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Lithium–sulfur (Li–S) battery features a high theoretical energy density, but the shuttle of soluble polysulfides between the two electrodes often results in a rapid capacity decay. Herein, a straightforward electrostatic adsorption strategy based on a cross‐linked polyimidazolium separator as a snaring shield of polysulfides is reported, which suppresses the undesirable migration of polysulfides to the anode. The porous ionic network (PIN)‐modified carbon nanotubes (CNTs) are successfully prepared and coated onto a commercial porous polypropylene membrane in a vacuum‐filtration step. The favorable affinity of the imidazolium ring toward polysulfide via the polar interaction and the electrostatic effect of ions mitigates the undesirable shuttle of polysulfides in the electrolyte, improving the Li─S battery in terms of rate performance and cycling life. Compared to the reference PIN‐free CNT‐coated separator, the PIN/CNT‐coated one has an increased initial capacity of 1.3 folds (up to 1394.8 mAh g−1 for PIN/CNT/PP‐3) at 0.1 C. [ABSTRACT FROM AUTHOR]

A co‐crystal FJU‐182 with a closed cage structure with photochromic phenomenon was formed using a tetraphenylene derivatives 4,4′,4′′,4′′′‐(anthracene‐9,10‐diylidenebis(methanediyl‐ylidene))tetrabenzoic acid self‐assembled with 1,3‐di(4‐pyridyl)propane in a solvent. It was also found that isomorphic crystals grown from different solvents exhibited different fluorescence. The electron paramagnetic resonance and X‐ray photoelectron spectroscopy data showed that the photochromic mechanism of crystal FJU‐182 was due to photoinduced electron transfer, while the different color change of crystals grown from different solvents was attributed to the size of solvent molecules. The I−V curves of the crystals FJU‐182 before and after illumination were also tested, and it was found that the conductivity of the crystals before the color change would be 3–8 times higher than the conductivity of the crystals after the color development. FJU‐182 provides a new case for electrochemical devices with photoelectric response. [ABSTRACT FROM AUTHOR]

The construction of hydrogen‐bonded organic framework materials by intermolecular hydrogen bonding forces has been rapidly developed in the last decade, among which, the strong intermolecular hydrogen bonding and functional binding sites exhibited by nitrogen‐containing functional groups have made them favorites for designing organic components to customize functionalized porous materials. This review systematically introduces the types of nitrogen‐containing monomers used to prepare porous hydrogen‐bonded organic backbones and the principles of their construction, summarizes the design advantages of crystalline materials from an elemental perspective, and presents the applications of such HOFs in the fields of gas adsorption/separation, molecular recognition, plasmonic conductivity, biomedical, and luminescent materials, etc. Finally, the prospects for the development of such materials are discussed and potential directions for future work are analyzed. [ABSTRACT FROM AUTHOR]

Background. Acute ST-segment elevation myocardial infarction (STEMI) is a serious multiple acute cardiovascular disease. This study investigated the effect of statins on the efficacy and prognosis of STEMI patients after emergency PCI. Methods. From October 2019 to January 2021, 98 patients with STEMI in our hospital were selected and divided into study group and control group. The study group took atorvastatin 40 mg 2 hours before surgery, 40 mg/day after surgery, and 20 mg/day 1 week later. The control group received 20 mg of atorvastatin every night after admission. The cardiac output, left ventricular ejection fraction, blood flow classification, vagus nerve function, heart rate deceleration force and chemoreflex sensitivity were compared between the two groups, and recorded the incidence of adverse reactions before and after treatment and 3 months after treatment. The number of major adverse cardiac events (MACEs) was also recorded. Results. Before treatment, there were no differences in CO, CI, and LVEF between the study and control groups. After treatment, CO, CI, and LVEF in the study group were significantly higher than those in the control group. Before treatment, there was no significant difference in TIMI blood flow classification among the groups, and after treatment, the study group was better than the control group. DC and ChRS were significantly higher in the study group than in the control group. There was no difference in the incidence of adverse reactions between the study group and the control group. However, the incidence of MACE in the study group was lower than that in the control group. Conclusion. Enhanced-dose atorvastatin for STEMI patients improved PCI treatment effect, cardiac function, and vagus nerve function and reduced the incidence of adverse cardiac events. Thus, statins are safe and worth considering. [ABSTRACT FROM AUTHOR]

