Improvement of Pre-check and Triage Efficiency and Guarantee of Maternal and Infant Safety in Pandemic Situation.

Objective: The objective of this study was to enhance the efficiency of pre-check and triage procedures in gynecology and obstetrics, while ensuring the safety of maternal and infant patients during the COVID-19 pandemic. Methods: Between March 2020 and July 2022, the workflow in gynecology and obstetrics was optimized, and the management of medical staff working in outpatient, ward, and obstetric ward settings was strengthened. Special protocols were developed and implemented for pregnant women, parturients, and neonates. Detailed procedures and routes were established for patient movement from outpatient areas to wards, with strict adherence to pandemic prevention and control measures. Information-based methods were employed to track and monitor the health status of high-risk pregnant women, parturients, and their families, facilitating accurate and efficient pre-check and triage processes. Results: The implementation of these measures yielded favorable outcomes. No cases of COVID-19 infection were reported among pregnant women and parturients admitted to Liangzhou Hospital. The source of infection was effectively controlled, ensuring the safety of the patients. Conclusion: This study demonstrates the significance of improving pre-check and triage efficiency, strengthening the management of medical staff, and implementing specialized measures for pregnant women, parturients, and neonates to ensure their safety during the COVID-19 pandemic. The established protocols and procedures can serve as a valuable reference for other healthcare facilities seeking to enhance their pandemic prevention and control strategies in gynecology and obstetrics settings.

Feasibility and accuracy of noninvasive continuous hemoglobin monitoring using transesophageal photoplethysmography in porcine model.

BACKGROUND: Continuous and noninvasive hemoglobin (Hb) monitoring during surgery is essential for anesthesiologists to make transfusions decisions. The aim of this study was to investigate the feasibility and accuracy of noninvasive and continuous Hb monitoring using transesophageal descending aortic photoplethysmography (dPPG) in porcine model. METHODS: Nineteen landrace pigs, aged 3 to 5 months and weighing 30 to 50 kg, were enrolled in this study. A homemade oximetry sensor, including red (660 nm) and infrared (940 nm) lights, was placed in the esophagus for dPPG signal detection to pair with the corresponding reference Hb values (Hbi-STAT) measured by blood gas analysis. The decrease and increase changes in Hb concentration were achieved by hemodilution and transfusion. Metrics, including alternating current (AC), direct current (DC), and AC/DC for both red and infrared light were extracted from the dPPG signal. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting the Hb "trigger threshold" of transfusion (Hb < 60 g/L and Hb > 100 g/L). Agreement and trending ability between Hb measured by dPPG (HbdPPG) and by blood gas analysis were analyzed by Bland-Altman method and polar plot graph. Error grid analysis was also performed to evaluate clinical significance of HbdPPG measurement. RESULTS: The dPPG signal was successfully detected in all of the enrolled experimental pigs, without the occurrence of a continuous loss of dPPG signal for 2 min during the entire measurement. A total of 376 pairs of dPPG signal and Hbi-STAT were acquired. ACred/DCred and ACinf/DCinf had moderate correlations with Hbi-STAT, and the correlation coefficients were 0.790 and 0.782, respectively. The areas under the ROC curve for ACred/DCred and ACinf/DCinf in predicting Hbi-STAT < 60 g/L were 0.85 and 0.75, in predicting Hbi-STAT > 100 g/L were 0.90 and 0.83, respectively. Bland-Altman analysis and polar plot showed a small bias (1.69 g/L) but a wide limit of agreement (-26.02-29.40 g/L) and a poor trend ability between HbdPPG and Hbi-STAT. Clinical significance analysis showed that 82% of the data lay within the Zone A, 18% within the Zone B, and 0% within the Zone C. CONCLUSION: It is feasible to establish a noninvasive and continuous Hb monitoring by transesophageal dPPG signal. The ACred/DCred extracted from the dPPG signal could provide a sensitive prediction of the Hb threshold for transfusion. The Hb concentration measured by dPPG signal has a moderate correlation with that measured by blood gas analysis. This animal study may provide an experimental basis for the development of bedside HbdPPG monitoring in the future.

