Catalytic asymmetric construction of chiral indole‐fused rings has become an important issue in the chemical community because of the significance of such scaffolds. In this work, we have ...accomplished the first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols by using indoles and 2‐naphthols as suitable reaction partners under the catalysis of chiral phosphoric acids, constructing enantioenriched indole‐fused six‐membered and seven‐membered rings in high yields with excellent enantioselectivities. In addition, this approach is used to realize the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which are found to show promising anticancer activity. More importantly, theoretical calculations of the reaction pathways and activation mode offer an in‐depth understanding of this class of indolylmethanols. This work not only settles the challenges in realizing catalytic asymmetric cycloadditions of indolyldimethanols but also provides a powerful strategy for the construction of enantioenriched indole‐fused rings.
The first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols enable the construction of enantioenriched indole‐fused rings in high yields with excellent enantioselectivities. This approach led to the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which show promising anticancer activity. Theoretical calculations offer an in‐depth understanding of this class of indolylmethanols.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC ...intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A new class of axially chiral styrene‐based thiourea tertiary amine catalysts, which have unique characteristics such as an efficient synthetic route, multiple chiral elements, and multiple ...activating groups, has been rationally designed. These new chiral catalysts have proven to be efficient organocatalysts, enabling the chemo‐, diastereo‐, and enantioselective (2+4) cyclization of 2‐benzothiazolimines with homophthalic anhydrides in good yields (up to 96 %) with excellent stereoselectivities (all >95:5 dr, up to 98 % ee). More importantly, theoretical calculations elucidated the important role of an axially chiral styrene moiety in controlling both the reactivity and enantioselectivity. This work not only represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, but also gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
A new class of axially chiral styrene‐based organocatalysts has been rationally designed. They enable the chemo‐, diastereo‐ and enantioselective (2+4) cyclization of 2‐benzothiazolimines. This work represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, and it gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause ...of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown.
lncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs.
The microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway.
MRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Numerous efficient synthetic methods for enantioselective indole functionalizations have emerged in recent years. This review summarizes the major achievements in the transition-metal-catalyzed ...enantioselective indole functionalization reactions since 2010 and focuses on C-C bond formation processes, including alkylations, arylations, cycloaddition reactions, and other reactions. It intends to give a compendious overview of the significant progress achieved in this area.
Recent progress on the transition-metal-catalyzed enantioselective functionalization reaction of indoles is reviewed, which is mainly focused on asymmetric indole alkylations, arylations, cycloaddition reactions, and other reactions.
We herein report a new coordination network that deforms in a smooth and reversible manner under either thermal or pressure stimulation. Concomitantly, the organic fluorophores coordinatively bound ...to the channel in a face‐to‐face arrangement respond to this structural deformation by finely adapting their conformation and arrangement. As a result, the material exhibits a remarkable dual‐stimuli‐responsive luminescence shift across almost the entire visible region: The emission color of the crystal gradually changes from cyan to green upon heating and then to red upon pressure compression. Furthermore, each stage exhibits a linear dependence of both the emission maximum and intensity on the stimulus and is fully reversible.
Coping with pressure and heat: In response to changes in temperature and pressure, the flexible scaffold of a luminescent coordination network underwent smooth and reversible structural deformation that regulated the conformation and arrangement of the emissive organic molecules coordinatively bound to the channel in the structure. As a result, a reversible fluorescence shift across almost the entire visible region was observed (see picture).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Catalytic hydrogenation or transfer hydrogenation of quinolines was thought to be a direct strategy to access dihydroquinolines. However, the challenge is to control the chemoselectivity and ...regioselectivity. Here we report an efficient partial transfer hydrogenation system operated by a cobalt-amido cooperative catalyst, which converts quinolines to 1,2-dihydroquinolines by the reaction with H
N·BH
at room temperature. This methodology enables the large scale synthesis of many 1,2-dihydroquinolines with a broad range of functional groups. Mechanistic studies demonstrate that the reduction of quinoline is controlled precisely by cobalt-amido cooperation to operate dihydrogen transfer from H
N·BH
to the N=C bond of the substrates.
