ABSTRACT
Developing highly efficient electrocatalysts for hydrogen oxidation reaction (HOR) under alkaline media is essential for the commercialization of alkaline exchange membrane fuel cell (AEMFC). However, the kinetics of HOR in alkaline media is complicated, resulting in orders of magnitude slower than that in acid, even for the state-of-the-art Pt/C. Here, we find that Ru-Ru2 P/C heterostructure shows HOR performance with a non-monotonous variation in a whole pH region. Unexpectedly, an inflection point located at pH≈7 is observed, showing an anomalous behavior that HOR activity under alkaline media surpasses acidic media. Combining experimental results and theoretical calculations, we propose the roles of discrepant reactive intermediates for pH-universal HOR, while H* and H2 O* adsorption strengths are responsible for acidic HOR, and OH* adsorption strength is essential for alkaline HOR. This work not only sheds light on fundamentally understanding the mechanism of HOR but also provides new designing principles for pH-targeted electrocatalysts.
ABSTRACT
Despite recent advances in diagnosis and treatment, osteosarcoma remains as the most common bone cancer in children and is associated with poor prognosis. Growing evidence has supported dysregulation of threonine and tyrosine protein kinase (TTK) expression as a hallmark of multiple cancers, however, its function in osteosarcoma remains to be elucidated. In the present study, we found that TTK was frequently overexpressed in osteosarcoma and associated with increased tumour growth and progression. Moreover, using both in vitro and in vivo assays, we provided evidence that TTK level was regulated by a molecular chaperone, heat shock protein 90 (Hsp90). Hsp90 directly interacted with TTK and prevents proteasome-dependent TTK degradation, leading to the accumulation of TTK in osteosarcoma cells. Elevated TTK promoted cancer cell proliferation and survival by activating cell-cycle progression and inhibiting apoptosis. Consistently, depletion of TTK by Hsp90 inhibition induced cell-cycle arrest, generated aneuploidy and eventually resulted in apoptotic cancer cell death. Together, our study revealed an important Hsp90-TTK regulatory axis in osteosarcoma cells to promote cancer cell growth and survival. These findings expand our knowledge on osteosarcoma pathogenesis and offer novel therapeutic options for clinical practice.
Subject(s)
Carcinogenesis , Gene Expression Regulation, Neoplastic/physiology , HSP90 Heat-Shock Proteins/metabolism , Osteosarcoma/enzymology , Protein-Tyrosine Kinases/metabolism , Animals , Apoptosis , Cell Line, Tumor , Female , Gene Expression Regulation, Enzymologic/physiology , HSP90 Heat-Shock Proteins/genetics , Humans , Mice , Neoplasms, Experimental , Osteosarcoma/genetics , Osteosarcoma/metabolism , Protein-Tyrosine Kinases/geneticsABSTRACT
OBJECTIVE: The purpose of this study was to investigate the effect of overexpression of transforming growth factor ß1 (TGF-ß1) and stromal cell-derived factor 1 (SDF-1) in cervical cancer-associated fibroblasts (CAFs) on regulating cell growth, invasion and migration. METHODS: CAF cells and normal fibroblast cells (NFs) were obtained from patients with cervical squamous cell carcinoma and multiple uterine leiomyomas, respectively. Immunofluorescence assay and western blot were used to determine the expression of Vimentin and α-smooth muscle actin (α-SMA). CCK-8 assay was used to detect cell viability. Giemsa dyer was used to detect the colony formation. Flow cytometry was used to detect the growth state of cells. Transwell assays were used to detect the migration and invasion. RESULTS: Vimentin and α-SMA expression in CAFs were significantly increased than those in NFs. In addition, TGF-ß1 and SDF-1 expression were notably increased, and transforming growth factor beta receptor 2 (TßRII) expression was markedly decreased in CAF cells than those in NFs. Similarly, TGF-ß1 and SDF-1 expression in the co-culture of CAFs and Hela cells were significantly increased, and cell proliferation, migration, invasion, colony formation and cell cycle progression were also promoted, while cell apoptosis was decreased. Those phenomena were reversed in the co-culture system with neutralizing antibodies to TGF-ß1 and SDF-1. Furthermore, exogenous TGF-ß1 and SDF-1 enhanced proliferation, colony formation, cell cycle progression, migration and invasion while decreased apoptosis of cells. These phenomena were also reversed by the addition of neutralizing antibodies to TGF-ß1 and SDF-1. CONCLUSION: Overexpression of TGF-ß1 and SDF-1 in CAFs can promote the growth, invasion and migration of cervical cancer cells.
Subject(s)
Cancer-Associated Fibroblasts , Neoplasms , Cancer-Associated Fibroblasts/metabolism , Cell Cycle , Cell Movement , Cell Proliferation , Chemokine CXCL12 , Fibroblasts/metabolism , Fibroblasts/pathology , HeLa Cells , Humans , Transforming Growth Factor beta1/metabolismABSTRACT
BACKGROUND: Hepatoblastoma (HB) is a common primary malignant liver tumour in children, mainly treated by means of traditional chemotherapy using platinum and doxorubicin (ADM). There has been limited progress in the research and development of new drugs for treating HB. METHODS: A tumour biopsy from a child with HB was implanted into immunodeficient mice. The primary tumour and patient-derived xenograft (PDX) tumour were extensively characterised by histology, immunohistochemistry (IHC), and humanisation identification. We used the PDX model to evaluate the anti-tumour effects of anlotinib oxaliplatin (L-OHP) and sorafenib on childhood HB. RESULTS: The established PDX model maintained the histological characteristics of the primary tumour. Anlotinib, L-OHP, and sorafenib can significantly inhibit the tumour growth in the PDX model. There was no obvious damage of the drugs to the heart, liver and kidney of the mice, and the side effects observed were light. CONCLUSION: We have successfully established a PDX model of childhood HB. The model retains important molecular characteristics of human primary tumours. Using the model, it was found that anlotinib, L-OHP, and sorafenib have a good inhibitory effect on the growth of childhood HB. This provides a preliminary research basis for the clinical application of the drugs.
Subject(s)
Hepatoblastoma , Liver Neoplasms , Animals , Hepatoblastoma/drug therapy , Heterografts , Humans , Indoles , Liver Neoplasms/drug therapy , Mice , Oxaliplatin , Quinolines , SorafenibABSTRACT
Vertical van der Waals heterojunctions (HJs) composed of a photocatalytic star material BiOCl monolayer and group-IV Xene monolayer (silicene, germanene etc.) were studied by using first-principles calculations. Formation energy analysis and molecular dynamics simulation show that the BiOCl/Xene bilayer HJs can exist stably up to room temperature. Owing to evident charge redistribution and accumulation occurring between the bilayers, electron-hole puddles form and charge carrier transfer and separation occur in the HJs, which are beneficial to the improvement of photocatalytic performance. The HJ energy bands maintain the Dirac cones with almost linear dispersion curves, suggesting low effective mass and high mobility of carriers, and can be effectively tuned by strain. Our results show that the BiOCl/Xene bilayer HJs with high separation efficiency and high mobility of carriers and strain-adjustable bandgaps provide varieties in the functionalities of 2D van der Waals HJs and show great potentials in photocatalytic applications.
ABSTRACT
PURPOSE: To compare United States and international drug pricing for commonly prescribed intravitreal and topical ophthalmic medications. DESIGN: Cross-sectional observational study. METHODS: For 25 commonly used ophthalmic medications (3 intravitreal, 22 topical), we obtained 2017 third quarter United States average wholesale price (AWP), drug acquisition cost, or consumer pricing through United States government health insurance plans (Veterans Affairs [VA], Medicaid, Medicare Part B, and Medicare Part D) and commercial drug plans (CVS Caremark and Navitus Health Solutions), online pricing without insurance through a large United States warehouse retailer (Costco), and international drug pricing through government-sponsored health plans in Italy, Spain, Turkey, Canada, and Japan. MAIN OUTCOME MEASURES: Drug acquisition costs and consumer pricing of ophthalmic drugs through various payment systems. All prices were converted to United States dollars. RESULTS: For intravitreal medications in the United States, aflibercept and ranibizumab were priced similarly to each other and were more expensive than dexamethasone implants. Pricing of aflibercept and ranibizumab through government health insurance plans in Italy, Spain, Turkey, Canada, and Japan were less expensive by as much as 84.3% compared with the United States. For topical medications in the United States, pricing varied significantly both across different classes of medications and also between nonbranded and branded medications. Drug acquisition costs through the VA and Medicaid were inexpensive on average, but pricing through a hospital-employee drug insurance plan offered the smallest range (between $2.35 and $60.00). In all 5 non-United States countries studied, each topical medication with the exceptions of cyclosporine emulsion and difluprednate was less than $100, and 94.4% of topical medications in these countries had a nonbranded or branded option that was less than $50. CONCLUSIONS: In the United States, for topical more than intravitreal medications, significant price variation exists across both different drug pricing systems and different medications. Price differentials between nonbranded and branded medications can be significant. Internationally, topical medications exhibited a more limited and lower price range compared with drug pricing in the United States.
