Exosomal circKIAA1797 Regulates Cell Progression and Glycolysis by Targeting miR-4429/PBX3 Pathway in Gastric Cancer.

In recent years, circular RNAs (circRNAs) are extensively studied in the progression of various types of cancer, while the mechanism of circKIAA1797 is rarely studied in gastric cancer (GC). Hence, this research aimed to investigate the expression of exosomal circKIAA1797 and its biological function in GC cells. Exosomes were extracted from the serum of GC patients and identified by transmission electron microscopy (TEM) and nanoparticle tracking analyzer (NTA). CD81, CD63, Bcl-2, Bax, and pre-leukemia transcription factor 3 (PBX3) protein levels were detected using western blot assay. circKIAA1797, microRNA-4429 (miR-4429), and PBX3 mRNA were determined by quantitative real-time PCR (RT-qPCR). Cell proliferation, migration, invasion, and apoptosis were assessed using colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, and flow cytometry assay. Glucose consumption and lactate production levels were examined using glycolysis detection kits. The interaction between miR-4429 and circKIAA1797 or PBX3 was identified using dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay. Xenograft mouse model assay was used to investigate the effect of exosomal circKIAA1797 in vivo. It was found that circKIAA1797 was up-regulated in GC tissues and cells, as well as in the exosomes derived from the serum of GC patients. Silencing of exosomal circKIAA1797 could hamper cell progression and glycolytic metabolism of GC. Mechanically, circKIAA1797 acted as a sponge of miR-4429 to regulate PBX3 expression. Moreover, the knockdown of exosomal circKIAA1797 repressed tumor growth in vivo. Our data demonstrated that knockdown of exosomal circKIAA1797 suppressed GC malignant phenotypes by regulating miR-4429/PBX3 axis, which might offer a promising therapeutic strategy for GC treatment.

The association of health insurance literacy and numeracy with financial toxicity and hardships among colorectal cancer survivors.

PURPOSE: In this study, we examined the association of financial hardship measured by material financial burden and financial toxicity with health insurance literacy and numeracy among colorectal cancer survivors. The lack of evidence on the impact of cost-related health literacy, specifically health insurance literacy and numeracy, on financial toxicity among cancer survivors warrants further research. METHODS: Between January and November 2019, we used a cross-sectional research design to collect surveys from 104 colorectal cancer survivors (diagnosed within last 5 years) from the Kentucky Cancer Registry. Survey items assessed health insurance literacy (measured by confidence and behaviors in choosing and using health insurance), numeracy, material financial burden, and financial toxicity, in addition to socio-demographic variables. Survey data were subsequently linked to the participant's cancer registry record. Data were analyzed using descriptive, bivariate, and multiple linear regression analyses. RESULTS: The mean financial toxicity score was 24.5, with scores ranging from 3 to 43 (higher scores indicating greater financial toxicity). Eighty percent of participants indicated they had experienced one or more material burdens related to their cancer. The majority had adequate health insurance (79%); however, the majority also had low numeracy (84%). After controlling for socio-demographic covariates, significant predictors of greater financial toxicity were high material burden scores, low health insurance literacy, and low numeracy. CONCLUSIONS: Findings indicate the need to develop programs and interventions aimed at improving health insurance literacy and numeracy as a strategy for reducing financial toxicity and hardships among colorectal cancer survivors.

A New Aortic Arch Inclusion Technique With Frozen Elephant Trunk for Type A Aortic Dissection.

