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1.
Phytochem Anal ; 35(5): 1036-1051, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38487966

RESUMEN

INTRODUCTION: Fructus Tribuli, the dried ripe fruit of Tribulus terrestris L., has various beneficial effects, including liver-calming and depression-relieving effects. Raw Fructus Tribuli (RFT) and stir-fried Fructus Tribuli (SFT) are included in the Chinese Pharmacopoeia 2020 edition (Ch. P 2020). However, owing to the lack of specific regulations on SFT-processing parameters in Ch. P 2020, it is difficult to ensure the quality of commercially available SFT. OBJECTIVE: The present study aimed to screen the quality markers (Q-markers) of RFT and SFT and optimize the processing technology of SFT based on the identified Q-markers. METHODS: First, the ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) technology as well as multiple statistical analysis along with network pharmacology was used to comprehensively identify the Q-markers of RFT and SFT. Then, based on single-factor experiments, the Box-Behnken design (BBD) response surface methodology (RSM) was used to optimize the processing technology of SFT and perform process validation. RESULTS: A total of 63 components were identified in RFT and SFT extracts. Terrestrosin D and Terrestrosin K were initially considered the Q-markers of RFT and SFT, respectively. The optimum processing technology conditions were 208°C, 14 min, and 60 r·min-1. Three batches of process validation were performed, and the mean composite score was 56.87, with a relative standard deviation (RSD) value of 1.13%. CONCLUSION: The content of steroidal saponin components in RFT was significantly different before and after stir-frying. Terrestrosin D and Terrestrosin K were validated as the Q-markers of RFT and SFT, respectively. The identification of Q-markers for RFT and SFT offered a clear index for optimizing the SFT-processing technology and provided a basis for the quality control of RFT and SFT decoction pieces.


Asunto(s)
Farmacología en Red , Tribulus , Cromatografía Líquida de Alta Presión/métodos , Tribulus/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/normas , Quimiometría/métodos , Espectrometría de Masas/métodos , Frutas/química , Control de Calidad
2.
Invest New Drugs ; 41(1): 44-52, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36355317

RESUMEN

The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Receptores ErbB/genética
3.
BMC Cardiovasc Disord ; 23(1): 156, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-36973644

RESUMEN

BACKGROUND AND OBJECTIVES: Real-time blood flow variation is crucial for understanding the dynamic development of coronary atherosclerosis. The main objective of this study is to investigate the effect of varying extent of stenosis on the hemodynamic features in left anterior descending coronary artery. METHODS: Various Computational fluid dynamics (CFD) models were constructed with patient-specific CT image data, using actual fractional flow reserve (FFR) as boundary conditions to provide a real-time quantitative description of hemodynamic properties. The hemodynamic parameters, such as the local and instantaneous wall shear stress (WSS), oscillating shear index (OSI) and relative residence time (RRT), blood flow velocity and pressure drop during various phases of cardiac cycle were provided in detail. RESULTS: There was no evident variation in hemodynamic parameters in the cases of less than 50% stenosis while there were abrupt and dramatic changes in hemodynamics when the stenosis aggravated from 60 to 70%. Furthermore, when the stenosis was beyond 70%, there existed substantial pressure difference, WSS, and blood flow velocity in the center of the stenosis. Although OSI and RRT increased along with the aggravation of stenosis, they appeared with obvious abnormalities across all cases, even in mild stenosis. CONCLUSION: The simulation could present a dynamic and comprehensive profile of how hemodynamic parameters vary in accordance with divergent severities of stenosis, which could serve as an effective reference for the clinicians to have a deeper insight into the pathological mechanism of coronary atherosclerosis and stenosis.