Objective. To explore the potential and mechanism of action of poricoic acid A (PAA) in treatment of cardiorenal injury and fibrosis due to cardiorenal syndrome (CRS). Materials and Methods. A CRS rat model was established by transabdominal subtotal nephrectomy (STNx). The experimental group was treated by gavage of PAA (10 mg/kg/day). After 8 weeks of treatment, echocardiography was utilized for detecting heart-related indexes in rats. HE and Masson staining were conducted to detect the degree of pathological damage and fibrosis in rat kidney tissue, respectively. In addition, serum blood urea nitrogen (BUN), serum creatinine (SCr), and 24-hour urine protein were measured biochemically. Also, the levels of inflammatory factors (IL-1β, IL-6, and IL-10) in rat kidneys were measured using ELISA. Western blot was used to examine the expression of NF-κB/MAPK pathway-related proteins. Results. In this study, a CRS rat model was successfully established by STNx surgery. PAA treatment could significantly alleviate the damage of heart and kidney function in CRS rats and reduce the pathological damage of kidney tissue and renal fibrosis. Meanwhile, PAA could also inhibit the renal inflammatory response through downregulating IL-1β and IL-6 levels in the kidney tissue and upregulating IL-10 level. Further mechanism exploration showed that the NF-κB/MAPK signaling pathway was significantly activated in CRS rats, while PAA treatment could markedly inhibit the NF-κB/MAPK signaling pathway activity in CRS rats. Conclusion. PAA can obviously improve the pathological damage and fibrosis of renal tissue in CRS rats and maintain the function of the heart and kidney. The above functions of PAA may be achieved by inhibiting the NF-κB/MAPK signaling pathway activity. Briefly speaking, PAA can serve as a potential drug for CRS treatment. [ABSTRACT FROM AUTHOR]

Summary: Macrophages are professional antigen‐presenting cells relying on the expression of class II major histocompatibility complex (MHC II) genes. Interferon‐γ (IFN‐γ) activates MHC II transcription via the assembly of an enhanceosome centred on class II trans‐activator (CIITA). In the present study, we investigated the role of the forkhead transcription factor FOXO3a in IFN‐ γ‐induced MHC II transcription in macrophages. Knockdown of FOXO3a, but not FOXO1 or FOXO4, diminished IFN‐γ‐induced MHC II expression in RAW cells. On the contrary, over‐expression of FOXO3a, but neither FOXO1 nor FOXO4, enhanced CIITA‐mediated trans‐activation of the MHC II promoter. IFN‐γ treatment promoted the recruitment of FOXO3a to the MHC II promoter. Co‐immunoprecipitation and RE‐ChIP assays showed that FOXO3a was a component of the MHC II enhanceosome forming interactions with CIITA, RFX5, RFXB and RFXAP. FOXO3a contributed to MHC II transcription by altering histone modifications surrounding the MHC II promoter. Of interest, FOXO3a was recruited to the type IV CIITA promoter and directly activated CIITA transcription by interacting with signal transducer of activation and transcription 1 in response to IFN‐γ stimulation. In conclusion, our data unveil a novel role for FOXO3a in the regulation of MHC II transcription in macrophages. [ABSTRACT FROM AUTHOR]

Compressive sensing enables fast magnetic resonance imaging (MRI) reconstruction with undersampled k-space data. However, in most existing MRI reconstruction models, the whole MR image is targeted and reconstructed without taking specific tissue regions into consideration. This may fails to emphasize the reconstruction accuracy on important and region-of-interest (ROI) tissues for diagnosis. In some ROI-based MRI reconstruction models, the ROI mask is extracted by human experts in advance, which is laborious when the MRI datasets are too large. In this paper, we propose a deep neural network architecture for ROI MRI reconstruction called ROIRecNet to improve reconstruction accuracy of the ROI regions in under-sampled MRI. In the model, we obtain the ROI masks by feeding an initially reconstructed MRI from a pre-trained MRI reconstruction network (RecNet) to a pre-trained MRI segmentation network (ROINet). Then we fine-tune the RecNet with a binary weighted ℓ 2 loss function using the produced ROI mask. The resulting ROIRecNet can offer more focus on the ROI. We test the model on the MRBrainS13 dataset with different brain tissues being ROIs. The experiment shows the proposed ROIRecNet can significantly improve the reconstruction quality of the region of interest. [ABSTRACT FROM AUTHOR]

