We develop a simple "mix-and-detection" method for the sensitive detection of telomerase from cancer cells under absolutely isothermal conditions. This method enables one-step and one-tube detection ...of telomerase with a detection limit of 3 cells, and it can be further applied for the screening of telomerase inhibitors and the discrimination of cancer cells from normal cells.
Nasopharyngeal carcinoma (NPC), the most common head and neck cancer, is characterized by distinct geographic distribution and familial aggregation. Multiple risk factors, including host genetics, ...environmental factor, and EBV infection, have been linked to the development of NPC, particularly in the familial clustering cases. However, the cause of NPC endemicity remains enigmatic due possibly to the complicated interplay between these risk factors. Recently, positive Epstein‐Barr virus (EBV) DNA loads at nasopharyngeal (NP) cavity has been found to reflect NPC development and applied in NPC screening. To examine whether the increased NP EBV loads could aggregate in the families and be affected by host genetics and environmental factor, EBV loads were obtained by 510 NP brushing samples from eligible unaffected individuals, who have two or more relatives affected with NPC, in 116 high‐risk NPC families. The correlation of relative pairs was estimated using S.A.G.E. (version 6.4, 2016), and host heritability of NP EBV loads was calculated with variance component models using SOLAR (version 8.4.2, 2019). In result, significant correlations of EBV loads were observed between parent‐offspring pairs and sibling‐sibling pairs (P < .001), but not in distant kin relationship pairs. Interestingly, after excluding the shared environmental factor within families, host genetics contributes significantly to NP EBV loads with a heritability of 56.41% (P = 1.00 × 10−7), and its effect was slightly elevated (68.86%, P = 3.40 × 10−6) in families with more NPC cases (≥3). These findings indicate that additional host‐genetic variants involved in the EBV local NP mucosal behavior may be especially important for the development of NPC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ginsenosides are the primary active components in the genus Panax, and great efforts have been made to elucidate the mechanisms underlying dammarane-type ginsenoside biosynthesis. However, there is ...limited information on oleanane-type ginsenosides. Here, high-performance liquid chromatography analysis demonstrated that oleanane-type ginsenosides (particularly ginsenoside Ro and chikusetsusaponin IV and IVa) are the abundant ginsenosides in Panax zingiberensis, an extremely endangered Panax species in southwest China. These ginsenosides are derived from oleanolic acid 3-O-ß-glucuronide, which may be formed from oleanolic acid catalyzed by an unknown oleanolic acid glucuronosyltransferase (OAGT). Transcriptomic analysis of leaves, stems, main roots, and fibrous roots of P. zingiberensis was performed, and a total of 46,098 unigenes were obtained, including all the identified homologous genes involved in ginsenoside biosynthesis. The most upstream genes were highly expressed in the leaves, and the UDP-glucosyltransferase genes were highly expressed in the roots. This finding indicated that the precursors of ginsenosides are mainly synthesized in the leaves and transported to different parts for the formation of particular ginsenosides. For the first time, enzyme activity assay characterized four genes (three from P. zingiberensis and one from P. japonicus var. major, another Panax species with oleanane-type ginsenosides) encoding OAGT, which particularly transfer glucuronic acid at C-3 of oleanolic acid to form oleanolic acid 3-O-ß-glucuronide. Taken together, our study provides valuable genetic information for P. zingiberensis and the genes responsible for synthesizing the direct precursor of oleanane-type ginsenosides.
Tripartite motif-containing protein 5α (TRIM5α) is generally known to block the postentry events of HIV-1. Here, we report an uncharacterized role for TRIM5α in the maintenance of viral latency. ...Knockdown of TRIM5α potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5α. TRIM5α suppresses TNFα-activated HIV-1 LTR-driven as well as NF-κB- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Mechanistically, TRIM5α binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-κB p50 and Sp1. ChIP‒qPCR analyses further reveal that the association of TRIM5α with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Conserved suppression effects of TRIM5α orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. These findings provide new insights into the molecular mechanisms by which proviral latency is initially established and activatable proviruses are resilenced by histone deacetylase recruitment.
A strain-based automated operational modal analysis algorithm is proposed to track the long-term dynamic behavior of a horizontal wind turbine under operational conditions. This algorithm is firstly ...validated by a scaled wind turbine model, and then it is applied to the dynamic strain responses recorded from a 5 MW wind turbine system. We observed variations in the fundamental frequency and 1f, 3f excitation frequencies due to the mass imbalance of the blades and aerodynamic excitation by the tower dam or tower wake. Inspection of the Campbell diagram revealed that the adverse resonance phenomenon and Sommerfeld effect causing excessive vibrations of the wind tower.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Membranes with ultrathin rejection layers can effectively achieve high water permeability. In the current study, we report a single-step fabrication of carbon nanotubes (CNTs)-loaded ultrathin film ...composite (uTFC) polyamide membranes using an electrospray-assisted interfacial polymerization method. In this method, amine and acyl chloride monomer solutions were electrosprayed into micro-droplets to allow a controlled growth of the polyamide rejection layer. At the same time, CNTs were uniformly dispersed under the action of the electrical field. The loading of CNTs in the polyamide rejection layer markedly enhance the water permeability of the membrane with a 2–6 folds enhancement. The simple and versatile electrospray-assisted interfacial polymerization method, which allows simultaneous control of rejection layer thickness and dispersion of nanomaterials, paves a new dimension for the preparation of high performance ultrathin nanocomposite membranes.
