Composition and constraints of lithium isotopes in cryoconite from various remote glacier areas of the Tibetan Plateau.

Lithium isotope is one of the most promising indicators for the study of continental silicate weathering, and lithium concentrations and its isotopic compositions in earth surface can provide a better understanding of the geochemical behavior and isotopic fractionation during weathering and erosion. This work focused on the composition and distribution of Li isotope in cryoconite deposited on various glacier areas in a large range of the Tibetan Plateau and surroundings, as well as its implications for cryoconite dust provenances. Results showed that δ7Li in cryoconite varied within the same order of magnitude (-2.14 ‰-7.74 ‰), which is characterized by geographic distribution of higher δ7Li value of cryoconite in northern glaciers (e.g. Yuzhufeng Glacier), and lower δ7Li value in southern glaciers. In comparison with other global materials, the cryoconite dust shows a lighter δ7Li isotopic composition due to constraints of climatic conditions and land surface weathering intensity. Compared with dust materials in the surrounding Asian dust sources (e.g. large deserts and Gobi), we find that, the primary sources of Li isotope in cryoconite of the northern locations were from both local dust/soils of the TP surface and the surrounding large deserts. Moreover, the products of anthropogenic activities (e.g. coal-burning) may also influence the isotopic composition of the cryoconite dust, and Li isotope may serve as potential tracers of anthropogenic source activities. Therefore, this work provides a complete view of the composition and distribution of Lithium isotopes in cryoconite from various glacier areas of the Tibetan Plateau, and the research significance of its transport processes and source constraints of Li isotopes in cryoconite is proposed.

Comparison on distribution and sources of typical major and toxic trace elements in various glacial watersheds of the northeast Tibetan Plateau.

Toxic and major elements, such as As and Fe, in watersheds can significantly impact the surrounding water environment and ecosystem. Thus, in this study, we conducted an investigation into the origins and spatial distribution of typical toxic trace elements (As and Mn) and crustal major elements (Al, Fe, and Ti) in suspended particulate matter (SPM) across various glacial watersheds located at different elevations in the northeastern Tibetan Plateau (NETP) from June to July in 2017. The results revealed that the mean value of each element followed the order of abundance in the samples, with Al having the highest mean value at 21307 µg/L, followed by Fe at 13366 µg/L, Ti at 1520 µg/L, Mn at 245 µg/L, and As at 66.6 µg/L. Moreover, our study identified high content of these elements from the Dabanshan Snowpack, Laohugou Glacier No.12, and Yuzhufeng Glacier in the upper reaches of the basin, which were found to be 9.9, 10.2, and 19.4 times higher, respectively, than that of the upper reaches of the Heihe River. We found that As and Mn exhibited clear indications of anthropogenic influence on a local and regional scale. The calculated enrichment factor (EF) demonstrated a significant As enrichment (EF>100) in the Qiyi and Lenglongling Glaciers, possibly resulting in the release of upstream glacier melt and anthropogenic-derived As deposition. Our findings suggested that the upstream region was primarily linked to glacier meltwater discharge. In contrast, the middle and lower reaches of the basin exhibited a more pronounced influence from local human activities. Based on the findings, the water environment of the glacier watershed appears to be in good condition overall. However, the presence of elevated levels of As element in the water system can be traced back to both anthropogenic and natural factors. As a result, ensuring the safety of the water supply for nearby residents is a matter of utmost concern. This study provides a comprehensive examination of hydrochemical variations and the overall water environment of high-altitude glacier basins in the NETP, offering valuable insights into the topic.

Insights on the distribution and environmental implications of the radio-isotope 235U in surface soils and glaciers of the Tibetan Plateau.

