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Ulcerative colitis (UC) is characterized by increased cell death in intestinal epithelial cell (IEC), which compromises gut barrier function and activates inflammation. Aberrant mitochondrial dynamics have been implicated in various forms of cell death, but it is currently unclear if they play a role in IEC death and colitis pathogenesis. This study aims to investigate the contribution of aberrant mitochondrial dynamics to colitis progression using cellular models, animal models, and clinical samples. The results revealed that IEC in mice with Dextran sulfate sodium salt (DSS)-induced colitis exhibited dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and Z-DNA binding protein 1 (ZBP1)-dependent PANoptosis, which is a combination of apoptosis, necroptosis, and pyroptosis. However, these processes and the pathogenesis of DSS-induced colitis were significantly attenuated in IEC-specific Drp1 heterozygous knockout mice. Importantly, ZBP1-PANoptosis and Drp1-mediated mitochondrial fission were observed in IEC of UC patients, exhibiting a positive correlation with disease severity. Mechanistically, hyperactivated mitochondrial fission induced mitochondrial reactive oxygen species production leading to PANoptosis through ZBP1 sulfenylation at Cys327 independently of its Zα domain. Saquinavir, an FDA-approved drug identified through in-silico screening alongside in vivo and in vitro experiments, inhibits mitochondrial fission thereby enhancing therapeutic efficacy in mice with colitis.

The objective of this study was to assess and compare the characteristics of Yu-Shiang Shredded Pork made with different ingredients by using physicochemical measurements and intelligent sensory analysis. The study revealed that there were 18 varied amino acids present, with the taste active values (TAVs) of Leu, Glu, Asp, Asn, and Ala all higher than 1.0. Intelligent sensory analysis showed that the samples lacking lettuce and fungus had similar aromas and flavors, while those lacking shredded pork and pickled chillies had distinct aromas and flavors. Moreover, VOCs (volatile organic compounds) were detected in five types of Yu-Shiang Shredded Pork, with 43, 42, 53, 36, and 50 identified in GC-MS (gas chromatography-mass spectrometry), respectively. Olefins (20.62 %–30.93 %) were the most abundant. GC-IMS (gas chromatography-ion mobility spectrometry) detected 68 volatiles flavor compounds, with esters having a significantly higher relative content than other compounds, indicating their significant role in the flavor formation process of Yu-Shiang Shredded Pork. Furthermore, the Orthogonal Partial Least Squares-discriminant analysis (OPLS-DA) model analysis identified 19 marker compounds that could differentiate the five types of Yu-Shiang Shredded Pork. These fundamental results lay the groundwork for future research on the connection between ingredients and the flavor characteristics of Yu-Shiang Shredded Pork.

The hot deformation behavior of Mg-6Gd-5Y-0.3Zr alloy at the temperatures of 673–748 K and the strain rates of 0.01–1.0 s−1 were investigated by hot compression experiments. On this basis, a physically based internal state variable (ISV) model coupling the microstructural evolution was established, in which the ISVs of the model included dislocation density, grain size and volume fraction of dynamic recrystallization (DRX). Besides, the recrystallized and un-recrystallized grain sizes were considered to characterize the evolution process of microstructure. By comparing the calculated and experimental flow stresses, the model was proved to be reliable. Then the model was imported into the finite element analysis (FEA) software ABAQUS to predict the ISV evolution of Mg-6Gd-5Y-0.3Zr alloy in the hot extrusion process. The comparative analysis of the simulation and experimental results further verified the applicability of the constitutive model established in this study.

Summary: Phosphopeptides presented by major histocompatibility complex (MHC) class I have been regarded as a pivotal type of cancer neoantigens that are recognized by T cells. The structural basis of single-phosphorylated peptide presentation has been well studied. Diphosphorylation with one interval between two sites is one of the prevalent forms of multisite-phosphorylated peptides. Herein, we determined the molecular basis of presentation of two P4/P6 double pS-containing peptides by HLA-B27 and compared them with unmodified and single-phosphorylated peptide complexes. These data clarified not only the HLA allele-specific presentation of phosphopeptides by MHC class I molecules but also the cooperativity of peptide conformation within P4 and P6 phosphorylation sites. The phosphorylation of P6 site can influence the binding mode of P4 phosphorylated site to HLA-B27. And we found the diphospho-dependent attenuated effect of peptide binding affinity. This study provides insights into the MHC presentation features of diphosphopeptides, which is different from monophosphopeptides.