Subject(s)
Angiogenesis Inhibitors/economics , Anti-Inflammatory Agents/economics , Drug Costs , Eye Diseases/drug therapy , Costs and Cost Analysis , Cross-Sectional Studies , Dexamethasone , Europe , Humans , Ranibizumab , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , United StatesABSTRACT
BACKGROUND: The survival of patients with acute myeloid leukemia (AML) with t(8;21) was reported to be shorter in China than in other countries. PATIENTS: We analyzed the correlation between different cytarabine (Ara-c) regimens and outcome in 255 t(8;21) AML patients in China who received postremission consolidation chemotherapy only. RESULTS: The 5-year overall survival (OS) of the high-dose Ara-c group (HDAC; 2≤ Ara-c ≤3 g/m2), intermediate-dose Ara-c group (MDAC; 1.0≤ Ara-c <2.0 g/m2), low-dose Ara-c group (LDAC; 0.2< Ara-c <1.0 g/m2) and standard-dose Ara-c group (SDAC; 0.1≤ Ara-c ≤0.2 g/m2) were 65.3, 39.4, 25.2 and 27.9%, respectively (p = 0.003). In the HDAC group, but not in the MDAC group, the 5-year OS of patients who achieved 3-4 cycles of chemotherapy was superior to those who underwent 1-2 cycles (84.4 vs. 43.6%, p < 0.05), and the 3-year OS of patients who achieved an accumulated 36 g/m2 of Ara-c was significantly higher compared to those who did not (85.3 vs. 39.2%, p < 0.05). Multivariate analysis indicated that factors such as WBC >3.5 × 109/l, PLT ≤30 × 109/l, and extramedullary infiltration were associated with a poor prognosis. CONCLUSION: The survival of t(8;21) AML patients treated with high-dose Ara-c (≥2 g/m2) was superior to other dose levels in postremission consolidation chemotherapy. Patient survival was improved by 3-4 cycles of chemotherapy with an accumulated concentration of 36 g/m2 of Ara-c. WBC >3.5 × 109/l, PLT ≤30 × 109/l and extramedullary infiltration could be indicative of a poor clinical prognosis.
Subject(s)
Cytarabine/administration & dosage , Remission Induction , Adult , Antineoplastic Combined Chemotherapy Protocols , China , Humans , Leukemia, Myeloid, Acute/chemically induced , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: To calculate the association between Medicare payment and service volume for 6 commonly performed glaucoma procedures. DESIGN: Retrospective, longitudinal database study. SUBJECTS: A 100% dataset of all glaucoma procedures performed on Medicare Part B beneficiaries within the United States from 2005 to 2009. METHODS: Fixed-effects regression model using Medicare Part B carrier data for all 50 states and the District of Columbia, controlling for time-invariant carrier-specific characteristics, national trends in glaucoma service volume, Medicare beneficiary population, number of ophthalmologists, and income per capita. MAIN OUTCOME MEASURES: Payment-volume elasticities, defined as the percent change in service volume per 1% change in Medicare payment, for laser trabeculoplasty (Current Procedural Terminology [CPT] code 65855), trabeculectomy without previous surgery (CPT code 66170), trabeculectomy with previous surgery (CPT code 66172), aqueous shunt to reservoir (CPT code 66180), laser iridotomy (CPT code 66761), and scleral reinforcement with graft (CPT code 67255). RESULTS: The payment-volume elasticity was nonsignificant for 4 of 6 procedures studied: laser trabeculoplasty (elasticity, -0.27; 95% confidence interval [CI], -1.31 to 0.77; P = 0.61), trabeculectomy without previous