Search

Changes in protein abundance and reversible protein phosphorylation (RPP) play important roles in regulating hypometabolism but have never been documented in overwintering frogs at high altitudes. To test the hypothesis that protein abundance and phosphorylation change in response to winter hibernation, we conducted a comprehensive and quantitative proteomic and phosphoproteomic analysis of the liver of the Xizang plateau frog, Nanorana parkeri, living on the Qinghai- Xizang Plateau. In total, 5 170 proteins and 5 695 phosphorylation sites in 1 938 proteins were quantified. Based on proteomic analysis, 674 differentially expressed proteins (438 up-regulated, 236 down-regulated) were screened in hibernating N. parkeri versus summer individuals. Functional enrichment analysis revealed that higher expressed proteins in winter were significantly enriched in immune-related signaling pathways, whereas lower expressed proteins were mainly involved in metabolic processes. A total of 4 251 modified sites (4 147 up-regulated, 104 down-regulated) belonging to 1 638 phosphoproteins (1 555 up-regulated, 83 down-regulated) were significantly changed in the liver. During hibernation, RPP regulated a diverse array of proteins involved in multiple functions, including metabolic enzymatic activity, ion transport, protein turnover, signal transduction, and alternative splicing. These changes contribute to enhancing protection, suppressing energy-consuming processes, and inducing metabolic depression. Moreover, the activities of phosphofructokinase, glutamate dehydrogenase, and ATPase were all significantly lower in winter compared to summer. In conclusion, our results support the hypothesis and demonstrate the importance of RPP as a regulatory mechanism when animals transition into a hypometabolic state. [ABSTRACT FROM AUTHOR]

“Shengdeng”, a group of Tibetan medicines with diverse biological origins, has long been utilized in Tibet for the treatment of rheumatoid arthritis. It showcases remarkable efficacy in alleviating rheumatism, reducing swelling, and relieving pain. This study aimed to clarify the plant species used as “Shengdeng” and summarize their botanical distribution, traditional uses, phytochemistry, and pharmacology to promote its utilization and development. “Shengdeng” is derived from a remarkable collection of 14 plant species belonging to six distinct families. Extensive phytochemical investigations have led to the identification of 355 chemical constituents within “Shengdeng”. Pharmacological studies conducted on “Shengdeng” have revealed a wide range of beneficial properties, including antioxidant, anticancer, antimicrobial, antiviral, antiparasitic, anti-inflammatory, and anti-arthritic activities. Notably, flavonoids and triterpenoids emerge as the predominant groups among these constituents, contributing to the therapeutic potential and diverse applications of “Shengdeng”. The present review provides a concise summary of the recent advancements in textual research concerning the herbal and botanical distribution, traditional uses, phytochemistry, and pharmacological activities of “Shengdeng”. It is crucial to note that future research on “Shengdeng” should prioritize the analysis of its active ingredients and the establishment of rigorous quality standards. These aspects are essential for ensuring consistency, efficacy, and safety in its clinical application. [ABSTRACT FROM AUTHOR]

Background and purpose: Cerebral small-vessel disease (CSVD) is prevalent worldwide and one of the major causes of stroke and dementia. For patients with CSVD at high altitude, a special environmental status, limited information is known about their clinical phenotype and specific neuroimaging change. We investigated the clinical and neuroimaging features of patients residing at high altitude by comparing with those in the plain, trying to explore the impact of high altitude environment on CSVD. Methods: Two cohorts of CSVD patients from the Tibet Autonomous Region and Beijing were recruited retrospectively. In addition to the collection of clinical diagnoses, demographic information and traditional vascular risk factors, the presence, location, and severity of lacunes and white matter hyperintensities were assessed by manual counting and using age-related white matter changes (ARWMC) rating scale. Differences between the two groups and influence of long-term residing in the plateau were analyzed. Results: A total of 169 patients in Tibet (high altitude) and 310 patients in Beijing (low altitude) were enrolled. Fewer patients in high altitude group were found with acute cerebrovascular events and concomitant traditional vascular risk factors. The median (quartiles) ARWMC score was 10 (4, 15) in high altitude group and 6 (3, 12) in low altitude group. Less lacunes were detected in high altitude group [0 (0, 4)] than in low altitude group [2 (0, 5)]. In both groups, most lesions located in the subcortical (especially frontal) and basal ganglia regions. Logistic regressions showed that age, hypertension, family history of stroke, and plateau resident were independently associated with severe white matter hyperintensities, while plateau resident was negatively correlated with lacunes. Conclusion: Patients of CSVD residing at high altitude showedmore severeWMH but less acute cerebrovascular events and lacunes in neuroimaging, comparing to patients residing at low altitude. Our findings suggest potential biphasic effect of high altitude on the occurrence and progression of CSVD. [ABSTRACT FROM AUTHOR]

