Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy.

Myocarditis has emerged as an immune-related adverse event of immune checkpoint inhibitor (ICI) cancer therapy associated with significant mortality. To ensure patients continue to safely benefit from life-saving cancer therapy, an understanding of fundamental immunological phenomena underlying ICI myocarditis is essential. We recently developed the NOD-cMHCI/II-/-.DQ8 mouse model that spontaneously develops myocarditis with lower mortality than observed in previous HLA-DQ8 NOD mouse strains. Our strain was rendered murine MHC class I and II deficient using CRISPR/Cas9 technology, making it a genetically clean platform for dissecting CD4+ T cell-mediated myocarditis in the absence of classically selected CD8+ T cells. These mice are highly susceptible to myocarditis and acute heart failure following anti-PD-1 ICI-induced treatment. Additionally, anti-PD-1 administration accelerates skeletal muscle myositis. Using histology, flow cytometry, adoptive transfers, and RNA sequencing analyses, we performed a thorough characterization of cardiac and skeletal muscle T cells, identifying shared and unique characteristics of both populations. Taken together, this report details a mouse model with features of a rare, but highly lethal clinical presentation of overlapping myocarditis and myositis following ICI therapy. This study sheds light on underlying immunological mechanisms in ICI myocarditis and provides the basis for further detailed analyses of diagnostic and therapeutic strategies.

Pre-administration of human umbilical cord mesenchymal stem cells has better therapeutic efficacy in rats with D-galactosamine-induced acute liver failure.

BACKGROUND: Acute liver failure (ALF) is characterized by an intense systemic inflammatory response, single or multiple organ system failure and high mortality. However, specific and effective treatments for ALF patients are still lacking. According to the current investigation, human umbilical cord mesenchymal stem cells (hUCMSCs) have shown remarkable potential to enhance the functional recovery of injured livers. We aimed to investigate the therapeutic effects of time-differentiated hUCMSCs administration regimens on ALF. METHODS: The rat model of ALF was induced by D-galactosamine (D-gal), and hUCMSCs were administered via the tail vein 12 h before or 2 h after induction. The potential mechanisms of hUCMSCs in treatment of ALF, regulation cell subset and secretion of inflammatory factors, were verified by co-culturing with PBMCs in vitro. Liver function indicators were detected by an automatic biochemistry analyzer and inflammatory factors were obtained by ELISA detection. The distribution of hUCMSCs in rats after administration was followed by quantitative real-time fluorescence PCR. RESULTS: The findings of the study discovered that administration of hUCMSCs 12 h prior to surgery could significantly improve the survival rate of rats, stabilize various liver function indicators in serum levels of ALT, AST, T-BIL, or ALB diminish inflammatory infiltration in liver tissue, and inhibit the secretion of inflammatory factors. CONCLUSION: Our data showed that pre-transplantation of hUCMSCs had a better therapeutic effect on ALF rats, providing empirical evidence for preclinical studies. Thus, the timing of hUCMSCs transplantation is necessary for the optimal clinical treatment effect.

Inhibition of RhoGEF/RhoA alleviates regorafenib resistance and cancer stemness via Hippo signaling pathway in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.

Topical Ophthalmic Liposomes Dual-Modified with Penetratin and Hyaluronic Acid for the Noninvasive Treatment of Neovascular Age-Related Macular Degeneration.

Introduction: Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance. Methods: Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue. Results: PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection. Conclusion: PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.

Safety and efficacy of remifentanil-propofol combination on "muscle relaxant-free" general anesthesia for therapeutic endoscopic retrograde cholangiopancreatography: a randomized controlled trial.

OBJECTIVE: To prospectively evaluate the safety and efficacy of a "muscle relaxant-free" general anesthesia using a combination of remifentanil and propofol, compared to propofol-based monitored anesthesia care and conventional general anesthesia during therapeutic endoscopic retrograde cholangiopancreatography (ERCP). METHODS: From September to December 2019, 360 patients scheduled for elective ERCP at the Endoscopy Center of the First Affiliated Hospital of Nanjing Medical University were randomly assigned to three different groups: Group MAC (propofol-based monitored anesthesia care, n=120), Group GA1 (general anesthesia with neuromuscular blocking agents, n=120), or Group GA2 (remifentanil-propofol combination-based muscle relaxant-free general anesthesia, n=120). RESULTS: The results showed that there was a significant difference in intraprocedural cardiopulmonary adverse events among the three groups (Group MAC, 37.5%; Group GA1, 19.2%; Group GA2, 17.5%; P < 0.001). Total time (from patient entry into the Endoscopy Center to departure) and room time (from patient entry into the endoscopy suit to departure) were shorter in Group GA2 and Group MAC compared to Group GA1 (P < 0.001). Additionally, endoscopist satisfaction levels were significantly higher in Group GA1 and Group GA2 compared to Group MAC (P < 0.001). CONCLUSION: The study found that administering propofol-remifentanil combination for "muscle relaxant-free" general anesthesia during therapeutic ERCP was safe and effective. This approach offered greater safety and endoscopist satisfaction than propofol-based monitored anesthesia care, as well as shorter total time and room time than conventional general anesthesia.

Global and tissue-specific aging effects on murine proteomes.

Maintenance of protein homeostasis degrades with age, contributing to aging-related decline and disease. Previous studies have primarily surveyed transcriptional aging changes. To define the effects of age directly at the protein level, we perform discovery-based proteomics in 10 tissues from 20 C57BL/6J mice, representing both sexes at adult and late midlife ages (8 and 18 months). Consistent with previous studies, age-related changes in protein abundance often have no corresponding transcriptional change. Aging results in increases in immune proteins across all tissues, consistent with a global pattern of immune infiltration with age. Our protein-centric data reveal tissue-specific aging changes with functional consequences, including altered endoplasmic reticulum and protein trafficking in the spleen. We further observe changes in the stoichiometry of protein complexes with important roles in protein homeostasis, including the CCT/TriC complex and large ribosomal subunit. These data provide a foundation for understanding how proteins contribute to systemic aging across tissues.

Effect of Lactobacillus (L. acidophilus NCIB1899, L. casei CRL 431, L. paracasei LP33) fermentation on free and bound polyphenolic, antioxidant activities in three Chenopodium quinoa cultivars.

The application of lactic acid bacteria (LAB) fermentation to the production of probiotic beverages is a common method for modifying the health-related functional characteristics and phytochemical content of such beverages. This study evaluated the effect of fermentation with Lactobacillus acidophilus NCIB1899, Lactobacillus casei CRL 431, and Lactobacillus paracasei LP33 on the total phenolic contents (PCs), flavonoid contents (FCs), phenolic profiles, and antioxidant capacities of the solvent-extractable (free) and cell-wall-bound (bound) fractions in quinoa varying in bran color. Compared with unfermented beverages, LAB fermentation significantly increased the free PCs and free FCs by 15.7%-79.4% and 7.6%-84.3%, respectively. The bound PCs increased, whereas bound FCs decreased in fermented black and red quinoa juice. The increments of procyanidin B2 , protocatechuic acid, p-hydroxybenzaldehyde, rutin, and kaempferol through 30 h fermentation exceeded 189%-622%, 13.8%-191%, 55.6%-100%, 48.5%-129%, and 120%-325%, respectively. However, the contents of catechin, procyanidin B1 , and ferulic acid decreased with fermentation. Overall, L. acidophilus NCIB1899, L. casei CRL431, and L. paracasei LP33 strains may be suitable for producing fermented quinoa probiotic beverages. L. acidophilus NCIB1899 was superior for fermentation to L. casei CRL431 and L. paracasei LP33. Red and black quinoa had significantly higher total (sum of free and bound) PC and FC concentrations and antioxidant capacities than white quinoa (p < 0.05) because of their higher concentrations of proanthocyanins and polyphenol, respectively. PRACTICAL APPLICATION: In this study, different LAB (L. acidophilus NCIB1899, L. casei CRL431, and L. paracasei LP33) were singly inoculated on aqueous solutions from quinoa to ferment probiotic beverage and to compare the metabolic capacity of LAB strains on nonnutritive phytochemicals (phenolic compounds). We observed that LAB fermentation greatly enhanced the phenolic and antioxidant activity of quinoa. The comparison indicated that the L. acidophilus NCIB1899 strain has the highest fermentation metabolic capacity.

Predictive value of NoSAS questionnaire combined with the modified Mallampati grade for hypoxemia during routine sedation for gastrointestinal endoscopy.

