Matrix stiffness-dependent PD-L2 deficiency improves SMYD3/xCT-mediated ferroptosis and the efficacy of anti-PD-1 in HCC.

INTRODUCTION: Heterogeneous tissue stiffening promotes tumor progression and resistance, and predicts a poor clinical outcome in patients with hepatocellular carcinoma (HCC). Ferroptosis, a congenital tumor suppressive mechanism, mediates the anticancer activity of various tumor suppressors, including immune checkpoint inhibitors, and its induction is currently considered a promising treatment strategy. However, the role of extracellular matrix (ECM) stiffness in regulating ferroptosis and ferroptosis-targeted resistance in HCC remains unclear. OBJECTIVES: This research aimed to explore how extracellular matrix stiffness affects ferroptosis and its treatment efficacy in HCC. METHODS: Ferroptosis analysis was confirmed via cell activity, intracellular ferrous irons, and mitochondrial pathology assays. Baseline PD-L2, SMYD3, and SLC7A11 (xCT) were evaluated in 67 sorafenib-treated patients with HCC (46 for non-responder and 21 for responder) from public data. The combined efficacy of shPD-L2, sorafenib, and anti-PD-1 antibody in HCC was investigated in vivo. RESULTS: Here, we revealed that matrix stiffness-induced PD-L2 functions as a suppressor of xCT-mediated ferroptosis to promote cancer growth and sorafenib resistance in patients with HCC. Mechanically, matrix stiffening induced the expression of PD-L2 by activating SMYD3/H3K4me3, which acts as an RNA binding protein to enhance the mRNA stability of FTL and elevate its protein level. Knockdown of PD-L2 significantly promoted xCT-mediated ferroptosis induced by RSL3 or sorafenib on stiff substrate via FTL, whereas its overexpression abolished these upward trends. Notably, PD-L2 deletion in combination with sorafenib and anti-PD-1 antibody significantly sensitized HCC cells and blunted cancer growth in vivo. Additionally, we found the ferroptosis- and immune checkpoint-related prognostic genes that combined PD-L2, SLC7A11 and SYMD3 well predict the clinical efficacy of sorafenib in patients with HCC. CONCLUSION: These findings expand our understanding of the mechanics-dependent PD-L2 role in ferroptosis, cancer progression and resistance, providing a basis for the clinical translation of PD-L2 as a therapeutic target or diagnostic biomarker.

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin.

Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti-HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion-related molecules on HBV replication. The in-depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA-histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA-dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. These data suggest that TRPV4 exerts multifaceted HBV-related synergistic factors and may serve as a therapeutic target for CHB.

Multispectral detection of dietary fiber content in Chinese cabbage leaves across different growth periods.

Multispectral imaging, combined with stoichiometric values, was used to construct a prediction model to measure changes in dietary fiber (DF) content in Chinese cabbage leaves across different growth periods. Based on all the spectral bands (365-970 nm) and characteristic spectral bands (430, 880, 590, 490, 690 nm), eight quantitative prediction models were established using four machine learning algorithms, namely random forest (RF), backpropagation neural network, radial basis function, and multiple linear regression. Finally, a quantitative prediction model of RF learning algorithm is constructed based on all spectral bands, which has good prediction accuracy and model robustness, prediction performance with R2 of 0.9023, root mean square error (RMSE) of 2.7182 g/100 g, residual predictive deviation (RPD) of 3.1220 > 3.0. In summary, this model efficiently detects changes in DF content across different growth periods of Chinese cabbage, which offers technical support for vegetable sorting and grading in the field.

Combined impact of alcohol consumption and metabolic syndrome on liver dysfunction in an elderly Chinese population.

Alcohol consumption and metabolic syndrome(MetS), both prevalent in the general population, frequently co-occur. They are recognized as significant contributors to liver dysfunction, yet their combined effect is often challenging to delineate. This study delves into the compounding influence of alcohol consumption and metabolic disorder on liver dysfunction within an elderly demographic in Zhejiang Province, China. Our findings spotlight a heightened risk of liver dysfunction among females, younger individuals, rural dwellers, those with minimal educational attainment, single individuals, and those diagnosed with MetS. We also discerned a positive correlation correlation between the number of MetS components and the propensity for liver dysfunction. Furthermore, the risk of liver dysfunction escalated in tandem with the frequency of alcohol consumption. Interestingly, a prolonged abstinence period (≥ 5 years) seemed to mitigate this risk. Our research underscores the significance of refraining from excessive alcohol consumption, embracing a healthy lifestyle, and managing MetS components-especially triglyceride levels-for effective prevention of liver dysfunction.