The grazing exclusion program used by the Tibetan government to protect the ecological environment has changed the vegetation and impacted the surface heat balance in North Tibet. However, little information is available to describe the influences of the current grazing exclusion program on local surface heat balance. This study uses the records of fenced grassland patch locations to identify the impact of grazing exclusion on surface heat balance in North Tibet. The records of fenced grassland patch locations, including the longitude, latitude, and elevation of the vertices of each fenced patch (polygon shapes), were provided by the agriculture and animal husbandry bureaus of the counties where the patches were located. ArcGIS 10.2 was used to create polygon shapes based on patch location records. Based on satellite data and the surface heat balance system determined by the model, values for changes in land surface temperature (LST), albedo and evapotranspiration (ET) induced by grazing exclusion were obtained. All of these can influence surface heat balance and alter the fluctuation of LST in the northern Tibetan Plateau. The LST trends for day and night showed an asymmetric diurnal variation, with a larger magnitude of warming in the day than cooling at night. The maximum decrease in absorbed shortwave of LST (–0.5 – –0.4 °C per decade) occurred in the central region, while the minimum decrease (–0.2 – –0.1 °C per decade) occurred in the eastern region. The decreased latent heat lead to the LST increased maximum (>1 °C per decade) occurred in the central region, The eastern region increased at a rate of 0.2–0.5 °C per decade, while the minimum increase (0–0.1 °C per decade) occurred in the northwestern region. [ABSTRACT FROM AUTHOR]

Grasslands occupy nearly three quarters of the land surface of the Qinghai-Tibet plateau (QTP) and play a critical role in regulating the ecological functions of the QTP. Ongoing climate change and human interference have greatly affected grasslands on the QTP. Differentiating human-induced and climate-driven vegetation changes is vital for both ecological understanding and the management of husbandry. In this study, we employed statistical analysis of annual records, various sources of remote sensing data, and an ecosystem process model to calculate the relative contribution of climate and human activities to vegetation vigor on the QTP. The temperature, precipitation and the intensity and spatial pattern of livestock grazing differed between the periods prior to and after the year 2000, which led to different vegetation dynamics. Overall, increased temperature and enhanced precipitation favored vegetation growth. However, their combined effects exhibited strong spatial heterogeneity. Specifically, increased temperature restrained vegetation growth in dry steppe regions during a period of slightly increasing precipitation from 1986 to 2000 and in meadow regions during a period of precipitation decline during 2000–2011, thereby making precipitation a dominant factor. An increase in precipitation tended to enhance vegetation growth in wet meadow regions during warm periods, and temperature was the limiting factor in Tibet during dry periods. The dominant role played by climate and human activities differed with location and targeted time period. Areas dominated by human activities are much smaller than those dominated by climate. The effects of grazing on grassland pasture were more obvious under unfavorable climate conditions than under suitable ones. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that infects cloven-hoofed animals. Neutralizing antibodies play critical roles in antiviral infection. Although five known antigen sites that induce neutralizing antibodies have been defined, studies on cross-protective antigen sites are still scarce. We mapped two cross-protective antigen sites using 13 bovine-derived broadly neutralizing monoclonal antibodies (bnAbs) capable of neutralizing 4 lineages within 3 topotypes of FMDV serotype O. One antigen site was formed by a novel cluster of VP3-focused epitopes recognized by bnAb C4 and C4-like antibodies. The cryo-electron microscopy (cryo-EM) structure of the FMDV-OTi (O/Tibet/99)-C4 complex showed close contact with VP3 and a novel interprotomer antigen epitope around the icosahedral 3-fold axis of the FMDV particle, which is far beyond the known antigen site 4. The key determinants of the neutralizing function of C4 and C4-like antibodies on the capsid were ßB (T65), the B-C loop (T68), the E-F loop (E131 and K134), and the H-I loop (G196), revealing a novel antigen site on VP3. The other antigen site comprised two group epitopes on VP2 recognized by 9 bnAbs (B57, B73, B77, B82, F28, F145, F150, E46, and E54), which belong to the known antigen site 2 of FMDV serotype O. Notably, bnAb C4 potently promoted FMDV RNA release in response to damage to viral particles, suggesting that the targeted epitope contains a trigger mechanism for particle disassembly. This study revealed two cross-protective antigen sites that can elicit cross-reactive neutralizing antibodies in cattle and provided new structural information for the design of a broad-spectrum molecular vaccine against FMDV serotype O. IMPORTANCE FMDV is the causative agent of foot-and-mouth disease (FMD), which is one of the most contagious and economically devastating diseases of domestic animals. The antigenic structure of FMDV serotype O is rather complicated, especially for those sites that can elicit a cross-protective neutralizing antibody response. Monoclonal neutralization antibodies provide both crucial defense components against FMDV infection and valuable tools for fine analysis of the antigenic structure. In this study, we found a cluster of novel VP3-focused epitopes using 13 bnAbs against FMDV serotype O from natural host cattle, which revealed two cross-protective antigen sites on VP2 and VP3. Antibody C4 targeting this novel epitope potently promoted viral particle disassembly and RNA release before infection, which may indicate a vulnerable region of FMDV. This study reveals new structural information about cross-protective antigen sites of FMDV serotype O, providing valuable and strong support for future research on broadspectrum vaccines against FMD. [ABSTRACT FROM AUTHOR]