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Multiple endocrine neoplasia type 1 (MEN1) is an inherited disease caused by mutations in the MEN1 gene encoding a nuclear protein menin. Among those different endocrine tumors of MEN1, the pancreatic neuroendocrine tumors (PNETs) are life-threatening and frequently implicated. Since there are uncertainties in genotype and phenotype relationship and there are species differences between humans and mice, it is worth it to replenish the mice model with human cell resources. Here, we tested whether the patient-origin induced pluripotent stem cell (iPSC) lines could phenocopy some defects of MEN1. In vitro β-cell differentiation revealed that the percentage of insulin-positive cells and insulin secretion were increased by at least two-fold in MEN1-iPSC derived cells, which was mainly resulted from significantly higher proliferative activities in the pancreatic progenitor stage (Day 7–13). This scenario was paralleled with increased expressions of prohormone convertase1/3 (PC1/3), glucagon-like peptide-1 (GLP-1), GLP-1R, and factors in the phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway, and the GLP-1R was mainly expressed in β-like cells. Blockages of either GLP-1R or PI3K significantly reduced the percentages of insulin-positive cells and hypersecretion of insulin in MEN1-derived cells. Furthermore, in transplantation of different stages of MEN1-derived cells into immune-deficient mice, only those β-like cells produced tumors that mimicked the features of the PNETs from the original patient. To the best of our knowledge, this was the first case using patient-origin iPSCs modeling most phenotypes of MEN1, and the results suggested that GLP-1R may be a potential therapeutic target for MEN1-related hyperinsulinemia. [ABSTRACT FROM AUTHOR]

In this work, we showed that immersing polymethyl methacrylate (PMMA)/poly alpha olefins (PAO6) microcapsules into the porous matrix can improve the lubrication properties of porous alumina ceramics dramatically. PMMA/PAO6 microcapsules were synthesized by microemulsion polymerization, and the microcapsules were immersed in the porous alumina ceramic matrix by vacuum impregnation. The lubrication behaviors of the porous alumina ceramics with PMMA/PAO6 microcapsules have been investigated under different loads. As compared with the unprocessed porous alumina ceramics, the coefficient of friction (COF) of the porous ceramics impregnated with microcapsules could be reduced to 4% of that without microcapsules, and the wear rate could be reduced by two orders of magnitude. No obvious change of the COF was noticed for the matrices with different pore sizes. The good self-lubrication properties were achieved by releasing the PAO6 in the microcapsules during the friction process. [ABSTRACT FROM AUTHOR]

• A 'skin-electrically heated fabric-environment' heat transfer model was established. • Temperature and inner layer's thermal resistance affect T sk a more than other factors. • A prediction model for resultant skin temperature was developed. • The optimization design balances human thermal comfort and energy saving. A 3D heat transfer model was developed to optimize the design of electric heating garments (EHGs) towards human thermal comfort and energy efficiency. The model deals with the thermal interaction between human skin, a three-layer electrical heating fabric system, and cold environments, allowing analysis of the heating process and resultant skin temperature. Three heat transfer mechanisms, namely conduction, convection and radiation, were considered. The real-time and final skin temperatures from simulation and measurement exhibited a difference below 4%, demonstrating the efficiency of the model. A steady-state parametric study was conducted using the validated numerical model. Five parameters, such as heating temperature, thermal resistance of the inner and outer fabrics, wind speed, and environmental air temperature, were involved. The results indicate that the heating temperature and thermal resistance of the inner fabric have a more noticeable effect on the temperature of the skin surface below the heated area compared to the other three factors. Apart from the heating temperature, the other four factors have a greater impact on the skin temperature of non-heated regions than that of the heated region. Multiple linear regression analysis was performed to establish a relationship between skin temperature and the five factors. Based on this analysis, a prediction model for skin temperature was developed and subsequently used to determine relevant parameters for EHGs. A method for optimizing the design of electrically heated clothing is proposed, which can achieve the dual goals of human thermal comfort and energy efficiency. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer, characterized by high morbidity and mortality rates, as well as unfavorable treatment outcomes. Tripartite motif-containing protein 47 (TRIM47) has been implicated in various diseases including tumor progression with the activity of E3 ubiquitin ligase. However, the precise regulatory mechanisms underlying the involvement of TRIM47 in HCC remain largely unexplored. Here, we provide evidence that TRIM47 exhibits heightened expression in tumor tissues, and its expression is in intimate association with clinical staging and patient prognosis. TRIM47 promotes HCC proliferation, migration, and invasion as an oncogene by in vitro gain- and loss-of-function experiments. TRIM47 knockdown results in HCC ferroptosis induction, primarily through CDO1 involvement to regulate GSH synthesis. Subsequent experiments confirm the interaction between TRIM47 and CDO1 dependent on B30.2 domain, wherein TRIM47 facilitates K48-linked ubiquitination, leading to a decrease in CDO1 protein abundance in HCC. Furthermore, CDO1 is able to counteract the promotional effect of TRIM47 on HCC biological functions. Overall, our research provides novel insight into the mechanism of TRIM47 in CDO1-mediated ferroptosis in HCC cells, highlighting its value as a potential target candidate for HCC therapeutic approaches. [Display omitted] • High expression of TRIM47 in HCC is correlated with poor outcome. • TRIM47 modulates HCC ferroptosis through CDO1 mediated GSH synthesis. • TRIM47 binds to CDO1 and regulates its ubiquitin modification. • TRIM47-CDO1 axis is essential to determine HCC progression. [ABSTRACT FROM AUTHOR]

