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1.
New Phytol ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533489

RESUMO

Phytohormone, particularly jasmonate (JA) and salicylate (SA) signaling plays a central role in plant responses to herbivore and pathogen attack. Generally, SA mediates resistance responses against biotrophic pathogens and phloem-feeding insects, while JA mediates responses against necrotrophic pathogens and chewing insects. The phytohormonal responses mediating rice resistance to a piercing-sucking herbivore, the brown planthopper (BPH), remains unknown. Here, we combined transcriptome analysis, hormone measurements, genetic analysis and a field study to address this issue. Infestation by BPH adult females resulted in significant transcriptional reprograming. The up-regulated genes were enriched in the JA signaling pathway. Consistently, the levels of JAs, but not SA, were dramatically increased in response to BPH attack. Two JA deficient lines (AOC and MYC2 knockout) and two SA deficient lines (nahG over-expression and NPR1 knockout) were constructed. BPH performed better on JA-deficient lines than on wild type (WT) plants, but similarly on SA-deficient and WT plants. During BPH attack, the accumulation of defensive secondary metabolites was attenuated in JA-deficient lines compared to WT plants. Moreover, MYC2 mutants were more susceptible to planthoppers than WT plants in nature. This study reveals that JA signaling functions in rice defense against BPH.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33591917

RESUMO

In this paper a PZT / Epoxy 1-3 piezoelectric composite based on picosecond laser etching technology is developed for the fabrication of high frequency ultrasonic transducer. The design, fabrication, theoretical analysis, and performance of the piezocomposite and transducer are presented and discussed. According to the test results, the area of the PZT pillar is 20.5 µm × 20.5 µm, the average width of the kerf is 4.5 µm, and the thickness of the piezocomposite is 38 µm. The fabricated 1-3 piezocomposite has a resonant frequency of 46.5 MHz, a parallel resonant frequency of 65 MHz, and an electromechanical coupling coefficient of 0.73. According to the wires phantom imaging, its imaging resolution can reach 50 µm. This study shows that the proposed picosecond laser micromachining technique can be applied in the fabrication of high frequency 1-3 piezocomposite and transducer.

3.
J Am Soc Nephrol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593824

RESUMO

BACKGROUND: Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy, the most common primary GN worldwide. Although serum levels of galactose-deficient IgA1 have a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly established. METHODS: To identify novel loci associated with galactose-deficient IgA1, we performed a quantitative genome-wide association study for serum galactose-deficient IgA1 levels, on the basis of two different genome-wide association study panels conducted in 1127 patients with IgA nephropathy. To test genetic associations with susceptibility to IgA nephropathy, we also enrolled 2352 patients with biopsy-diagnosed IgA nephropathy and 2632 healthy controls. Peripheral blood samples from 59 patients and 27 healthy controls were also collected for gene expression analysis. RESULTS: We discovered two loci, in C1GALT1 and GALNT12, that achieved genome-wide significance, explaining about 3.7% and 3.4% of variance in serum galactose-deficient IgA1 levels, respectively. We confirmed the previously reported association of C1GALT1 with serum galactose-deficient IgA1 levels, but with a different lead single-nucleotide polymorphism (rs10238682; ß=0.26, P=1.20×10-9); the locus we identified at GALNT12 (rs7856182; ß=0.73, P=2.38×10-9) was novel. Of more interest, we found that GALNT12 exhibits genetic interactions with C1GALT1 in both galactose-deficient IgA1 levels (P=1.40×10-2) and disease risk (P=6.55×10-3). GALNT12 mRNA expression in patients with IgA nephropathy was significantly lower compared with healthy controls. CONCLUSIONS: Our data identify GALNT12 as a novel gene associated with galactose-deficient IgA1 and suggest novel genetic interactions. These findings support a key role of genetically conferred dysregulation of galactose-deficient IgA1 in the development of IgA nephropathy.

