Temporal-Specific Sex and Injury-Dependent Changes on Neurogranin-Associated Synaptic Signaling After Controlled Cortical Impact in Rats.

Extensive effort has been made to study the role of synaptic deficits in cognitive impairment after traumatic brain injury (TBI). Neurogranin (Ng) is a calcium-sensitive calmodulin (CaM)-binding protein essential for Ca2+/CaM-dependent kinase II (CaMKII) autophosphorylation which subsequently modulates synaptic plasticity. Given the loss of Ng expression after injury, additional research is warranted to discern changes in hippocampal post-synaptic signaling after TBI. Under isoflurane anesthesia, adult, male and female Sprague-Dawley rats received a sham/control or controlled cortical impact (CCI) injury. Ipsilateral hippocampal synaptosomes were isolated at 24 h and 1, 2, and 4 weeks post-injury, and western blot was used to evaluate protein expression of Ng-associated signaling proteins. Non-parametric Mann-Whitney tests were used to determine significance of injury for each sex at each time point. There were significant changes in the hippocampal synaptic expression of Ng and associated synaptic proteins such as phosphorylated Ng, CaMKII, and CaM up to 4 weeks post-CCI, demonstrating TBI alters hippocampal post-synaptic signaling. This study furthers our understanding of mechanisms of cognitive dysfunction within the synapse sub-acutely after TBI.

Poisson representation: a bridge between discrete and continuous models of stochastic gene regulatory networks.

Stochastic gene expression dynamics can be modelled either discretely or continuously. Previous studies have shown that the mRNA or protein number distributions of some simple discrete and continuous gene expression models are related by Gardiner's Poisson representation. Here, we systematically investigate the Poisson representation in complex stochastic gene regulatory networks. We show that when the gene of interest is unregulated, the discrete and continuous descriptions of stochastic gene expression are always related by the Poisson representation, no matter how complex the model is. This generalizes the results obtained in Dattani & Barahona (Dattani & Barahona 2017 J. R. Soc. Interface 14, 20160833 (doi:10.1098/rsif.2016.0833)). In addition, using a simple counter-example, we find that the Poisson representation in general fails to link the two descriptions when the gene is regulated. However, for a general stochastic gene regulatory network, we demonstrate that the discrete and continuous models are approximately related by the Poisson representation in the limit of large protein numbers. These theoretical results are further applied to analytically solve many complex gene expression models whose exact distributions are previously unknown.

Experimental traumatic brain injury increases epichaperome formation.

Under normal conditions, heat shock proteins work in unison through dynamic protein interactions collectively referred to as the "chaperome." Recent work revealed that during cellular stress, the functional interactions of the chaperome are modified to form the "epichaperome," which results in improper protein folding, degradation, aggregation, and transport. This study is the first to investigate this novel mechanism of protein dishomeostasis in traumatic brain injury (TBI). Male and female adult, Sprague-Dawley rats received a lateral controlled cortical impact (CCI) and the ipsilateral hippocampus was collected 24 h 1, 2, and 4 weeks after injury. The epichaperome complex was visualized by measuring HSP90, HSC70 and HOP expression in native-PAGE and normalized to monomeric protein expression. A two-way ANOVA examined the effect of injury and sex at each time-point. Native HSP90, HSC70 and HOP protein expression showed a significant effect of injury effect across all time-points. Additionally, HSC70 and HOP showed significant sex effects at 24 h and 4 weeks. Altogether, controlled cortical impact significantly increased formation of the epichaperome across all proteins measured. Further investigation of this pathological mechanism can lead to a greater understanding of the link between TBI and increased risk of neurodegenerative disease and targeting the epichaperome for therapeutics.

Trend analysis of dependence between rainfall and storm tides in coastal cities.

Compound flooding from rainfall and storm tides is prone to occur in coastal cities. The identification of them is essential for controlling urban flooding. First, the dependence between rainfall and storm tides is quantified by Kendall's τ, Spearman's ρ, and tail dependence coefficient. Then, a bivariate copula-based probability distribution model is built to calculate the joint and conditional probability of rainfall and storm tides. Finally, MK and SQMK methods are employed to detect the trends of the dependence and joint probability. The results show that: (1) The dependence between strong rainfall and corresponding storm tides is much higher than that of small rainfall and storm tides, and the effect of tropical cyclones may be one of the reasons. (2) The dependence between rainfall and storm tides is the largest in October and the smallest in July. More attention should be paid to the compound flooding caused by rainfall and storm tides in October for Haikou. (3) The upper tail dependence coefficient of the rainfall and storm tides is significantly greater than the lower tail dependence coefficient and exhibits a significant positive trend. The results can provide additional insights into the effect of rainfall and storm tides for coastal flood management.