PreS1BP mediates inhibition of Hepatitis B virus replication by promoting HBx protein degradation.

BACKGROUND: PreS1-binding protein (PreS1BP), recognized as a nucleolar protein and tumor suppressor, influences the replication of various viruses, including vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1). Its role in hepatitis B virus (HBV) replication and the underlying mechanisms, however, remain elusive. METHODS: We investigated PreS1BP expression levels in an HBV-replicating cell and animal model and analyzed the impact of its overexpression on viral replication metrics. HBV DNA, covalently closed circular DNA (cccDNA), hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg), and HBV RNA levels were assessed in HBV-expressing stable cell lines under varying PreS1BP conditions. Furthermore, co-immunoprecipitation and ubiquitination assays were used to detect PreS1BP- hepatitis B virus X protein (HBx) interactions and HBx stability modulated by PreS1BP. RESULTS: Our study revealed a marked decrease in PreS1BP expression in the presence of active HBV replication. Functional assays showed that PreS1BP overexpression significantly inhibited HBV replication and transcription, evidenced by the reduction in HBV DNA, cccDNA, HBsAg, HBcAg, and HBV RNA levels. At the molecular level, PreS1BP facilitated the degradation of HBx in a dose-dependent fashion, whereas siRNA-mediated knockdown of PreS1BP led to an increase in HBx levels. Subsequent investigations uncovered that PreS1BP accelerated HBx protein degradation via K63-linked ubiquitination in a ubiquitin-proteasome system-dependent manner. Co-immunoprecipitation assays further established that PreS1BP enhances the recruitment of the proteasome 20S subunit alpha 3 (PSMA3) for interaction with HBx, thereby fostering its degradation. CONCLUSIONS: These findings unveil a previously unidentified mechanism wherein PreS1BP mediates HBx protein degradation through the ubiquitin-proteasome system, consequentially inhibiting HBV replication. This insight positions PreS1BP as a promising therapeutic target for future HBV interventions. Further studies are warranted to explore the clinical applicability of modulating PreS1BP in HBV therapy.

Has-miR-300-GADD45B promotes melanoma growth via cell cycle.

Response to oncogenic factors like UV, GADD45 family in skin participates in scavenging ROS, DNA repair and cell cycle control. Because of this, the previous study of the chronic UVB injury model has found that hsa-miR-300 can conduct intercellular transport by exosomes and target regulation of GADD45B. Whether the hsa-miR-300-GADD45B still regulates tumor development by cell cycle pathway is unclear. Through transcriptomic analysis of primary (n=39) and metastatic (n=102) melanoma, it was confirmed that in metastatic samples, some of the 97 down-regulated genes participate in maintaining skin homeostasis while 42 up-regulated genes were enriched in cancer-related functions. Furthermore, CDKN1A, CDKN2A, CXCR4 and RAD51 in the melanoma pathway, were also differentially expressed between normal skin and melanoma. CDKN1A and CDKN2A were also found to be involved in TP53-dependent cell cycle regulation. In conclusion, it was speculated that CDKN1A, CDKN2A, TP53, GADD45B and hsa-miR-300 may have regulatory relationships. It was demonstrated that there is a bidirectional regulation between hsa-miR-300 and TP53. In addition, miR-300 can regulate CDKN1A by GADD45B/TP53 and promote melanoma growth by accelerating the cell cycle transition from G1/S to G2 phase.

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis.

BACKGROUND: Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC). AIM: To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications. METHODS: According to the inclusion and exclusion criteria, 27 patients with ALC and 24 healthy controls (HCs) were selected, and plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces. Also, the correlation between metabolites and clinical features was analyzed. RESULTS: More than 300 common metabolites were identified in the plasma and feces of patients with ALC. Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways. Compared to HCs, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. Moreover, we established a P/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score. CONCLUSION: The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC. These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF ß1/Smad3 and NF-κB signaling pathways.

