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1.
Plant Cell ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371546

RESUMO

The Arabidopsis (Arabidopsis thaliana) root epidermis consists of a position-dependent pattern of root-hair cells and non-hair cells. Underlying this cell-type patterning is a network of transcription factors including a central MYB-bHLH-WD40 complex containing WEREWOLF (WER), GLABRA 3/ENHANCER OF GLABRA 3 (GL3/EGL3), and TRANSPARENT TESTA GLABRA 1 (TTG1). In this study, we used a genetic enhancer screen to identify apum23-4, a mutant allele of the ribosome biogenesis factor (RBF) gene PUMILIO 23 (APUM23), which caused prospective root-hair cells to instead adopt the non-hair cell fate. We discovered that this cell fate switch relied on MYB23, a MYB protein encoded by a WER target gene and acting redundantly with WER. In the apum23-4 mutant, MYB23 exhibited ectopic expression that was WER-independent and instead required ANAC082, a recently identified ribosomal stress response mediator. We examined additional RBF mutants that produced ectopic non-hair cells and determined that this cell fate switch is generally linked to defects in ribosome biogenesis. Further, the flagellin peptide flg22 triggers the ANAC082-MYB23-GL2 pathway. Taken together, our study provides a molecular explanation for root epidermal cell fate switch in response to ribosomal defects and, more generally, it demonstrates a novel regulatory connection between stress conditions and cell fate control in plants.

2.
Thorac Cancer ; 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32310341

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis to synthesize the available evidence regarding short-term outcomes between minimally invasive esophagectomy (MIE) and open esophagectomy (OE). METHODS: Studies were identified by searching databases including PubMed, EMBASE, Web of Science and Cochrane Library up to March 2019 without language restrictions. Results of these searches were filtered according to a set of eligibility criteria and analyzed in line with PRISMA guidelines. RESULTS: There were 33 studies included with a total of 13 269 patients in our review, out of which 4948 cases were of MIE and 8321 cases were of OE. The pooled results suggested that MIE had a better outcome regarding all-cause respiratory complications (RCs) (OR = 0.56, 95% CI = 0.41-0.78, P = <0.001), in-hospital duration (SMD = -0.51; 95% CI = -0.78-0.24; P = <0.001), and blood loss (SMD = -1.44; 95% CI = -1.95-0.93; P = <0.001). OE was associated with shorter duration of operation time, while no statistically significant differences were observed regarding other outcomes. Additionally, subgroup analyses were performed for a number of different postoperative events. CONCLUSIONS: Our study indicated that MIE had more favorable outcomes than OE from the perspective of short-term outcomes. Further large-scale, multicenter randomized control trials are needed to explore the long-term survival outcomes after MIE versus OE.

3.
J Exp Med ; 217(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32271880

RESUMO

Hyperactivation of YAP has been commonly associated with tumorigenesis, and emerging evidence hints at multilayered Hippo-independent regulations of YAP. In this study, we identified a new MST4-YAP axis, which acts as a noncanonical Hippo signaling pathway that limits stress-induced YAP activation. MST4 kinase directly phosphorylated YAP at Thr83 to block its binding with importin α, therefore leading to YAP cytoplasmic retention and inactivation. Due to a consequential interplay between MST4-mediated YAP phospho-Thr83 signaling and the classical YAP phospho-Ser127 signaling, the phosphorylation level of YAP at Thr83 was correlated to that at Ser127. Mutation of T83E mimicking MST4-mediated alternative signaling restrained the activity of both wild-type YAP and its S127A mutant mimicking loss of classical Hippo signal. Depletion of MST4 in mice promoted gastric tumorigenesis with diminished Thr83 phosphorylation and hyperactivation of YAP. Moreover, loss of MST4-YAP signaling was associated with poor prognosis of human gastric cancer. Collectively, our study uncovered a noncanonical MST4-YAP signaling axis essential for suppressing gastric tumorigenesis.