•A single-step fabrication method was reported for CNTs-loaded ultrathin polyamide membranes.•The growth of the polyamide rejection layer can be effectively controlled.•CNTs were uniformly dispersed on the ultrathin polyamide layer.•The obtained uTFC membrane had markedly enhanced water permeability of 2–6 folds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Regeneration of injured neurons in complicated three-dimensional (3D) microenvironments is a key approach for treating neurodegenerative diseases. Microfluidics provides a versatile tool to ...recapitulate cellular microenvironments in vitro, but it still remains a big challenge to construct a microfluidic platform incorporating extracellular matrix (ECM) structures and highly controlled 3D gradients of soluble factors to study the regeneration of injured neurons. In this work, we developed a microfluidic device which can provide multiple adjustable gradients in a 3D ECM to investigate the regeneration of injured central nervous system (CNS) neurons in response to natural small molecules. With interconnecting but independently controlled central channels, asymmetrically designed side channels and a series of microgrooves connecting the central channels, spatially and temporally controlled 3D biochemical gradients can be generated inside collagen hydrogel in the central channels. This allows quantitative analysis of guided axon growth and the orientational regeneration of injured dopaminergic neurons by 3D chemical gradients of three natural molecules. This study demonstrates a promising microfluidic platform for the generation of highly controlled 3D biochemical gradients in an ECM to quantitatively study neuronal responses, thereby potentially facilitating drug screening and optimization of treatment protocols for neurodegenerative diseases.
Ga 2 O 3 is one of the most suitable semiconductor materials for performing deep UV photoelectric detection. In this work, a self-powered deep UV photodetector based on a Ga 2 O 3 /BFO heterojunction ...is fabricated via solution spin-coating and metal-organic chemical vapor deposition (MOCVD) methods. Without biasing driven, the device achieves an extreme low dark current (<inline-formula> <tex-math notation="LaTeX">{I}_{dark} </tex-math></inline-formula>) of 8.38 fA, a photo-to-dark current ratio ( PDCR ) of <inline-formula> <tex-math notation="LaTeX">1.66\times10 </tex-math></inline-formula> 5 , a high specific detectivity (<inline-formula> <tex-math notation="LaTeX">{D} \ast </tex-math></inline-formula>) of <inline-formula> <tex-math notation="LaTeX">6.1\times 10^{12} </tex-math></inline-formula> Jones and an open-circuit voltage (<inline-formula> <tex-math notation="LaTeX">{V}_{\textit {oc}} </tex-math></inline-formula>) of 0.55 V responding to deep UV irradiation (254 nm in this work). Through analyzing the band diagram of the heterojunction, the intrinsic physical characteristics of the photodetector are discussed. Results show that the photodetector has excellent deep UV signal detecting ability, indicating that Ga 2 O 3 /BFO heterojunction is a potential candidate for performing self-powered deep UV photodetection.
Fibroblast growth factor 21 (FGF21) is produced by cardiac cells, may acts in an autocrine manner, and was suggested to has a cardioprotective role in atherosclerosis. Wide QRS complex and heart ...rate-corrected QT interval (QTc interval) prolongation are associated to dangerous ventricular arrhythmias and cardiovascular disease mortality. Yet, the role of FGF21 in cardiac arrhythmia has never been studied. The aim of the study was to investigate the relationship between plasma FGF21 and the QRS duration and QTc interval in patients with stable angina.
Three hundred twenty-one consecutive stable angina patients were investigated. Plasma FGF21 was measured through ELISA, and each subject underwent 12-lead electrocardiography.
FGF21 plasma levels were positively associated with the QRS duration (β = 0.190, P = 0.001) and QTc interval (β = 0.277, P < 0.0001). With increasing FGF21 tertiles, the patients had higher frequencies of wide QRS complex and prolonged QTc interval. After adjusting for patients' anthropometric parameters, the corresponding odd ratios (ORs) for wide QRS complex of the medium and high of FGF21 versus the low of FGF21 were 1.39 (95% CI 0.51-3.90) and 4.41 (95% CI 1.84-11.59), respectively, and p for trend was 0.001. Furthermore, multiple logistic regression analysis also showed the corresponding odd ratios (ORs) for prolonged QTc interval of the medium and high of FGF21 versus the low of FGF21 were 1.02 (95% CI 0.53-1.78) and 1.93 (95% CI 1.04-3.60) respectively with the p for trend of 0.037. In addition, age- and sex-adjusted FGF21 levels were positively associated with fasting glucose, HbA1c, creatinine, and adiponectin, but negatively associated with albumin, and the estimated glomerular filtration rate.
This study indicates that plasma FGF21 is associated with wide QRS complex and prolonged corrected QT interval in stable angina patients, further study is required to investigate the role of plasma FGF21 for the underlying pathogenesis.
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