Cyanidin-3-O-glucoside alleviates ethanol-induced liver injury by promoting mitophagy in a Gao-binge mouse model of alcohol-associated liver disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of liver disease-related deaths worldwide. Unfortunately, approved medications for the treatment of this condition are quite limited. One promising candidate is the anthocyanin, Cyanidin-3-O-glucoside (C3G), which has been reported to protect mice against hepatic lipid accumulation, as well as fibrosis in different animal models. However, the specific effects and mechanisms of C3G on ALD remain to be investigated. EXPERIMENTAL APPROACH: In this report, a Gao-binge mouse model of ALD was used to investigate the effects of C3G on ethanol-induced liver injury. The mechanisms of these C3G effects were assessed using AML12 hepatocytes. RESULTS: C3G administration ameliorated ethanol-induced liver injury by suppressing hepatic oxidative stress, as well as through reducing hepatic lipid accumulation and inflammation. Mechanistically, C3G activated the AMPK pathway and enhanced mitophagy to eliminate damaged mitochondria, thus reducing mitochondria-derived reactive oxidative species in ethanol-challenged hepatocytes. CONCLUSIONS: The results of this study indicate that mitophagy plays a potentially important role underlying the hepatoprotective action of C3G, as demonstrated in a Gao-binge mouse model of ALD. Accordingly, C3G may serve as a promising, new therapeutic drug candidate for use in ALD.

LAMP-visualized photofuel cell self-powered dual-mode sensing platform for detection of transmissible gastroenteritis virus.

The detection of transmissible gastroenteritis virus (TGEV) is of great significance to reduce the loss of pig industry. A LAMP-visualization/PFC self-powered dual-mode output sensor platform was constructed to detect TGEV by combining a simple and intuitive photoelectrochromic material with a highly sensitive PFC self-powered sensing platform without external power supply. The PFC sensing substrate was constructed using CdS nanoparticles modified ZnO NRs (CdS/ZnO NRs) as the photoanode, which exhibited high photoactivity, and Prussian blue (PB) as the cathode. After LAMP reaction on the optical anode, visual signals caused by PB discolorimetry can be detected semi-quantitatively, or PFC power density electrical signals collected by electrochemical workstation can be used. The output power density value is logarithm of TGEV concentration. The linear relationship was good within the detection range of 0.075 fg/µL-7.5 ng/µL, with a detection limit of 0.025 fg/µL (S/N = 3). This multi-signal output sensing platform provides more choices for quantifying TGEV detection results, and the two methods can be mutually verified, which meets the needs of different scenarios and improves the reliability of detection. It has a good effect in the actual sample detection, without the use of expensive and complex instruments, and has a broad application prospect.

Mycobacterium tuberculosis inhibits METTL14-mediated m6A methylation of Nox2 mRNA and suppresses anti-TB immunity.

Internal N6-methyladenosine (m6A) modifications are among the most abundant modifications of messenger RNA, playing a critical role in diverse biological and pathological processes. However, the functional role and regulatory mechanism of m6A modifications in the immune response to Mycobacterium tuberculosis infection remains unknown. Here, we report that methyltransferase-like 14 (METTL14)-dependent m6A methylation of NAPDH oxidase 2 (Nox2) mRNA was crucial for the host immune defense against M. tuberculosis infection and that M. tuberculosis-secreted antigen EsxB (Rv3874) inhibited METTL14-dependent m6A methylation of Nox2 mRNA. Mechanistically, EsxB interacted with p38 MAP kinase and disrupted the association of TAB1 with p38, thus inhibiting the TAB1-mediated autophosphorylation of p38. Interaction of EsxB with p38 also impeded the binding of p38 with METTL14, thereby inhibiting the p38-mediated phosphorylation of METTL14 at Thr72. Inhibition of p38 by EsxB restrained liquid-liquid phase separation (LLPS) of METTL14 and its subsequent interaction with METTL3, preventing the m6A modification of Nox2 mRNA and its association with the m6A-binding protein IGF2BP1 to destabilize Nox2 mRNA, reduce ROS levels, and increase intracellular survival of M. tuberculosis. Moreover, deletion or mutation of the phosphorylation site on METTL14 impaired the inhibition of ROS level by EsxB and increased bacterial burden or histological damage in the lungs during infection in mice. These findings identify a previously unknown mechanism that M. tuberculosis employs to suppress host immunity, providing insights that may empower the development of effective immunomodulators that target M. tuberculosis.

