Mitochondrial nutrients improve immune dysfunction in the type 2 diabetic Goto-Kakizaki rats.

The development of type 2 diabetes is accompanied by decreased immune function and the mechanisms are unclear. We hypothesize that oxidative damage and mitochondrial dysfunction may play an important role in the immune dysfunction in diabetes. In the present study, we investigated this hypothesis in diabetic Goto-Kakizaki rats by treatment with a combination of four mitochondrial-targeting nutrients, namely, R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide and biotin. We first studied the effects of the combination of these four nutrients on immune function by examining cell proliferation in immune organs (spleen and thymus) and immunomodulating factors in the plasma. We then examined, in the plasma and thymus, oxidative damage biomarkers, including lipid peroxidation, protein oxidation, reactive oxygen species, calcium and antioxidant defence systems, mitochondrial potential and apoptosis-inducing factors (caspase 3, p53 and p21). We found that immune dysfunction in these animals is associated with increased oxidative damage and mitochondrial dysfunction and that the nutrient treatment effectively elevated immune function, decreased oxidative damage, enhanced mitochondrial function and inhibited the elevation of apoptosis factors. These effects are comparable to, or greater than, those of the anti-diabetic drug pioglitazone. These data suggest that a rational combination of mitochondrial-targeting nutrients may be effective in improving immune function in type 2 diabetes through enhancement of mitochondrial function, decreased oxidative damage, and delayed cell death in the immune organs and blood

Single Inclusive Jet Production in pApA Collisions at NLO in the small-xx regime

We present the first complete NLO prediction with full jet algorithm implementation for the single inclusive jet production in $pA$ collisions within the CGC effective theory. Our prediction is fully differential over the final state physical kinematics, which allows the implementation of any IR safe observable including the jet clustering procedure. The NLO calculation is organized with the aid of the power counting proposed in [1] which gives rise to the novel soft contributions in the CGC factorization. We achieve the fully-differential calculation by constructing suitable subtraction terms to handle the singularities in the real corrections. The subtraction contributions can be exactly integrated analytically. We present the NLO cross section with the jets constructed using the anti-$k_T$ algorithm. The NLO calculation demonstrates explicitly the validity of the CGC factorization in jet production. Furthermore, as a byproduct of the subtraction method, we also derive the fully analytic cross section for the forward jet production in the small-$R$ limit. We show that in the small-$R$ approximation, the forward jet cross section can be factorized into a semi-hard cross section that produces a parton and the semi-inclusive jet functions. We argue that this feature holds for generic jet production and jet substructure observables in the CGC framework. Last, we show numerical analyses of the derived formula to validate our calculations. We justify when the small-$R$ approximation is appropriate. Like forward hadron production, the obtained NLO result also exhibits the negativity of the cross section in the large jet transverse regime, which signals the need for the threshold resummation. A sketch of the threshold resummation in the CGC framework is presented based on the multiple emission picture.Comment: 67 pages, multiple figures, comments welcome, reference update

The geochemical characteristics of Cretaceous volcanics in southern Hainan Island and implications for tectonic evolution in the South China Sea

The southeastern Eurasian plate, where the South China Sea (SCS) is located, lies in a complex tectonic setting between the Pacific and Tethys tectonic belts. It is widely accepted that the tectonics of the SCS area were influenced by subduction in the late Mesozoic, but there is still controversy over whether it was paleo-Pacific subduction or Tethyan subduction. Volcanic activity in the south of Hainan Island was intense during the Cretaceous, and geochemical analysis of the collected basaltic andesite, andesite and rhyolite samples in this study indicate those intermediate-acid series igneous rocks are high-K calc-alkaline or calc-alkaline. Some andesites have high MgO contents and Mg# values (2.04–5.34 wt% and 36.83–55.29; Mg# = 100× Mg2+/(Mg2+ + TFe2+). Light rare earth elements (LREEs) and large ion lithophile elements (LILEs) are enriched in all the samples, but high field strength elements (HFSEs) are depleted. The negative Eu anomalies are more obvious in the rhyolites than andesites. The geochemical characteristics of the volcanic arc igneous rocks show that the mid-Cretaceous tectonic setting of Hainan Island can be classified as an Andean active continental margin. During the mid-Cretaceous, intermediate volcanism occurred in Hainan Island and its adjacent areas. The zircon-saturation temperatures of the acid volcanic rocks in study area exhibit relatively low values (ranging from 746°C–790°C). Unlike igneous rocks forming in the coastal area east of the South China Block at the same time, no A-type granitoids with alkaline dark minerals appear in Hainan Island. During the late Mesozoic, the western SCS, where Hainan Island was located, may not have been affected by the subduction of the paleo-Pacific Plate, but rather Neotethyan subduction which dominated the Cretaceous magmatic and tectonic activities along the western margin of the SCS. This finding helps to understand the late Mesozoic tectonic evolution of the southeastern edge of the Eurasian plate

A Label-Free Platform for Identification of Exosomes from Different Sources.

