TRIM5 as a promising diagnostic biomarker of hepatocellular carcinoma: integrated analysis and experimental validation.

The TRIM family is associated with the membrane, and its involvement in the progression, growth, and development of various cancer types has been researched extensively. However, the role played by the TRIM5 gene within this family has yet to be explored to a great extent in terms of hepatocellular carcinoma (HCC). The data of patients relating to mRNA expression and the survival rate of individuals diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA) database. UALCAN was employed to examine the potential link between TRIM5 expression and clinicopathological characteristics. In addition, enrichment analysis of differentially expressed genes (DEGs) was conducted as a means of deciphering the function and mechanism of TRIM5 in HCC. The data in the TCGA and TIMER2.0 databases was utilized to explore the correlation between TRIM5 and immune infiltration in HCC. WGCNA was performed as a means of assessing TRIM5-related co-expressed genes. The "OncoPredict" R package was also used for investigating the association between TRIM5 and drug sensitivity. Finally, qRT-PCR, Western blotting (WB) and immunohistochemistry (IHC) were employed for exploring the differential expression of TRIM5 and its clinical relevance in HCC. According to the results that were obtained from the vitro experiments, mRNA and protein levels of TRIM5 demonstrated a significant upregulation in HCC tissues. It is notable that TRIM5 expression levels were found to have a strong association with the infiltration of diverse immune cells and displayed a positive correlation with several immune checkpoint inhibitors. The TRIM5 expression also displayed promising clinical prognostic value for HCC patients.

3D Oxide-Derived Ru Catalyst for Ultra-Efficient Hydrogenation of Levulinic Acid to γ-Valerolactone.

γ-valerolactone (GVL) is a key value-added chemical catalytically produced from levulinic acid (LA), an important biomass derivative platform chemical. Here an ultra-efficient 3D Ru catalyst generated by in situ reduction of RuZnOx nanoboxes is reported; the catalyst features a well-defined structure of highly dispersed in situ oxide-derived Ru (IOD-Ru) clusters (≈1 nm in size) spatially confined within the 3D nanocages with rich mesopores, which guarantees a maximized atom utilization with a high exposure of Ru active sites as well as a 3D accessibility for substrate molecules. The IOD-Ru exhibits ultrahigh performance for the hydrogenation of LA into GVL with a record-breaking turnover frequency (TOF) up to 59400 h-1 , 14 times higher than that of the ex situ reduction of RuZnOx nanoboxes catalyst. Structural characterizations and theoretical calculations collectively indicate that the defect-rich and coordination-unsaturated IOD-Ru sites can boost the activation of the carbonyl group in LA with a significantly lowered energy barrier of hydrogenation.

Anti-biofilm mechanism of a synthetical low molecular weight poly-d-mannose on Salmonella Typhimurium.

In this study, a low molecular weight poly-d-mannose (LMWM) was separated from a mixed polysaccharide synthesized previously. Monosaccharide composition, Fourier-Transform infrared spectroscopy (FT-IR), periodate oxidation and smith degradation were determined. After safety evaluation, the inhibition of LMWM on the different biofilm formation stages of Salmonella enterica serovar Typhimurium (S. Typhimurium) was tested in vitro. Furthermore, the effect of LMWM on the adhesion of S. Typhimurium to Caco-2 cells and cell surface hydrophobicity (CSH) were observed. Results indicated that LMWM was a homopolysaccharide without cytotoxicity and hemolysis, containing both α-mannose and ß-mannose. It showed obvious anti-biofilm activity on S. Typhimurium and mainly activated on the initial adhesion and formation stage, even better than the commercial S. cerevisiae mannan (CM). LMWM inhibited the adhesion of S. Typhimurium on Caco-2 cells with the inhibition rate of 61.04 % at 2 mg/ml. Meanwhile, LMWM decreased the hydrophobicity of S. Typhimurium cell surface. In conclusion, the inhibitory effect on S. Typhimurium biofilm was not caused by bacteriostatic or bactericidal activity of LMWM. The specific anti-adhesion and the decrease of bacterial CSH by LMWM may closely relate to anti-biofilm mechanism. This study provides some supports for the application of LMWM as antibiotics alternative on S. Typhimurium in the future.