A signal "switch-on" photoelectrochemical sensor based on a 3D-FM/BiOI heterostructure for the sensitive detection of l-ascorbic acid.

A highly efficient 3D flower MoS2 (3D-FM)-based heterostructure photocatalyst (3D-FM/BiOI) was successfully obtained via a simple hydrothermal synthesis strategy. 3D-FM/BiOI showed prominent photoelectrochemical performance, distinguished stability and good selectivity. The introduction of 3D-FM, by promoting the photoelectric property attributed to it, facilitated the separation of photogenerated electron-hole pairs. Since the redox process of l-ascorbic acid (l-AA) resulted in an increasing photocurrent of 3D-FM/BiOI, a signal "switch-on" photoelectrochemical sensor (PECS) was designed to sensitively determine l-AA for the first time. Under optimized conditions, the 3D-FM/BiOI PECS worked over a wide range from 1 µM to 0.8 mM with a low detection limit of 0.05 µM (S/N = 3). The PECS was successfully exploited for l-AA sensing in human urine with excellent accuracy and applicability, demonstrating its practical precision and superb serviceability. Furthermore, the 3D-FM/BiOI PECS exhibited satisfactory selectivity and stability, providing a great potential platform for the construction of an l-AA sensor in various practical samples and complicated environments.

Photochromic visual sensing chip for isothermal amplification detection of porcine transmissible gastroenteritis virus.

The outbreak of transmissible gastroenteritis virus (TGEV) will cause huge economic losses to the whole pig industry. Hence, there is urgent need to develop a rapid and ultrasensitive method for detection of TGEV. As a nucleic acid detection technique, loop-mediated isothermal amplification (LAMP) can achieve quantitative detection of targeted nucleic acids with high sensitivity and selectivity. Nevertheless, the signal outputs of LAMP method must be acquired by complicated instruments. In this work, we firstly developed a LAMP photochromic sensing chip for porcine TGEV detection by combination of the photochromic sensing chip and nucleic acid amplification. The detection signal was based on color change of electrochromic material rather than electrical signal, and thus the detection signal can be obtained by visualization without relying on complicated instrument. The entire test was performed with small fluorinated indium tin oxide electrodes modified with zinc oxide (ZnO) (a photocatalytic material) and Prussian blue (PB) (an electrochromic material). When photoinduced electrons produced by ZnO were injected into PB under light, the PB was reduced to Prussian white. The higher the concentration of TGEV, the more double-stranded DNA was produced after amplification. The amplified product produced greater impedance, and fewer electron was transferred, which affect the corresponding color change of PB. The sensing chip also showed highly sensitive response to TGEV, with the minimum limit of detection was determined to be 2.5 fg/µL. The sensing chip developed herein will provide a new avenue for DNA amplification detection by visualization.

Bacteria-based biochar as a persulfate activator to degrade organic pollutants.

Carbon-based catalysts for activating persulfate to drive advanced oxidation processes (AOPs) are widely used in wastewater treatment. In this study, Shewanella oneidensis MR-1, a typical ferric reducing electroactive microorganism, was utilized as the raw material of biochar (BC) to prepare a novel green catalyst (MBC). The effect of MBC on activating persulfate (PS) to degrade rhodamine B (RhB) was evaluated. Experimental results showed that MBC could effectively activate PS to degrade RhB to reach 91.70% within 270 min, which was 47.4% higher than that of pure strain MR-1. The increasing dosage of PS and MBC could improve the removal of RhB. Meanwhile, MBC/PS can well perform in a wide pH range, and MBC showed good stability, achieving 72.07% removal of RhB with MBC/PS after 5 cycles. Furthermore, the free radical quenching test and EPR experiments confirmed the presence of both free radical and non-free radical mechanisms in the MBC/PS system, with •OH, SO4•- and 1O2 contributing to the effective degradation of RhB. This study successfully provided a new application for bacteria to be used in the biochar field.

