The altering cellular components and function in tumor microenvironment during remissive and relapsed stages of anti-CD19 CAR T-cell treated lymphoma mice

Anti-CD19 chimeric antigen receptor (CAR) T cells represent a highly promising strategy for B-cell malignancies. Despite the inspiring initial achievement, remission in a notable fraction of subjects is short-lived, and relapse remains a major challenge. Tumor microenvironment (TME) was proved to be aroused by CAR T cells; however, little is known about the dynamic characteristics of cellular components in TME especially during the different phases of disease after anti-CD19 CAR T-cell treatment. We took advantage of an immunocompetent model receiving syngeneic A20 lymphoma cells to dissect the changes in TME with or without CAR T-cell injection. We found that anti-CD19 CAR T-cell treatment attenuated the symptoms of lymphoma and significantly prolonged mice survival through eradicating systemic CD19+ cells. Increased myeloid subsets, including CD11c+ DCs and F4/80+ macrophages with higher MHC II and CD80 expression in bone marrow, spleen, and liver, were detected when mice reached remission after anti-CD19 CAR T treatment. Compared to mice without anti-CD19 CAR T administration, intrinsic T cells were triggered to produce more IFN-γ and TNF-α. However, some lymphoma mice relapsed by day 42 after therapy, which coincided with CAR T-cell recession, decreased myeloid cell activation and increased Treg cells. Elevated intrinsic T cells with high PD-1 and TIGIT exhaust signatures and attenuated cytotoxicity in TME were associated with the late-stage relapse of CAR T-cell treatment. In summary, the cellular compositions of TME as allies of CAR T cells may contribute to the anti-tumor efficacy at the initial stage, whereas anti-CD19 CAR T-cell disappearance and host response immunosuppression may work together to cause lymphoma relapse after an initial, near-complete elimination phase

Research progress on the clinical application and mechanism of iguratimod in the treatment of autoimmune diseases and rheumatic diseases

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren ‘s syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod’s unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future

MODELLING, SIMULATION, FABRICATION AND CHARACTERISATION OF ALGAN/GAN FIN-GATE HIGH ELECTION MOBILITY TRANSISTERS (FIN-HEMTS)

Ph.DDOCTOR OF PHILOSOPHY (FOE

Electrostatic force evolution during the tip-induced ferroelectric domain switching

10.1063/5.0068617Journal of Applied Physics13019194101-19410

Research on the Composting Technology of Cattle and Sheep Manure Based on Intelligent and Efficient Composting Equipment and the Evaluation Standard of Decomposition Degree

The Inner Mongolia Autonomous Region is a crucial area in China with a significant advantage in animal husbandry, particularly in cattle and sheep farming. However, the disposal of the large quantities of manure produced during farming has severely impacted the industry’s healthy development. Proper treatment of the manure can convert it into organic fertilizer beneficial to farmland; otherwise, it will cause substantial environmental pollution. This study focuses on existing composting equipment and addresses the issues of cattle and sheep manure mixture ratios and compost maturity evaluation. Through experiments on the mixture of cattle and sheep manure, the optimal ratio for converting cattle and sheep manure into organic fertilizer was determined. Additionally, a fuzzy mathematical evaluation model was employed, along with experimental data, to establish a comprehensive evaluation system for aerobic compost maturity based on multiple indicators, revealing the variation patterns of maturity levels under different mixture ratios. The test results revealed that the composting equipment effectively controls the composting process, shortens the composting cycle, ensures the complete decomposition of organic matter, and meets national standards for livestock and poultry manure treatment. Regarding temperature and humidity, oxygen concentration, seed germination rate, pH value, electrical conductivity (EC), nitrogen, phosphorus, potassium content, and carbon-to-nitrogen ratio, the mixed compost of cattle and sheep manure in various ratios met the relevant standards for agricultural application. Various ratios of organic fertilizers containing cattle and sheep manure significantly promoted the growth of maize, wheat, and mung bean crops. Specifically, the compost decomposition cycle was shortest when sheep and cattle dung were mixed at a ratio of 2:1, while it was longest for all cattle dung. Finally, a fuzzy mathematical comprehensive evaluation model was established by selecting four indicators: water content, carbon-to-nitrogen ratio, apparent score, and germination index. The study demonstrates that the equipment and method offer significant advantages in efficiently treating cattle and sheep manure and producing organic fertilizer, thereby providing strong support for the sustainable development of animal husbandry

Research on Simulation Design of MOS Driver for Micro-LED

Micro-LED is a new technology applied in the display field, which has the advantages of self-illumination, low power consumption, high brightness, long life and ultra-high resolution, and has broad application prospects. Using MOS devices to drive micro-LED can enable each unit to have its own drive, thus improving the yield and reducing the subsequent repair processes. In this paper, Sentaurus TCAD simulation software is used to design and simulate NMOS/PMOS devices and their driving circuits. For the first time, CMOS inverters are used to directly drive Micro-LED. Three kinds of driving circuits are compared and analyzed according to their simulation results in output characteristics and transient characteristics. In terms of switching characteristics caused by output characteristics, a CMOS inverter driving a micro-LED circuit has no problems of incomplete turn-off and has greater advantages. In the switching characteristics aspect caused by transient characteristics, PMOS driving a micro-LED circuit has the shortest turn-on time and greater advantages. When compared with a micro-LED driven by an access current-limiting resistor, a micro-LED driven by a direct drive has a smaller on-time value and greater advantages

Trap Characterization Techniques for GaN-Based HEMTs: A Critical Review

Gallium nitride (GaN) high-electron-mobility transistors (HEMTs) have been considered promising candidates for power devices due to their superior advantages of high current density, high breakdown voltage, high power density, and high-frequency operations. However, the development of GaN HEMTs has been constrained by stability and reliability issues related to traps. In this article, the locations and energy levels of traps in GaN HEMTs are summarized. Moreover, the characterization techniques for bulk traps and interface traps, whose characteristics and scopes are included as well, are reviewed and highlighted. Finally, the challenges in trap characterization techniques for GaN-based HEMTs are discussed to provide insights into the reliability assessment of GaN-based HEMTs

Can Melatonin Improve the Osteopenia of Perimenopausal and Postmenopausal Women? A Meta-Analysis

Objective. To assess the effectiveness and safety of melatonin for perimenopausal and postmenopausal women with osteopenia. Methods. In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of melatonin versus placebo or western medicine in perimenopausal and postmenopausal women with osteopenia. The study’s registration number is CRD42018086238. The primary outcomes included bone mineral density (BMD) and T-score. Result. From 551 articles retrieved, three trials involving 121 patients were included. Due to the high-to-substantial heterogeneity (BMD: I2=96.9%, P=0.000; T-score: I2=74.9%, and P=0.019), the statistical analysis of BMD and T-score was abandoned. A systematic review was undergone for the two outcomes. Compared with the control group, melatonin may increase osteocalcin (WMD 4.97; 95% CI 3.14, 6.79; P<0.00001). Conclusion. Based on current evidence, melatonin might be used as a safe nutritional supplement to improve bone density in perimenopausal and postmenopausal women, but its efficacy needs to be further affirmed