4.
Phys Chem Chem Phys ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33594394

RESUMO

Searching for high-performance electrode materials is an important topic in rechargeable batteries. Using first-principles calculations, we systematically explore the potential application of a two-dimensional BP2 monolayer as a cathode material for Li-ion and Na-ion batteries. The pristine BP2 monolayer exhibits metallic characteristics, which facilitate the transportation of electrons. The Li and Na atoms bind strongly to the BP2 monolayer, indicating a good structural stability. Furthermore, the geometrical structure of BP2 is well maintained during the adsorption process. The Li and Na ions prefer to move along the zigzag direction with relatively low energy barriers. Especially, the ultralow Na diffusion barrier (0.03 eV) implies that monolayer BP2 has an excellent charge/discharge capability. The specific capacity and average electrode potential of Li (Na) are 619.45 (279.93) mA h g-1 and 2.89 (2.49) V, respectively. These results reveal that the BP2 monolayer is an appealing cathode material for alkali-metal batteries.

5.
Phytochemistry ; 184: 112673, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33556841

RESUMO

The Melodinus species have been proved to be good resources of bisindole alkaloids. Six bisindole alkaloids were isolated from the leaves and stems of Melodinus cochinchinensis (Lour.) Merr. guided by HRESIMS data analysis. Among them, melokhanines K-M, epi-scandomelonine, and epi-scandomeline possessed aspidosperma-scandine skeleton linked by a C-C bond while meloyine II had a scandine-scandine skeleton. The structures were established by extensive spectroscopic analysis of their HRESIMS and NMR data. Melokhanines K-M were undescribed compounds, while epi-scandomelonine, epi-scandomeline and meloyine II were known compounds, which were reported from Melodinus species for the first time. The anti-inflammatory and cytotoxic activities of the isolates were also evaluated in vitro. Melokhanine K and meloyine II showed potent inhibitory activity on the production of nitric oxide, interleukin-6, and tumor necrosis factor-α in LPS-induced RAW 264.7 macrophages, whereas epi-scandomelonine and epi-scandomeline exhibited certain cytotoxic activity against MOLT-4 cells with IC50 values 5.2 and 1.5 µM, respectively.

6.
J Agric Food Chem ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560835

RESUMO

Endogenous ceramide is considered to be associated with the progress of insulin resistance. However, the effects of dietary exogenous glucosylceramides and ceramides on insulin resistance are unclear. A model of fructose-induced male Sprague Dawley rats was used to compare the effects of sea-cucumber-derived glucosylceramides and ceramides on insulin resistance. Both glucosylceramides and ceramides significantly improved glucose tolerance, reduced the concentrations of serum glucose and glycosylated hemoglobin, and alleviated the accompanied hypertension. Ceramides significantly enhanced glycogen levels in skeletal muscle, whereas glucosylceramides significantly increased the hepatic glycogen levels. Moreover, glucosylceramides alleviated insulin resistance by inhibiting gluconeogenesis, promoting glycogen synthesis and insulin signal transduction in the liver; meanwhile, ceramides were mainly due to the promotion of glycogen synthesis and insulin signal transduction in skeletal muscle. Additionally, glucosylceramides and ceramides effectively attenuated inflammation in adipose tissue. These results indicate that glucosylceramides and ceramides have potential value in the prevention and alleviation of insulin resistance.

