Snapshot compressive imaging (SCI) refers to compressive imaging systems where multiple frames are mapped into a single measurement, with video compressive imaging and hyperspectral compressive ...imaging as two representative applications. Though exciting results of high-speed videos and hyperspectral images have been demonstrated, the poor reconstruction quality precludes SCI from wide applications. This paper aims to boost the reconstruction quality of SCI via exploiting the high-dimensional structure in the desired signal. We build a joint model to integrate the nonlocal self-similarity of video/hyperspectral frames and the rank minimization approach with the SCI sensing process. Following this, an alternating minimization algorithm is developed to solve this non-convex problem. We further investigate the special structure of the sampling process in SCI to tackle the computational workload and memory issues in SCI reconstruction. Both simulation and real data (captured by four different SCI cameras) results demonstrate that our proposed algorithm leads to significant improvements compared with current state-of-the-art algorithms. We hope our results will encourage the researchers and engineers to pursue further in compressive imaging for real applications.
The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary ...to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.
The first highly diastereo‐ and enantioselective multicomponent reaction of diazooxindoles, nitrosoarenes, and nitroalkenes using a newly developed hydrogen‐bond catalyst has been successfully ...developed for the efficient construction of a series of spirooxindole derivatives with excellent functional‐group tolerance. Spirooxindoles are formed in excellent yields and stereoselectivities, and the method represents an unprecedented approach for trapping the active intermediate with a nitroalkene to form biologically important compounds having three contiguous stereogenic centers with excellent asymmetric induction.
Multiple players: The first highly stereoselective multicomponent reaction of diazooxindoles, nitrosoarenes, and nitroalkenes with a newly developed hydrogen‐bond catalyst has been successfully developed. The spirooxindole products are isolated in excellent yields and stereoselectivities, and contain three contiguous stereogenic centers. R′′′=aryl or alkyl.
ObjectiveSolid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated ...fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC).DesignAnti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses.ResultsA negative correlation between WNT2+ CAFs and active CD8+ T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades.ConclusionsCAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.
The synthesis of new functionally diverse alkenyl‐derived Cr‐MIL‐101s (MIL=material of Institute Lavoisier) was realized by a novel and convenient postsynthetic modification (PSM) protocol by means ...of the carboncarbon bond‐forming Mizoroki–Heck reaction. The new PSM protocol demonstrates a broad scope of substrates with excellent tolerance of functionality under mild reaction conditions. Moreover, a new metal–organic framework (MOF) that bears both alkenyl and thiol side chains prepared by means of the tandem PSM method has shown excellent adsorbent ability in removing mercury ions from water.
Mercurial temperament: The synthesis of new functionally diverse alkenyl‐derived Cr‐MIL‐101s (MIL=material of Institute Lavoisier) was realized by a convenient postsynthetic modification protocol through the CC bond‐forming reaction (see figure). A MOF that bears both alkenyl and thiol side chains was prepared. It shows excellent adsorbent ability in removing Hg ions from water.
Asymmetric cross‐couplings based on 1,2‐carbon migration from B‐ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by ...1,2‐boron shift have remained to be unaddressed synthetic challenge. Here, Ir‐catalyzed asymmetric allylic alkylation enabled by 1,2‐boron shift was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of allylic carbonates at the elevated temperature. Notably, the highly valuable (bis‐boryl)alkenes have enabled an array of diversifications to access versatile molecules. Extensive experimental and computational studies were conducted to elucidate the reaction mechanism of DKR process and clarify the origin of excellent enantioselectivities.
We have developed an Ir‐catalyzed asymmetric allylic alkylation via 1,2‐boron shift to access enantioenriched gem‐diborylalkenes. In this reaction, excellent enantioselectivities were obtained by simply improving the reaction temperature via an impressive DKR process. DFT calculations and extensive mechanistic studies were conducted to elucidate the reaction mechanism and the origin of excellent enantioselectivities.
