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Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo (China) Holdings Co., Ltd, Shanghai, China. Background The effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) edoxaban for the treatment of patients with non-valvular atrial fibrillation (NVAF) have been investigated globally. Data from mainland China, however, is scarce. Purpose To report baseline characteristics of unselected NVAF patients receiving edoxaban in routine clinical practice. Methods ETNA-AF-China is a multi-center, prospective, observational study designed to evaluate effectiveness and safety of edoxaban for stroke preventions in 89 sites across mainland China with 2-year follow-up. Enrollment started on February 2021 and ended on October 2022. Patients having history of NVAF, prescribed edoxaban, and providing written informed consent were eligible. This descriptive analysis of the baselines data is based on a snapshot from November 2022. Results A total of 5,000 patients were enrolled and data of 4749 patients with full edoxaban treatment information at baseline were analyzed (60 mg: 2559, 30 mg: 2190). Overall, mean (SD) patient age was 70.2 (9.55) years, with 1660 (35.0 %) patients ≥ 75 years. Male patients constituted 57.0 %. The average calculated creatinine clearance rate, CHA2DS2-VASc scores and HAS-BLED scores were 71.3 (27.8) mL/min, 2.88 (1.41) and 1.83 (1.04), respectively. Patients with perceived frailty, history of stroke, history of bleeding comprised 6.46 %, 8.78 %, 2.21% of the overall population, respectively (Table). The majority of patients (79.0 %) received recommended dose according to label criteria, with similar percentages observed among economic regions (East, 81.5 %; Northeast, 78.4 %; Middle, 76.0 %; West, 76.8 %). A numerically larger percentage of patients receiving non-recommended 30 mg were categorised as high risk for either stroke or bleeding (presence of prior stroke, prior major bleeding or prior ICH, or a CHA2DS2-VASc score ≥ 4; 34.1 % vs 25.6 %), frail assessed by physician (10.6 % vs 3.3 %), and had stage 3 chronic renal disease (58.8 % vs 39.4 %) compared with patients receiving recommended 60 mg. Those prescribed a non-recommended 60 mg vs those with recommended 30 mg were less likely to be considered stroke or bleeding high risk (40.2 % vs 46.8 %), and advanced renal disease (≥ stage 4, 10.7% vs 13.8 %) (Figure). Conclusion In this real-world study, edoxaban was predominantly prescribed with elder NVAF patients, on dose of 60 mg. Most of Chinese patients adhered to edoxaban approved label and the deviation from dose recommendation appears to be influenced by physician’s consideration of patient’s characteristics (such as stroke or bleeding high risk). More data profiles of ETNA-AF-China concerning effectiveness and safety study are collecting at the follow-up period.

This research aimed to understand the differences in research methods adopted between Chinese and international e-commerce research and provided suggestions and recommendations for further research agenda in e-commerce post-COVID-19. This research studied 4,425 Chinese publications between 2015 and 2019 compared to international reviews in e-commerce research. Twelve findings were discussed: 1) Most of China's e-commerce publications (80.24%) did not state any research method. 2) Mixed methods have been well-adopted in China's e-commence research (35.05%), including quantitative-mixed, qualitative-mixed, and quantitative-qualitative mixed methods. They were highly adopted compared to other studies. 3) Survey methods (27.97%) were predominantly single research - purely quantitative method in Chinese research, but they were still behind international research. 4) Case studies (14.05%) were adopted as the second single method in Chinese research. This finding was significantly different from international views. 5) There were different views on whether laboratory experiments should be considered a research method. 6) Document and text analysis methods were reported by Chinese scholars (6.48%), but less and even not be reported internationally. 7) The focus group method was less adopted internationally. 8) The content analysis method (0.84%) was less adopted in Chinese research and was not reported by international scholars. 9) The observation method (0.6%) was less adopted in Chinese research but more adopted in Ain et al. (2019) (2%). Other international studies reported no studies. 10) Interviews (0.36%) were least adopted in Chinese research but highly reported by international scholars. 11) Field study, secondary, and Delphi methods were only adopted in international research, and 12) The correlational research method was not reported in e-commerce research. The main contributions of this study could be stated: Being valuable for researchers interested in Chinese e-commerce research; Adding research value for comparing reviews in e-commerce research methods.

肾动脉纤维肌性结构不良导致肾动脉狭窄继发的高血压常为难治性高血压，通过合理的影像学诊断尽早明确病因是正确治疗的开端。该文报道了一例因脑出血就诊而发现高血压的青少年男性患者，通过数字减影血管造影、双肾CT血管造影及卡托普利介入肾动态显像等影像学检查最终诊断为孤立肾肾动脉纤维肌性结构不良致肾动脉狭窄，并分析了不同影像学检查在该病诊断中的价值，以供临床参考。.