USP10 promotes intrahepatic cholangiocarcinoma cell survival and stemness via SNAI1 deubiquitination.

Cancer cell stemness contributes significantly to intrahepatic cholangiocarcinoma (ICC) progression. However, the roles of deubiquitinating enzymes (DUBs) in ICC modulation are poorly understood. Ubiquitin specific peptidase 10 (USP10) was highly expressed in ICC spheres. The interaction between USP10 and snail family transcriptional repressor 1 (SNAI1) reduced the polyubiquitination of the SNAI1 protein and stabilized the SNAI1 protein. USP10 knockdown in RBE cells inhibited cell proliferation, promoted cell apoptosis and decreased the diameter of the formed spheres and the expression levels of CD44, EpCAM, OCT4 and SOX2. SNAI1 overexpression alleviated the effect of USP10 knockdown in RBE cells. In addition, the knockdown of USP10 attenuated the ability of RBE cells to form tumors subcutaneously in nude mice. Our results revealed that USP10 attenuates ICC cell malignancy by deubiquitinating SNAI1, indicating that USP10 could be developed as a therapeutic target for ICC treatment.

Olfactomedin 4 deletion exacerbates nonalcoholic fatty liver disease through P62-dependent mitophagy in mice.

BACKGROUND & AIMS: Olfactomedin 4 (OLFM4) is a glycoprotein that is related to obesity and insulin resistance. This study aims to investigate the role and mechanisms of OLFM4 in nonalcoholic fatty liver disease (NAFLD). APPROACH & RESULTS: OLFM4 expression levels were significantly increased in liver samples from NAFLD patients and in cellular and mouse models of NAFLD. Cell lines deficient in or overexpressing OLFM4 and Olfm4-/- mice were established to study its role in NAFLD. OLFM4 deficiency significantly aggravated diet-induced hepatic steatosis and inflammation, while re-expression of OLFM4 ameliorated diet-induced hepatic steatosis and inflammation in mice. Mechanistically, OLFM4 deficiency disrupted mitochondrial structure and decreased mitophagy in hepatocytes, thereby aggravating hepatic lipogenesis, inflammation, and insulin resistance. Moreover, OLFM4 directly interacted with P62, and OLFM4 deficiency decreased mitophagy in both cellular and mouse models of NAFLD through a P62-dependent mechanism. We also show that blocking the P62-ZZ-domain using XRK3F2 prevented diet-induced NAFLD in Olfm4-/- mice. CONCLUSION: OLFM4 is significantly upregulated in NAFLD, and OLFM4 deletion exacerbates NAFLD through P62-dependent mitophagy.

Roles of sulfur-containing compounds in fermented beverages with 2-furfurylthiol as a case example.

Aroma is a critical component of the flavor and quality of beverages. Among the volatile chemicals responsible for fragrance perception, sulfur compounds are unique odorants due to their extremely low odor threshold. Although trace amounts of sulfur compounds can enhance the flavor profile of beverages, they can lead to off-odors. Sulfur compounds can be formed via Maillard reaction and microbial metabolism, imparting coffee aroma and altering the flavor of beverages. In order to increase the understanding of sulfur compounds in the field of food flavor, 2-furfurylthiol (FFT) was chosen as a representative to discuss the current status of their generation, sensory impact, enrichment, analytical methods, formation mechanisms, aroma deterioration, and aroma regulation. FFT is comprehensively reviewed, and the main beverages of interest are typically baijiu, beer, wine, and coffee. Challenges and recommendations for FFT are also discussed, including analytical methods and mechanisms of formation, interactions between FFT and other compounds, and the development of specific materials to extend the duration of aroma after release.