4.
J Ethnopharmacol ; 254: 112611, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32088246

RESUMO

ETHNOPHAMACOLOGICAL RELEVANCE: The Chinese herbal prescription JieZe-1 (JZ-1) is based on the modification of Yihuang Tang, which was first described in Fu Qingzhu Nvke by the famous Qing Dynasty doctor Shan Fu as a treatment for leukorrheal diseases. As an in-hospital preparation, JZ-1 has been used in Tongji Hospital for many years to treat various infectious diseases of the lower female genital tract, including cervicitis, vaginitis, genital herpes and condyloma acuminatum. Our previous studies have shown that JZ-1 has curative effects on Candida albicans, Trichomonas vaginalis and Ureaplasma urealyticum infections. AIM OF THE STUDY: Genital herpes is among the most common sexually transmitted diseases (STDs) worldwide and is mainly caused by herpes simplex virus type-2 (HSV-2). Current therapies can relieve symptoms in patients but do not cure or prevent the spread of the virus. This study was designed to investigate the effect of JZ-1 on HSV-2 infection and its mechanism, which is based on autophagy induction, to provide new ideas and a basis for the study of antiviral drugs. MATERIALS AND METHODS: Evaluation of the antiviral activity of JZ-1 was conducted by MTT assay and western blotting. Then, Western blot and immunofluorescence analyses, observations through transmission electron microscopy and experiments with the recombinant lentivirus vector mRFP-GFP-LC3B were used to monitor autophagic flux in VK2/E6E7 cells. To explore the mechanism by which JZ-1 regulates autophagy, western blotting and real-time quantitative PCR (qRT-PCR) were used to determine the expression of phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway proteins and to detect changes in critical molecules in the pathway after the application of a PI3K inhibitor. Additionally, the mRNA expression levels of inflammatory cytokines, namely, IL-6, IFN-α, IFN-ß and TNF-α, were measured with qRT-PCR. RESULTS: HSV-2 infection inhibited autophagy in the VK2/E6E7 cells. Further study revealed that the activation of the PI3K/Akt/mTOR pathway induced by HSV-2 infection may result in the blocked autophagic flux and inhibited autophagosome and autolysosome formation. JZ-1 exhibited significant antiviral activity in the VK2/E6E7 cells, which showed increased cell vitality and reduced viral protein expression, namely, earliest virus-specific infected cell polypeptides 5 (ICP5) and glycoprotein D (gD). We found that JZ-1 treatment inhibited the upregulation of the PI3K/Akt/mTOR pathway proteins and promoted autophagy to combat HSV-2 infection, while PI3K inhibitor pretreatment prevented the enhanced autophagy induced by JZ-1. Moreover, JZ-1 attenuated the increase in inflammatory cytokines that had been induced HSV-2 infection. CONCLUSION: Our results showed that JZ-1 protects against HSV-2 infection, and this beneficial effect may be mediated by inducing autophagy via inhibition of the PI3K/Akt/mTOR signaling axis.

5.
World J Gastroenterol ; 26(6): 614-626, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32103871

RESUMO

BACKGROUND: This study determined the composition and diversity of intestinal microflora in patients with colorectal adenoma (CRA), which may provide precedence for investigating the role of intestinal microflora in the pathogenesis of colorectal tumors, the composition of intestinal microflora closely related to CRA, and further validating the possibility of intestinal flora as a biomarker of CRA. AIM: To study the relationship between intestinal microflora and CRA. METHODS: This is a prospective control case study from October 2014 to June 2015 involving healthy volunteers and patients with advanced CRA. High-throughput sequencing and bioinformatics analysis were used to investigate the composition and diversity of intestinal microflora in 36 healthy subjects and 49 patients with advanced CRA. Endpoints measured were operational taxonomic units of intestinal flora, as well as their abundance and diversity (α and ß types). RESULTS: In this study, the age, gender, body mass index, as well as location between controls and patients had no significant differences. The mucosa-associated gut microbiota diversity and bacterial distribution in healthy controls and colorectal adenomas were similar. The operational taxonomic unit, abundance, and α and ß diversity were all reduced in patients with CRA compared to controls. At the phylum level, the composition of intestinal microflora was comparable between patients and controls, but the abundance of Proteobacteria was increased, and Firmicutes and Bacteroides were significantly decreased (P < 0.05). The increase in Halomonadaceae and Shewanella algae, and reduction in Coprococcus and Bacteroides ovatus, could serve as biomarkers of CRA. High-throughput sequencing confirms the special characteristics and diversity of intestinal microflora in healthy controls and patients with CRA. CONCLUSION: The diversity of intestinal microflora was decreased in patients with CRA. An increase in Halomonadaceae and Shewanella algae are markers of CRA.

