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BackgroundBreast cancer (BC) is the leading cause of cancer−related mortality in females and the most common malignancy with high morbidity worldwide. It is imperative to develop new biomarkers and therapeutic targets for early diagnosis and effective treatment in BC.MethodsWe revealed the oncogene function of cadherin 1 (CDH1) via bioinformatic analysis in BC. Moreover, miRNA database was utilized to predict miRNAs upstream of CDH1. Expression of CDH1-related miRNAs in BC and their values in BC stemness and prognosis were analyzed through TCGA‐BRCA datasets. In addition, Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were performed to explore the potential functions and signaling pathways of CDH1 in combination with CDH1-related miRNAs in BC progression. Finally, the differential expressions of soluble E-cadherin (sE-cad), which is formed by the secretion of CDH1-encoded E-cadherin into serum, analyzed by enzyme-linked immunosorbent assay (ELISA). Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression level of CDH1-related miRNAs in serum samples.ResultsThe mRNA and protein expressions of CDH1 were elevated in BC tissues compared with normal counterparts. Moreover, CDH1 overexpression was positively correlated with BC stage, metastatic, stemness characteristics, and poor prognosis among patients. In predictive analysis, miR-340, miR-185, and miR-20a target CDH1 and are highly expressed in BC. miR-20a overexpression alone was strongly associated with high stemness characteristics and poor prognosis of BC. Additionally, GO, KEGG, and hallmark effect gene set analysis demonstrated that CDH1 in combination with overexpression of miR-340, miR-185, or miR-20a participated in multiple biological processes and underly signaling pathways involving in tumorigenesis and development of BC. Finally, we provide experimental evidence that the combined determination of serum sE-cad and miR-20a in BC has highly diagnostic efficiency.ConclusionsThis study provides evidence for CDH1 as an oncogene in BC and suggests that miR-20a may regulate the stemness characteristics of BC to exert a pro-oncogenic effect by regulating CDH1. Moreover, sE-cad and miR-20a in serum can both be used as valid noninvasive markers for BC diagnosis.

Adeno-associated virus (AAV) is a human parvovirus with defects and no disease.AAV vector, as an ideal carrier for the transduction of target genes, has certain advantages in long-term gene correction and gene therapy by transferring foreign bases into cells by using the virus's capacity to infect cells.Due to its advantages of extensive host, strong safety and continuous expression of foreign genes, AAV has been used in gene therapy for a variety of tumor.

Abstract Background The NLRP3 inflammasome plays an important role in mediating podocyte injury in various kidney diseases. The aim of this study was to investigate whether NLRP3 expression associated with podocyte injury was involved in the pathogenesis of IgA nephropathy (IgAN). Methods NLRP3 inflammasomes and macrophage marker (F4/80) were detected in the renal tissues of IgAN patients. Association between kidney NLRP3 levels and the clinical feature of IgAN patients was analyzed. Podocytes were incubated with serum containing dys-glycosylated IgA1 protein isolated from IgAN patients. Expression of NLRP3 inflammasomes, F4/80, inflammatory cytokine and renal fibrosis marker were measured using RT-PCR and Western blotting. Results Renal NLRP3 inflammasome expression was significantly increased in IgAN patients compared to normal control tissues. Moreover, co-expression of NLRP3 and F4/80 could be observed in the podocytes of IgAN patients. Patients with eGFR

The E2F family of transcription factors (E2Fs) consist of eight genes in mammals. These genes encode ten proteins that are usually classified as transcriptional activators or transcriptional repressors. E2Fs are important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis, the DNA damage response and apoptosis. A growing body of evidence demonstrates that cancer stem cells (CSCs) are key players in tumor development, metastasis, drug resistance and recurrence. This review focuses on the role of E2Fs in CSCs and notes that many signals can regulate the activities of E2Fs, which in turn can transcriptionally regulate many different targets to contribute to various biological characteristics of CSCs, such as proliferation, self-renewal, metastasis, and drug resistance. Therefore, E2Fs may be promising biomarkers and therapeutic targets associated with CSCs pathologies. Finally, exploring therapeutic strategies for E2Fs may result in disruption of CSCs, which may prevent tumor growth, metastasis, and drug resistance.