OBJECTIVE: Our aims were to describe a new surgical technique for the treatment of type A aortic dissection (TAAD) and to report the operative outcomes of 154 patients. SUMMARY BACKGROUND DATA: Surgical treatment of TAAD is complicated and carries a high mortality risk. To lower this risk, we developed a simplified procedure in which a stent graft was implanted as frozen elephant trunk (FET), and the proximally trimmed vascular graft was sutured from the inside of the aortic arch using the inclusion technique under moderate hypothermic circulatory arrest and antegrade selective cerebral perfusion. METHODS: We conducted a retrospective analysis of 154 cases of TAAD treated with our novel technique (93 men and 61 women, 52.5 ±â€Š11.4 years). Computed tomography angiography was performed before discharge and at 6 months postoperatively. RESULTS: In-hospital mortality rate was 5.19%, with paraplegia occurring in 2 patients (1.3%) and stroke in 6 (3.9%). The rate of closure of the aortic arch false lumen was 77.8%, with a 69.2% rate of descending thoracic aorta thrombosis at discharge. The survival rate was 91.1% at a mean follow-up of 21 ±â€Š10 months, with rates of aortic arch false lumen closure of 92.4% and descending thoracic aorta thrombosis of 74.3% at 6 months postoperatively. CONCLUSIONS: The aortic arch inclusion technique with FET provides a safe alternative for TAAD treatment, with satisfactory operative results. Short-term follow-up results are encouraging, and long-term outcomes need further evaluation.

Disruption or reduced expression of the orotidine-5'-decarboxylase gene pyrG increases citric acid production: a new discovery during recyclable genome editing in Aspergillus niger.

BACKGROUND: Aspergillus niger is a filamentous fungus used for the majority of global citric acid production. Recent developments in genome editing now enable biotechnologists to engineer and optimize A. niger. Currently, however, genetic-leads for maximizing citric acid titers in industrial A. niger isolates is limited. RESULTS: In this study, we try to engineer two citric acid A. niger production isolates, WT-D and D353, to serve as platform strains for future high-throughput genome engineering. Consequently, we used genome editing to simultaneously disrupt genes encoding the orotidine-5'-decarboxylase (pyrG) and non-homologous end-joining component (kusA) to enable use of the pyrG selection/counter selection system, and to elevate homologous recombination rates, respectively. During routine screening of these pyrG mutant strains, we unexpectedly observed a 2.17-fold increase in citric acid production when compared to the progenitor controls, indicating that inhibition of uridine/pyrimidine synthesis may increase citric acid titers. In order to further test this hypothesis, the pyrG gene was placed under the control of a tetracycline titratable cassette, which confirmed that reduced expression of this gene elevated citric acid titers in both shake flask and bioreactor fermentation. Subsequently, we conducted intracellular metabolomics analysis, which demonstrated that pyrG disruption enhanced the glycolysis flux and significantly improved abundance of citrate and its precursors. CONCLUSIONS: In this study, we deliver two citric acid producing isolates which are amenable to high throughput genetic manipulation due to pyrG/kusA deletion. Strikingly, we demonstrate for the first time that A. niger pyrG is a promising genetic lead for generating citric acid hyper-producing strains. Our data support the hypothesis that uridine/pyrimidine biosynthetic pathway offer future avenues for strain engineering efforts.

Time-course effects of antioxidants and phase II enzymes on diesel exhaust particles-induced oxidative damage in the mouse lung.

Mechanisms responsible for diesel exhaust particle (DEP)-induced toxicity in respiratory disorders are poorly understood, recent experimental and controlled exposure studies suggested that oxidative stress might be involved. To investigate the time-course effects DEP on nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, mice were intratracheal instilled with 100 µg DEP/mouse and sacrificed after 30 min, 6 h, 12 h, 24 h, 48 h, and 72 h. We measured reactive oxygen species (ROS) as well as Nrf2 and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and phase II enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM) in the lungs. Additionally, histopathological changes were examined. At 6 h, ROS peaked, most of the enzymes were activated, and the histology showed the lungs were damaged. At 12 h, ROS returned to normal level and CAT activity decreased, while protein expression of Nrf2, HO-1, NQO1, GCLC, and GCLM increased, and the lungs were recovering from damage. After 24 h, ROS started to decrease and Nrf2 showed a decreasing trend at both gene and protein levels, while the lung damage had been entirely restored. These results suggested that a single exposure to DEP induce transient oxidative stress in the lungs, with time-dependent effects on Nrf2 and antioxidant enzymes and phase II enzymes.

