Cardioprotective effect of Cinnamamide derivative compound 10 against myocardial ischemia-reperfusion through regulating cardiac autophagy via Sirt1.

BACKGROUND AND PURPOSE: Our previous research discovered that cinnamamide derivatives are a new type of potential cardioprotective agents myocardial ischemia-reperfusion (MIR) injury, among which Compound 10 exhibits wonderful beneficial action in vitro. However, the exact mechanism of Compound 10 still needs to be elucidated. EXPERIMENTAL APPROACH: The protective effect of Compound 10 was determined by detecting the cell viability and LDH leakage rate in H9c2 cells subjected to H2O2. Alterations of electrocardiogram, echocardiography, cardiac infarct area, histopathology and serum myocardial zymogram were tested in MIR rats. Additionally, the potential mechanism of Compound 10 was explored through PCR. Network pharmacology and Western blotting was conducted to monitor levels of proteins related to autophagic flux and mTOR, autophagy regulatory substrate, induced by Compound 10 both in vitro and in vivo, as well as expressions of Sirtuins family members. KEY RESULTS: Compound 10 significantly ameliorated myocardial injury, as demonstrated by increased cell viability, decreased LDH leakage in vitro, and declined serum myocardial zymogram, ST elevation, cardiac infarct area and improved cardiac function and microstructure of heart tissue in vivo. Importantly, Compound 10 markedly enhanced the obstruction of autophagic flux and inhibited excessive autophagy initiation against MIR by decreased ATG5, Rab7 and increased P-mTOR and LAMP2. Furthermore, Sirt1 knockdown hindered Compound 10's regulation on mTOR, leading to interrupted cardiac autophagic flux. CONCLUSIONS AND IMPLICATIONS: Compound 10 exerted cardioprotective effects on MIR by reducing excessive autophagy and improving autophgic flux blockage. Our work would take a novel insight in seeking effective prevention and treatment strategies against MIR injury.

Wnt/ß-catenin-driven EMT regulation in human cancers.

Metastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial-mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/ß-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3ß that destructs ß-catenin, while ligand-receptor interaction impairs GSK-3ß function to increase ß-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/ß-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance ß-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/ß-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/ß-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression.

Biodegradation of polyethylene terephthalate by Tenebrio molitor: Insights for polymer chain size, gut metabolome and host genes.

Polyethylene terephthalate (PET or polyester) is a commonly used plastic and also contributes to the majority of plastic wastes. Mealworms (Tenebrio molitor larvae) are capable of biodegrading major plastic polymers but their degrading ability for PET has not been characterized based on polymer chain size molecular size, gut microbiome, metabolome and transcriptome. We verified biodegradation of commercial PET by T. molitor larvae in a previous report. Here, we reported that biodegradation of commercial PET (Mw 29.43 kDa) was further confirmed by using the δ13C signature as an indication of bioreaction, which was increased from - 27.50‰ to - 26.05‰. Under antibiotic suppression of gut microbes, the PET was still depolymerized, indicating that the host digestive enzymes could degrade PET independently. Biodegradation of high purity PET with low, medium, and high molecular weights (MW), i.e., Mw values of 1.10, 27.10, and 63.50 kDa with crystallinity 53.66%, 33.43%, and 4.25%, respectively, showed a mass reduction of > 95%, 86%, and 74% via broad depolymerization. Microbiome analyses indicated that PET diets shifted gut microbiota to three distinct structures, depending on the low, medium, and high MW. Metagenome sequencing, transcriptomic, and metabolic analyses indicated symbiotic biodegradation of PET by the host and gut microbiota. After PET was fed, the host's genes encoding degradation enzymes were upregulated, including genes encoding oxidizing, hydrolyzing, and non-specific CYP450 enzymes. Gut bacterial genes for biodegrading intermediates and nitrogen fixation also upregulated. The multiple-functional metabolic pathways for PET biodegradation ensured rapid biodegradation resulting in a half-life of PET less than 4 h with less negative impact by PET MW and crystallinity.

The pan-cancer landscape of glutamate and glutamine metabolism: A comprehensive bioinformatic analysis across 32 solid cancer types.