6.
Ann Thorac Surg ; 109(5): 1551-1557, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31987829

RESUMO

BACKGROUND: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a promising checkpoint. However, its features and prognostic value remain undetermined in esophageal squamous cell carcinoma (ESCC). This study evaluated the prognostic value of TIM-3 expression and its relationship with programmed cell death 1 (PD-1) and CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected ESCC. METHODS: Expression levels of TIM-3, PD-1, and CD8+ TILs in ESCC were determined by immunohistochemistry. The association between clinicopathologic features or clinical outcomes and TIM-3 expression was analyzed. RESULTS: A total of 183 patients with ESCC who had undergone esophagectomy without implementation of neoadjuvant therapy at the Second Affiliated Hospital of Soochow University in Suzhou, China from January 2009 to December 2014 were included. PD-1 positivity (P = .032) and high CD8+ TIL density (P = .035) significantly correlated with positive TIM-3 expression. TIM-3 positivity was an independent risk factor for recurrence-free survival (RFS) (P < .001) and overall survival (OS) (P < .001). Subgroup analysis revealed that the TIM-3+PD-1+CD8 low group had the worst RFS and OS, whereas the TIM-3-PD-1-CD8 high group had the best RFS and OS (RFS: log-rank test P < .001; OS: log-rank test P < .001). CONCLUSIONS: Positive TIM-3 expression was associated with PD-1 positivity and high CD8+ TIL density and was an independent risk factor for RFS and OS in ESCC. Furthermore, the combination of TIM-3 and PD-1 expression or CD8+ TIL density could further stratify patients into different groups with distinct prognosis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31931089

RESUMO

OBJECTIVES: Previous studies have shown that cognitive impairment plays a key role in suicide, an important factor leading to premature death in schizophrenia (SCZ) patients. Empathy has received extensive attention recently; however, the relationship of empathy with suicide in schizophrenia is still unknown. The main aim of this study was to investigate the prevalence of suicide attempts and its association with empathy and other characteristics in Chinese chronic SCZ patients. METHODS: The suicide attempt data, together with demographic characteristics and clinical variables were collected from 627 chronic inpatients with schizophrenia. We utilized the Positive and Negative Syndrome Scale (PANSS) for the psychopathological symptoms, and the Interpersonal Reactivity Index (IRI) for affective and cognitive empathy in this study. RESULTS: We found a suicide attempt rate of 11.3% in chronic SCZ patients. Compared to non-attempters, suicide attempters were more likely to be women, had younger age and higher education levels, as well as higher positive symptoms and depressive factor score, but lower negative symptoms of PANSS (all p < .05). Moreover, after controlling the confounding factors, suicide attempters scored higher in Personal Distress subscale of IRI (F1, 455 = 5.446, p = .020) than non-attempters. CONCLUSIONS: The prevalence of suicide attempt is high in chronic SCZ patients. Its risk factors include some demographic and clinical variables. Moreover, suicide attempters experienced stronger personal distress, suggesting that stronger empathy may be a risk factor of suicide.