Accurate and ultrasensitive detection for PEDV based on photoelectrochemical sensing coupling loop-mediated isothermal amplification.

Porcine epidemic diarrhea (PED) is a serious disease requiring a simple and accurate detection method. Accordingly, this study developed a novel, ultrasensitive photoelectrochemical (PEC) sensing platform using the loop-mediated isothermal amplification (LAMP) technique (LAMP-PEC). An amino (-NH2)-modified LAMP product is obtained by amplification of the PED virus gene with specially designed primers. The generated NH2-modified LAMP product is assembled on the surface of an electrode by forming imine linkages between aldehyde and amino groups based on the Schiff base reaction. A stable photocurrent is provided by a CdIn2S4 photoactive material, which possesses high photoelectric conversion efficiency. Amplified DNA assembled on the electrode surface increases steric hindrance and hinders electrons from moving from the electrode to electron acceptors, which decreases the photocurrent. This strategy can detect PEDV with a low detection limit of 0.3 fg µL-1 and a wide linear range of 1 × 10-3-1 × 102 pg/µL. The sensing platform has excellent specificity and sensitivity and can be used for the quantitative detection of many other pathogens with the assistance of LAMP.

Significance of Triple Detection of p16/ki-67 Dual-Staining, Liquid-Based Cytology and HR HPV Testing in Screening of Cervical Cancer: A Retrospective Study.

In addition to liquid-based cytology (LBC) and HR HPV testing, p16/ki-67 dual-staining is another method for cervical cancer screening. The combination of any two methods can improve the accuracy of screening, but some cervical lesions are still missed or misdiagnosed. In this retrospective study, the significance of LBC, HR HPV testing and especially p16/ki-67 dual-staining in cervical lesion screening was evaluated with reference to histological diagnosis. At the same time, we tried to explore the value of p16/ki-67 dual-staining combined with LBC and HR HPV testing (triple detection) in improving the diagnostic specificity of CIN2+ and reducing the missed diagnosis of CIN2+ lesions. We found that p16/ki-67 dual-staining was valuable in identifying cervical CIN2+ lesions and reducing the missed diagnosis of CIN2+ in HPV negative patients. More than 96% of CIN2+ patients were positive for two or three tests of triple detection. Whole positive triple detection can effectively predict high grade cervical lesions. In conclusion, the triple detection can distinguish almost all cervical CIN2+ lesions. Our data put forward and highlight the feasibility and significance of triple detection in cervical lesion screening.

Enhanced cathodic electrochemiluminescent microcystin-LR aptasensor based on surface plasmon resonance of Bi nanoparticles.

Sensitive testing for Microcystins-LR (MC-LR) is needed because of its serious environmental and human health hazards. In this work, a new type of surface plasmon resonance (SPR) enhanced cathodic electrochemiluminescence (ECL) aptasensing platform was designed in which boron and nitrogen co-doped graphene quantum dots (BN-GQDs) were used as the luminary and bismuth nanoparticles (Bi NPs) were used as the SPR source. SPR effect of non-precious metal Bi NPs can induce and enhance ECL signal of BN-GQDs because the fluorescence spectrum of BN-GQDs overlaps well with the ultraviolet-visible absorption spectrum of Bi NPs. On this basis, a sensitive sensing system based on the Bi NPs and BN-GQDs was established for MC-LR detection. The results showed that the ECL sensing signal obtained was linear with the negative logarithm of the target MC-LR concentration in the range of 0.01-5000 pM, and the detection limit was 0.003 pM. In addition, the sensor had high stability and good reproducibility, which can be applied to the detection of MC-LR in actual samples. The method had good specificity and can not be disturbed by its homolog, which can be used for sensitive and reliable detection of complex samples.

Observation and rationalization of nitrogen oxidation enabled only by coupled plasma and catalyst.