Glutamine metabolism is a hallmark of cancer metabolism, which matters in the progression of the tumor. This synthetic study conducted a large-scale systematic analysis at the pan-cancer level on the glutamate and glutamine metabolism (GGM) across 32 solid tumors from the TCGA database. The glutamine metabolism activity was quantified through a scoring system. This study revealed that the GGM score in tumor tissues was up-regulated in 13 cancer types (BCLA, BRCA, COAD, KICH, KIRP, LUAD, LUSC, PAAD, PRAD, READ, STAD, THYM, UCEC) and down-regulated in 4 cancer types (CHOL, GBM, LIHC, THCA), exhibiting tissue specificity. The mRNA expression levels of glutamine metabolism-related genes were relatively high, and GLUL exhibited the highest expression level. The expression levels were up-regulated with copy number amplification. ALDH18A1, PYCR1, and PYCR2 show a significant upregulation in protein levels in cancer tissues compared to normal tissues, making them potential pan-cancer therapeutic targets. For the TME related to glutamine metabolism, the GGM score exhibited significant immune and stromal environment inhibitory effects in all involved tumors. Up-regulated GGM score indicated the widespread promotion of drug resistance at the pan-cancer level. GGM score and glutamine metabolism-related genes signature tended to be risk factors for the overall survival of cancer patients.

MULTIPLE MACHINE LEARNING METHODS AND COMPARATIVE TRANSCRIPTOMICS IDENTIFY PIVOTAL GENES FOR ISCHEMIA-REPERFUSION INJURY IN HUMAN DONOR TISSUE UNDERGOING ORTHOTOPIC LIVER TRANSPLANTATION.

ABSTRACT: Background: Hepatic ischemia-reperfusion injury (HIRI) is a major complication affecting patient prognosis during the period after orthotopic liver transplantation (OLT). Although an increasing number of scientists have investigated the molecular biology of ischemia-reperfusion injury (IRI) during OLT in animal and cellular models in recent years, studies using comprehensive and high-quality sequencing results from human specimens to screen for key molecules are still lacking. Aims: The objective of this study is to explore the molecular biological pathways and key molecules associated with HIRI during OLT through RNA sequencing and related bioinformatics analysis techniques. Methods: The study was done by performing mRNA sequencing on liver tissue samples obtained from 15 cases of in situ liver transplantation patients who experienced ischemia and reperfusion injury within 1 year at Guizhou Medical University, and combined with bioinformatics analysis and machine learning methods, we identified the genes and transcription factors that are closely associated with IRI during in situ liver transplantation surgery. Results: There were 877 differentially expressed genes (DEGs) identified in the included liver samples, of which 817 DEGs were upregulated and 60 were downregulated. Functional enrichment analysis revealed significant enrichment of immune-related terms, such as inflammation, defense responses, responses to cytokines, immune system processes, and cellular activation. In addition, core gene enrichment analysis after cytoHubba screening suggested that liver reperfusion injury might be associated with translation-related elements as a pathway together with protein translation processes. Machine learning with the weighted correlation network analysis screening method identified PTGS2, IRF1, and CDKN1A as key genes in the reperfusion injury process. Conclusions: This study demonstrated that the pathways and genomes whose expression is altered throughout the reperfusion process might be critical for the progression of HIRI during OLT.

Primary lipoblastic nerve sheath tumor in an inguinal lymph node mimicking metastatic tumor: a case report and literature review.

Lipoblastic nerve sheath tumors of soft tissue are characterized as schwannoma tumors that exhibit adipose tissue and lipoblast-like cells with signet-ring morphology. They have been documented to arise in various anatomic locations, including the thigh, groin, shoulder, and retroperitoneum. However, to our knowledge, this tumor has not been previously reported as a lymph node primary. We present herein the first case of a benign primary lipoblastic nerve sheath tumor arising in an inguinal lymph node in a 69-year-old man. Microscopic examination revealed a multinodular tumor comprising fascicles of spindle cells, as well as adipocytic and lipoblast-like signet-ring cell component in the context of schwannoma. Despite the presence of some bizarre cells with nuclear atypia, no obvious mitotic activity or necrosis was observed. Immunohistochemical analysis showed strong and diffuse expression of S-100, SOX10, CD56, and NSE in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes. Sequencing analysis of the neoplasm identified six non-synonymous single nucleotide variant genes, specifically NF1, BRAF, ECE1, AMPD3, CRYAB, and NPHS1, as well as four nonsense mutation genes including MRE11A, CEP290, OTOA, and ALOXE3. The patient remained alive and well with no evidence of recurrence over a period of ten-year follow-up.

The role of N6-methyladenosine methylation in PAHs-induced cancers.