Atom ratio between 235U and 238U is often used as an indicator of U contamination as the isotopic signature of products generated by the nuclear and military industry significantly vary from the natural isotopic ratio of U. In this study, surface soils and glaciers samples were collected in the Tibetan Plateau (TP) and its surrounding areas and analyzed for U isotopic composition. Results show that the 235U/238U atom ratios in the surface soils of the TP ranges from 0.007122 to 0.007615, with an average value of 0.007378 ± 0.00011; while in the snow/ice dust from high-altitude glaciers it ranges from 0.007254 to 0.007687, with an average value of 0.007345 ± 0.000128. These ratios are slightly higher than the typical crustal value, indicating that the TP was affected by an anthropogenic input of 235U, especially in its northeast and southwest sectors. The variability of our results suggests that the spatial distribution of this contamination is not uniform, pointing to differences in the potential sources and transmission paths of radioactive particles. Combining the knowledge of past tests and activities conducted in the geographic areas around the TP with the knowledge of prevailing winds, we hypothesize that the observed 235U contamination in the TP surface soils and glaciers may have originated mainly from the previous nuclear related activities in surrounding areas (e.g., north Gobi Desert and South Asia). In addition, the horizontal and vertical wind field around the Tibetan Plateau, as well as the atmospheric aerosol optical thickness data also demonstrated the possible transport paths of the radionuclides, that is, originated from in northern Gobi desert and South Asia and reached the TP crossing the Himalayas.

Identification of icaritin derivative IC2 as an SCD-1 inhibitor with anti-breast cancer properties through induction of cell apoptosis.

BACKGROUND: Breast cancer is the most common malignancy affecting women, yet effective targets and related candidate compounds for breast cancer treatment are still lacking. The lipogenic enzyme, stearoyl-CoA desaturase-1 (SCD1), has been considered a potential target for breast cancer treatment. Icaritin (ICT), a prenylflavonoid derivative from the Traditional Chinese Medicine Epimedii Herba, has been reported to exert anticancer effects in various types of cancer. The purpose of the present study was to explore the effect of the new ICT derivative, IC2, targeting SCD1 on breast cancer cells and to explore the specific mechanism. METHODS: Immunohistochemistry and semiquantitative evaluation were performed to detect the expression level of SCD1 in normal and tumor samples. Computer-aided drug design (CADD) technology was used to target SCD1 by molecular docking simulation, and several new ICT derivatives were prepared by conventional chemical synthesis. Cell viability was evaluated by an MTT assay and dead cell staining. SCD1 expression in cancer cells was determined by Western blot and qRT-PCR analyses. The enzymatic activity of SCD1 was evaluated by detecting the conversion rate of [d31] palmitic acid (PA) using Gas chromatography-mass spectrometry (GC-MS). DAPI staining, flow cytometry and Western blot were used to detect cell apoptosis. Mitochondrial membrane potential and reactive oxygen species (ROS) assays were used to determine cell mitochondrial function. Lentiviral transduction was utilized to generate SCD1-overexpressing cell lines. RESULTS: We found that SCD1 was overexpressed and correlated with poor prognosis in breast cancer patients. Among a series of ICT derivatives, in vitro data showed that IC2 potentially inhibited the viability of breast cancer cells, and the mechanistic study revealed that IC2 treatment resulted in ROS activation and cellular apoptosis. We demonstrated that IC2 inhibited SCD1 activity and expression in breast cancer cells in a dose-dependent manner. Moreover, SCD1 overexpression alleviated IC2-induced cytotoxicity and apoptosis in breast cancer cells. CONCLUSIONS: The new ICT derivative, IC2, was developed to induce breast cancer cell apoptosis by inhibiting SCD1, which provides a basis for the development of IC2 as a potential clinical compound for breast cancer treatment.

Controllable Droplet Sliding on a Smart Shape-Memory Slippery Surface.

Recently, slippery surfaces with controllable droplet sliding have aroused much attention in both fundamental research and realistic applications. However, for almost all existing surfaces, constant stimuli such as heat, light, magnetic field, etc., are indispensable. Herein, by constructing pit structures on a shape memory polymer and further infusing oil with low surface tension, we report a shape memory slippery surface that can overcome the above imperfection. Based on the shape memory performance, the surface can memorize a diverse pit size as the surface is stretched or recovered. With the variation of pit structure, the sliding performances for both water and organic liquid droplets can be reversibly adjusted between the rolling and pinning states. This work, based on the shape memory effect, reports smart droplet sliding control through regulating the surface microstructure, which not only provides a strategy for droplet sliding control, but also offers some ideas for designing novel intelligent slippery surfaces.

Synthesis and biological evaluation of new series of quinazoline derivatives as EGFR/HER2 dual-target inhibitors.

