We studied the pseudo-homeothermic synaptic behaviors by integrating complimentary metal–oxide–semiconductor-compatible materials (hafnium oxide, aluminum oxide, and silicon substrate). A wide range ...of temperatures, from 25 °C up to 145 °C, in neuronal dynamics was achieved owing to the homeothermic properties and the possibility of spike-induced synaptic behaviors was demonstrated, both presenting critical milestones for the use of emerging memristor-type neuromorphic computing systems in the near future. Biological synaptic behaviors, such as long-term potentiation, long-term depression, and spike-timing-dependent plasticity, are developed systematically, and comprehensive neural network analysis is used for temperature changes and to conform spike-induced neuronal dynamics, providing a new research regime of neurocomputing for potentially harsh environments to overcome the self-heating issue in neuromorphic chips.
Together with the development of two-dimensional (2D) materials, transition metal dichalcogenides (TMDs) have become one of the most popular series of model materials for fundamental sciences and ...practical applications. Due to the ever-growing requirements of customization and multi-function, dozens of modulated structures have been introduced in TMDs. In this review, we present a systematic and comprehensive overview of the structure modulation of TMDs, including point, linear and out-of-plane structures, following and updating the conventional classification for silicon and related bulk semiconductors. In particular, we focus on the structural characteristics of modulated TMD structures and analyse the corresponding root causes. We also summarize the recent progress in modulating methods, mechanisms, properties and applications based on modulated TMD structures. Finally, we demonstrate challenges and prospects in the structure modulation of TMDs and forecast potential directions about what and how breakthroughs can be achieved.
This review provides a comprehensive overview of recent advances in the structure modulation of 2D transition metal chalcogenides, covering structure characteristics, methodology, mechanisms, applications, corresponding challenges and prospects.
The first effective organopolymerization of the biorenewable “non‐polymerizable” γ‐butyrolactone (γ‐BL) to a high‐molecular‐weight metal‐free recyclable polyester is reported. The superbase ...tert‐Bu‐P4 is found to directly initiate this polymerization through deprotonation of γ‐BL to generate reactive enolate species. When combined with a suitable alcohol, the tert‐Bu‐P4‐based system rapidly converts γ‐BL into polyesters with high monomer conversions (up to 90 %), high molecular weights (Mn up to 26.7 kg mol−1), and complete recyclability (quantitative γ‐BL recovery).
Recyclable and renewable: The fast organopolymerization of the biorenewable non‐strained γ‐butyrolactone has led to a high‐molecular‐weight metal‐free polyester with complete recyclability. The monomer has been long believed to be a non‐polymerizable monomer because of its stable five‐membered ring structure.
Background
The neutrophil-to-lymphocyte ratio (NLR) has been reported to be both a prognostic biomarker for cancer and associated with inflammation, but its predictive role in tumor immunity is not ...clear. The present study examined the correlations of the NLR and immune suppression with the prognoses in patients with esophageal squamous cell carcinoma (ESCC).
Methods
We performed a retrospective review of 1168 patients who were newly diagnosed with stage T1N(+) and T2–T4 ESCC at our hospital. The NLR of each ESCC patient prior to treatment was calculated, and the associations of the NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations of the proportion of myeloid-derived suppressor cells (MDSCs) and level of interleukin (IL)-6 with the NLR were assessed in 242 ESCC patients.
Results
An elevated NLR was significantly correlated with advanced-stage disease and reduced overall survival (OS) of ESCC patients. Furthermore, the levels of IL-6 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognoses of ESCC, and the NLR was positively correlated with MDSC levels in the circulation and IL-6 staining intensity in tumor specimens. Moreover, a high NLR was significantly associated with reduced OS in the 926 patients treated with concomitant chemoradiotherapy, but not in the 242 patients who underwent surgical intervention.
Conclusion
The NLR may represent a clinically useful biomarker to guide ESCC treatment decisions. Patients with a higher NLR may be an optimal subgroup for IL-6- and MDSC-targeted therapy.
Catalytic asymmetric cycloadditions of reactive ketene intermediates provide new opportunities for the production of chiral heterocyclic molecules. Though known for over 100 years, ketenes still ...remain underexplored in the field of transition-metal (TM)-catalyzed asymmetric cycloadditions because (1) ketenes, as highly electron-deficient species, are possibly unstable to low-valence TMs (i.e., decarbonylation or aggregation) and (2) the conventional thermal synthesis of ketenes from acyl chlorides and amines may be incompatible with TM catalysis (i.e., reactive acyl chloride and amine hydrochloride byproducts). Herein, we detail the unprecedented asymmetric 4+2 cycloaddition of vinyl benzoxazinanones with a variety of ketene intermediates via sequential visible-light photoactivation and palladium catalysis. It is well demonstrated that the traceless and transient generation of ketenes from α-diazoketones through visible-light-induced Wolff rearrangement is important for the success of present cycloaddition. Furthermore, chiral palladium catalysts with a new, chiral hybrid P, S ligand enable asymmetric cycloaddition with high reaction selectivity and enantiocontrol.
Poly‐ADP‐ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA‐deficient tumors. However, over 40% of BRCA‐deficient patients fail to respond to PARPi. Here, we ...report that thioparib, a next‐generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi‐sensitive and ‐resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1‐dependent DNA damage and replication stress, causing S‐phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR‐mediated DNA repair while increasing RAD51 foci formation. Notably, the on‐target inhibition of PARP7 by thioparib‐activated STING/TBK1‐dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome‐scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next‐generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier‐generation PARPi.