A simpler definition of MAFLD precisely predicts incident metabolic diseases: a 7-year cohort study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel definition proposed in 2020 with a relatively complex set of criteria. Thus, simplified criteria that are more applicable are required. This study aimed to develop a simplified set of criteria for identifying MAFLD and predicting MAFLD-related metabolic diseases. METHODS: We developed a simplified set of metabolic syndrome-based criteria for MAFLD, and compared the performance of the simplified criteria with that of the original criteria in predicting MAFLD-related metabolic diseases in a 7-year follow-up. RESULTS: In the 7-year cohort, a total of 13,786 participants, including 3372 (24.5%) with fatty liver, were enrolled at baseline. Of the 3372 participants with fatty liver, 3199 (94.7%) met the MAFLD-original criteria, 2733 (81.0%) met the simplified criteria, and 164 (4.9%) were metabolic healthy and met neither of the criteria. During 13,612 person-years of follow-up, 431 (16.0%) fatty liver individuals newly developed T2DM, with an incidence rate of 31.7 per 1000 person-years. Participants who met the simplified criteria had a higher risk of incident T2DM than those who met the original criteria. Similar results were observed for incident hypertension, and incident carotid atherosclerotic plaque. CONCLUSION: The MAFLD-simplified criteria are an optimized risk stratification tool for predicting metabolic diseases in fatty liver individuals.

High-Sensitivity Wearable Sensor Based On a MXene Nanochannel Self-Adhesive Hydrogel.

To address the shortcomings of traditional filler-based wearable hydrogels, a new type of nanochannel hydrogel sensor is fabricated in this work through a combination of the unique structure of electrospun fiber textile and the properties of a double network hydrogel. Unlike the traditional Ti3C2Tx MXene-based hydrogels, the continuously distributed Ti3C2Tx MXene in the nanochannels of the hydrogel forms a tightly interconnected structure similar to the neuron network. As a result, they have more free space to flip and perform micromovements, which allows one to significantly increase the electrical conductivity and sensitivity of the hydrogel. According to the findings, the Ti3C2Tx MXene nanochannel hydrogel has excellent mechanical properties as well as self-adhesion and antifreezing characteristics. The hydrogel sensor successfully detects different human motions and physiological signals (e.g., low pulse signals) with high stability and sensitivity. Therefore, the proposed Ti3C2Tx MXene-based hydrogel with a unique structure and properties is very promising in the field of flexible wearable devices.

HADHA alleviates hepatic steatosis and oxidative stress in NAFLD via inactivation of the MKK3/MAPK pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a liver metabolic syndrome and still lacks effective treatments because the molecular mechanism underlying the development of NAFLD is not completely understood. We investigated the role of Hydroxyl CoA dehydrogenase alpha subunit (HADHA) in the pathogenesis of NAFLD. METHODS: HADHA expression was detected both in NAFLD cell and mice, and knockdown of HADHA in free fatty acids (FFA)-treated L02 or overexpression of HADHA in high fat diet (HFD)-fed mice was used to detected the influence of HADHA on hepatic steatosis, mitochondrial dysfunction, and oxidative stress by regulating of MKK3/MAPK signaling. RESULTS: Our data revealed that HADHA expression was decreased in FFA-treated L02 cells and in HFD-fed mice. Knockdown of HADHA markedly aggravated hepatic steatosis, inflammation and oxidative stress in FFA-treated L02 cells, which was associated with the activation of MKK3/MAPK signalling pathways. Moreover, oxidative stress and liver lesions were improved in NAFLD mice by upregulation of HADHA. Importantly, we demonstrated that overexpression of HADHA inhibited the expression of p-MAPK in NAFLD mice, reducing lipid accumulation and steatosis. CONCLUSION: HADHA may function as a protective factor in the progression of NAFLD by alleviating abnormal metabolism and oxidative stress by suppressing MKK3/MAPK signalling pathway activation, providing a new target for the treatment of NAFLD.

The associations between modifiable risk factors and nonalcoholic fatty liver disease: A comprehensive Mendelian randomization study.

BACKGROUND AND AIMS: Early identification of modifiable risk factors is essential for the prevention of nonalcoholic fatty liver disease (NAFLD). We aimed to systematically explore the relationships between genetically predicted modifiable risk factors and NAFLD. APPROACH AND RESULTS: We applied univariable and multivariable Mendelian randomization analyses to explore the relationships between 35 modifiable risk factors and NAFLD. We also evaluated the combined results in three independent large genome-wide association studies. Genetically predicted alcohol frequency, elevated serum levels of liver enzymes, triglycerides, C-reactive protein, and obesity traits, including body mass index, waist circumference, and body fat mass, were associated with increased risks of NAFLD (all with p < 0.05). Poor physical condition had a suggestive increased risk for NAFLD (odds ratio [OR] = 2.63, p  = 0.042). Genetically instrumented type 2 diabetes (T2DM), hypothyroidism, and hypertension all increased the risk for NAFLD, and the ORs (95% confidence interval) were 1.508 (1.20-1.90), 13.08 (1.53-111.65), and 3.11 (1.33-7.31) for a 1-U increase in log-transformed odds, respectively. The positive associations of T2DM and hypertension with NAFLD remained significant in multivariable analyses. The combined results from the discovery and two replication datasets further confirmed that alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension significantly increase the risk of NAFLD, whereas higher education and high-density lipoprotein cholesterol (HDL-cholesterol) could lower NAFLD risk. CONCLUSIONS: Genetically predicted alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension were associated with an increased risk of NAFLD, whereas higher education and HDL-cholesterol were associated with a decreased risk of NAFLD.

Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study.

Background and aim: Previous observational studies have suggested a paradoxical relationship between iron status and the risk of non-alcoholic fatty liver disease (NAFLD). Observed associations in these epidemiological studies fail to show sequential temporality and suffer from problems of confounding. Therefore, we performed a bidirectional two-sample Mendelian randomization (MR) to evaluate the relationship between serum iron status and NAFLD. Methods: The inverse weighted method (IVW) meta-analysis with the fixed-effect model was the main method to estimate the relationship between iron status, including serum ferritin, iron, transferrin saturation (TSAT) and total iron-binding capacity (TIBC), and NAFLD. Weighted median, penalized weighted median, and MR Robust Adjusted Profile Score (MR RAPS) methods were used as additional analyses. Sensitivity analyses were performed with Cochran's Q test, MR-Egger regression, Steiger filtering, and the MR PRESSO test. Results: Iron status, including serum ferritin, iron, and TSAT, was associated with an increased risk of NAFLD (odds ratio (OR) (95% confidence interval (CI)): 1.25 (1.06, 1.48); 1.24 (1.05, 1.46), 1.16 (1.02, 1.31), respectively). In contrast, minimal effects of NAFLD on serum ferritin, iron, TSAT, and TIBC were observed (OR (95% CI): 1.01 (1.00, 1.02), 1.01 (1.00, 1.02), 1.03 (1.01, 1.05), 1.03 (1.01, 1.05), respectively). Conclusions: Our findings corroborated the causal associations between serum ferritin, iron, TSAT, and NAFLD, which might suggest the potential benefits of iron-related therapy. In addition, NAFLD might, in turn, slightly affect iron homeostasis indicated as serum ferritin, iron, TSAT, and TIBC, but this needs to be further confirmed.

MicroRNA-376b-3p ameliorates nonalcoholic fatty liver disease by targeting FGFR1 and regulating lipid oxidation in hepatocytes.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease whose molecular mechanisms remain unclear. This study aimed to explore the role and mechanisms of microRNA-376b-3p in NAFLD. MATERIALS AND METHODS: We used a microarray to reveal hepatic microRNA expression profiles and validated their expression in cellular and mouse models via qRT-PCR. In vitro, the expression of microRNA-376b-3p was increased by a microRNA-376b-3p mimic and decreased by a microRNA-376b-3p inhibitor. The role and potential mechanisms of microRNA-376b-3p in NAFLD were investigated in mice injected with lentiviral vectors before high-fat diet (HFD) feeding, and the direct target gene was explored using a dual-luciferase reporter gene assay and confirmed by Western blotting. KEY FINDINGS: Microarray analysis and subsequent validation showed that the expression of microRNA-376b-3p was downregulated by nearly 90 % in the livers of HFD-fed mice and by >50 % in free fatty acid-stimulated hepatocytes. Overexpression of microRNA-376b-3p markedly ameliorated hepatic lipid accumulation, which was attributable to an increase in fatty acid oxidation. Conversely, inhibition of miR-376b-3p exhibited the opposite effects. The luciferase reporter assay indicated that Fgfr1 is a direct target gene of miR-376b-3p. Fgfr1 intervention eliminated the effect of miR-376b-3p on the lipid oxidation pathway and hepatocyte steatosis, which suggests that miR-376b-3p regulates fatty acid oxidation by targeting Fgfr1 to influence NAFLD development. SIGNIFICANCE: miR-376b-3p was downregulated in NAFLD and has a novel regulatory role in lipid oxidation through a miR-376b-3p-Fgfr1-dependent mechanism. Thus, miR-376b-3p may serve as a potential diagnostic marker or therapeutic target for NAFLD.

All-trans Retinoic Acid has Limited Therapeutic Effects on Cognition and Hippocampal Protein Expression After Controlled Cortical Impact.