Systems metabolic engineering for citric acid production by Aspergillus niger in the post-genomic era.

Citric acid is the world's largest consumed organic acid and is widely used in beverage, food and pharmaceutical industries. Aspergillus niger is the main industrial workhorse for citric acid production. Since the release of the genome sequence, extensive multi-omic data are being rapidly obtained, which greatly boost our understanding of the citric acid accumulation mechanism in A. niger to a molecular and system level. Most recently, the rapid development of CRISPR/Cas9 system facilitates highly efficient genome-scale genetic perturbation in A. niger. In this review, we summarize the impact of systems biology on the citric acid molecular regulatory mechanisms, the advances in metabolic engineering strategies for enhancing citric acid production and discuss the development and application of CRISPR/Cas9 systems for genome editing in A. niger. We believe that future systems metabolic engineering efforts will redesign and engineer A. niger as a highly optimized cell factory for industrial citric acid production.

GREACE-assisted adaptive laboratory evolution in endpoint fermentation broth enhances lysine production by Escherichia coli.

BACKGROUND: Late-stage fermentation broth contains high concentrations of target chemicals. Additionally, it contains various cellular metabolites which have leaked from lysed cells, which would exert multifactorial stress to industrial hyperproducers and perturb both cellular metabolism and product formation. Although adaptive laboratory evolution (ALE) has been wildly used to improve stress tolerance of microbial cell factories, single-factor stress condition (i.e. target product or sodium chloride at a high concentration) is currently provided. In order to enhance bacterial stress tolerance to actual industrial production conditions, ALE in late-stage fermentation broth is desired. Genome replication engineering assisted continuous evolution (GREACE) employs mutants of the proofreading element of DNA polymerase complex (DnaQ) to facilitate mutagenesis. Application of GREACE coupled-with selection under stress conditions is expected to accelerate the ALE process. RESULTS: In this study, GREACE was first modified by expressing a DnaQ mutant KR5-2 using an arabinose inducible promoter on a temperature-sensitive plasmid, which resulted in timed mutagenesis introduction. Using this method, tolerance of a lysine hyperproducer E. coli MU-1 was improved by enriching mutants in a lysine endpoint fermentation broth. Afterwards, the KR5-2 expressing plasmid was cured to stabilize acquired genotypes. By subsequent fermentation evaluation, a mutant RS3 with significantly improved lysine production capacity was selected. The final titer, yield and total amount of lysine produced by RS3 in a 5-L batch fermentation reached 155.0 ± 1.4 g/L, 0.59 ± 0.02 g lysine/g glucose, and 605.6 ± 23.5 g, with improvements of 14.8%, 9.3%, and 16.7%, respectively. Further metabolomics and genomics analyses, coupled with molecular biology studies revealed that mutations SpeBA302V, AtpBS165N and SecYM145V mainly contributed both to improved cell integrity under stress conditions and enhanced metabolic flux into lysine synthesis. CONCLUSIONS: Our present study indicates that improving a lysine hyperproducer by GREACE-assisted ALE in its stressful living environment is efficient and effective. Accordingly, this is a promising method for improving other valuable chemical hyperproducers.

MACBETH: Multiplex automated Corynebacterium glutamicum base editing method.

CRISPR/Cas9 or Cpf1-introduced double strand break dramatically decreases bacterial cell survival rate, which hampers multiplex genome editing in bacteria. In addition, the requirement of a foreign DNA template for each target locus is labor demanding and may encounter more GMO related regulatory hurdle in industrial applications. Herein, we developed a multiplex automated Corynebacterium glutamicum base editing method (MACBETH) using CRISPR/Cas9 and activation-induced cytidine deaminase (AID), without foreign DNA templates, achieving single-, double-, and triple-locus editing with efficiencies up to 100%, 87.2% and 23.3%, respectively. In addition, MACBETH was applied to generate a combinatorial gene inactivation library for improving glutamate production, and pyk&ldhA double inactivation strain was found to improve glutamate production by 3-fold. Finally, MACBETH was automated with an integrated robotic system, which would enable us to generate thousands of rationally engineered strains per month for metabolic engineering of C. glutamicum. As a proof of concept demonstration, the automation platform was used to construct an arrayed genome-scale gene inactivation library of 94 transcription factors with 100% success rate. Therefore, MACBETH would be a powerful tool for multiplex and automated bacterial genome editing in future studies and industrial applications.