Exosomes contain cell- and cell-state-specific cargos of proteins, lipids, and nucleic acids and play significant roles in cell signaling and cell-cell communication. Current research into exosome-based biomarkers has relied largely on analyzing candidate biomarkers, i.e., specific proteins or nucleic acids. However, this approach may miss important biomarkers that are yet to be identified. Alternative approaches are to analyze the entire exosome system, either by "omics" methods or by techniques that provide "fingerprints" of the system without identifying each individual biomolecule component. Here, we describe a platform of the latter type, which is based on surface-enhanced Raman spectroscopy (SERS) in combination with multivariate analysis, and demonstrate the utility of this platform for analyzing exosomes derived from different biological sources. First, we examined whether this analysis could use exosomes isolated from fetal bovine serum using a simple, commercially available isolation kit or necessitates the higher purity achieved by the "gold standard" ultracentrifugation/filtration procedure. Our data demonstrate that the latter method is required for this type of analysis. Having established this requirement, we rigorously analyzed the Raman spectral signature of individual exosomes using a unique, hybrid SERS substrate made of a graphene-covered Au surface containing a quasi-periodic array of pyramids. To examine the source of the Raman signal, we used Raman mapping of low and high spatial resolution combined with morphological identification of exosomes by scanning electron microscopy. Both approaches suggested that the spectra were collected from single exosomes. Finally, we demonstrate for the first time that our platform can distinguish among exosomes from different biological sources based on their Raman signature, a promising approach for developing exosome-based fingerprinting. Our study serves as a solid technological foundation for future exploration of the roles of exosomes in various biological processes and their use as biomarkers for disease diagnosis and treatment monitoring

Atmospheric turbulence and land - atmosphere energy transfer characteristics in the surface layer of the Northern slope of Mt. Qomolangma area : abstract

Based on the turbulent data collected at Quzong site, on the northern slope of Mt. Qomolangma, from April 2005 to March 2006, macro-scale turbulent statistical characteristics and land-atmosphere energy transfer before and after the onset of southwest monsoon were acquired by the eddy correlation method. It was found that Monin-Obukhov similarity theory is applicable for Mt. Qomolangma area. The relationship between normalized wind speed standard deviation and atmospheric stability, variances of normalized temperature and humidity standard deviation with atmospheric stability were simulated in the study. It was also found that energy balance components (net radiation flux, sensible heat flux, latent heat flux and soil heat flux) and surface heating filed had evident diurnal and seasonal changes. Especially under the influence of southwest monsoon, the sensible heat flux and latent heat flux in Quzong area have evident opposite changing trends. The variation characteristics of other surface parameters (surface reflectance and Bowen ratio) is very clear before and after the breakout of southwest monsoon

Spatiotemporal Variation Characteristics of Groundwater Storage and Its Driving Factors and Ecological Effects in Tibetan Plateau

Known as the “Asian Water Tower”, the Tibetan Plateau (TP) is a rich water resource and serves an important ecological function. Climate change may cause changes to the water cycle, and these changes may affect the alpine vegetation growth. However, the variation characteristics of groundwater storage (GWS) and its driving factors and associated ecological effects in the TP are poorly understood. In this study, terrestrial water storage changes retrieved by GRACE (Gravity Recovery and Climate Experiment) were combined with GLDAS (Global Land Data Assimilation System) to estimate the GWS changes in the TP. The temporal and spatial variation characteristics of GWS were identified using linear regression and the modified Mann–Kendall (MMK) test, respectively. The analyses showed that the GWS of the TP decreased at an average rate of −0.89 mm/a from January 2003 to December 2021, but since January 2016, it gradually recovered at a rate of 1.47 mm/a. This shows that the GWS in the eastern and northern parts of the TP is decreasing, while the GWS in the western and southern parts is increasing. The influence of climate change on GWS in time and space was determined using the correlation analysis method. Decreased precipitation and permafrost degradation caused by increasing temperatures will lead to a decrease in GWS. On the other hand, rising temperatures may result in an increase in GWS in regions where glaciers are distributed. In this study, the ecological effects were represented by the relationship between GWS and vegetation change. A decline in GWS means that the vegetation will not receive enough water, leading to a decrease in the NDVI and the eventual degradation of grassland to sand, desert, or other kinds of unused land on the TP. On the other hand, an increase in GWS would promote vegetation restoration. The results of this study offer a new opportunity to reveal the groundwater changes in a cryosphere region and to assess the impact of changes in hydrological conditions on ecology.</p

Kava Components Down-Regulate Expression of AR and AR Splice Variants and Reduce Growth in Patient-Derived Prostate Cancer Xenografts in Mice

Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5′6′-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR