Syntaxin6 contributes to hepatocellular carcinoma tumorigenesis via enhancing STAT3 phosphorylation.

BACKGROUND: Syntaxin6 (STX6) is a SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein complex located in the trans-Golgi network and endosomes, which is closely associated with a variety of intracellular membrane transport events. STX6 has been shown to be overexpressed in a variety of human malignant tumors such as esophageal, colorectal, and renal cell carcinomas, and participates in tumorigenesis and development. METHODS: Based on clinical public database and clinical liver samples analysis, the expression of STX6 in hepatocellular carcinoma (HCC) tissues was investigated. The effects of STX6 on proliferation, migration and invasion of HCC cell in vitro and in vivo were evaluated through gain- and loss-of-function studies. We further performed RNA-seq analysis and protein interactome analysis, to further decifer the detailed mechanisms of STX6 in the regulation of the JAK-STAT pathway in HCC. RESULTS: STX6 expression was upregulated in HCC tissues and its expression was highly correlated with the high histological grade of the tumor. STX6 promoted HCC cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, STX6 mediated tumor progression depending on promoting the activation of JAK-STAT signaling pathway. Receptor for activated protein kinase C (RACK1) as an essential adaptor protein mediating STX6 regulation of JAK-STAT pathway. Specifically, STX6 interacted with RACK1 and then recruited signal transducer and activator of transcription 3 (STAT3) to form a protein-binding complex and activates STAT3 transcriptional activity. CONCLUSIONS: This study provided a novel concept that STX6 exerted oncogenic effects by activating the STAT3 signaling pathway, and STX6 might be a promising therapeutic target for HCC.

Exploring the molecular mechanisms by which per- and polyfluoroalkyl substances induce polycystic ovary syndrome through in silico toxicogenomic data mining.

The pathogeny of polycystic ovary syndrome (PCOS) is intricate, with endocrine disruptors (EDCs) being acknowledged as significant environmental factors. Research has shown a link between exposure to per- and polyfluoroalkyl substances (PFAS) and the development and progression of PCOS, although the precise mechanism is not fully understood. This study utilized toxicogenomics and comparative toxicogenomics databases to analyze data and investigate how PFAS mixtures may contribute to the development of PCOS. The results indicated that 74 genes are associated with both PFAS exposure and PCOS progression. Enrichment analysis suggested that cell cycle regulation and steroid hormone synthesis may be crucial pathways through which PFAS mixtures participate in the development of PCOS, involving important genes such as CCNB1 and SRD5A1. Furthermore, the study identified transcription factors (TFs) and miRNAs that may be involved in the onset and progression of PCOS, constructing regulatory networks encompassing TFs-mRNA interactions and miRNA-mRNA relationships to elucidate their regulatory roles in gene expression. By utilizing data mining techniques based on toxicogenomic databases, this study provides relatively comprehensive insights into the association between exposure factors and diseases compared to traditional toxicology studies. These findings offer new perspectives for further in vivo or in vitro investigations and contribute to understanding the pathogenesis of PCOS, thereby providing valuable references for identifying clinical treatment targets.

Improvement on wheat bread quality by in situ produced dextran-A comprehensive review from the viewpoint of starch and gluten.

Deterioration of bread quality, characterized by the staling of bread crumb, the softening of bread crust and the loss of aroma, has caused a huge food waste and economic loss, which is a bottleneck restriction to the development of the breadmaking industry. Various bread improvers have been widely used to alleviate the issue. However, it is noteworthy that the sourdough technology has emerged as a pivotal factor in this regard. In sourdough, the metabolic breakdown of carbohydrates, proteins, and lipids leads to the production of exopolysaccharides, organic acids, aroma compounds, or prebiotics, which contributes to the preeminent ability of sourdough to enhance bread attributes. Moreover, sourdough exhibits a "green-label" feature, which satisfies the consumers' increasing demand for additive-free food products. In the past two decades, there has been a significant focus on sourdough with in situ produced dextran due to its exceptional performance. In this review, the behaviors of bread crucial compositions (i.e., starch and gluten) during dough mixing, proofing, baking and bread storing, as well as alterations induced by the acidic environment and the presence of dextran are systemically summarized. From the viewpoint of starch and gluten, results obtained confirm the synergistic amelioration on bread quality by the coadministration of acidity and dextran, and also highlight the central role of acidification. This review contributes to establishing a theoretical foundation for more effectively enhancing the quality of wheat breads through the application of in situ produced dextran.

