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The blood–brain barrier (BBB) controls the flow of substances to maintain a homeostatic environment in the brain, which is highly regulated and crucial for the normal function of the central nervous system (CNS). Brain endothelial cells (bECs), which are directly exposed to blood, play the most important role in maintaining the integrity of the BBB. Unlike endothelial cells in other tissues, bECs have two unique features: specialized endothelial tight junctions and actively suppressed transcellular vesicle trafficking (transcytosis). These features help to maintain the relatively low permeability of the CNS barrier. In addition to the predominant role of tight junctions in the BBB, caveolae-mediated adsorptive transcytosis has attracted much interest in recent years. The active suppression of transcytosis is dynamically regulated during development and in response to diseases. Altered caveolae-mediated transcytosis of bECs has been reported in several neurological diseases, but the understanding of this process in bECs is limited. Here, we review the process of caveolae-mediated transcytosis based on previous studies and discuss its function in the breakdown of the BBB in neurological disorders.

Drought stress limits seedling growth, hindering morphological development and population establishment. Artocarpus nanchuanensis, a critically endangered species endemic to the karst regions of southwest China, exhibits poor population structure and limited natural regeneration in the wild, with water deficit during the seedling stage identified as a major factor contributing to its endangered status. Elucidating the physiological and molecular mechanisms underlying drought tolerance in A. nanchuanensis seedlings is essential for improving their drought adaptability and facilitating population recovery. In this study, 72 two-year-old seedlings were divided into two groups: drought (PEG) and ethephon (PEG + Ethephon), and subjected to drought-rehydration experiments. The results showed that exogenous application of 100 mg·L−1 ethephon significantly improved stomatal conductance and photosynthetic pigment content in A. nanchuanensis seedlings. Under drought stress, the PEG + Ethephon group exhibited rapid stomatal closure, maintaining water balance and higher photosynthetic pigment levels. After rehydration, the PEG + Ethephon group significantly outperformed the PEG group in terms of photosynthetic rate. Ethephon treatment reduced H2O2 and MDA levels, enhanced antioxidant enzyme activity (SOD, CAT, POD, GR), and increased osmotic regulator activity (soluble sugars, soluble proteins, and proline), improving ROS-scavenging capacity and reducing oxidative damage. Ethephon application significantly enhanced ethylene accumulation in seedlings, while drought stress stimulated the concentrations of key ethylene biosynthetic enzymes (SAMS, ACS, and ACO), thereby further contributing to improved drought resistance. Transcriptomic data revealed that drought stress significantly upregulated key ethylene biosynthesis genes, with expression levels increasing with stress duration and rapidly decreasing after rehydration. WGCNA analysis identified eight key drought-resistance genes, providing valuable targets for future research. This study provides the first mechanistic insight into the physiological and molecular responses of A. nanchuanensis seedlings to drought and rehydration, underscoring the central role of endogenous ethylene in drought tolerance. Ethephon treatment effectively enhanced ethylene accumulation and biosynthetic enzyme activity, thereby improving drought adaptability. These findings lay a theoretical foundation for subsequent molecular functional studies and the conservation biology of this endangered species.

Designing actuators that can modulate power, achieve high energy efficiency, and ensure safe collision remains a challenge, especially for dynamic energy robot systems (DERS) with high‐performance requirements. Herein, a novel multi‐configuration elastic actuator (MCEA) is proposed based on a controllable planetary differential mechanism (PDM) with one power port from three springs. These springs, positioned between the inner gear ring and the fixed housing shell, are regulated by a single servo motor through a ratchet–pawl mechanism. This setup enables the springs to absorb energy during collisions, reducing impact and subsequently releasing this energy to boost power output. The inner gear ring functions as a controllable one‐way rotating element, acting either as an input or output for power. The MCEA's ability to manage power modulation and energy flow is demonstrated through experiments that highlight its potential for safe collision management, energy recycling, and power modulation. Experiment results indicate that the maximum output power of the MCEA in the proposed hybrid elastic actuation (HEA) mode is 8.05 times higher than that in the traditional actuation (TA) mode. A single‐legged robot with a four‐link mechanism is also built to validate the considerable performance in the application of legged robots, showing considerable adaptability and prospects for DERS. This study introduces a novel multi‐configuration elastic actuator (MCEA) for dynamic energy robot systems, featuring a planetary differential mechanism and energy‐absorbing springs. This actuator enhances power modulation, energy recycling, and collision safety. Experiments reveal an 8.05‐fold increase in maximum output power over traditional modes, demonstrating the significant potential for dynamic energy robot systems.

