Epstein-barr virus-encoded microRNA-BART18-3p promotes colorectal cancer progression by targeting de novo lipogenesis

The Epstein-Barr virus (EBV) genome encodes a cluster of 22 viral microRNAs, called miR-BamHI-A rightward transcripts (miR-BARTs), which are shown to promote the development of cancer. Here, this study reports that EBV-miR-BART18-3p is highly expressed in colorectal cancer (CRC) and is closely associated with the pathological and advanced clinical stages of CRC. Ectopic expression of EBV-miR-BART18-3p leads to increased migration and invasion capacities of CRC cells in vitro and causes tumor metastasis in vivo. Mechanistically, EBV-miR-BART18-3p activates the hypoxia inducible factor 1 subunit alpha/lactate dehydrogenase A axis by targeting Sirtuin, which promotes lactate accumulation and acetyl-CoA production in CRC cells under hypoxic condition. Increased acetyl-CoA utilization subsequently leads to histone acetylation of fatty acid synthase and fatty acid synthase-dependent fat synthesis, which in turn drives de novo lipogenesis. The oncogenic role of EBV-miR-BART18-3p is confirmed in the patient-derived tumor xenograft mouse model. Altogether, the findings define a novel mechanism of EBV-miR-BART18-3p in CRC development through the lipogenesis pathway and provide a potential clinical intervention target for CRC

UFO2: A unified pre-training framework for online and offline speech recognition

In this paper, we propose a Unified pre-training Framework for Online and Offline (UFO2) Automatic Speech Recognition (ASR), which 1) simplifies the two separate training workflows for online and offline modes into one process, and 2) improves the Word Error Rate (WER) performance with limited utterance annotating. Specifically, we extend the conventional offline-mode Self-Supervised Learning (SSL)-based ASR approach to a unified manner, where the model training is conditioned on both the full-context and dynamic-chunked inputs. To enhance the pre-trained representation model, stop-gradient operation is applied to decouple the online-mode objectives to the quantizer. Moreover, in both the pre-training and the downstream fine-tuning stages, joint losses are proposed to train the unified model with full-weight sharing for the two modes. Experimental results on the LibriSpeech dataset show that UFO2 outperforms the SSL-based baseline method by 29.7% and 18.2% relative WER reduction in offline and online modes, respectively.Comment: Accepted by ICASSP 202

NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats

The reactive oxygen species- (ROS-) induced nod-like receptor protein-3 (NLRP3) inflammasome triggers sterile inflammatory responses and pyroptosis, which is a proinflammatory form of programmed cell death initiated by the activation of inflammatory caspases. NLRP3 inflammasome activation plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Our present study investigated whether diabetes aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. Type 1 diabetic rat model was established by intraperitoneal injection of streptozotocin (60 mg/kg). MI/R was induced by ligating the left anterior descending artery (LAD) for 30 minutes followed by 2 h reperfusion. H9C2 cardiomyocytes were exposed to high glucose (HG, 30 mM) conditions and hypoxia/reoxygenation (H/R) stimulation. The myocardial infarct size, CK-MB, and LDH release in the diabetic rats subjected to MI/R were significantly higher than those in the nondiabetic rats, accompanied with increased NLRP3 inflammasome activation and increased pyroptosis. Inhibition of inflammasome activation with BAY11-7082 significantly decreased the MI/R injury. In vitro studies showed similar effects, as BAY11-7082 or the ROS scavenger N-acetylcysteine, attenuated HG and H/R-induced H9C2 cell injury. In conclusion, hyperglycaemia-induced NLRP3 inflammasome activation may be a ROS-dependent process in pyroptotic cell death, and NLRP3 inflammasome-induced pyroptosis aggravates MI/R injury in diabetic rats

A new fluorescent chemosensor for highly selective and sensitive detection of inorganic phosphate (Pi) in aqueous solution and living cells

In this work, a new fluorescence chemosensor, FP-Fe3+ was developed for the detection of Pi in aqueous solution and living cells. The unique ligand, FP displayed a high affinity to Fe3+ (Ka = 1.40 × 106 M-1) in the presence of other competing cations, accompanied with a dramatic fluorescence quenching. The specific interaction of Pi and FP-Fe3+ ensemble led to the liberation of fluorophore, FP, and thus the fluorescence was recovered. The dose-dependent fluorescence enhancement of FP-Fe3+ showed a good linearity with a detection limit of 300 nM for Pi. The extraordinary performance of the present chemosensor, including high sensitivity, selectivity, and good biocompatibility enable the investigation of fluorescent response for Pi in living cells by confocal microscope. Quantitative monitoring of intracellular Pi was achieved by the flow cytometry analysis

Visualization of fluoride ions in vivo using a gadolinium(III)-coumarin complex-based fluorescence/MRI dual-modal probe

A new Gadolinium(III)-coumarin complex, DO3A-Gd-CA, was designed and prepared as a dual-modal probe for simultaneous fluorescence and relaxivity responses to fluoride ions (F-) in aqueous media and mice. DO3A-Gd-CA was designed by using Gd(III) center as an MRI signal output unit and fluoride binding site, and the 4-(diethylamino)-coumarin-3-carboxylic acid (CA) as a fluorescence reporter. Upon the addition of fluoride ions to the solution of DO3A-Gd-CA, the liberation of the coordinated CA ligand led to a 5.7-fold fluorescence enhancement and a 75% increase in the longitudinal relaxivity (r₁). The fluorescent detection limit for fluoride ions was determined to be 8 μM based on a 3σ/slope. The desirable features of the proposed DO3A-Gd-CA, such as high sensitivity and specificity, reliability at physiological pH and low cytotoxicity enable its application in visualization of fluoride ion in mice. The successful in vivo imaging indicates that DO3A-Gd-CA could be potentially used in biomedical diagnosis fields

