Blockade of the protein–protein interaction between the transmembrane protein programmed cell death protein 1 (PD‐1) and its ligand PD‐L1 has emerged as a promising immunotherapy for treating ...cancers. Using the technology of mirror‐image phage display, we developed the first hydrolysis‐resistant D‐peptide antagonists to target the PD‐1/PD‐L1 pathway. The optimized compound DPPA‐1 could bind PD‐L1 at an affinity of 0.51 μM in vitro. A blockade assay at the cellular level and tumor‐bearing mice experiments indicated that DPPA‐1 could also effectively disrupt the PD‐1/PD‐L1 interaction in vivo. Thus D‐peptide antagonists may provide novel low‐molecular‐weight drug candidates for cancer immunotherapy.
Protein chemical synthesis and mirror‐image phage display were combined to develop a proteolysis‐resistant D‐peptide antagonist (DPPA‐1) which targets the immune checkpoint protein PD‐L1 (the ligand for PD‐1, the programmed cell death protein 1). DPPA‐1 was found to inhibit the PD‐1/PD‐L1 protein–protein interaction at the cellular level. IgV=immunoglobulin‐like variable.
Predicting burn-through point (BTP) in advance is a quite critical task for the sintering process. However, sintering is a complex physicochemical reaction process, and the strong spatial–temporal ...correlations of data make the multistep prediction task very challenging. The previous BTP multistep prediction model only extracts spatial features in the high-level layers, leaving the spatial features in the low-level layers not learned. Specifically, the previous model only considers the relationships between the process variables and BTP, ignoring the spatial coupling relations among process variables. Further, the existing loss function is mainly based on Euclidean distance, which cannot learn dynamic information of multistep prediction sequence. To tackle these problems, in this article, we propose a 3-D convolution-based BTP multistep prediction model to simultaneously capture spatial–temporal features. First, the 3-D convolution is employed to capture the spatial–temporal features from low-level to high-level layers at the same time. Second, a spatial–temporal recalibration block is proposed to further refine the extracted features to increase the contributions of informative features and suppress the less useful ones. Finally, we design a time-aware multistep prediction loss function to dynamically weigh the similarity between the actual sequence and the predicted sequence. The experimental results on two real-world BTP datasets demonstrate the effectiveness and feasibility of the proposed model on the BTP multistep prediction task.
Electrochemical water splitting has been considered as an efficient way for the production of clean hydrogen fuel. To achieve high efficiency and reduce the cost of electrolyzers, non-precious ...bifunctional electrocatalysts, which can operate in the same electrolyte, are highly required. Here, we report a facile method for synthesizing self-supported NiMo nitride nanowire arrays as high-performance, binder-free bifunctional electrocatalysts. The binder-free electrodes exhibit excellent catalytic activities with a current density of 10 mA cm −2 at overpotentials of 22 mV for the hydrogen evolution reaction and 230 mV for the oxygen evolution reaction, respectively. Remarkably, to drive a current density of 10 mA cm −2 , the full water splitting system assembled with the self-supported nanowire arrays only needs a cell voltage of 1.507 V, significantly lower than that of the electrolyzer based on Pt/C and IrO 2 catalysts (1.540 V). Furthermore, the full water splitting system assembled with the self-supported NiMo nitride nanowire arrays shows an outstanding durability with a negligible current change at a large current density of 370 mA cm −2 for 30 h continuous electrolysis. The results presented here demonstrate that the development of self-supported electrodes is an efficient way for fabricating a high-performance, low-cost, robust and stable full water splitting device.
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•The state-of-the-art XGBoost algorithm is chosen as the mapping function of the tensile strength and plasticity.•The important features are ranked, based on the XGBoost model.•The ...key features are selected as variables for improved PSO optimization.•Results are analyzed theoretically, and proven to be effective and reliable.
Exploring the relationships between the properties of steels and their compositions and manufacturing parameters is extremely crucial and indispensable to understanding the science of materials, and subsequently developing new materials. Tensile strength and plasticity, as two important properties of steels, are key to the improvement and optimization of the mechanical properties of steels. In the present paper, we propose an optimization model combining XGBoost algorithm with improved PSO to address the continuous multivariable optimization problem. The main goal is to determine the mapping functions between the tensile strength and plasticity and their influencing factors, based on a diversity of machine learning models such as Linear Regression, SVM, XGBoost, etc. After evaluating the performance these models, we then select the XGBoost model with highest accuracy as the mapping function, which has not been done in previous studies. Moreover, the determined mapping function serves as the fitness value of particle swarm optimization, after which the tensile strength and plasticity optimization with many variables is realized. Finally, the experimental results are analyzed theoretically, and proven to be effective and reliable.
The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood.
COVID-19 survivors were ...recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated.
Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase.
Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae.
Key Scientific Research Projects of Henan Higher Education Institutions
Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as ...being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self-renewal.
Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has ...been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.
A Lewis acid (AgI, NiII, or FeII) catalyzed, CuII-mediated thiolation reaction between heteroarenes and thiols was achieved with good yield under base-free conditions. DMSO could serve as an ...effective methylthiolation reagent for the synthesis of heterocyclic methyl thioethers.
Abstract
The preparation of hierarchical zeolites with reduced diffusion limitation and enhanced catalyst efficiency has become a vital focus in the field of zeolites and porous materials chemistry ...within the past decades. This review will focus on the diffusion and catalyst efficiency of hierarchical zeolites and industrial catalysts. The benefits of diffusion and catalyst efficiency at two levels of hierarchies (zeolitic component level and industrial catalyst level) from a chemical reaction engineering point of view will be analysed. At zeolitic component level, three types of mesopores based on the strategies applied toward enhancing the catalyst effectiveness factor are presented: (i) ‘functional mesopores’ (raising effective diffusivity); (ii) ‘auxiliary mesopores’ (decreasing diffusion length); and (iii) ‘integrated mesopores’ (a combination thereof). At industrial catalyst level, location and interconnectivity among the constitutive components are revealed. The hierarchical pore interconnectivity in multi-component zeolite based industrial catalysts is exemplified by fluid catalytic cracking and bi-functional hydroisomerization catalysts. The rational design of industrial zeolite catalysts at both hierarchical zeolitic component and catalyst body levels can be fully comprehended using the advanced in situ and/or operando spectroscopic, microscopic and diffraction techniques.
Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still ...lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.
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