RING finger protein 13 protects against nonalcoholic steatohepatitis by targeting STING-relayed signaling pathways.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Recent studies show that innate immunity-related signaling pathways fuel NAFLD progression. This study aims to identify potent regulators of innate immunity during NAFLD progression. To this end, a phenotype-based high-content screening is performed, and RING finger protein 13 (RNF13) is identified as an effective inhibitor of lipid accumulation in vitro. In vivo gain- and loss-of-function assays are conducted to investigate the role of RNF13 in NAFLD. Transcriptome sequencing and immunoprecipitation-mass spectrometry are performed to explore the underlying mechanisms. We reveal that RNF13 protein is upregulated in the liver of individuals with NASH. Rnf13 knockout in hepatocytes exacerbate insulin resistance, steatosis, inflammation, cell injury and fibrosis in the liver of diet-induced mice, which can be alleviated by Rnf13 overexpression. Mechanically, RNF13 facilitates the proteasomal degradation of stimulator of interferon genes protein (STING) in a ubiquitination-dependent way. This study provides a promising innate immunity-related target for NAFLD treatment.

The deubiquitinating enzyme USP19 facilitates hepatocellular carcinoma progression through stabilizing YAP.

Hippo pathway plays a crucial role in the progression of hepatocellular carcinoma (HCC), and yes-associated protein (YAP) is one of the major factors of the Hippo pathway. However, the mechanism of abnormal YAP activation in HCC has not been well elucidated. Here, we screened a Deubiquitinating enzymes' (DUB) siRNA library targeting DUBs, and identified Ubiquitin Specific Peptidase 19 (USP19) as a specific deubiquitinating enzyme of YAP in HCC, which could stabilize YAP at K76 and K90 sites via removing the K48- and K11-linked ubiquitin chains. USP19 knockdown decreased the expression of YAP protein and its target gene (CTGF, CYR61, ANKRD1) expression. Through substantial in vivo and in vitro experiments, we prove that USP19 facilities the proliferation and migration of HCC. More importantly, we found that USP19 was upregulated in HCC tissues and associated with poor prognosis. In general, our research revealed a novel post-translational mechanism between USP19 and YAP in HCC, suggesting that USP19 may be a pivotal therapeutic target for HCC treatment.

Experimental study on the seepage mutation of natural karst collapse pillar (KCP) fillings over mass outflow.

Conduction between the unique geological formation karst collapse pillar (KCP) and the fractures caused by mining in the coal seam floor can lead to catastrophic water inrush disasters in many coalmines in Northern China. It is widely recognized that seepage mutation induced by the migration/loss of KCP fillings (highly broken rocks filling the fractured rocks) happens during occurrence of the KCP-related water inrush. However, roles of fluid path (mining-induced fracture) scale and KCP filling porosity in seepage mutation evolution remain unclear. Here, we conducted seepage tests on natural KCP fillings containing rock particles of different sizes. The filling specimens were deformed to different porosities from 14 to 26% through axial compression, and small to large fluid paths were simulated by seepage plates with distinct pore sizes from 2.5 to 12.5 mm. We found that seepage mutation occurs with significant permeability enhancement by 2 orders of magnitude under a pore diameter of 12.5 mm and a specimen porosity of 26%. There is a strong linear relationship between specimen permeability and Reynolds number (Re) over seepage mutation. The mutation is caused by the sudden collapse of the specimen skeleton and subsequent quick outflow of the particles. Therefore, it is inferred that the KCP-related water inrush is more likely to happen when highly porous KCP fillings are present and mining-induced fractures are well developed.

CNN-LSTM Hybrid Model to Promote Signal Processing of Ultrasonic Guided Lamb Waves for Damage Detection in Metallic Pipelines.