surgery (elasticity, -0.42; 95% CI, -0.85 to 0.01; P = 0.053), trabeculectomy with previous surgery (elasticity, -0.28; 95% CI, -0.83 to 0.28; P = 0.32), and aqueous shunt to reservoir (elasticity, -0.47; 95% CI, -3.32 to 2.37; P = 0.74). Two procedures yielded significant associations between Medicare payment and service volume. For laser iridotomy, the payment-volume elasticity was -1.06 (95% CI, -1.39 to -0.72; P < 0.001): for every 1% decrease in CPT code 66761 payment, laser iridotomy service volume increased by 1.06%. For scleral reinforcement with graft, the payment-volume elasticity was -2.92 (95% CI, -5.72 to -0.12; P = 0.041): for every 1% decrease in CPT code 67255 payment, scleral reinforcement with graft service volume increased by 2.92%. CONCLUSIONS: This study calculated the association between Medicare payment and service volume for 6 commonly performed glaucoma procedures and found varying magnitudes of payment-volume elasticities, suggesting that the volume response to changes in Medicare payments, if present, is not uniform across all Medicare procedures.
Subject(s)
Filtering Surgery/statistics & numerical data , Glaucoma/surgery , Health Care Costs/statistics & numerical data , Medicare Part B/economics , Ophthalmology/statistics & numerical data , Aged , Databases, Factual , Female , Follow-Up Studies , Glaucoma Drainage Implants/statistics & numerical data , Health Services Research , Humans , Iridectomy/statistics & numerical data , Laser Coagulation/statistics & numerical data , Male , Practice Patterns, Physicians'/statistics & numerical data , Retrospective Studies , Trabeculectomy/statistics & numerical data , United StatesABSTRACT
PURPOSE: To calculate the relationship between Medicare payment and service volume for the 3 highest-volume retina procedures: intravitreal injection (Current Procedural Terminology [CPT] code 67028), laser treatment for retinal edema (CPT code 67210), and laser treatment for proliferative retinopathy (CPT code 67228). DESIGN: Retrospective, longitudinal database study. PARTICIPANTS: One hundred percent dataset of all retina procedures performed on Medicare Part B beneficiaries within the United States from 2005 through 2009. METHODS: Fixed-effects regression model using Medicare Part B carrier data for all 50 states and the District of Columbia, controlling for time-invariant carrier-specific characteristics, national trends in service volume, Medicare beneficiary population, number of ophthalmologists, and income per capita. MAIN OUTCOME MEASURES: Medicare payment-service volume elasticities, defined as the percent change in service volume per 1% change in Medicare payment, for intravitreal injection, laser treatment for retinal edema, and laser treatment for proliferative retinopathy. RESULTS: For all 3 retina procedures, the regression coefficients representing the Medicare payment-service volume elasticity were nonsignificant: intravitreal injection elasticity, -0.75 (95% confidence interval [CI], -1.62 to 0.13; P = 0.09); laser treatment for retinal edema elasticity, 0.14 (95% CI, -0.38 to 0.65; P = 0.59); and laser treatment for proliferative retinopathy elasticity, 0.05 (95% CI, -0.26 to 0.35; P = 0.77). CONCLUSIONS: This study found no evidence suggesting that there is an association between Medicare payment and service volume for the 3 highest-volume retina procedures from 2005 through 2009.
