receptors expression is useful in the interpretation of 18F-FDG PET/CT. This study’s purpose was to analyze whether 18F-FDG PET/CT was valuable for helping newly diagnosed breast cancer patients find suspected or unsuspected metastasis lesions based on the proportion of receptors expression.Materials and MethodsEighty newly diagnosed breast cancer patients were divided into six groups, containing N0 (no extraaxillary lymph node metastasis), N1 (extraaxillary lymph node metastasis), M0 (no distant metastasis), and M1 (distant metastasis) groups, C0 (no unsuspected metastasis), and C1 (unsuspected metastasis and treatment plan changed) detected by PET/CT. The main data, including the proportion of receptors ER (estrogen receptor), PR (progesterone receptor), and Her-2 (human epidermal growth factor receptor 2) status, were extracted. Simple correlation and logistic regression were preformed to analyze the association between them.ResultsPatients in N1 group had lower proportion of ER (%) and PR (%) than that in N0 group (ER: 2 [0–80] vs. 80 [15–95]; PR: 1 [0–10] vs. 20 [0–45], p

Since 2018, the outbreak and prevalence of the African swine fever virus (ASFV) in China have caused huge economic losses. Less virulent ASFVs emerged in 2020, which led to difficulties and challenges for early diagnosis and control of African swine fever (ASF) in China. An effective method of monitoring ASFV antibodies and specific antibodies against ASFV to promote the development of prevention techniques are urgently needed. In the present study, ASFV p17 was successfully expressed in CHO cells using a suspension culture system. An indirect enzyme-linked immunosorbent assay (ELISA) based on purified p17 was established and optimized. The monoclonal antibody (mAb) against p17 recognized a conservative linear epitope (3TETSPLLSH11) and exhibited specific reactivity, which was conducive to the identification of recombinant porcine reproductive and respiratory syndrome virus (PRRSV) expressing p17. The ELISA method efficiently detected clinical ASFV infection and effectively monitored the antibody levels in vivo after recombinant PRRSV live vector virus expressing p17 vaccination. Overall, the determination of the conserved linear epitope of p17 would contribute to the in-depth exploration of the biological function of the ASFV antigen protein. The indirect ELISA method and mAb against ASFV p17 revealed efficient detection and promising application prospects, making them ideal for epidemiological surveillance and vaccine research on ASF.

Immunoglobin G4-related disease (IgG4-RD) is one of the newly discovered autoimmune diseases characterized by elevated serum IgG4 concentrations and multi-organ fibrosis. Despite considerable research and recent advances in the identification of underlying immunological processes, the etiology of this disease is still not clear. Adaptive immune cells, including different types of T and B cells, and cytokines secreted by these cells play a vital role in the pathogenesis of IgG4-RD. Antigen-presenting cells are stimulated by pathogens and, thus, contribute to the activation of naïve T cells and differentiation of different T cell subtypes, including helper T cells (Th1 and Th2), regulatory T cells, and T follicular helper cells. B cells are activated and transformed to plasma cells by T cell-secreted cytokines. Moreover, macrophages, and some important factors (TGF-β, etc.) promote target organ fibrosis. Understanding the role of these cells and cytokines implicated in the pathogenesis of IgG4-RD will aid in developing strategies for future disease treatment and drug development. Here, we review the most recent insights on IgG4-RD, focusing on immune dysregulation involved in the pathogenesis of this autoimmune condition.

Atrial fibrillation (AF) is the most common persistent arrhythmia, but the mechanism of AF has not been fully elucidated, and existing approaches to diagnosis and treatment face limitations. Recently, exosomes have attracted considerable interest in AF research due to their high stability, specificity and cell-targeting ability. The aim of this review is to summarize recent literature, analyze the advantages and limitations of exosomes, and to provide new ideas for their use in understanding the mechanism and improving the diagnosis and treatment of AF.