Increasing evidence has revealed that microRNAs (miRNAs) act as key players in the regulation of tumor growth and metastasis in epithelial ovarian cancer (EOC). However, the clinical role and functional effects of miR-1294 in EOC remain unknown.We examined the expression of miR-1294 in 69 cases of EOC tissues and cell lines by quantitative Real-time polymerase chain reaction (qRT-PCR). The associations of miR-1294 expression with clinicopathologic features and overall survival of EOC patients were analyzed. Biological functional effects of miR-1294 expression on cell growth were analyzed using Cell Counting Kit-8 (CCK8) assays and flow cytometry assays in vitro.In the present study, we identified that miR-1294 expression was lower in 76 specimens of EOC compared to adjacent normal tissues. Lower miR-1294 expression was related to FIGO stage, lymph node metastasis and shorter overall survival rate in EOC patients. Multivariate Cox analysis demonstrated that miR-1294 expression was an independent prognostic indicator of EOC patients. Gain function assays showed that miR-1294 overexpression inhibited cell proliferation and cell cycle progression in EOC.Our results indicated that miR-1294 acted as a prognostic biomarker and potential target of EOC treatment.

This paper introduces a compact LIDAR system designed to inspect overhead transmission line for maintenance purposes. This LIDAR system is carried by a small unmanned helium airship, which is guided by GPS and laser ranging to fly automatically along the power-line over a limited distance. The 3D coordinates of the power line, power tower and power line channel features are gathered by LIDAR. Test have been accomplished using this blimp-based compact LIDAR power-line inspection system. Its inspections of a 500kV power lines also shows the high efficient inspection, less risk to personnel and more inspections per day compared with manual inspection.

To investigate the expression of long non-coding RNA ZNF667-AS1 in cervical cancer and its effect on the proliferation of cervical cancer cell line, SiHa cells.The expression level of ZNF667-AS1 from two microarray datasets (GSE63514 and GSE6791) and TCGA (The Cancer Genome Atlas) were selected to analyze the difference between cervical cancer tissues and normal cervical tissues with bioinformatics methods. Then, the prognosis of ZNF667-AS1 was calculated in TCGA. The expression of LncRNA ZNF667-AS1 in 30 normal cervical tissues and 60 cervical cancer tissue samples was explored using qRT-PCR. In addition, analysis of the clinical data found that the expression of LncRNA ZNF667-AS1 was correlated with the total survival, tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage. At last, the proliferative ability was detected by CCK8 and colon formation assay.Search the relevant microarray datasets using the keywords "cervical cancer" and "GPL570" from the Gene Expression Omnibus (GEO) database. Afterwards, two microarray datasets (GSE63514 and GSE6791) were selected to analyze the differentially expressed genes in cervical cancer tissues and normal cervical tissues using bioinformatics methods. The results showed that the expression of LncRNA ZNF667-AS1 in cervical cancer was significantly lower than that in normal cervical tissues. 30 normal cervical tissues and 60 cervical cancer tissue samples were selected to extract total RNA for qRT-PCR experiment, and found that the expression of LncRNA ZNF667-AS1 in cervical cancer tissues was lower than that in normal cervical tissues, which was consistent with that of TCGA. Analysis of the clinical data found that the expression of LncRNA ZNF667-AS1 was correlated with the total survival, tumor size and FIGO stage. Compared with the negative control group, the proliferation ability and cell cloning ability of cells with over-expressed LncRNA ZNF667-AS1 were significantly decreased (p0.001), indicating that overexpression of ZNF667-AS1 inhibited the proliferation of SiHa cells.Expression of LncRNA ZNF667-AS1 was significantly lower in cervical cancer tissues, and its expression was negatively correlated with the overall survival, tumor size and FIGO stage. ZNF667-AS1 inhibited the proliferation of cervical cancer cells and was expected to be the biomarker and potential therapeutic target for predicting cervical cancer and determining its prognosis.