Asunto(s)
Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Vasos Coronarios , Constricción Patológica , Modelos Cardiovasculares , Hemodinámica , Velocidad del Flujo Sanguíneo , Estrés Mecánico
4.
Entropy (Basel) ; 25(11)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37998204

RESUMEN

Compute-and-Forward (CoF) is an innovative physical layer network coding strategy, designed to enable receivers in wireless communications to effectively utilize interference. The key idea of CoF is to implement integer combinations based on the codewords from multiple transmitters, rather than decoding individual source codewords. Although CoF is widely used in wireless relay networks, there are still some problems to be solved, such as rank failure, single antenna reception, and the shortest vector problem. In this paper, we introduce a successive extended CoF (SECoF) as a pioneering solution tailored for multi-source, multi-relay, and multi-antenna wireless relay networks. First, we analyze the traditional CoF, and design a SECoF method combining the concepts of matrix projection and successive interference cancellation, which overcomes the problem of CoF rate tending to zero and rank failure and improves the network performance. Secondly, we obtain an approximate solution to the integer-value coefficient vectors by using the LLL lattice-based resolution algorithm. In addition, we deduce the corresponding concise formulas of SECoF. Simulation results show that the SECoF has strong robustness and the approaches outperform the state-of-the-art methods in terms of computation rate, rank failure probability, and outage probability.

5.
Zhonghua Nan Ke Xue ; 29(3): 269-274, 2023 Mar.
Artículo en Zh | MEDLINE | ID: mdl-38597710

RESUMEN

Long non-coding RNA (lncRNA) is an RNA molecule transcribed by RNA polymerase II, longer than 200 nt, and not translated into proteins. During gonadal development and spermatogenesis, lncRNAs are involved in epigenetic mechanisms, including DNA methylation, chromatin remodeling, and histone tail modification, which play important regulatory roles at the transcriptional or post-transcriptional level. Epigenomics including lncRNA is considered to be the second dimension of DNA sequence that can be adapted to environmental factors to specifically regulate gene expressions in some cells. Based on the functional action mechanism of lncRNAs, we reviewed the advances in the studies of lncRNAs in the direction of spermatogenesis and male infertility and analyzed the potential of lncRNAs as a biomarker of male infertility. The potential application of lncRNA in the treatment of male infertility diseases can be further explored based on the lncRNA target, RNA interference, competitive binding closed target and structural disruption of lncRNAs.


Asunto(s)
Infertilidad Masculina , ARN Largo no Codificante , Masculino , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Espermatogénesis/genética , Epigénesis Genética , Metilación de ADN , Infertilidad Masculina/genética
6.
Angew Chem Int Ed Engl ; 62(44): e202312170, 2023 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-37710398

RESUMEN

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi-autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi-targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano-encapsulated system for tail vein administration also features a good anti-tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down-regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi-dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi-targeted Pt complex that can trigger Golgi stress-mediated dual-regulation of autophagic flux and autophagy-apoptosis crosstalk for highly efficient cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias , Platino (Metal)/farmacología , Autofagia , Aparato de Golgi/metabolismo , Cisplatino/farmacología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/metabolismo , Neoplasias/metabolismo
7.
Org Biomol Chem ; 20(10): 2096-2101, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35195125

RESUMEN

A modular and generic method for the Buchwald-Hartwig amination reactions of relatively unreactive aryl esters as acyl electrophiles and aryl chlorides as aryl electrophiles has been developed, leading to the efficient synthesis of amides/amines under air conditions and with low catalyst loadings. The success of this catalytic protocol is mainly attributed to the modification of the Pd-IPr skeleton with sterically hindered and electron-donating anisole groups. This method also features good functional group tolerance and excellent chemoselectivities. In summary, the results presented herein suggest the possibility of developing a versatile and general protocol for diverse electrophiles to undergo the Buchwald-Hartwig amination reactions, avoiding too much consideration of the reaction conditions for the substrate-dependent C-N bond formations.