Hepatic ischemia-reperfusion injury (HIRI) is a common phenomenon in liver transplantation and liver surgery. This article is aimed at clarifying the role of pemafibrate in HIRI through JAK2/STAT3β/PPARα. In the experiment, we divided Balb/c into seven groups, namely, normal control (NC), Sham, PEM (1.0 mg/kg), IRI, IRI + PEM (0.1 mg/kg), IRI + PEM (0.5 mg/kg), and IRI + PEM (1.0 mg/kg). We used biochemical assay, histopathological evaluation, immunohistochemistry, RT-PCR and qRT-PCR, ELISA analysis, and other methods to determine the level of serum AST, ALT, IL-1β, and TNF-α in the liver at three time points (2 h, 8 h, and 24 h) after reperfusion of apoptosis factor, autophagy factor, and the JAK2/STAT3/PPARα content in tissues. Our experiment results showed that the pemafibrate can effectively reduce the level of hepatic IR injury. In addition, pemafibrate has anti-inflammatory, antiapoptotic, and antiautophagy effects, which are mediated by the JAK2/STAT3β/PPARα pathway. [ABSTRACT FROM AUTHOR]

The gene expression profile of abdominal aortic aneurysm (AAA) neck is not fully understood. The etiology of AAA is considered to be related to atherosclerosis and the inflammatory response, involving congenital, genetic, metabolic, and other factors. The level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to those of cholesterol, oxidized low-density lipoprotein, and triglycerides. PCSK9 inhibitors have significant effects on lowering LDL-cholesterol, reversing atherosclerotic plaques, and reducing the risk of cardiovascular events and have been approved by several lipid-lowering guidelines. This work was aimed to investigate the potential role of PCSK9 in the neck of AAA. We extracted the expression dataset (GSE47472) containing 14 AAA patients and 8 donors and single-cell RNAseq (scRNA-seq) data (GSE164678) of CaCl2-induced (AAA) samples from the Gene Expression Omnibus dataset. Through bioinformatics methods, we found that PCSK9 was up-regulated in the proximal neck of human AAA. In AAA, PCSK9 was mainly expressed in fibroblasts. Additionally, immune check-point PDCD1LG2 was also expressed higher in AAA neck than donor, while CTLA4, PDCD1, and SIGLEC15 were down-regulated in AAA neck. The expression of PCSK was correlated with PDCD1LG2, LAG3, and CTLA4 in AAA neck. Additionally, some ferroptosis-related genes were also down-regulated in AAA neck. PCSK9 was also correlated with ferroptosis-related genes in AAA neck. In conclusion, PCSK9 was highly expressed in AAA neck, and may exert its role through interacting with immune check-points and ferroptosis-related genes. [ABSTRACT FROM AUTHOR]