Efficient hemicellulose removal from lignocellulose by induced electric field-aided dilute acid pretreatment.

This study evaluated the effectiveness of induced electric field (IEF) as a novel electrotechnology to assist dilute acid pretreatment of wheat straw (WS) at atmospheric pressure and low temperature (90 °C). The effects of acid concentration and duration on cellulose recovery, hemicellulose and lignin removal were investigated. Meanwhile, the differences between IEF pretreatment and hydrothermal pretreatment were compared by quantitative and qualitative analysis. The optimal pretreatment condition was acid concentration 1 % with the period of 5 h. Under the parameters, the hemicellulose removal of WS after IEF pretreatment was up to 73.6 %, and the enzymatic efficiency was 55.8 %. In addition, the irregular surface morphology, diminished functional groups associated with hemicellulose, increased specific surface area and pore volume, as well as improved thermal stability of the residual WS support the remarkable effect of IEF pretreatment. The feasibility of IEF pretreatment is might be due to the fact that the magneto-induced electric field promotes ionization of H+ and formation of hydrated hydrogen ions, increasing the acidity of the medium. Secondly, electroporation disrupts the anti-degradation structure of WS and increases the accessibility of cellulose to cellulases. It indicated that IEF is a green and efficient strategy for assisting the separation of hemicellulose from lignocellulose.

Effect of Static Magnetic Field on the Quality of Pork during Super-Chilling Storage.

Fresh pork tenderloin was stored at -3 °C under different static magnetic fields (SMF) of 0, 4, and 10 mT (control, MF-4, and MF-10) to investigate their physicochemical properties changes during storage of 8 days. The initial equilibrium temperature of the samples stored with 4 mT MF was found to be -2.3 °C, which was slightly lower (0.3 °C) than that the control value. The super-chilling phenomenon on the pork was then observed, as the samples stored under the magnetic field did not freeze throughout storage period, but the control experienced a sudden change in temperature after 138 h and then froze. The preservation effect of MF-4 on meat quality was the best in all treatment groups. MF-4 achieved a higher water-retention rate, with drip and cook losses of 6.5% and 29.0% lower than the control, respectively. Meanwhile, the MF-4 effectively delayed the color change in the meat during the storage and the texture hardening after cooking, and effectively controlled the growth of the total volatile saline nitrogen content on the samples. In addition, MF-4 delayed the reduction in myofibrillar protein solubility, sulfhydryl content, and emulsification capacity, indicating that this field inhibited the denaturation of myofibrillar protein. This study can be considered as an application reference of magnetic fields during meat storage at a super-chilled temperature.

Effect of constant-current pulsed electric field thawing on proteins and water-holding capacity of frozen porcine longissimus muscle.

This study explored the effect of constant-current pulsed electric field thawing (CC-T) on the proteins and water-holding capacity of pork. Fresh meat (FM), and frozen meat after constant-voltage thawing (CV-T), air thawing (AT) and water immersion thawing (WT) were considered as controls. The results indicated that CC-T had a higher thawing rate than conventional thawing during ice-crystal melting stage (-5 to -1 °C). It also showed a lower water migration and thawing loss, maintaining pH and shear force closer to FM. Meanwhile, CC-T decreased myoglobin oxidation, resulting in a favorable surface color. The results of protein solubility, differential scanning calorimetry, total sulfhydryl, carbonyl and surface hydrophobicity demonstrated that CC-T reduced myofibrillar protein oxidative denaturation by suppressing the formation of disulfide and carbonyl bonds, thus enhancing solubility and thermal stability. Additionally, microstructural observation found that CC-T maintained a relatively intact muscle fiber structure by reducing muscle damage and myosin filament denaturation.