Subject(s)
Health Care Costs/statistics & numerical data , Intravitreal Injections/statistics & numerical data , Laser Coagulation/statistics & numerical data , Medicare Part B/economics , Practice Patterns, Physicians'/statistics & numerical data , Aged , Angiogenesis Inhibitors/economics , Current Procedural Terminology , Female , Follow-Up Studies , Health Expenditures , Humans , Macular Degeneration/drug therapy , Macular Edema/surgery , Male , Retinal Neovascularization/surgery , Retrospective Studies , United StatesABSTRACT
The proliferation and high plasticity of vascular smooth muscle cells (vSMCs) are the major reasons for restenosis of vein grafts. N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), specific inhibitor of γ-secretase, has been shown to regulate vSMC proliferation and differentiation through the Notch signaling pathway, but the pathophysiological importance of these findings in venous grafts has not yet been determined. A rat vein graft model was employed wherein the left jugular vein was surgically interposed into the left common carotid artery. Daily subcutaneous injections of DAPT or placebo (DMSO) were administered postoperatively (control animals received no treatment). We showed that DAPT can inhibit restenosis of vein grafts by inhibiting vSMC proliferation and increasing apoptosis in vivo. Notch1 signaling was highly active during the development of intima thickening. By blocking the Notch signaling pathway, the γ-secretase inhibitor DAPT can significantly attenuated intima thickening. These changes in vein grafts coincided with enhanced binding of myocardin to the smooth muscle-specific protein SM22 and smooth muscle myosin heavy chain at the promoters of vSMC differentiation-specific genes. These studies showed that DAPT can restore the vSMC phenotype and inhibit vSMC proliferation through suppression of the Notch1 signaling pathway, and thus opens a new avenue for the treatment of restenosis in vein grafts.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Blood Vessel Prosthesis , Dipeptides/pharmacology , Hyperplasia/metabolism , Receptor, Notch1/metabolism , Tunica Intima/drug effects , Animals , Cell Proliferation/drug effects , Cells, Cultured , Hyperplasia/pathology , Male , Muscle, Smooth, Vascular/cytology , Phenotype , Rats , Rats, Wistar , Signal Transduction/drug effects , Tunica Intima/metabolism , Tunica Intima/pathologyABSTRACT
OBJECTIVE: Notch signaling has been implicated in the development of pulmonary arterial hypertension (PH) as reflected by increased expression of Notch member proteins that induce the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Soluble Jagged1 (sJag1) has been shown to inhibit Notch signaling in vitro and in vivo; however, its capacity to suppress PH remains unknown. APPROACH AND RESULTS: Notch1, Notch3, Jagged1, and Herp2 protein were highly expressed in both the mouse model of hypoxia-induced PH and the rat model of monocrotaline-induced PH. By attenuation and reversal of multiple pathological processes that were associated with PH, adenoviral sJag1 transfection significantly reduced the proliferation and enhanced the apoptosis of PASMCs in PH, whereas vehicle had no effect. The sJag1 inhibitory effect on Notch activation is likely related to its interference with ligand-induced signaling. Importantly, the administration with adenoviral sJag1 improved the survival rate of PH rats. Furthermore, sJag1 can restore the PH-PASMCs phenotype from the dedifferentiated to the differentiated state, by giving a positive effect on the physical binding of myocardin to the CC(A/T)nGG (CArG)-containing regions of vascular smooth muscle cells-specific promoters. CONCLUSIONS: Our results demonstrated that the potential therapeutic use of the sJag1 may not only inhibit the proliferation of PASMCs but also restore the PH-PASMCs phenotype from the dedifferentiated to the differentiated state through interference with Notch-Herp2 signaling.
Subject(s)
Calcium-Binding Proteins/metabolism , Genetic Therapy , Hypertension, Pulmonary/prevention & control , Intercellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Receptors, Notch/metabolism , Signal Transduction , Adenoviridae/genetics , Animals , Binding Sites , Calcium-Binding Proteins/genetics , Cell Differentiation , Cell Proliferation , Cells, Cultured , Disease Models, Animal , Genetic Therapy/methods , Genetic Vectors , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/pathology , Hypoxia/complications , Intercellular Signaling Peptides and Proteins/genetics , Jagged-1 Protein , Male , Membrane Proteins/genetics , Mice, Inbred C57BL , Monocrotaline , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , Nuclear Proteins/metabolism , Phenotype , Promoter Regions, Genetic , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Rats , Rats, Sprague-Dawley , Receptor, Notch1/metabolism , Receptor, Notch3 , Serrate-Jagged Proteins , Time Factors , Trans-Activators/metabolism , Transduction, Genetic , TransfectionABSTRACT
PURPOSE: To assess the feasibility of routine use of electromagnetic image guidance systems in orbital decompression. METHODS: Six consecutive patients underwent stereotactic-guided three wall orbital decompression using the novel Fusion ENT Navigation System (Medtronic), a portable and expandable electromagnetic guidance system with multi-instrument tracking capabilities. The system consists of the Medtronic LandmarX System software-enabled computer station, signal generator, field-generating magnet, head-mounted marker coil, and surgical tracking instruments. In preparation for use of the LandmarX/Fusion protocol, all patients underwent preoperative non-contrast CT scan from the superior aspect of the frontal sinuses to the inferior aspect of the maxillary sinuses that includes the nasal tip. RESULTS: The Fusion ENT Navigation System (Medtronic™) was used in 6 patients undergoing maximal 3-wall orbital decompression for Graves' orbitopthy after a minimum of six months of disease inactivity. Preoperative Hertel exophthalmometry measured more than 27 mm in all patients. The navigation system proved to be no more difficult technically than the traditional orbital decompression approach. CONCLUSION: Electromagnetic image guidance is a stereotactic surgical navigation system that provides additional intraoperative flexibility in orbital surgery. Electromagnetic image-guidance offers the ability to perform more aggressive orbital decompressions with reduced risk.