7.
J Med Internet Res ; 23(2): e24813, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599615

RESUMO

BACKGROUND: The adoption rate of electronic health records (EHRs) in hospitals has become a main index to measure digitalization in medicine in each country. OBJECTIVE: This study summarizes and shares the experiences with EHR adoption in China and in the United States. METHODS: Using the 2007-2018 annual hospital survey data from the Chinese Health Information Management Association (CHIMA) and the 2008-2017 United States American Hospital Association Information Technology Supplement survey data, we compared the trends in EHR adoption rates in China and the United States. We then used the Bass model to fit these data and to analyze the modes of diffusion of EHRs in these 2 countries. Finally, using the 2007, 2010, and 2014 CHIMA and Healthcare Information and Management Systems Services survey data, we analyzed the major challenges faced by hospitals in China and the United States in developing health information technology. RESULTS: From 2007 to 2018, the average adoption rates of the sampled hospitals in China increased from 18.6% to 85.3%, compared to the increase from 9.4% to 96% in US hospitals from 2008 to 2017. The annual average adoption rates in Chinese and US hospitals were 6.1% and 9.6%, respectively. However, the annual average number of hospitals adopting EHRs was 1500 in China and 534 in the US, indicating that the former might require more effort. Both countries faced similar major challenges for hospital digitalization. CONCLUSIONS: The adoption rates of hospital EHRs in China and the United States have both increased significantly in the past 10 years. The number of hospitals that adopted EHRs in China exceeded 16,000, which was 3.3 times that of the 4814 nonfederal US hospitals. This faster adoption outcome may have been a benefit of top-level design and government-led policies, particularly the inclusion of EHR adoption as an important indicator for performance evaluation and the appointment of public hospitals.

8.
Phytochemistry ; 184: 112656, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33524854

RESUMO

Three previously undescribed pyridyl-steroidal glycoalkaloids, solanindiosides A‒C, one rare 23S,26R-hydroxylated spirostanoid saponin, and two steroidal alkaloid aglycones, solanindins A and B, derived from the acid hydrolysis of solanindiosides A‒C, were isolated from the fruits of Solanum violaceum, together with five known analogues, including two rare steroidal glycosides, two lignans and a diterpene. Structurally, they comprise a 16ß-methoxy-23-deoxy-22,26-epimino-cholest-type skeleton moiety, and a 16ß-methoxy-3,23-dideoxy-22,26-epimino-cholest-3,5-dien derivative. The hitherto undescribed structures were established on the basis of extensive spectroscopic analyses. Configurations of sugar moieties were resolved by chemical derivations. Solanindiosides A‒C, (22R,23S,25R,26R)-spirost-5-ene-3ß,23,26-triol3-O-ß-d-xylopyranosyl-(1→3)-ß-d-glucopyranoside, solanindins A and B, and (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol were evaluated for their cytotoxic and antibacterial activities. (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol showed the most potent cytotoxic activity against MCF-7 cells (IC50 = 4.386 ± 0.098 µM), while solanindin B displayed some inhibitory effects against Staphylococcus aureus Rosenbach with MIC50 value of 37.32 ± 0.793 µM. In addition, (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol induced dose dependent apoptosis effect in MCF-7 cells.

9.
Ren Fail ; 43(1): 340-346, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33567936

RESUMO

BACKGROUND: Growth differentiation factor 15(GDF15) is a distant member of the superfamily of the transforming growth factor beta (TGF-ß). It has been established that increased GDF15 levels are associated with an increased risk of cardiovascular disease. However, the detail effect of GDF15 on cardiovascular system in patients with chronic kidney disease (CKD) needs detail analysis. METHODS: Patients with CKD who did not need dialysis were enrolled in the study. Blood pressure (BP), endothelial function, pulse wave velocity (PWV) and heart rate variability (HRV) were taken in all subjects. Plasma GDF15 concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: Among the 355 participants, the mean age was 57.4 (±14.2) years old and the mean estimated glomerular filtration rate (eGFR) was 50.1 (±33.2) mL/min/1.73m2. The average plasma GDF15 level was 1394.7 (±610.1) pg/mL. Higher GDF15 concentrations were significantly associated with decreased eGFR and increased urine protein-to-creatinine ratio (uPCR). In multivariable models, after adjusting for potential confounders, plasma GDF15 has negative concerning with HRV parameters including the standard deviation of the normal-to-normal (NN) interval (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) and Triangular Index. CONCLUSION: We observed there was a link between increased plasma of GDF15 and decreased HRV. The mechanisms and prediction of GDF15 in the cardiovascular disease with CKD needs further discussion and study.