It is generally believed that EGFR/HER2 dual-target inhibitors may overcome the resistance of EGFR TKIs caused by HER2 overexpression. The structure-based synthesis and biological evaluation of quinazoline derivatives as EGFR/HER2 dual-target inhibitors has been studied in this paper. II-1, II-2, III-3, III-4 displayed comparable inhibitory potency against EGFR and HER2 and II-1 showed remarkable antiproliferative activities against NCI-H358/PC-9/Calu-3/NCI-H1781 (EGFR IC50 = 0.30 nM, HER2 IC50 = 6.07 nM, NCI-H358 GI50 = 23.30 nM, PC-9 GI50 = 1.95 nM, Calu-3 GI50 = 23.13 nM NCI-H1781 GI50 = 41.61 nM).

Mechanistic study on photochemical generation of I•/I2•- radicals in coastal atmospheric aqueous aerosol.

The reactive iodine species may exhibit significant impacts on many global atmospheric issues and the I•/I2•- radicals play key roles for inducing the formation of these reactive iodine species. However, the current understanding on the formation of I•/I2•- radicals in atmospheric aqueous aerosol is still quite limited. The results reported herein suggest that I•/I2•- can be produced simultaneously in aqueous aerosol by several sunlight-driven photochemical pathways including direct photo-dissociation of soluble organic iodine (SOI) at rates of 0.10-1.34 × 10-9 M ns-1 and 0.99-5.68 × 10-7 M µs-1, •OH-mediated oxidation of I- at 0.03-1.41 × 10-8 M ns-1 and 0.05-4.10 × 10-6 M µs-1, and 3DOM⁎-induced oxidation of I- at 1.57-1.65 × 10-9 M ns-1 and 0.99-5.68 × 10-7 M µs-1 for generation of I• and I2•-, respectively. Meanwhile, the pathway of eaq--initiated stepwise reduction of IO3- to I2(aq) and further photolyzed into I• plays negligible role in formation of I•/I2•- due to the low reaction rates and severe quenching effect of eaq- by dissolved O2. Our work presented the new data on mechanism and kinetics for comprehensive elucidation of I•/I2•- formation in coastal atmospheric aqueous aerosol and would help to better understand the transformation mechanism of iodine species, pathways of iodine cycling and the associated environmental impacts involving atmospheric reactive iodine radicals.

Photo-generated hydroxyl radicals contribute to the formation of halogen radicals leading to ozone depletion on and within polar stratospheric clouds surface.

Polar stratospheric clouds (PSCs), of which the surface is a dynamic liquid water layer and might consist of aqueous HNO3 and H2O2, is a well-known key meteorological condition contributing to the ozone hole in the polar stratosphere. PSCs has been considered to provide abundant surface for the heterogeneous reactions causing the formation of the Cl2 and HOCl, which are further photolyzed into Cl and ClO radicals leading to the ozone destruction. Here we demonstrated that the sunlight drives the massive and stable production of OH radicals in aqueous HNO3 and its main photo-induced byproduct HNO2. We also found that the photo-generated OH radicals in aqueous HNO3, HNO2 and H2O2 have the remarkable capability to react with the dissolved HCl, Cl- and Br- to form halogen radicals. In addition, we observed that the H2O2 can react with dissolved HCl and Br- in darkness to form and release Cl2 and Br2 gases, which could further be photolyzed into reactive halogen radicals whenever sunlight is available. All these findings suggest that, except for the well-known heterogeneous reactions, photochemical reactions involving the aqueous HNO3 and H2O2 on and within PSCs surface might constitute another important halogen activation pathway for ozone destruction. This study may shed deeper insights into the mechanism of halogen radicals resulting in ozone depletion in polar stratosphere.

Synthesis and biological evaluation of novel 5,6-dihydrobenzo[h]quinazoline derivatives as FLT3 inhibitors.

Fms-like tyrosine kinase 3 (FLT3) is widely expressed and often mutated in acute myeloid leukemia (AML), which makes it an important target for the treatment of AML. The structure-based synthesis and biological evaluation of 5,6-dihydrobenzo[h]quinazoline derivatives as FLT3 inhibitors have been studied in this paper. III-1a, III-1c, III-2a, III-2c, and III-4a displayed comparable inhibitory potency against FLT3-ITD and showed remarkable antiproliferative activities against MV4-11.

New insights into heavy metal elements deposition in the snowpacks of mountain glaciers in the eastern Tibetan Plateau.

