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1.
BMC Genomics ; 22(1): 53, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446101

RESUMO

BACKGROUND: Genome-wide change of polyadenylation (polyA) sites (also known as alternative polyadenylation, APA) is emerging as an important strategy of gene regulation in response to stress in plants. But little is known in woody perennials that are persistently dealing with multiple abiotic stresses. RESULTS: Here, we performed a genome-wide profiling of polyadenylation sites under heat and cold treatments in Populus trichocarpa. Through a comprehensive analysis of polyA tail sequences, we identified 25,919 polyA-site clusters (PACs), and revealed 3429 and 3139 genes shifted polyA sites under heat and cold stresses respectively. We found that a small proportion of genes possessed APA that affected the open reading frames; and some shifts were commonly identified. Functional analysis of genes displaying shifted polyA tails suggested that pathways related to RNA metabolism were linked to regulate the APA events under both heat and cold stresses. Interestingly, we found that the heat stress induced a significantly more antisense PACs comparing to cold and control conditions. Furthermore, we showed that a unique cis-element (AAAAAA) was predominately enriched downstream of PACs in P. trichocarpa genes; and this sequence signal was only absent in shifted PACs under the heat condition, indicating a distinct APA mechanism responsive to heat tolerance. CONCLUSIONS: This work provides a comprehensive picture of global polyadenylation patterns in response to temperatures stresses in trees. We show that the frequent change of polyA tail is a potential mechanism of gene regulation responsive to stress, which are associated with distinctive sequence signatures.

2.
J Cell Mol Med ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33269546

RESUMO

Liver fibrogenesis is a complex scar-forming process in the liver. We suggested that the liver first responded to chronic injuries with gradual changes, then reached the critical state and ultimately resulted in cirrhosis rapidly. This study aimed to identify the tipping point and key molecules driving liver fibrosis progression. Mice model of liver fibrosis was induced by thioacetamide (TAA), and liver tissues were collected at different time-points post-TAA administration. By dynamic network biomarker (DNB) analysis on the time series of liver transcriptomes, the week 9 post-TAA treatment (pathologically relevant to bridging fibrosis) was identified as the tipping point just before the significant fibrosis transition, with 153 DNB genes as key driving factors. The DNB genes were functionally enriched in fibrosis-associated pathways, in particular, in the top-ranked DNB genes, Tgfb3 negatively regulated Mmp13 in the interaction path and they formed a bistable switching system from a dynamical perspective. In the in vitro study, Tgfb3 promoted fibrogenic genes and down-regulate Mmp13 gene transcription in an immortalized mouse HSC line JS1 and a human HSC line LX-2. The presence of a tipping point during liver fibrogenesis driven by DNB genes marks not only the initiation of significant fibrogenesis but also the repression of the scar resolution.

3.
ACS Omega ; 5(43): 27953-27961, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33163778

RESUMO

Fulvic acid (FA) is a complex organic mixture composed of small molecules. The structure and composition of FA vary greatly because of the different raw materials used for preparing FA. In this work, FA was extracted from shallow low-rank lignite by hydrogen peroxide (H2O2) in a microwave field, and the functional groups of FA were characterized. The optimal extraction process was determined, with the H2O2 concentration being the key factor affecting the yield of FA. Thermogravimetric analysis showed that FA was mainly composed of low molecular weight and readily pyrolyzed compounds. As shown by Fourier transform infrared spectroscopy, in the process of FA extraction by H2O2 oxidation of lignite, the content of -COOH increased, long-chain aliphatic compounds decreased, stretching vibrations of aromatic ring skeletons disappeared, and aromatic ring substitution became mainly tri- or disubstitution. Fluorescence spectroscopy indicated that FA had a low degree of aromaticity. X-ray photoelectron spectroscopy qualitatively and quantitatively revealed that the main modes of carbon-oxygen bonding in FA were C-O-, COO-, and C=O. Thus, this study not only lays a foundation for studying the composition and structure of coal-based FA but also opens a new avenue for a clean and efficient utilization of lignite.

