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Immune checkpoint blockade therapies targeting the PD-L1/PD-1 axis have demonstrated clear clinical benefits. Improved understanding of the underlying regulatory mechanisms might contribute new insights into immunotherapy. Here, we identify transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) as a modulator of PD-L1 post-translational modifications in tumor cells. Mechanistically, TMUB1 competes with HECT, UBA and WWE domain-containing protein 1 (HUWE1), a E3 ubiquitin ligase, to interact with PD-L1 and inhibit its polyubiquitination at K281 in the endoplasmic reticulum. Moreover, TMUB1 enhances PD-L1 N-glycosylation and stability by recruiting STT3A, thereby promoting PD-L1 maturation and tumor immune evasion. TMUB1 protein levels correlate with PD-L1 expression in human tumor tissue, with high expression being associated with poor patient survival rates. A synthetic peptide engineered to compete with TMUB1 significantly promotes antitumor immunity and suppresses tumor growth in mice. These findings identify TMUB1 as a promising immunotherapeutic target.

As China enters an ageing society, the number of elderly people is rising sharply, resulting in a continuous increase in the cost and burden of caring for the elderly. Frailty is an important cause of loss of self-care ability and elderly care problems in elderly people, which means that frailty is associated with a decline not only in physiological functions, but in multiple areas as well, such as mental ability and socioeconomic functioning, and is considered an important geriatric syndrome that affects the quality of life of the elderly. Comprehensive Geriatric Assessment (CGA) is a multi-dimensional and multi-disciplinary assessment process or model specifically for elderly patients. As a core tool in geriatric medicine, it uses a multi-dimensional and multi-disciplinary approach to assess the physical condition, functional status, mental health and social environment status of the elderly, and accordingly a treatment plan is developed to maintain and improve the functional status of the elderly and enhance their quality of life to the most extent. However, the use of CGA is not entirely consistent in China and abroad. This paper reviews the existing studies on frailty in the elderly, analyses the advantages and shortcomings of CGA used in frail elderly patients, and finds that interventions for frail patients at home and abroad have been valued increasingly. The development of domestic interventional studies on frailty is still in the initial stage, and most of these studies use a design of a randomized controlled trial with a sample of chronic disease inpatients. In contrast, such studies have been widely carried out abroad, in which CGA has been applied to the management of cancer patients and patients in the perioperative period besides chronic disease patients and frail community-dwelling older people. The frailty status in the elderly can be scientifically and comprehensively assessed by the CGA, and based on which targeted interventions can be implemented to prevent or delay the development of frailty, but it is generally time-consuming, and there are many difficulties in the management of the assessment recipients. In the future, it is necessary to advance the clinical application of CGA, or develop a more rapid, comprehensive and authoritative tool based on CGA for frailty assessment in the elderly, so as to provide comprehensive and personalized medical services and health guidance for frail elderly population through standardised assessment.

In order to quickly and comprehensively find out the types and spatial distribution characteristics of the main hidden disasters in Tanhuigou Coal Mine and analyze its potential threat to the coal mine, the methods of on-site inquiry, data access, investigation of surrounding coal mines, rapid scanning of surface unmanned aerial vehicle(UAV) visible light+thermal infrared imaging, ground reconnaissance, underground investigation and detection were adopted to conduct all-round sky-ground-underground investigation of the coal mine. The water hazard factors affecting coal mine safety production are found out, including Miaogou surface water, old empty water, roof sandstone water, and poorly sealed drilling holes; the fire factors include 1-2 coal room pillar goaf, residual coal in mine roadway, ground collapse cracks, etc. The disaster-causing factors related to roof/ground pressure mainly include hard roof, roof hanging in room mining area, isolated working face, etc. The potential threats of hidden factors to coal mines are studied and analyzed.

Taking the fire-threatened mines in the shallow buried coal seam of the Jurassic coalfield in northern Shaanxi Province as the research object, the high-resolution UAV visible light and thermal infrared dual-light low-altitude remote sensing, handheld infrared thermal imager, wind speed measuring instrument, spherical bladder sampler, bundle tube detection and sampling, gas chromatography, borehole temperature measurement, borehole peeping and other technical means are used to comprehensively carry out rapid exploration of hidden disaster factors in the sky, ground, hole and underground comprehensive mining work surface, closed wall, roadway and other potential air leakage channels. We systematically summarize the types and characteristics of hidden disaster factors in ground, hole and underground air leakage channels of shallow buried coal seam in Jurassic coal field in northern Shaanxi province, construct a four-in-one “sky-ground-hole-well” rapid investigation technology system for hidden disaster factors in shallow buried coal seam coal mine air leakage channels, and apply the technical system to the fire-threatened Dequan Coal Mine for the exploration, quickly determine the type of air leakage channel, spatial distribution characteristics, combine with the fire prevention project to achieve the rapid extinguishing of the fire area and the overall rapid control of the temperature of the hidden high temperature area of the coal mine to ensure the safe, green and efficient mining of the mine.

