Malignant progression of liver cancer progenitors requires lysine acetyltransferase 7-acetylated and cytoplasm-translocated G protein GαS.

BACKGROUND AND AIMS: Hepatocarcinogenesis goes through HCC progenitor cells (HcPCs) to fully established HCC, and the mechanisms driving the development of HcPCs are still largely unknown. APPROACH AND RESULTS: Proteomic analysis in nonaggregated hepatocytes and aggregates containing HcPCs from a diethylnitrosamine-induced HCC mouse model was screened using a quantitative mass spectrometry-based approach to elucidate the dysregulated proteins in HcPCs. The heterotrimeric G stimulating protein α subunit (GαS) protein level was significantly increased in liver cancer progenitor HcPCs, which promotes their response to oncogenic and proinflammatory cytokine IL-6 and drives premalignant HcPCs to fully established HCC. Mechanistically, GαS was located at the membrane inside of hepatocytes and acetylated at K28 by acetyltransferase lysine acetyltransferase 7 (KAT7) under IL-6 in HcPCs, causing the acyl protein thioesterase 1-mediated depalmitoylation of GαS and its cytoplasmic translocation, which were determined by GαS K28A mimicking deacetylation or K28Q mimicking acetylation mutant mice and hepatic Kat7 knockout mouse. Then, cytoplasmic acetylated GαS associated with signal transducer and activator of transcription 3 (STAT3) to impede its interaction with suppressor of cytokine signaling 3, thus promoting in a feedforward manner STAT3 phosphorylation and the response to IL-6 in HcPCs. Clinically, GαS, especially K28-acetylated GαS, was determined to be increased in human hepatic premalignant dysplastic nodules and positively correlated with the enhanced STAT3 phosphorylation, which were in accordance with the data obtained in mouse models. CONCLUSIONS: Malignant progression of HcPCs requires increased K28-acetylated and cytoplasm-translocated GαS, causing enhanced response to IL-6 and driving premalignant HcPCs to fully established HCC, which provides mechanistic insight and a potential target for preventing hepatocarcinogenesis.

BM-MSCs display altered gene expression profiles in B-cell acute lymphoblastic leukemia niches and exert pro-proliferative effects via overexpression of IFI6.

BACKGROUND: The tumor microenvironment (TME) is a supportive environment responsible for promoting the growth and proliferation of tumor cells. Current studies have revealed that the bone marrow mesenchymal stem cells (BM-MSCs), a type of crucial stromal cells in the TME, can promote the malignant progression of tumors. However, in the adult B-cell acute lymphoblastic leukemia (B-ALL) microenvironment, it is still uncertain what changes in BM-MSCs are induced by leukemia cells. METHODS: In this study, we mimicked the leukemia microenvironment by constructing a BM-MSC-leukemia cell co-culture system. In vitro cell experiments, in vivo mouse model experiments, lentiviral transfection and transcriptome sequencing analysis were used to investigate the possible change of BM-MSCs in the leukemia niche and the potential factors in BM-MSCs that promote the progression of leukemia. RESULTS: In the leukemia niche, the leukemia cells reduced the MSCs' capacity to differentiate towards adipogenic and osteogenic subtypes, which also promoted the senescence and cell cycle arrest of the MSCs. Meanwhile, compared to the mono-cultured MSCs, the gene expression profiles of MSCs in the leukemia niche changed significantly. These differential genes were enriched for cell cycle, cell differentiation, DNA replication, as well as some tumor-promoting biofunctions including protein phosphorylation, cell migration and angiogenesis. Further, interferon alpha-inducible protein 6 (IFI6), as a gene activated by interferon, was highly expressed in leukemia niche MSCs. The leukemia cell multiplication was facilitated evidently by IFI6 both in vitro and in vivo. Mechanistically, IFI6 might promote leukemia cell proliferation by stimulating SDF-1/CXCR4 axis, which leads to the initiation of downstream ERK signaling pathway. As suggested by further RNA sequencing analysis, the high IFI6 level in MSCs somewhat influenced the gene expression profile and biological functions of leukemia cells. CONCLUSIONS: BM-MSCs in the leukemia niche have varying degrees of changes in biological characteristics and gene expression profiles. Overexpression of IFI6 in BM-MSCs could be a key factor in promoting the proliferation of B-ALL cells, and this effect might be exerted through the SDF-1/CXCR4/ERK signal stimulation. Targeting IFI6 or related signaling pathways might be an important measure to reduce the leukemia cell proliferation.