4.
Gastroenterology ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217448

RESUMO

BACKGROUND & AIMS: RNA N6-methyladenosine (m6A) modification has recently emerged as a new regulatory mechanism in cancer progression. We aimed to explore the role of m6A regulatory enzyme METTL3 in colorectal cancer (CRC) pathogenesis and its potential as a therapeutic target. METHODS: The expression and clinical implication of METTL3 were investigated in multiple human CRC cohorts. The underlying mechanisms of METTL3 in CRC were investigated by integrative m6A-sequencing, RNA-sequencing and ribosome profiling analyses. The efficacy of targeting METTL3 in CRC treatment was elucidated in CRC cell lines, patient-derived CRC organoids and Mettl3 knockout mouse models. RESULTS: Using targeted CRISPR/Cas9 dropout screening, we identified METTL3 as the top essential m6A regulatory enzyme in CRC. METTL3 was overexpressed in 62.2% (79/127) and 88.0% (44/50) of primary CRC from two independent cohorts. High METTL3 expression predicted poor survival in CRC patients (n=374, P < .01). Functionally, silencing METTL3 suppressed tumorigenesis in CRC cells, human-derived primary CRC organoids and Mettl3 knockout mouse models. We discovered the novel functional m6A methyltransferase domain of METTL3 in CRC cells by domain-focused CRISPR screen and mutagenesis assays. Mechanistically, METTL3 directly induced m6A-GLUT1-mTORC1 axis as identified by integrated m6A-sequencing, RNA-sequencing, Ribosome-sequencing and functional validation. METTL3 induced GLUT1 translation in m6A-dependent manner, which subsequently promoted glucose uptake and lactate production, leading to the activation of mTORC1 signaling and CRC development. Furthermore, inhibition of mTORC1 potentiated the anticancer effect of METTL3 silencing in CRC patient-derived organoids and METTL3 transgenic mouse models. CONCLUSIONS: METTL3 promotes CRC by activating m6A-GLUT1-mTORC1 axis. METTL3 is a promising therapeutic target for the treatment of CRC.

5.
Gastroenterology ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920015

RESUMO

BACKGROUND & AIMS: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention. METHODS: The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S thermophilus was identified by mass spectrometry and followed by ß-galactosidase activity assay. The mutant strain of S thermophilus was constructed by homologous recombination. The effect of S thermophilus on the gut microbiota composition was assessed by shotgun metagenomic sequencing. RESULTS: Oral gavage of S thermophilus significantly reduced tumor formation in both Apcmin/+ and azoxymethane-injected mice. Coincubation with S thermophilus or its conditioned medium decreased the proliferation of cultured CRC cells. ß-Galactosidase was identified as the critical protein produced by S thermophilus by mass spectrometry screening and ß-galactosidase activity assay. ß-Galactosidase secreted by S thermophilus inhibited cell proliferation, lowered colony formation, induced cell cycle arrest, and promoted apoptosis of cultured CRC cells and retarded the growth of CRC xenograft. The mutant S thermophilus without functional ß-galactosidase lost its tumor-suppressive effect. Also, S thermophilus increased the gut abundance of known probiotics, including Bifidobacterium and Lactobacillus via ß-galactosidase. ß-Galactosidase-dependent production of galactose interfered with energy homeostasis to activate oxidative phosphorylation and downregulate the Hippo pathways kinases, which partially mediated the anticancer effects of S thermophilus. CONCLUSION: S thermophilus is a novel prophylactic for CRC prevention in mice. The tumor-suppressive effect of S thermophilus is mediated at least by the secretion of ß-galactosidase.