Synopsis
PARP inhibitors (PARPi) resistance is ubiquitous in the clinic. A newly discovered pan‐PARP inhibitor, thioparib, is highly effective against olaparib‐resistant cancer models, which suggests that therapeutic vulnerabilities still exist in PARPi‐resistant tumors.
Thioparib is a novel, potent, and orally bioavailable pan‐PARP inhibitor.
Thioparib overcomes primary and acquired olaparib resistance in vitro and in vivo.
Thioparib suppresses HR‐mediated DNA repair.
Thioparib induces a robust type I interferon response.
PARP inhibitors (PARPi) resistance is ubiquitous in the clinic. A newly discovered pan‐PARP inhibitor, thioparib, is highly effective against olaparib‐resistant cancer models, which suggests that therapeutic vulnerabilities still exist in PARPi‐resistant tumors.
Van der Waals (vdW) heterodiodes based on two-dimensional (2D) materials have shown tremendous potential in photovoltaic detectors and solar cells. However, such 2D photovoltaic devices are limited ...by low quantum efficiencies due to the severe interface recombination and the inefficient contacts. Here, we report an efficient MoS
/AsP vdW hetero-photodiode utilizing a unilateral depletion region band design and a narrow bandgap AsP as an effective carrier selective contact. The unilateral depletion region is verified via both the Fermi level and the infrared response measurements. The device demonstrates a pronounced photovoltaic behavior with a short-circuit current of 1.3 μA and a large open-circuit voltage of 0.61 V under visible light illumination. Especially, a high external quantum efficiency of 71%, a record high power conversion efficiency of 9% and a fast response time of 9 μs are achieved. Our work suggests an effective scheme to design high-performance photovoltaic devices assembled by 2D materials.
Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid ...adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPC
MAF-4
-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPC
MAF-4
-800 exhibited optimal water-sorption performance of 306 mg g
−1
at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPC
MAF-4
-800 achieved an unprecedentedly high water production rate of 380 mg g
−1
h
−1
at 40% RH, and could produce 1.77 L kg
−1
freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.
A MOF-derived nanoporous carbon (NPC
MAF-4
-800) with multiple N-doped sites, considerable porous characteristics and inherent photothermal properties demonstrated a superior water-production rate under a relatively arid climate.
Abstract
BRCA1 mutation carriers have a higher risk of developing triple-negative breast cancer (TNBC), which is a refractory disease due to its non-responsiveness to current clinical targeted ...therapies. Using the Sleeping Beauty transposon system in Brca1-deficient mice, we identified 169 putative cancer drivers, among which
Notch1
is a top candidate for accelerating TNBC by promoting the epithelial-mesenchymal transition (EMT) and regulating the cell cycle. Activation of NOTCH1 suppresses mitotic catastrophe caused by BRCA1 deficiency by restoring S/G2 and G2/M cell cycle checkpoints, which may through activation of ATR-CHK1 signalling pathway. Consistently, analysis of human breast cancer tissue demonstrates NOTCH1 is highly expressed in TNBCs, and the activated form of NOTCH1 correlates positively with increased phosphorylation of ATR. Additionally, we demonstrate that inhibition of the NOTCH1-ATR-CHK1 cascade together with cisplatin synergistically kills TNBC by targeting the cell cycle checkpoint, DNA damage and EMT, providing a potent clinical option for this fatal disease.
Summary
Background
Liver fibrosis is the strongest histological risk factor for liver‐related complications and mortality in metabolic dysfunction‐associated fatty liver disease (MAFLD). Second ...harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) is a powerful tool for label‐free two‐dimensional and three‐dimensional tissue visualisation that shows promise in liver fibrosis assessment.
Aim
To investigate combining multi‐photon microscopy (MPM) and deep learning techniques to develop and validate a new automated quantitative histological classification tool, named AutoFibroNet (Automated Liver Fibrosis Grading Network), for accurately staging liver fibrosis in MAFLD.
Methods
AutoFibroNet was developed in a training cohort that consisted of 203 Chinese adults with biopsy‐confirmed MAFLD. Three deep learning models (VGG16, ResNet34, and MobileNet V3) were used to train pre‐processed images and test data sets. Multi‐layer perceptrons were used to fuse data (deep learning features, clinical features, and manual features) to build a joint model. This model was then validated in two further independent cohorts.
Results
AutoFibroNet showed good discrimination in the training set. For F0, F1, F2 and F3‐4 fibrosis stages, the area under the receiver operating characteristic curves (AUROC) of AutoFibroNet were 1.00, 0.99, 0.98 and 0.98. The AUROCs of F0, F1, F2 and F3‐4 fibrosis stages for AutoFibroNet in the two validation cohorts were 0.99, 0.83, 0.80 and 0.90 and 1.00, 0.83, 0.80 and 0.94, respectively, showing a good discriminatory ability in different cohorts.
Conclusion
AutoFibroNet is an automated quantitative tool that accurately identifies histological stages of liver fibrosis in Chinese individuals with MAFLD.
Deep learning (DL) model and joint model (AutoFibroNet). Both deep learning models are used for automated classification and quantification of liver fibrosis stages, in which the AutoFibroNet uses multi‐layer perceptron (MLP) to integrate clinical features, manual features and DL features before classification.
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