Xanthate wastewater is a serious threat to the surrounding environment of mining sites, and it is important to use visible light photocatalytic technology to remove xanthatefrom wastewater. In this paper, a simple hydrothermal calcination synthesis route was used to grow submicron-sized CuO onto the surface of g-C 3 N 4 for the degradation of xanthate in mineral processing wastewater. The results showed that the CuO/g–C 3 N 4 –0.4 composite catalyst degraded xanthate with an efficiency of 83.2% in 120 min, which was 6.2 times higher than that of pure g-C 3 N 4. The catalyst materials were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy. It was found that the excellent photocatalytic performance of the composite was attributed to the construction of S-scheme CuO/g–C 3 N 4 –Xheterojunction, which not only broadened the light absorption range but also retained the strong redox ability of holes and electrons to participate in the reaction while efficiently separating the photoinduced carriers. Based on the results of active substance capture, an S-scheme charge transfer model was proposed and the photodegradation mechanism of xanthate was reasonably elucidated. • Copper CuO/g-C 3 N 4 photocatalysts has a degradation efficiency of 83.2% for xanthate under visible light. • Growing submicron-sized CuO onto g-C 3 N 4 surfaces by a simple hydrothermal calcination method. • The improvement of photocatalytic activity is due to the improvement of effective separation rate of electrons and holes. [ABSTRACT FROM AUTHOR]

Teeth-based age and sex estimation is an important task in mass disasters, criminal scenes, and archeology. Although various methods have been proposed, most of them are subjective and influenced by observers' experiences. In this study, we aimed to develop a deep learning model for automatic dental age and sex estimation from orthopantomograms (OPGs) and compare to manual methods. A large dataset of 15,195 OPGs (age range, 16 ~ 50 years; mean age, 29.65 years ± 9.36 [SD]; 10,218 females) was used to train and test a hybrid deep learning model which is a combination of convolutional neural network and transformer model. The final performance of this model was evaluated on additional independent 100 OPGs and compared to the manual method for external validation. In the test of 1413 OPGs, the mean absolute error (MAE) of age estimation was 2.61 years by this model. The accuracy and the area under the receiver operating characteristic curve (AUC) of sex estimation were 95.54% and 0.984. The heatmap indicated that the crown and pulp chamber of premolars and molars contain the most age-related information. In the additional independent 100 OPGs, this model achieved an MAE of 3.28 years for males and 3.79 years for females. The accuracy of this model was much higher than that of the manual models. Therefore, this model has the potential to assist radiologists in automated age and sex estimation. [ABSTRACT FROM AUTHOR]

Phosphatases of regenerating liver (PRLs) are dual‐specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans (C. elegans). Structurally, this phosphatase in C. elegans, named PRL‐1, consisted of a conserved signature sequence WPD loop and a single C(X)5R domain. Besides, by Western blot, immunohistochemistry and immunofluorescence staining, PRL‐1 was proved to mainly express in larval stages and express in intestinal tissues. Afterward, by feeding‐based RNA‐interference method, knockdown of prl‐1 prolonged the lifespan of C. elegans but also improved their healthspan, such as locomotion, pharyngeal pumping frequency, and defecation interval time. Furthermore, the above effects of prl‐1 appeared to be taken without acting on germline signaling, diet restriction pathway, insulin/insulin‐like growth factor 1 signaling pathway, and SIR‐2.1 but through a DAF‐16‐dependent pathway. Moreover, knockdown of prl‐1 induced the nuclear translocation of DAF‐16, and upregulated the expression of daf‐16, sod‐3, mtl‐1, and ctl‐2. Finally, suppression of prl‐1 also reduced the ROS. In conclusion, suppression of prl‐1 enhanced the lifespan and survival quality of C. elegans, which provides a theoretical basis for the pathogenesis of PRLs in related human diseases. [ABSTRACT FROM AUTHOR]