Background: Although ST-segment elevation (STE) has been used synonymously with acute coronary occlusion (ACO), current STE criteria miss nearly one-third of ACO and result in a substantial amount of false catheterization laboratory activations. As many other electrocardiographic (ECG) findings can reliably indicate ACO, we sought whether a new ACO/non-ACO myocardial infarction (MI) paradigm would result in better identification of the patients who need acute reperfusion therapy. Methods: A total of 3000 patients were enrolled in STEMI, non-STEMI and control groups. All ECGs were reviewed by two cardiologists, blinded to any outcomes, for the current STEMI criteria and other subtle signs. A combined ACO endpoint was composed of peak troponin level, troponin rise within the first 24 h and angiographic appearance. The dead or alive status was checked from hospital records and from the electronic national database. Results: In non-STEMI group, 28.2% of the patients were re-classified by the ECG reviewers as having ACO. This subgroup had a higher frequency of ACO, myocardial damage, and both in-hospital and long-term mortality compared to non-STEMI group. A prospective ACOMI/non-ACOMI approach to the ECG had superior diagnostic accuracy compared to the STE/non-STEMI approach in the prediction of ACO and long-term mortality. In Cox-regression analysis early intervention in patients with non-ACO-predicting ECGs was associated with a higher long-term mortality. Conclusions: We believe that it is time for a new paradigm shift from the STEMI/non-STEMI to the ACOMI/non-ACOMI in the acute management of MI. (DIFOCCULT study; ClinicalTrials.gov number, NCT04022668.)

Peripartum cardiomyopathy (PPCM) is a rare form of dilated cardiomyopathy that is associated with high maternal morbidity and mortality. Onset is usually between the last month of pregnancy and up to the fifth month postpartum. PPCM usually presents with signs and symptoms of heart failure and rarely with thromboembolic complications. The true incidence of thromboemboli in PPCM is unknown. Herein we report an unusual case of PPCM in a previously healthy woman who presented with recurrent transient ischemic attacks due to thrombus in the left ventricle. Resumo: A miocardiopatia periparto (MPP) é uma forma rara de miocardiopatia dilatada, associada a elevada mortalidade e morbilidade materna. A doença manifesta-se habitualmente entre o último mês de gravidez até ao 5.° mês depois do parto. A MPP apresenta-se habitualmente com sinais e sintomas de insuficiência cardíaca e, raramente, com complicações tromboembólicas. A verdadeira incidência de tromboembolismo na MPP não é conhecida. Apresentamos um caso, pouco habitual, de MPP em mulher previamente saudável que se apresentou com acidentes isquémicos transitórios recorrentes, devido à presença de trombo no ventrículo esquerdo. Keywords: Peripartum cardiomyopathy, Transient ischemic attacks, Transthoracic echocardiography, Palavras-chave: Miocardiopartia periparto, Acidente isquémico transitório, Ecocardiografia transtorácica

A new method of numerical simulating prediction and decontamination effect evaluation for abrasive jet decontamination to radioactively contaminated metal is proposed. Based on the Computational Fluid Dynamics and Discrete Element Model (CFD-DEM) coupled simulation model, the motion patterns and distribution of abrasives can be predicted, and the decontamination effect can be evaluated by image processing and recognition technology. The impact of three key parameters (impact distance, inlet pressure, abrasive mass flow rate) on the decontamination effect is revealed. Moreover, here are experiments of reliability verification to decontamination effect and numerical simulation methods that has been conducted. The results show that: 60Co and other homogeneous solid solution radioactive pollutants can be removed by abrasive jet, and the average removal rate of Co exceeds 80%. It is reliable for the proposed numerical simulation and evaluation method because of the well goodness of fit between predicted value and actual values: The predicted values and actual values of the abrasive distribution diameter are Ф57 and Ф55; the total coverage rate is 26.42% and 23.50%; the average impact velocity is 81.73 m/s and 78.00 m/s. Further analysis shows that the impact distance has a significant impact on the distribution of abrasive particles on the target surface, the coverage rate of the core area increases at first, and then decreases with the increase of the impact distance of the nozzle, which reach a maximum of 14.44% at 300 mm. It is recommended to set the impact distance around 300 mm, because at this time the core area coverage of the abrasive is the largest and the impact velocity is stable at the highest speed of 81.94 m/s. The impact of the nozzle inlet pressure on the decontamination effect mainly affects the impact kinetic energy of the abrasive and has little impact on the distribution. The greater the inlet pressure, the greater the impact kinetic energy, and the stronger the decontamination ability of the abrasive. But in return, the energy consumption is higher, too. For the decontamination of radioactively contaminated metals, it is recommended to set the inlet pressure of the nozzle at around 0.6 MPa. Because most of the Co elements can be removed under this pressure. Increasing the mass and flow of abrasives appropriately can enhance the decontamination effectiveness. The total mass of abrasives per unit decontamination area is suggested to be 50 g because the core area coverage rate of the abrasive is relatively large under this condition; and the nozzle wear extent is acceptable.

Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.

The anti-phagocytosis signal, CD47, prevents phagocytosis when it interacts with signal-regulatory protein alpha (SIRPα) on macrophages. Given the vital role of CD47 in immune response, further investigation on the regulation of CD47 in tumor microenvironment is needed. Herein, we identified that interferon-gamma (IFN-γ), one of the most important cytokines in the immune and inflammatory response, up-regulated CD47 expression in cancer cells and this effect could be inhibited by the JAK1/2 inhibitor ruxolitinib, as well as siRNA-mediated silencing of JAK1, STAT1, and IRF1. The IFN-γ-induced surface expression of CD47 contributed to a stronger binding affinity to SIRPα and a decrease in phagocytosis of cancer cells by macrophages. Knockdown of JAK1, STAT1, or IRF1 by siRNA reversed the decreased phagocytosis caused by IFN-γ. Besides, analysis from TCGA revealed that IFNG had a positive correlation with CD47 in various types of cancer, which was supported by the increased surface CD47 expression after IFN-γ treatment in different types of cancer cells. The discovery of IFN-γ-induced up-regulation of CD47 in cancer cells unveils another feedback inhibitory mechanism of IFN-γ, thus providing insights into cancer immunotherapy targeting CD47.

CD47 is overexpressed in various types of cancers and it can directly bind with SIRPα, which is mainly located on macrophages. The binding of CD47-SIRPα transmits a “don't eat me” signal, which can prevent cancer cells from immune clearance. Targeting the phagocytosis checkpoint of CD47-SIRPα axis has shown remarkable anticancer effect in preclinical and clinical research, which indicates the potential application of CD47-SIRPα blockade for cancer treatment. In this case, the comprehensive description of the regulation of CD47 in different types of cancer cells has significant implications for furthering our understanding of the role of CD47 in cancer. Based on the current reports, we summarized the regulatory factors, i.e., cytokines, oncogenes, microRNAs as well as enzymes, of CD47 expression in cancer cells. Accordingly, we also proposed several points needing further research, hoping to provide useful insights for the future investigation on the regulation of CD47 in cancers.

Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8 + T cells in the tumor microenvironment (TME). Depletion of CD8 + T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hepatocellular carcinoma (HCC) is a common malignant tumor. At present, early diagnosis of HCC is difficult and therapeutic methods are limited. Radiomics can achieve accurate quantitative evaluation of the lesions without invasion, and has important value in the diagnosis and treatment of HCC. Radiomics features can predict the development of cancer in patients, serve as the basis for risk stratification of HCC patients, and help clinicians distinguish similar diseases, thus improving the diagnostic accuracy. Furthermore, the prediction of the treatment outcomes helps determine the treatment plan. Radiomics is also helpful in predicting the HCC recurrence, disease-free survival and overall survival. This review summarized the role of radiomics in the diagnosis, treatment and prognosis of HCC., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Unlike the most of α-alkoxy coordination in α-hydroxycarboxylates to vanadium, novel α-hydroxy coordination to vanadium(IV) has been observed for a series of chiral and achiral monomeric α-hydroxycarboxylato vanadyl complexes [VO(H2cit)(bpy)]·2H2O (1), [VO(Hmal)(bpy)]·H2O (2), [VO(H2cit)(phen)]·1.5H2O (3), [VO(Hmal)(phen)]·H2O (4), and [(Δ)VO(S-Hcitmal)(bpy)]·2H2O (5), [VO(H2cit)(phen)]2·6.5H2O (6), which were isolated from the reactions of vanadyl sulfate with α-hydroxycarboxylates and N-heterocycle ligands in acidic solution. The complexes feature a tridentate citrate, malate or citramalate that chelates to vanadium atom through their α-hydroxy, α-carboxy and β-carboxy groups; while the other β-carboxylic acidic group of citrate is free to participate strong hydrogen bonds with lattice water molecule. The neutral α-hydroxy group also forms strong intermolecular hydrogen bonds with water molecule and the negatively-charged α-carboxy group in the environment. The inclusion of a hydrogen ion in α-alkoxy group results in the formation of a series of neutral complexes with one less positive charge. There are two different configurations of citrate with respect to the trans-position of axial oxo group, where the complex with trans-hydroxy configuration seems more stable with less hindrance. The average bond distances of V-Ohydroxy and V-Oα-carboxy are 2.196 and 2.003Å respectively, which are comparable to the VO distance (2.15Å) of homocitrate in FeV-cofactor of V-nitrogenase. A new structural model is suggested for R-homocitrato iron vanadium cofactor as VFe7S9C(R-Hhomocit) (H4homocit=homocitric acid) with one more proton in homocitrate ligand., (Copyright © 2014 Elsevier Inc. All rights reserved.)