8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 74-80, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950793

RESUMO

Objective: To develop an assay for determination of 8-oxo-2'-deoxyguanosine and cotinine in human urine by hydrophilic chromatography tandem mass spectrometry (HILIC-MS/MS) with isotope dilution. Methods: The urine supernatant was 1∶5 diluted with 3 mmol/L ammonium formate aqueous solution containing 15N 5-8-OHdG and D 3-cotinine as internal standard. After being filtered through a 0.22 µm water filter, the sample solution was injected into ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for analysis. Separation was performed on ACQUITY UPLC® BEH HILIC column (50 mm×3.0 mm, 1.7 µm) with isocratic elution (A∶B=10∶90) at 40 ℃. The mobile phase was composed with acetonitrile (B) and 3 mmol/L ammonium formate water soulution (A). The flow rate was 0.3 mL/min. Positive ion scan-multiple reaction monitoring (MRM) mode were used for monitoring and internal standard curves were applied for quantification. Results: Good linearity was obtained under the optimal conditions. Detection limits for 8-OHdG and cotinine were 0.064 µg/L and 0.035 µg/L respectively, the quantitation limits were 0.21 µg/L and 0.12 µg/L respectively, and the recoveries of the spiked urine samples were 92.6%-102% and 102%-106% respectively. Statistical analysis of 40 urine sample determination results obtained by using the above assay showed that there were significant differences in tobacco smoke exposure and tobacco-specific nitrosamine intake between active and passive smoker ( P<0.05). The concentration of NNAL and cotinine were higher in urine samples of active smoker. Tobacco smoke exposure was positively correlated with tobacco specific nitrosamine intake in both active and passive smokers (the correlation coefficients were 0.487 and 0.786 respectively, P<0.05). Conclusion: We successfully established a simple and fast assay for simultaneously detecting 8-oxo-2'-deoxyguanosine and cotinine in human urine. It was sensitive and accurate for quntification via the calibration by the isotope internal standards, and can meet the needs of batch analysis.


Assuntos
8-Hidroxi-2'-Desoxiguanosina , Cromatografia Líquida de Alta Pressão , Cotinina , Espectrometria de Massas em Tandem , Urinálise , 8-Hidroxi-2'-Desoxiguanosina/urina , Cotinina/urina , Humanos , Isótopos/química , Urinálise/métodos
9.
Clin Neurophysiol ; 131(3): 725-733, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32000073

RESUMO

OBJECTIVE: Cognitive deficits are core symptoms of schizophrenia; however, their pathophysiological mechanisms are still unclear. A sensory gating deficit, as reflected by P50 suppression, has been repeatedly shown in schizophrenia patients, which may be associated with cognitive deficits in this disorder. The present study was to examine the relationship between the P50 suppression and cognitive deficits in patients with schizophrenia, which is still under-investigated. METHOD: We recruited 38 chronic schizophrenia patients and 32 matched healthy controls, and assessed their cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and P50 suppression with the electroencephalography system. RESULTS: The total and its 4 index scores (all p < 0.05) except for the visuospatial/ constructional index of RBANS were significantly lower in patients compared with healthy controls. However, only the language and attention passed Bonferroni corrections. Patients displayed a significantly higher P50 ratio, higher S2 amplitude, and lower S1 amplitude (all p < 0.05) than healthy controls. Interestingly, only in the patients, the S1 amplitude was associated with both language and attention, and the S2 amplitude with both visuospatial/ constructional and language (all p < 0.05), although all of these significances did not pass the Bonferroni corrections. The P50 ratio was not associated with any of the RBANS scores (all p > 0.05). CONCLUSIONS: Our results suggest the P50 suppression deficits in Chinese patients with schizophrenia, which may be associated with cognitive impairments of this illness. Moreover, the amplitude of S1 and the amplitude of S2 may be involved in the different cognitive domain deficits in schizophrenia patients. SIGNIFICANCE: This study suggests that the P50 components may possibly be effective biomarkers for cognitive deficits in patients with schizophrenia.