Compressed sensing (CS) theory assures us that we can accurately reconstruct magnetic resonance images using fewer k-space measurements than the Nyquist sampling rate requires. In traditional CS-MRI inversion methods, the fact that the energy within the Fourier measurement domain is distributed non-uniformly is often neglected during reconstruction. As a result, more densely sampled low frequency information tends to dominate penalization schemes for reconstructing MRI at the expense of high frequency details. In this paper, we propose a new framework for CS-MRI inversion in which we decompose the observed k-space data into "subspaces" via sets of filters in a lossless way, and reconstruct the images in these various spaces individually using off-the-shelf algorithms. We then fuse the results to obtain the final reconstruction. In this way, we are able to focus reconstruction on frequency information within the entire k-space more equally, preserving both high and low frequency details. We demonstrate that the proposed framework is competitive with state-of-the-art methods in CS-MRI in terms of quantitative performance, and often improves an algorithm's results qualitatively compared with its direct application to k-space. Unlabelled Image • The MRI measurements distribute non-uniformly in k-space. • A divide-and-conquer (DAC) approach for compressed sensing MRI is proposed. • The DAC approach can fully utilize the statistical characteristics of each k-space subspace. • The DAC approach often improves an undersampled MRI algorithm's results. [ABSTRACT FROM AUTHOR]

Background and Aims: The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction‐associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all‐cause and cause‐specific mortality among MAFLD individuals of different genders. Methods: Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all‐cause and cause‐specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all‐cause mortality. Results: In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all‐cause and cause‐specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004–1.014; female, HRs: 1.032, 95% CIs: 1.022–1.042). In males with MAFLD, a linear association with all‐cause mortality was observed for weekly alcohol consumption (p for non‐linearity =.21). Conversely, in females with MAFLD, the risk of all‐cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non‐linearity <.05). Conclusions: Our findings indicate that any increase in weekly alcohol consumption was associated with increased all‐cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female. [ABSTRACT FROM AUTHOR]

Fibrosis following injury is a common adaptive response in the liver, which can lead to irreparable and life-threatening cirrhosis and hepatocellular carcinoma without effectual intervention. The molecular mechanisms underlying fibrogenic response in the liver remains poorly understood. Here we report that mice with deficiency in myocardin-related transcription factor A (MRTF-A) showed resistance to thioacetamide (TAA)-induced liver fibrosis with significantly reduced expression of pro-fibrogenic genes when compared to wild type littermates. Over-expression of MRTF-A enhanced whereas depletion of MRTF-A alleviated pro-fibrogenic transcription induced by TGF-β, a major pro-fibrogenic factor in hepatic stellate cells (HSCs). Mechanistically, MRTF-A silencing in HSCs impacted the chromatin structure by reducing the deposition of methylated histone H3K4 on the promoters of pro-fibrogenic genes. Further analyses revealed that MRTF-A interacted with and recruited several key epigenetic factors involved in H3K4 methylation, including ASH2, WDR5, and SET1, to the promoters of pro-fibrogenic genes in response to TGF-β treatment. Over-expression of ASH2, WDR5, or SET1 enhanced the transactivation of pro-fibrogenic gene promoters by TGF-β in an MRTF-A-dependent manner. In conclusion, MRTF-A regulates liver fibrosis by epigenetically tuning the TGF-β signaling pathway in HSCs. [ABSTRACT FROM AUTHOR]

Frontispiece: Hydrogen-Bonded Organic Frameworks: Functionalized Construction Strategy by Nitrogen-Containing Functional Group Functionalized, hydrogen-bonded organic framework materials, nitrogen-containing functional groups, porous materials Keywords: functionalized; hydrogen-bonded organic framework materials; nitrogen-containing functional groups; porous materials EN functionalized hydrogen-bonded organic framework materials nitrogen-containing functional groups porous materials 1 1 1 07/29/22 20220726 NES 220726 Four modification strategies of nitrogen-containing functional groups in the design of hydrogen-bonded organic framework materials are discussed in the Review by Zhang, Liu et al. (DOI: 10.1002/chem.202200422). [Extracted from the article]

Elaborately designed multifunctional electrocatalysts capable of promoting Li+ and CO2 transport are essential for upgrading the cycling stability and rate capability of Li‐CO2 batteries. Hydrogen‐bonded organic frameworks (HOFs) with open channels and easily functionalized surfaces hold great potential for applications in efficient cathodes of Li‐CO2 batteries. Herein, a robust HOFS (HOF‐FJU‐1) is introduced for the first time as a co‐catalyst in the cathode material of Li‐CO2 batteries. HOF‐FJU‐1 with cyano groups located periodically in the pore can induce homogeneous deposition of discharge products and accommodate volumetric expansion of discharge products during cycling. Besides, HOF‐FJU‐1 enables effective interaction between Ru0 nanoparticles and cyano groups, thus forming efficient and uniform catalytic sites for CRR/CER. Moreover, HOF‐FJU‐1 with regularly arranged open channels are beneficial for CO2 and Li+ transport, enabling rapid redox kinetic conversion of CO2. Therefore, the HOF‐based Li‐CO2 batteries are capable of stable operation at 400 mA g−1 for 1800 h and maintain a low overpotential of 1.96 V even at high current densities up to 5 A g−1. This work provides valuable guidance for developing multifunctional HOF‐based catalysts to upgrade the longevity and rate capability of Li‐CO2 batteries. [ABSTRACT FROM AUTHOR]