Polycyclic aromatic hydrocarbons (PAHs), which are a wide range of environmental toxicants, may act on humans through inhalation, ingestion, and skin contact, resulting in a range of toxic reactions. Epidemiological studies showed that long-term exposure to PAHs in the occupational and living environment results in a substantial rise in the incidence rate of many cancers in the population, so the prevention and treatment of these diseases have become a major worldwide public health problem. N6-methyladenosine (m6A) modification greatly affects the metabolism of RNA and is implicated in the etiopathogenesis of many kinds of diseases. In addition, m6A-binding proteins have an important role in disease development. The abnormal expression of these can cause the malignant proliferation, migration, invasion, and metastasis of cancers. Furthermore, a growing number of studies revealed that environmental toxicants are one of the cancer risk factors and are related to m6A modifications. Exposure to environmental toxicants can alter the methylation level of m6A and the expression of the m6A-binding protein, thus promoting the occurrence and development of cancers through diverse mechanisms. m6A may serve as a biomarker for early environmental exposure. Through the study of m6A, we can find the health injury early, thus providing a new sight for preventing and curing environmental health-related diseases.

Global research trends on the links between intestinal microbiota and liver diseases: a bibliometric analysis.

The number of articles on the relationships between the intestinal microbiota and liver diseases has continued to increase. The aim of this study was to assess publications on this topic, identify research hotspots, and predict trends of future research. Articles on this topic published from 2001 to 2021 were obtained from the Web of Science Core Collection. Bibliometric analysis and visualization were performed to identify research hotspots and trends with the use of the online bibliometric analysis platform, VOSviewer, and CiteSpace. In total, 4415 articles were included for bibliometric analysis. The annual output of research on this topic gradually increased over the past 21 years. China contributed the most publications (1254), while the United States was the core (centrality = 0.35) of the country-cooperation network and Schnabl B published the most articles (n = 80). High-frequency keywords included "gut microbiota", "inflammation", "obesity", "insulin resistance", "disease", "fatty liver disease", "metabolism", and "probiotics". The keywords that have burst in recent years include "intestinal microbiota", "dysbiosis", and "gut-liver axis". The relationships between dysbiosis of the intestinal microbiota and liver diseases, such as nonalcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), are current research hotspots. Treatment for NAFLD, nonalcoholic steatohepatitis, cirrhosis, and HCC via regulation of the intestinal microbiota is predicted as a research hotspot in the following years, especially immunotherapy for HCC. These findings should prove helpful to scholars to direct future research on the relationships between the intestinal microbiota and liver diseases.

Integrative analysis of the gut microbiota and faecal and serum short-chain fatty acids and tryptophan metabolites in patients with cirrhosis and hepatic encephalopathy.

OBJECTIVE: The purpose of this study was to describe the changes in the gut microbiome of patients with cirrhosis and hepatic encephalopathy (HE), as well as quantify the variations in short-chain fatty acid (SCFA) and tryptophan metabolite levels in serum and faeces. METHODS: Fresh faeces and serum were collected from 20 healthy volunteers (NC group), 30 cirrhosis patients (Cir group), and 30 HE patients (HE group). Then, 16S rRNA sequencing and metabolite measurements were performed using the faeces. Gas chromatography‒mass spectrometry and ultrahigh-performance liquid chromatography-tandem mass spectrometry were used to measure SCFA and tryptophan levels, respectively. The results were analysed by SIMCA16.0.2 software. Differences in species were identified using MetaStat and t tests. The correlations among the levels of gut microbes and metabolites and clinical parameters were determined using Spearman correlation analysis. RESULTS: Patients with cirrhosis and HE had lower microbial species richness and diversity in faeces than healthy volunteers; these patients also had altered ß-diversity. Serum valeric acid levels were significantly higher in the HE group than in the Cir group. Serum SCFA levels did not differ between the Cir and NC groups. Serum melatonin and 5-HTOL levels were significantly higher in the HE group than in the Cir group. The Cir and NC groups had significant differences in the levels of eight serum tryptophan metabolites. Furthermore, the levels of faecal SCFAs did not differ between the HE and Cir groups. Faecal IAA-Ala levels were significantly lower in the HE group than in the Cir group. There were significant differences in the levels of 6 faecal SCFAs and 7 faecal tryptophan metabolites between the Cir and NC groups. Certain gut microbes were associated with serum and faecal metabolites, and some metabolites were associated with certain clinical parameters. CONCLUSION: Reduced microbial species richness and diversity were observed in patients with HE and cirrhosis. In both serum and faeces, the levels of different SCFAs and tryptophan metabolites showed varying patterns of change. In HE patients, the levels of some serum tryptophan metabolites, and not SCFAs, were correlated with liver function and systemic inflammation. Systemic inflammation in patients with cirrhosis was correlated with faecal acetic acid levels. In summary, this study identified metabolites important for HE and cirrhosis.