Magnetic metal organic frameworks (MOFs) composite for removal of lead and malachite green in wastewater

We designed and synthesized a magnetic metal organic frameworks (MOFs) composite, Cu-MOFs/FeO as the adsorbent for removal of lead (Pb(II)) and malachite green (MG) in wastewater. This Cu-MOFs/FeO can be easily prepared by in-situ growth of Cu-MOFs with doping FeO nanoparticles. The prepared Cu-MOFs/FeO composite was well characterized by SEM, XRD, and FTIR spectra. The adsorption experiments found that Cu-MOFs/FeO can serve as adsorbent for removal of Pb(II) and MG simultaneously. The adsorption capacities were found to be 113.67 mg/g for MG and 219.00 mg/g for Pb, respectively, which are significantly higher than reported materials. Adsorption isotherm, kinetics and recyclability of Cu-MOFs/FeO for removal of Pb(II) and MG were then studied. Adsorption of Pb(II) and MG exhibited Freundlich adsorption isotherm model, with the adsorption kinetics of available second-order kinetic. Physical adsorption for MG and chemical adsorption for Pb(II) were confirmed by Dubinin-Radushkevich (D-R) isothermal adsorption model. The adsorption of Pb(II) and MG in real water samples were then studied. The FeO/Cu-MOFs was found to be recyclable for removal of Pb(II) and MG, can be explored as the potential adsorbent for waste water treatment

Germline Stem Cell Gene PIWIL2 Mediates DNA Repair through Relaxation of Chromatin

DNA damage response (DDR) is an intrinsic barrier of cell to tumorigenesis initiated by genotoxic agents. However, the mechanisms underlying the DDR are not completely understood despite of extensive investigation. Recently, we have reported that ectopic expression of germline stem cell gene PIWIL2 is associated with tumor stem cell development, although the underlying mechanisms are largely unknown. Here we show that PIWIL2 is required for the repair of DNA-damage induced by various types of genotoxic agents. Upon ultraviolet (UV) irradiation, silenced PIWIL2 gene in normal human fibroblasts was transiently activated after treatment with UV light. This activation was associated with DNA repair, because Piwil2-deficienct mouse embryonic fibroblasts (mili-/- MEFs) were defective in cyclobutane pyrimidine dimers (CPD) repair after UV treatment. As a result, the UV-treated mili-/- MEFs were more susceptible to apoptosis, as characterized by increased levels of DNA damage-associated apoptotic proteins, such as active caspase-3, cleaved Poly (ADP-ribose) polymerase (PARP) and Bik. The impaired DNA repair in the mili-/- MEFs was associated with the reductions of histone H3 acetylation and chromatin relaxation, although the DDR pathway downstream chromatin relaxation appeared not to be directly affected by Piwil2. Moreover, guanine–guanine (Pt-[GG]) and double strand break (DSB) repair were also defective in the mili-/- MEFs treated by genotoxic chemicals Cisplatin and ionizing radiation (IR), respectively. The results indicate that Piwil2 can mediate DNA repair through an axis of Piwil2 → histone acetylation → chromatin relaxation upstream DDR pathways. The findings reveal a new role for Piwil2 in DNA repair and suggest that Piwil2 may act as a gatekeeper against DNA damage-mediated tumorigenesis

The impact of type 2 diabetes and its management on the prognosis of patients with severe COVID‐19

Background Although type 2 diabetes mellitus (T2DM) patients with coronavirus disease 2019 (COVID‐19) develop a more severe condition compared to those without diabetes, the mechanisms for this are unknown. Moreover, the impact of treatment with antihyperglycemic drugs and glucocorticoids is unclear. Methods From 1584 COVID‐19 patients, 364 severe/critical COVID‐19 patients with clinical outcome were enrolled for the final analysis, and patients without preexisting T2DM but elevated glucose levels were excluded. Epidemiological data were obtained and clinical status evaluation carried out to assess the impact of T2DM and its management on clinical outcomes. Results Of 364 enrolled severe COVID‐19 inpatients, 114 (31.3%) had a history of T2DM. Twenty‐seven (23.7%) T2DM patients died, who had more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury compared with non‐DM patients. In severe COVID‐19 patients with T2DM, we demonstrated a higher risk of all‐cause fatality with glucocorticoid treatment (adjusted hazard ratio [HR], 3.61; 95% CI, 1.14‐11.46; P = .029) and severe hyperglycemia (fasting plasma glucose ≥11.1 mmol/L; adjusted HR, 11.86; 95% CI, 1.21‐116.44; P = .034). Conclusions T2DM status aggravated the clinical condition of COVID‐19 patients and increased their critical illness risk. Poor fasting blood glucose (≥ 11.1 mmol/L) and glucocorticoid treatment are associated with poor prognosis for T2DM patients with severe COVID‐19