8.
Entropy (Basel) ; 24(6)2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35741496

RESUMEN

Recently, deep neural network-based image compressed sensing methods have achieved impressive success in reconstruction quality. However, these methods (1) have limitations in sampling pattern and (2) usually have the disadvantage of high computational complexity. To this end, a fast multi-scale generative adversarial network (FMSGAN) is implemented in this paper. Specifically, (1) an effective multi-scale sampling structure is proposed. It contains four different kernels with varying sizes so that decompose, and sample images effectively, which is capable of capturing different levels of spatial features at multiple scales. (2) An efficient lightweight multi-scale residual structure for deep image reconstruction is proposed to balance receptive field size and computational complexity. The key idea is to apply smaller convolution kernel sizes in the multi-scale residual structure to reduce the number of operations while maintaining the receptive field. Meanwhile, the channel attention structure is employed for enriching useful information. Moreover, perceptual loss is combined with MSE loss and adversarial loss as the optimization function to recover a finer image. Numerous experiments show that our FMSGAN achieves state-of-the-art image reconstruction quality with low computational complexity.

9.
Zhonghua Nan Ke Xue ; 28(1): 61-65, 2022 Jan.
Artículo en Zh | MEDLINE | ID: mdl-37459080

RESUMEN

The ubiquitin-proteasome system (UPS) is an adenosine triphosphate (ATP)-dependent enzymatic machinery that targets substrate proteins for degradation by the 26S proteasome by tagging them with an isopeptide chain composed of covalently linked molecules of ubiquitin, a small chaperone protein. UPS is the main pathway of protein degradation in eukaryotic cells, and plays an important role in spermatogenesis. The dysfunction of various ubiquitin systems results in impaired sperm development with abnormal morphology and function, which is highly associated with male infertility. This review focuses on the roles of UPS in histone-to-protamine exchange, acrosome formation, sperm mitochondrial degradation and regulation of sperm function and quality.

10.
Pharmacology ; 106(9-10): 498-508, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34352791

RESUMEN

BACKGROUND: Non-small-cell lung carcinoma is one of the most frequently diagnosed cancers. Cisplatin (CDDP) is a currently applied standard anticancer agent for advanced lung cancers. Although effectively clinical response was achieved initially, a large fraction of lung cancer patients developed cisplatin resistance. Therefore, understanding the molecular mechanisms of chemoresistance is crucial for anti-lung cancer therapy. Long non-coding RNA (lncRNA)-X-inactive-specific transcript (XIST) has been reported to be positively associated with multiple cancers. Currently, the precise role and mechanism of XIST in cisplatin resistance of lung cancer have not been elucidated. METHODS: The expression levels of miR-101-3p and lncRNA XIST were detected by qRT-PCR. Cisplatin-resistant lung cancer cell line was established by selecting the survival cells under gradually increased cisplatin treatments. The cell proliferation was detected by MTT assay, and the cellular glucose metabolism rate was evaluated by Seahorse metabolic flux analysis and glucose uptake and lactate product assays. Glycolysis-related protein expression levels were detected by Western blot. Dual luciferase reporter was constructed to determine the lncRNA-miRNA interaction. RESULTS: Here, we report XIST is significantly upregulated in lung cancer tissues compared with normal lung tissues. In addition, cisplatin-resistant lung cancer cells displayed remarkably elevated XIST expression. We demonstrated that miR-101-3p functioned as a tumor suppressor in lung cancer and sensitized lung cancer cells to cisplatin. Bioinformatics analysis predicted miR-101-3p could be a potential target of XIST through direct binding with it as a competing endogenous RNA, which was further validated from lung tumor tissues and cell lines by luciferase assay. Intriguingly, XIST significantly promoted cellular glycolysis rate of lung cancer cells. The extracellular acidification rate, glucose uptake, and lactate product were elevated by XIST overexpression. On the contrary, miR-101-3p effectively suppressed glycolysis rate. Finally, we demonstrated silencing XIST significantly recovered miR-101-3p expression and downregulated expression of glycolysis key enzymes, a phenotype could be further overridden by miR-101-3p inhibition. CONCLUSIONS: This study reveals a new molecular mechanism for the lncRNA-XIST-promoted cisplatin resistance via sponging miR-101-3p, leading to de-repression of cellular glycolysis. Moreover, these findings warrant further in vivo investigations to study XIST as a potential target to overcome cisplatin resistance.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Resistencia a Antineoplásicos/fisiología , MicroARNs/biosíntesis , ARN Largo no Codificante/biosíntesis , Adulto , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias
11.
Angew Chem Int Ed Engl ; 60(28): 15340-15343, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-33899272

RESUMEN

G-quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4-DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF-G4 (a promoter G4) shows that Pt1 matches 3'-G-tetrad of VEGF-G4 through Cl- -dissociation and loop rearrangement of VEGF-G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate-determining binding step, Cl- -dissociation upon G4-binding, is 2-3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4-binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.