Elaborately designed multifunctional electrocatalysts capable of promoting Li+ and CO2 transport are essential for upgrading the cycling stability and rate capability of Li‐CO2 batteries. Hydrogen‐bonded organic frameworks (HOFs) with open channels and easily functionalized surfaces hold great potential for applications in efficient cathodes of Li‐CO2 batteries. Herein, a robust HOFS (HOF‐FJU‐1) is introduced for the first time as a co‐catalyst in the cathode material of Li‐CO2 batteries. HOF‐FJU‐1 with cyano groups located periodically in the pore can induce homogeneous deposition of discharge products and accommodate volumetric expansion of discharge products during cycling. Besides, HOF‐FJU‐1 enables effective interaction between Ru0 nanoparticles and cyano groups, thus forming efficient and uniform catalytic sites for CRR/CER. Moreover, HOF‐FJU‐1 with regularly arranged open channels are beneficial for CO2 and Li+ transport, enabling rapid redox kinetic conversion of CO2. Therefore, the HOF‐based Li‐CO2 batteries are capable of stable operation at 400 mA g−1 for 1800 h and maintain a low overpotential of 1.96 V even at high current densities up to 5 A g−1. This work provides valuable guidance for developing multifunctional HOF‐based catalysts to upgrade the longevity and rate capability of Li‐CO2 batteries. [ABSTRACT FROM AUTHOR]

Summary: Background: Liver fibrosis is the strongest histological risk factor for liver‐related complications and mortality in metabolic dysfunction‐associated fatty liver disease (MAFLD). Second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) is a powerful tool for label‐free two‐dimensional and three‐dimensional tissue visualisation that shows promise in liver fibrosis assessment. Aim: To investigate combining multi‐photon microscopy (MPM) and deep learning techniques to develop and validate a new automated quantitative histological classification tool, named AutoFibroNet (Automated Liver Fibrosis Grading Network), for accurately staging liver fibrosis in MAFLD. Methods: AutoFibroNet was developed in a training cohort that consisted of 203 Chinese adults with biopsy‐confirmed MAFLD. Three deep learning models (VGG16, ResNet34, and MobileNet V3) were used to train pre‐processed images and test data sets. Multi‐layer perceptrons were used to fuse data (deep learning features, clinical features, and manual features) to build a joint model. This model was then validated in two further independent cohorts. Results: AutoFibroNet showed good discrimination in the training set. For F0, F1, F2 and F3‐4 fibrosis stages, the area under the receiver operating characteristic curves (AUROC) of AutoFibroNet were 1.00, 0.99, 0.98 and 0.98. The AUROCs of F0, F1, F2 and F3‐4 fibrosis stages for AutoFibroNet in the two validation cohorts were 0.99, 0.83, 0.80 and 0.90 and 1.00, 0.83, 0.80 and 0.94, respectively, showing a good discriminatory ability in different cohorts. Conclusion: AutoFibroNet is an automated quantitative tool that accurately identifies histological stages of liver fibrosis in Chinese individuals with MAFLD. [ABSTRACT FROM AUTHOR]

Efficient presentation of alien antigens triggers activation of T lymphocytes and robust host defense against invading pathogens. This pathophysiological process relies on the expression of major histocompatibility complex (MHC) molecules in antigen presenting cells such as macrophages. Aberrant MHC II transactivation plays a crucial role in the pathogenesis of atherosclerosis. Class II transactivator (CIITA) mediates MHC II induction by interferon gamma (IFN-γ). CIITA activity can be fine-tuned at the post-translational level, but the mechanisms are not fully appreciated. We investigated the role of protein arginine methyltransferase 1 (PRMT1) in this process. We report here that CIITA interacted with PRMT1. IFN-γ treatment down-regulated PRMT1 expression and attenuated PRMT1 binding on the MHC II promoter. Over-expression of PRMT1 repressed MHC II promoter activity while PRMT1 depletion enhanced MHC II transactivation. Mechanistically, PRMT1 methylated CIITA and promoted CIITA degradation. Therefore, our data reveal a previously unrecognized role for PRMT1 in suppressing CIITA-mediated MHC II transactivation. [ABSTRACT FROM AUTHOR]