Preoperative prediction of disease-free survival in pancreatic ductal adenocarcinoma patients after R0 resection using contrast-enhanced CT and CA19-9.

OBJECTIVES: To investigate the efficiency of a combination of preoperative contrast-enhanced computed tomography (CECT) and carbohydrate antigen 19-9 (CA19-9) in predicting disease-free survival (DFS) after R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 138 PDAC patients who underwent curative R0 resection were retrospectively enrolled and allocated chronologically to training (n = 91, January 2014-July 2019) and validation cohorts (n = 47, August 2019-December 2020). Using univariable and multivariable Cox regression analyses, we constructed a preoperative clinicoradiographic model based on the combination of CECT features and serum CA19-9 concentrations, and validated it in the validation cohort. The prognostic performance was evaluated and compared with that of postoperative clinicopathological and tumor-node-metastasis (TNM) models. Kaplan-Meier analysis was conducted to verify the preoperative prognostic stratification performance of the proposed model. RESULTS: The preoperative clinicoradiographic model included five independent prognostic factors (tumor diameter on CECT > 4 cm, extrapancreatic organ infiltration, CECT-reported lymph node metastasis, peripheral enhancement, and preoperative CA19-9 levels > 180 U/mL). It better predicted DFS than did the postoperative clinicopathological (C-index, 0.802 vs. 0.787; p < 0.05) and TNM (C-index, 0.802 vs. 0.711; p < 0.001) models in the validation cohort. Low-risk patients had significantly better DFS than patients at the high-risk, defined by the model preoperatively (p < 0.001, training cohort; p < 0.01, validation cohort). CONCLUSIONS: The clinicoradiographic model, integrating preoperative CECT features and serum CA19-9 levels, helped preoperatively predict postsurgical DFS for PDAC and could facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT: We constructed a simple model integrating clinical and radiological features for the prediction of disease-free survival after curative R0 resection in patients with pancreatic ductal adenocarcinoma; this novel model may facilitate preoperative identification of patients at high risk of recurrence and metastasis that may benefit from neoadjuvant treatments. KEY POINTS: • Existing clinicopathological predictors for prognosis in pancreatic ductal adenocarcinoma (PDAC) patients who underwent R0 resection can only be ascertained postoperatively and do not allow preoperative prediction. • We constructed a clinicoradiographic model, using preoperative contrast-enhanced computed tomography (CECT) features and preoperative carbohydrate antigen 19-9 (CA19-9) levels, and presented it as a nomogram. • The presented model can predict disease-free survival (DFS) in patients with PDAC better than can postoperative clinicopathological or tumor-node-metastasis (TNM) models.

Expansion of exhausted CD8+ T cells associates with increased pulmonary fungal infection risk in anti-melanoma differentiation associated gene 5 dermatomyositis.

OBJECTIVES: Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM). METHODS: Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed. RESULTS: CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828). CONCLUSIONS: CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.

Critical pulse in multi-shot femtosecond laser ablation on metallic surfaces.

Thermal effect remains a thorny issue for femtosecond-laser surface engineering and nanostructuring on metallic targets with high pulse energies or high repetition rates, which needs to be paid adequate attentions. Herein, we have experimentally investigated the heat diffusion and accumulations during single-shot and multi-shot femtosecond laser ablation on metallic surfaces. We have for the first time observed a novel phenomenon that the thermal effect was intensified abruptly when the laser-pulse number goes over a threshold (approximately between 10 and 20 for aluminum alloy with laser fluence of 6 J cm-2), accompanied with a dramatic reduction of ablated depth and complicated plasma dynamics. Based on both optical and thermodynamic analysis, we introduced a defocusing-dominated plasma-assistant model for this abnormal thermal effect. This work explored the critical experimental parameters for femtosecond-laser surface modification and processing in micro-scale engineering applications.