Hepatocellular carcinoma (HCC) is one of the most common human malignancies worldwide with very poor prognosis. Resistance to targeted therapeutic drugs such as sorafenib remains one of the major ...challenges in clinical treatment. In the present study, PARP1 was found to be highly expressed in human embryonic stem cells, but progressively decreased upon specified hepatic differentiation. Reactivation of PARP1 expression was also detected in HCC residual tumors after sorafenib treatment in xenograft mouse model, indicating the potential important roles of PARP1 in stem cell pluripotency and HCC sorafenib treatment resistance. Overexpression of PARP1 was frequently observed in HCC patients, and closely associated with poor clinical outcome. Treatment of Sorafenib induced activation of DNA damage repair signaling, which is highly active and essential for maintenance of stem cell pluripotency in HCC residual tumors. PARP inhibitor Olaparib extensively suppressed the DNA damage repair signaling, and significantly inhibited the global pluripotent transcriptional network. The repression of key pluripotent transcriptional factors and DNA damage repair signaling by Olaparib was mainly through CHD1L-mediated condensation of the chromatin structure at their promotor regions. The global reshaping of the pluripotent transcriptome by Olaparib might reinforce Sorafenib in eliminating HCC residual tumors and enhance therapeutic efficiency.
Continued development of the Sonogashira coupling has made it a well established and versatile reaction for the straightforward formation of C-C bonds, forging the carbon skeletons of broadly useful ...functionalized molecules. However, asymmetric Sonogashira coupling, particularly for C(sp
)-C(sp) bond formation, has remained largely unexplored. Here we demonstrate a general stereoconvergent Sonogashira C(sp
)-C(sp) cross-coupling of a broad range of terminal alkynes and racemic alkyl halides (>120 examples) that are enabled by copper-catalysed radical-involved alkynylation using a chiral cinchona alkaloid-based P,N-ligand. Industrially relevant acetylene and propyne are successfully incorporated, laying the foundation for scalable and economic synthetic applications. The potential utility of this method is demonstrated in the facile synthesis of stereoenriched bioactive or functional molecule derivatives, medicinal compounds and natural products that feature a range of chiral C(sp
)-C(sp/sp
/sp
) bonds. This work emphasizes the importance of radical species for developing enantioconvergent transformations.
Growing evidences suggest that cancer stem cells exhibit many molecular characteristics and phenotypes similar to their ancestral progenitor cells. In the present study, human embryonic stem cells ...are induced to differentiate into hepatocytes along hepatic lineages to mimic liver development in vitro. A liver progenitor specific gene, RALY RNA binding protein like (RALYL), is identified. RALYL expression is associated with poor prognosis, poor differentiation, and metastasis in clinical HCC patients. Functional studies reveal that RALYL could promote HCC tumorigenicity, self-renewal, chemoresistance, and metastasis. Moreover, molecular mechanism studies show that RALYL could upregulate TGF-β2 mRNA stability by decreasing N6-methyladenosine (m
A) modification. TGF-β signaling and the subsequent PI3K/AKT and STAT3 pathways, upregulated by RALYL, contribute to the enhancement of HCC stemness. Collectively, RALYL is a liver progenitor specific gene and regulates HCC stemness by sustaining TGF-β2 mRNA stability. These findings may inspire precise therapeutic strategies for HCC.
The development of enantioconvergent cross‐coupling of racemic alkyl halides directly with heteroarene C(sp2)−H bonds has been impeded by the use of a base at elevated temperature that leads to ...racemization. We herein report a copper(I)/cinchona‐alkaloid‐derived N,N,P‐ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp2)−H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α‐chiral alkylated azoles, such as 1,3,4‐oxadiazoles, oxazoles, and benzodoxazoles as well as 1,3,4‐triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp2)−H bond and the involvement of alkyl radical species under the reaction conditions.
The use of a cinchona‐alkaloid‐derived N,N,P‐ligand leads to the direct enantioconvergent coupling of racemic alkyl bromides with azole C(sp2)−H bonds by copper catalysis. The key to success is the ligand‐enabled facile oxidative addition at approximately room temperature that suppresses product racemization at elevated temperature. This method provides a range of enantioenriched α‐chiral alkylated azoles.
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