6.
Cancer Manag Res ; 12: 5293-5299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753948

RESUMO

Purpose: This study aimed to retrospectively analyze the failure patterns and clinical outcomes in patients with locally advanced cervical esophageal carcinoma (CEC) after definitive radiotherapy (RT), and illustrate the mapping of regional failures. Patients and Methods: We reviewed 82 patients with CEC confirmed as squamous cell carcinoma who had completed definitive RT from August 2008 to December 2017. Data on clinical characteristics were collected from the medical records system. Patterns of treatment failures and the survival follow-up were analyzed. Results: The median age was 58 (38-78) years. In 37 patients, the lesions were limited to the cervical esophagus, while in the remaining 45 patients, the disease got beyond the cervical esophagus (pharynx or thoracic esophagus involved). While 10 patients had stage Ⅱ disease, 72 had stage III disease. The completed median dose for 95% PGTV and 95% PTV was 66 Gy and 58 Gy. While the median follow-up was 27.6 months, the median progression-free survival (PFS) and overall survival (OS) was 16.1 and 28.3 months, respectively. The 3-year PFS and OS was 30.3% and 45.3%, respectively. Treatment failures were reported in 55 patients, of which 22, 8, 7, 9, 2, 3, and 4 patients had developed local, regional, distant, local-regional, regional-distant, local-distant and local-regional-distant failure, respectively. Of the 41 relapsed nodal sites, 28 were located "in-field" whereas 1 was "marginal" and 12 were "out-field". The most frequent regional relapses were at level VIb, IV and the upper-middle mediastinum. Conclusion: Regional recurrences focused on lower neck and upper-middle mediastinum, and mainly "in-field", after definitive RT in patients with CEC.

7.
Zookeys ; 954: 1-15, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821201

RESUMO

A new species of glomeridellid millipede is described from Guizhou Province, southern China: Tonkinomeris huzhengkuni sp. nov. This new epigean species differs very clearly in many structural details, being sufficiently distinct morphologically and disjunct geographically from T. napoensis Nguyen, Sierwald & Marek, 2019, the type and sole species of Tonkinomeris Nguyen, Sierwald & Marek, 2019, which was described recently from northern Vietnam. The genus Tonkinomeris is formally relegated from Glomeridae and assigned to the family Glomeridellidae, which has hitherto been considered strictly Euro-Mediterranean in distribution and is thus new to the diplopod faunas of China and Indochina. Tonkinomeris is re-diagnosed and shown to have perhaps the basalmost position in the family Glomeridellidae. Its relationships are discussed, both morphological and zoogeographical, within and outside the Glomeridellidae, which can now be considered as relict and basically Oriental in origin. Because of the still highly limited array of DNA-barcoding sequences of the COI mitochondrial gene available in the GenBank, the first molecular phylogenetic analysis of Glomerida attempted here shows our phylogram to be too deficient to consider meaningful.

8.
Comp Immunol Microbiol Infect Dis ; 71: 101499, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32505765

RESUMO

There has been an increasing interest in finding new formulations that qualify as vaccine adjuvants, which must be safe, stable, and have the capacity to stimulate a strong immune response. In this study, a basic formulation of a water-in-oil-in-water (W/O/W) adjuvant CV13 was developed, and ginseng stem-leaf saponins (GSLS) were added as an immune booster into oil phase. The physicochemical properties of the adjuvant were tested. Furthermore, the immune activity and the adjuvant effects, as indicated by the foot-and-mouth disease virus (FMDV) antigen were evaluated. The results showed that CV13 was similar in appearance to ISA 206 and could package FMDV antigen into a stable W/O/W emulsion. The FMD vaccine prepared with CV13 alone or CV13 containing GSLS achieved pharmaceutical characteristics comparable to a vaccine prepared with ISA 206, moreover the structural stability of the CV 13 vaccine was found to be better. Mice that were immunized with the FMD vaccine prepared with CV13 containing GSLS presented a significantly higher LPBE antibody titer and splenocyte proliferation rate than those immunized with a vaccine prepared with CV13 alone (p < 0.05). In addition, there was no significant difference between the groups that were immunized with FMD vaccine prepared with CV13 containing GSLS and ISA206 in terms of cellular and humoral immune response. In this paper, CV13 containing GSLS shows excellent immunologic adjuvant effect in mice model, and this new adjuvant may provide a potential choice for FMD vaccine production in the future.