Comprehensive optimization of the metabolomic methodology for metabolite profiling of Corynebacterium glutamicum.

Metabolomics has been a potential tool for strain improvement through analyzing metabolite changes in the context of different conditions. However, the availability of a universal metabolite profiling analysis is still a big challenge. In this study, we presented an optimized liquid chromatography-tandem mass spectrometry-based metabolomics methodology for Corynebacterium glutamicum, an important industrial workhorse. It was found that quenching the cellular metabolism with 5-fold volume of - 20 °C 40% methanol was highly recommended due to its lower cell damage rate and higher intracellular metabolite recovery rate. For extracting intracellular metabolites, ethanol/water (3:1, v/v) at 100 °C combined with acidic acetonitrile/water (1:1, v/v, with 0.1% formic acid) at - 20 °C achieved the unbiased metabolite profiling of C. glutamicum. The established methodology was then applied to investigate the intracellular metabolite differences between C. glutamicum ATCC 13032 and an mscCG-deleted mutant under biotin limitation condition. It was observed that in the presence of the functional L-glutamate exporter MscCG, biotin limitation led to accumulation of intracellular 2-oxoglutarate but not L-glutamate. Deletion of mscCG severely inhibited L-glutamate excretion and resulted in a dramatical increase of intracellular L-glutamate, which in turn affected the metabolite profile. The optimized metabolomics methodology holds promise for promoting studies on metabolic mechanism of C. glutamicum.

Increased plasma olfactomedin 2 after interventional therapy is a predictor for restenosis in lower extremity arteriosclerosis obliterans patients.

Animal studies have indicated that olfactomedin 2 (OLFM2) is involved in the process of vascular remolding. The aim of the present study was to investigate circulating OLFM2 levels in lower extremity arteriosclerosis obliterans (LEASO) patients and the association of OLFM2 with postoperative restenosis in patients. A total of 203 LEASO patients were enrolled in the present study. Plasma OLFM2 was measured before and 6 h after interventional therapy. After 6 months, patients were divided into a restenosis group and a non-restenosis group. Inter-group and intra-group differences in plasma OLFM2 were compared. The correlation between plasma OLFM2 and the severity of restenosis was analyzed by Spearman's correlation analysis. An receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of plasma OLFM2 on restenosis. Logistic regression was used to determine the risk factors for restenosis. Postoperative OLFM2 in the restenosis group was significantly higher compared with the non-restenosis group (34.07 ± 5.76 ng/mL vs. 19.53 ± 2.99 ng/mL). No significant difference in preoperative plasma OLFM2 levels was identified between the two groups (10.92 ± 2.49 ng/mL vs. 11.54 ± 3.18 ng/mL). Postoperative OLFM2 levels were positively correlated with the severity of restenosis (r = 0.728, p < .001). The area under the ROC curve was 0.902 (95% confidence interval (CI): 0.874-0.965), with a cutoff value of 26.91 ng/mL (95% CI: 26.16-28.32). Plasma OLFM2 was an independent risk factor for restenosis. Our results suggest that plasma OLFM2 is a potential biomarker for restenosis and may be a novel target for the treatment of restenosis.

Aorto-Cutaneous Fistula after Surgical Treatment of Stanford Type A Aortic Dissection.