10.
Cancer Res ; 80(3): 510-523, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31551363

RESUMO

The tumor suppressor gene ATRX is frequently mutated in a variety of tumors including gliomas and liver cancers, which are highly unresponsive to current therapies. Here, we performed a genome-wide synthetic lethal screen, using CRISPR-Cas9 genome editing, to identify potential therapeutic targets specific for ATRX-mutated cancers. In isogenic hepatocellular carcinoma (HCC) cell lines engineered for ATRX loss, we identified 58 genes, including the checkpoint kinase WEE1, uniquely required for the cell growth of ATRX null cells. Treatment with the WEE1 inhibitor AZD1775 robustly inhibited the growth of several ATRX-deficient HCC cell lines in vitro, as well as xenografts in vivo. The increased sensitivity to the WEE1 inhibitor was caused by accumulated DNA damage-induced apoptosis. AZD1775 also selectively inhibited the proliferation of patient-derived primary cell lines from gliomas with naturally occurring ATRX mutations, indicating that the synthetic lethal relationship between WEE1 and ATRX could be exploited in a broader spectrum of human tumors. As WEE1 inhibitors have been investigated in several phase II clinical trials, our discovery provides the basis for an easily clinically testable therapeutic strategy specific for cancers deficient in ATRX. SIGNIFICANCE: ATRX-mutant cancer cells depend on WEE1, which provides a basis for therapeutically targeting WEE1 in ATRX-deficient cancers.See related commentary by Cole, p. 375.

11.
ISA Trans ; 96: 245-254, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31303339

RESUMO

This study mainly investigates the problem of distributed tracking control for time-varying delay existing multiple Euler-Lagrange systems considering full-state constraints and input saturation under the directed graph. Specifically, the system under consideration consists of system uncertainties and external disturbances. In the control law design, a distributed observer is first designed that the followers can obtain the leader's time-varying information. Then the barrier Lyapunov function technique is used to make sure the system errors can converge to a certain range while the anti-windup method is utilized to overcome the influence of control input saturation. Further, in order to prevent chattering, an adaptive law is given. Numerical simulations are given to verify the proposed algorithms.

12.
Schizophr Res ; 215: 105-112, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31780341

RESUMO

OBJECTIVE: Cognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point. METHODS: A total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system. RESULTS: The MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all p < 0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both p < 0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all p > 0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all p > 0.05). CONCLUSIONS: Our findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment.

13.
J Chromatogr A ; 1614: 460710, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31784082

RESUMO

To monitor the existing and emerging halogenated carboxylic acids (HCAs) in drinking water, a sensitive and rapid ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry method for simultaneous target quantification of 10 haloacetic acids (HAAs) and semi-target screening of 19 HCAs was developed. After filtration, drinking water samples were injected into the instrument. HCAs were separated on an HSS T3 column and detected by a type of non-target scan in the electrospray ionization negative mode. For target quantification of 10 HAAs, good linearity was obtained and the correlation coefficients were higher than 0.995. The limits of detection were in the range of 0.050-2.0 µg/L. The recoveries were in the range of 89.7%-108%, 83.4%-121%, 77.1%-116% and 80.2%-104% at levels of 2.5, 5.0, 10 and 20 µg/L, respectively, with relative standard deviations of 1.26%-16.9%. For semi-target screening of 19 HCAs, several criteria including accurate m/z, predicted retention time, deduced fragment ions and simulated isotope pattern were used for identification. The method was applied to analyzing 41 drinking water samples successfully. Five HAAs were detected by target quantification, with dichloroacetic acid and trichloroacetic acid exceeding the limits suggested by the U.S. Environmental Protection Agency and the World Health Organization. Eight HCAs were preliminary identified by semi-target screening, and three of them were further confirmed with reference standards purchased later.