One of the hallmark events during liver fibrosis is the transition of quiescent hepatic stellate cells (HSC) into activated myofibroblasts, which are responsible for the production and deposition of pro-fibrogenic proteins. The epigenetic mechanism underlying HSC trans-differentiation is not fully understood. In the present study we investigated the contribution of histone H3K9 demethylase KDM4 in this process. We report that expression levels of KDM4 were down-regulated during HSC activation paralleling the up-regulation of alpha smooth muscle cell actin (Acta2), a marker of mature myofibroblast. Furthermore, HSCs isolated from mice induced to develop liver fibrosis exhibit lowered KDM4 expression compared to the control mice. In accordance, KDM4 depletion with siRNA accelerated HSC activation. Of interest, the loss of KDM4 was mirrored by the repression of miR-29, an antagonist of liver fibrosis, during HSC activation both in vitro and in vivo. KDM4 knockdown resulted in the down-regulation of miR-29 expression. Mechanistically, the sequence-specific transcription factor SREBP2 interacted with KDM4 to activate miR-29 transcription. In conclusion, our data delineate a novel epigenetic mechanism underlying HSC activation. Targeting this axis may yield potential therapeutics against liver fibrosis. • KDM4 levels are down-regulated in activated HSCs both in vitro and in vivo. • KDM4 suppresses HSC activation. • SREBP2 is down-regulated in activated HSCs and suppresses HSC activation. • KDM4 interacts with SREBP2 to activate miR-29 transcription. [ABSTRACT FROM AUTHOR]

Background: Due to the low incidence and histological heterogeneity, the molecular features and underlying carcinogenic mechanisms of thymic epithelial tumors (TETs) are yet to be fully elucidated, especially for different subtypes of TETs. Methods: Tumor tissue samples of 43 TETs with distinct histological subtypes were collected. We analyzed the molecular characteristics in different subtypes based on whole exome sequencing data. Results: The mutational profiles of the different subtypes of TETs varied. Compared with thymomas, thymic carcinomas (TCs) had a higher mutation frequency of MYO16 (33% vs. 3%, p = 0.024) and a lower frequency of ZNF729 mutations (0% vs. 35%, p = 0.044). No significant difference was observed in the median tumor mutation burden across different subtypes. The value of copy number variation burden, weighted genome instability index, and the number of amplified segments were all higher in TCs than thymomas, and they also tended to be higher in B3 thymoma than in non‐B3 thymomas, while they had no significant differences between B3 thymoma and TCs. Clustering analyses revealed that Wnt, MAPK, Hedgehog, AMPK, and cell junction assembly signaling pathways were exclusively enriched in non‐B3 thymomas, lysine degradation pathway in B3 thymoma, and extracellular matrix‐receptor (ECM‐receptor) interaction, positive regulation of cell cycle process, and activation of innate immune response pathways in TCs. Conclusions: This study revealed distinct molecular landscapes of different subtypes of TETs, suggesting diverse pathogenesis of non‐B3 thymomas, B3 thymomas, and TCs. Our findings warrant further validation in future large‐scale studies and may provide a theoretical basis for potential personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Two Ag-MOCPs with different dimensional electron transfer Channels were used for electrocatalytic conversion CO 2 to CO. [Display omitted] • New Ag-MOCP materials for CO 2 RR electrocatalysts were synthesized. • CO 2 -to-CO conversion was boosted with the regulation of the electron transfer channel. • The FE CO for Ag-MOCP-2 with multi-dimensional electron transfer channels is higher than that for Ag-MOCP-1 with single channel at most given potentials. • The mechanism of its reaction was further explored by DFT calculation. Although, electrons transfer plays an important role in achieving the electrocatalytic CO 2 reduction reaction (CO 2 RR), it is scarce to regulate the electron transfer channels for enhancing the performance of CO 2 RR via rational design. Here, based on different solvothermal conditions, two metal–organic coordination polymers (MOCPs, Ag-MOCP-1 and Ag-MOCP-2) electrocatalyst for CO 2 RR were obtained by the same Ag ions and 5-phenyltetrazolium ligands. Single crystal X-ray diffraction showed Ag-MOCP-2 with intra-&inter-layer C H···π and π···π interactions, while Ag-MOCP-1 with intra-layer π···π interactions. The intra-&inter-layer π interactions in Ag-MOCP-2 makes it show multi-dimensional electron transfer channels, which enable Ag-MOCP-2 with higher electron conductivities and lower band gap than Ag-MOCP-1. And the Faradaic efficiency of CO for Ag-MOCP-2 with 78.3 % is higher than that for Ag-MOCP-1 with 69.1 % at −1.08 V vs RHE, and the maximum difference can reach 22 % at −1.48 V vs RHE. Based on the same central metal and organic ligands of the two MOCPs, we believe that multi-dimensional electron transfer channels make a predominant contribution for improving CO 2 RR performance in this work. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a comorbidity commonly presenting with metabolic-dysfunction-associated fatty liver disease (MAFLD); however, few tests for interaction have been reported. Our target was to evaluate the prognostic implications of DM in patients with different forms of MAFLD. Methods: Using data from the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, we screened 14,797 participants aged 20–74 who received ultrasound examinations from 1988–1994. Among them, 4599 patients met the diagnosis of MAFLD, and we defined mortality as the outcome event. Survival analysis of competitive risk events was performed using Cox regression and sub-distributed risk ratio (SHR). Results: During 21.1 years of follow-up, cardiovascular diseases seemed to be the most common cause of death among MAFLD patients. Of them, DM was present in 25.48% and was independently associated with increased risk of all-cause mortality (HRs: 1.427, 95% CIs: 1.256–1.621, p < 0.001) and cause-specific mortality (cardiovascular-related mortality (HRs: 1.458, 95% CIs: 1.117–1.902, p = 0.005), non-cardiovascular-related mortality (HRs: 1.423, 95% CIs: 1.229–1.647, p < 0.001), and non-cancer-related mortality (HRs: 1.584, 95% CIs: 1.368–1.835, p < 0.001), respectively). Surprisingly, this association was more significant for young patients (p-value for interaction <0.001). Moreover, DM had a greater risk of all-cause and cause-specific mortality among overweight and obese MAFLD patients (p-value for interaction <0.001). Conclusions: DM increased the risk of all-cause and cause-specific mortality (cardiovascular-related, non-cardiovascular-related, and non-cancer-related) in MAFLD patients, especially in younger patients with excess obesity. [ABSTRACT FROM AUTHOR]