Tooth Wear and Tribological Investigations in Dentistry.

Dental or tooth wear is a physiological process in the life cycle of teeth. Loss of the occlusal surface may cause excessive tooth wear. Several factors may contribute to tooth wear with different intensities and duration in the oral cavity. The oral cavity is generally compared to a tribological system to determine the various types of wear between teeth and restorative materials and assess the amount of dental wear. However, it is challenging to investigate in vitro and in vivo wear owing to the complexity of tooth wear; thus, a clear correlation between in vitro and in vivo data could not be established. This review is aimed at providing an insight into the etiology of tooth wear and tribological investigations in dentistry.

Impacts of physical-chemical property of polyethylene on depolymerization and biodegradation in yellow and dark mealworms with high purity microplastics.

Yellow and dark mealworms (Tenebrio molitor and Tenebrio obscurus) biodegrade commercial polyethylene (PE) materials at a high rate. We examined the impact of physical and chemical properties on biodegradation using high purity microplastics (MPs). These included high-density polyethylene (HDPE), low-density polyethylene (LDPE), and linear low-density polyethylene (LLDPE), all with different weight average molecular weights (Mw) and different crystallinity degrees in T. molitor and T. obscurus larvae. The biodegradation extent in the two mealworms was similar but strongly depended on the polymer type in sequence, since LDPE > LLDPE> HDPE (with respective Mw of 222.5, 110.5 and 182 kDa). When LDPE MPs with Mw of 0.84, 6.4 and 106.8 kDa and HDPE with Mw of 52, 105 and 132.7 kDa were tested, the PE MPs with lower Mw showed a greater extent of depolymerization. The results of dominance analysis indicated that less branching structure and higher crystallinity degree negatively impacted depolymerization and biodegradation. Py-GC/MS analysis confirmed the breaking of the macromolecule backbone as well as the formation of oxidized functional groups after all the tested PE materials passed through the mealworm intestine. The results demonstrated that molecular weight, PE type, branching, and crystallinity degree significantly affect the biodegradation capability of PE by the mealworms, and possibly by other biological systems as well.

Laparoscopic Pancreaticoduodenectomy in Elderly Patients: Systematic Review and Meta-Analysis.

Background: The safety and efficacy of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients who often suffer from pre-existing conditions (e.g., cardiovascular diseases) and poor functional reserve remain unclear. This meta-analysis aimed to evaluate the safety and efficacy of LPD in elderly patients. Methods: A systematic literature search was conducted using the PubMed, Embase, Web of Science, and Cochrane Library databases. All studies published from their inception to January 2022 reporting perioperative outcomes after LPD in elderly patients were included in the search (Group 1, comparing the perioperative outcomes of LPD and OPD in elderly patients; Group 2, comparing the perioperative outcomes after LPD between elderly and non-elderly patients). The evaluated outcomes included perioperative mortality, postoperative complications, conversion, operative time, estimated blood loss (EBL), postoperative hospital stay (POHS), and readmission. Results: In total 8 studies were included in the meta-analysis. Pooled analysis of Group 1 showed that EBL, 90-day mortality, major morbidity, bile leak, POH, abdominal infection, reoperation, POP, POCE, and readmission were not significantly different between the LPD and the OPD group. LPD was associated with longer operative time, lower POPF rate, lower DEG rate, and shorter POHS. Pooled analysis of Group 2 showed that mortality, major morbidity, POPF, DEG, bile leak, POH, abdominal infection, reoperation, conversion, operative time, EBL, and readmission were not significantly different between the elderly and the non-elderly group. The POHS of elderly group was significantly longer than non-elderly group. Conclusion: LPD may be a safe and feasible procedure for elderly patients and is associated with short POHS.

Effect of Controlled Microtopography on Osteogenic Differentiation of Mesenchymal Stem Cells.

Various kinds of controlled microtopographies can promote osteogenic differentiation of mesenchymal stem cells (MSCs), such as microgrooves, micropillars, and micropits. However, the optimal shape, size, and mechanism remain unclear. In this review, we summarize the relationship between the parameters of different microtopographies and the behavior of MSCs. Then, we try to reveal the potential mechanism between them. The results showed that the microgrooves with a width of 4-60 µm and ridge width <10 µm, micropillars with parameters less than 10 µm, and square micropits had the full potential to promote osteogenic differentiation of MSCs, while the micromorphology of the same size could induce larger focal adhesions (FAs), well-organized cytoskeleton, and superior cell areas. Therefore, such events are possibly mediated by microtopography-induced mechanotransduction pathways.

