The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
Summary
Background
Clostridium difficile infection is a major cause of nosocomial diarrhoea.
Aim
To evaluate long‐term (≥90 days) efficacy and safety of faecal microbiota transplantation for C. ...difficile infection and explore the factors affecting the faecal microbiota transplantation outcomes.
Methods
MEDLINE, the Cochrane Library and EMBASE were searched and only observational studies that utilised faecal microbiota transplantation for C. difficile infection with long‐term follow‐up duration (≥90 days) were included. Primary cure rate, overall recurrence rate and early (<90 days) and late (≥90 days) recurrence rate were calculated.
Results
Eighteen observational studies with 611 patients were included. The primary cure rate was 91.2% (95% confidence interval, CI 86.7–94.8%). The overall recurrence rate was 5.5% (95% CI 2.2–10.3%). The early recurrence rate and late recurrence rate were 2.7% (95% CI 0.7–6.0%) and 1.7% (95% CI 0.4–4.2%) respectively. Most adverse events were expected, short‐lived, self‐limited and manageable. The association between faecal microbiota transplantation therapy and adverse events such as inflammatory bowel disease flare, infectious disease and autoimmune disease was a concern but remained insignificant. Old age (≥65 years) was identified as a risk factor for after faecal microbiota transplantation therapy. Upper gastrointestinal administration also results in less frequent primary cure.
Conclusions
Faecal microbiota transplantation seems to be a highly effective and robust therapy for recurrent C. difficile infection. However, more quality studies, such as randomised controlled trials and cohort studies with control groups, are needed to confirm its long‐term efficacy and safety.
Large-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. ...Traditional experimental implementations need N
units such as Mach-Zehnder interferometers (MZIs) for an input dimension N to realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and only N MZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on the MNIST and Fashion-MNIST datasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.
Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued ...representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle and Spiral), and handwriting recognition. Strong learning capabilities (i.e., high accuracy, fast convergence and the capability to construct nonlinear decision boundaries) are achieved by our complex-valued ONC compared to its real-valued counterpart.
Summary
We performed a systematic review and meta-analysis of randomized clinical trials. Early administration of bisphosphonates (BPs) after surgery did not appear to delay fracture healing time ...either radiologically or clinically. Furthermore, the anti-resorptive efficacy of BPs given immediately after surgical repair should positively affect the rate of subsequent fractures.
Introduction
Bisphosphonates (BPs) are widely used in the prophylaxis and treatment of osteoporosis. However, early administration of BPs after surgical repair of a fracture may limit the reserve capacity of bone to heal. The aim of this review and meta-analysis was to analyze the benefits and adverse effects of early administration of BPs and give recommendations regarding when BPs should be utilized.
Methods
We identified randomized controlled trials comparing the early administration of BPs to placebo, delayed BP treatment, or no therapy in adult patients after surgery. The search was performed in PubMed, the Cochrane Library, and Embase.
Results
Ten studies with 2888 patients were included. Four trials used alendronate, three trials used zoledronic, two trials used risedronate, and one trial used etidronate. Early administration of BPs was considered less than 3 months after surgery. Patients treated with BP therapy had no significant differences in radiological fracture healing times compared with patients in the control group (mean difference MD 0.47, 95 % confidence interval CI −2.75 to 3.69). There were also no significant differences in the rate of delay or nonunion of fracture healing (odds ratio OR 0.98, 95 % CI 0.64 to 1.50). However, the bone mineral density (BMD) of total hips did significantly improve after 12 months of treatment with BPs. And most bone turnover markers of patients in the study group were significantly decreased.
Conclusions
Early administration of BPs after surgery did not appear to delay fracture healing time either radiologically or clinically. Furthermore, according to the changes in BMD and bone turnover markers, the anti-resorptive efficacy of BPs given immediately after surgical repair should positively affect the rate of subsequent fractures.
Angiogenesis is one of the critical biological elements affecting the development and progression of cancer. Long non-coding RNAs (lncRNAs) are important regulators and aberrantly expressed in ...various types of human cancer. Our previous studies indicated that lncRNA taurine upregulated 1 (TUG1) implicated in the regulation of blood-tumor barrier permeability; however, its role in glioblastoma angiogenesis still unclear. Here we demonstrated that TUG1 was up-expressed in human glioblastoma tissues and glioblastoma cell lines. Knockdown of TUG1 remarkably suppressed tumor-induced endothelial cell proliferation, migration and tube formation as well as reducing spheroid-based angiogenesis ability in vitro, which are the critical steps for tumor angiogenesis. Besides, knockdown of TUG1 significantly increased the expression of mircroRNA-299 (miR-299), which was down-expressed in glioblastoma tissues and glioblastoma cell lines. Bioinformatics analysis and luciferase reporter assay revealed that TUG1 influenced tumor angiogenesis via directly binding to the miR-299 and there was a reciprocal repression between TUG1 and miR-299 in the same RNA-induced silencing complex. Moreover, knockdown of TUG1 reduced the expression of vascular endothelial growth factor A (VEGFA), which was defined as a functional downstream target of miR-299. In addition, knockdown of TUG1, shown in the in vivo studies, has effects on suppressing tumor growth, reducing tumor microvessel density and decreasing the VEGFA expression by upregulating miR-299 in xenograft glioblastoma model. Overall, the results demonstrated that TUG1 enhances tumor-induced angiogenesis and VEGF expression through inhibiting miR-299. Also, the inhibition of TUG1 could provide a novel therapeutic target for glioblastoma treatment.