Effect of magnetic fields on the structure, properties, baking performance of frozen wheat dough at different frozen stage.

As an emerging physical technology, magnetic fields have been used to improve the quality of frozen and refrigerated foods. This study compared the effect of applying a static magnetic field (2 mT) at different stages of freezing and storage on the quality of frozen dough. Results suggested that the magnetic field significantly impacted frozen dough quality. It not only prevented the formation of ice crystals during the pre-freezing stage but also inhibited ice crystal growth during the following frozen storage. This effect helped to maintain the integrity of gluten proteins and their adhesion to starch granules by preventing the breakage of disulfide bonds and the depolymerization of gluten macromolecules. It was also observed that yeast inactivation and glutathione release were reduced, resulting in improved air retention and air production capacity of the dough. This, in turn, led to a more appealing volume and texture quality of the finished bread.

Effects of wheat starch content on its flour and frozen dough bread.

The refined wheat flour was mixed with different types of wheat starch in different addition levels, their microstructure, chemical bonds in the dough and baking characteristics of 0-8 weeks frozen dough bread were studied. With the increase of A-Type starch granules and whole wheat starch, the pores of gluten network first decreased and then increased. Conversely, an increase in B-Type starch granules consistently reduced gluten network porosity. With the increase of whole wheat starch, the content of free sulfhydryl group and hydrophobic interaction decreased gradually. Minimal additions of B-Type granules were found to enhance the specific volume of fresh bread, whereas increased quantities improved the specific volume of frozen dough bread. The addition of a small quantity of A- or B-Type granules enhances the freezing stability of bread. This study provides effective information for elucidating the effects of wheat starch on the frozen dough and bread properties in protein-starch matrix.

Repurposing disulfiram with CuET nanocrystals: Enhancing anti-pyroptotic effect through NLRP3 inflammasome inhibition for treating inflammatory bowel diseases.

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing drugs. Recently, disulfiram (DSF), a drug primarily used for alcohol addiction treatment, has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis, a form of programmed cell death. The therapeutic activity of DSF can be further enhanced by the presence of Cu2+, although the underlying mechanism of this enhancement remains unclear. In this study, we investigated the mechanistic basis of Cu2+-induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate (CuET) complex. CuET exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of action. However, despite its potent activity, CuET suffered from poor solubility and limited permeability, as revealed by our druggability studies. To overcome these intrinsic limitations, we developed a scalable method to prepare CuET nanocrystals (CuET NCs) using a metal coordination-driven self-assembly approach. Pharmacokinetic studies demonstrated that CuET NCs exhibited a 6-fold improvement in bioavailability. Notably, CuET NCs exhibited high biodistribution in the intestine, suggesting their potential application for the treatment of inflammatory bowel diseases (IBDs). To evaluate their therapeutic efficacy in vivo, we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis symptoms. Our findings highlight the discovery of CuET as a potent anti-pyroptotic agent, and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.

Impacts of free nitrous acid on stabilizing food waste and sewage sludge for anaerobic digestion.

This work investigated the effectiveness of free nitrous acid (FNA) in enhancing organic waste solubilization to improve biogas production in anaerobic digestion (AD). The results indicated that FNA pretreatment can enhance soluble organic content and control H2S odor in tested organic wastes, including food waste, sewage sludge, and their combination. However, a significant decrease (>50 %) in FNA concentration was found in the reactors, possibly due to denitrifier-driven NO2- consumption. Biochemical methane potential (BMP) tests showed a 25 ± 8 % enhancement in CH4 production in the reactors fed with mixed substrate pretreated with 2.9 mg FNA-N/L. However, the presence of NO2- (325.6-2368.0 mg N/L) in some BMP reactors, due to carryover from FNA pretreatment, adversely affected CH4 production (>55 %) and prolonged lag time (>4.2 times). These findings are valuable for researchers and practitioners in waste management, offering insights for implementing FNA pretreatment to enhance the biodegradability of organic wastes in AD.