Traumatic brain injury (TBI) is known to impair synaptic function, and subsequently contribute to observed cognitive deficits. Retinoic Acid (RA) signaling modulates expression of synaptic plasticity proteins and is involved in hippocampal learning and memory. All trans-retinoic acid (ATRA), a metabolite of Vitamin A, has been identified as a potential pharmacotherapeutic for other neurological disorders due to this role. This study conducted an ATRA dose response to determine its therapeutic effects on cognitive behaviors and expression of hippocampal markers of synaptic plasticity and RA signaling proteins after experimental TBI. Under isoflurane anesthesia, adult male Sprague Dawley rats received either controlled cortical impact (CCI, 2.5 mm deformation, 4 m/s) or control surgery. Animals received daily intraperitoneal injection of 0.5, 1, 5, or 10 mg/kg of ATRA or vehicle for 2 weeks. Animals underwent motor and spatial learning and memory testing. Hippocampal expression of synaptic plasticity proteins neurogranin (Ng), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 sub-unit, as well as RA signaling proteins STRA6, ADLH1a1, CYP26A1 and CYP26B1 were evaluated by western blot at 2-weeks post-injury. ATRA treatment significantly recovered Ng synaptic protein expression, while having no effect on motor performance, spatial learning, and memory, and GluA1 expression after TBI. RA signaling protein expression is unchanged 2 weeks after TBI. Overall, ATRA administration after TBI showed limited therapeutic benefits compared to the vehicle.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease.

BACKGROUND: Recently, nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic-associated fatty liver disease (MAFLD). Based on the definition for MAFLD, a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature. AIM: To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD. METHODS: Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups. The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction. The histologic features were compared according to different metabolic disorders and liver enzyme levels. RESULTS: MAFLD individuals had a higher NAFLD activity score (P = 0.002) and higher severity of hepatic steatosis (42.6% Grade 1, 42.6% Grade 2, and 14.8% Grade 3 in MAFLD; 81.8% Grade 1, 13.6% Grade 2, and 4.5% Grade 3 in non-MAFLD; P = 0.007) than the non-MAFLD group. Lobular and portal inflammation, hepatic ballooning, fibrosis grade, and the presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis were comparable between the two groups. The higher the liver enzyme levels, the more severe the grades of hepatic steatosis (75.0% Grade 1 and 25.0% Grade 2 in normal liver function; 56.6% Grade 1, 39.6% Grade 2, and 3.8% Grade 3 in increased liver enzyme levels; 27.8% Grade 1, 27.8% Grade 2, and 44.4% Grade 3 in liver injury; P < 0.001). Patients with liver injury (alanine aminotransferase > 3 × upper limit of normal) presented a higher severity of hepatocellular ballooning (P = 0.021). Moreover, the grade of steatosis correlated significantly with hepatocellular ballooning degree (r = 0.338, P = 0.002) and the presence of NASH (r = 0.466, P < 0.001). CONCLUSION: Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD. Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

Comprehensive risk assessment of algae and shellfish in the middle route of South-to-North Water Diversion Project.

Since the main canal of the middle route of South-to-North Water Diversion Project was put into operation, the species, quantity, and biomass of algae and shellfish have responded quickly to the environment, and a single dominant species has appeared in the community, demonstrating the remarkably abnormal proliferation property of algae and shellfish. In order to evaluate the safety risk of abnormal proliferation of algae and shellfish in the middle route and realize dynamic analysis of all kinds of influencing factors, a comprehensive risk evaluation system of algae and shellfish in the middle route of South-to-North Water Diversion Project based on comprehensive weighting and four-element connection number was constructed by integrating the analytic hierarchy process (AHP) and the weight assignment theory of criteria importance through intercriteria (CRITIC). The system consists of 21 evaluation indexes selected from risk factors and carriers. Taking Henan section in the middle route as an example, comprehensive risk evaluation system of algae and shellfish in the middle route of South-to-North Water Diversion Project was applied to calculate the partial connection number of each order and obtain the risk development trend of each indicator. The results showed that algae and shellfish in the middle route were in a very safe state at the safety risk level of level I. Finally, reasonable measures to reduce the risks facing algae and shellfish in the middle route of South-to-North Water Diversion Project are given, which effectively make up the deficiency of existing evaluation methods.

Esophageal Mucosal Autograft for Preventing Stricture After Widespread Endoscopic Submucosal Dissection of Superficial Esophageal Lesions.

