Explore the vast range of titles available.

T-cell receptor–engineered T-cell therapy and chimeric antigen receptor T-cell therapy are 2 types of adoptive T-cell therapy that genetically modify natural T cells to treat cancers. Although chimeric antigen receptor T-cell therapy has yielded remarkable efficacy for hematological malignancies of the B-cell lineages, most solid tumors fail to respond significantly to chimeric antigen receptor T cells. T-cell receptor–engineered T-cell therapy, on the other hand, has shown unprecedented promise in treating solid tumors and has attracted growing interest. In order to create an unbiased, comprehensive, and scientific report for this fast-moving field, we carefully analyzed all 84 clinical trials using T-cell receptor–engineered T-cell therapy and downloaded from ClinicalTrials.gov updated by June 11, 2018. Informative features and trends were observed in these clinical trials. The number of trials initiated each year is increasing as expected, but an interesting pattern is observed. NY-ESO-1, as the most targeted antigen type, is the target of 31 clinical trials; melanoma is the most targeted cancer type and is the target of 33 clinical trials. Novel antigens and underrepresented cancers remain to be targeted in future studies and clinical trials. Unlike chimeric antigen receptor T-cell therapy, only about 16% of the 84 clinical trials target against hematological malignancies, consistent with T-cell receptor–engineered T-cell therapy’s high potential for solid tumors. Six pharma/biotech companies with novel T-cell receptor–engineered T-cell ideas and products were examined in this review. Multiple approaches have been utilized in these companies to increase the T-cell receptor’s affinity and efficiency and to minimize cross-reactivity. The major challenges in the development of the T-cell receptor–engineered T-cell therapy due to tumor microenvironment were also discussed here.

High-strength aluminum alloys are important for lightweighting vehicles and are extensively used in aircraft and, increasingly, in automobiles. The highest-strength aluminum alloys require a series of high-temperature “bakes” (120° to 200°C) to form a high number density of nanoparticles by solid-state precipitation. We found that a controlled, room-temperature cyclic deformation is sufficient to continuously inject vacancies into the material and to mediate the dynamic precipitation of a very fine (1- to 2-nanometer) distribution of solute clusters. This results in better material strength and elongation properties relative to traditional thermal treatments, despite a much shorter processing time. The microstructures formed are much more uniform than those characteristic of traditional thermal treatments and do not exhibit precipitate-free zones. These alloys are therefore likely to be more resistant to damage.

Summary The ability to interpret daily and seasonal fluctuations, latitudinal and vegetation canopy variations in light and temperature signals is essential for plant survival. However, the precise molecular mechanisms transducing the signals from light and temperature perception to maintain plant growth and adaptation remain elusive. We show that far‐red light induces PHYTOCHROME‐INTERACTING TRANSCRIPTION 4 (SlPIF4) accumulation under low‐temperature conditions via phytochrome A in Solanum lycopersicum (tomato). Reverse genetic approaches revealed that knocking out SlPIF4 increases cold susceptibility, while overexpressing SlPIF4 enhances cold tolerance in tomato plants. SlPIF4 not only directly binds to the promoters of the C‐REPEAT BINDING FACTOR (SlCBF) genes and activates their expression but also regulates plant hormone biosynthesis and signals, including abscisic acid, jasmonate and gibberellin (GA), in response to low temperature. Moreover, SlPIF4 directly activates the SlDELLA gene (GA‐INSENSITIVE 4, SlGAI4) under cold stress, and SlGAI4 positively regulates cold tolerance. Additionally, SlGAI4 represses accumulation of the SlPIF4 protein, thus forming multiple coherent feed‐forward loops. Our results reveal that plants integrate light and temperature signals to better adapt to cold stress through shared hormone pathways and transcriptional regulators, which may provide a comprehensive understanding of plant growth and survival in a changing environment.

Recently, vortex beams have been widely studied and applied because they carry orbital angular momentum (OAM). It is widely acknowledged in the scientific community that fractional OAM does not typically exhibit stable propagation; notably, the notion of achieving stable propagation with dual-fractional OAM within a single optical vortex has been deemed impracticable. Here, we address the scientific problem through the combined modulation of phase and polarization, resulting in the generation of a dual-fractional OAM vector vortex beam that can stably exist in free space. Applying this unique characteristic, we derive an integrated analytical model to calculate the focused electromagnetic fields and Poynting vector distributions based on Debye vector diffraction integral. Utilizing phase stitching technology, this research combines two fractional topological charges to investigate the properties of dual-fractional OAM optical vortices with diverse polarization conditions. Furthermore, the transmission characteristics of these optical vortices are meticulously analyzed. This work not only enriches the types of vortex beams but also provides a novel optical tool, potentially transformative for applications in optical communications, optical manipulation, and optical imaging.