Level of humanistic care ability and its influencing factors among nursing aides in long-term care facilities.

OBJECTIVE: To determine the level and influencing factors of the humanistic care ability (HCA) in nursing aides, thus providing a baseline for its improvement. METHODS: This study investigated 302 nursing aides in six long-term care facilities (LTCFs) in Suzhou between December 2021 and June 2022 by convenience sampling. A descriptive questionnaire and the Caring Ability Inventory were applied in this study. RESULTS: The HCA was at a low level, and its influencing factors were education level, marital status, personality, reason for employment, and the degree of perceived care from colleagues (p<0.05). CONCLUSIONS: Nursing aides' HCA needs to be strengthened urgently. Nursing aides with poor education, widowed, single, and an introversion type of personality should receive more attention. Additionally, creating a warm atmosphere among colleagues and cultivating the nursing aides' motivation for eldercare will help improve their HCA.

Collagens I and V differently regulate the proliferation and adhesion of rat islet INS-1 cells through the integrin ß1/E-cadherin/ß-catenin pathway.

Extracellular matrix (ECM) plays an important role in tissue repair, cell proliferation, and differentiation. Our previous study showed that collagen I and collagen V differently regulate the proliferation of rat pancreatic ß cells (INS-1 cells) through opposite influences on the nuclear translocation of ß-catenin. In this study, we investigated the ß-catenin pathway in INS-1 cells on dishes coated with collagen I or V. We found that nuclear translocation of the transcription factor Yes-associated protein (YAP) was enhanced by collagen I and suppressed by collagen V, but had no effect on INS-1 cell proliferation. Morphologically, INS-1 cells on collagen V-coated dishes showed stronger cell-to-cell adhesion, while the cells on collagen I-coated dishes showed weaker cell-to-cell adhesion in comparison with the cells on non-coated dishes. E-cadherin played an inhibitory role in the proliferation of INS-1 cells cultured on collagen I or collagen V coated dishes via regulation of the nuclear translocation of ß-catenin. Integrin ß1 was enhanced with collagen I, while it was repressed with collagen V. The integrin ß1 pathway positively regulated the cell proliferation. Inhibition of integrin ß1 pathway restored the protein level of E-cadherin and inhibited the nuclear translocation of ß-catenin in the cells on collagen I-coated dishes, but no effect was observed in the cells on collagen V-coated dishes. In conclusion, collagen I enhances the proliferation of INS-1 cells via the integrin ß1 and E-cadherin/ß-catenin signaling pathway. In INS-1 cells on collagen V-coated dishes, both integrin ß1 and E-cadherin/ß-catenin signal pathways are involved in the inhibition of proliferation.

A Novel Mutant of rLj-RGD3 (rLj-112) Suppressed the Proliferation and Metastasis of B16 Cells through the EGFR Signaling Pathway.