10.
Zookeys ; 930: 153-198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32390752

RESUMO

Based on all available information, 339 species from 71 genera, 26 families, and eleven orders of Diplopoda have hitherto been recorded from mainland China, the fauna thus being very rich, albeit far from completely known, comprising various zoogeographic elements and populating very different environments. Diplopods mainly occur in various woodlands, in caves, and high in the mountains. Most species (> 90 %, usually highly localised, including 160 cavernicoles), 18 genera, and one family are strictly endemic to continental China. Mapping not only the horizontal, but also the vertical distributions of Diplopoda in China shows the bulk of the fauna to be expectedly restricted to forested lowland and mountain biomes or their remnants. Yet some Chordeumatida, Callipodida, Polydesmida, Julida, and even Spirobolida seem to occur only in the subalpine to alpine environments and thus may provisionally be considered as truly high-montane. The long-acknowledged notions of China being a great biogeographic zone transitional between the Palaearctic and Oriental regions generally find good support in millipede distributions, in particular at the higher taxonomic levels (generic, familial, and ordinal). While the Palaearctic/Holarctic components expectedly dominate the fauna of the northern parts of the country, the Oriental ones prevail in its south and along the Pacific coast. Both realms are increasingly mixed and intermingled towards China's centre. However, in addition to the above traditional views, based on distribution patterns alone, southern China seems to harbour a rather small, but highly peculiar faunal nucleus or origin centre of its own, whence Himalaya, Myanmar, Thailand, Indochina and/or Taiwan could have become populated by younger lineages. The millipede fauna of continental China is thus a tangled mixture of zoogeographic elements of various origins and ages, both relict and more advanced. The few anthropochores must have been the latest faunal "layer" to populate China.

11.
Zootaxa ; 4722(1): zootaxa.4722.1.3, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32230637

RESUMO

The millipede, Niponia nodulosa Verhoeff, 1931 is recorded from Jiangsu and Zhejiang provinces, eastern China, for the first time. Two new species of the genus Epanerchodus Attems, 1901 are described from the Jiangzhe Area: Epanerchodus campus n. sp. and Epanerchodus bishou n. sp..


Assuntos
Artrópodes , Animais , China
12.
Ecotoxicol Environ Saf ; 194: 110378, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32146194

RESUMO

The primary purpose of this study was to systematically explore the complete metabolic pathway and tolerance mechanism of strain DNB-S1 to dibutyl phthalate (DBP), and the effect of DBP on energy metabolism of DNB-S1. Here, DNB-S1, a strain of Pseudomonas sp. that was highly effective in degrading DBP, was identified, and differentially expressed metabolites and metabolic networks of DBP were studied. The results showed that the differentially expressed metabolites were mainly aromatic compounds and lipid compounds, with only a few toxic intermediate metabolites. It speculated that phthalic acid, salicylic acid, 3-hydroxybenzoate acid, 3-Carboxy-cis, cis-muconate, fumarypyravate were intermediate metabolites of DBP. Their up-regulation indicated that there were two metabolic pathways in the degradation of DBP (protocatechuate pathway and gentisate pathway), which had been verified by peak changes at 290 nm, 320 nm, 330 nm, and 375 nm in the enzymatic method. Also, aspartate, GSH, and other metabolites were up-regulation, indicating that DNB-S1 had a high tolerance to DBP and maintained cell homeostasis, which was also one of the essential reasons to ensure the efficient degradation of DBP. Altogether, this study firstly proposed two pathways to degrade DBP and comprehensively explored the effect of DBP on the metabolic function of DNB-S1, which enriched the study of microbial metabolism of organic pollutants, and which provided a basis for the application of metabolomics.


Assuntos
Dibutilftalato/metabolismo , Poluentes Ambientais/metabolismo , Pseudomonas/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Biodegradação Ambiental , Dibutilftalato/toxicidade , Metabolismo Energético/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Pseudomonas/efeitos dos fármacos , Pseudomonas/crescimento & desenvolvimento
13.
Cell Discov ; 6: 4, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32025334

RESUMO

Metabolic surgery has been increasingly recommended for obese diabetic patients, but questions remain as to its molecular mechanism that leads to improved metabolic parameters independently of weight loss from a network viewpoint. We evaluated the role of the Roux limb (RL) in Roux-en-Y gastric bypass (RYGB) surgery in nonobese diabetic rat models. Improvements in metabolic parameters were greater in the long-RL RYGB group. Transcriptome profiles reveal that amelioration of diabetes state following RYGB differs remarkably from both normal and diabetic states. According to functional analysis, RYGB surgery significantly affected a major gene group, i.e., the newly changed group, which represented diabetes-irrelevant genes abnormally expressed after RYGB. We hypothesize that novel "dysfunctions" carried by this newly changed gene group induced by RYGB rebalance diabetic states and contribute to amelioration of metabolic parameters. An unusual increase in cholesterol (CHOL) biosynthesis in RL enriched by the newly changed group was concomitant with ameliorated metabolic parameters, as demonstrated by measurements of physiological parameters and biodistribution analysis using [14C]-labeled glucose. Our findings demonstrate RYGB-induced "dysfunctions" in the newly changed group as a compensatory role contributes to amelioration of diabetes. Rather than attempting to normalize "abnormal" molecules, we suggest a new disease treatment strategy of turning "normal" molecules "abnormal" in order to achieve a new "normal" physiological balance. It further implies a novel strategy for drug discovery, i.e. targeting also on "normal" molecules, which are traditionally ignored in pharmaceutical development.