This study aims to explore tooth growth variation by regions and ethnicity in China, and to validate the modified Tibetan so as to assist in proposing a better approach. A total of 1320 orthopantomograms of Han children aged 4–14.99 were retrospectively collected from eastern and western regions of China. The Demirjian method and modified Tibetan method were applied. Results showed that dental maturity scores (DMS) in eastern children were significantly greater than western children. Age was overestimated by both methods in eastern children. MAE was 0.88 and 1.3 years by Demirjian method, 1.01 and 1.21 years by modified Tibetan method in eastern girls and boys respectively. In western children, age was significantly underestimated in girls and slightly overestimated by Demirjian method; by modified method, age was generally overestimated. MAE was 0.79 and 0.84 years by Demirjian method, 0.51 and 0.69 years by modified Tibetan method in girls and boys respectively. The current study reveals that tooth growth was significantly advanced in Eastern Han children compared with Western Han children. Ethnic variation between Eastern Han and Tibetan Chinese was substantial. Neither method was sufficiently accurate in Eastern Han children. The modified Tibetan method was reliable in Western Han children. [ABSTRACT FROM AUTHOR]

Background: Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. Methods: Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. Results: Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. Conclusion: Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells. [ABSTRACT FROM AUTHOR]

Background: Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. Methods: Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. Results: Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. Conclusion: Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global epidemic and poses a major threat to public health. In addition to COVID-19 manifesting as a respiratory disease, patients with severe disease also have complications in extrapulmonary organs, including liver damage. Abnormal liver function is relatively common in COVID-19 patients; its clinical manifestations can range from an asymptomatic elevation of liver enzymes to decompensated hepatic function, and liver injury is more prevalent in severe and critical patients. Liver injury in COVID-19 patients is a comprehensive effect mediated by multiple factors, including liver damage directly caused by SARS-CoV-2, drug-induced liver damage, hypoxia reperfusion dysfunction, immune stress and inflammatory factor storms. Patients with chronic liver disease (especially alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma) are at increased risk of severe disease and death after infection with SARS-CoV-2, and COVID-19 aggravates liver damage in patients with chronic liver disease. This article reviews the latest SARS-CoV-2 reports, focusing on the liver damage caused by COVID-19 and the underlying mechanism, and expounds on the risk, treatment and vaccine safety of SARS-CoV-2 in patients with chronic liver disease and liver transplantation. [Display omitted] • COVID-19 is commonly involved liver injury, even more prevalent in severe or critical conditions. • Multiple pathological events are linked with those injuries including IL6, clotting, vascular damages and drug-induced. • Pre-existed liver diseases increase the severity and death rates of COVID-19. • The treatments of chronic liver diseases should not interrupted during the epidemic. • Patients with chronic liver diseases should be vaccinated to prevent COVID-19. [ABSTRACT FROM AUTHOR]

Hepatic ischemia-reperfusion (IR) injury is a clinically significant process that frequently occurs in liver transplantation, partial hepatectomy, and hemorrhagic shock. The aim of this study was to explore the effectiveness of luteolin in hepatic IR injury and the underlying mechanism. BALB/c mice were randomly divided into six groups, including normal controls (NC), luteolin (50 mg/kg), sham procedure, IR+25 mg/kg luteolin, and IR+50 mg/kg luteolin group. Serum and tissue samples were collected at 6 and 24 h after reperfusion to assay liver enzymes, inflammatory factors, expression of proteins associated with apoptosis and autophagy, and factors associated with the extracellular signal-regulated kinase/peroxisome proliferator-activated receptor alpha (ERK/PPARα) pathway. Luteolin preconditioning decreased hepatocyte injury caused by ischemia-reperfusion, downregulated inflammatory factors, and inhibited apoptosis and autophagy. Luteolin also inhibited ERK phosphorylation and activated PPARα. [ABSTRACT FROM AUTHOR]