15.
Biomed Res Int ; 2019: 4820167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662978

RESUMO

Pupil blocking force (PBF) can indicate the potential risk of pupil block (PB), which is considered as a main pathogenic factor of primary angle-closure glaucoma (PACG). However, the effect of PB on the PBF under different pupil diameters and iris-lens channel (ILC) distance was unknown. Besides, a simple and practical method to assess PBF has not been reported yet. In this study, 21 finite element models of eyes with various pupil diameters (2.4 mm-2.6 mm) and ILC (2 µm-20 µm) were constructed and were conducted to simulate aqueous humor flow by fluid-solid coupling numerical simulation. PBF in each model was calculated based on the numerical simulation results and was fitted using response surface methodology. The results demonstrated that ILC distance had a more significant effect than pupil diameter on PBF. With the decrease of ILC distance, the PBF increased exponentially. When the reduced distance was lower than 5 µm, the PBF exploded quickly, resulting in a high risk of iris bomb. The PBF also varied with pupil diameter, especially under the condition of narrow ILC. Both ILC distance and pupil diameter could explain more than 97% variation in PBF, and a second-order empirical model has been developed to be a good predictor of PBF. Based on the linear relationship between anterior chamber deformation and PBF, a threshold value of PBF was given to guide clinical decisions. This study could be used to investigate PACG pathological correlation and its pathogenesis, so as to provide a reference value for clinical diagnosis of PACG.

16.
BMC Vet Res ; 15(1): 311, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477115

RESUMO

BACKGROUND: Norovirus (NoV) is recognized as a highly contagious enteric pathogen of mammals, and bovine norovirus (BNoV) is associated with calf diarrhoea and has caused great economic losses in the cattle industry. RESULTS: Here, we describe a case of emerging calf diarrhoea on a cattle farm in Henan Province, Central China. BNoV was the only enteric pathogen detected in outbreaks according to tests for enteric viruses, bacteria and parasites. The complete genome of the newly identified strain CH-HNSC-2018 was successfully sequenced and found to be 7342 nucleotides in length. Sequence and phylogenetic analyses revealed that CH-HNSC-2018 belongs to GIII.2 BNoV. Further analysis of the major capsid protein demonstrated that it is separated by specific genetic distances from previous BNoV strains identified in China and has 4 new amino acid (aa) mutations, 134A, 327 T, 380 L and 423A, in the VP1 protein and 11 aa substitutions in the hypervariable P2 subdomain, suggesting that the BNoV strains circulating in China are diverse. CONCLUSIONS: This is the first detection of GIII.2 BNoV in the VP1 region in China. This report should form a basis for further molecular studies on NoV and bovine enteric viruses in China.


Assuntos
Infecções por Caliciviridae/veterinária , Doenças dos Bovinos/virologia , Diarreia/veterinária , Genótipo , Norovirus/isolamento & purificação , Filogenia , Animais , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Bovinos , China/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/veterinária , Doenças Transmissíveis Emergentes/virologia , Diarreia/epidemiologia , Diarreia/virologia , Surtos de Doenças/veterinária , Norovirus/genética
17.
Plant Physiol ; 181(3): 1239-1256, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31492737

RESUMO

The Arabidopsis (Arabidopsis thaliana) root epidermis exhibits a position-dependent pattern of root-hair and nonhair cell types. A highly orchestrated network of gene regulatory interactions, including the R2R3-type MYB transcription factor WEREWOLF (WER), is responsible for generating this cell pattern during root development. In this study, we identified a novel wer mutant from a genetic enhancer screen, designated wer-4, that exhibits an abnormal pattern of root-hair and nonhair cells. We established that wer-4 bears a single-residue substitution (D105N) in the DNA-binding R3 MYB repeat of WER, which differentially affects the transcription of WER target genes, including GLABRA2, CAPRICE, TRIPTYCHON, and ENHANCER OF TRY AND CPC1 This modulation of the gene regulatory network leads to altered levels and distributions of cell fate regulators in the differentiating epidermal cells that ultimately generate the abnormal cell-type pattern. We also created several WER variants with substitutions at the Asp-105 position, and these exhibited a variety of gene expression and cell-type pattern alterations, further supporting the critical role of this residue. These findings provide insight into WER protein function and its importance in generating the proper balance of downstream transcriptional factors in the gene regulatory network that establishes root epidermal cell fate.