Human umbilical cord mesenchymal stem cells promoted tumor cell growth associated with increased interleukin-18 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is experiencing a concerning rise in both incidence and mortality rates. Current therapeutic strategies are limited in their effectiveness, largely due to the complex causes of the disease and significant levels of drug resistance. Given the latest developments in human umbilical cord mesenchymal stem cells (hUC-MSCs) research, there is a debate over the continued use of stem cell transplantation for treating tumors. Consequently, this study seeks to explore the role of hUC-MSCs in the management of HCC. METHODS AND RESULTS: HUC-MSCs increased the number (10.75 ± 1.50) in the DEN/TCPOBOP-induced mice hepatoma model, compared with DMSO group (7.25 ± 1.71). Moreover, the liver index in hUC-MSCs group (0.21 ± 0.06) was greater than that in DMSO group (0.09 ± 0.01). Immunohistochemical (IHC) analysis revealed that while hUC-MSCs did not alter Foxp3 expression, they significantly stimulated Ki67 expression, indicative of increased tumor cellular proliferation. Additionally, immunofluorescence (IF) studies showed that hUC-MSCs increased CD8+ T cell counts without affecting macrophage numbers. Notably, granzyme B expression remained nearly undetectable. We observed that serum IL-18 levels were higher in the hUC-MSCs group (109.66 ± 0.38 pg/ml) compared to the DMSO group (91.14 ± 4.37 pg/ml). Conversely, IL-1ß levels decreased in the hUC-MSCs group (63.00 ± 0.53 pg/ml) relative to the DMSO group (97.38 ± 9.08 pg/ml). CONCLUSIONS: According to this study, hUC-MSCs promoted the growth of liver tumors. Therefore, we proposed that hUC-MSCs are not suitable for treating HCC, as they exhibit clinically prohibited abnormalities.

YAP1 suppression inhibits autophagy and improves the efficacy of anti-PD-1 immunotherapy in hepatocellular carcinoma.

Anti-PD-1 immunotherapy is a promising treatment for hepatocellular carcinoma (HCC), but some patients with HCC do not experience clinical benefits. Autophagy promotes tumor progression and participates in drug resistance. Previous studies have revealed that suppressing the expression level of Yes-associated protein 1 (YAP1) improves anti-PD-1 therapy efficacy. Therefore, the relationship between YAP1 expression and autophagy activity during anti-PD-1 treatment was investigated in this study. A positive correlation was found between the expression level of YAP1 and LC3B by analyzing The Cancer Genome Atlas (TCGA), UALCAN databases, and HCC tissue microarray. Meanwhile, YAP1 expression and autophagy constituted positive feedback, in which YAP1 inhibition decreased the autophagy activity in liver tumor cells by hepatocyte-specific Yap1 knockout mice. Further, anti-PD-1 treatment increased autophagy and YAP1 expression levels in the cancer tissues from DEN/TCPOBOP-induced liver cancer mice. Finally, Yap1 knockout suppressed autophagy and improved anti-PD-1 therapy efficacy in hepatocyte-specific Yap1 knockout mice with liver tumors. These results suggested that YAP1 suppression was sensitized to anti-PD-1 treatment and inhibited autophagy activity in liver tumor cells. YAP1 is a promising target for improving the efficacy of anti-PD-1 immunotherapy in HCC.

[Study on mechanism of icariin-induced ferroptosis in HepG2 hepatoma carcinoma cells through PPARG/FABP4/GPX4 pathway].

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.

Phosphonium Iodide Featuring Blue Thermally Activated Delayed Fluorescence for Highly Efficient X-ray Scintillator.

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I-) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100%. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (kISC) and reverse intersystem crossing rate (kRISC), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy·s-1. This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance.

Heterogeneous Iridium Single-Atom Molecular-like Catalysis for Epoxidation of Ethylene.