14.
Heart Rhythm ; 17(6): 1025-1033, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32068183

RESUMO

BACKGROUND: Although ∼20% of the elderly population develops atrial fibrillation (AF), little is known about the mechanisms. Heart failure with preserved ejection fraction (HFpEF), which is associated with AF, is more common in aged women than in men. OBJECTIVE: The purpose of this study was to identify potential mechanisms of AF in an age-related HFpEF model. METHODS: In aged female Fischer F344 rats (21- to 24-month-old), which are prone to HFpEF, we induced AF by atrial pacing. Young Fischer F344 female rats (3- to 4-month-old) and age-matched Sprague Dawley female rats (27-month-old) served as controls. Phenotyping included echocardiography to assess left ventricular structure/function; in vivo electrophysiology and ex vivo high-resolution optical mapping to assess AF vulnerability; systemic and atrial inflammatory profiling; atrial histology; and expression of inflammasome signaling proteins. RESULTS: Aged rats developed left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, and pulmonary congestion, without ejection fraction impairment, thus meeting the criteria for HFpEF. Increased serum inflammatory markers, hypertension, and obesity further characterize aged females. Sinoatrial and atrioventricular node dysfunction was associated with the high inducibility of AF in aged rats. Ex vivo electrical activation mapping revealed abnormal ß-adrenergic responsiveness and slowed conduction velocity. Atrial inflammasome signaling was enhanced in aged rats, which may contribute to fibrotic remodeling and high AF susceptibility. CONCLUSION: Together, our data demonstrate that aging-related atrial remodeling and HFpEF are associated with atrial enlargement, fibrosis, conduction abnormalities, and nodal dysfunction, favoring a substrate conducive to AF.

15.
Can J Cardiol ; 36(4): 564-576, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32046907

RESUMO

BACKGROUND: Myocardial infarction and heart failure are associated with reduced voltage-gated Na+ current (INa) that promotes arrhythmias and sudden deaths. We have previously shown that the Wnt/ß-catenin signalling (Wnt signalling), which is active in heart disease, reduces cardiac INa, suggesting that Wnt signalling may be a potential therapeutic target. However, because Wnt signalling is required for the homeostasis of many noncardiac tissues, administration of Wnt inhibitors to heart patients would cause significant side effects. The present study aims to elucidate the molecular mechanisms of cardiac INa inhibition by Wnt, which would identify cardiac-specific therapeutic targets. METHODS: Wnt signalling was activated in neonatal rat ventricular myocytes by Wnt3a protein. Adenovirus expressing Wnt3a was injected into the adult rat ventricle. CRISPR/Cas9 and chromatin immunoprecipitation were used for mechanistic studies. RESULTS: Wnt signalling activation in neonatal rat ventricular myocytes reduced Nav1.5 protein and Scn5a mRNA, but increased Tbx3, a known suppressor of Scn5a. Chromatin immunoprecipitation showed that Wnt signalling inhibits Scn5a expression through downstream mediator (TCF4) binding to both Tbx3 and Scn5a promoters. Overexpression or knockdown of Tbx3 directly modified Nav1.5 and INa, whereas CRISPR/Cas9-induced mutations at TCF4 binding sites within the Scn5a promoter attenuated Wnt inhibition of Scn5a and Nav1.5. In adult rat hearts, adenovirus expressing Wnt3a reduced Nav1.5, increased QRS duration in electrocardiogram, and increased the susceptibility to ventricular tachycardia. CONCLUSIONS: Wnt signalling inhibits the Na+ channel by direct and indirect (via Tbx3) suppression of Scn5a transcription. Strategies to block TCF4 binding to the Tbx3 and Scn5a promoters would represent novel strategies for cardiac-specific inhibition of the Wnt pathway to rescue INa and prevent sudden cardiac deaths.