It is well established that the tumor suppressor p53 plays major roles in regulating apoptosis and cell cycle progression. In addition, recent studies have demonstrated that p53 is actively involved in regulating cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates c-Maf and Prox1, two important transcription factors to control cell differentiation in the ocular lens. In the present study, we present further evidence to show that p53 can regulate lens differentiation by controlling expression of the differentiation genes coding for the lens crystallins. First, the αA and βA3/A1 gene promoters or introns all contain putative p53 binding sites. Second, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from lens epithelial cells directly binds to the p53 binding sites found in these crystallin gene promoters or introns. Third, exogenous wild type p53 induces dose-dependent expression of the luciferase reporter gene driven by different crystallin gene promoters and the exogenous dominant negative mutant p53 causes dose-dependent inhibition of the same crystallin genes. Fourth, ChIP assays revealed that p53 binds to crystallin gene promoters in vivo. Finally, in the p53 knockout mouse lenses, expression levels of various crystallins were found down-regulated in comparison with those from the wild type mouse lenses. Together, our results reveal that p53 directly regulates expression of different sets of genes to control lens differentiation.

Our previous studies demonstrated that upon activation, monocytes (Mo) were able to sensitize peripheral blood T (PBT) cells to apoptosis induced by treatment with PMA. However, it is unknown what gene products provide the death signal to the sensitized PBT cells and how activated Mo enable PBT cells to become susceptible to apoptosis. Here, we show that PBT cells, but not Mo, express functional Fas ligand upon treatment with PMA. Moreover, this Mo-dependent T cell apoptosis could be blocked by a Fas-Ig fusion protein, as well as by a nonlytic mAb against Fas molecule. These results strongly suggest involvement of Fas-Fas ligand interaction in the death of PBT cells. Unlike Fas-induced apoptosis, however, Mo-dependent T cell death was completely inhibited by overexpression of the Bcl-2 protein, and PMA alone was sufficient to trigger apoptosis in T cells when Mo were included in culture. Furthermore, anti-CD11a, anti-CD18, or anti-CD45/CD45RA mAbs; could prevent PBT cells from death triggered by PMA plus Mo, suggesting that these Ags participate in the apoptotic process. The participation of CD45RA in the death of PBT cells was further demonstrated by the observation that the J45.01 cell line, a CD45-deficient variant of Jurkat cells, did not undergo apoptosis by this Mo-dependent mechanism. When transfected with cDNA encoding CD45RA, J45.01 cells acquired apoptotic response to PMA stimulation in the presence of Mo to a similar, but lesser, degree than normal Jurkat cells.

The peptides recognized by CD8+ CTL normally arise by proteolysis of intracellular proteins. To learn whether these peptides are generated similarly in diverse cell types, we examined the variety and abundance of naturally processed peptides that derive from a ubiquitous enzyme, alpha-ketoglutarate dehydrogenase, and are recognized in association with the class I MHC protein, Ld, by a CTL clone (2C). A characteristic set of three peptides was found in diverse tissues, but their abundance varied greatly, apparently unrelated to differences in class I MHC expression, e.g., they were surprisingly abundant in liver. We also found in liver a fourth naturally processed peptide (p2Ca-Y4, LSPYPFDL) that differs by one oxygen atom from a previously characterized natural peptide (p2Ca, LSPFPFDL). CTL discrimination between these peptides in association with the same class I MHC protein, Kb, demonstrates the striking specificity that can be exhibited by low affinity T cell reactions.

A novel solid-state film system comprising of the Graphene Oxide (GO) and particle lens is studied for its enhanced saturable absorption and tunable optical nonlinearity. A silica microsphere, which functions as a particle lens, can redistribute the light through the focusing effect and generate a high intensity focusing beam known as the photonic nanojet (PNJ). By applying the local field enhancement of the PNJ, the normalized peak transmittance of the GO film can be enhanced around 38% after hybridizing it with silica microspheres. The tunable nonlinearity is investigated by varying the concentration of silica microspheres. Meanwhile, such ultrathin solid-state hybrid system can be easily fabricated and coated on various types of substrates, which can be a promising candidate for applications on integrated photonics and ultrafast laser devices.

Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP-1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP-1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP-1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP-1 with morpholino oligomers leads to partial (PP-lα knockdown) or complete (PP-lβ or PP-lγ knockdown) death of the injected embryos. The survived embryos from PP-1α knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP-1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream targets mediating the effects of PP-1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP-1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.