Developing efficient and simple catalysts to reveal the key scientific issues in the epoxidation of ethylene has been a long-standing goal for chemists, whereas a heterogenized molecular-like catalyst is desirable which combines the best aspects of homogeneous and heterogeneous catalysts. Single-atom catalysts can effectively mimic molecular catalysts on account of their well-defined atomic structures and coordination environments. Herein, we report a strategy for selective epoxidation of ethylene, which exploits a heterogeneous catalyst comprising iridium single atoms to interact with the reactant molecules that act analogously to ligands, resulting in molecular-like catalysis. This catalytic protocol features a near-unity selectivity (99%) to produce value-added ethylene oxide. We investigated the origin of the improvement of selectivity for ethylene oxide for this iridium single-atom catalyst and attributed the improvement to the π-coordination between the iridium metal center with a higher oxidation state and ethylene or molecular oxygen. The molecular oxygen adsorbed on the iridium single-atom site not only helps to strengthen the adsorption of ethylene molecule by iridium but also alters its electronic structure, allowing iridium to donate electrons into the double bond π* orbitals of ethylene. This catalytic strategy facilitates the formation of five-membered oxametallacycle intermediates, leading to the exceptionally high selectivity for ethylene oxide. Our model of single-atom catalysts featuring remarkable molecular-like catalysis can be utilized as an effective strategy for inhibiting the overoxidation of the desired product. Implementing the concepts of homogeneous catalysis into heterogeneous catalysis would provide new perspectives for the design of new advanced catalysts.

Benefit of [18F] FDG PET/CT in the diagnosis and salvage treatment of recurrent nasopharyngeal carcinoma.

PURPOSE: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). METHODS: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. RESULTS: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). CONCLUSION: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS.

Dihydroartemisinin promoted FXR expression independent of YAP1 in hepatocellular carcinoma.

Loss of FXR, one of bile acid receptors, enlarged livers. Yes-associated protein 1 (YAP1), a dominant oncogene, promotes hepatocellular carcinoma (HCC). However, the relationship between FXR and YAP1 was unspecified in bile acid homeostasis in HCC. Here, we used TIMER2.0, the Cancer Genome Atlas (TCGA) Database, and Kaplan-Meier Plotter Database and discovered that FXR was positively correlated with better prognosis in liver cancer patients. Our previous research showed that dihydroartemisinin (DHA) inhibited cell proliferation in HepG2 and HepG22215 cells. However, the relationship of YAP1 and the bile acid receptor FXR remains elusive during DHA treatment. Furthermore, we showed that DHA improved FXR and reduced YAP1 in the liver cancer cells and mice. Additionally, the expression of nucleus protein FXR was enhanced in Yap1LKO mice with liver cancer. DHA promoted the expression level of whole and nuclear protein FXR independent of YAP1 in Yap1LKO mice with liver cancer. DHA declined cholesterol 7α-hydroxylase, but not sterol 27-hydroxylase, and depressed cholic acid and chenodeoxycholic acid of liver tissue in Yap1LKO mice with liver cancer. Generally, our results suggested that DHA improved FXR and declined YAP1 to suppress bile acid metabolism. Thus, we suggested that FXR acted as a potential therapeutic target in HCC.

Unveiling of incubation and absorption-enhanced effects occurring during multi-shot femtosecond laser ablation of aluminum and steel surfaces.

Interactions between ultrafast lasers and metal targets are crucial in various laser micro/nano-machinings. However, the underlying incubation and absorption-enhancement mechanisms remain elusive, which hinders the quality control of laser processing. Herein, we studied the incubation effect and absorption enhancement during multi-shot femtosecond-laser ablations via combining experiments and hydrodynamic simulations, taking aluminum alloy and stainless steels as paradigm materials. Accumulation effects of heat and damage-induced deformation were revealed by the evolutions of microstructures induced by low-energy femtosecond lasers. The calculated ablation thresholds were reduced with shot number, demonstrating the incubation effect. Calculation of threshold fluence via crater diameter is better than ablation depth, because that the latter is determined by different parameters at low- and high-energy conditions. Experimental observations and hydrodynamic simulations indicated that the enhanced absorption could be attributed to several factors, including laser-induced surface micro/sub-micro structures, photoionization, and plasma evolutions.

The relationship between the CUN-BAE body fatness index and incident diabetes: a longitudinal retrospective study.