Atmospheric heavy metals have important environmental and health threats. To investigate atmospheric deposition and contamination of heavy metal elements in the glaciers of the eastern Tibetan Plateau (ETP), we collected the surface snow (cryoconites) samples in the Lenglongling Glacier (LG), the Gannan Snowpack (GS), the Dagu Glacier (DG), the Hailuogou Glacier (HG) and Yulong Snow-mountain Glacier (YG) in summer 2017. Samples were analyzed for concentrations and enrichment factors (EFs) of Al and trace elements (Pb, Co, Cd, Ba, Mn, Ga, Sc, V, Zn, Cr, Ni, Cu, Rb, Sb, Cs, As, Mo, Li) using inductively coupled plasma-mass spectrometry (ICP-MS). Results showed that the concentrations and EFs of heavy metals (e.g. Sb, Cu, Cr, Ni, As, Mo) were generally high value in YG, GS and LG, while were relatively low value in DG and HG, implying that ETP glaciers may have been affected by atmospheric anthropogenic pollutants deposition to varying degrees. Comparing the heavy metal concentrations in the glaciers with those in the precipitation of middle/eastern China cities and also the South Asian cities, we find that the glacial heavy metal concentrations were generally low level, though the anthropogenic pollutants were still significantly enriched. Taking the spatial distribution of As and Ni concentration/EFs in the glaciers and surrounding urban precipitation as an example, we find that the heavy metal pollutants were probably transported to the glaciers through three routes from the surrounding densely populated area of Asia. The MODIS AOD and NCEP/NCAR wind vector also demonstrated that the atmospheric pollutants originated from anthropogenic emissions of urban areas of both South Asia, and northwest and east China, mainly caused by the large scale atmospheric circulation (e.g. the South Asian Monsoon, westerlies and Eastern Asian Summer Monsoon). Therefore, control of these potential pollution emission sources of the surrounding densely populated areas in Asia could be important to ETP glaciers in future perspectives.

Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors.

As a class III receptor tyrosine kinase (RTK), FMS-like tyrosine kinase 3 (FLT3) is always overexpressed in many cases of acute leukemia. This paper studies the structure-based synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Encouragingly, compounds 15b, 16b, 24a, and 24c showed excellent biological activities in a low nanomolar range. In particular, compound 16b demonstrated significant inhibitory potency against FLT3-ITD (IC50 = 5.60 nM) and better antiproliferative activity than quizartinib against MV4-11 cell line (IC50 = 0.176 nM). It is indicated that compound 16b for the treatment of acute myeloid leukemia could be very promising.

Enhanced photodegradation of applied dithianon fungicides on plant leaves by dissolved substances in atmosphere under simulated sunlight.

Photolysis of pesticides has been widely investigated for evaluating their environmental behavior and agricultural effectiveness after crop spraying. However, little information about the effects of the water-soluble substances in atmosphere on photodegradation of pesticides is available. In current study, we found that photolysis of applied dithianon fungicides on real plant leaves was much faster than that in sealed stock aqueous suspensions under simulated sunlight. To simulate the natural conditions, for the first time, photodegradation of dithianon in air-saturated solutions containing typical dissolved atmospheric substances (DAS) including CO2 (HCO3-/CO32-), NO2 (NO3-), Fe3+ (Fe3+-complexes), and humic-like substances (HULIS) exposed to simulated solar irradiations were carried out in lab-scale. Fulvic acid (FA) was used as a surrogate for atmospheric HULIS in this study. The dithianon photodegradation was significantly enhanced in the presence of DAS and the photo-generated reactive species such as ·OH, 1O2, CO3·- and 3FA∗ play important roles according to the results of reactive species quenching, electron spin resonance spectroscopy, and laser flash photolysis experiments. Moreover, the photodegraded intermediates and final products of dithianon on plant leaves have been identified by HPLC-MS analysis, and its possible photodegradation pathways were proposed. This work indicated that, except for direct photolysis, indirect photosensitive degradation induced by the dissolved photo-active substances in atmosphere should be considered for evaluating the degradation of the applied pesticides on crops.

Molecular characterization and overexpression of mnp6 and vp3 from Pleurotus ostreatus revealed their involvement in biodegradation of cotton stalk lignin.