Crocin, the main effective component of saffron, exerts protective effects against ischemia/reperfusion injury during strokes. However, the effects of crocin in myocardial ischemia/reperfusion injury, and the mechanisms involved, remain unknown. Pretreated with crocin for 7 days, C57BL/6N mice were subjected to 30 min of myocardial ischemia followed by 12h of reperfusion (for cardiac function and infarct size, cell apoptosis and necrosis). Neonatal mouse cardiomyocytes were subjected to 2 h of hypoxia followed by 4 h of reoxygenation. NMCM's survival was assessed during hypoxia and reoxygenation in the presence or absence of the autophagy inhibitor 3-methyladenine or the inducer rapamycin. Western blotting was used to evaluate AMPK, Akt, and autophagy-related proteins. Autophagosome was observed using electron microscopy. In the in vivo experiment, crocin pretreatment significantly attenuated infarct size, myocardial apoptosis and necrosis, and improved left ventricular function following ischemia/reperfusion. In vitro data revealed that autophagy was induced during hypoxia, the levels of which were intensely elevated during reoxygenation. Crocin significantly promoted autophagy during ischemia, accompanied with the activation of AMPK. In contrast, crocin overtly inhibited autophagy during reperfusion, accompanied with Akt activation. Induction and inhibition of autophagy mitigated crocin induced protection against NMCMs injury during hypoxia and reoxygenation, respectively. Our data suggest that crocin demonstrated a myocardial protective effect via AMPK/mTOR and Akt/mTOR regulated autophagy against ischemia and reperfusion injury, respectively. [ABSTRACT FROM AUTHOR]

Two water stable phosphate‐amidinium charge‐assisted hydrogen‐bonded organic frameworks (HOFs), HOF‐FJU‐12 ([DPBA⋅PAM]0.5 ⋅ 0.2DMF⋅H2O) and HOF‐FJU‐13 ([DPBA ⋅ 1.5PAM] ⋅ 1.5DMF⋅H2O) (DPBA=3,5‐diphosphonobenzoic acid, PAM=terephtalimidamide, DMF=N,N‐Dimethylformamide) have been synthesized and structurally characterized. Single‐crystal X‐ray diffraction shows that HOF‐FJU‐13 is a layered structure with continuous hydrogen‐bonding networks along a axis, which plays an important role in proton conduction. The highest proton conductivity of HOF‐FJU‐13 (1.14×10−4 S/cm) is about 7.4 times higher than that of HOF‐FJU‐12 (1.54×10−5 S/cm) under the conditions of 60 °C and 98 % relative humidity. [ABSTRACT FROM AUTHOR]

