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21.
Vogelsang  David F.  Maleczka  Robert E.  Lee  Andre 《SILICON》2022,14(13):7555-7565
Silicon - Bisfunctional dichlorosilanes were reacted with tetrasilanol of double-decker shaped octaphenylsilsesquioxane (DDSQ) to form fully condensed DDSQ compounds. The crystallographic and...  相似文献   
22.
We try to identify the determinants of regional variation in both exploitative and exploratory innovative competencies. Hereby, we focus on how a knowledge-creation mechanism with specialized externalities differs from one with diversified externalities. Innovative competence in the US is measured by local patenting performance; exploitative and exploratory patenting performances are distinguished by the degree of backward citation. Based on the extended knowledge-production function, including the two agglomeration externalities, our findings show that specialized externalities are associated with exploitation, while diversified externalities are positively related with both exploration and exploitation, regardless of industrial sectors.  相似文献   
23.
7,7,8,8-Tetracyanoquinomethane (TCNQ) was added to polyvinylpyrrolidone (PVP)/CuO composites to modify and prevent agglomeration of the particles, and thus the CuO particles were well dispersed to a small size, thereby increasing CO2 solubility and separation performance. When the separation performance of the PVP/CuO/TCNQ composite membrane was measured for CO2/N2 gases, a CO2 separation of about 174 was measured. This improvement in performance was attributed to the fact that TCNQ was applied to PVP and CuO to prevent agglomeration between particles with surface modification. Due to TCNQ, CuO could be dispersed to a small size in PVP; the bonds between chains in PVP weakened; the interaction between molecules weakened; and the free volume increased, as confirmed by FT-IR, TGA, and UV–Vis spectroscopy.  相似文献   
24.
Cardiovascular abnormality-mediated retinal ischemia causes severe visual impairment. Retinal ischemia is involved in enormous pathological processes including oxidative stress, reactive gliosis, and retinal functional deficits. Thus, maintaining retinal function by modulating those pathological processes may prevent or protect against vision loss. Over the decades, nicotinamide mononucleotide (NMN), a crucial nicotinamide adenine dinucleotide (NAD+) intermediate, has been nominated as a promising therapeutic target in retinal diseases. Nonetheless, a protective effect of NMN has not been examined in cardiovascular diseases-induced retinal ischemia. In our study, we aimed to investigate its promising effect of NMN in the ischemic retina of a murine model of carotid artery occlusion. After surgical unilateral common carotid artery occlusion (UCCAO) in adult male C57BL/6 mice, NMN (500 mg/kg/day) was intraperitoneally injected to mice every day until the end of experiments. Electroretinography and biomolecular assays were utilized to measure ocular functional and further molecular alterations in the retina. We found that UCCAO-induced retinal dysfunction was suppressed, pathological gliosis was reduced, retinal NAD+ levels were preserved, and the expression of an antioxidant molecule (nuclear factor erythroid-2-related factor 2; Nrf2) was upregulated by consecutive administration of NMN. Our present outcomes first suggest a promising NMN therapy for the suppression of cardiovascular diseases-mediated retinal ischemic dysfunction.  相似文献   
25.
Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.  相似文献   
26.
Chloroquine (CQ) is an antimalaria drug that has been widely used for decades. However, CQ-induced pruritus remains one of the major obstacles in CQ treatment for uncomplicated malaria. Recent studies have revealed that MrgprX1 plays an essential role in CQ-induced itch. To date, a few MrgprX1 antagonists have been discovered, but they are clinically unavailable or lack selectivity. Here, a cell-based high-throughput screening was performed to identify novel antagonists of MrgprX1, and the screening of 2543 compounds revealed two novel MrgprX1 inhibitors, berbamine and closantel. Notably, berbamine potently inhibited CQ-mediated MrgprX1 activation (IC50 = 1.6 μM) but did not alter the activity of other pruritogenic GPCRs. In addition, berbamine suppressed the CQ-mediated phosphorylation of ERK1/2. Interestingly, CQ-induced pruritus was significantly reduced by berbamine in a dose-dependent manner, but berbamine had no effect on histamine-induced, protease-activated receptors 2-activating peptide-induced, and deoxycholic acid-induced itch in mice. These results suggest that berbamine is a novel, potent, and selective antagonist of MrgprX1 and may be a potential drug candidate for the development of therapeutic agents to treat CQ-induced pruritus.  相似文献   
27.