The ultrasonic guided lamb wave approach is an effective non-destructive testing (NDT) method used for detecting localized mechanical damage, corrosion, and welding defects in metallic pipelines. The signal processing of guided waves is often challenging due to the complexity of the operational conditions and environment in the pipelines. Machine learning approaches in recent years, including convolutional neural networks (CNN) and long short-term memory (LSTM), have exhibited their advantages to overcome these challenges for the signal processing and data classification of complex systems, thus showing great potential for damage detection in critical oil/gas pipeline structures. In this study, a CNN-LSTM hybrid model was utilized for decoding ultrasonic guided waves for damage detection in metallic pipelines, and twenty-nine features were extracted as input to classify different types of defects in metallic pipes. The prediction capacity of the CNN-LSTM model was assessed by comparing it to those of CNN and LSTM. The results demonstrated that the CNN-LSTM hybrid model exhibited much higher accuracy, reaching 94.8%, as compared to CNN and LSTM. Interestingly, the results also revealed that predetermined features, including the time, frequency, and time-frequency domains, could significantly improve the robustness of deep learning approaches, even though deep learning approaches are often believed to include automated feature extraction, without hand-crafted steps as in shallow learning. Furthermore, the CNN-LSTM model displayed higher performance when the noise level was relatively low (e.g., SNR = 9 or higher), as compared to the other two models, but its prediction dropped gradually with the increase of the noise.

Ganoderenic acid D-loaded functionalized graphene oxide-based carrier for active targeting therapy of cervical carcinoma.

Ganoderenic acid D (GAD), extracted from the Chinese herb Ganoderma lucidum, was loaded onto a graphene oxide-polyethylene glycol-anti-epidermal growth factor receptor (GO-PEG-EGFR) carrier to develop a targeting antitumor nanocomposite (GO-PEG@GAD). The carrier was fabricated from PEG and anti-EGFR aptamer modified GO. Targeting was mediated by the grafted anti-EGFR aptamer, which targets the membrane of HeLa cells. Physicochemical properties were characterized by transmission electron microscopy, dynamic light scattering, X-ray powder diffraction, and Fourier transform infrared spectroscopy. High loading content (77.3 % ± 1.08 %) and encapsulation efficiency (89.1 % ± 2.11 %) were achieved. Drug release continued for approximately 100 h. The targeting effect both in vitro and in vivo was confirmed by confocal laser scanning microscopy (CLSM) and imaging analysis system. The mass of the subcutaneous implanted tumor was significantly decreased by 27.27 ± 1.23 % after treatment with GO-PEG@GAD compared with the negative control group. Moreover, the in vivo anti-cervical carcinoma activity of this medicine was due to activation of the intrinsic mitochondrial pathway.

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia-endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathway and enhancing endothelial angiogenic metabolism to promote angiogenesis. These results suggest that Gal3 may be a novel and effective target in the treatment of retinal angiogenesis.

Abnormally elevated EZH2-mediated H3K27me3 enhances osteogenesis in aortic valve interstitial cells by inhibiting SOCS3 expression.

BACKGROUND AND AIMS: The osteogenic transition of aortic valve interstitial cells (AVICs) plays a critical role for the progression of calcific aortic valve disease (CAVD). Enhancer of zeste homolog 2 (EZH2) is an important methyltransferase for histone H3 Lys27 (H3K27) that has been found to be involved in osteogenesis. Here, we investigated the effect and mechanism of EZH2 in CAVD progression. METHODS: High throughout mRNA sequencing, qRT-PCR and immunoblot were performed to screen differentially expressed genes in non-CAVD and CAVD aortic valves. To investigate the role of EZH2 and SOCS3 in osteogenesis, AVICs were treated with siRNA, adenovirus and specific inhibitors, then osteogenic markers and mineralized deposits were examined. In vivo, the morphology and function of aortic valves were investigated by HE stain and echocardiography in ApoE-/- mice fed a long-term western diet (WD). RESULTS: We discovered that EZH2 was upregulated and SOCS3 was downregulated in calcified aortic valves. In AVICs, inhibition or silencing of EZH2 attenuated the osteogenic responses. On the other hand, demethylases inhibitor (GSK-J4) enhanced osteogenic transition of AVICs. Moreover, SOCS3 knockdown enhanced the expression of osteogenic markers, while SOCS3 overexpression suppressed osteogenesis and calcification. The chromatin immunoprecipitation and restored experiments indicated that EZH2 directly targeted SOCS3 to promote osteogenic responses of AVICs. In vivo, treatment with EZH2 inhibitor through intraperitoneal injection attenuated aortic valve thickening, calcification and dysfunction induced by WD. CONCLUSIONS: Collectively, we found that EZH2-mediated H3K27me3 enhanced osteogenesis and microcalcification of AVICs via inhibiting SOCS3 expression, which provides potential targets for future therapeutic interventions of CAVD.

