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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.

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.

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.

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.

BACKGROUND:Since the onset of combination antiretroviral therapy use, the incidence of HIV-associated dementia and of HIV encephalitis has fallen dramatically. The present study investigates the extent of white matter hyperintensities (WMHs) among individuals with HIV disease, and factors that predict their presence and their impact on psychomotor speed. METHODS:A total of 322 men participating in the Multicenter AIDS Cohort Study (185 HIV-infected, age: 57.5 ± 6.0) underwent MRI scans of the brain. T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images were obtained and processed using an automated method for identifying and measuring WMHs. WMH burden was expressed as the log10 transformed percentage of total white matter. RESULTS:There were no significant associations between WMHs and HIV disease. However, the extent of WMHs was predicted by age more than 60 (β = 0.17), non-white race (β = 0.14), glomerular filtration rate (β = -0.11), and the presence of diabetes (β = 0.12). There were no interactions between HIV status and age (β = -0.03) or between age and diabetes (β = 0.07). However, the interaction between HIV infection and diabetes was significant (β = 0.26). The extent of WMHs was significantly associated with performance on measures of psychomotor speed (β = 0.15). CONCLUSION:In today's therapeutic environment, in HIV-infected and HIV seronegative individuals, those factors which affect the cerebrovasculature are the best predictors of WMHs. Diabetes has a specific impact among HIV-infected, but not uninfected, men, suggesting the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions.

In view of the problems of slow speed, long cycle and terrain limitation in the investigation of hidden disasters on the surface of traditional coal mines, taking the shallow coal seam production coal mine in Shenbei Mining Area of Jurassic coalfield in northern Shaanxi Province as an example, the low-altitude remote sensing technology of visible light+infrared thermal imaging of unmanned aerial vehicle was adopted to realize the rapid scanning of hidden disasters on the surface of coal mines. The results show that the extension length, direction and scale of ground fissures can be quickly identified and calculated according to the flying height, azimuth angle and shooting width of UAV. Quickly check out surface water bodies such as rivers, ponds and springs through visible light images; infrared and visible light fusion mode can quickly capture and track the abnormal points of surface high temperature and determine the scope of hidden fire area; identify the exposure of surface bedrock and revise the scope of burnt rock again; delineate the location, scale and potential danger zone of waste rock hill; it is found that villagers steal mining holes and identify other hidden disaster-causing factors such as dangerous geological bodies.