Bioinformatics Identification of Regulatory Genes and Mechanism Related to Hypoxia-Induced PD-L1 Inhibitor Resistance in Hepatocellular Carcinoma.

The combination of a PD-L1 inhibitor and an anti-angiogenic agent has become the new reference standard in the first-line treatment of non-excisable hepatocellular carcinoma (HCC) due to the survival advantage, but its objective response rate remains low at 36%. Evidence shows that PD-L1 inhibitor resistance is attributed to hypoxic tumor microenvironment. In this study, we performed bioinformatics analysis to identify genes and the underlying mechanisms that improve the efficacy of PD-L1 inhibition. Two public datasets of gene expression profiles, (1) HCC tumor versus adjacent normal tissue (N = 214) and (2) normoxia versus anoxia of HepG2 cells (N = 6), were collected from Gene Expression Omnibus (GEO) database. We identified HCC-signature and hypoxia-related genes, using differential expression analysis, and their 52 overlapping genes. Of these 52 genes, 14 PD-L1 regulator genes were further identified through the multiple regression analysis of TCGA-LIHC dataset (N = 371), and 10 hub genes were indicated in the protein-protein interaction (PPI) network. It was found that POLE2, GABARAPL1, PIK3R1, NDC80, and TPX2 play critical roles in the response and overall survival in cancer patients under PD-L1 inhibitor treatment. Our study provides new insights and potential biomarkers to enhance the immunotherapeutic role of PD-L1 inhibitors in HCC, which can help in exploring new therapeutic strategies.

Flexible solar cells based on foldable silicon wafers with blunted edges.

Flexible solar cells have a lot of market potential for application in photovoltaics integrated into buildings and wearable electronics because they are lightweight, shockproof and self-powered. Silicon solar cells have been successfully used in large power plants. However, despite the efforts made for more than 50 years, there has been no notable progress in the development of flexible silicon solar cells because of their rigidity1-4. Here we provide a strategy for fabricating large-scale, foldable silicon wafers and manufacturing flexible solar cells. A textured crystalline silicon wafer always starts to crack at the sharp channels between surface pyramids in the marginal region of the wafer. This fact enabled us to improve the flexibility of silicon wafers by blunting the pyramidal structure in the marginal regions. This edge-blunting technique enables commercial production of large-scale (>240 cm2), high-efficiency (>24%) silicon solar cells that can be rolled similarly to a sheet of paper. The cells retain 100% of their power conversion efficiency after 1,000 side-to-side bending cycles. After being assembled into large (>10,000 cm2) flexible modules, these cells retain 99.62% of their power after thermal cycling between -70 °C and 85 °C for 120 h. Furthermore, they retain 96.03% of their power after 20 min of exposure to air flow when attached to a soft gasbag, which models wind blowing during a violent storm.

Surface Feature Prediction for Laser Ablated 40Cr13 Stainless Steel Based on Extreme Learning Machine.

Determining an optimal combination of laser process parameters can significantly improve the efficiency and quality of 40Cr13 steel surface processing. In this study, two machine learning models (ELMSS and ELMPS) were proposed to predict the processing results of surface features to optimize process parameters. The prediction accuracies of the proposed models were always higher than those of traditional back propagation (BP) and radial basis function (RBF) neural networks, and the calculation time of the proposed models was significantly reduced. In comparison, the prediction accuracy ranking for ablation depth was ELMSS (92.6%), BP (89.8%), and RBF (89.6%), and for the ablation width, it was ELMSS (98.3%), BP (97.4%), and RBF (96.1%). The material removal rate was 92.4%, 91.1%, and 89.1% for ELMSS, BP, and RBF, respectively. Finally, the prediction accuracy ranking for surface roughness was 86.8%, 80.7%, and 79.5% for ELMPS, BP, and RBF, respectively. After optimization by the genetic algorithm, the prediction accuracies of the proposed models for the depth, width, material removal rate, and surface roughness reached 94.0%, 99.0%, 93.2%, and 91.2%, respectively. With the support of ELMSS and ELMPS, the results of the surface features can be predicted before machining and the appropriate process parameters can be selected in advance.

Construction of Functionally Compartmental Inorganic Photocatalyst-Enzyme System via Imitating Chloroplast for Efficient Photoreduction of CO2 to Formic Acid.

Inorganic photocatalyst-enzyme systems are a prominent platform for the photoreduction of CO2 to value-added chemicals and fuels. However, poor electron transfer kinetics and enzyme deactivation by reactive oxygen species in the photoexcitation process severely limit catalytic efficiency. In chloroplast, enzymatic CO2 reduction and photoexcitation are compartmentalized by the thylakoid membrane, which protects enzymes from photodamage, while the tightly integrated photosystem facilitates electron transfer, promoting photocatalysis. By mimicking this strategy, we constructed a novel functionally compartmental inorganic photocatalyst-enzyme system for CO2 reduction to formate. To accomplish efficient electron transfer, we first synthesized an integrated artificial photosystem by conjugation of the cocatalyst (a Rh complex) onto thiophene-modified C3N4 (TPE-C3N4), demonstrating an NADH regeneration rate of 9.33 µM·min-1, 2.33 times higher than that of a homogeneous counterpart. The enhanced NADH regeneration activity was caused by the tightly conjugated structure of the artificial photosystem, enabling rapid electron transfer from TPE-C3N4 to the Rh complex. To protect formate dehydrogenase (FDH) from photoinduced deactivation, FDH was encapsulated into MAF-7, a metal-organic framework (MOF) material, to compartmentalize FDH from the toxic photoexcitation process, similar to the function of the thylakoid membrane. Moreover, the triazole linkers of MAF-7 possess both hydrophilicity and pH-buffering capacity providing a stable microenvironment for FDH, which could enhance enzyme stability in photosynthesis. The synergy between the enhanced electron transfer of TPE-C3N4 for NADH cofactor regeneration and MOF-protection of the redox enzyme enables the construction of a functionally compartmental inorganic photocatalyst-enzyme association system, promoting CO2 photoconversion to formic acid with a yield of 16.75 mM after 9 h of illumination, 3.24 times greater than that of the homogeneous reaction counterpart.