10.
Reprod Biol ; 21(2): 100485, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33607572

RESUMO

Epididymal protease inhibitor (EPPIN) is differentially expressed in the reproductive tissues (such as testicles, outlet tubes, epididymis, vas deferens, and seminal vesicles). Its critical role in sperm function and male reproduction has shed light on EPPIN as a candidate target for male contraceptive vaccines. In this study, we endeavored to further reveal the mechanism through which EPPIN exerts its function. We created a mouse model of reduced Eppin expression by microinjecting small interfering RNA targeting Eppin expression into seminiferous tubules of mice. This mouse model was then used to explore the effects of low Eppin expression on sperm function, which was assessed by Computer Assisted Semen Analysis and patch clamp recording of T-type Ca2+ current in spermatogenic cells. We found that the sperm motility significantly declined when Eppin was downregulated. Further investigation demonstrated that Eppin downregulation significantly affected T-type Ca2+ currents and messenger RNA expression of three subtypes of T-type Ca2+ channels in spermatogenic cells. These findings indicate that low Eppin gene expression induces decreased T-type Ca2+ currents and mRNA expression, which in turn results in the reduced sperm motility.

11.
IEEE Trans Image Process ; 30: 2888-2897, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33539298

RESUMO

In this paper, we propose a new method to super-resolve low resolution human body images by learning efficient multi-scale features and exploiting useful human body prior. Specifically, we propose a lightweight multi-scale block (LMSB) as basic module of a coherent framework, which contains an image reconstruction branch and a prior estimation branch. In the image reconstruction branch, the LMSB aggregates features of multiple receptive fields so as to gather rich context information for low-to-high resolution mapping. In the prior estimation branch, we adopt the human parsing maps and nonsubsampled shearlet transform (NSST) sub-bands to represent the human body prior, which is expected to enhance the details of reconstructed human body images. When evaluated on the newly collected HumanSR dataset, our method outperforms state-of-the-art image super-resolution methods with  âˆ¼ 8× fewer parameters; moreover, our method significantly improves the performance of human image analysis tasks (e.g. human parsing and pose estimation) for low-resolution inputs.

12.
Cell Death Dis ; 12(2): 176, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579894

RESUMO

It is well-established that long-term exposure of the vasculature to metabolic disturbances leads to abnormal vascular tone, while the physiological regulation of vascular tone upon acute metabolic challenge remains unknown. Here, we found that acute glucose challenge induced transient increases in blood pressure and vascular constriction in humans and mice. Ex vivo study in isolated thoracic aortas from mice showed that glucose-induced vascular constriction is dependent on glucose oxidation in vascular smooth muscle cells. Specifically, mitochondrial membrane potential (ΔΨm), an essential component in glucose oxidation, was increased along with glucose influx and positively regulated vascular smooth muscle tone. Mechanistically, mitochondrial hyperpolarization inhibited the activity of myosin light chain phosphatase (MLCP) in a Ca2+-independent manner through activation of Rho-associated kinase, leading to cell contraction. However, ΔΨm regulated smooth muscle tone independently of the small G protein RhoA, a major regulator of Rho-associated kinase signaling. Furthermore, myosin phosphatase target subunit 1 (MYPT1) was found to be a key molecule in mediating MLCP activity regulated by ΔΨm. ΔΨm positively phosphorylated MYPT1, and either knockdown or knockout of MYPT1 abolished the effects of glucose in stimulating smooth muscle contraction. In addition, smooth muscle-specific Mypt1 knockout mice displayed blunted response to glucose challenge in blood pressure and vascular constriction and impaired clearance rate of circulating metabolites. These results suggested that glucose influx stimulates vascular smooth muscle contraction via mitochondrial hyperpolarization-inactivated myosin phosphatase, which represents a novel mechanism underlying vascular constriction and circulating metabolite clearance.