Molecular pathogenesis: Connections between viral hepatitis-induced and non-alcoholic steatohepatitis-induced hepatocellular carcinoma.

Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.

Deep Learning Empowered Structural Health Monitoring and Damage Diagnostics for Structures with Weldment via Decoding Ultrasonic Guided Wave.

Welding is widely used in the connection of metallic structures, including welded joints in oil/gas metallic pipelines and other structures. The welding process is vulnerable to the inclusion of different types of welding defects, such as lack of penetration and undercut. These defects often initialize early-age cracking and induced corrosion. Moreover, welding-induced defects often accompany other types of mechanical damage, thereby leading to more challenges in damage detection. As such, identification of weldment defects and interaction with other mechanical damages at their early stage is crucial to ensure structural integrity and avoid potential premature failure. The current strategies of damage identification are achieved using ultrasonic guided wave approaches that rely on a change in physical parameters of propagating waves to discriminate as to whether there exist damaged states or not. However, the inherently complex nature of weldment, the complication of damages interactions, and large-scale/long span structural components integrated with structure uncertainties pose great challenges in data interpretation and making an informed decision. Artificial intelligence and machine learning have recently become emerging methods for data fusion, with great potential for structural signal processing through decoding ultrasonic guided waves. Therefore, this study aimed to employ the deep learning method, convolutional neural network (CNN), for better characterization of damage features in terms of welding defect type, severity, locations, and interaction with other damage types. The architecture of the CNN was set up to provide an effective classifier for data representation and data fusion. A total of 16 damage states were designed for training and calibrating the accuracy of the proposed method. The results revealed that the deep learning method enables effectively and automatically extracting features of ultrasonic guided waves and yielding high precise prediction for damage detection of structures with welding defects in complex situations. In addition, the effectiveness and robustness of the proposed methods for structure uncertainties using different embedding materials, and data under noise interference, was also validated and findings demonstrated that the proposed deep learning methods still exhibited a high accuracy at high noise levels.

Association Between Dietary Fiber Intake and Heart Failure Among Adults: National Health and Nutrition Examination Survey 2009-2018.

Objective: To explore the association between dietary fiber and heart failure (HF). Methods: Data were collected from the 2009-2018 National Health and Nutrition Examination Survey. Dietary fiber intake data were obtained from two 24-h dietary recall interviews. Logistic regression and restricted cubic spline models were used to explore the association of dietary intakes of total, cereal, fruit, and vegetable fiber with HF prevalence. Results: A total of 21869 adults were included in this study. After adjusting for multiple confounding factors, the odds ratios (OR) and 95% confidence intervals (CI) for HF was 0.49 (0.28 to 0.87, P for trend = 0.016) for the highest tertile versus lowest tertile of total fiber intake. Similar results were observed for cereal but not fruit and vegetable fiber intake. Dose-response analysis indicated that dietary intake of total and cereal fiber were inversely associated with HF in a linear manner. Conclusion: Intakes of total and cereal fiber were inversely associated with HF in adults.

The Pharmacological Rationales and Molecular Mechanisms of Ganoderma lucidum Polysaccharides for the Therapeutic Applications of Multiple Diseases.

As a versatile Chinese herb, Ganoderma lucidum (Leyss. ex Fr.) Karst (G. lucidum) has been applied to treat multiple diseases in clinics and improve the quality of life of patients. Among all of its extracts, the main bioactive components are G. lucidum polysaccharides (GLPs), which possess many therapeutic effects, such as antitumor, immunoregulatory, anti-oxidant, antidiabetic, antibacterial, and antifungal effects and neuroprotection activities. This review briefly summarized the recent studies of the pharmacological rationales of GLPs and their underlying molecular signaling transmission mechanisms in treating diseases. Until now, the clear mechanisms of GLPs for treating diseases have not been reported. In this review, we used the keywords of "Ganoderma lucidum polysaccharides" and "tumor" to search in PubMed (years of 1992-2020), then screened and obtained 160 targets of antitumor activities in the literatures. The network pharmacology and mechanism framework were employed in this study as powerful approaches to systematically analyze the complicated potential antitumor mechanisms and targets of GLPs in cancer. We then found that there are 69 targets and 21 network pathways in "Pathways in cancer". Besides, we summarized the effects of GLPs and the models and methods used in the research of GLPs. In conclusion, GLPs have been studied extensively, but more in-depth research is still needed to determine the exact mechanisms and pathways. Therefore, this review might provide new insights into the vital targets and pathways for researchers to study the pharmacological mechanisms of GLPs for the treatment of diseases.

