A one‐pot approach for the asymmetric synthesis of C2‐tetrasubstituted indolin‐3‐ones from 2‐substituted indoles was developed via merging transition metal catalysis with organocatalysis. This ...strategy involves two processes, including CuI catalyzed oxidative dearomatization of 2‐substituted indoles using O2 as green oxidant, and followed by an proline‐promoted asymmetric Mannich reaction with ketones or aldehydes. A series of C2‐tetrasubstituted indolin‐3‐ones were obtained in 35–86% yields, 2:1‐>20:1 dr and 48–99% ee. Moreover, the synthetic 2‐tetrasubstituted indolin‐3‐ones could be easily transformed into 1H‐1,3 oxazino 3,4‐aindol‐5(3H)‐ones via a 4+1 cyclization process. In addition, the synthetic compound 3 s show certain antibacterial activity against S. aureus ATCC25923 and multi‐drug resistance bacterial strain of S. aureus (20151027077) and its MIC values up to 8 μg/mL and 16 μg/mL, respectively.
RNA modifications are recently emerged epigenetic modifications. These diverse RNA modifications have been shown to regulate multiple biological processes, including development. RNA modifications ...are dynamically controlled by the "writers, erasers, and readers", where RNA modifying proteins are able to add, remove, and recognize specific chemical modification groups on RNAs. However, little is known about the ontogenic expression of these RNA modifying proteins in various organs, such as liver. In the present study, the hepatic mRNA expression of selected RNA modifying proteins involve in m6A, m1A, m5C, hm5C, m7G, and Ψ modifications was analyzed using the RNA-seq technique. Liver samples were collected from male C57BL/6 mice at several ages from prenatal through neonatal, infant, child to young adult. Results showed that most of the RNA modifying proteins were highly expressed in prenatal mouse liver with a dramatic drop at birth. After birth, most of the RNA modifying proteins showed a downregulation trend during liver maturation. Moreover, the RNA modifying proteins that belong to the same enzyme family were expressed at different abundances at the same ages in mouse liver. In conclusion, this study unveils that the mRNA expression of RNA modifying proteins follows specific ontogenic expression patterns in mice liver during maturation. These data indicated that the changes in expression of RNA modifying proteins might have a potential role to regulate gene expression in liver through alteration of RNA modification status.
Summary Background The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the ...contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. Methods We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3–4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m2 cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0–2·27 Gy per fraction with five daily fractions per week for 6–7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60–66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m2 adjuvant cisplatin and 800 mg/m2 per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov , number NCT00677118. Findings 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3–61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81–90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78–88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49–1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 21% of 205 patients treated with adjuvant chemotherapy). Interpretation Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. Funding Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010–178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).
Mucosal-associated invariant T (MAIT) cells have important functions in immune responses against pathogens and in diseases, but mechanisms controlling MAIT cell development and effector lineage ...differentiation remain unclear. Here, we report that IL-2/IL-15 receptor β chain and inducible costimulatory (ICOS) not only serve as lineage-specific markers for IFN-γ-producing MAIT1 and IL-17A-producing MAIT17 cells, but are also important for their differentiation, respectively. Both IL-2 and IL-15 induce mTOR activation, T-bet upregulation, and subsequent MAIT cell, especially MAIT1 cell, expansion. By contrast, IL-1β induces more MAIT17 than MAIT1 cells, while IL-23 alone promotes MAIT17 cell proliferation and survival, but synergizes with IL-1β to induce strong MAIT17 cell expansion in an mTOR-dependent manner. Moreover, mTOR is dispensable for early MAIT cell development, yet pivotal for MAIT cell effector differentiation. Our results thus show that mTORC2 integrates signals from ICOS and IL-1βR/IL-23R to exert a crucial role for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.
BACKGROUNDEmerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis ...(UC), although the mechanism of FMT is unclear. AIMTo evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice. METHODSDextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry. RESULTSCompared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1. CONCLUSIONFMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.
Abstract
In this work, we study effects of different types of system-reservoir interactions on work costs and operating regimes of thermal machines by considering a quantum system consisting of two ...subsystems embedded in both independent and common reservoirs. The model allows us to make a contrast between three configurations of system-reservoir interactions, namely, the three-body one, the two-body one with and without intrasystem interaction between two subsystems. After establishing general formulations of thermodynamics quantities, we derive specific forms of heat and work with respect to these three configurations based on a model with two coupled qubits. It is shown that both the amount and sign of work are closely related to ways of system-reservoir interactions, by which six types of operating regimes of machines are constructed for a given setting. We find that different modes of system-reservoir interactions lead to different numbers of operating regimes of machines on the one hand, and on the other hand machines of the same kinds can appear in different scenarios of system-reservoir interactions, but which one is superior over others relies on intervals of parameters. A possible implementation of the setup based on the platform of circuit quantum electrodynamics is discussed briefly. We then generalize the bipartite model to multipartite case and derive the corresponding formulations of thermodynamics quantities. Our results indicate that interacting manners of system-reservoir play an important role in modifying thermodynamics process and can thus be utilized in designing quantum thermal machines with requisite functions.