BACKGROUND: Hepatic fibrosis is a serious condition, and the development of hepatic fibrosis can lead to a series of complications. However, the pathogenesis of hepatic fibrosis remains unclear, and effective therapy options are still lacking. Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1 (NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis, but its role in diseases including hepatic fibrosis remains undefined. Therefore, additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment. AIM: To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1. METHODS: Twenty-four male C57BL/6 mice were randomized and separated into three groups, comprising the normal, fibrosis, and calcitriol treatment groups, and liver fibrosis was modeled by carbon tetrachloride (CCl4). To evaluate the level of hepatic fibrosis in every group, serological and pathological examinations of the liver were conducted. TGF-ß1 was administered to boost the in vitro cultivation of LX-2 cells. NS3TP1, α-smooth muscle actin (α-SMA), collagen I, and collagen III in every group were examined using a Western blot and real-time quantitative polymerase chain reaction. The activity of the transforming growth factor beta 1 (TGFß1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected. The statistical analysis of the data was performed using the Student's t test. RESULTS: NS3TP1 promoted the activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhanced hepatic fibrosis via the TGFß1/Smad3 and NF-κB signaling pathways, as evidenced by the presence of α-SMA, collagen I, collagen III, p-smad3, and p-p65 in LX-2 cells, which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference. The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression, as shown by the luciferase assay. NS3TP1 inhibited the apoptosis of HSCs. Moreover, both Smad3 and p65 could bind to NS3TP1, and p65 increased the promoter activity of NS3TP1, while NS3TP1 increased the promoter activity of TGFß1 receptor I, as indicated by coimmunoprecipitation and luciferase assay results. Both in vivo and in vitro, treatment with calcitriol dramatically reduced the expression of NS3TP1. Calcitriol therapy-controlled HSCs activation, proliferation, and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice. Furthermore, calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1. CONCLUSION: Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique, prospective therapeutic target in hepatic fibrosis.

HCBP6-induced activation of brown adipose tissue and upregulated of BAT cytokines genes.

Brown adipose tissue is a thermogenic organ, which consumes chemical energy as heat to protect animals from low temperature and metabolic diseases. However, the role and mechanism of the new factor that up-regulates the heat-generating capacity of brown adipose tissue is still unclear. Here, we found that hepatitis C virus core binding protein 6 (HCBP6), as a key regulator gene in the homeostasis of liver lipid metabolism, is an important enhancer for activating brown fat to ensure thermogenesis. HCBP6 upregulates the expression of UCP1 and increases the number of mitochondria in brown adipocytes. In the BAT of HCBP6-knockout mice induced by a high-fat diet, UCP1 and BAT activity-related genes Pgc1α, Cidea and oxidation phosphorylation-related genes (OXPHOS) were significantly reduced. In addition, the transcriptomics results show that the loss of HCBP6 caused disorder of the metabolic pathway, the expression of brown adipocyte development genes was significantly reduced, and the expression of most BAT cytokine genes was reduced. In conclusion, HCBP6 increased ucp1-dependent thermogenesis in BAT and improved liver lipid metabolism, possibly by enhancing the activity of brown fat and changing the expression of BAT cytokine genes.

miR-98-5p as a novel biomarker suppress liver fibrosis by targeting TGFß receptor 1.

BACKGROUND: Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies have showed that microRNAs (miRNAs) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. But the miRNAs expression profiling and the differentially expressed miRNAs in patients with HBV-related liver fibrosis were little known. This study aims to have a record of a systemic screening for liver fibrosis-associated miRNAs in patients infected with HBV. METHODS: A IlluminaHiSeq sequencing of plasma miRNAs from the HBV-related liver fibrosis patients (S2/3, n = 8) based on Scheuer's staging criteria and from healthy volunteers 42 (n = 7) was performed. Cluster analysis and target gene prediction were performed for the differentially expressed miRNAs. Gene ontology (GO) analysis and KEGG pathway enrichment analysis also were performed on the differentially expressed target miRNA genes. RESULTS: Compared with the healthy control group, 77 miRNAs were screened out from the liver fibrosis group, among which 51 miRNAs were up-regulated and 26 miRNAs were down-regulated. Eventually, miR-98-5p was identified as a candidate predictor of liver fibrosis progression. miR-98-5p is reduced in activated LX2 cells, and miR-98-5p overexpression inhibited the HSCs activation. Mechanically, MiR-98-5p prevents liver fibrosis by targeting TGFbR1 and blocking TGFb1/Smad3 signaling pathway. Furthermore, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. Serum miR-98-5p level was significantly lower in patients with liver fibrosis than in healthy controls and HBV carriers. CONCLUSIONS: The expression of miRNAs in patients with liver fibrosis is significantly different from that of healthy volunteers. Many signal pathways of hepatic fibrosis are regulated by miRNAs. The potential value of miR-98-5p is as diagnostic biomarkers and therapeutic targets for HBV-related liver fibrosis.