COVID-19, Economic Impact, Mental Health, and Coping Behaviors: A Conceptual Framework and Future Research Directions.

The COVID-19 pandemic has caused serious economic and social consequences. Recent research shows that the pandemic has not only caused a physical health crisis but also caused many psychological and mental crises. Based on the contemporary cognitive-behavioral models, this article offers a conceptual analysis of how the pandemic affects individual mental health and coping behaviors from the perspective of individual economic status, individual context, and social context. The analysis shows that (1) the pandemic has led to increased economic uncertainty, increased unemployment and underemployment pressure, increased income uncertainty, and different degrees of employment pressure and economic difficulties; (2) these difficulties have stimulated different levels of mental health problems, ranging from perceived insecurity (environmental, food safety, etc.), worry, fear, to stress, anxiety, depression, etc., and the mental health deterioration varies across different groups, with the symptoms of psychological distress are more obvious among disadvantageous groups; and (3) mental health problems have caused behavior changes, and various stress behaviors such as protective behaviors and resistive behaviors. Future research directions are suggested.

A Game Model for Medical Service Pricing Based on the Diagnosis Related Groups.

Background: Currently there are various issues that exist in the medical institutions in China as a result of the price-setting in DRGs, which include the fact that medical institutions tend to choose patients and that the payment standard for complex cases cannot reasonably compensate the cost. Objective: The main objective is to prevent adverse selection problems in the operations of a diagnosis-related groups (DRGs) system with the game pricing model for scientific and reasonable pricing. Methods: The study proposes an improved bargaining game model over three stages, with the government and patients forming an alliance. The first stage assumes the alliance is the price maker in the Stackelberg game to maximize social welfare. Medical institutions are a price taker and decide the level of quality of medical service to maximize their revenue. A Stackelberg equilibrium solution is obtained. The second stage assumes medical institutions dominate the Stackelberg game and set an optimal service quality for maximizing their revenues. The alliance as the price taker decides the price to maximize the social welfare. Another Stackelberg equilibrium solution is achieved. The final stage establishes a Rubinstein bargaining game model to combine the Stackelberg equilibrium solutions in the first and second stage. A new equilibrium between the alliance and medical institutions is established. Results: The results show that if the price elasticity of demand increases, the ratio of cost compensation on medical institutions will increase, and the equilibrium price will increase. The equilibrium price is associated with the coefficient of patients' quality preference. The absolute risk aversion coefficient of patients affects government compensation and total social welfare. Conclusion: In a DRGs system, considering the demand elasticity and the quality preference of patients, medical service pricing can prevent an adverse selection problem. In the future, we plan to generalize these models to DRGs pricing systems with the effects of competition of medical institutions. In addition, we suggest considering the differential compensation for general hospitals and community hospitals in a DRGs system, in order to promote the goal of hierarchical diagnosis and treatment.

Mental Health and the Role of Physical Activity During the COVID-19 Pandemic.

The COVID-19 pandemic and its related public health restrictions are having an increasingly serious impact on mental health, and measures need to be taken to curb this trend. The positive relationship between physical exercise and mental health has been well-established, but during the COVID-19 pandemic, with various restrictions, the space and facilities for physical exercise are limited. This article explores the relationship between physical exercise and mental health during the COVID-19 pandemic based on the latest research findings published in 2019-2021. We offer a novel model that consists of three central arguments. First, physical exercises during COVID-19, especially supervised exercises, are conducive to enhancing happiness and improving mental health. Second, physical exercise reduces people's anxiety, sadness and depression during the COVID-19 pandemic. Third, the maintenance and improvement of mental health are related to the intensity and frequency of physical exercise. Intensive and frequent physical exercise are conducive to maintaining mental health. Finally, this article proposes important directions for future research.