The SQUAMOSA promoter binding protein-like (SPL)SPL family genes play an important role in regulating plant growth and development, synthesis of secondary metabolites, and resistance to stress. Understanding of the role of the SPL family in tobacco is still limited. In this study, 42 NtSPL genes were identified from the genome of the tobacco variety TN90. According to the results of the conserved motif and phylogenetic tree, the NtSPL genes were divided into eight subgroups, and the genes in the same subgroup showed similar gene structures and conserved domains. The cis-acting element analysis of the NtSPL promoters showed that the NtSPL genes were regulated by plant hormones and stresses. Twenty-eight of the 42 NtSPL genes can be targeted by miR156. Transcriptome data and qPCR results indicated that the expression pattern of miR156-targeted NtSPL genes was usually tissue specific. The expression level of miR156 in tobacco was induced by Cd stress, and the expression pattern of NtSPL4a showed a significant negative correlation with that of miR156. These results suggest that miR156-NtSPL4a may mediate the tobacco response to Cd stress. This study lays a foundation for further research on the function of the NtSPL gene and provides new insights into the involvement of NtSPL genes in the plant response to heavy metal stress.

The vertical fracture propagation morphology in sand-coal interbedded reservoirs is predominantly governed by interlayer mechanical relationships, intra-layer petrophysical properties, and fracturing operation parameters. This study conducted physical simulation experiments on sand-coal interbedded combinations using a large-scale true triaxial hydraulic fracturing system, investigating the effects of in-situ stress, injection rate, interfacial cementation strength, rock stacking patterns, and fracturing fluid viscosity on vertical fracture morphology. The experimental findings reveal: The vertical stress difference coefficient can be defined as the interlayer penetration criterion. Specifically, when the minimum vertical stress difference coefficient requirement is satisfied while other conditions act as secondary factors, fracture penetration across layers becomes feasible. However, due to coal seams’ inherent characteristics of well-developed cleat systems and strong water absorbency, achieving interlayer penetration proves more challenging in coal layers compared to sandstone formations. A higher injection rate facilitates fracture communication with adjacent layers and interfacial intersections, while controlled injection rates prove effective in restraining fracture height extension. Fractures exhibit greater penetration capability through high-strength cemented interfaces, whereas they preferentially propagate along low-strength interfacial zones; Elevated fracturing fluid viscosity promotes energy retention by minimizing fluid loss, thereby enhancing interlayer penetration—this viscosity-dependent mechanism provides an effective approach for fracture height containment.

Argininosuccinate synthase (ASS1) is a ubiquitous enzyme in mammals that catalyzes the formation of argininosuccinate from citrulline and aspartate. ASS1 genetic deficiency in patients leads to an autosomal recessive urea cycle disorder citrullinemia, while its somatic silence or down-regulation is very common in various human cancers. Here, we show that ASS1 functions as a tumor suppressor in breast cancer, and the pesticide spinosyn A (SPA) and its derivative LM-2I suppress breast tumor cell proliferation and growth by binding to and activating ASS1. The C13-C14 double bond in SPA and LM-2I while the Cys97 (C97) site in ASS1 are critical for the interaction between ASS1 and SPA or LM-2I. SPA and LM-2I treatment results in significant enhancement of ASS1 enzymatic activity in breast cancer cells, particularly in those cancer cells with low ASS1 expression, leading to reduced pyrimidine synthesis and consequently the inhibition of cancer cell proliferation. Thus, our results establish spinosyn A and its derivative LM-2I as potent ASS1 enzymatic activator and tumor inhibitor, which provides a therapeutic avenue for tumors with low ASS1 expression and for those non-tumor diseases caused by down-regulation of ASS1. Arginine addiction induced by argininosuccinate synthase (ASSN1) deficiency has been exploited to treat ASS1-deficient cancers. Here, the authors show an alternative therapeutic approach where ASS1 activity is increased by the pesticide spinosyn A and is shown to inhibit breast cancer cell proliferation.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree Camptotheca acuminata. CPT inhibits topoisomerase I. It possesses various antitumor activities and is mainly used in the treatment of colon, ovarian, liver, and bone cancers as well as leukemia. CPT inhibits the expressions of inflammatory genes and can prevent death from chronic inflammation. Therefore, we investigated the effect of CPT treatment in ulcerative colitis (UC) using DSS-induced UC mouse model; after that, we explored its potential mechanisms. Here, we found that CPT exerted protection on DSS-induced UC in rats. In addition, the administration prominently reduced the disease activity index as well as colon length of the model rats and remarkably reduced the inflammatory cytokines. Further, CPT significantly reduced several vital proinflammatory proteins in LPS-induced RAW264.7 cells. In summary, our findings demonstrate that CPT is hopefully to act as a therapeutic agent for UC.