Effects of degree of deacetylation on hemostatic performance of partially deacetylated chitin sponges.

Chitin/chitosan hemostatic materials have long been studied for uncontrolled hemorrhage, an urgent clinical problem due to severe blood-vessel damage or hemophilia. As one of the basic structural parameters of chitin, the degree of deacetylation (DD) significantly affects the material's physical, chemical, as well as biological properties. In this study, partially deacetylated chitins with a wide range of DD (23-81%) were prepared by homogeneous deacetylation, and sponges with these various chitins were fabricated by freeze-drying to study the effects of DD on their hemostatic properties. Among all sponge samples, the chitosan sponge with a DD of 48% showed the highest water absorption, whole blood adsorption, RBC adsorption rate, and the best hemostatic performance in an uncontrolled bleeding model of the rat femoral artery, demonstrating that a certain proportion of acetyl amino and amino groups could also activate the coagulation system and promote the adhesion of platelet and erythrocyte.

S6K1 inhibits HBV replication through inhibiting AMPK-ULK1 pathway and disrupting acetylation modification of H3K27.

AIMS: To investigated the effect of S6K1 on the replication and transcription of HBV DNA using multiple cell models. MAIN METHODS: The pgRNA, total HBV RNA and HBV DNA level were detected by Real-time PCR. The HBcAg expression by Western blot and the activity of four HBV promoters, such as preS1, preS2/S, core, and X promoters by using dual luciferase reporter assay. Moreover, we determined S6K1 interacted with HBcAg in both cytoplasm and nucleus through Immunofluorescence, co-immunoprecipitation (CoIP) and Western blot. KEY FINDINGS: S6K1 inhibited HBV DNA replication and cccDNA-dependent transcription in HBV-expressing stable cell lines. The mechanistic study revealed that S6K1 suppressed HBV DNA replication by inhibiting AMPK-ULK1 autophagy pathway, and the nuclear S6K1 suppressed HBV cccDNA-dependent transcription by inhibiting the acetylation modification of H3K27. In addition, HBV capsid protein (HBcAg) suppressed the phosphorylation level of S6K1Thr389 by interacting with S6K1, indicating a viral antagonism of S6K1-mediated antiviral mechanism. SIGNIFICANCE: The p70 ribosomal S6 kinase (S6K1) is a serine/threonine protein kinase, and it plays a significant role in different cellular processes. It has been previously reported that S6K1 affects hepatitis B virus (HBV) replication but the underlying mechanism remains unclear. In this study, our data suggested that the activation of S6K1 restricts HBV replication through inhibiting AMPK-ULK1 autophagy pathway and H3K27 acetylation. These findings indicated that S6K1 might be a potential therapeutic target for HBV infection.

Structural Visualization of Septum Formation in Staphylococcus warneri Using Atomic Force Microscopy.

Cell division of Staphylococcus adopts a "popping" mechanism that mediates extremely rapid separation of the septum. Elucidating the structure of the septum is crucial for understanding this exceptional bacterial cell division mechanism. Here, the septum structure of Staphylococcus warneri was extensively characterized using high-speed time-lapse confocal microscopy, atomic force microscopy, and electron microscopy. The cells of S. warneri divide in a fast popping manner on a millisecond timescale. Our results show that the septum is composed of two separable layers, providing a structural basis for the ultrafast daughter cell separation. The septum is formed progressively toward the center with nonuniform thickness of the septal disk in radial directions. The peptidoglycan on the inner surface of double-layered septa is organized into concentric rings, which are generated along with septum formation. Moreover, this study signifies the importance of new septum formation in initiating new cell cycles. This work unravels the structural basis underlying the popping mechanism that drives S. warneri cell division and reveals a generic structure of the bacterial cell.IMPORTANCE This work shows that the septum of Staphylococcus warneri is composed of two layers and that the peptidoglycan on the inner surface of the double-layered septum is organized into concentric rings. Moreover, new cell cycles of S. warneri can be initiated before the previous cell cycle is complete. This work advances our knowledge about a basic structure of bacterial cell and provides information on the double-layered structure of the septum for bacteria that divide with the "popping" mechanism.

