Overexpression of thioredoxin-interacting protein (TXNIP) is associated with reduced insulin sensitivity and β-cell apoptosis. We have previously shown that W2476 inhibited high glucose-induced TXNIP expression at both mRNA and protein levels in INS-1E cells. In this study, we describe structural modification and optimization of W2476 leading to three more active derivatives, 8d, 8g, and 9h, capable of suppressing TXNIP expression in BG73 and INS-1E cells, increasing insulin production, and reducing high glucose-induced apoptosis in INS-1E cells.
The successive flood-heat extreme (SFHE) event, which threatens the securities of human health, economy, and building environment, has attracted extensive research attention recently. However, the potential changes in SFHE characteristics and the global population exposure to SFHE under anthropogenic warming remain unclear. Here, we present a global-scale evaluation of the projected changes and uncertainties in SFHE characteristics (frequency, intensity, duration, land exposure) and population exposure under the Representative Concentration Pathway (RCP) 2.6 and 6.0 scenarios, based on the multi-model ensembles (five global water models forced by four global climate models) within the Inter-Sectoral Impact Model Intercomparison Project 2b framework. The results reveal that, relative to the 1970-1999 baseline period, the SFHE frequency is projected to increase nearly globally by the end of this century, especially in the Qinghai-Tibet Plateau (>20 events/30-year) and the tropical regions (e.g., northern South America, central Africa, and southeastern Asia, >15 events/30-year). The projected higher SFHE frequency is generally accompanied by a larger model uncertainty. By the end of this century, the SFHE land exposure is expected to increase by 12 % (20 %) under RCP2.6 (RCP6.0), and the intervals between flood and heatwave in SFHE tend to decrease by up to 3 days under both RCPs, implying the more intermittent SFHE occurrence under future warming. The SFHE events will lead to the higher population exposure in the Indian Peninsula and central Africa (<10 million person-days) and eastern Asia (<5 million person-days) due to the higher population density and the longer SFHE duration. Partial correlation analysis indicates that the contribution of flood to the SFHE frequency is greater than that of heatwave for most global regions, but the SFHE frequency is dominated by the heatwave in northern North America and northern Asia.
Drought affects vegetation growth to a large extent. Understanding the dynamic changes of vegetation during drought is of great significance for agricultural and ecological management and climate change adaptation. The relations between vegetation and drought have been widely investigated, but how vegetation loss and restoration in response to drought remains unclear. Using the standardized precipitation evapotranspiration index (SPEI) and the normalized difference vegetation index (NDVI) data, this study developed an evaluation framework for exploring the responses of vegetation loss and recovery to meteorological drought, and applied it to the humid subtropical Pearl River basin (PRB) in southern China for estimating the loss and recovery of three vegetation types (forest, grassland, cropland) during drought using the observed NDVI changes. Results indicate that vegetation is more sensitive to drought in high-elevation areas (lag time 8 months). Vegetation loss (especially in cropland) is found to be more sensitive to drought duration than drought severity and peak. No obvious linear relationship between drought intensity and the extent of vegetation loss is found. Regardless of the intensity, drought can cause the largest probability of mild loss of vegetation, followed by moderate loss, and the least probability of severe loss. Large spatial variability in the probability of vegetation loss and recovery time is found over the study domain, with a higher probability (up to 50 %) of drought-induced vegetation loss and a longer recovery time (>7 months) mostly in the high-elevation areas. Further analysis suggests that forest shows higher but cropland shows lower drought resistance than other vegetation types, and grassland requires a shorter recovery time (4.2-month) after loss than forest (5.1-month) and cropland (4.8-month).
Intestinal parasites, such as Eimeria, are common among plateau pika (Ochotona curzoniae). The gut microbiome is an essential driver of the host response to gastrointestinal parasites. However, the effects of intestinal protozoal parasites on the temporal variations in the gut microbiome and behavioral and physiological activities remain unknown. Our study conducted treatments involving experimental feeding of pika with Eimeria oocysts or anticoccidia under laboratory conditions to focus on the parasite-associated alterations in gut bacterial communities, host behavioral activity, physiology, and host-bacteria relationships. The results showed insignificant differences in bacterial community structures among treatments on the basis of Bray-Curtis distance metrics, whereas the patterns of temporal alterations in the bacterial communities were changed by the treatments. Bacterial alpha diversities did not vary with the treatments, and experimental feeding with Eimeria slowed down the decrement rate of alpha diversity. Furthermore, few bacterial members were significantly changed by the treatments-only the genus Ruminococcus and the species Ruminococcus flavefaciens, which were associated with energy metabolism. Experimental feeding with Eimeria modified the temporal variations in the bacterial members, including a lower loss rate of the relative abundance of the dominant families Muribaculaceae and Ruminococcaceae in the group with Eimeria experimental feeding. Moreover, a shifting energy trade-off was suggested by the parasite-induced increments in thyroid hormones (triiodothyronine and tetraiodothyronine) and decrements in exploration behavior in the group with Eimeria feeding. However, we did not detect specific connections between gut bacterial communities and pika behaviors and physiology in terms of energy trade-offs. Further in-depth research is needed to examine the role of Eimeria-modified differences in the gut bacteria of plateau pika.
Flavor is a crucial parameter for assessing the sensory quality of yak milk. However, there is limited information regarding the factors influencing its taste. In this study, the effects of endogenous lipoprotein lipase (LPL) on the volatile flavor components of yak milk under storage conditions of 4 °C, 18 °C and 65 °C were analyzed via headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) combined with orthogonal partial least-squares (OPSL) discrimination, and the reasons for the changes in yak milk flavors were investigated. Combined with the difference in the changes in volatile flavor substance before and after the action of LPL, LPL was found to have a significant effect on the flavor of fresh yak milk. Fresh milk was best kept at 4 °C for 24 h and pasteurized for more than 24 h. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to characterize the volatile components in yak milk under various treatment conditions. Twelve substances with significant influence on yak milk flavor were identified by measuring their VIP values. Notably, 2-nonanone, heptanal, and ethyl caprylate exhibited OAV values greater than 1, indicating their significant contribution to the flavor of yak milk. Conversely, 4-octanone and 2-heptanone displayed OAV values between 0.1 and 1, showing their important role in modifying the flavor of yak milk. These findings can serve as monitoring indicators for assessing the freshness of yak milk.