Abstract
Summary
The interaction between tumor and immune system plays a crucial role in both cancer development and treatment response. To facilitate comprehensive investigation of tumor–immune ...interactions, we have designed a user-friendly web portal TISIDB, which integrated multiple types of data resources in oncoimmunology. First, we manually curated 4176 records from 2530 publications, which reported 988 genes related to anti-tumor immunity. Second, genes associated with the resistance or sensitivity of tumor cells to T cell-mediated killing and immunotherapy were identified by analyzing high-throughput screening and genomic profiling data. Third, associations between any gene and immune features, such as lymphocytes, immunomodulators and chemokines, were pre-calculated for 30 TCGA cancer types. In TISIDB, biologists can cross-check a gene of interest about its role in tumor–immune interactions through literature mining and high-throughput data analysis, and generate testable hypotheses and high quality figures for publication.
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http://cis.hku.hk/TISIDB
Supplementary information
Supplementary data are available at Bioinformatics online.
Precise design of low‐cost, efficient and definite electrocatalysts is the key to sustainable renewable energy. Herein, this work develops a targeted‐anchored and subsequent spontaneous‐redox ...strategy to synthesize nickel‐iron layered double hydroxide (LDH) nanosheets anchored with monodispersed platinum (Pt) sites (Pt@LDH). Intermediate metal‐organic frameworks (MOF)/LDH heterostructure not only provides numerous confine points to guarantee the stability of Pt sites, but also excites the spontaneous reduction for PtII. Electronic structure, charge transfer ability and reaction kinetics of Pt@LDH can be effectively facilitated by the monodispersed Pt moieties. As a result, the optimized Pt@LDH that with the 5% ultra‐low content Pt exhibits the significant increment in electrochemical water splitting performance in alkaline media, which only afford low overpotentials of 58 mV at 10 mA cm−2 for hydrogen evolution reaction (HER) and 239 mV at 10 mA cm−2 for oxygen evolution reaction (OER), respectively. In a real device, Pt@LDH can drive an overall water‐splitting at low cell voltage of 1.49 V at 10 mA cm−2, which can be superior to most reported similar LDH‐based catalysts. Moreover, the versatility of the method is extended to other MOF precursors and noble metals for the design of ultrathin LDH supported monodispersed noble metal electrocatalysts promoting research interest in material design.
A targeted‐anchored and subsequent spontaneous‐redox strategy is developed to synthesize nickel‐iron layered double hydroxide (LDH) nanosheets anchored with monodispersed platinum (Pt) sites (Pt@LDH). As‐prepared Pt@LDH‐4h can drive an overall water‐splitting at low cell voltage of 1.49 V at 10 mA cm−2, which can be superior to most reported similar LDH‐based catalysts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
: Walking while performing cognitive and motor tasks simultaneously interferes with gait performance and may lead to falls in older adults with mild cognitive impairment (MCI). Executive function, ...which seems to play a key role in dual-task gait performance, can be improved by combined physical and cognitive training. Virtual reality (VR) has the potential to assist rehabilitation, and its effect on physical and cognitive function requires further investigation. The purpose of this study was to assess the effects of VR-based physical and cognitive training on executive function and dual-task gait performance in older adults with MCI, as well as to compare VR-based physical and cognitive training with traditional combined physical and cognitive training.
: Thirty-four community-dwelling older adults with MCI were randomly assigned into either a VR-based physical and cognitive training (VR) group or a combined traditional physical and cognitive training (CPC) group for 36 sessions over 12 weeks. Outcome measures included executive function Stroop Color and Word Test (SCWT) and trail making test (TMT) A and B, gait performance (gait speed, stride length, and cadence) and dual-task costs (DTCs). Walking tasks were performed during single-task walking, walking while performing serial subtraction (cognitive dual task), and walking while carrying a tray (motor dual task). The GAIT Up system was used to evaluate gait parameters including speed, stride length, cadence and DTCs. DTC were defined as 100 * (single-task gait parameters - dual-task gait parameters)/single-task gait parameters.
: Both groups showed significant improvements in the SCWT and single-task and motor dual-task gait performance measures. However, only the VR group showed improvements in cognitive dual-task gait performance and the DTC of cadence. Moreover, the VR group showed more improvements than the CPC group in the TMT-B and DTC of cadence with borderline significances.
: A 12-week VR-based physical and cognitive training program led to significant improvements in dual-task gait performance in older adults with MCI, which may be attributed to improvements in executive function.
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