Heterogeneous catalysts coupled with non-thermal plasmas (NTP) are known to achieve reaction yields that exceed the contributions of the individual components. Rationalization of the enhancing potential of catalysts, however, remains challenging because the background contributions from NTP or catalysts are often non-negligible. Here, we first demonstrate platinum (Pt)-catalyzed nitrogen (N2) oxidation in a radio frequency plasma afterglow at conditions at which neither catalyst nor plasma alone produces significant concentrations of nitric oxide (NO). We then develop reactor models based on reduced NTP- and surface-microkinetic mechanisms to identify the features of each that lead to the synergy between NTP and Pt. At experimental conditions, NTP and thermal catalytic NO production are suppressed by radical reactions and high N2 dissociation barrier, respectively. Pt catalyzes NTP-generated radicals and vibrationally excited molecules to produce NO. The model construction further illustrates that the optimization of productivity and energy efficiency involves tuning of plasma species, catalysts properties, and the reactor configurations to couple plasma and catalysts. These results provide unambiguous evidence of synergism between plasma and catalyst, the origins of that synergy for N2 oxidation, and a modeling approach to guide material selection and system optimization.

Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions.

Background: Most tumors have an enhanced glycolysis flux, even when oxygen is available, called the aerobic glycolysis or the Warburg effect. Metabolic reprogramming promotes cancer progression, and is even related to the tumorigenesis. However, it is not clear whether the observed metabolic changes act as a driver or a bystander in cancer development. Methods: In this study, the metabolic characteristics of oral precancerous cells and cervical precancerous lesions were analyzed by metabolomics, and the expression of glycolytic enzymes in cervical precancerous lesions was evaluated by RT-PCR and Western blot analysis. Results: In total, 115 and 23 metabolites with reliable signals were identified in oral cells and cervical tissues, respectively. Based on the metabolome, oral precancerous cell DOK could be clearly separated from normal human oral epithelial cells (HOEC) and oral cancer cells. Four critical differential metabolites (pyruvate, glutamine, methionine and lysine) were identified between DOK and HOEC. Metabolic profiles could clearly distinguish cervical precancerous lesions from normal cervical epithelium and cervical cancer. Compared with normal cervical epithelium, the glucose consumption and lactate production increased in cervical precancerous lesions. The expression of glycolytic enzymes LDHA, HK II and PKM2 showed an increased tendency in cervical precancerous lesions compared with normal cervical epithelium. Conclusions: Our findings suggest that cell metabolism may be reprogrammed at the early stage of tumorigenesis, implying the contribution of metabolic reprogramming to the development of tumor.

HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer.

Cervical cancer is the fourth most common malignant tumor in women worldwide. The persistent infection of high-risk Human Papillomavirus (hrHPV) is considered to be the primary cause of this disease. As an innate immune receptor, the nucleotide-binding oligomerization domain protein-1 (NOD1) recognizes the pathogen-associated molecular pattern (PAMP), subsequently initiating immune responses. NOD1 is also involved in the apoptotic signaling pathway and mutates in many cancer cells. In the study, we revealed that NOD1 expression decreased during the progression of cervical intraepithelial neoplasia to cervical cancer and that HPV16 E6/E7 oncoproteins induced down-regulation of NOD1. Moreover, the activation of NOD1 promoted the apoptosis of HPV16-positive cervical cancer cells. The data indicated that the dysregulation of NOD1-mediated inflammation and apoptosis may contribute to cervical intraepithelial neoplasia progression and cervical cancer.

Upregulated circ_0005576 facilitates cervical cancer progression via the miR-153/KIF20A axis.

Circular RNAs (circRNAs) are a novel group of noncoding RNAs characterized by a covalently closed loop. An increasing evidence suggests that deregulated circRNAs exert their essential regulatory roles in oncogenesis. However, little is explored on the biological role of novel circRNAs in cervical cancer (CC) progression. In the present study, we analyzed two GSE microarrays to screen for CC-specific circRNAs and found two circRNAs both expressed in CC cells and tissues. Among them, circ_0005576 was significantly overexpressed in both CC tissues and cell lines. Furthermore, upregulated circ_0005576 was positively associated with advanced FIGO stage, lymph node metastasis, but was negatively related with overall survival of CC patients. Additionally, circ_0005576 knockdown induced a suppressed cell growth, colony formation and metastasis of HeLa and SiHa cells. Mechanistically, circ 0005576 was mainly located in the cytoplasm and served as a sponge of miR-153-3p to increase kinesin family member 20A (KIF20A) expression. Rescue assays further validated the effects of circ_0005576/miR-153-3p/KIF20A axis on CC proliferation, migration and invasion. In conclusion, our research reveals a novel circ_0005576/miR-153-3p/KIF20A axis promoting CC progression, which may suggest a new insight into the pathogenesis of CC.