Assuntos
Miócitos Cardíacos/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canais de Sódio/fisiologia , Via de Sinalização Wnt , Animais , Regulação da Expressão Gênica , Ventrículos do Coração/citologia , Ratos
16.
BMC Public Health ; 19(1): 1722, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870346

RESUMO

BACKGROUND: To reveal the ethnic disparity in the pneumonia-specific mortality rates of children under the age of 5 years (PU5MRs) and provide suggestions regarding priority interventions to reduce preventable under-five-years-of-age deaths. METHODS: Data were obtained from the Direct Report System of Maternal and Child Health in Sichuan. The Cochran-Armitage trend test was used to assess the time trend. The Cochran-Mantel-Haenszel test and Chi-square test were used to examine the differences in the PU5MRs among different groups. RESULTS: The PU5MRs in the minority and nonminority counties decreased by 53.7 and 42.3% from 2010 to 2017, respectively. The PU5MRs of the minority counties were 4.81 times higher than those of the nonminority counties in 2017. The proportion of pneumonia deaths to total deaths in Sichuan Province increased from 11.7% in 2010 to 15.5% in 2017. The pneumonia-specific mortality rates of children in the categories of 0-28 days, 29 days-11 months, and 12-59 months were reduced by 55.1, 38.8, and 65.5%, respectively, in the minority counties and by 35.5, 43.1, and 43.7%, respectively, in the nonminority counties. CONCLUSIONS: PU5MRs declined in Sichuan, especially in the minority counties, while ethnic disparity still exists. Although the PU5MRs decreased more for the minority counties as a fraction of all mortality, the absolute number of such deaths were higher, and therefore more children in these counties continue to die from pneumonia than from the non-minority counties. Priority should be given to strategies for preventing and controlling child pneumonia, especially for postneonates, in the minority counties.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Grupos Minoritários/estatística & dados numéricos , Pneumonia/etnologia , Pneumonia/mortalidade , Distribuição de Qui-Quadrado , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Recém-Nascido
17.
Radiat Oncol ; 14(1): 225, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831042

RESUMO

PURPOSE: The purpose of this study was to determine the associations between pathological complete remission (pCR) and clinical outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received preoperative radiotherapy or chemoradiotherapy in a phase 3 clinical study. METHODS: A total of 222 newly diagnostic stage III/IVM0 HNSCC patients were randomly assigned to a preoperative concurrent chemoradiotherapy group (n = 104) or preoperative radiotherapy alone group (n = 118). Over a mean follow-up of 59 months, 72 patients were defined as non-responders to preoperative therapy and subsequently underwent resection of the primary lesion with or without neck dissection. The relationship between the pathological tumor response of the primary lesion and treatment prognosis was analyzed. Kaplan-Meier and Cox regression multivariate analyses were performed to evaluate the impact of pCR on local control (LC), overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). RESULTS: Among the 72 non-responders, 25 patients, 10 in the chemotherapy group and 15 in the radiotherapy group, achieved pCR. The 5-year LC, OS, PFS, and DMFS of pCR patients and non-pCR patients were 93.2% vs. 67.7% (p = 0.007), 83.3% vs. 39.7% (p = 0.0006), 76.1% vs. 44.0% (p = 0.009), and 90.4% vs. 56.3% (p = 0.005), respectively. In multivariate analysis, pCR is also an independent prognostic factor in prognosis, with statistically significant differences. CONCLUSION: pCR after preoperative radiotherapy or concurrent chemoradiotherapy is a good prognostic factor in locally advanced HNSCC. TRIAL REGISTRATION: Number:ChiCTR-TRC-114004322 Date:05 Mar, 2014.