Ganoderic acid improves 5-fluorouracil-induced cognitive dysfunction in mice.

5-Fluorouracil (5-FU) is a chemotherapeutic drug with a good anti-cancer effect on various types of cancers, such as colorectal cancer and breast cancer. However, previous studies have found that 5-FU could induce cognitive deficit in clinics. As ganoderic acid, isolated from Ganoderma lucidum, has a protective effect on neurons, this study investigated the effects of ganoderic acid (GA) against 5-FU-induced cognitive dysfunction with a series of behavioral tests and related indicators. Experimental results showed that GA significantly prevented the reduction of spatial and non-spatial memory in 5-FU-treated mice. In addition, GA not only ameliorated the damage to hippocampal neurons and mitochondrial structure, but also significantly improved abnormal protein expression of mitochondrial biogenesis related marker PGC-1α, and mitochondrial dynamics related markers MFN2, DRP1 and FIS1 in the hippocampi of 5-FU-treated mice. Moreover, GA could up-regulate the expression of neuronal survival and growth-related proteins, such as BDNF, p-ERK, p-CREB, p-Akt, p-GSK3ß, Nrf2, p-mTOR, and p-S6, in the hippocampi of 5-FU-treated mice. These results suggest that GA could prevent cognitive dysfunction in mice treated with 5-FU via preventing mitochondrial impairment and enhancing neuronal survival and growth, which provide evidence for GA as a promising adjunctive therapy for chemotherapy related cognitive impairment in clinics.

Antimetastatic Effects of Ganoderma lucidum Polysaccharide Peptide on B16-F10-luc-G5 Melanoma Mice With Sleep Fragmentation.

Ganoderma lucidum (Lingzhi) polysaccharide peptide (GL-pp) is a component of the globally acknowledged traditional Chinese medicine Ganoderma lucidum; Ganoderma lucidum is known for its sedative, hypnotic, immune regulatory, antitumor, and other pharmacological effects. In recent years, sleep disorders have been linked to many diseases and human body disorders, including cancer. Some experimental studies in mice found that sleep fragmentation could promote tumor development and progression. However, effects on GL-pp on tumor metastasis under circumstances of sleep disorders have rarely been studied. Thus, in this study, we used mice with sleep fragmentation (SF) bearing B16-F10-luc-G5 melanoma tumors to investigate the effect of SF on melanoma metastasis. Furthermore, we investigated the antitumor and antimetastatic effects of GL-pp (80 mg/kg) in mice suffering from SF and bearing B16-F10-luc-G5. Then, whole proteomics was used to analyze the differences in protein expression in the lung tissue between SF mice bearing B16-F10-luc-G5 with and without GL-pp administration. High-throughput pyrosequencing of 16S rRNA was also used to analyze the impact of GL-pp on the gut microbiota composition in SF mice bearing B16-F10-luc-G5. Last, the effects of GL-pp on macrophage polarization and TNF-α serum levels were detected. Collectively, we found that SF significantly facilitated the B16-F10-luc-G5 melanoma tumor metastasis in mice, while GL-pp significantly reduced B16-F10-luc-G5 melanoma tumor metastasis under the condition of SF, in which proteomics and gut microbiota had been changed greatly.

Tripartite motif 16 ameliorates nonalcoholic steatohepatitis by promoting the degradation of phospho-TAK1.

Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma and liver disorders have become the leading causes for the need of liver transplantation in developed countries. Lipotoxicity plays a central role in NASH progression by causing endoplasmic reticulum stress and disrupting protein homeostasis. To identify key molecules that mitigate the detrimental consequences of lipotoxicity, we performed integrative multiomics analysis and identified the E3 ligase tripartite motif 16 (TRIM16) as a candidate molecule. In particular, we found that lipid accumulation and inflammation in a mouse NASH model is mitigated by TRIM16 overexpression but aggravated by its depletion. Multiomics analysis showed that TRIM16 suppressed NASH progression by attenuating the activation of the mitogen-activated protein kinase (MAPK) signaling pathway; specifically, by preferentially interacting with phospho-TAK1 to promote its degradation. Together, these results identify TRIM16 as a promising therapeutic target for the treatment of NASH.