The c-Jun N-terminal kinases (JNKs) constitute one of the three major types of mitogen-activated protein kinases. Previous studies showed that JNK mediates multiple signaling transduction pathways implicated in cell proliferation, differentiation, inflammation, stress response and apoptosis in mammals. In the present study, we use goldfish as a model system and demonstrate that JNK kinases are necessary to promote embryonic survival and regulate eye development in vertebrates. During goldfish development, JNK1 and JNK2 are expressed at every stage from cleavage to hatching larvae. JNK3 is turned on at the gastrulation stage and then expressed at similar level to that of JNK2. JNK1 activity remains slightly fluctuated during different developmental stages. Inhibition of JNK activity caused massive apoptosis of blastula cells and significant death of goldfish embryos, which are associated with altered expression of the anti-apoptotic regulator, Mcl-1 and the proapoptotic regulator, Bak. These results provide novel information regarding the mechanisms by which JNKs promote embryonic survival. In addition, the embryos that survived inhibition of JNK activity displayed severe phenotype in the eye with clear microphthalmia and lens coloboma. To confirm that the observed phenotype is derived from JNK activity deficiency, we expressed JNK dominant negative mutant (DNM-JNK) in goldfish. Expression of DNM-JNK also caused similar phenotypes with altered expression of pax-6, Sox-2 and β-crystallin. Together, our results demonstrate that JNKs play important roles in promoting survival of vertebrate embryos and regulating development of vertebrate eye.

The classical, α β -subunit form (Q2) of green tomato pyrophosphate fructose-6-phosphate 1-phosphotransferase (PFP, EC 2.7.1.90), a cytosolic enzyme functional in carbohydrate metabolism, was rapidly inactivated on incubation with the oxidant 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB). Analysis of the DTNB-treated sample by a fluorescence procedure revealed that inactivation was accompanied by oxidation of sulfhydryl groups, primarily on the α-subunit. Phosphate metabolites—fructose 2,6-bisphosphate, fructose 1,6-bisphosphate, Pi, and PPi—protected against DTNB inactivation to varying degrees. The Km values for fructose 6-phosphate and PPi were not changed by DTNB treatment, but the capability for activation by fructose 2,6-bisphosphate was severely diminished. The oxidative inactivation of PFP was reversed by dithiothreitol, but not by monothiols (reduced glutathione or β-mercaptoethanol). Reactivation was accompanied by restoration of the ability to undergo activation by fructose 2,6-bisphosphate. The findings suggest that sulfhydryl groups are essential for the activation of PFP by fructose 2,6-bisphosphate and raise the possibility that a reversible change in their redox status can take place under certain conditions. Evidence that this is the case was obtained with a preparation from wheat flour which, in the absence of an added oxidant, required reduction by a dithiol for activation by fructose 2,6-bisphosphate (dithiothreitol and reduced thioredoxin h).

In response to changes in the external environment cells must initiate a coordinated program of gene expression for them to adapt. IEX-1 (immediate early response gene X-1) is precisely regulated by multiple transcription factors among which p53, NF-kappaB/rel, Sp1 and c-Myc play central roles, to ensure rapid and transient expression of IEX-1 in cells under a variety of stress conditions. Overexpression of IEX-1 renders some cells sensitive to apoptosis and accelerates cell cycle progression, but reduces proliferation of other cells, whereas disruption of IEX-1 expression is associated with decreases in both apoptosis and cell cycle progression. In sharp contrast to in vitro studies, in vivo constitutive expression of IEX-1 prevents activated T cells but not B cells from apoptosis, as shown using IEX-1-transgenic mice that target IEX-1 expression specifically to lymphocytes driven by the Emu enhancer. The animals developed a lupus-like disease and subsequently a high incidence of T cell lymphomas when they aged, due to insufficient apoptosis of T cells. These varied effects of IEX-1 on cell death and cell cycle progression in a cell-context dependent fashion implicate that IEX-1 is involved in more than one signaling pathway, understanding of which will certainly improve our knowledge with respect to cancer biology, cell death and cell cycle regulation.

A purification procedure which yields a near homogenous preparation of phosphoenolpyruvate (PEP) carboxylase from the leaves of Zea mays is reported. The enzyme had a final specific activity of 33.3 micromoles per minute per milligram protein. Size exclusion high performance liquid chromatography and dynamic laser-light scattering spectroscopy showed that PEP carboxylase exists in an equilibrium of aggregates. Enzyme predominantly in the dimeric configuration is less active (when assayed at sub-optimal Mg-PEP concentrations, less than 0.4 millimolar) than when in its tetrameric arrangement. The difference in activity diminishes and disappears as the concentration of the substrate Mg-PEP increases. The substrate drives the equilibrium toward the tetramer, while malate, an inhibitor of PEP carboxylase, shifts the equilibrium toward the dimer. It thus appears that the quaternary structure (oligomeric state) of maize PEP carboxylase can be regulated by the naturally occurring effector molecules Mg-PEP and malate which in turn can control the enzyme's activity.