Lj-RGD3, which contains three Arg⁻Gly⁻Asp (RGD) motifs, was first identified from the buccal glands of Lampetra japonica and has been shown to suppress the tumor progression in the previous studies. Apart from the three RGD motifs, Lj-RGD3 is also characterized by its high content of histidine in its amino acid sequence. In order to clarify whether the histidine-rich characterization of Lj-RGD3 is also associated with its anti-tumor activity, mutants were designed in which the three RGD motifs (Lj-112), or all histidines (Lj-27) or both (Lj-26) were deleted. Furthermore, a mutant (Lj-42) in which all histidines and three RGD motifs were respectively substituted with alanines and three Ala⁻Gly⁻Asp (AGD) motifs, as well as a mutant (Lj-41) in which all histidines were substituted with alanines was synthesized to avoid alterations in structure which might further cause changes in the peptides' functions. After recombination and purification, recombinant Lj-112 (rLj-112), recombinant Lj-27 (rLj-27), recombinant Lj-41 (rLj-41), and recombinant Lj-RGD3 (rLj-RGD3) exhibited anti-proliferative activity in B16 cells, respectively; while recombinant Lj-26 (rLj-26) and recombinant Lj-42 (rLj-42) did not affect the proliferation of B16 cells significantly. In addition, the anti-proliferative activity of rLj-112 in B16 cells was due to apoptosis. Typical apoptosis features were observed, including chromatin condensation, fragmented DNA, and increased levels of cleaved caspase 3/caspase 7/nuclear enzyme poly (ADP-ribose) polymerase (PARP) in B16 cells. Similar to rLj-RGD3, rLj-112 was also capable of suppressing the migration and invasion of B16 cells by disturbing the F-actin arrangement. After labeling with FITC, rLj-112 was found localized in the cytoplasm of B16 cells, which induced the internalization of epidermal growth factor receptor (EGFR), suggesting that rLj-112 might block the EGFR mediated signaling pathway. Actually, the phosphorylation level of EGFR and its downstream signal molecules including Akt, PI3K, p38, and ERK1/2 was reduced in the rLj-112 treated B16 cells. In vivo, rLj-112 also inhibited the growth, weight, and volume of the tumors in B16 xenografted C57BL/6 mice without reducing their body weight, indicating that rLj-112 might be safe and might be used as an effective anti-tumor drug in the near future.

Multi-Server Multi-User Multi-Task Computation Offloading for Mobile Edge Computing Networks.

This paper studies mobile edge computing (MEC) networks where multiple wireless devices (WDs) offload their computation tasks to multiple edge servers and one cloud server. Considering different real-time computation tasks at different WDs, every task is decided to be processed locally at its WD or to be offloaded to and processed at one of the edge servers or the cloud server. In this paper, we investigate low-complexity computation offloading policies to guarantee quality of service of the MEC network and to minimize WDs' energy consumption. Specifically, both a linear programing relaxation-based (LR-based) algorithm and a distributed deep learning-based offloading (DDLO) algorithm are independently studied for MEC networks. We further propose a heterogeneous DDLO to achieve better convergence performance than DDLO. Extensive numerical results show that the DDLO algorithms guarantee better performance than the LR-based algorithm. Furthermore, the DDLO algorithm generates an offloading decision in less than 1 millisecond, which is several orders faster than the LR-based algorithm.

Bismuth oxymetallate-modified biochar derived from Euryale ferox husk for efficient removal of Congo red from wastewater: adsorption behavior and mechanisms.

Using Euryale ferox husk as raw material, pristine biochar (EBC), Bi2MoO6-modified biochar (BM-EBC), and BiFeO3-modified biochar (BF-EBC) were prepared and employed for decontaminating Congo red (CR) from wastewater. Compared with EBC (217.59 mg/g) and BF-EBC (359.49 mg/g), a superior adsorption capacity of 460.77 mg/g was achieved by BM-EBC. Based on the evaluation results of the Freundlich and pseudo-second-order models, multilayer chemisorption was suggested as the adsorption mechanism. The adsorption process of BM-EBC was spontaneous and endothermic, and the rate-limiting step pertained to liquid film diffusion and intraparticle diffusion. The underlying removal mechanism was explored via SEM, BET, FTIR, XPS, Raman spectra, and Zeta potential analyses. The introduction of bismuth oxymetallates with their high number of M-O (M: Bi, Mo, Fe) structural elements provided the adsorbent with enlarged surface areas and reinforced oxygen functional groups, thereby promoting pore filling, π-π interactions, hydrogen bonding, and complexation, leading to enhanced adsorption capacity. These results demonstrate that Euryale ferox husk biochar modified by bismuth oxymetallates has high prospects for valorizing biomass waste and removing CR from wastewater.

Converted paddy to upland in saline-sodic land could improve soil ecosystem multifunctionality by enhancing soil quality and alleviating microbial metabolism limitation.