Assuntos
Quimiorradioterapia/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Indução de Remissão , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Taxa de Sobrevida
18.
Micromachines (Basel) ; 11(1)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861476

RESUMO

With the fast development of the fifth-generation cellular network technology (5G), the future sensors and microelectromechanical systems (MEMS)/nanoelectromechanical systems (NEMS) are presenting a more and more critical role to provide information in our daily life. This review paper introduces the development trends and perspectives of the future sensors and MEMS/NEMS. Starting from the issues of the MEMS fabrication, we introduced typical MEMS sensors for their applications in the Internet of Things (IoTs), such as MEMS physical sensor, MEMS acoustic sensor, and MEMS gas sensor. Toward the trends in intelligence and less power consumption, MEMS components including MEMS/NEMS switch, piezoelectric micromachined ultrasonic transducer (PMUT), and MEMS energy harvesting were investigated to assist the future sensors, such as event-based or almost zero-power. Furthermore, MEMS rigid substrate toward NEMS flexible-based for flexibility and interface was discussed as another important development trend for next-generation wearable or multi-functional sensors. Around the issues about the big data and human-machine realization for human beings' manipulation, artificial intelligence (AI) and virtual reality (VR) technologies were finally realized using sensor nodes and its wave identification as future trends for various scenarios.

19.
Genes (Basel) ; 11(1)2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878242

RESUMO

We previously demonstrated that 20 mM sucrose promotes the upper axillary bud outgrowth in two-node stems of Chrysanthemum morifolium. In this study, we aimed to screen for potential genes involved in this process. Quantitative reverse transcription (qRT)-PCR analysis of sugar-related genes in the upper axillary bud of plants treated with 20 mM sucrose revealed the specific expression of the gene CmSWEET17. Expression of this gene was increased in the bud, as well as the leaves of C. morifolium, following exogenous sucrose treatment. CmSWEET17 was isolated from C. morifolium and a subcellular localization assay confirmed that the protein product was localized in the cell membrane. Overexpression of CmSWEET17 promoted upper axillary bud growth in the two-node stems treatment as compared with the wild-type. In addition, the expression of auxin transporter genes CmAUX1, CmLAX2, CmPIN1, CmPIN2, and CmPIN4 was upregulated in the upper axillary bud of CmSWEET17 overexpression lines, while indole-3-acetic acid content decreased. The results suggest that CmSWEET17 could be involved in the process of sucrose-induced axillary bud outgrowth in C. morifolium, possibly via the auxin transport pathway.


Assuntos
Chrysanthemum/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Proteínas de Plantas/metabolismo , Sacarose/farmacologia , Membrana Celular/metabolismo , Chrysanthemum/efeitos dos fármacos , Chrysanthemum/genética , Chrysanthemum/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Distribuição Tecidual
20.
PeerJ ; 7: e7968, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687280

RESUMO

Background: As the most frequently occurred tumor in biliary tract, cholangiocarcinoma (CCA) is mainly characterized by its late diagnosis and poor outcome. It is therefore urgent to identify specific genes and pathways associated with its progression and prognosis. Materials and Methods: The differentially expressed genes in The Cancer Genome Atlas were analyzed to build the co-expression network by Weighted gene co-expression network analysis (WGCNA). Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted for the selected genes. Module-clinical trait relationships were analyzed to explore the association with clinicopathological parameters. Log-rank tests and cox regression were used to identify the prognosis-related genes. Results: The most related modules with CCA development were tan module containing 181 genes and salmon module with 148 genes. GO analysis suggested enrichment terms of digestion, hormone transport and secretion, epithelial cell proliferation, signal release, fibroblast activation, response to acid chemical, wnt, Nicotinamide adenine dinucleotide phosphate metabolism. KEGG analysis demonstrated 15 significantly altered pathways including glutathione metabolism, wnt, central carbon metabolism, mTOR, pancreatic secretion, protein digestion, axon guidance, retinol metabolism, insulin secretion, salivary secretion, fat digestion. Key genes of SOX2, KIT, PRSS56, WNT9A, SLC4A4, PRRG4, PANX2, PIR, RASSF8, MFSD4A, INS, RNF39, IL1R2, CST1, and PPP3CA might be potential prognostic markers for CCA, of which RNF39 and PRSS56 also showed significant correlation with clinical stage. Discussion: Differentially expressed genes and key modules contributing to CCA development were identified by WGCNA. Our results offer novel insights into the characteristics in the etiology, prognosis, and treatment of CCA.

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