Vascular cambium is the continuation of meristem activity at the top of plants, which promotes lateral growth of plants. The vascular cambium evolved as an adaptation for secondary growth, initially in early seed plants, and became more refined in the evolution of gymnosperms and angiosperms. In angiosperms, it is crucial for plant growth and wood formation. The vascular cambium is regulated by a complex interplay of phytohormones, which are chemical messengers that coordinate various aspects of plant growth and development. This paper synthesizes the current knowledge on the regulatory effects of primary plant hormones and peptide signals on the development of the cambium in forest trees, and it outlines the current research status and future directions in this field. Understanding these regulatory mechanisms holds significant potential for enhancing our ability to manage and cultivate forest tree species in changing environmental conditions. [ABSTRACT FROM AUTHOR]

Background: Employing a custom 60‐channel single‐transmit/32‐channel receive Tic‐Tac‐Toe (TTT) coil in 7T MRI imaging has enhanced the resolution and contrast for identifying White Matter Hyperintensities (WMHs), which are critical markers in Alzheimer's disease and related dementias (AD/ADRD). Method: The method involves resecting the left hemisphere of the brain, excluding the cerebellum, followed by embalming in 10% formalin. 1.5% agar and 30% sucrose by weight are heated and mixed for embedding in the container. The brain is positioned in the cutting guide and inserted into the base (Figure 1). Agar is meticulously poured ensuring minimal air bubble formation in the sulci and ventricles with additional agar pipetted as needed. The lid is then attached, more agar is added until the container is filled, and the cap is secured. The container is sealed in plastic to safeguard the coil from potential liquid damage and isolate the tissue/formalin while scanning. The imaging protocol includes a B1+ map at 3.2mm, MP2RAGE at 0.4mm, GRE at.37mm, and T2‐SPACE at.36mm all isotropic resolutions. The high‐resolution T2‐weighted SPACE is used for WMH segmentation and quantification. The MP2RAGE provides a T1‐weighted image for further data analysis registration to gross anatomy as well as in vivo scans. Result: This protocol has been applied to 120 brain specimens to date, with representative MR images in Figure 2. The techniques afford pathologists flexibility in slicing the brain into coronal or axial parallel 5 mm slabs at various angles. See Figure 3 for a visual representation of the progression of the container design and of the cutting process. Conclusion: This innovative combination of the cutting guide, container, and the custom 7T TTT coil is reusable and reliable. It accommodates various brain sizes, offers precise cutting options, ensures fast and accurate image registration to in vivo and gross anatomy, and achieves homogeneous B1 fields, culminating in superior research data. The described method is subject to ongoing refinement for enhanced efficiency, with iterative optimization of the container's shape, size, and function through 3D printing. This work was supported by the National Institutes of Health under award numbers R01MH111265, R01AG063525, T32MH119168, and U19AG068054. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Compared to males, females have an accelerated trajectory of cognitive decline in Alzheimer's disease (AD). The neurobiological factors underlying the more rapid cognitive decline in AD in females remain unclear. This study explored how sex‐dependent alterations in hippocampal connectivity over 2 years are associated with cerebrovascular and amyloid pathologies in normal aging. METHODS: Thirty‐three females and 21 males 65 to 93 years of age with no cognitive impairment performed a face‐name associative memory functional magnetic resonance imaging (fMRI) task with a 2‐year follow‐up. We acquired baseline carbon 11‐labeled Pittsburgh compound B ([11C]PiB) positron emission tomography (PET) and T2‐weighted fluid‐attenuated inversion recovery (T2‐FLAIR) MRI to quantify amyloid β (Aβ) burden and white matter hyperintensity (WMH) volume, respectively. RESULTS: Males had increased hippocampal‐prefrontal connectivity over 2 years, associated with greater Aβ burden. Females had increased bilateral hippocampal functional connectivity, associated with greater WMH volume. DISCUSSION: These findings suggest sex‐dependent compensatory mechanisms in the memory network in the presence of cerebrovascular and AD pathologies and may explain the accelerated trajectory of cognitive decline in females. [ABSTRACT FROM AUTHOR]