An aorto-cutaneous fistula is a rare complication that occurs after aortic surgery. Due to its rarity, postoperative complications are not normally highlighted in most standard teaching. We report here a case of aorto-cutaneous fistula after surgical treatment of a Stanford type A aortic dissection (AD) in a 67-year-old Chinese male. The patient presented with severe right heart dysfunction and a mass was found in the upper-middle of his chest, which started bleeding in the next years. On admission, preoperative aortic computed tomography angiography (CTA) showed a huge hematoma located in the anterior superior mediastinum and a shunt between the embedding cavity of the aortic root and right atrium. An emergent procedure was performed. Intraoperatively, we found two leaks approximately 2 mm from the anastomosis of the greater curvature of the ascending aortic graft and stented graft after the hematoma was cleared and we confirmed the shunt had a large amount of blood flow after a right atrium incision. After the surgery, the patient was diagnosed with a cerebral hemorrhage, and his family decided to refuse therapy on the third postoperative day (p.o.d.).

A Vaginal Stillbirth after Aortic Surgery of Type B Aortic Dissection in a Pregnant Woman.

Acute aortic dissection occurring during pregnancy poses great danger to both the mother and fetus. Cesareans are usually performed before or after the aortic repair depending on the conditions of the mother and fetus. Here we report our experience in treating a 32-week pregnant woman with a type B aortic dissection, whose baby had died before admission. A cesarean section was initially arranged after emergency aortic repair. However, the patient started to deliver the fetus vaginally after the aortic surgery and the stillborn baby was delivered vaginally. This case report provides new insight into the method of delivery in a pregnant woman with an aortic dissection.

Characterization of Maternal and Fetal CYP3A-Mediated Progesterone Metabolism.

INTRODUCTION: Progesterone is critical for maintaining pregnancy and onset of labor. We evaluated CYP450-mediated progesterone meta-bolism, specifically the contribution of CYP3A isoforms. MATERIALS AND METHODS: In vitro progesterone metabolism was characterized in human liver microsomes (HLMs) with and without selective cytochrome P450 inhibitors and in recombinant CYP3A4, CYP3A5, and CYP3A7. 6ß-hydroxyprogesterone (6ß-OHP) and 16α-hydroxyprogesterone (16α-OHP) metabolites were quantified by HPLC/UV and fit to the Michaelis-Menten equation to determine Km and Vmax. The effect of CYP3A5 expression on progesterone clearance was determined by in vitro in vivo extrapolation. RESULTS: Ketoconazole inhibited formation of both 6ß-OHP and 16α-OHP more than 95%. 6ß-OHP and 16α-OHP were both produced by CYP3A4 (2.3 and 1.3 µL/min/pmol, respectively) to a greater extent than by CYP3A5 (0.09 and 0.003 µL/min/pmol) and CYP3A7 (0.004 and 0.003 µL/min/pmol). CONCLUSIONS: Maternal clearance of progesterone by hepatic CYP450's is driven primarily by CYP3A4, with limited contributions from CYP3A5 and CYP3A7.

Tet-on, or Tet-off, that is the question: Advanced conditional gene expression in Aspergillus.

In Aspergillus, controlled gene expression is often achieved using the reverse tetracycline-controlled transactivator (rtTA) dependent Tet-on system, whereby transcription is activated in a titratable manner by addition of the tetracycline derivative doxycycline. The complementary Tet-off system utilises the tetracycline-controlled transactivator (tTA) component to quantitatively reduce gene expression. In this study, we utilised a synthetic biological approach to engineer highly optimised Tet-off conditional expression systems in Aspergillus niger and Aspergillus fumigatus. Steps for delivery of these tools include utilising codon optimised cassette components, testing several promoters for improved genetic stability and validating two modified luciferase reporters for highly accurate measurements of gene expression. The Tet-off cassettes developed in this study enable facile and quantitative functional analysis, as validated by Tet-off analysis of genes involved in chitin synthesis and cell wall polarity in A. niger, and para-aminobenzoic acid synthesis in A. fumigatus. We also used a racA(G18V) dominant allele to demonstrate that Tet-off in A. niger enables gene over-expression and downregulation in a single isolate. Additionally, we used the improved luciferase reporters to show that the Tet-off cassette in A. niger enables quantification of gene oscillations. In order to demonstrate that synthetic biological approaches developed here are broadly applicable to engineering transcriptional circuits in filamentous fungi, we used our strategy for improving cassette stability by promoter replacement in the A. niger Tet-on system, which resulted in a modified Tet-on cassette with higher stability in recipient genomes.