BACKGROUND: The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index has been recommended as an ideal indicator of body fat and exhibited significant correlation with cardiometabolic risk factors. However, whether the CUN-BAE index correlates with incident diabetes in Asian populations is unknown. Therefore, this longitudinal study was designed to evaluate the association between baseline CUN-BAE index and type 2 diabetes mellitus (T2DM). METHODS: This retrospective longitudinal study involved 15,464 participants of 18-79 years of age in the NAGALA (NAfld in the Gifu Area Longitudinal Analysis) study over the period of 2004-2015. Cox proportional hazards regression was performed to test the relationship between the baseline CUN-BAE index and diabetes incidence. Further stratification analysis was conducted to ensure that the results were robust. The diagnostic utility of the CUN-BAE index was tested by the receiver operating characteristic (ROC) curve. RESULTS: Over the course of an average follow-up of 5.4 years, 373 (2.41%) participants developed diabetes. A higher diabetes incidence was associated with higher CUN-BAE quartiles (P for trend< 0.001). Each 1 unit increase in CUN-BAE index was associated with a 1.08-fold and 1.14-fold increased risk of diabetes after adjustment for confounders in males and females, respectively (both P < 0.001). Stratification analysis demonstrated a consistent positive correlation between baseline CUN-BAE and diabetes incidence. Moreover, based on ROC analysis, CUN-BAE exhibited a better capacity for diabetes prediction than both body mass index (BMI) and waist circumference (WC) in both sexes. CONCLUSIONS: The baseline CUN-BAE level was independently related to the incidence of diabetes. Increased adiposity determined by CUN-BAE could be used as a strong nonlaboratory predictor of incident diabetes in clinical practice.

Dihydroartemisinin broke the tumor immunosuppressive microenvironment by inhibiting YAP1 expression to enhance anti-PD-1 efficacy.

The efficacy of anti-PD-1 therapy is not as expected in hepatocellular carcinoma (HCC). YAP1 was overexpressed and activated in HCC. The mechanism of YAP1 in HCC immune escape is unclear. Anti-PD-1 treatment increased YAP1 expression in liver tumor cells, and exhausted CD4+ and CD8+ T cells in the blood and spleen of liver tumor mice. YAP1 knockdown suppressed PD-L1 expression, which was involved in JAK1/STAT1, 3 pathways. Moreover, Yap1 knockout elevated CD4+ and CD8+ T cells in liver tumor niche. Consistently, verteporfin, YAP1 inhibitor, decreased TGF-ß and IFN-γ in liver tumor niche and exhausted CD8+ T cell in the spleen. DHA suppressed YAP1 expression and break immune evasion in liver tumor niche, characterized by decreased PD-L1 in liver tumor cells and increased CD8+ T cell infiltration. Furthermore, DHA combined with anti-PD-1 treatment promoted CD4+ T cell infiltration in the spleen and CD8+ T cell in tumor tissues of mice. In summary, YAP1 knockdown in liver tumor cells suppressed PD-L1 expression and recruited cytotoxic T lymphocytes (CTLs), leading to break immune evasion in tumor niche. Mechanistically, YAP1 knockdown suppressed PD-L1 expression, which was involved in JAK1/STAT1, 3 pathways. Finally, DHA inhibited YAP1 expression, which not only inhibited liver tumor proliferation but also break the immunosuppressive niche in liver tumor tissues and improve the effect of anti-PD-1 therapy.

A bioartificial transgenic porcine whole liver expressing human proteins alleviates acute liver failure in pigs.

BACKGROUND: Preventing heterologous protein influx in patients is important when using xenogeneic bioartificial livers (BALs) to treat liver failure. The development of transgenic porcine livers synthesizing human proteins is a promising approach in this regard. Here, we evaluated the safety and efficacy of a transgenic porcine liver synthesizing human albumin (hALB) and coagulation factor VII (hFVII) within a bioartificial system. METHODS: Tibetan miniature pigs were randomly subjected to different interventions after surgery-induced partially ischemic liver failure. Group A (n = 4) was subjected to basic treatment; group B (n = 4) was to standard medical treatment and wild-type porcine BAL perfusion, and group C (n = 2) was to standard medical treatment and transgenic BAL perfusion. Biochemical parameters, coagulation status, survival time, and pathological changes were determined. Expressions of hALB and hFVII were detected using immunohistochemistry and enzyme-linked immunosorbent assays. RESULTS: The survival time in group A was 9.75 ± 1.26 days; this was shorter than that in both perfused groups, in which all animals reached an endpoint of 12 days (P = 0.006). Ammonia, bilirubin, and lactate levels were significantly decreased, whereas albumin and fibrinogen levels were increased after perfusion (all P < 0.05). hALB and hFVII were detected in transgenic BAL-perfused pig serum and ex vivo in the liver tissues. CONCLUSIONS: The humanized transgenic pig livers could synthesize and secrete hALB and hFVII ex vivo in a whole organ-based bioartificial system, while maintaining their metabolism, detoxification, transformation, and excretion functions, which were comparable to those observed in wild-type porcine livers. Therefore, the use of transgenic bioartificial whole livers is expected to become a new approach in treating acute liver failure.