Water-Mediated Reduction of Aqueous N-Nitrosodimethylamine with Pd.

Pd-catalyzed reduction has emerged as a promising treatment strategy to remove the recalcitrant disinfection byproduct N-nitrosodimethylamine (NDMA). However, the reaction pathways remain unexplored, and questions remain about how water solvent influences NDMA reduction mechanisms and selectivity. Here, we compute the energies and barriers of all relevant elementary steps in NDMA reduction by H2 on Pd(111) using density functional theory. We further calculate water-assisted H-shuttling for all hydrogenation reactions explicitly and include water solvation for all elementary reactions implicitly. We parametrize microkinetic models to predict product formation rates and selectivities over a wide range of NDMA concentrations. We show that H2O-mediated H-shuttling lowers the reaction barriers for all hydrogenation reactions involved in NDMA reduction while implicit solvation has negligible impact on the reaction and activation energies. We further conduct batch experiments with SiO2-supported Pd nanoparticles and compare them with the microkinetic models. The predicted rates, selectivity, and apparent activation energy from the model parametrized with both explicit H2O-mediated H-shuttling and implicit solvation correspond well with experimental observations. Models that ignore water as an H-shuttle or solvent fail to recover the experimental rates and apparent activation energy. We identified the rate-determining steps of the reaction and show the reaction flow pathways of the complicated reaction network. Finally, we demonstrate that water-mediated H-shuttling changes the rate-determining steps and reaction flows of elementary reactions.

Upregulation of lncRNA ADAMTS9-AS2 Promotes Salivary Adenoid Cystic Carcinoma Metastasis via PI3K/Akt and MEK/Erk Signaling.

Neurotropic infiltrative growth and distant metastasis are the main causes of death in salivary adenoid cystic carcinoma (SACC) patients. Long noncoding RNAs (lncRNAs) are involved in many human neoplasms, however, their potential roles in SACC are unclear. In our study, we found that ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2) was significantly upregulated in SACC patients with metastasis and SACC-lung metastasis (LM) cells. Moreover, ADAMTS9-AS2 expression was closely associated with the prognosis and distant metastasis in SACC patients. Next, we found that c-myc could specifically bind to the promoter of ADAMTS9-AS2 and activated its transcription. Knockdown of ADAMTS9-AS2 significantly inhibited migration and invasion of SACC cells in vitro and distant lung metastasis in vivo. Furthermore, ADAMTS9-AS2, which mainly expressed in the cytoplasm, shared microRNA (miRNA) response elements with Integrin α6 (ITGA6). Overexpression of ADAMTS9-AS2 competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated degradation, and thus it activated the activity of PI3K/Akt and MEK/Erk signaling and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and invasion in SACC by competing with miR-143-3p. This sheds a new insight into the regulation mechanism of ADAMTS9-AS2, and it provides a possible application for the SACC treatment.

LncRNA KCNQ1OT1 regulates proliferation and cisplatin resistance in tongue cancer via miR-211-5p mediated Ezrin/Fak/Src signaling.

Numerous findings have demonstrated that long noncoding RNA (lncRNA) dysregulation plays a key role in many human neoplasms, including tongue squamous cell carcinoma (TSCC), yet the potential mechanisms of lncRNAs in chemo-resistance remain elusive. Our research showed that the lncRNA KCNQ1OT1 was upregulated in chemo-insensitive TSCC tissues compared with chemo-sensitive TSCC specimens. Meanwhile, high KCNQ1OT1 expression was closely correlated with poor prognosis. Furthermore, KCNQ1OT1 promoted TSCC proliferation and conferred TSCC resistance to cisplatin-induced apoptosis in vitro and in vivo. Using online database analysis, we predicted that the lncRNA KCNQ1OT1 facilitates tumor growth and chemo-resistance by acting as a competing endogenous RNA (ceRNA) to modulate the expression of miR-211-5p. And miR-211-5p upregulation significantly impaired TSCC proliferation and resumed TSCC chemo-sensitivity, which is contrary to the function of lncRNA KCNQ1OT1. Luciferase experiments confirmed that miR-211-5p harbor binding sites for the 3'-UTRof Ezrin mRNA, and Ezrin/Fak/Src signaling was activated in cisplatin-resistant TSCC cells. Finally, miR-211-5p inhibition in sh-KCNQ1OT1-expressing TSCC cells rescued the suppressed cell proliferation and cisplatin resistance induced by KCNQ1OT1 knockdown. In summary, our study has elucidated the role of the oncogenic lncRNA KCNQ1OT1 in TSCC growth and chemo-resistance, which may serve as a new target for TSCC therapy.