Study of injectable Blueberry anthocyanins-loaded hydrogel for promoting full-thickness wound healing.

Injectable hydrogels with high anti-inflammatory and wound-healing properties are highly desirable for clinical application. In the present study, injectable hydrogels were prepared based on carboxymethyl chitosan and oxidized hyaluronic acid. Blueberry anthocyanins (BA), which are known for their antioxidant and antiinflammatory properties, were successfully loaded into the hydrogels. The gelation kinetics and mechanical properties of the hydrogels were investigated. Oxidized hyaluronic acid with an oxidation degree of 38.1% conferred a suitable gelation time (~70 s) and mechanical properties (76.0 kPa compression stress at strain of 80%) of the hydrogel. The injectable BA-loaded hydrogel significantly accelerated the wound healing process in a full-thickness skin wound model in rats, promoted epithelial and tissue regeneration, exerted antiinflammatory effects, and promoted collagen deposition and angiogenesis. Besides, the hydrogel could upregulate the expression of VEGF and IL-10 proteins, downregulate the NF-κB level, and promote macrophage transformation from M1 phenotype to M2. The promotion of the BA-loaded hydrogel on wound healing were mainly realized by its biological effects, including antioxidant and anti-inflammatory effects, and regulation of various wound healing related factors. The results suggested that BA and the hydrogels exert synergistic effects in promoting wound healing. Injectable BA-loaded hydrogels appear to be promising candidates for wound healing application.

HCBP6 deficiency exacerbates glucose and lipid metabolism disorders in non-alcoholic fatty liver mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), which often accompanied by metabolic syndrome, such as obesity, diabetes and dyslipidemia, has become a global health problem. Our previous results show that HCV core protein binding protein 6 (HCBP6) could maintain the triglyceride homeostasis in liver cells. However, the role of HCBP6 in NAFLD and its associated metabolic disorders remains incompletely understood. METHODS: Hepatic HCBP6 expression was determined by qRT-PCR, Western blot and immunohistochemistry analysis. HCBP6 knockout (HCBP6-KO) mice were constructed and fed a high-fat diet (HFD) to induce NAFLD. The effects of HCBP6 on glucose and lipid metabolism were measured by HE staining, qRT-PCR, Western blot and GTT. Wild-type and HCBP6-KO mice kept on a HFD were treated with ginsenosides Rh2, and HE staining and GTT were used to study the function of Rh2 in metabolism disorders. RESULTS: HCBP6 is reduced in HFD-fed mice. HCBP6 deficiency increased the body weight, aggravated fatty liver and deteriorated lipid homeostasis as well as glucose homeostasis in HFD-induced mouse model of NAFLD. Moreover, HCBP6-KO mice failed to maintain body temperature upon cold challenge. Mechanistically, HCBP6 could regulate lipolysis and fatty acid oxidation via activation of AMKP in vivo. In addition, HCBP6 expression was upregulated by ginsenosides Rh2. Accordingly, ginsenosides Rh2 administrations improved HFD-induced fatty liver and glucose tolerance. CONCLUSIONS: These findings indicated that HCBP6 is essential in maintaining lipid and glucose homeostasis and body temperature. HCBP6 augmented by ginsenosides Rh2 may be a promising therapeutic strategy for the treatment of metabolic disorders in NAFLD mice.

Superfine grinding induced amorphization and increased solubility of α-chitin.

As the most common structure of chitin, α-chitin is insoluble in common aquatic and organic solvents, and is very difficult to be processed due to its highly ordered crystalline structure and the large number of intermolecular and intramolecular hydrogen bonds. Amorphization of α-chitin has been proved to be a valid measure for improving its subsequent functionalization efficiency and depolymerization yield. In this study, superfine grinding (SFG) was introduced to make α-chitin amorphous, and it was found that SFG effectively reduced the particle size, changed the microstructure, and significantly reduced the crystallinity of α-chitin. Chitin with crystallinity as low as 8.39 % was obtained after 60 min of SFG treatment, and the amorphous chitin became readily dissolved in 10 % NaOH solution after one round of freezing-thawing process. As continuous manner could be employed, SFG might be a powerful and efficient method for preparing amorphous chitin to help its processing and modification of various applications.

TAF and TDF attenuate liver fibrosis through NS5ATP9, TGFß1/Smad3, and NF-κB/NLRP3 inflammasome signaling pathways.