The genetic basis of character association related to differentiation found in the primary gene pool of rice was investigated based on the genomic distribution of quantitative trait loci (QTLs). ...Major evolutionary trends in cultivated rice of Asiatic origin ( Oryza sativa) and its wild progenitor ( O. rufipogon) are: (1) differentiation from wild to domesticated types (domestication), (2) ecotype differentiation between the perennial and annual types in wild races, and (3) the Indica versus Japonica type differentiation in cultivated races. Using 125 recombinant inbred lines (RILs) derived from a cross between an Indica cultivar of O. sativa and a strain of O. rufipogon carrying some Japonica-like characteristics, we mapped 147 markers, mostly RFLPs, on 12 chromosomes. Thirty-seven morphological and physiological quantitative traits were evaluated, and QTLs for 24 traits were detected. The mapped loci showed a tendency to form clusters that are composed of QTLs of the domestication-related traits as well as Indica/Japonica diagnostic traits. QTLs for perennial/annual type differences did not cluster. This cluster phenomenon could be considered "multifactorial linkages" followed by natural selection favoring co-adapted traits. Further, it is possible that the clustering phenomenon is partly due to pleiotropy of some unknown key factor(s) controlling various traits through diverse metabolic pathways. Chromosomal regions where QTL clusters were found coincided with the regions harboring genes or gene blocks where the frequency of cultivar-derived alleles in RILs is higher than expected. This distortion may be partly due to unconscious selection favoring cultivated plant type during the establishment of RILs.
Highlights • Lixisenatide, a novel drug treatment for diabetes, shows neuroprotective effects. • Lixisenatide prevented the Aβ25–35 induced impairment in spatial learning. • The drug prevented the ...Aβ25–35 induced block of LTP in the hippocampus. • The drug inhibited the Aβ25–35 induced activation of glycogen synthase kinase 3β.
This paper introduces luminance gradient as a metric for evaluating common non-uniform luminous environments. Luminance gradient is defined as the largest change rate and the polarity of spatial ...luminance variation on a large surface or across the entire field of view in high resolution. The metric, a visualization method, and a freely available MatLab code for plotting luminance gradient maps have been developed. The retinal resolution of pixels for mapping luminance gradient has also been identified. A camera-aided measurement method of luminance gradient is proposed, which is demonstrated in two case studies of the evaluation of different types of luminous environments. Moreover, this study explored whether luminance gradient could also be obtained from computer simulations using lighting software programs AGI32 and HeliosPro.
Summary
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economically significant pathogen that has adversely affected China's swine industry. Currently, a novel type 2 PRRSV, ...called the NADC30‐like strain, is epidemic in numerous provinces of China, and commercial vaccines provide limited protection for infected animals. The extensive recombination phenomenon among NADC30‐like PRRSVs is identified as a unique molecular characteristic of the virus. However, our understanding of how recombination influences NADC30‐like PRRSVs is largely inadequate. In this study, we analysed the genetic characteristics of a recombinant NADC30‐like PRRSV (SC‐d) and examined its pathogenicity compared with a non‐recombinant NADC30‐like PRRSV (SD‐A19) and a highly pathogenic PRRSV (HuN4). SC‐d has three discontinuous deletions in nsp2, consistent with NADC30 isolated from the United States in 2008. Furthermore, we identified four recombination breakpoints in the SC‐d genome, which separated the SC‐d genome into four regions (regions A, B, C and D). Regions A and C are closely related to the JXA1‐like strain, one of the earliest Chinese HP‐PRRSV strains, and regions B and D are closely related to the NADC30 strain. Moreover, SC‐d inoculated piglets exhibited a persistent fever, moderate weight loss, mild thymus atrophy and obvious microscopic lung lesions. In summary, the recombinant NADC30‐like PRRSV SC‐d strain displayed a higher pathogenicity than the non‐recombinant NADC30‐like PRRSV SD‐A19 strain; however, the pathogenicity of the NADC30‐like PRRSV SC‐d was lower compared with the HP‐PRRSV HuN4 strain in piglets. Our findings demonstrate that recombination is responsible for the enormous genetic diversity and pathogenicity variance of the NADC30‐like PRRSV in China. This study provides a theoretical basis for developing a more reasonable PRRSV control and prevention strategy.
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