Gasdermin E (GSDME) has an important role in inducing secondary necrosis/pyroptosis. Upon apoptotic stimulation, it can be cleaved by activated caspase-3 to generate its N-terminal fragment ...(GSDME-NT), which executes pyroptosis by perforating the plasma membrane. GSDME is expressed in many human lung cancers including A549 cells. Paclitaxel and cisplatin are two representative chemotherapeutic agents for lung cancers, which induce apoptosis via different action mechanisms. However, it remains unclear whether they can induce GSDME-mediated secondary necrosis/pyroptosis in lung A549 cancer cells. Here we showed that both paclitaxel and cisplatin evidently induced apoptosis in A549 cells as revealed by the activation of multiple apoptotic markers. Notably, some of the dying cells displayed characteristic morphology of secondary necrosis/pyroptosis, by blowing large bubbles from the cellular membrane accompanied by caspase-3 activation and GSDME-NT generation. But the ability of cisplatin to induce this phenomenon was much stronger than that of paclitaxel. Consistent with this, cisplatin triggered much higher activation of caspase-3 and generation of GSDME-NT than paclitaxel, suggesting that the levels of secondary necrosis/pyroptosis correlated with the levels of active caspase-3 and GSDME-NT. Supporting this, caspase-3 specific inhibitor (Ac-DEVD-CHO) suppressed cisplatin-induced GSDME-NT generation and concurrently reduced the secondary necrosis/pyroptosis. Besides, GSDME knockdown significantly inhibited cisplatin- but not paclitaxel-induced secondary necrosis/pyroptosis. These results indicated that cisplatin induced higher levels of secondary necrosis/pyroptosis in A549 cells than paclitaxel, suggesting that cisplatin may provide additional advantages in the treatment of lung cancers with high levels of GSDME expression.
Herein we report a catalytic asymmetric dearomatization reaction of electron‐deficient heteroarenes with α‐substituted isocyanoacetates through an interrupted Barton–Zard reaction. A range of ...optically active pyrrolo3,4‐bindole derivatives was obtained in good yields (up to 97 %) with high stereoselectivities (up to >20:1 dr and 97 % ee), using a catalytic system consisting of a cinchona‐derived amino‐phosphine and silver oxide. This reaction features wide substrate scope and mild conditions, and provides a new strategy for developing asymmetric dearomatization reactions.
Catalytic asymmetric dearomatization reaction of electron‐deficient heteroarenes with α‐substituted isocyanoacetate ester through an interrupted Barton–Zard reaction is reported. A range of optically active pyrrolo3,4‐bindole derivatives was obtained in good reactivity (up to 99 % yield) with high stereoselectivities (up to >20:1 dr, 97 % ee) in the presence of 2.5 mol % Ag2O and amino‐phosphine L1.
Strigolactones （SLs）, a group of carotenoid derived terpenoid lactones, are root-to-shoot phytohormones sup- pressing shoot branching by inhibiting the outgrowth of axillary buds. DWARF 53 （D53）, the ...key repressor of the SL signaling pathway, is speculated to regulate the downstream transcriptional network of the SL response. However, no downstream transcription factor targeted by D53 has yet been reported. Here we report that Ideal Plant Architecture 1 （IPA1）, a key regulator of the plant architecture in rice, functions as a direct downstream component of D53 in reg- ulating tiller number and SL-induced gene expression. We showed that D53 interacts with IPA1 in vivo and in vitro and suppresses the transcriptional activation activity of IPA1. We further showed that IPA1 could directly bind to the D53 promoter and plays a critical role in the feedback regulation of SL-induced D53 expression. These findings re- veal that IPA1 is likely one of the long-speculated transcription factors that act with D53 to mediate the SL-regulated tiller development in rice.
The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from ...MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4
T cells compared to CD8
T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer.
The long‐term variability of total, direct and diffuse solar radiation across China during 1958–2016 is investigated based on a ground‐measured daily radiation dataset. Missing data are estimated ...using a 3‐day average moving window and a backpropagation artificial neural network (BP network). The BP network achieves better estimates of direct (R2 = 0.32–0.96) than diffuse radiation (R2 = 0.00–0.81). A dimming period during 1958–1990 and a “From Dimming to Brightening” transition between 1990 and 1993 have been detected across China. The declining ratio of direct to diffuse radiation suggests a degrading air quality caused by increasing aerosols in eastern China. To study the aerosol effect on radiation, two empirical models are developed from 2000–2016 using the ground‐measured total radiation, sunshine duration and satellite‐retrieved total aerosol concentration. Both models perform well in the estimate of direct (R2 = 0.71–0.89) and diffuse radiation (R2 = 0.63–0.95). The increasing total radiation in eastern China since 2000 is mainly contributed by diffuse radiation. Besides, small anthropogenic aerosols can increase diffuse fraction, the proportion of diffuse in total radiation, whereas large natural aerosols may reduce it. The BP network and empirical models exhibit a better agreement in the estimate of direct than diffuse radiation in eastern China, which highlights the impact of aerosols on diffuse radiation in the recent decade.