13.
Neurochem Res ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33586092

RESUMO

Alzheimer's disease (AD) is a growing health concern worldwide. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify differentially expressed miRNAs (DEmiRNAs) and genes specific to AD, we used bioinformatic analyses to investigate candidate miRNA-mRNA pairs involved in the pathogenesis of AD. We focused on differentially expressed genes (DEGs) that are targets of DEmiRNAs. The GEO2R tool and the HISAT2-DESeq2 software were used to identify DEmiRNAs and DEGs. Bioinformatic tools available online, such as TAM and the Database for Annotation, Visualization and Integrated Discovery (DAVID), were used to perform functional annotation and enrichment analysis. Targets of miRNAs were predicted using the miRTarBase. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, which are available online, were utilized to construct protein-protein interaction (PPI) networks and identify hub genes. Furthermore, transcription factors (TFs) encoded by the DEGs were predicted using the TransmiR database and TF-miRNA-mRNA networks were constructed. Finally, the expression profile of a hub gene in peripheral blood mononuclear cells was compared between healthy individuals and AD patients. We identified 26 correlated miRNA-mRNA pairs. In the parietal lobe, miRNA-mRNA pairs involved in protein folding were enriched, and in the frontal lobe, miRNA-mRNA pairs involved in synaptic transmission, abnormal protein degradation, and apoptosis were enriched. In addition, HSP90AB1 in peripheral blood mononuclear cells was found to be significantly downregulated in AD patients, and this was consistent with its expression profile in the parietal lobe of AD patients. Our results provide brain region-specific changes in miRNA-mRNA associations in AD patients, further our understanding of potential underlying molecular mechanisms of AD, and reveal promising diagnostic and therapeutic targets for AD.

14.
J Health Commun ; : 1-9, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33587023

RESUMO

The pervasiveness of prolonged screen viewing (SV) in adolescence is of significant concern given its well-documented implications with various health outcomes. Based on Social Cognitive Theory (SCT), this study explored how a wide range of individual, environmental, and behavioral factors correlate with adolescents' SV duration. The study used adolescents' self-reported data from the cross-sectional Family Life, Activity, Sun, Health and Eating (FLASHE) study implemented by the National Cancer Institute (NCI). Findings indicated that adolescents' SV duration were different across various age and ethnic groups. It was positively associated with emotion regulation and negatively connected with self-efficacy in limiting screen time. Compared to un-authoritative parenting style, authoritative parenting had an advantage in curbing adolescents' screen use. General media susceptibility strongly correlated with SV duration. Perception of peers' behaviors (descriptive norm) and how peers would react adversely (injunctive norm) were both connected with SV duration. SV duration was negatively connected with physical activity whereas positively linked with sedentary behavior. Theoretical and practical implications were outlined, as well as limitations and directions for future research.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33609770

RESUMO

BACKGROUND: It is unclear if there is the influence of asthma on contracting COVID-19, or having worse outcomes from COVID-19 disease. OBJECTIVE: To explore the prevalence of asthma in COVID-19 patients and the relationship between asthma and COVID-19 patients with poor outcomes. METHODS: The pooled prevalence of asthma in COVID-19 patients and corresponding 95% confidence interval (CI) were estimated. The pooled effect size (ES) was used to evaluate the association between asthma and COVID-19 patients with poor outcomes. RESULTS: The pooled prevalence of asthma in COVID-19 patients worldwide was 8.3% (95% CI 7.6-9.0%) based on 116 articles (119 studies) with 403,392 cases. The pooled ES based on unadjusted effect estimates showed that asthma was not associated with the reduced risk of poor outcomes in COVID-19 patients (ES 0.91, 95% CI 0.78-1.06). Similarly, the pooled ES based on unadjusted effect estimates revealed that asthma was not associated with the reduced risk of mortality in COVID19 patients (ES 0.88, 95% CI 0.73-1.05). However, the pooled ES based on adjusted effect estimates indicated that asthma was significantly associated with the reduced risk of mortality in COVID-19 patients (ES 0.80, 95% CI 0.74-0.86). CONCLUSION: The pooled prevalence of asthma in COVID-19 patients was similar to that in the general population, and asthma might be an independent protective factor for the death of COVID-19 patients, which suggests that we should pay high attention to COVID-19 patients with asthma and take locally tailored interventions and treatment. Further well-designed studies with large sample sizes are required to verify our findings.