Soil salinization is one of the major soil degradation threats worldwide, and parameters related to soil quality and ecosystem multifunctionality (EMF) are crucial for evaluating the success of reclamation efforts in saline-sodic wasteland (WL). Microbial metabolic limitation is also one of the main factors that influences EMF in agricultural cropping systems. A ten-year localization experiment was conducted to reveal the key predictors of soil quality index (SQI) values, microbial metabolic characteristics, and EMF in different farmland cropping systems. A random forest model showed that the ß-glucosidase (BG), cellobiosidase (CBH) and saturated hydraulic conductivity (SHC) of the SQI factors were the main driving forces of soil EMF. Compared to monoculture models, such as paddy field (PF) or upland field (UF), the converted paddy field to upland field (CF) cropping system was most effective at improving EMF in reclaimed saline-sodic WL, increasing this metric by 275.35 %. CF integrates practices from both PF and UF planting systems, improved soil quality and relieves microbial metabolic limitation. Specifically, both CF and PF significantly reduced soil pH (by 16-23 %) and sodium adsorption ration (SAR) (by 65-83 %) and significantly reduced the abundance of large macroaggregates. Moreover, CF significantly improved soil saturated hydraulic conductivity relative to PF and UF (p < 0.05), indicating an improvement in soil physical properties. Overall, although reclamation improved SQI compared to WL (0.25), the EMF of CF (0.56) was significantly higher than that of other treatments (p < 0.05). Thus, while increasing SQI can improve soil EMF, it was not as effective alone as it was when combined with more comprehensive efforts that focus on improving various soil properties and alleviating microbial metabolic limitations. Therefore, our results suggested that future saline-sodic wasteland reclamation efforts should avoid monoculture systems to enhance soil EMF.

One-dimensional hybrid copper halides with high-efficiency photoluminescence as scintillator.

A new one-dimensional hybrid [APCHA]Cu2I4 was designed and applied as an X-ray scintillator. It exhibits broad-band green emission with a high PLQY of 74.80% and excellent stability. It demonstrates radioluminescence property with a light yield of 28 336 photons MeV-1, detection limit of 41 nGyair s-1, and high spatial limit of 13.95 lp mm-1 in X-ray imaging.

Identification of a novel monocyte/macrophage-related gene signature for predicting survival and immune response in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematological tumor with poor immunotherapy effect. This study was to develop a monocyte/macrophage-related prognostic risk score (MMrisk) and identify new therapeutic biomarkers for AML. We utilized differentially expressed genes (DEGs) in combination with single-cell RNA sequencing to identify monocyte/macrophage-related genes (MMGs). Eight genes were selected for the construction of a MMrisk model using univariate Cox regression analysis and LASSO regression analysis. We then validated the MMrisk on two GEO datasets. Lastly, we investigated the immunologic characteristics and advantages of immunotherapy and potential targeted drugs for MMrisk groups. Our study identified that the MMrisk is composed of eight MMGs, including HOPX, CSTB, MAP3K1, LGALS1, CFD, MXD1, CASP1 and BCL2A1. The low MMrisk group survived longer than high MMrisk group (P < 0.001). The high MMrisk group was positively correlated with B cells, plasma cells, CD4 memory cells, Mast cells, CAFs, monocytes, M2 macrophages, Endothelial, tumor mutation, and most immune checkpoints (PD1, Tim-3, CTLA4, LAG3). Furthermore, drug sensitivity analysis showed that AZD.2281, Axitinib, AUY922, ABT.888, and ATRA were effective in high-risk MM patients. Our research shows that MMrisk is a potential biomarker which is helpful to identify the molecular characteristics of AML immunology.

Dual roles of CD11b+CD33+HLA-DR-/lowCD14- myeloid-derived suppressor cells with a granulocytic morphology following allogeneic hematopoietic stem cell transplantation: from inflammation promoters to immune suppressors within 90 days.