BACKGROUND: The incidence of hypoxemia during painless gastrointestinal endoscopy remains a matter of concem. To date, there is no recognized simple method to predict hypoxemia in digestive endoscopic anesthesia. The NoSAS (neck circumference, obesity, snoring, age, sex) questionnaire, an objective and simple assessment scale used to assess obstructive sleep apnea (OSA), combined with the modified Mallampati grade (MMP), may have certain screening value. This combination may allow anesthesiologists to anticipate, manage, and consequently decrease the occurrence of hypoxemia. METHODS: This study was a prospective observational trial. The primary endpoint was the incidence of hypoxaemia defined as pulse oxygen saturation (SpO2) < 95% for 10 s. A total of 2207 patients admitted to our hospital for painless gastrointestinal endoscopy were studied. All patients were measured for age, height, weight, body mass index, neck circumference, snoring, MMP, and other parameters. Patients were divided into hypoxemic and non-hypoxemic groups based on the SpO2. The ROC curve was plotted to evaluate the screening value of the NoSAS questionnaire separately and combined with MMP for hypoxemia. The total NoSAS score was evaluated at cut-off points of 8 and 9. RESULTS: With a NoSAS score ≥ 8 as the critical value for analysis, the sensitivity for hypoxemia was 58.3%, the specificity was 88.4%, and the area under the ROC was 0.734 (P < 0.001, 95% CI: 0.708-0.759). With a NoSAS score ≥ 9 as a critical value, the sensitivity for hypoxemia was 36.50%, the specificity rose to 96.16%, and the area under the ROC was 0.663 (P < 0.001, 95% CI: 0.639-0.688). With the NoSAS Score combined with MMP for analysis, the sensitivity was 78.4%, the specificity was 84%, and the area under the ROC was 0.859 (P < 0.001, 95%CI:0.834-0.883). CONCLUSIONS: As a new screening tool, the NoSAS questionnaire is simple, convenient, and useful for screening hypoxemia. This questionnaire, when paired withMMP, is likely to be helpful for the screening of hypoxemia.

Prognostic value of miR-219-5p in relation to mortality in patients with small cell lung cancer: a retrospective, observational cohort study in China.

OBJECTIVES: Small cell lung cancer (SCLC) is a lethal human malignancy, and previous studies support the contribution of microRNA to cancer progression. The prognostic value of miR-219-5p in patients with SCLC remains unclear. This study aimed to evaluate the predictive value of miR-219-5p with respect to mortality in patients with SCLC and to incorporate miR-219-5p level into a prediction model and nomogram for mortality. DESIGN: Retrospective observational cohort study. SETTING AND PARTICIPANTS: Our main cohort included data from 133 patients with SCLC between 1 March 2010 and 1 June 2015 from the Suzhou Xiangcheng People's Hospital. Data from 86 patients with non-SCLC at Sichuan Cancer Hospital and the First Affiliated Hospital of Soochow University were used for external validation. OUTCOME MEASURES: Tissue samples were taken during admission and stored, and miR-219-5p levels were measured at a later date. A Cox proportional hazard model was used for survival analyses and for analysing risk factors to create a nomogram for mortality prediction. The accuracy of the model was evaluated by C-index and calibration curve. RESULTS: Mortality in patients with a high level of miR-219-5p (≥1.50) (n=67) was 74.6%, while mortality in the low-level group (n=66) was 100.0%. Based on univariate analysis, we included significant factors (p<0.05) in a multivariate regression model: patients with high level of miR-219-5p (HR 0.39, 95% CI 0.26-0.59, p<0.001), immunotherapy (HR 0.44, 95% CI 0.23-0.84, p<0.001) and prognostic nutritional index score >47.9 (HR=0.45, 95% CI 0.24-0.83, p=0.01) remained statistically significant factors for improved overall survival. The nomogram had good accuracy in estimating the risk, with a bootstrap-corrected C-index of 0.691. External validation indicated an area under the curve of 0.749 (0.709-0.788). CONCLUSIONS: The miR-219-5p level was associated with a reduced risk of mortality in patients with SCLC. A nomogram incorporating MiR-219-5p level and clinical factors demonstrated good accuracy in estimating the risk of overall mortality. Prospective validation of the prognostic nomogram is needed.

Propofol Suppresses Glioma Tumorigenesis by Regulating circ_0047688/miR-516b-5p/IFI30 Axis.