16.
Oncologist ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33611805

RESUMO

BACKGROUND: Both protracted irinotecan and anti-angiogenesis therapy have shown promising efficacy against Ewing sarcoma (EWS). We conducted a phase Ib/II trial to first define the proper dose of irinotecan in combination with vincristine and anlotinib in refractory or recurrent EWS patients (phase Ib) and subsequently evaluate their efficacy (phase II). METHODS: Patients diagnosed with recurrent or refractory EWS were enrolled and further categorized into cohort A (≥ 16 years) or cohort B (< 16 years). In the dose-defining phase Ib portion, anlotinib was given daily at a fixed dose of 12 mg or 8 mg on days 1-14 within a 21-day cycle, while a 3+3 design with dose de-escalation was used to determine the most appropriate dose of irinotecan in each cohort starting from an initial dose of 20 mg/m2 /d dx5x2. Recommended phase 2 dose (RP2D) was defined as the highest dose at which no more than 30% patients experienced a dose-limiting toxicity (DLT) during the first two treatment courses. The next dose-expanding phase II portion employed a conventional two-stage study design model. The primary endpoint was objective response rate at 12 weeks (ORR12w ), while the secondary endpoints included overall survival (OS), progression-free survival (PFS) and failure-free survival (FFS). RESULTS: A total of 41 patients finally received the treatment regimen, including 29 in cohort A and 12 in cohort B. For cohort A, the first five patients were treated at initial level in phase Ib portion, and two of them subsequently experienced delayed-onset diarrhea as a DLT. Additional six patients were then treated at a lower dose of 15 mg/m2 . At the end of phase Ib trial, no DLT was found and the RP2D was determined. Notably, 23 out of 24 patients in cohort A in phase II portion were available for response evaluation at 12 weeks, with one complete response (CR), 14 partial response (PR) [including two complete metabolic response (CMR) who had a negative PET/CT scan but exhibited abnormal lesions on MR scan], two stable disease (SD) and six progressive disease (PD). ORR12w was determined to be 62.5%. For cohort B, no DLT was observed in the first six patients treated at the initial dose level which was then used as RP2D. At last, 12 patients were included in cohort B. The ORR12w was 83.3% with four CR, six PR (including one CMR) and two PD. Although high efficacy, cohort B was halted prematurely due to slow enrollment. The most frequently observed Grade 3/4 adverse events were leukopenia (28.5%), neutropenia (24.4%), anemia (8.7%) and diarrhea (3.7%). CONCLUSION: The combination of vincristine, irinotecan and anlotinib demonstrated an acceptable toxicity profile and promising clinical efficacy in patients with advanced EWS. IMPLICATIONS FOR PRACTICE: This is the first trial to evaluated irinotecan-based regimen in combination with anti-angiogenesis TKIs in Ewing sarcoma. A 3+3 design with dose de-escalation was used to determine the most appropriate dose of irinotecan in each cohort. The next dose-expanding phase II portion employed a conventional two-stage study design model. The objective response rate was 62.5% for adults and 83.3% for children. Median overall survival was not matured. We demonstrated that the combination of vincristine, irinotecan and anlotinib demonstrated an acceptable toxicity profile and promising clinical efficacy in patients with advanced EWS.

17.
J Org Chem ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606932

RESUMO

A visible-light-driven, photocatalyst-free route starting from easily accessed ortho-hydroxycinnamic esters and O-perfluoropyridin-4-yl oximes has been successfully developed to rapidly assemble a wide range of 3-cyanoalkyl coumarins. This process does not require addition of external photocatalysts, exhibiting beneficial features including mild reaction conditions, synthetic simplicity, and excellent substrate compatibility. Extensive mechanistic investigations revealed that the in situ generated phenolate anions served as photosensitizers to drive this photoinduced transformation.