Due to the sudden change in temperature in spring, Chinese cabbage, a leafy vegetable cultivated for consumption, loses its commercial value due to the onset of bolting—the phenomenon of switching from vegetative to reproductive growth. In this study, we applied clustered regularly interspaced short palindromic repeats/(CRISPR)-associated system 9 (CRISPR/Cas9) technology to analyze AGAMOUS-like genes. We performed functional analysis of AGL19 and AGL24 genes related to bolting and flowering using CRISPR/Cas9-mediated Chinese cabbage transformation. Single-guide RNA (sgRNA) sequences were created with a low off-targeting probability to construct gene-editing vectors. Agrobacterium-mediated transformation was conducted, and tentative E0 AGL-edited lines were analyzed using molecular biotechnological methods. Two AGL19-edited lines with nucleotide sequence mutations in the target sequence of the AGL19 genes and four AGL24-edited lines with nucleotide sequence mutations in the target sequence of the AGL24 genes showed particularly late bolting compared to the inbred line ‘CT001.’ Generational progression using bud pollination obtained T-DNA-free E1 AGL-edited lines, which also showed late bolting. The loss of function of the AGL protein was caused by the occurrence of an indel mutation in the AGL19 and AGL24 genes, which results in an early stop codon. Furthermore, frameshift mutations led to structural changes and the introduction of an early stop codon in the AGL19 and AGL24 proteins. Our results indicate that CRISPR/Cas9-mediated editing of AGAMOUS-like genes results in a late-bolting phenotype and that CRISPR/Cas9 is a useful technology for analyzing gene function in Chinese cabbage (Brassica rapa ssp. pekinensis).  相似文献   
28.
Circadian rhythms, including sleep/wake cycles as well as hormonal, immune, metabolic, and cell proliferation rhythms, are fundamental biological processes driven by a cellular time-keeping system called the circadian clock. Disruptions in these rhythms due to genetic alterations or irregular lifestyles cause fundamental changes in physiology, from metabolism to cellular proliferation and differentiation, resulting in pathological consequences including cancer. Cancer cells are not uniform and static but exist as different subtypes with phenotypic and functional differences in the tumor microenvironment. At the top of the heterogeneous tumor cell hierarchy, cancer stem cells (CSCs), a self-renewing and multi-potent cancer cell type, are most responsible for tumor recurrence and metastasis, chemoresistance, and mortality. Phenotypically, CSCs are associated with the epithelial–mesenchymal transition (EMT), which confers cancer cells with increased motility and invasion ability that is characteristic of malignant and drug-resistant stem cells. Recently, emerging studies of different cancer types, such as glioblastoma, leukemia, prostate cancer, and breast cancer, suggest that the circadian clock plays an important role in the maintenance of CSC/EMT characteristics. In this review, we describe recent discoveries regarding how tumor intrinsic and extrinsic circadian clock-regulating factors affect CSC evolution, highlighting the possibility of developing novel chronotherapeutic strategies that could be used against CSCs to fight cancer.  相似文献   
29.
30.
Glucocorticoids are steroids involved in key physiological processes such as development, metabolism, inflammatory and stress responses and are mostly used exogenously as medications to treat various inflammation-based conditions. They act via the glucocorticoid receptor (GR) expressed in most cells. Exogenous glucocorticoids can negatively impact the function of the Leydig cells in the testis, leading to decreased androgen production. However, endogenous glucocorticoids are produced by the adrenal and within the testis, but whether their action on GR in Leydig cells regulates steroidogenesis is unknown. This study aimed to define the role of endogenous GR signalling in adult Leydig cells. We developed and compared two models; an inducible Cre transgene driven by expression of the Cyp17a1 steroidogenic gene (Cyp17-iCre) that depletes GR during development and a viral vector-driven Cre (AAV9-Cre) to deplete GR in adulthood. The delivery of AAV9-Cre ablated GR in adult mouse Leydig cells depleted Leydig cell GR more efficiently than the Cyp17-iCre model. Importantly, adult depletion of GR in Leydig cells caused reduced expression of luteinising hormone receptor (Lhcgr) and of steroidogenic enzymes required for normal androgen production. These findings reveal that Leydig cell GR signalling plays a physiological role in the testis and highlight that a normal balance of glucocorticoid activity in the testis is important for steroidogenesis.  相似文献   
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