Phosvitin-based hydrogels prepared in AmimCl under magnetic field treatment: Structural characteristics, biological functions, and application in skin wound healing.

Due to the serious bacterial infection of skin and the waste of petroleum-based materials, there is an urgent need to develop natural biodegradable wound dressings with high antibacterial activity. Phosvitin (PSV) has shown its natural antioxidant and antibacterial properties, making it an excellent material for preparing wound healing dressings. In this study, we investigated the effect of magnetic field on the preparation of PSV-Microcrystalline Cellulose (MCC) composite hydrogels in 1-Allyl-3-methylimidazolium chloride (AmimCl) system. The results showed that the prepared hydrogels exhibited homogeneous surface structure, suitable swelling capacity and elasticity modulus, and sufficient thermal stability. The excellent antibacterial and antioxidant activities of hydrogels were mainly resulting from AmimCl and PSV, respectively, and the properties were enhanced after magnetic field treatment. The proteomics analysis indicated that AmimCl can readily penetrate the biological membranes of Staphylococcus aureus (S. aureus), upsetting the metabolism and reducing the virulence. The hydrogels showed great blood compatibility. Compared with the commercial materials, the 5 mT-treated hydrogels presented a comparable wound healing rate in the full-thickness skin injury model. On day 7, the wound healing rate of the 5 mT group reached approximately 84.40 %, which was significantly higher than that of the control group, 72.88 % (P < 0.05). In conclusion, our work provides experience for the development of biodegradable materials combined in ionic liquids and magnetic field, and explores their applications in wound healing dressings.

Insights into starch-based gels: Selection, fabrication, and application.

Starch a natural polymer, has made significant advancements in recent decades, offering superior performance and versatility compared to synthetic materials. This review discusses up-to-date diverse applications of starch gels, their fabrication techniques, and their advantages over synthetic materials. Starch gels renewability, biocompatibility, biodegradability, scalability, and affordability make them attractive. Also, advanced theoretical foundations and emerging industrial technologies could further expand their scope and functions inspiring new applications.

Pancoronary plaque characteristics in STEMI patients with rapid plaque progression: An optical coherence tomography study.

BACKGROUND: Non-culprit plaque progression is associated with recurrent cardiac ischemic events and worse clinical outcomes. Given that atherosclerosis is a systemic disease, the pancoronary characteristics of patients with rapid plaque progression are unknown. This study aims to identify pancoronary plaque features in patients with ST-segment elevation myocardial infarction (STEMI) with and without rapid plaque progression, focused on the patient level. METHODS AND RESULTS: From January 2017 to July 2019, 291 patients underwent 3-vessel optical coherence tomography imaging at the time of the primary procedure and a follow-up angiography interval of 12 months. The final analysis included 237 patients. Overall, 308 non-culprit lesions were found in 78 STEMI patients with rapid plaque progression, and 465 non-culprit plaques were found in 159 STEMI patients without rapid plaque progression. These patients had a higher pancoronary vulnerability (CLIMA-defined high-risk plaque: 47.4% vs. 33.3%; non-culprit plaque rupture: 25.6% vs. 14.5%) and a significantly higher prevalence of other vulnerable plaque characteristics (i.e., lipid-rich plaque, cholesterol crystal, microchannels, calcification, spotty calcification, and thrombus) at baseline versus those without rapid plaque progression. Lesions with rapid progression were highly distributed at the LAD, tending to be near the bifurcation. In multivariate analysis, age ≥ 65 years was an independent predictor of subsequent rapid lesion progression at the patient level, whereas microchannel, spotty calcification, and cholesterol crystal were independent predictors for STEMI patients ≥65 years old. CONCLUSIONS: STEMI patients with subsequent rapid plaque progression had higher pancoronary vulnerability and commonly presented vulnerable plaque morphology. Aging was the only predictor of subsequent rapid plaque progression.