Temporal variation of annual average sunshine duration over six regions during 1958–2016. A dimming period from 1958 to 1990 has been detected but the declining trend of total radiation does not persist to 1990s. The “From Dimming to Brightening” transition between 1990 and 1993 is detected over six regions. Moreover, increasing total radiation has been observed after 2000 over six regions except for TP. The declining direct/diffuse ratio contributed by the declining direct radiation and increasing diffuse radiation indicates the deterioration of air quality in eastern China since 1958. In contrast, large direct/diffuse ratios above 1 suggest relatively good air quality in TP and NW during 1958–2016.
Glioblastoma is the most frequent and lethal primary central nervous system tumor in adults, accounting for around 15% of intracranial neoplasms and 40–50% of all primary malignant brain tumors, with ...an annual incidence of 3–6 cases per 100,000 population. Despite maximum treatment, patients only have a median survival time of 15 months. Metformin is a biguanide drug utilized as the first-line medication in treating type 2 diabetes. Recently, researchers have noticed that metformin can contribute to antineoplastic activity. The objective of this study is to investigate the mechanism of metformin as a potential adjuvant treatment drug in glioblastoma. Glioblastoma cell lines U87MG, LNZ308, and LN229 were treated with metformin, and several cellular functions and metabolic states were evaluated. First, the proliferation capability was investigated using the MTS assay and BrdU assay, while cell apoptosis was evaluated using the annexin V assay. Next, a wound-healing assay and mesenchymal biomarkers (N-cadherin, vimentin, and Twist) were used to detect the cell migration ability and epithelial–mesenchymal transition (EMT) status of tumor cells. Gene set enrichment analysis (GSEA) was applied to the transcriptome of the metformin-treated glioblastoma cell line. Then, DCFH-DA and MitoSOX Red dyes were used to quantify reactive oxygen species (ROS) in the cytosol and mitochondria. JC-1 dye and Western blotting analysis were used to evaluate mitochondrial membrane potential and biogenesis. In addition, the combinatory effect of temozolomide (TMZ) with metformin treatment was assessed by combination index analysis. Metformin could decrease cell viability, proliferation, and migration, increase cell apoptosis, and disrupt EMT in all three glioblastoma cell lines. The GSEA study highlighted increased ROS and hypoxia in the metformin-treated glioblastoma cells. Metformin increased ROS production, impaired mitochondrial membrane potential, and reduced mitochondrial biogenesis. The combined treatment of metformin and TMZ had U87 as synergistic, LNZ308 as antagonistic, and LN229 as additive. Metformin alone or combined with TMZ could suppress mitochondrial transcription factor A, Twist, and O6-methylguanine-DNA methyltransferase (MGMT) proteins in TMZ-resistant LN229 cells. In conclusion, our study showed that metformin decreased metabolic activity, proliferation, migration, mitochondrial biogenesis, and mitochondrial membrane potential and increased apoptosis and ROS in some glioblastoma cells. The sensitivity of the TMZ-resistant glioblastoma cell line to metformin might be mediated via the suppression of mitochondrial biogenesis, EMT, and MGMT expression. Our work provides new insights into the choice of adjuvant agents in TMZ-resistant GBM therapy.
The electrocatalytic transformation of carbon dioxide (CO2) to formate is a promising route for highly efficient conversion and utilization of CO2 gas, due to the low production cost and the ease of ...storage of formate. In this work, porous poly(ionic liquid) (PPIL)‐based tin‐silver (Sn‐Ag) bimetallic hybrids (PPILm‐SnxAg10‐x) are prepared for high‐performance formate electrolytic generation. Under optimal conditions, an excellent formate Faradaic efficiency of 95.5% with a high partial current density of 214.9 mA cm−2 is obtained at −1.03 V (vs reversible hydrogen electrode). Meanwhile, the high selectivity of formate (>≈83%) is maintained in a wide potential range (>630 mV). Mechanistic studies demonstrate that the presence of Ag‐species is vital for the formation, maintenance, and high dispersion of tetravalent Sn(IV)‐species, which accounts for the active sites for CO2‐to‐formate conversion. Further, the introduction of Ag‐species significantly enhances the activity by increasing the electron density near the Fermi energy level.