•The static magnetic properties of NiZnCoZr ferrite nanopowders have been investigated.•The dielectric constant increases with the increase of Zr substitution.•The relaxation peak of tan δ∼T curves ...is observed for x≥0.10.•Electrical transport behavior is found to follow the impurity semiconductor.•The dc resistivity increases at transition temperature with Zr substitution.
Zr-substituted NiZnCo ferrite nanopowders, Ni0.4−xZn0.5ZrxCo0.1Fe2.0O4 (0≤x≤0.20), were synthesized by the sol-gel auto-combustion method. The effects of Zr substitution on the structural, magnetic and electrical properties have been investigated. The DTA and TG results indicate that there are three steps of combustion process. The X-ray diffraction patterns show that the lattice parameter and the average crystallite size increase with the increase of Zr substitution. The saturation magnetization increases with the increase of Zr substitution when x≤0.05, and then decreases when x>0.05. Meanwhile, the coercivity initially decreases with the increase of Zr substitution when x≤0.05, and then increases when x>0.05. The polarization behavior for all the samples in the test frequency range from100Hz to10MHz obeys the charge polarization mechanism, which happens since the frequency of the hopping of electron exchange between Fe2+ and Fe3+ ions are far from the frequency of alternating-current field. And the dielectric constant increases with the increase of Zr substitution. The relaxation peak of the frequency dependence of dielectric loss is observed for x≥0.10, which is due to the frequency of charge hopping between the Fe2+ and Fe3+ exactly matches with the frequency of the external applied field. Electrical transport behavior of the ferrite nanopowders is found to follow the impurity semiconductor, and the effect of Zr substitution on the temperature dependence of dc resistivity is observed.
In recent years, considerable efforts have been devoted to the construction of efficient enzyme mimetics, which have significant advantages of simple synthesis, good stability and design flexibility. ...In this paper, we described that graphene dots (GDs) possess highly-efficient peroxidase-like catalytic activity, and its activity is much higher than graphene oxide (GO) with large size. They can catalyze the oxidation of peroxidase substrate 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue product, which can be used for H2O2 detection by measuring the absorbance change. This catalytic reaction can be also used for other analyte detection by monitoring the generation or consumption of H2O2, such as glucose and reduced glutathione (GSH). The GDs-based system permits detection of as low as 10nM H2O2, which is much lower than that of other nanomaterials-catalyzed methods. Meanwhile, the detection limit of this system is 0.5μM for glucose and 0.5μM for GSH, respectively. Furthermore, the proposed system also shows high selectivity and is capable of sensing in complicated biological samples such as cell lysate. Due to their high catalytic activity, high diffusion and excellent biocompatibility, GDs can be expected to be applied in various fields, such as biotechnology, medical diagnostics and environmental monitoring.
•GDs possess highly-efficient peroxidase-like catalytic activity, which is much higher than GO.•The system permits detection of 10nM H2O2, it is lower than other nanomaterials-catalyzed methods.•The system shows high selectivity and is capable of sensing in complicated biological samples.•GDs have other advantages, such as good biocompatibility and easily combining with biomolecules.
Lithium–sulfur (Li–S) batteries exhibit outstanding energy density and material sustainability. Enormous effects have been devoted to the sulfur cathode to address redox kinetics and polysulfide ...intermediates shuttle. Recent attentions are gradually turning to the protection of the lithium metal anodes, since electrochemical performances of Li–S batteries are closely linked to the working efficiency of the anode side, especially in pouch cells that adopt stringent test protocols. This Perspective article summarizes critical issues encountered in the lithium metal anode, and outlines possible solutions to achieve efficient working lithium anode in Li–S batteries. The lithium metal anode in Li–S batteries shares the common failure mechanisms of volume fluctuation, nonuniform lithium flux, electrolyte corrosion and lithium pulverization occurring in lithium metal batteries with oxide cathodes, and also experiences unique polysulfide corrosion and massive lithium accumulation. These issues can be partially addressed by developing three-dimensional scaffold, exerting quasi-solid reaction, tailoring native solid electrolyte interphase (SEI) and designing artificial SEI. The practical evaluation of Li–S batteries highlights the importance of pouch cell platform, which is distinguished from coin-type cells in terms of lean electrolyte-to-sulfur ratio, thin lithium foil, as well as sizable total capacity and current that are loaded on pouch cells. This Perspective underlines the development of practically efficient working lithium metal anode in Li–S batteries.
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Challenges and possible strategies of lithium mental anodes in lithium–sulfur batteries are discussed, and the importance of pouch cell is emphasized to evaluate practical battery performances.
IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor ...progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thoroughly investigated. In the present study, we showed that IQGAP1 was overexpressed in ESCC tumor tissues, and its overexpression was correlated with the invasion depth of ESCC. Importantly, by using RNA interference (RNAi) technology we successfully silenced IQGAP1 gene in two ESCC cell lines, EC9706 and KYSE150, and for the first time found that suppressing IQGAP1 expression not only obviously reduced the tumor cell growth, migration and invasion in vitro but also markedly inhibited the tumor growth, invasion, lymph node and lung metastasis in xenograft mice. Furthermore, Knockdown of IQGAP1 expression in ESCC cell lines led to a reversion of epithelial to mesenchymal transition (EMT) progress. These results suggest that IQGAP1 plays crucial roles in regulating ESCC occurrence and progression. IQGAP1 silencing may therefore develop into a promising novel anticancer therapy.
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