Correlation between the expressions of metastasis-associated factor-1 in colon cancer and vacuolar ATP synthase.

BACKGROUND: Clinical prognosis often worsens due to high recurrence rates following radical surgery for colon cancer. The examination of high-risk recurrence factors post-surgery provides critical insights for disease evaluation and treatment planning. AIM: To explore the relationship between metastasis-associated factor-1 in colon cancer (MACC1) and vacuolar ATP synthase (V-ATPase) expression in colon cancer tissues, and recurrence rate in patients undergoing radical colon cancer surgery. METHODS: We selected 104 patients treated with radical colon cancer surgery at our hospital from January 2018 to June 2021. Immunohistochemical staining was utilized to assess the expression levels of MACC1 and V-ATPase in these patients. RESULTS: The rates of MACC1 and V-ATPase positivity were 64.42% and 67.31%, respectively, in colon cancer tissues, which were significantly higher than in paracancerous tissues (P < 0.05). Among patients with TNM stage III, medium to low differentiation, and lymph node metastasis, the positive rates of MACC1 and V-ATPase were significantly elevated in comparison to patients with TNM stage I-II, high differentiation, and no lymph node metastasis (P < 0.05). The rate of MACC1 positivity was 76.67% in patients with tumor diameters > 5 cm, notably higher than in patients with tumor diameters ≤ 5 cm (P < 0.05). We observed a positive correlation between MACC1 and V-ATPase expression (rs = 0.797, P < 0.05). The positive rates of MACC1 and V-ATPase were significantly higher in patients with recurrence compared to those without (P < 0.05). Logistic regression analysis revealed TNM stage, lymph node metastasis, MACC1 expression, and V-ATPase expression as risk factors for postoperative colon cancer recurrence (OR = 6.322, 3.435, 2.683, and 2.421; P < 0.05). CONCLUSION: The upregulated expression of MACC1 and V-ATPase in colon cancer patients appears to correlate with clinicopathological features and post-radical surgery recurrence.

Acetylation is required for full activation of the NLRP3 inflammasome.

Full activation of the NLRP3 inflammasome needs two sequential signals: a priming signal, followed by a second, assembly signal. Several studies have shown that the two signals trigger post-translational modification (PTM) of NLRP3, affecting activity of the inflammasome, however, the PTMs induced by the second signal are less well characterized. Here, we show that the assembly signal involves acetylation of NLRP3 at lysine 24, which is important for the oligomerization and the actual assembly of NLRP3 without affecting its recruitment to dispersed trans-Golgi network (dTGN). Accordingly, NLRP3 inflammasome activation is impaired in NLRP3-K24R knock-in mice. We identify KAT5 as an acetyltransferase able to acetylate NLRP3. KAT5 deficiency in myeloid cells and pharmacological inhibition of KAT5 enzymatic activity reduce activation of the NLRP3 inflammasome, both in vitro and in vivo. Thus, our study reveals a key mechanism for the oligomerization and full activation of NLRP3 and lays down the proof of principle for therapeutic targeting of the KAT5-NLRP3 axis.

Advances in neuroimaging studies of alcohol use disorder (AUD).

Alcohol use disorder (AUD) is a worldwide problem and the most common substance use disorder. Chronic alcohol consumption may have negative effects on the body, the mind, the family, and even society. With the progress of current neuroimaging methods, an increasing number of imaging techniques are being used to objectively detect brain impairment induced by alcoholism and serve a vital role in the diagnosis, prognosis, and treatment assessment of AUD. This article organizes and analyzes the research on alcohol dependence concerning the main noninvasive neuroimaging methods, structural magnetic resonance imaging, functional magnetic resonance imaging, and electroencephalography, as well as the most common noninvasive brain stimulation - transcranial magnetic stimulation, and intersperses the article with joint intra- and intergroup studies, providing an outlook on future research directions.