PurposeCurrent research on the aging of bony orbit is usually done manually, which is inefficient and has a large error. In this paper, automatic segmentation of bony orbit based on deep learning and automatic calculation of the parameters of the segmented orbital contour (area and height of bony orbit) are presented.MethodsThe craniofacial CT scanning data of 595 Chinese were used to carry out three-dimensional reconstruction and output the craniofacial images. The orbital contour images are obtained automatically by UNet++ segmentation network, and then the bony orbital area and height were calculated automatically by connected component analysis.ResultsThe automatic segmentation method has an Intersection of Union of 95.41% in craniofacial CT images. During the aging, the bony orbital area of males increased with age, while that of females decreased, and the area in male was larger than that in female (P < 0.05). The distance from equal points 10 and 40–90 to the supraorbital rim was significantly larger (P < 0.05). Except for the equal point 90, the distance from equal points to the inferior orbital rim was obviously larger (P < 0.05). In the females, the distance from equal points 50–70 to inferior orbital rim was significantly lower (P < 0.05).ConclusionThe method proposed here can automatically and accurately study image dataset of large-scale bony orbital CT imaging. UNet++ can achieve high-precision segmentation of bony orbital contours. The bony orbital area of Chinese changes with aging, and the bony orbital height changes different between males and females, which may be caused by the different position and degree of orbital bone resorption of males and females in the process of aging.

T cell exhaustion, mediated by the expression of inhibitory receptor proteins, significantly reduces their anti-tumor efficacy. Therefore, strategies aimed at degrading membrane proteins have emerged as promising approaches for enhancing the therapeutic effectiveness of Chimeric Antigen Receptor (CAR) T cells and improving cancer treatment outcomes. In this study, we developed a Clathrin-Mediated Endocytosis Targeting Chimera (CleTAC), an innovative platform designed to facilitate membrane protein degradation via the clathrin-mediated endocytosis pathway. CleTAC employs the YVKM motif to interact with the AP2 complex, driving the internalization of targeted membrane proteins (proteins of interest, POI) along with associated cell membrane components. These internalized complexes are subsequently trafficked to lysosomes for degradation. We conducted multiple validations using flow cytometry, Western blotting, and and experiments to verify its degradation efficiency. Additionally, we integrated CleTAC targeting CTLA4 membrane proteins into a CAR construct and evaluated its impact on CAR-T cell functionality and tumor suppressive efficacy using both cellular assays and animal tumor models. We demonstrated that CleTAC effectively and specifically mediates the degradation of EGFP and CTLA4 proteins on the cell surface. When incorporated into a CAR construct, CleTAC targeting CTLA4 enhanced CAR-T cell anti-tumor activity, as evidenced by improved functional assays and tumor suppression in animal models. These findings establish CleTAC as a versatile and effective tool for modulating membrane protein levels and enhance anti-tumor efficacy in CAR-T cells. Our results highlight CleTAC as a promising therapeutic tool with substantial clinical potential to significantly enhance CAR-T cell therapy and advance current oncology treatment strategies.