Subject(s)
Decompression, Surgical/methods , Electromagnetic Phenomena , Exophthalmos/surgery , Graves Disease/surgery , Surgery, Computer-Assisted/methods , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Orbit/surgery , Retrospective StudiesABSTRACT
Objective: In the domain of competitive events, Latin dance athletes have always suffered competitive anxiety, which is a prevalent and prevailing psychological facet, in pre-, intra-, and post-competitive engagements. Usually, the implementation of systematic desensitization training is an efficacious approach to reduce competitive anxiety levels in routine sports to fortify psychological resilience of athletes (like swimming, volleyball, and basketball). This study focuses on the effect of systematic desensitization training on competition anxiety in the training of Latin dancers to establish good mental ability and promote the competitive ability of athletes. Methodology: The "Sports Competition Anxiety Test Questionnaire" was used to evaluate and classify the competitive anxiety levels of 150 Latin dance athletes. Then, the top 48 participants were selected (24 in the intervention cohort and 24 in the non-intervention cohort) as the study participants after stratifying anxiety score levels from the highest to the lowest. The intervention group was treated with an 8-week psychological intervention by employing systematic desensitization training techniques (encompassing imagery desensitization and in vivo desensitization). The anxiety levels of the subjects were quantified by employing the "Sport Competition Trait Anxiety Inventory" (CCTAI-C) and the "Competitive State Anxiety Inventory" (CSAI-2) to scrutinize the efficacy of systematic desensitization training in regulating competitive anxiety levels among Latin dance athletes. Results: After applying systematic desensitization training, the intervention group displayed a notable reduction in sport cognitive trait anxiety. Specifically, there was a decrease of 29.37% in social evaluation anxiety, 20.31% in competition preparation anxiety, 16.98% in performance anxiety, 25.16% in failure anxiety, 34.47% in opponent's ability anxiety, and 25.16% in injury anxiety. Moreover, for competitive state anxiety, cognitive state anxiety and somatic state anxiety decreased by 39.19 and 21.43%. The state self-confidence increased by 14.42%. Conclusion: The result indicated that systematic desensitization training not only mitigates anxiety but also positively intervenes in sports-related anxiety. Moreover, systematic desensitization training can significantly diminish competitive anxiety among Latin dance athletes to bolster confidence during competitions. Integrating desensitization training into the regular regimen of Latin dance practice has the potential to fortify dancers' psychological resilience against anxiety.
ABSTRACT
BACKGROUND: Recent studies reported that terminal nucleotidyltransferase 5A (TENT5A) is highly expressed in glioblastoma and associated with poor prognosis. In this work, we aim to specify the expression level of TENT5A in different grades of glioma and explore its role in glioma progression. METHODS: GEPIA online tools were used to perform the bioinformatic analysis. qRT-PCR, Western blot, and Immunohistochemistry were performed in glioma cells or tissues. Furthermore, CCK8, colony formation, transwell, flow cytometry and scratch assays were performed. RESULTS: TENT5A was highly expressed in glioma and its level was associated with the pathological grade of glioma. Knockdown of TENT5A suppressed cell proliferation, colony formation ability, cell invasion and migration. Overexpression of TENT5A was lethal to the glioma cells. CONCLUSION: Our data showed that the expression of TENT5A is associated with the pathological grade of glioma. Knockdown of TENT5A decreased the ability of proliferation, invasion and migration of glioma cells. High levels of TENT5A in glioma cells are lethal. Therefore, TENT5A could be a new target for glioma treatment.