Inhibitory effect of methyleugenol on IgE-mediated allergic inflammation in RBL-2H3 cells.

Allergic diseases, such as asthma and allergic rhinitis, are common. Therefore, the discovery of therapeutic drugs for these conditions is essential. Methyleugenol (ME) is a natural compound with antiallergic, antianaphylactic, antinociceptive, and anti-inflammatory effects. This study examined the antiallergic effect of ME on IgE-mediated inflammatory responses and its antiallergy mechanism in the mast cell line, RBL-2H3. We found that ME significantly inhibited the release of ß-hexosaminidase, tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 4, and was not cytotoxic at the tested concentrations (0-100 µM). Additionally, ME markedly reduced the production of the proinflammatory lipid mediators prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4). We further evaluated the effect of ME on the early stages of the FcεRI cascade. ME significantly inhibited Syk phosphorylation and expression but had no effect on Lyn. Furthermore, it suppressed ERK1/2, p38, and JNK phosphorylation, which is implicated in proinflammatory cytokine expression. ME also decreased cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO) phosphorylation and cyclooxygenase-2 (COX-2) expression. These results suggest that ME inhibits allergic response by suppressing the activation of Syk, ERK1/2, p38, JNK, cPLA2, and 5-LO. Furthermore, the strong inhibition of COX-2 expression may also contribute to the antiallergic action of ME. Our study provides further information about the biological functions of ME.

Boosting anaerobic digestion of long chain fatty acid with microbial electrolysis cell combining metal organic framework as cathode: Biofilm construction and metabolic pathways.

The role of metal organic framework (MOF) modified cathode in promoting long chain fatty acid (LCFA) methanation was identified in microbial electrolysis cell coupled anaerobic digestion (MEC-AD) system. The maximum methane production rate of MEC-AD-MOF achieved 49.8 ± 3.4 mL/d, which increased by 41 % compared to MEC-AD-C. The analysis of bio-cathode biofilm revealed that microbial activity, distribution, population, and protein secretion prompted by MOF cathode, which in turn led to an acceleration of electron transfer between the cathode and microbes. Specifically, the relative abundance of acetate-oxidizing bacterium (Mesotoga) in MEC-AD-MOF was 1.5-3.6 times higher than that in MEC-AD-C, with a co-metabolized enrichment of Methanobacterium. Moreover, MOF cathode reinforced LCFA methanation by raising the relative abundance of genes coded key enzymes involved in CO2-reducing pathway, and elevating the tolerance of microbes to LCFA inhibition. These results indicate that MOF can enhance biofilm construction in MEC-AD, thereby improving the treatment performance of lipid wastewater.

Pan-cancer integrated analysis of ANKRD1 expression, prognostic value, and potential implications in cancer.