Introduction: Granulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions. Methods: G-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in G-MDSCs were analyzed via RNA sequencing to investigate functional transitions. Results: G-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes. Conclusion: Our findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Directional methanolysis of kitchen waste for the co-production of methyl levulinate and fatty acid methyl esters: Catalytic strategy and machine learning modeling.

To add value to ordinary kitchen waste, heterogeneous acid-base catalytic methanolysis was conducted to produce high-value liquid biofuels, methyl levulinate (ML) and fatty acid methyl esters (FAMEs). Yields of 53.3 % ML and 98.5 % FAME were achieved by methanolysis of kitchen waste under the co-catalysis of carbon-silica composite (C/Si-SO3H) and zirconium modified ultrastable Y zeolite (Zr/USY). These target products can be easily recovered from the methanolic phase and can be purified at the end of the reaction. The collaborative combination of C/Si-SO3H and Zr/USY exhibited higher activity than their commercial counterpart. This strategy can be applied to differently composed kitchen waste and kitchen waste with different water content. Product yields were predicted using an artificial neural network method, and the relative importance of the influencing factors was investigated by the random forest method. The systematic insight gained from this work supports the value-added utilization of kitchen waste.

Mitochondrial IRG1 traps MCL-1 to induce hepatocyte apoptosis and promote carcinogenesis.

Hepatocarcinogenesis is initiated by repeated hepatocyte death and liver damage, and the underlying mechanisms mediating cell death and the subsequent carcinogenesis remain to be fully investigated. Immunoresponsive gene 1 (IRG1) and its enzymatic metabolite itaconate are known to suppress inflammation in myeloid cells, and its expression in liver parenchymal hepatocytes is currently determined. However, the potential roles of IRG1 in hepatocarcinogenesis are still unknown. Here, using the diethylnitrosamine (DEN)-induced hepatocarcinogenesis mouse model, we found that IRG1 expression in hepatocytes was markedly induced upon DEN administration. The DEN-induced IRG1 was then determined to promote the intrinsic mitochondrial apoptosis of hepatocytes and liver damage, thus enhancing the subsequent hepatocarcinogenesis. Mechanistically, the mitochondrial IRG1 could associate and trap anti-apoptotic MCL-1 to inhibit the interaction between MCL-1 and pro-apoptotic Bim, thus promoting Bim activation and downstream Bax mitochondrial translocation, and then releasing cytochrome c and initiating apoptosis. Thus, the inducible mitochondrial IRG1 promotes hepatocyte apoptosis and the following hepatocarcinogenesis, which provides mechanistic insight and a potential target for preventing liver injury and HCC.

Value of three-dimensional visualization of preoperative prostatic magnetic resonance imaging based on measurements of anatomical structures in predicting positive surgical margin after radical prostatectomy.

Background: Positive surgical margin (PSM) or apical positive surgical margin (APSM) is an established predictive factor of biochemical recurrence or disease progression in prostate cancer (PCa) patients after radical prostatectomy. Since there are limited usable magnetic resonance imaging (MRI)-based models, we sought to explore the role of three-dimensional (3D) visualization for preoperative MRI in the prediction of PSM or APSM. Methods: From December 2016 to April 2022, 149 consecutive PCa patients who underwent radical prostatectomy were retrospectively selected from the Second Affiliated Hospital of Dalian Medical University. According to the presence of PSM or APSM, patients were divided into a PSM group (n=41) and a without PSM group (n=108) and into an APSM group (n=33) and a without APSM group (n=116). Twenty-one parameters, including prostate apical shape, PCa distance to the membranous urethra, and pubic angle, were measured on 3D visualization of MRI. The development of the nomogram models was built by the findings of multivariate logistic regression analysis for significant factors. Results: To predict the probability of PSM, a longer PCa distance to the membranous urethra (OR=0.136, p=0.019) and the distance from the anterior peritoneum to the anterior border of the coccyx (work space AP, OR=0.240, p=0.030) were independent protective factors, while a type 3 prostate apical shape (OR=8.262, p=0.025) and larger pubic angle 2 (OR=5.303, p=0.029) were identified as independent risk factors. The nomogram model presented an area under the curve (AUC) of the receiver operating characteristic curve (ROC) of PSM of 0.777. In evaluating the incidence of APSM, we found that the distance to the membranous urethra (OR=0.135, p=0.014) was associated with a low risk of APSM, while larger pubic angle 1 (OR=4.666, p=0.043) was connected to a higher risk of APSM. The nomogram model showed that the AUC of APSM was 0.755. Conclusion: As 3D visualization for preoperative MRI showed good performance in predicting PSM or APSM, the tool might be potentially valuable, which also needs to be validated by multicenter, large-scale, prospective studies.

Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Catalytic conversion of carbohydrates into 5-ethoxymethylfurfural using γ-AlOOH and CeO2@B2O3 catalyst synergistic effect.

Selective catalytic conversion of carbohydrates to 5-ethoxymethylfurfural (EMF) is a critical approach to the biorefinery. In this work, solid acid catalysts of γ-AlOOH and CeO2@B2O3 were used to convert carbohydrates to EMF in a one-pot process, performed in an ethanol/DMSO solvent system. The synergistic effect of γ-AlOOH and CeO2@B2O3 was studied. Furthermore, the morpho-structural properties of the catalysts were characterized, and the effects of reaction time, reaction temperature, catalyst load, and the amount of cosolvent on the conversion of glucose to EMF were examined and optimized. Under the reaction conditions of 170 °C for 20 h, glucose, sucrose, cellobiose, inulin and starch were used as raw materials, and the EMF yield range was 9.2-27.7%. The results showed that the synergistic effect of γ-AlOOH and CeO2@B2O3 further causes the combination of multiple acid sites with different types and strength distributions. Particularly, the collaboration between weak, medium-strong, and strong acid, as well as between Lewis and Brønsted acidity, is of great significance for EMF generation. The reusability experiments showed that the combined catalytic system was easily separated and maintained catalytic activity for five successive reactions without further intermediate regeneration steps. This work provides a promising route for the catalytic conversion of biomass-derived carbohydrates into EMF.

Silibinin improves L-cell mass and function through an estrogen receptor-mediated antioxidative mechanism.

BACKGROUND: Silibinin, a major component of milk thistle extract silymarin, promotes hypoglycemia by activating estrogen receptor (ER) α and ß-mediated pathways in pancreatic ß-cells. Glucagon-like peptide-1 (GLP-1) is the enteroendocrine peptide produced in L-cells, and it controls glucose homeostasis through multiple pathways. The effect of silibinin on L-cell mass and function is still unknown. PURPOSE: The protective effect of silibinin on palmitate (PA)-treated intestinal L-cell line GLUTag cells and the SHRSP•Z-Leprfa/Izm-Dmcr (SP•ZF) diabetic rat model was investigated in current study. METHODS: After pre-incubation with 50 µM silibinin for 4 h, GLUTag cells were treated with 0.125 mM PA. MTT, Annexin V/PI apoptosis, Hoechst 33342 staining, western blot, DCFH-DA, GLP-1 ELISA, qRT-PCR and immunofluorescence analyses were undertaken to determine ER-dependent protection of silibinin against PA-induced cellular damage. The differential protein expression of GLUTag cells under different treatments was examined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). The SP•ZF diabetic rat model was chosen for in vivo study. After 4 weeks of gastric gavage with 100 or 300 mg kg-1 of silibinin, the physiological indexes of the rats were measured. Cells expressing GLP-1, 8­hydroxy-2'-deoxyguanosine (8-OHdG), ERα, and/or ERß in duodenum tissues were detected by immunofluorescence. RESULTS: The current study showed that the GLUTag cells preincubated with silibinin activated the transcription factor nuclear erythroid-2 like factor-2 (Nrf2)-antioxidant pathway, reduced reactive oxygen species (ROS) generation, and improved cell survival and GLP-1 content, while the antioxidative effect of silibinin was blocked by the selective ERα antagonist MPP or ERß antagonist PHTPP in GLUTag cells. Our proteomics data further revealed that ERα or ß inactivation reduced glutathione peroxide and proteins associated with endocytosis and reproduction, thus at least partially reversing the protective effect of silibinin. SP•ZF rats received silibinin treatment showed increased serum GLP-1 content and improved glucose homeostasis. Furthermore, silibinin upregulated ERα and ß levels and reduced the level of 8-OHdG in GLP-1-positive cells. CONCLUSIONS: Our study showed that silibinin improved L-cell mass and function through an ER-mediated antioxidant pathway, and the proteomics analysis revealed for the first time the differential regulation of proteins by PA and silibinin in GLUTag cells.