Fungal secretory heme peroxidase (Class II POD) plays a significant role in biomass conversion due to its lignin-degrading activity. In this study, genome-wide identification and bioinformatics were performed to analyze P leurotus ostreatus peroxidases (PoPODs). A total of six manganese peroxidases (MnPs) and three versatile peroxidases (VPs) were obtained. Bioinformatics analysis and qRT-PCR showed that P. ostreatus mnp6 (Pomnp6) and P. ostreatus vp3 (Povp3) could be involved in lignin degradation. Both Pomnp6 and Povp3 transgenetic fungi showed significantly increased lignin degradation of cotton stalks. 1H-NMR revealed that Pomnp6 and Povp3 may preferentially degrade S-lignin in cotton stalks and mainly break ß-O-4' bond linkages and hydroxyl. These results support the possible utility of Pomnp6 and Povp3 in natural straw resources and development of sustainable energy.

Systematic Analysis of the Pleurotus ostreatus Laccase Gene (PoLac) Family and Functional Characterization of PoLac2 Involved in the Degradation of Cotton-Straw Lignin.

Fungal laccases play important roles in the degradation of lignocellulose. Although some PoLacs have been reported in several studies, still no comprehensive bioinformatics study of the LAC family in Pleurotus ostreatus has been reported. In this study, we identified 12 laccase genes in the whole genome sequence of P. ostreatus and their physical characteristics, gene distribution, phylogenic relationships, gene structure, conserved motifs, and cis-elements were also analyzed. The expression patterns of 12 PoLac genes at different developmental stages and under different culture substrates were also analyzed. The results revealed that PoLac2 and PoLac12 may be involved in the degradation of lignin and the formation of the fruiting body, respectively. Subsequently, we overexpressed PoLac2 in P. ostreatus by the Agrobacterium tumefaciens-mediated transformation (ATMT) method. The transformants' laccase activity increased in varying degrees, and the gene expression level of PoLac2 in transformants was 2-8 times higher than that of the wild-type strain. Furthermore, the lignin degradation rate by transgenic fungus over 30 days was 2.36-6.3% higher than that of wild-type. Our data show that overexpression of PoLac2 significantly enhanced the lignin degradation of cotton-straw. To our knowledge, this study is the first report to demonstrate the functions of PoLac2 in P. ostreatus.

Comparison of the transcriptomic analysis between two Chinese white pear (Pyrus bretschneideri Rehd.) genotypes of different stone cells contents.

Stone cell content is thought to be one of the key determinants for fruit quality in pears. However, the molecular mechanism of stone cell development remains poorly understood. In this study, we found that the stone cell clusters (SCCs) distribution and area in 'Dangshan Su' (with abundant stone cells) were higher as compared to 'Lianglizaosu' (low stone cell content bud sport of 'Dangshan Su') based on the histochemical staining, and the correlations of lignin content with stone cell content and SCC area was significant. The fruits of 'Dangshan Su' and 'Lianglizaosu' at three different developmental stages (23 and 55 days after flowering and mature) were sampled for comparative transcriptome analysis to explore the metabolic pathways associated with stone cell development. A total of 42444 unigenes were obtained from two varieties, among which 7203 differentially expressed genes (DEGs) were identified by comparison of the six transcriptomes. Specifically, many DEGs associated with lignin biosynthesis were identified, including coumaroylquinate 3-monooxygenase (C3H), shikimate O-hydroxycinnamoyltransferase (HCT), ferulate 5-hydroxylase (F5H), cinnamyl alcohol dehydrogenase (CAD) and peroxidase (POD), as well as genes related to carbon metabolism, such as sorbitol dehydrogenase-like (SDH-like) and ATP-dependent 6-phosphofructokinase (ATP-PFK). At the peak of the stone cell content (55 days after flowering), the expression level of these genes in 'Dangshan Su' was significantly increased compared with 'Lianglizaosu', indicating that these genes were closely related to stone cell development. We validated the transcriptional levels of 33 DEGs using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The results were consistent with the transcriptome analysis, indicating the reliability of transcriptome data. In addition, subcellular localization analysis of three DEGs in lignin synthesis (PbC3H, PbF5H and PbPOD) revealed that these proteins are mainly distributed in the cell membrane and cytoplasm. These results provide new insights into the molecular mechanism of stone cell formation.