We report an experimental study of the formation and evolution of laminar thermal structures generated by a small heat source, with a focus on their correlation to the thermal boundary layer and effects of heating time $t_{heat}$. The experiments are performed over the flux Rayleigh number ($Ra_f$) range $2.1\times 10^6 \leq Ra_f \leq 3.6\times 10^{7}$ and the Prandtl number ($Pr$) range $28.6 \leq Pr \leq 904.7$. The corresponding Rayleigh number ($Ra= t_{heat}\,Ra_{f}/\tau _0\,Pr$) range is $900 \leq Ra \leq 4\times 10^{4}$ , where $\tau _0$ is a diffusion time scale. For thermal structures generated by continuous heating (i.e. starting plumes), their formation process exists three characteristic times that are well reflected by changes in the thermal boundary layer thickness. These characteristic times, denoted as $t_{emit}$ , $t_{recover}$ and $t_{static}$ , correspond to the moments when the plume emission begins and completes, and when the thermal boundary layer becomes quasi-static, respectively. Their $Ra_f$ – $Pr$ dependencies are found to be $t_{emit}/\tau _0\sim Ra_f^{-0.41}\,Pr^{0.41}$ , $t_{recover}/\tau _0\sim Ra_f^{-0.48}\,Pr^{0.48}$ and $t_{static}/\tau _0\sim Ra_f^{-0.49}\,Pr^{0.33}$ , respectively. Thermal structures generated by finite $t_{heat}$ exhibit similar evolution dynamics once $t_{heat} \ge t_{emit}$ , with the accelerating stage behaving like starting plumes and the decay stage like thermals (i.e. a finite amount of buoyant fluids). It is further found that their maximum rising velocity experiences a transition in the $Ra$ -dependence from $Ra$ to $(Ra\ln Ra)^{0.5}$ at $Ra \simeq 6000$ ; and their maximum acceleration reaches the value of starting plumes at $t_{heat}\simeq t_{recover}$ , and remains unchanged for larger $t_{heat}$. In particular, the maximum rising velocity for the cases with $t_{heat} = t_{recover}$ follows a scaling relation $Ra_f^{0.37}\,Pr^{-0.37}$ , in contrast to the relation $Ra_f^{0.48}\,Pr^{-0.48}$ for starting plumes. This study provides a more comprehensive understanding of laminar thermal structures, which are relevant to a range of processes in nature and laboratory systems such as Rayleigh–Bénard convection. [ABSTRACT FROM AUTHOR]

Background and Purpose: Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non‐intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke. Methods: This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched. Results: Forty‐eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing. Conclusions: RIC is safe, feasible, and effective in the treatment of stroke. Large‐scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment. [ABSTRACT FROM AUTHOR]

In order to solve the problems such as high density of gas drainage hole, small influence range of single hole drainage, little amount of drainage, frequent carrying of drilling rig and low working efficiency, using high pressure combined water jet technology, we optimize the design of front and back nozzles and steering gear. On the basis of the axial hole, the technology of multiple radial branch holes extraction is realized. The results of the study show that with multi-combination high-pressure nozzle and hose combined with coal rock breaking and small radius turning of steering device, the dynamic kinetic energy load is applied to the coal body to realize dynamic damage and fracture of coal and rock mass, and the gas permeability of coal seam can be rapidly improved.

Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program. In this study, an integrated strategy of combining phylogenetic data and bioactivity tests with a metabolomics-based dereplication approach was applied to fast track the selection process. A total of 521 actinomycetial strains affiliated to 40 genera in 23 families were isolated from 13 different mangrove soil samples by the culture-dependent method. A total of 179 strains affiliated to 40 different genera with a unique colony morphology were selected to evaluate antibacterial activity against 12 indicator bacteria. Of the 179 tested isolates, 47 showed activities against at least one of the tested pathogens. Analysis of 23 out of 47 active isolates using UPLC-HRMS-PCA revealed six outliers. Further analysis using the OPLS-DA model identified five compounds from two outliers contributing to the bioactivity against drug-sensitive A. baumannii. Molecular networking was used to determine the relationship of significant metabolites in six outliers and to find their potentially new congeners. Finally, two Streptomyces strains (M22, H37) producing potentially new compounds were rapidly prioritized on the basis of their distinct chemistry profiles, dereplication results, and antibacterial activities, as well as taxonomical information. Two new trioxacarcins with keto-reduced trioxacarcinose B, gutingimycin B (16) and trioxacarcin G (20), together with known gutingimycin (12), were isolated from the scale-up fermentation broth of Streptomyces sp. M22. Our study demonstrated that metabolomics tools could greatly assist classic antibiotic discovery methods in strain prioritization to improve efficiency in discovering novel antibiotics from those highly productive and rich diversity ecosystems.