Asunto(s)
Antineoplásicos/farmacología , G-Cuádruplex/efectos de los fármacos , Compuestos Organoplatinos/farmacología , Antineoplásicos/química , Sitios de Unión/efectos de los fármacos , Células HeLa , Humanos , Cinética , Estructura Molecular , Compuestos Organoplatinos/química
12.
J Mol Cell Cardiol ; 138: 115-135, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31783035

RESUMEN

AIMS: There is a large subpopulation of multinucleated polyploid cardiomyocytes (M*Pc CMs) in the adult mammalian heart. However, the pathophysiological significance of increased M*Pc CMs in heart disease is poorly understood. We sought to determine the pathophysiological significance of increased M*Pc CMs during hypoxia adaptation. METHODS AND RESULTS: A model of hypoxia-induced cardiomyocyte (CM) multinucleation and polyploidization was established and found to be associated with less apoptosis and less reactive oxygen species (ROS) production. Compared to mononucleated diploid CMs (1*2c CMs), tetraploid CMs (4c CMs) exhibited better mitochondria quality control via increased mitochondrial autophagy (mitophagy). RNA-seq revealed Prkaa2, the gene for AMPKα2, was the most obviously up-regulated autophagy-related gene. Knockdown of AMPKα2 increased apoptosis and ROS production and suppressed mitophagy in 4c CMs compared to 1*2c CMs. Rapamycin, an autophagy activator, alleviated the adverse effect of AMPKα2 knockdown. Furthermore, silencing PINK1 also increased apoptosis and ROS in 4c CMs and weakened the adaptive superiority of 4c CMs. Finally, AMPKα2-/- mutant mice exhibited exacerbation of apoptosis and ROS production via decreases in AMPKα2-mediated mitophagy in 4c CMs compared to 1*2c CMs during hypoxia. CONCLUSIONS: Compared to 1*2c CMs, hypoxia-induced 4c CMs exhibited enhanced mitochondria quality control and less apoptosis via AMPKα2-mediated mitophagy. These results suggest that multinucleation and polyploidization allow CM to better adapt to stress via enhanced mitophagy. In addition, activation of AMPKα2 may be a promising target for myocardial hypoxia-related diseases.


Asunto(s)
Adaptación Fisiológica , Células Gigantes/patología , Mitofagia , Miocitos Cardíacos/patología , Poliploidía , Adenilato Quinasa/metabolismo , Animales , Animales Recién Nacidos , Apoptosis , Hipoxia de la Célula , Silenciador del Gen , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas Quinasas/metabolismo , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
13.
J Cell Biochem ; 121(8-9): 3814-3824, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31692094