One-step thermal synthesis of nickel nanoparticles modified graphene sheets for enzymeless glucose detection.

The development of accurate, reliable and low cost devices for glucose detection is one of the most important scientific and technological hotspots. In this study, we proposed a unique one-step thermal synthesis strategy to synthesize nickel (Ni) nanoparticles modified graphene (GE) sheets by using metal-oleate complex as the precursor and sodium sulfate as a template. With the assistance of sodium sulfate particles, Ni nanoparticles with particle size of about 99.2nm were homogenously anchored on graphene nanosheets in the product. The electrochemical behavior of the nanocomposite towards enzyme-free glucose oxidation was investigated systematically by cyclic voltammetry and amperometric measurements. The results reveal that the GE/Ni nanocomposite exhibited excellent electrocatalytic response to glucose with a wide linear range of 0.01-2.5mM, a low detection limit of 0.79µM, and a high sensitivity of 388.4µA mM-1cm-2. In addition, no significant interference was observed from potential interference species. The simple, efficient and scalable synthesis and the excellent catalytic performance endow the GE/Ni nanocomposite great potential application in enzymeless glucose detection.

The combined application of urinary liquid-based cytology with fluorescence in situ hybridization and p16/Ki-67 dual immunostaining is valuable for improving the early diagnosis of upper tract urothelial carcinomas.

OBJECTIVES: To evaluate the diagnostic values of urine liquid-based cytology (LBC), fluorescence in situ hybridization (FISH), and p16/Ki-67 dual immunostaining in the detection of upper tract urothelial carcinomas (UTUCs). METHODS: Sixty-one patients with UTUCs were retrospectively analyzed. All patients were diagnosed both by urine cytology and by FISH, and histologically confirmed as UTUCs. Thirty-two patients had been stained with p16/Ki-67 dual labeling. RESULTS: The sensitivities for low-grade UTUCs (LGUTUCs) and high-grade UTUCs (HGUTUCs) were 33.3% and 67.4% by LBC, 60% and 69.6% by FISH, and 12.5% and 66.7% by p16/Ki-67 dual labeling, respectively. CONCLUSIONS: Our results indicated that LBC was more suitable to identify HGUTUCs, FISH was highly valuable for predicting LGUTUCs, and p16/Ki-67 dual labeling was useful for distinguishing HGUTUCs from LGUTUCs. The combined application of these methods may improve the sensitivity or accuracy in the detection or diagnosis of UTUCs.

Facile synthesis and enhanced catalytic performance of reduced graphene oxide decorated with hexagonal structure Ni nanoparticles.

In this study, reduced graphene oxide (RGO) supported Ni nanoparticles were synthesized by a facile in-situ refluxing approach using triethylene glycol as both reductive and dispersing agent. The as-synthesized RGO/Ni nanocomposites were characterized by X-ray diffraction, Raman spectroscopy and transmission electron microscopy, which revealed that Ni nanoparticles with hexagonal close-packed structure were homogeneously dispersed on the surface of RGO sheets. The catalytic activity and electrochemical properties of the RGO/Ni nanocomposites were investigated. It is found that the RGO/Ni nanocomposites exhibit markedly enhanced catalytic activity toward the reduction of p-nitrophenol by NaBH4, which is comparable to noble metal catalyst. The RGO/Ni nanocomposites also exhibited excellent electrocatalytic response to glucose. The linear range, detection limit and sensitivity were estimated to be 0.01-3.0mM (R2=0.997), 2.8µM and 535.258µAmM-1cm-2, respectively. It is expected that this facile method presented here could be extended to synthesize other RGO/metal nanocomposites with various functions.