Through regulating the reaction solvent and temperature, two Tb-based metal–organic frameworks, ((CH3)2NH2)2[Tb9(μ3-OH)8(μ2-OH)3(PTB)6]·(DMF)14·(H2O)19 (1) and ((CH3)2NH2)3{[Tb9(μ3-O)2(μ3-OH)12(H2O)6][Tb3(μ3-O)(HCO2)3 (PTB)6]}·(DMF)12·(H2O)7 (2) (H3PTB = pyridine-2,4,6-tribenzoic acid), have been synthesized. Structural analysis showed that the cluster node of 1 is a Tb9 cluster, while 2 contains two different nodes of a Tb3 cluster and a Tb9 cluster, which leads to their different pore structures and may potentially separate C2H2/CO2. Gas adsorption demonstrates that both MOFs can separate C2H2 and CO2, but 2 has a more optimized pore environment than 1 and can exhibit better selective separation of C2H2/CO2. [ABSTRACT FROM AUTHOR]

Hepatic ischemia-reperfusion injury (IRI) is a common complication secondary to liver transplantation. Extensive death of hepatocytes, typically in the form of apoptosis, is observed in and contributes to IRI. In the present study we investigated the role of BRG1 (encoded by Smarca4), a chromatin remodeling protein, in the pathogenesis of liver IRI focusing on the transcriptional mechanism and translational potential. Smarca4 f/f mice were crossed to Alb -Cre mice to generate hepatocytes-specific BRG1 knockout mice (CKO). Alterations in cellular transcriptome were evaluated by RNA-seq. BRG1 expression was up-regulated in liver tissues of mice subjected to I/R and in hepatocytes exposed to hypoxia-reoxygenation (H/R). Compared to wild type (WT) littermates, the BRG1 CKO mice displayed significant amelioration of liver injury following ischemia-reperfusion as evidenced by decreased ALT/AST levels and cell apoptosis. Primary hepatocytes isolated from the CKO mice were protected from H/R-induced apoptosis compared to those from the WT mice. RNA-seq analysis revealed phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, also known as NOXA) as a novel target for BRG1. Consistently, NOXA knockdown attenuated liver IRI in mice. More importantly, administration of a small-molecule BRG1 inhibitor (PFI-3) protected the mice from liver IRI. Our data uncover a pivotal role for BRG1 in liver IRI and suggest that targeting BRG1 with small-molecule inhibitors can be considered as a reasonable therapeutic strategy. [ABSTRACT FROM AUTHOR]

Trans-differentiation, or activation, of hepatic stellate cells (HSCs) is a hallmark event in liver fibrosis although the underlying mechanism is not fully appreciated. Serum response factor (SRF) is a pleiotropic sequence-specific transcription factor with a ubiquitous expression pattern. In the present study, we investigated the effect of HSC-specific ablation of SRF on liver fibrosis in vivo and the underlying mechanism. We report that SRF bound to the promoter regions of pro-fibrogenic genes, including collagen type I (Col1a1/Col1a2) and alpha smooth muscle actin (Acta2), with greater affinity in activated HSCs compared to quiescent HSCs. Ablation of SRF in HSCs in vitro downregulated the expression of fibrogenic genes by dampening the accumulation of active histone marks. SRF also interacted with MRTF-A, a well-documented co-factor involved in liver fibrosis, on the pro-fibrogenic gene promoters during HSC activation. In addition, SRF directly regulated MRTF-A transcription in activated HSCs. More importantly, HSC conditional SRF knockout (CKO) mice developed a less robust pro-fibrogenic response in the liver in response to CCl4 injection and BDL compared to wild-type littermates. In conclusion, our data demonstrate that SRF may play an essential role in HSC activation and liver fibrosis. Key messages: • SRF deficiency decelerates activation of hepatic stellate cells (HSCs) in vitro. • SRF epigenetically activates pro-fibrogenic transcription to promote HSC maturation. • SRF interacts with MRTF-A and contributes to MRTF-A transcription. • Conditional SRF deletion in HSCs attenuates BDL-induced liver fibrosis in mice. • Conditional SRF ablation in HSCs attenuates CCl4-induced liver fibrosis in mice. [ABSTRACT FROM AUTHOR]