Cell division cycle-associated (CDCA) gene family members are essential cell proliferation regulators and play critical roles in various cancers. However, the function of the CDCA family genes in gliomas remains unclear. This study aims to elucidate the role of CDCA family members in gliomas using in vitro and in vivo experiments and bioinformatic analyses. We included eight glioma cohorts in this study. An unsupervised clustering algorithm was used to identify novel CDCA gene family clusters. Then, we utilized multi-omics data to elucidate the prognostic disparities, biological functionalities, genomic alterations, and immune microenvironment among glioma patients. Subsequently, the scRNA-seq analysis and spatial transcriptomic sequencing analysis were carried out to explore the expression distribution of CDCA2 in glioma samples. In vivo and in vitro experiments were used to investigate the effects of CDCA2 on the viability, migration, and invasion of glioma cells. Finally, based on ten machine-learning algorithms, we constructed an artificial intelligence-driven CDCA gene family signature called the machine learning-based CDCA gene family score (MLCS). Our results suggested that patients with the higher expression levels of CDCA family genes had a worse prognosis, more activated RAS signaling pathways, and more activated immunosuppressive microenvironments. CDCA2 knockdown inhibited the proliferation, migration, and invasion of glioma cells. In addition, the MLCS had robust and favorable prognostic predictive ability and could predict the response to immunotherapy and chemotherapy drug sensitivity. • An integration analysis of CDCA gene family in gliomas by multiple omics data. • Novel CDCA family clusters with distinct signaling, genomic features, TIME, and prognosis. • Experiments showed CDCA2 acted as an oncogene in gliomas by RAS signaling. • An artificial intelligence-driven CDCA family signature was developed. • The MLCS was a stable and robust biomarker for prognosis and immunotherapy. [ABSTRACT FROM AUTHOR]

Hepatic ischemia/reperfusion injury (HIRI) is a common complication of liver surgery requiring hepatic disconnection, such as hepatectomy and liver transplantation. The aim of this study was to investigate the effects of cordycepin on HIRI and to elucidate the underlying mechanisms. Balb/c mice were randomly divided into six groups: a normal control group, sham group, H-cordycepin group, HIRI group, L-cordycepin (25 mg/kg) + HIRI group, and H-cordycepin (50 mg/kg) + HIRI group. Mice were subjected to I/R, and cordycepin was intragastrically administered for seven consecutive days before surgery. Orbital blood and liver specimens were collected at 6 and 24 h after HIRI. Serum levels of ALT and AST were decreased in the cordycepin pretreatment groups. Notably, cordycepin attenuated the inflammatory response and the production of proapoptosis proteins, while increasing expression of antiapoptosis proteins and decreasing expression of autophagy-linked proteins. Furthermore, cordycepin inhibited activation of the MAPK/NF-κB signaling pathway. Collectively, these results indicate that cordycepin pretreatment ameliorated hepatocyte injury caused by HIRI. As compared with the HIRI group, cordycepin pretreatment mitigated the inflammatory response and inhibited apoptosis and autophagy via regulation of the MAPK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

This study aimed to reveal the effects of icaritin (ICT) on lipotoxicity induced by palmitate (PA) in hepatic cells and steatosis in high-fat diet (HFD)-fed mice as well as exploring the potential mechanisms. Primary mouse hepatocytes and human hepatoma Huh7 cells were used to evaluate ICT effect in vitro. HFD-fed mice were used to evaluate the ICT effect in vivo. In vitro study indicated that ICT significantly rescued PA-induced steatosis, mainly through a combination of robust increased mitochondrial respiration, fatty acid oxidation and mildly decreased synthesis of fatty acid. An HFD-fed mouse model with 8 weeks HFD-fed showed metabolic disorders, while ICT application significantly reduced the weight, serum glucose levels, insulin resistance, hepatic steatosis level and adipose contents. In consistent with the observations in cell lines, ICT rescued the HFD-impaired functions and contents of key factors related to fatty acid β-oxidation through elevated expression of peroxisome proliferator-activated receptor α (PPARα). Meanwhile, it also reversed the decreased phosphoryl levels of AKT and glucogen synthase kinase 3 (GSK3β), leading to the improvement of insulin resistance. ICT administration had a therapeutic effect on PA- or HFD-induced hepatic steatosis and metabolic disorders. It may provide a novel strategy to construct preventive and therapeutic means for hepatic steatosis. [ABSTRACT FROM AUTHOR]