18.
Front Physiol ; 10: 1102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507457

RESUMO

Toll-like receptor 2 (TLR2), which recognizes several lipopeptides and transduces inflammatory signaling, promotes the pathogenesis of diet-induced dyslipidemia and obesity. TLR2-deficient mice were shown to have improved insulin sensitivity and reduced diet-induced metabolic syndrome. Previous studies demonstrated that prenatal lipopolysaccharide (LPS) exposure causes dyslipidemia accompanied by increased body weight and insulin resistance in offspring. To determine whether TLRs are involved in this complex abnormal phenotype, we analyzed TLR2 and TLR4 expression levels in adipose tissues from offspring with prenatal LPS-exposure (offspring-pLPS) and compared these levels to those of control offspring with prenatal saline-exposure (offspring-pSaline). TLR2 expression was specifically upregulated in the adipose tissue of offspring-pLPS mice. However, unexpectedly, TLR2-deficient offspring-pLPS mice not only presented with an abnormal phenotype comparable to that of wild-type offspring-pLPS mice but also exhibited significantly more severe hyperlipidemia. Our further analyses revealed a dramatic upregulation of TLR4 expression and overactivation of the TLR4/Myd88 signaling pathway in TLR2-deficient offspring-pLPS adipose tissue. Our finding suggests a compensatory genetic interaction between TLR2 and TLR4 in the context of prenatal inflammatory stimulation, and this interaction likely contributes to the prenatal inflammation-induced hyperlipidemia and lipid overload-induced obesity, thus providing a potential mechanism for the fetal origin of adult metabolic diseases.

19.
Thorac Cancer ; 10(8): 1725-1735, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31293066

RESUMO

BACKGROUND: Lower thoracic esophageal cancer (LTEC) with celiac node metastasis and upper thoracic esophageal cancer (UTEC) with supraclavicular node metastasis were previously categorized as M1a diseases. Our study aimed to investigate whether the clinical significance of supraclavicular and celiac lymph node metastasis should be reevaluated in thoracic esophageal cancer. METHODS: A total of 6178 patients with thoracic esophageal cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2015. Treatment strategies and outcomes (OS, overall survival; CSS, cancer-specific survival) of patients with different nodal status were reviewed. The Cox proportional hazards regression model was applied to evaluate the prognostic factors. Statistical analyses were performed in all subgroups. RESULTS: Multivariate analysis identified supraclavicular node metastasis but not celiac node metastasis as an independent predictor of both OS and CSS in LTEC. However, metastasis to supraclavicular or celiac nodes was not an independent predictor of OS and CSS in UTEC. Surgery was not associated with increased OS and CSS for UTEC with celiac or supraclavicular node metastasis but was favored as a predictor of better OS and CSS for LTEC with celiac or supraclavicular node metastasis. Radiotherapy benefited OS and CSS in LTEC involving celiac or supraclavicular nodes and in UTEC involving celiac nodes, while only OS benefited from radiotherapy in UTEC involving supraclavicular nodes. CONCLUSIONS: These results provide preliminary evidence that the clinical significance of supraclavicular and celiac lymph node metastasis should be reevaluated in thoracic esophageal cancer with different prognostic information according to the primary sites.

20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(2): 315-319, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31016950

RESUMO

There are so many biomechanical risk factors related with glaucoma and their relationship is much complex. This paper reviewed the state-of-the-art research works on glaucoma related mechanical effects. With regards to the development perspectives of studies on glaucoma biomechanics, a completely novel biomechanical evaluation factor -- Fractional Flow Reserve (FPR) for glaucoma was proposed, and developing clinical application oriented glaucoma risk assessment algorithm and application system by using the new techniques such as artificial intelligence and machine learning were suggested.


Assuntos
Glaucoma/diagnóstico , Algoritmos , Inteligência Artificial , Fenômenos Biomecânicos , Humanos , Pressão Intraocular , Aprendizado de Máquina , Medição de Risco , Fatores de Risco
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