BACKGROUND: Although esophageal mucosal autograft prevents esophageal stricture after widespread endoscopic submucosal dissec- tion and has been reported as a new technique, it is relatively unproven in clinical practice. This prospective study was conducted to evaluate our experience using esophageal mucosal autograft to prevent strictures after widespread endoscopic submucosal dissection in patients with widespread superficial esophageal lesions. METHODS: Between October 2017 and June 2018, 15 patients with widespread superficial esophageal lesions were consecutively treated with widespread endoscopic submucosal dissection and then underwent esophageal mucosal autograft. The main outcomes measured included esophageal epithelialization and esophageal stricture. RESULTS: The median longitudinal diameter of the widespread superficial esophageal lesions was 5.2 cm. All 15 patients were success- fully treated with widespread endoscopic submucosal dissection and esophageal mucosal autograft, and the median procedural time was 182 minutes. During follow-up (median, 23 months), esophageal epithelialization was found in 13 patients (86.7%), and 7 patients experienced esophageal stricture (46.7%). In those 7 patients, the esophageal strictures were successfully relieved after endoscopic bal- loon dilation or endoscopic radial incision. No complications related to endoscopic balloon dilation/endoscopic radial incision occurred. Additionally, local recurrence was found in 1 patient with poorly differentiated squamous cell carcinoma, and further surgical resection was performed. CONCLUSIONS: Esophageal mucosal autograft appears to be an efficient approach to reconstructing local esophageal epithelium and might have a potential role in preventing esophageal stricture after widespread endoscopic submucosal dissection. However, as a new technique, it needs more improvement to enhance its role in preventing esophageal stricture after widespread endoscopic submucosal dissection.

3-Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma.

BACKGROUND AND: AIMS: The prognosis of hepatocellular carcinoma (HCC) remains dismal, and its molecular pathogenesis has not been completely defined. The enzyme 3-mercaptopyruvate sulfurtransferase (MPST) regulates endogenous hydrogen sulfide (H2 S) biosynthesis. However, the role of MPST in HCC has never been intensively investigated. METHODS: MPST protein expression was analysed in HCC tumour tissues and matched adjacent tissues. The effect of MPST on HCC progression was studied in vitro and in vivo. RESULTS: The mRNA and protein expression of MPST was significantly downregulated in HCC samples compared with their paired nontumour counterparts. A low MPST expression was associated with larger tumour size and a worse overall survival. Overexpression of MPST in HCC cells inhibited cell proliferation and induced apoptosis. MPST overexpression also significantly suppressed the growth of tumour xenografts in nude mice, whereas silencing MPST by intratumour delivery of siRNA substantially promoted tumour growth. Moreover, diethylnitrosamine-induced mouse HCC was aggravated by MPST gene knockout. Mechanistically, MPST suppressed the cell cycle associated with H2 S production and inhibition of the AKT/FOXO3a/Rb signalling pathway in HCC development. In addition, MPST expression negatively correlated with that of pRb in HCC specimens and the combination of these two parameters is a more powerful predictor of poor prognosis. CONCLUSIONS: MPST may function as a tumour suppressor gene that plays an essential role in HCC proliferation and liver tumorigenesis. It is a candidate predictor of clinical outcome in patients with HCC and may be used as a biomarker and intervention target for new therapeutic strategies.

Heteroatom-doped porous carbon microspheres derived from ionic liquid-lignin solution for high performance supercapacitors.

In this work, nitrogen and phosphorus dual-doped alkali lignin-based carbon microspheres (MLCM) were prepared by pre-oxidation and carbonization of ionic liquid ([Mmim]DMP) -lignin solution and used as green-based supercapacitor electrode materials. Compared with the directly carbonized alkali lignin carbon (LC), MLCM had a spherical structure with higher specific surface area (938.1 m2/g) and pore volume (0.64 cm3/g). Moreover, MLCM materials showed superior electrochemical performance. In the 1 mol/L H2SO4 electrolyte system, MLCM presented the highest specific capacitance of 338.2F/g at a current density of 0.8 A/g. Furthermore, MLCM was used as a positive and negative electrode material to assemble a symmetrical supercapacitor. The resultant device maintained excellent cycle stability after 5000 times of charging and discharging process at 2 A/g. Overall, the facile, green and sustainable synthesis strategy of heteroatom-doped porous carbon microspheres developed in this work opens a new avenue for the fabrication of high-performance carbon electrode materials, especially based on abundant and renewable lignin.