RESUMEN

Non-small cell lung cancer (NSCLC) is the main type of lung malignancy. Early diagnosis and treatments for NSCLC are far from satisfactory due to the limited knowledge of the molecular mechanisms regarding NSCLC progression. Long noncoding RNA (lncRNA) ZNFX1 antisense RNA1 (ZFAS1) has been implicated for its functional role in the progression of malignant tumors. This study aimed to determine the ZFAS1 expression from lung cancer clinical samples and to explore the molecular mechanisms underlying ZFAS1-modulated NSCLC progression. Experimental assays revealed that clinical samples and cell lines of lung malignant tumors showed an upregulation of ZFSA1. ZFAS1 expression was markedly upregulated in the lung tissues from patients with advanced stage of this malignancy. The loss-of-function assays showed that knockdown of ZFAS1-suppressed NSCLC cell proliferative, as well as invasive potentials, increased NSCLC cell apoptotic rates in vitro and also attenuated tumor growth of NSCLC cells in the nude mice. Further experimental evidence showed that ZFAS1 inversely affected miR-150-5p expression and positively affected high-mobility group AT-hook 2 (HMGA2) expression in NSCLC cell lines. MiR-150-5p inhibition or HMGA2 overexpression counteracted the effects of ZFAS1 knockdown on NSCLC cell proliferative, invasive potentials and apoptotic rates. In light of examining the clinical lung cancer samples, miR-150-5p expression was downregulated and the HMGA2 expression was highly expressed in the lung cancer tissues compared with normal ones; the ZFAS1 expression showed a negative correlation with miR-150-5p expression but a positive correlation with HMGA2 expression in lung cancer tissues. To summarize, we, for the first time, demonstrated the inhibitory effects of ZFAS1 knockdown on NSCLC cell progression, and the results from mechanistic studies indicated that ZFAS1-mediated NSCLC progression cells via targeting miR-150-5p/HMGA2 signaling.

14.
Cancer Cell Int ; 20: 350, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32742197

RESUMEN

BACKGROUND: This study aims to investigate the mechanism underlying the high level of long non-coding RNA FOXD3-AS1 in cisplatin-resistant NSCLC cells. METHODS: Cisplatin-resistant cells were generated from A549 cells. CCK-8 were used to evaluate cell proliferation. The FOXD3-AS1, miR-127-3p, MDM2 and MRP1 mRNA expression levels were confirmed by qRT-PCR. Protein levels of MDM2 and MRP1 were determined by western blot assay. Luciferase reporter and RNA pull-down assays were evaluated the relationship between miR-127-3p and FOXD3-AS1/MDM2. In vivo tumor growth was evaluated in a xenograft nude mice model. RESULTS: FOXD3-AS1 was up-regulated in cisplatin-resistant NSCLC cells (A549/DDP and H1299/DDP cells) in comparison with their parental cell lines. Overexpression of FOXD3-AS1 promoted cisplatin-resistance in A549 and H1299 cells; while FOXD3-AS1 knockdown sensitized A549/DDP and H1299/DDP cells to cisplatin treatment. FOXD3-AS1 regulated miR-127-3p expression by acting as a competing endogenous RNA, and miR-127-3p repressed MDM2 expression via targeting the 3'UTR. MiR-127-3p overexpression and MDM2 knockdown both increased the chemo-sensitivity in A549/DDP cells; while miR-127-3p knockdown and MDM2 overexpression both promoted chemoresistance in A549 cells. Further rescue experiments revealed that miR-127-3p knockdown or MDM2 overexpression counteracted the suppressive effects of FOXD3-AS1 knockdown on chemo-resistance and MRP1 expression in A549/DDP cells. In vivo studies showed that FOXD3-AS1 knockdown potentiated the antitumor effects of cisplatin treatment. Inspection of clinical samples showed the upregulation of FOXD3-AS1 and MDM2, and down-regulation of miR-127-3p in NSCLC tissues compared to normal adjacent tissues. CONCLUSION: In conclusion, our results suggest that LncRNA FOXD3-AS1 promotes chemo-resistance of NSCLC cells via directly acting on miR-127-3p/MDM2 axis. Our findings may provide novel perspectives for the treatment of NSCLC in patients resistant to chemotherapy.

15.
J Org Chem ; 85(16): 10719-10727, 2020 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-32664733

RESUMEN

A range of indolizine smoothly underwent visible-light-induced intermolecular [3+2] annulations with internal alkynes to afford pyrrolo[2,1,5-cd]indolizine in good to excellent yields with high regioselectivity. Through this cascade reaction, a series of fluoroactive fused indolizines with a large π-system were conveniently synthesized. The usage of visible light as energy source with air as a stoichiometric oxidant under simple conditions makes this process attractive and practical.

