Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis.

BACKGROUND: Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. METHOD: Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. RESULTS: Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. CONCLUSION: The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

Interpretable Predicting Creep Rupture Life of Superalloys: Enhanced by Domain-Specific Knowledge.

Evaluating and understanding the effect of manufacturing processes on the creep performance in superalloys poses a significant challenge due to the intricate composition involved. This study presents a machine-learning strategy capable of evaluating the effect of the heat treatment process on the creep performance of superalloys and predicting creep rupture life with high accuracy. This approach integrates classification and regression models with domain-specific knowledge. The physical constraints lead to significantly enhanced prediction accuracy of the classification and regression models. Moreover, the heat treatment process is evaluated as the most important descriptor by integrating machine learning with superalloy creep theory. The heat treatment design of Waspaloy alloy is used as the experimental validation. The improved heat treatment leads to a significant enhancement in creep performance (5.5 times higher than the previous study). The research provides novel insights for enhancing the precision of predicting creep rupture life in superalloys, with the potential to broaden its applicability to the study of the effects of heat treatment processes on other properties. Furthermore, it offers auxiliary support for the utilization of machine learning in the design of heat treatment processes of superalloys.

Box-copper catalyzed cascade asymmetric amidation for chiral exo-methylene aminoindoline derivatives.

Enantioselective copper-catalyzed cascade inter- and intramolecular amidation was achieved between ethynyl benzoxazinanones and α-halohydroxamates in the presence of an indapybox ligand. The one-pot cascade transformation was triggered by the attack of hydroxamates to dipolar copper-allenylidene intermediates, followed by a nucleophilic annulation reaction. Thus, a series of exo-methylene 3-aminoindoline derivatives were obtained in good yields with high enantioselectivities under mild reaction conditions.

Chiral Bidentate Phosphoramidite-Pd Catalyzed Asymmetric Decarboxylative Dipolar Cycloaddition for Multistereogenic Tetrahydrofurans with Cyclic N-Sulfonyl Ketimine Moieties.

An asymmetric [3 + 2] cycloaddition of vinyl ethylenecarbonates (VECs) and (E)-3-arylvinyl substituted benzo[d] isothiazole 1,1-dioxides has been developed using the Pd complex of a bidentate phosphoramidite (Me-BIPAM) as the catalyst, providing a wide variety of chiral multistereogenic vinyltetrahydrofurans in good yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, 99% ee).

Chiral Binaphthyl Box-Copper-Catalyzed Enantioselective Tandem Michael-Ketalization Annulations for Optically Active Aryl and Heteroaryl Fused Bicyclicnonanes.

The combination of chiral binaphthyl box-copper(II) with triflimide (Tf2NH) was identified as an efficient catalytic system for the asymmetric Michael/ketalization of (E)-2-hydroxyaryl-2-oxobut-3-enoates or (E)-ethyl 4-(2-aminoaryl)-2-oxobut-3-enoates with pyrazolone derivatives. The corresponding asymmetric tandem reactions provided a series of enantioenriched aryl and heteroaryl fused 2,8-O,O- or O,N-bicyclo[3.3.1]nonanes in high yields with excellent enantio- and diastereoselectivities.

Chiral N-Heterocyclic-Carbene-Catalyzed Cascade Asymmetric Desymmetrization of Cyclopentenediones with Enals: Access to Optically Active 1,3-Indandione Derivatives.

A chiral N-heterocyclic-carbene-catalyzed cascade asymmetric desymmetrization reaction of cyclopentenediones with enals has been successfully initiated, followed with tandem aldol annulation, aromatization, as well as sequential methylation. The reactions proceeded well under mild reaction conditions, with broad substrate scope and good functional group tolerance, providing a rapid access to highly functionalized chiral 2,2-disubstituted 1,3-indandione derivatives containing an all-carbon quaternary stereogenic center in moderate to good yields with high enantioselectivities.