Propofol has recently attracted increasing attention for its anti-tumor property in cancers, including glioma. Circular RNAs (circRNAs) can act as key regulators in various cancers. However, the relationship between propofol and circ_0047688 in glioma is still unclear. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays. Cell migration and invasion were determined using transwell assay. Cell apoptosis was detected by flow cytometry. Protein levels and RNA levels were detected by western blot assay and real-time quantitative polymerase chain reaction (RT­qPCR), respectively. The intermolecular interaction was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. A mouse xenograft model was established for in vivo experiments. Propofol inhibited cell proliferation, migration, and invasion and accelerated apoptosis in glioma cells. Circ_0047688 was upregulated in glioma tissues and cells, and propofol downregulated circ_0047688 in a dose-dependent manner. Circ_0047688 knockdown inhibited glioma cell progression and its overexpression abated the anti-tumor role of propofol in glioma cells. Moreover, miR-516b-5p was a direct target of circ_0047688, and circ_0047688 promoted glioma cell progression by sponging miR-516b-5p. In addition, IFI30 was a direct target of miR-516b-5p, and miR-516b-5p inhibited glioma cell malignant behaviors by targeting IFI30 in propofol-treated cells. Furthermore, circ_0047688 overexpression could weaken the anti-tumor role of propofol in vivo. Propofol inhibited glioma progression via modulating circ_0047688/miR-516b-5p/IFI30 axis, providing a potential therapeutic strategy for treatment of glioma.

Anesthesia management for tracheoesophageal fistula closed with a new gastrointestinal occluder device: a case report.

BACKGROUND: Tracheoesophageal fistula (TEF) is a rare but life-threatening complication after esophagectomy. A new gastrointestinal occluder device provides treatment for TEF patients. However, TEF-related pneumonia and respiratory failure increase the difficulty of anesthesia management, especially in airway management. CASE PRESENTATION: A 64-year-old man with thoracic esophageal cancer underwent esophagectomy and gastric tube reconstruction one year ago. The patient presented with recurrent cough and sputum after surgery. Gastroscopy revealed a fistula between the esophagogastric anastomotic site and membrane of the trachea. Therefore, the patient received implantation of a new gastrointestinal occluder device under gastroscopy combined with tracheoscopy. Airway management under general anesthesia was discussed with an interdisciplinary decision, and cuffed endotracheal tube with an inner diameter of 5.5 mm was chosen. This airway management ensured adequate oxygenation during the operation and provided sufficient space for the operation of the tracheoscope in the trachea. Finally, the TEF disappeared after the operation, and the patient was administered an oral diet on the first postoperative day. CONCLUSIONS: The implantation of a new gastrointestinal occluder device under gastroscopy combined with tracheoscopy provides a new treatment for TEF patients. This case report suggests that it is important to select an endotracheal tube with an appropriate inner diameter that can not only meet the requirements of ventilation but also does not affect the operation of tracheoscopy in the trachea.

Evolution of polyphenolic, anthocyanin, and organic acid components during coinoculation fermentation (simultaneous inoculation of LAB and yeast) and sequential fermentation of blueberry wine.

This research aims to investigate the effects of both sequential fermentation and coinoculation fermentation with yeast and lactic acid bacterial (LAB) on the dynamics of changes in basic quality parameters and organic acid, anthocyanin, and phenolic components as well as antioxidant activity during the fermentation of blueberry. The coculture-fermented blueberry wine showed significant decreases in total phenolics, flavonoids, and anthocyanins,by 23.9%, 15.9%, and 13.7%, respectively, as compared with those before fermentation Fermentation changed the contents of organic acids in each group, with a more than 7-fold increase in lactic acid contents as well as a more than 4-fold reduction in quinic acid and malic acid contents. The content of all investigated anthocyanins first increased and then decreased. Moreover, different fermentation strategies exerted a profound influence on the dynamic change in phenolic components during fermentation; specifically, most of the phenolic acids showed a trend of increasing first, then decreasing, and finally increasing. Gallic acid, p-coumaric acid, quercetin, and myricetin were increased by 116.9%, 130.1%, 127.2% and 177.6%, respectively, while syringic acid, ferulic acid, cinnamic acid, and vanillic acid were decreased by 49.5%, 68.5%, and 37.1% in sequentially fermented blueberry wine. Coinoculation fermentation with yeast and LAB produces faster dynamic variations and higher organic acid, anthocyanin, and phenolic profiles than sequential inoculation fermentation. PRACTICAL APPLICATION: In this work, brewing technology of sequential fermentation and coinoculation fermentation with yeast and LAB (Lactobacillus plantarum SGJ-24 and Oenococcus oeni SD-2a) was adopted to ferment blueberry wine. This is an innovative technology of fruit wine brewing technology to produce wine products. Compared with traditional sequential brewing, simultaneous inoculation brewing can significantly accelerate the brewing process of fruit wine and slightly improve the quality of fruit wine in terms of active ingredients.