Hepatocytes resume proliferation following liver injuries to compensate for the loss of liver mass. Robust liver regeneration is an intrinsic and pivotal process that facilitates restoration of liver anatomy and function. In the present study we investigated the role of ubiquitin-specific peptidase 47 (USP47) in liver regeneration. Proliferation of hepatocytes was evaluated by Ki67 staining in vivo and EdU incorporation in vitro. DNA-protein interaction was evaluated by chromatin immunoprecipitation (ChIP). USP47 expression was up-regulated in hepatocytes isolated from mice subjected to partial hepatectomy (PHx) or exposed to HGF treatment. Ingenuity pathway analysis revealed E2F1 as a primary regulator of USP47 transcription. Reporter assay and ChIP assay confirmed that E2F1 directly bound to the USP47 promoter and activated USP47 transcription. Consistently, E2F1 knockdown abrogated USP47 induction by HGF. Compared to the wild type littermates, USP47 knockout mice displayed compromised liver regeneration following PHx. In addition, USP47 inhibition by a small-molecule compound impaired liver regeneration in mice. On the contrary, USP47 over-expression enhanced proliferation of hepatocytes in vitro and promoted liver regeneration in mice. Importantly, a positive correlation between USP47 expression and hepatocyte proliferation was identified in patients with acute liver failure (ALF). Our data suggest that USP47, transcriptionally activated by E2F1, plays an essential role in liver regeneration. [ABSTRACT FROM AUTHOR]

Fibrosis is a common pathophysiological process following liver injury and can lead to, if left unattended to, irreversible end-stage liver disease such as cirrhosis. Hepatic stellate cells (HSCs) are a major contributor to liver fibrosis. Here we investigated the involvement of angiogenic factor with G patch and FHA domains 1 (Aggf1) in HSC activation and the underlying mechanisms. Aggf1 expression was down-regulated in the livers in three different mouse models of liver fibrosis following injury. Aggf1 expression was also suppressed in activated HSCs when compared to quiescent HSCs. Over-expression of Aggf1 alleviated liver fibrosis in mice and in cultured HSCs. RNA-sequencing (RNA-seq) analysis performed in HSCs revealed that Aggf1-dependent transcription regulates several key fibrogenic pathways. Mechanistically, Aggf1 regulated liver fibrogenesis by forming a complex with the inhibitor SMAD protein (SMAD7) thereby leading to diminished SMAD3 binding to the pro-fibrogenic gene promoters. On the contrary, SMAD7 knockdown abrogated the effect of Aggf1 and rescued HSC activation. Aggf1 expression was silenced during HSC activation/liver fibrogenesis as a result of DNA methylation. Treatment with a DNA methyltransferase inhibitor (5-Azacytidine) restored Aggf1 expression and repressed liver fibrosis in an Aggf1-dependent manner. In conclusion, our data illustrate a previously unknown role for Aggf1 and shed light on the development of novel therapeutic solutions against liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: Using fluorescence in situ hybridisation (FISH) to detect any gain of chromosomes 3, 7, or 17 and loss of the 9p21 locus has been proven to be sensitive in the diagnosis of pancreatobiliary tumors. However, both genetic and environmental factors contribute to the pathogenesis of pancreatobiliary tumors. Therefore, it is unknown whether this method is suitable for Chinese patients with pancreatobiliary tumors. This study aims to compare the sensitivity, specificity, predictive values and accuracy of cytology, ERCP/MRCP and FISH based on Chinese patients with pancreatobiliary tumors,and to analyze differences between brushing-based and formalin-fixed paraffin-embedded (FFPE)-based FISH.Methods: A total of 66 brush cytology specimens obtained during ERCP were detected by FISH and cytology test respectively to compare the sensitivity, specificity, predictive values and accuracy. Besides, FFPE-based FISH was performed on 46 corresponding paraffin sections of pancreatobiliary tumors obtained by surgical resection.Results: Our findings demonstrate that FISH greatly improves diagnostic sensitivity and negative predictive value compared to ERCP/MRCP and cytology without much reduction in specificity and positive predictive value. However, our results also indicate that FFPE-based FISH could not effectively identify the false-negative of brushing-based FISH.Conclusions: We believe that FISH can effectively distinguish true positive and false positive results of cytological or radiological suspicions of malignancy. However, FFPE-based FISH still does not precisely recognize the false-negative of brushing-based FISH. Both cytology-based and PPFE-based FISH had limitation in some specimens. [ABSTRACT FROM AUTHOR]