Porous poly(ionic liquid) (PPIL)‐based tin‐silver (Sn‐Ag) bimetallic hybrids (PPILm‐SnxAg10‐x) are synthesized for high‐efficient electrocatalytic carbon dioxide (CO2)‐to‐formate conversion. An excellent formate selectivity of 95.5% with a high partial current density of 214.9 mA cm−2 is achieved at −1.03 V (vs. reversible hydrogen electrode). Besides, the formate selectivity of > ≈83% is maintained in a wide potential range (>630 mV).
Enterohemorrhagic Escherichia coli (EHEC) is one major type of contagious and foodborne pathogens. The type VI secretion system (T6SS) has been shown to be involved in the bacterial pathogenicity and ...bacteria-bacteria competition. Here, we show that EHEC could secrete a novel effector KatN, a Mn-containing catalase, in a T6SS-dependent manner. Expression of katN is promoted by RpoS and OxyR and repressed by H-NS, and katN contributes to bacterial growth under oxidative stress in vitro. KatN could be secreted into host cell cytosol after EHEC is phagocytized by macrophage, which leads to decreased level of intracellular reactive oxygen species (ROS) and facilitates the intramacrophage survival of EHEC. Finally, animal model results show that the deletion mutant of T6SS was attenuated in virulence compared with the wild type strain, while the deletion mutant of katN had comparable virulence to the wild type strain. Taken together, our findings suggest that EHEC could sense oxidative stress in phagosome and decrease the host cell ROS by secreting catalase KatN to facilitate its survival in the host cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Streamflow prediction in ungauged basins (PUB) is challenging, and Long Short‐Term Memory (LSTM) is widely used to for such predictions, owing to its excellent migration performance. Traditional LSTM ...forced by meteorological data and catchment attribute data barely highlight the optimum data integration strategy for LSTM and its migration from data‐rich basins to ungauged ones. In this study, we experimented with 1,897 global catchments and found that LSTM‐corrected Global Hydrological Models (GHMs) outperformed uncorrected GHMs, improving the median Nash‐Sutcliff efficiency (NSE) from 0.03 to 0.66. Notably, there was a large gap between traditional LSTM modeling in ungauged basins and autoregressive modeling in data‐rich basins, and GHM‐forced LSTM were an effective way to close this gap in ungauged basins. The spatial heterogeneity of the performance of GHM‐forced LSTM was mainly influenced by three metrics (dryness, the leaf area index and latitude), which described the hydrological similarity among catchments. Weaker hydrological similarity among continental catchments results in larger variability in GHM‐forced LSTM, with the best performance in Siberia (NSE, 0.54) and the worst in North America (NSE, 0.10). However, the migration performance of GHM‐forced LSTM was significantly improved (NSE, 0.63) in ungauged basins when hydrological similarity was considered. This study stressed the advantages of GHM‐forced LSTM and due significance should be attached to hydrological similarities among catchments to improve hydrological prediction in ungauged catchments.
Key Points
Compared to Global Hydrological Models, GHM‐forced LSTM improved the median Nash‐Sutcliff efficiency (NSE) from 0.03 to 0.66
Three metrics (dryness, the leaf area index, and latitude) helped to quickly identify hydrological similarities between catchments
GHM‐forced LSTM reached a high NSE value of 0.63 for prediction in ungauged basins when hydrological similarity is considered
Organic pollutants, such as polychlorinated dJbenzo-p-dioxins and polychlofinated dibenzofurans （PCDD/Fs）, polychlodnated biphenyls （PCBs）, antibiotics, herbicides, and bisphenol A （BPA）, are ...commonly found in agricultural environments. They are released into the environment as a result of their use for human health purposes and farm management activities, and are often discharged as waste-water effluents. Most of these organic pollutants are taken up by plants through roots and leaves, and when they enter the tissue, they cause serious damage to the plants. Although the toxicity of organic pollutants to plants, especially to plant cells, has been intensively studied, a systematic review of these studies is lacking. Here we review researches on the toxicity of organic pollutants, their uptake, and translocation in plants. Our objective is to assemble existing knowledge concerning the interaction of organic pollutants with plants, which should be useful for the development of plant-based systems for removing pollutants from aquatic and agricultural environments.
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