18.
Stem Cell Reports ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33606990

RESUMO

Loss-of-function mutations in the forkhead box N1 (FOXN1) gene lead to nude severe combined immunodeficiency, a rare inherited syndrome characterized by athymia, severe T cell immunodeficiency, congenital alopecia, and nail dystrophy. We recently produced FOXN1 mutant nude rabbits (NuRabbits) by using CRISPR-Cas9. Here we report the establishment and maintenance of the NuRabbit colony. NuRabbits, like nude mice, are hairless, lack thymic development, and are immunodeficient. To demonstrate the functional applications of NuRabbits in biomedical research, we show that they can successfully serve as the recipient animals in xenotransplantation experiments using human induced pluripotent stem cells or tissue-engineered blood vessels. Our work presents the NuRabbit as a new member of the immunodeficient animal model family. The relatively large size and long lifespan of NuRabbits offer unique applications in regenerative medicine, cancer research, and the study of a variety of other human conditions, including immunodeficiency.

19.
Biosci Biotechnol Biochem ; 85(3): 675-686, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33589896

RESUMO

Gangliosides (GLSs) are ubiquitously distributed in all tissues but highly enriched in nervous system. Currently, it is unclear how exogenous GLSs regulate neuritogenesis, although neural functions of endogenous GLSs are widely studied. Herein, we evaluated the neuritogenic activities and mechanism of sea urchin gangliosides (SU-GLSs) in vitro. These different glycosylated SU-GLSs, including GM4(1S), GD4(1S), GD4(2A), and GD4(2G), promoted differentiation of NGF-induced PC12 cells in a dose-dependent and structure-selective manner. Sulfate-type and disialo-type GLSs exhibited stronger neuritogenic effects than monosialoganglioside GM1. Furthermore, SU-GLSs might act as neurotrophic factors possessing neuritogenic effects, via targeting tyrosine-kinase receptors (TrkA and TrkB) and activating MEK1/2-ERK1/2-CREB and PI3K-Akt-CREB pathways. This activation resulted in increased expression and secretion of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These pathways were verified by specific inhibitors. Our results confirmed the neuritogenic functions of SU-GLS in vitro and indicated their potential roles as natural nutrition for neuritogenesis.

20.
Life Sci ; 272: 119242, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33607155

RESUMO

AIMS: Recent studies have shown that enhancement of fatty acid utilization through feeding animals a high fat diet (HFD) attenuated cardiac dysfunction in heart failure (HF). Here, we aimed to examine the temporal effects of HFD feeding on cardiac function in mice with heart failure and its underlying mechanism. MAIN METHODS: Pressure overload-induced HF was established via transverse aortic constriction (TAC) surgery. After surgery, the mice were fed on either normal diet or HFD for 8 or 16 weeks. KEY FINDINGS: HFD feeding exerted opposite effects on cardiac function at different time points post-surgery. Short-term HFD feeding (8 wk) protected the heart against pressure overload, inhibiting cardiac hypertrophy and improving cardiac function, while long-term HFD feeding (16 wk) aggravated cardiac dysfunction in TAC mice. Short-term HFD feeding elevated cardiac fatty acid utilization, while long-term HFD feeding showed no significant effects on cardiac fatty acid utilization in TAC mice. Specifically, an increase in cardiac fatty acid utilization was accompanied with activated mitophagy and improved mitochondrial function. Palmitic acid treatment (400 µM, 2 h) stimulated fatty acid oxidation and mitophagy in neonatal myocytes. Mechanistically, fatty acid utilization stimulated mitophagy through upregulation of Parkin. Cardiac-specific knockdown of Parkin abolished the protective effects of short-term HFD feeding on cardiac function in TAC mice. SIGNIFICANCES: These results suggested that short-term but not long-term HFD feeding protects against pressure overload-induced heart failure through activation of mitophagy, and dietary fat intake should be used with caution in treatment of heart failure.

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