Thyroid hormone (TH) plays a crucial role in regulating glucose metabolism. However, the potential impact of the FT3/FT4 ratio, which reflects peripheral sensitivity to thyroid hormones, on glycemic variability in patients with type 2 diabetes (T2DM), has not been previously reported. To investigate the correlation between the FT3/FT4 ratio and glycemic variability in individuals with T2DM. In this retrospective analysis, a total of 468 inpatients with T2DM underwent continuous glucose monitoring (CGM) systems for a period of 6–14 days. Baseline clinical characteristics, laboratory tests, and CGM parameters were documented to investigate the correlation between FT3/FT4 ratio and CGM parameters. The levels of HBA, MG, SD, CV, LAGE, MODD and TAR2Scale were all higher in FT3/FT4Q1 compared with FT3/FT4Q2, FT3/FT4Q3 and FT3/FT4Q4 (all P  < 0.01). Additionally, TIR was lower in FT3/FT4Q1 compared with the other quartiles ( P  < 0.01). Smooth curve fitting and saturation effect analysis revealed that there are curve-like relationships between the FT3/FT4 ratio and SD, MAGE, MODD and TAR2Scale. The inflection points of the fitted curves were found to be at FT3/FT4 = 0.279, 0.237, 0.253 and 0.282 respectively (all P  < 0.05). Prior to the inflection point, the FT3/FT4 ratio was negatively related to SD, MAGE, MODD and TAR2Scale (all P  < 0.05). Furthermore, The FT3/FT4 ratio exhibits a negative linear correlation with HBA and MG, while demonstrating a positive linear relationship with TIR (all P  < 0.05). Binary logistic regression demonstrated that the FT3/FT4 ratio was independently related to HBA ( P  = 0.001), MG ( P  = 0.01), TAR2Scale ( P  = 0.003), LAGE ( P  = 0.014) and MAGE ( P  < 0.001). The increased FT3/FT4 ratio within a certain range (FT3/FT4 ≤ 0.282) is associated with decreased blood glucose variability and increased TIR. The FT3/FT4 ratio may act as a potential independent protective factor for glycemic fluctuation and glycemic control in patients with T2DM when it increases within a specific range.

Due to the unique geographical environment of the plateau, large-scale damage and destruction of fractured surrounding rock often occur during geotechnical engineering construction as a result of high-temperature cycles. Therefore, this study aims to investigate the mechanical properties and damage characteristics of fractured granite under the influence of cyclic temperature, uniaxial compression tests were conducted on granite specimens with pre-existing fractures at cyclic temperatures of 30 °C, 50 °C, 70 °C, 100 °C, and 130 °C. The study integrated analyses of characteristic stress, acoustic emission parameters, damage variables, fractal dimensions, and SEM to explore the mechanical properties and damage features of granite. The results indicated that at a 45° fracture inclination and a temperature of 70 °C, granite exhibited a distinct turning point in mechanical properties and damage characteristics. At the same cyclic temperature, granite with a 45° pre-existing fracture showed significant decreases in peak stress, elastic modulus, and σci/σm ratios, with the AE b-value drop point noticeably earlier, and both cumulative AE ring count and total energy reduced. The damage variable quickly reached its maximum, and the development of internal microcracks in the specimen is highly orderly. At the same fracture inclination, peak stress, elastic modulus, and σci/σm slightly increased at 70 °C, while AE ring counts and total energy were lower, indicating the degree of internal thermal damage in the specimen has significantly decreased, and the development of internal microcracks in the specimen has shown a marked reduction in orderliness. These findings provide theoretical insight into the meso-damage and failure mechanisms of granite influenced by different cyclic temperatures and fracture inclinations.

Background Necrotizing enterocolitis (NEC) is an inflammatory gastrointestinal disease in premature neonates with high mortality and morbidity, while the underlining mechanism of intestinal injury and profound neurological dysfunction remains unclear. Here, we aimed to investigate the involvement of NLPR3 inflammasome activation in NEC-related enterocolitis and neuroinflammation, especially long-term cognitive impairment, meanwhile, explore the protective effect of NLRP3 inhibitor MCC950 on NEC in mice. Methods NLRP3 inflammasome activation in the intestine and brain was assessed in the NEC mouse model, and NLRP3 inhibitor MCC950 was administrated during the development of NEC. Survival rate, histopathological injury of the intestine and brain, and expression of mature IL-1β and other pro-inflammatory cytokines were analyzed. Long-term cognitive impairment was evaluated by behavioral test. Results The expression of NLRP3 and mature IL-1β in the intestine and brain was greatly upregulated in NEC mice compared to the controls. MCC950 treatment efficiently improved NEC survival rate, reduced intestinal and brain inflammation, and ameliorated the severity of pathological damage in both organs. Additionally, in vivo blockage of NLRP3 inflammasome with MCC950 in early life of NEC pups potently protected against NEC-associated long-term cognitive impairment. Conclusions Our findings suggest that NLRP3 inflammasome activation participates in NEC-induced intestinal and brain injury, and early intervention with NLRP3 inhibitor may provide beneficial therapeutic effect on NEC infants.

Under the severe situation of increasing global climate change, it is urgent to improve the ability of cities to cope with climate change and achieve sustainable development. As a key institutional arrangement for China’s climate adaptation, the climate-resilient city initiative has been piloted in 67 cities across two batches since 2017, aiming to foster urban resilience through systematic governance. Based on complex adaptive system theory, this study constructs an urban ecological resilience evaluation framework under the “Pressure–State–Response” (PSR) model. Using panel data from 243 prefecture-level cities from 2010 to 2022 and a difference-in-differences model, it empirically examines the impact of climate-resilient city construction on ecological resilience, further exploring the moderating mechanism of government attention to environmental protection and spatial heterogeneity effects. Key findings include the following: (1) climate-resilient city construction significantly enhances urban ecological resilience, with pilot cities experiencing an average increase of approximately 0.74%; (2) government attention to environmental protection strengthens policy effectiveness, demonstrating a significant positive moderating effect; and (3) policy effects show notable regional variations, with more pronounced improvements in resource-based cities, western regions, and ecologically vulnerable areas.

Due to the advantages of wide coverage, continuous remote monitoring, and high measurement accuracy, the spaceborne multi‐channel surveillance radar has been widely used for the air moving target detection and tracking. In this paper, the minimum detection velocity (MDV) definition for the aerial target detection performance evaluation in a spaceborne multi‐channel radar system is analysed, where three kinds of MDV definitions based on empirical formula, output signal‐to‐clutter‐plus‐noise ratio (SCNR) loss criterion, and output SCNR criterion are discussed in detail based on theoretical analysis and simulation verification. The analysis results will provide valuable reference for the practical spaceborne radar system designment with the air target detection mode.