BACKGROUND: This study aimed to investigate the roles and mechanisms of tenofovir alafenamide fumarate (TAF)/tenofovir disoproxil fumarate (TDF) in treating liver fibrosis. METHODS: The effects of TAF/TDF on carbon tetrachloride (CCl4)-induced liver fibrosis in C57BL/6 wild-type or nonstructural protein 5A transactivated protein 9 (NS5ATP9) knockout mice were studied. The differentiation, activation, and proliferation of LX-2 cells after TAF/TDF treatment were tested in vitro. The expression of NS5ATP9 and activities of transforming growth factor-ß1 (TGFß1)/Sekelsky mothers against decapentaplegic homolog 3 (Smad3) and NF-κB/NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were detected in TAF/TDF-treated mice and LX-2 cells. The genes related to extracellular matrix accumulation were detected in vivo and in vitro after NS5ATP9 silencing or knockout. RESULTS: TAF/TDF significantly inhibited CCl4-induced liver fibrosis in mice, and regulated the differentiation, activation, and proliferation of hepatic stellate cells (HSCs). Furthermore, TAF/TDF suppressed the activities of TGFß1/Smad3 and NF-κB/NLRP3 inflammasome signaling pathways in vivo and in vitro. NS5ATP9 inhibited liver fibrosis through TGFß1/Smad3 and NF-κB signaling pathways. TAF/TDF upregulated the expression of NS5ATP9 in vivo and in vitro. Finally, TAF/TDF could only show marginal therapeutic effects when NS5ATP9 was silenced and knocked out in vivo and in vitro. CONCLUSIONS: TAF/TDF prevented progression and promoted reversion of liver fibrosis through assembling TGFß1/Smad3 and NF-κB/NLRP3 inflammasome signaling pathways via upregulating the expression of NS5ATP9. TAF/TDF also regulated the differentiation, activation, and proliferation of HSCs. The findings provided strong evidence for the role of TAF/TDF as a new promising therapeutic strategy in liver fibrosis.

P7TP3 inhibits tumor development, migration, invasion and adhesion of liver cancer through the Wnt/ß-catenin signaling pathway.

The effect of hepatitis C virus p7 trans-regulated protein 3 (P7TP3) in the development of hepatocellular carcinoma (HCC) is still unknown. The present study aimed to investigate the role and mechanism of P7TP3 in HCC. P7TP3 was significantly decreased in HCC tissues when compared with corresponding liver tissues immediately around the tumor (LAT) from seven HCC patients. Fewer and smaller colonies originated from HepG2-P7TP3 cells when compared to HepG2-NC cells. Overexpression of P7TP3 in HepG2 cells significantly repressed the growth of HCC xenografts in nude mice. Furthermore, wound-healing tests, Transwell assays, Matrigel Transwell assays, adhesion assays, CCK-8 assays, flow cytometry and western blotting analysis showed that P7TP3 protein expression inhibited migration, invasion, adhesion, proliferation and cell cycle progression in HCC cell lines. Moreover, P7TP3 suppressed the activity of the Wnt/ß-catenin signaling pathway, and was restored by Wnt3a, which is an activator of the Wnt/ß-catenin signaling pathway. Consistently, ß-catenin was highly expressed by P7TP3 silencing, and restored by XAV939, an inhibitor of the Wnt/ß-catenin signaling pathway. Finally, microRNA (miR)-182-5p suppressed the expression of target gene P7TP3 by directly interacting with the 3'-UTR region. Taken together, P7TP3, the direct target gene of miR-182-5p, inhibited HCC by regulating migration, invasion, adhesion, proliferation and cell cycle progression of liver cancer cell through the Wnt/ß-catenin signaling pathway. These findings provide strong evidence that P7TP3 functions as a new promising tumor suppressor in HCC.

Is CuO Suitable for Improving the Electrochemical Properties of g-C3N4?

G-C3N4 has a bright application prospect as an electrode material of supercapacitors, which makes it a concern. In order to increase the specific capacitance of g-C3N4, we consider to combine it with a metal oxide with high theoretical specific capacitance and utilize the synergistic effect. As a common metal oxide, CuO has the characteristics of high theoretical capacitance, high chemical stability, simple preparation and environmental friendliness. A composite containing CuO nanobelts and graphitic C3N4 (g-C3N4) was successfully synthesized by a chemical precipitation method. Various testing methods were used to explore its composition, microstructure and electrochemical properties to discuss whether CuO is suitable for improving the electrochemical properties of g-C3N4.