JMJD4-demethylated RIG-I prevents hepatic steatosis and carcinogenesis.

BACKGROUND: Hepatocarcinogenesis is driven by necroinflammation or metabolic disorders, and the underlying mechanisms remain largely elusive. We previously found that retinoic acid-inducible gene-I (RIG-I), a sensor for recognizing RNA virus in innate immune cells, is mainly expressed by parenchymal hepatocytes in the liver. However, its roles in hepatocarcinogenesis are unknown, which is intensively investigated in this study. METHODS: DEN-induced necroinflammation-driven hepatocarcinogenesis and STAM NASH-hepatocarcinogenesis were carried out in hepatocyte-specific RIG-I knockout mice. The post-translational modification of RIG-I was determined by mass spectrometry, and specific antibodies against methylated lysine sites and the RIG-I lysine mutant mice were constructed to identify the functions of RIG-I methylation. RESULTS: We interestingly found that DEN-induced hepatocarcinogenesis was enhanced, while NASH-induced hepatocarcinogenesis was suppressed by hepatocyte-specific RIG-I deficiency. Further, IL-6 decreased RIG-I expression in HCC progenitor cells (HcPCs), which then viciously promoted IL-6 effector signaling and drove HcPCs to fully established HCC. RIG-I expression was increased by HFD, which then enhanced cholesterol synthesis and steatosis, and the in-turn NASH and NASH-induced hepatocarcinogenesis. Mechanistically, RIG-I was constitutively mono-methylated at K18 and K146, and demethylase JMJD4-mediated RIG-I demethylation suppressed IL-6-STAT3 signaling. The constitutive methylated RIG-I associated with AMPKα to inhibit HMGCR phosphorylation, thus promoting HMGCR enzymatic activity and cholesterol synthesis. Clinically, RIG-I was decreased in human hepatic precancerous dysplastic nodules while increased in NAFLD livers, which were in accordance with the data in mouse models. CONCLUSIONS: Decreased RIG-I in HcPCs promotes necroinflammation-induced hepatocarcinogenesis, while increased constitutive methylated RIG-I enhances steatosis and NASH-induced hepatocarcinogenesis. JMJD4-demethylated RIG-I prevents both necroinflammation and NASH-induced hepatocarcinogenesis, which provides mechanistic insight and potential target for preventing HCC.

[Determination of 1, 1-dichloro-l-nitroethane in air of workplaces by gas chromatography].

OBJECTIVE: To establish a gas chromatography method for detecting the concentration of 1,1-dichloro-1-nitroethane in air of workplaces. METHOD: 1,1-dichloro-1-nitroethane in air of workplaces was collected by activated charcoal tube, absorbed using carbon disulfide and analyzed by Gas Chromatography (FID) with FFAP capillary column. RESULTS: The linear rang of 1,1-dichloro-1-nitroethane in this method was 4.0-858.2 microg/ml, the linear regression formula was Y = 283X-1076, the correlation coefficient was 0.9999, the lowest detection concentration was 0.4 mg/m3 (3L sampling air), the relative standard deviation (RSD) was 1.8%-4.1%, the desorption efficiency was 88.5%-90.6%, the breakthrough volume was > 0.7 mg, the sampling efficiency was 100%, the samples could be kept at ambient temperature for at least 7 days. CONCLUSION: The indicators of this method were conformed to the requirements of "Guide for establishing occupational health standards--Determination methods of air chemicals in workplace". This method could be used to detect 1,1-dichloro-1-nitroethane in air of workplaces.