There is substantial evidence demonstrating the crucial role of inflammation in oncogenesis. ANKRD1 has been identified as an anti-inflammatory factor and is related to tumor drug resistance. However, there have been no studies investigating the prognostic value and molecular function of ANKRD1 in pan-cancer. In this study, we utilized the TCGA, GTEx, GSCALite, ENCORI, CTRP, DAVID, AmiGO 2, and KEGG databases as well as R language, to explore and visualize the role of ANKRD1 in tumors. We employed the ROC curve to explore its diagnostic significance, while the Kaplan-Meier survival curve and Cox regression analysis were used to investigate its prognostic value. Additionally, we performed Pearson correlation analysis to evaluate the association between ANKRD1 expression and DNA methylation, immune cell infiltration, immune checkpoints, TMB, MSI, MMR, and GSVA. Our findings indicate that ANKRD1 expression is dysregulated in pan-cancer. The ROC curve revealed that ANKRD1 expression is highly sensitive and specific in diagnosing CHOL, LUAD, LUSC, PAAD, SKCM, and UCS (AUC > 85.0%, P < 0.001). Higher ANKRD1 expression was related to higher overall survival (OS) in LGG, but with lower OS in COAD and STAD (P < 0.001). Moreover, Cox regression and nomogram analyzes suggested that ANKRD1 is an independent factor for COAD, GBM, HNSC, and LUSC. Dysregulation of ANKRD1 expression in pan-cancer involves DNA methylation and microRNA regulation. Using the CTRP database, we discovered that ANKRD1 may influence the half-maximal inhibitory concentration (IC50) of several anti-tumor drugs. ANKRD1 expression showed significant correlations with immune cell infiltration (including cancer-associated fibroblast and M2 macrophages), immune checkpoints, TMB, MSI, and MMR. Furthermore, ANKRD1 is involved in various inflammatory and immune pathways in COAD, GBM, and LUSC, as well as cardiac functions in HNSC. In vitro experiments demonstrated that ANKRD1 promotes migration, and invasion activity, while inhibiting apoptosis in colorectal cancer cell lines (Caco2, SW480). In summary, ANKRD1 represents a potential prognostic biomarker and therapeutic target in human cancers, particularly in COAD.

Recovery capability of anaerobic digestion from ammonia stress: Metabolic activity, energy generation, and genome-centric metagenomics.

Excessive ammonia stresses anaerobic digestion (AD) significantly. Although there has been progress in understanding AD under ammonia exposure, investigations on AD liberated from ammonia exposure are limited. Here, the recovery capability of AD from ammonia stress was evaluated, by examining specific methanogenic activity, energy-conserving capability, microbial community succession, and metabolic pathway reconstruction. The findings demonstrated that ammonia stress relief resulted in < 50% methane recovery, with propionate conversion identified as the critical impediment to AD reactivation. Energy generation could not recovered either. Efforts to mitigate ammonia stress failed to restore acetoclastic methanogens, e.g., Methanothrix soehngenii, and proved futile in awakening propionate oxidizers, e.g., Desulfobulbus. Interestingly, a symbiotic metabolism emerged, prevailing in stress-relieved AD due to its energy-conserving advantage. This study underscores the importance of targeted interventions, including stimulating acetoclastic methanogenesis, propionate oxidation, and energy generation, as priorities for AD recovery following ammonia stress, rather than focusing solely on ammonia level management.

Preparation and Properties of GO/ZnO/nHAp Composite Microsphere Bone Regeneration Material.

The purpose of this study is to explore the possibility of using graphene-zinc oxide-hydroxyapatite (GO/ZnO/nHAp) composite microspheres as bone regeneration materials by making use of the complementary advantages of nanocomposites, so as to provide reference for the clinical application of preventing and solving bacterial infection after implantation of synthetic materials. Firstly, GO/ZnO composites and hydroxyapatite nanoparticles were synthesized using the hydrothermal method, and then GO/ZnO/nHAp composite microspheres were prepared via high-temperature sintering. The graphene-zinc oxide-calcium phosphate composite microspheres were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), energy dispersion spectroscopy (EDS), water contact angle measurement, degradation and pH determination, and differential thermal analysis (DiamondTG/DTA). The biocompatibility, osteogenic activity, and antibacterial activity of GO/ZnO/nHAp composite microspheres were further studied. The results of the cell experiment and antibacterial experiment showed that 0.5% and 1% GO-ZnO-nHAp composite microspheres not only had good biocompatibility and osteogenic ability but also inhibited Escherichia coli and Staphylococcus aureus by more than 45% and 70%. Therefore, GO/ZnO/nHAp composite microspheres have good physical and chemical properties and show good osteogenic induction and antibacterial activity, and this material has the possibility of being used as a bone regeneration material.