Enhanced nitrogen removal in an electrochemically coupled biochar-amended constructed wetland microcosms: The interactive effects of biochar and electrochemistry.

The interactive effects of both biochar (BC) and electrochemistry (EC) can affect nitrogen (N) removal process. However, little is known about how this function in constructed wetland (CW) systems. In this study, an electrochemically (EC) coupled BC-amended saturated subsurface vertical flow constructed wetland (BECW) systems were established to enhance nitrogen (N) removal. Other three CW systems: without BC and EC (CW); with EC only (ECW); and with BC only (BCW) were performed as controls. Results indicated that the total nitrogen (59.88%-93.03%) and nitrate­nitrogen (83.14%-100%) of the BECW system were significantly enhanced (p < 0.05) compared with the control systems. Treated WWTP tail-water could meet Class-IV of the Surface Water Quality Standard (GB3838-2002) in China by the BECW system. The enhanced N removal in the BECW system could be attributed to (1) the autotrophic denitrification process in which H2 and Fe2+ provided by the cathode and anode acted as electron donors; and (2) BC addition acting as substrate could improve the activity, diversity and richness of microorganisms. Microbial community analysis further indicated that high N removal in the BECW system was significantly dependent on the synergy between the heterotrophic and autotrophic denitrifiers, facilitated by BC and EC interaction. Results illustrate that the BECW system is a feasible and eco-sustainable technology for treating low C/N tail-water from WWTPs. This work provides a novel and fundamental understanding of the electrochemically coupled biochar-amended CW system. These results could serve as a theoretical basis for the engineered applications in the deep purification of WWTPs' tail-water.

Fabrication of AQ2S/GR composite photosensitizer for the simulated solar light-driven degradation of sulfapyridine.

Chlorination has been intensively investigated for use in water disinfection and pollutant elimination due to its efficacy and convenience; however, the generation and transportation of chlorine and hypochlorite are energy-consuming and complicated. In this study, a novel binary photosensitizer consisting of anthraquinone-2-sulfonate (AQ2S) and graphene was synthesized via a π-π stack adsorption method; this compound could allow for the chlorination of organic pollutants using on-site chlorine generation. In this photosensitive degradation process, sulfapyridine (SPY) was selected as a model pollutant and was decomposed by the reactive species (Cl2 •-, Cl• and O2 •-) generated during the photosensitive oxidation of chloride. The synthesized AQ2S/graphene exhibited superior activity, and the degradation rate of SPY was over 90 % after 12 h of visible light irradiation with a kinetic constant of 0.2034h-1. Results show that 20 mg AQ2S/GR at a 21 % weight percentage of AQ2S in a pH 7 SPY solution with 1 mol/L Cl- achieved the highest kinetics rate at 0.353 h-1. Free radical trapping experiments demonstrated that Cl2 •- and O2 •- were the dominant species involved in SPY decomposition under solar light. The reusability and stability of this composite were verified by conducting a cycle experiment over five successive runs. The capacity of photodegradation still remained over 90 % after these 5 runs. The current study provides an energy-efficient and simple-operational approach for water phase SPY control.

A biochar-promoted V2O5/g-C3N4 Z-Scheme heterostructure for enhanced simulated solar light-driven photocatalytic activity.

A ternary biochar/vanadium pentoxide/graphite like carbon nitride (BC/V2O5/g-C3N4 denoted BC/VO/CN) composite was prepared by a simple hydrothermal method and its photocatalytic performance was investigated under simulated solar irradiation. The BC/VO/CN was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy, and photoluminescence spectroscopy. Within the BC/VO/CN composites VO nanoparticles were highly crystalline and intertwined with the lamellas of CN, resulting in the formation of well-defined Z-type heterostructures. The photocatalytic activity was evaluated using Rhodamine B as a model pollutant. Under simulated solar (230-780 nm) irradiation the as-prepared BC/VO/CN hybrid materials demonstrated highly improved photocatalytic activity compared to CN, VO and VO/CN. The cause of the solar enhancement could be ascribed to the formation of Z-type heterojunctions between VO and CN, which promoted faster electron-hole separation and more efficient charge transfer. BC, as an electron transfer medium, accelerated the transfer of photogenerated charge carriers and inhibited their recombination.