A tumor microenvironment-responsive micelle co-delivered radiosensitizer Dbait and doxorubicin for the collaborative chemo-radiotherapy of glioblastoma.

Glioblastoma is rather recalcitrant to existing therapies and effective interventions are needed. Here we report a novel microenvironment-responsive micellar system (ch-K5(s-s)R8-An) for the co-delivery of the radiosensitizer Dbait and the chemotherapeutic doxorubicin (DOX) to glioblastoma. Accordingly, the ch-K5(s-s)R8-An/(Dbait-DOX) micelles plus radiotherapy (RT) treatment resulted in a high degree of apoptosis and DNA damage, which significantly reduced cell viability and proliferation capacity of U251 cells to 64.0% and 16.3%, respectively. The angiopep-2-modified micelles exhibited substantial accumulation in brain-localized U251 glioblastoma xenografts in mice compared to angiopep-2-lacking micelles. The ch-K5(s-s)R8-An/(Dbait-DOX) + RT treatment group exhibited the smallest tumor size and most profound tumor tissue injury in orthotopic U251 tumors, leading to an increase in median survival time of U251 tumor-bearing mice from 26 days to 56 days. The ch-K5(s-s)R8-An/(Dbait-DOX) micelles can be targeted to brain-localized U251 tumor xenografts and sensitize the tumor to chemotherapy and radiotherapy, thereby overcoming the inherent therapeutic challenges associated with malignant glioblastoma.

The role of daurisoline treatment in hepatocellular carcinoma: Inhibiting vasculogenic mimicry formation and enhancing sensitivity to sorafenib.

BACKGROUND: Vasculogenic mimicry (VM) is a newly described tumor vascular phenomenon that is independent of traditional angiogenesis and provides an adequate blood supply for tumor growth. VM has been consistently observed in different cancer types. Hence, inhibition of VM may be considered a new anticancer therapeutic strategy. PURPOSE: This study aimed to elucidate the potential anticancer effect of daurisoline (DS) on hepatocellular carcinoma (HCC) and the potential molecular mechanism by which DS inhibits VM. We also verified whether combination treatment with sorafenib and DS constitutes a novel therapeutic approach to prevent HCC progression. METHODS: The effects of DS on proliferation were evaluated by Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. 4',6-Diamidino-2-phenylindole (DAPI) staining and flow cytometric analysis were employed to investigate its effects on apoptosis. Western blot analysis, Matrigel tube formation assays, pulldown assays and immunofluorescence staining were applied to validate the potential mechanism by which DS inhibits VM. Mouse xenograft models were used to evaluate anticancer activities. RESULTS: DS inhibited HCC cell proliferation, induced HCC cell apoptosis and repressed VM formation by inactivating RhoA/ROCK2-mediated AKT and ERK-p38 MAPK signaling. Additionally, DS dramatically sensitized HCC cell lines to sorafenib, a curative anticancer drug for patients with advanced HCC. CONCLUSIONS: Our study provides insights into the molecular mechanisms underlying DS-induced inhibition of VM, which may facilitate the development of a novel clinical anti-HCC drug. Moreover, our findings suggest that the combination of DS and sorafenib constitutes a potential therapeutic strategy for HCC.

Viscozyme L hydrolysis and Lactobacillus fermentation increase the phenolic compound content and antioxidant properties of aqueous solutions of quinoa pretreated by steaming with α-amylase.

In this work, red quinoa was successively subjected to α-amylase steaming, complex enzyme Viscozyme (R) L hydrolysis, and lactic acid bacteria (LAB) fermentation. The total phenolic compound content (TPC), flavonoid content (TFC), and antioxidant capacities of the solvent-extractable (free) and bound fractions and the individual phenolic compounds released were determined. Compared to steaming with α-amylase, enzymatic hydrolysis and fermentation of quinoa resulted in approximately 82.6, 26.9, 36.3, and 45.2% increases in the TPC (the sum of free and bound fractions), TFC, DPPH, and ORAC values, respectively. HPLC-QqQ-MS/MS analysis showed that enzymolysis and fermentation increased the content of protocatechuic acid, catechin, procyanidin B2 , and quercetin by 126.3, 101.9, 524, and 296.3%, respectively. Moreover, a major proportion of individual phenolic compounds existed as bound form. The results indicated that complex enzymatic hydrolysis and LAB fermentation were practical and useful to release promising polyphenols. This research provides a basis for the processing of quinoa beverages rich in phenolic compounds. PRACTICAL APPLICATION: In this work, liquefying with α-amylase, hydrolyzing with cellulolytic enzyme mixture, and fermenting with Lactic acid bacteria (LAB), successively, were exploited to process quinoa. This is an innovative method of quinoa processing to produce beverage products. Complex enzymatic hydrolysis and fermentation with LAB can significantly enhance phenolic compound, especially protocatechuic acid, catechin, procyanidin B2 , and quercetin. In additional, LAB fermentation is very beneficial to improve the antioxidant activity of quinoa. We also found that a major proportion of phenolic compounds existed as bound forms in quinoa.