Electromagnetic Radiation Effects on MgO-Based Magnetic Tunnel Junctions: A Review.

Magnetic tunnel junctions (MTJs) have been widely utilized in sensitive sensors, magnetic memory, and logic gates due to their tunneling magnetoresistance. Moreover, these MTJ devices have promising potential for renewable energy generation and storage. Compared with Si-based devices, MTJs are more tolerant to electromagnetic radiation. In this review, we summarize the functionalities of MgO-based MTJ devices under different electromagnetic irradiation environments, with a focus on gamma-ray radiation. We explore the effects of these radiation exposures on the MgO tunnel barriers, magnetic layers, and interfaces to understand the origin of their tolerance. This review enhances our knowledge of the radiation tolerance of MgO-based MTJs, improves the design of these MgO-based MTJ devices with better tolerances, and provides information to minimize the risks of irradiation under various irradiation environments. This review starts with an introduction to MTJs and irradiation backgrounds, followed by the fundamental properties of MTJ materials, such as the MgO barrier and magnetic layers. Then, we review and discuss the MTJ materials and devices' radiation tolerances under different irradiation environments, including high-energy cosmic radiation, gamma-ray radiation, and lower-energy electromagnetic radiation (X-ray, UV-vis, infrared, microwave, and radiofrequency electromagnetic radiation). In conclusion, we summarize the radiation effects based on the published literature, which might benefit material design and protection.

Theoretical Exploration of Properties of Iron-Silicon Interface Constructed by Depositing Fe on Si(111)-(7×7).

Exploring the properties of magnetic metal on the semiconductor surface is of great significance for the application of magnetic recording materials. Herein, DFT calculations are carried out to explore the properties of the iron-silicon interface structures (nFe/DASF) formed by depositing n Fe atoms on the reconstructed Si(111)-(7×7) surface (DASF). The stable nFe/DASF structures are studied in the cases of the adsorption and permeation of Fe atoms on the DASF. In both cases, Fe atoms are not very dispersed and prefer binding with Si atoms rather than the adsorbed Fe atoms, because the Fe-Si interaction is stronger than the Fe-Fe interaction. As the n value increases, the average binding energy (Eb_ave) of Fe generally firstly becomes more negative and then becomes less negative, with the presence of a 7Fe wheel as a stable geometry on the upmost surface. The presence of the 7Fe wheel is attributed to the enhanced Fe-Si interaction in this wheel compared to other geometries. CO adsorption occurs at the central Fe site of the 7Fe wheel which is greatly influenced by the surrounding Si atoms but is little influenced by the additional Fe atoms in the interlayer.

Photosynthesis of Benzonitriles on BiOBr Nanosheets Promoted by Vacancy Associates.

Photocatalytic organic functionalization reactions represent a green, cost-effective, and sustainable synthesis route for value-added chemicals. However, heterogeneous photocatalysis is inefficient in directly activating ammonia molecules for the production of high-value-added nitrogenous organic products when compared with oxygen activation in the formation of related oxygenated compounds. In this study, we report the heterogeneous photosynthesis of benzonitriles by the ammoxidation of benzyl alcohols (99 % conversion, 93 % selectivity) promoted using BiOBr nanosheets with surface vacancy associates. In contrast, the main reaction of catalysts with other types of vacancy sites is the oxidation of benzyl alcohol to benzaldehyde or benzoic acid. Experimental measurements and theoretical calculations have demonstrated a specificity of vacancy type with respect to product selectivity, which arises from the adsorption and activation of NH3 and O2 that is required to promote subsequent C-N coupling and oxidation to nitrile. This study provides a better understanding of the role of vacancies as catalytic sites in heterogeneous photocatalysis.