16.
Nucleic Acids Res ; 46(D1): D281-D287, 2018 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-29126312

RESUMEN

Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. A knowledge base with the systematic collection and curation of context specific transcriptome-wide methylations is critical for elucidating their biological functions as well as for developing bioinformatics tools. Since its inception in 2014, the Met-DB (Liu, H., Flores, M.A., Meng, J., Zhang, L., Zhao, X., Rao, M.K., Chen, Y. and Huang, Y. (2015) MeT-DB: a database of transcriptome methylation in mammalian cells. Nucleic Acids Res., 43, D197-D203), has become an important resource for methyltranscriptome, especially in the N6-methyl-adenosine (m6A) research community. Here, we report Met-DB v2.0, the significantly improved second version of Met-DB, which is entirely redesigned to focus more on elucidating context-specific m6A functions. Met-DB v2.0 has a major increase in context-specific m6A peaks and single-base sites predicted from 185 samples for 7 species from 26 independent studies. Moreover, it is also integrated with a new database for targets of m6A readers, erasers and writers and expanded with more collections of functional data. The redesigned Met-DB v2.0 web interface and genome browser provide more friendly, powerful, and informative ways to query and visualize the data. More importantly, MeT-DB v2.0 offers for the first time a series of tools specifically designed for understanding m6A functions. Met-DB V2.0 will be a valuable resource for m6A methyltranscriptome research. The Met-DB V2.0 database is available at http://compgenomics.utsa.edu/MeTDB/ and http://www.xjtlu.edu.cn/metdb2.


Asunto(s)
Adenosina/análogos & derivados , Bases de Datos Genéticas , ARN/metabolismo , Transcriptoma , Adenosina/metabolismo , Animales , Humanos , Metilación , Ratones , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo
17.
Pestic Biochem Physiol ; 167: 104592, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32527425

RESUMEN

Bacillus thuringiensis (Bt) Cry1Fa and Cry1Ab proteins are important Cry toxins due to their high, selective toxicity against a number of lepidopteran species, including important pests of corn and cotton. Competition binding assays are a classical tool for investigating Cry toxin interactions with target pest insects. We developed a fluorescence-based binding assay and assessed Cry1Fa and Cry1Ab toxin binding to brush border membrane preparations from lepidopteran corn pests including Ostrinia nubilalis (European corn borer, ECB), Diatraea grandiosella (south western corn borer, SWCB), and Helicoverpa zea (corn earworm, CEW). Homologous and heterologous competition binding assays with fluorophore-(Alexa488)-labeled Cry1Fa toxin showed that Cry1Fa shares binding site(s) with Cry1Ab toxin in ECB, and SWCB for which Cry1Ab has higher affinity than Cry1Fa. Apart from the shared binding sites, Cry1Ab and Cry1Fa bind an additional site(s) in ECB and SWCB. In CEW, Cry1Fa and Cry1Ab each, has a high affinity binding site(s), which binds the heterologous toxin with low affinity. The Cry1Ab-Cry1Fa toxin binding models for ECB, SWCB and CEW based on our results are considered in the context of what is known about acquired cross-resistance against Cry1Ab and Cry1Fa toxins.


Asunto(s)
Bacillus thuringiensis , Mariposas Nocturnas , Animales , Proteínas Bacterianas , Sitios de Unión , Endotoxinas , Proteínas Hemolisinas , Larva , Microvellosidades , Zea mays
18.
BMC Surg ; 20(1): 96, 2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32381083