Autophagy, an accomplice or antagonist of drug resistance in HCC?

Hepatocellular carcinoma (HCC) is a highly lethal malignancy characterized by poor prognosis and a low 5-year survival rate. Drug treatment is proving to be effective in anti-HCC. However, only a small number of HCC patients exhibit sensitive responses, and drug resistance occurs frequently in advanced patients. Autophagy, an evolutionary process responsible for the degradation of cellular substances, is closely associated with the acquisition and maintenance of drug resistance for HCC. This review focuses on autophagic proteins and explores the intricate relationship between autophagy and cancer stem cells, tumor-derived exosomes, and noncoding RNA. Clinical trials involved in autophagy inhibition combined with anticancer drugs are also concerned.

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents.

Cancer stem cells (CSCs) show a self-renewal capacity and differentiation potential that contribute to tumor progression and therapy resistance. However, the underlying processes are still unclear. Elucidation of the key hallmarks and resistance mechanisms of CSCs may help improve patient outcomes and reduce relapse by altering therapeutic regimens. Here, we reviewed the identification of CSCs, the intrinsic and extrinsic mechanisms of therapy resistance in CSCs, the signaling pathways of CSCs that mediate treatment failure, and potential CSC-targeting agents in various tumors from the clinical perspective. Targeting the mechanisms and pathways described here might contribute to further drug discovery and therapy.

Structure, dynamics and transport behavior of migrating corrosion inhibitors on the surface of calcium silicate hydrate: a molecular dynamics study.

The incorporation of a corrosion inhibitor into a cement-based material can enhance the durability of the reinforced concrete. In this study, molecular dynamics simulation is utilized to study the interfacial structure and dynamic behavior of a solution with three migrating corrosion inhibitors (MCI) functionalized by hydroxyl (-OH), carboxyl (-COO-), and phenyl (-PH) groups in calcium silicate hydrate (CSH) gel pores. The transport rate of inhibitors is greatly dependent on the polarity of the functional group: -PH > -OH > -COO-. The slow migration rate of the inhibitor with -OH and -COO- is attributed to the chemical bond formed between CSH and MCI. The silicate chains near the CSH surface can provide plenty of non-bridging oxygen sites to accept the H-bond from the hydroxyl group in the inhibitor molecule. The surface calcium atom can capture the -COO- by forming an ionic COO-Ca bond. Furthermore, the hydration structure of the inhibitor molecule also influences its transport properties. The inhibitor functionalized by the carboxyl group, associating with the neighboring water molecules, forms ion-water clusters, and the inhibitor molecule and its hydration shell with a long resident time retard the migration rate. Hopefully, this study is able to provide molecules for the development of a migration-type corrosion inhibitor to elongate the service life of cement-based materials.

Non-Coding RNA m6A Modification in Cancer: Mechanisms and Therapeutic Targets.

Recently, N6-methyl-adenosine (m6A) ribonucleic acid (RNA) modification, a critical and common internal RNA modification in higher eukaryotes, has generated considerable research interests. Extensive studies have revealed that non-coding RNA m6A modifications (e.g. microRNAs, long non-coding RNAs, and circular RNAs) are associated with tumorigenesis, metastasis, and other tumour characteristics; in addition, they are crucial molecular regulators of cancer progression. In this review, we discuss the relationship between non-coding RNA m6A modification and cancer progression from the perspective of various cancers. In particular, we focus on important mechanisms in tumour progression such as proliferation, apoptosis, invasion and metastasis, tumour angiogenesis. In addition, we introduce clinical applications to illustrate more vividly that non-coding RNA m6A modification has broad research prospects. With this review, we aim to summarize the latest insights and ideas into non-coding RNA m6A modification in cancer progression and targeted therapy, facilitating further research.