ABSTRACT
Black gram (Vigna mungo (L.) Hepper) is a pulses crop with good digestible protein and a high carbohydrate content, so it is widely consumed as human food and animal feed. Trichomes are large, specialized epidermal cells that confer advantages on plants under biotic and abiotic stresses. Genes regulating the development of trichomes are well characterized in Arabidopsis and tomato. However, little is known about trichome development in black gram. In this study, a high-density map with 5734 bin markers using an F2 population derived from a trichome-bearing and a glabrous cultivar of black gram was constructed, and a major quantitative trait locus (QTL) related to trichomes was identified. Six candidate genes were located in the mapped interval region. Fourteen single-nucleotide polymorphisms (SNPs) or insertion/deletions (indels) were associated with those genes. One indel was located in the coding region of the gene designated as Scaffold_9372_HRSCAF_11447.164. Real-time quantitative PCR (qPCR) analysis demonstrated that only one candidate gene, Scaffold_9372_HRSCAF_11447.166, was differentially expressed in the stem between the two parental lines. These two candidate genes encoded the RNA polymerase-associated protein Rtf1 and Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A). These results provide insights into the regulation of trichome development in black gram. The candidate genes may be useful for creating transgenic plants with improved stress resistance and for developing molecular markers for trichome selection in black gram breeding programs.
Subject(s)
Vigna , Animals , Humans , Vigna/genetics , Trichomes/genetics , Plant Breeding , Quantitative Trait Loci , Genes, Plant , Bromodomain Containing Proteins , Chromosomal Proteins, Non-Histone/geneticsABSTRACT
Rice bean [Vigna umbellata (Thunb.) Ohwi and Ohashi], an annual legume in the genus Vigna, is a promising crop suitable for cultivation in a changing climate to ensure food security. It is also a medicinal plant widely used in traditional Chinese medicine; however, little is known about the medicinal compounds in rice bean. In this study, we assessed the diuretic effect of rice bean extracts on mice as well as its relationship with the contents of eight secondary metabolites in seeds. Mice gavaged with rice bean extracts from yellow and black seeds had higher urinary output (5.44-5.47 g) and water intake (5.8-6.3 g) values than mice gavaged with rice bean extracts from red seeds. Correlation analyses revealed significant negative correlations between urine output and gallic acid (R = -0.70) and genistein (R = -0.75) concentrations, suggesting that these two polyphenols negatively regulate diuresis. There were no obvious relationships between mice diuresis-related indices (urine output, water intake, and weight loss) and rutin or catechin contents, although the concentrations of both of these polyphenols in rice bean seeds were higher than the concentrations of the other six secondary metabolites. Our study findings may be useful for future research on the diuretic effects of rice bean, but they should be confirmed on the basis of systematic medical trials.
Subject(s)
Diuretics , Polyphenols , Seeds , Animals , Mice , Diuretics/pharmacology , Seeds/chemistry , Polyphenols/pharmacology , Polyphenols/analysis , Male , Plant Extracts/pharmacology , Vigna/chemistry , Gallic Acid/pharmacology , Genistein/pharmacology , Catechin/pharmacology , Catechin/analysis , Rutin/pharmacology , Rutin/analysis , Diuresis/drug effectsABSTRACT
Purpose: We examined the performance of artificial intelligence chatbots on the PREview Practice Exam, an online situational judgment test for professionalism and ethics. Methods: We used validated methodologies to calculate scores and descriptive statistics, χ2 tests, and Fisher's exact tests to compare scores by model and competency. Results: GPT-3.5 and GPT-4 scored 6/9 (76th percentile) and 7/9 (92nd percentile), respectively, higher than medical school applicant averages of 5/9 (56th percentile). Both models answered 95 + % of questions correctly. Conclusions: Chatbots outperformed the average applicant on PREview, suggesting their potential for healthcare training and decision-making and highlighting risks of online assessment delivery.