RESUMEN

BACKGROUND: Osteoporotic thoracolumbar burst fracture (OTLBF) is common in seniors. Due to the fracture of the posterior vertebra and spinal canal occupancy, the risk of cement leakage and spine injury is high in OTLBF patients, thus the application of vertebroplasty and kyphoplasty is limited in these patients. This study aims to investigate the efficacy and safety of the modified percutaneous kyphoplasty (MPKP) in the treatment of OTLBF. METHODS: Clinical data of the OTLBF patients treated with MPKP and the osteoporotic thoracolumbar compression fracture (OTLCF) patients undergone PKP from January 2014 to June 2016 were collected. The key procedure of the MPKP was to fill the bone cavity with gel-foam by the first balloon inflation and to press the gel-foam by a second balloon inflation. Pain intensity, Oswestry disability index (ODI), and bone cement leakage of the patients in the two groups were analyzed. RESULTS: In the burst fracture group, the overall spinal canal occupancy was relatively low, and the maximum occupancy was 1/3 of the sagittal diameter of the spinal canal. The surgical duration was longer in the burst fracture group (39.0 ± 5.0 min with 95% CI: 37.7, 40.3) than in the compression fracture group (31.7 ± 4.3 min with 95% CI: 31.1, 32.3), and the difference between the two groups was statistically significant (Z = -8.668 and P = 0.000). Both the Oswestry disability index (ODI) and the visual analog scales (VAS) were apparently improved, but there was no significant difference between the two groups. Cement leakage occurred in 13 out of the 53 cases (24.5%) in the burst fracture group and 35 out of the 193 cases (18.1%) in the compression fracture group, and there was no significant difference between the two groups (Z = - 1.038 and P = 0.299). Neither group had consequential symptoms, such as spinal cord lesion, pain, and numbness of the peripheral nerve. CONCLUSION: Similar to the efficacy of PKP in the treatment of OTLCF, MPKP efficiently reduced the cement leakage rate and improved the safety of the surgery, although it prolonged the surgical duration and introduced more surgical steps.


Asunto(s)
Cementos para Huesos , Fracturas por Compresión/cirugía , Cifoplastia/métodos , Fracturas Osteoporóticas/cirugía , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Resultado del Tratamiento , Vertebroplastia/métodos , Escala Visual Analógica
19.
Sensors (Basel) ; 20(18)2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32942579

RESUMEN

In the skeleton-based human action recognition domain, the spatial-temporal graph convolution networks (ST-GCNs) have made great progress recently. However, they use only one fixed temporal convolution kernel, which is not enough to extract the temporal cues comprehensively. Moreover, simply connecting the spatial graph convolution layer (GCL) and the temporal GCL in series is not the optimal solution. To this end, we propose a novel enhanced spatial and extended temporal graph convolutional network (EE-GCN) in this paper. Three convolution kernels with different sizes are chosen to extract the discriminative temporal features from shorter to longer terms. The corresponding GCLs are then concatenated by a powerful yet efficient one-shot aggregation (OSA) + effective squeeze-excitation (eSE) structure. The OSA module aggregates the features from each layer once to the output, and the eSE module explores the interdependency between the channels of the output. Besides, we propose a new connection paradigm to enhance the spatial features, which expand the serial connection to a combination of serial and parallel connections by adding a spatial GCL in parallel with the temporal GCLs. The proposed method is evaluated on three large scale datasets, and the experimental results show that the performance of our method exceeds previous state-of-the-art methods.


Asunto(s)
Algoritmos , Movimiento , Redes Neurales de la Computación , Esqueleto/fisiología , Humanos
20.
Sensors (Basel) ; 18(7)2018 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-29933555

RESUMEN

Research in human action recognition has accelerated significantly since the introduction of powerful machine learning tools such as Convolutional Neural Networks (CNNs). However, effective and efficient methods for incorporation of temporal information into CNNs are still being actively explored in the recent literature. Motivated by the popular recurrent attention models in the research area of natural language processing, we propose the Attention-aware Temporal Weighted CNN (ATW CNN) for action recognition in videos, which embeds a visual attention model into a temporal weighted multi-stream CNN. This attention model is simply implemented as temporal weighting yet it effectively boosts the recognition performance of video representations. Besides, each stream in the proposed ATW CNN framework is capable of end-to-end training, with both network parameters and temporal weights optimized by stochastic gradient descent (SGD) with back-propagation. Our experimental results on the UCF-101 and HMDB-51 datasets showed that the proposed attention mechanism contributes substantially to the performance gains with the more discriminative snippets by focusing on more relevant video segments.

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