Transmitted by the whitefly Bemisia tabaci, tomato yellow leaf curly virus (TYLCV) has posed serious threats to plant growth and development. Plant innate immune systems against various threats ...involve WRKY Group III transcription factors (TFs). This group participates as a major component of biological processes in plants.
In this study, 6 WRKY Group III TFs (SolyWRKY41, SolyWRKY42, SolyWRKY53, SolyWRKY54, SolyWRKY80, and SolyWRKY81) were identified, and these TFs responded to TYLCV infection. Subcellular localization analysis indicated that SolyWRKY41 and SolyWRKY54 were nuclear proteins in vivo. Many elements, including W-box, were found in the promoter region of Group III TFs. Interaction network analysis revealed that Group III TFs could interact with other proteins, such as mitogen-activated protein kinase 5 (MAPK) and isochorismate synthase (ICS), to respond to biotic and abiotic stresses. Positive and negative expression patterns showed that WRKY Group III genes could also respond to TYLCV infection in tomato. The DNA content of TYLCV resistant lines after SolyWRKY41 and SolyWRKY54 were subjected to virus-induced gene silencing (VIGS) was lower than that of the control lines.
In the present study, 6 WRKY Group III TFs in tomato were identified to respond to TYLCV infection. Quantitative real-time-polymerase chain reaction (RT-qPCR) and VIGS analyses demonstrated that Group III genes served as positive and negative regulators in tomato-TYLCV interaction. WRKY Group III TFs could interact with other proteins by binding to cis elements existing in the promoter regions of other genes to regulate pathogen-related gene expression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bladder cancer is one of the most common cancers worldwide. The immune response and immune cell infiltration play crucial roles in tumour progression. Immunotherapy has delivered breakthrough ...achievements in the past decade in bladder cancer. Differentially expressed genes and immune-related genes (DEIRGs) were identified by using the edgeR package. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for functional enrichment analysis of DEIRGs. Survival-associated IRGs were identified by univariate Cox regression analysis. A prognostic model was established by univariate COX regression analysis, and verified by a validation prognostic model based on the GEO database. Patients were divided into high-risk and low-risk groups based on the median risk score value for immune cell infiltration and clinicopathological analyses. A regulatory network of survival-associated IRGs and potential transcription factors was constructed to investigate the potential regulatory mechanisms of survival-associated IRGs. Nomogram and ROC curve to verify the accuracy of the model. Quantitative real-time PCR was performed to validate the expression of relevant key genes in the prognostic model. A total of 259 differentially expressed IRGs were identified in the present study. KEGG pathway analysis of IRGs showed that the "cytokine-cytokine receptor interaction" pathway was the most significantly enriched pathway. Thirteen survival-associated IRGs were selected to establish a prognostic index for bladder cancer. In both TCGA prognostic model and GEO validation model, patients with high riskscore had worse prognosis compared to low riskscore group. A high infiltration level of macrophages was observed in high-risk patients. OGN, ELN, ANXA6, ILK and TGFB3 were identified as hub survival-associated IRGs in the network. EBF1, WWTR1, GATA6, MYH11, and MEF2C were involved in the transcriptional regulation of these survival-associated hub IRGs. The present study identified several survival-associated IRGs of clinical significance and established a prognostic index for bladder cancer outcome evaluation for the first time.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
To evaluate the effect of SGLT2 inhibitor (SGLT2i) on albuminuria, nephrin (NPH) and transforming-growth-factor-beta
1
(TGF-β1) levels in urine and low-grade inflammation in type 2 diabetes ...(T2D) patients. A randomized, blank-controlled clinical trial included 68 T2D patients and 10 controls. Based on the urinary albumin-to-creatinine ratio (UACR), 68 diabetic patients were stratified into three levels, UACR < 30 mg/g, UACR ≧ 30 mg/g to ≦ 300 mg/g and UACR ˃ 300 mg/g, who were randomized (1:1:1) to receive SGLT2i treatment for 12 weeks. The concentrations of NPH and TGF-β1 in urine were measured as indications of podocyte injury and renal fibrosis. Low-grade inflammation was assessed by the levels of IL-6, TNFα and hsCRP. After 12 weeks of SGLT2i treatment, the levels of UACR and NPH decreased, UTGF-β1 increased in the T2D with microalbuminuria and macroalbuminuria groups, NPH (1.12 0.59, 1.29 vs. 0.71 0.41, 1.07 µg/ml,
P
= 0.022) and (1.29 0.99, 1.96 vs. 0.93 0.57, 1.31 µg/ml,
P
= 0.002), UTGF-β1 (4.88 ± 1.31 vs. 7.27 ± 1.21 pg/ml,
P
< 0.001) and (4.30 ± 1.34 vs. 6.78 ± 2.59 pg/ml,
P
< 0.001), respectively. The changes in NPH were positively correlated with the UACR and negatively correlated with UTGF-β1 in T2D with albuminuria. SGLT2i alleviate nephrin loss and enhance TGF-β1 excretion in urine in T2DM with albuminuria. The anti-albuminuric effect of SGLT2i could be attributed to mitigating podocyte apoptosis and attenuating renal fibrosis.
Trial registration
This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
TP53 alterations are frequent relapse‐acquired mutations in childhood acute lymphoblastic leukemia (ALL). The present study evaluated the clinical significance of relapsed childhood ALL in Taiwan. ...Diagnostic and/or relapsed bone marrow or peripheral blood was obtained from 111 children with relapsed ALL who were initially treated by using Taiwan Pediatric Oncology Group (TPOG) ALL protocols from January 1997 to May 2018. Mutations were detected by PCR and sequencing, as well as by multiplex ligation‐dependent probe amplification to detect copy number alterations. Copy number and/or sequence alterations of TP53 were detected in 29% (28 of 98) and in 46% (6 of 13) of patients with relapsed B‐cell and T‐cell ALL, respectively. This incidence was much higher than that in several similar studies conducted in Caucasian populations. Seventy percent of all TP53 alterations were gained at relapse in 67 matched samples by back‐tracking matched diagnostic samples. TP53 alterations were associated with lower 5‐year event‐free survival (EFS) and overall survival (OS) rates (P = .013 and P = .0002, respectively). Multivariate analysis confirmed the prognostic significance of TP53 alterations. Forty‐five patients received hematopoietic stem‐cell transplantations post‐relapse. Patients with TP53 alterations (14/45) had inferior 5‐year EFS and OS than patients without TP53 alterations after transplantation (P = .002 and P = .001, respectively). The significance of these TP53 alterations for patients who received transplantations was confirmed by multivariate analysis. In conclusion, TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.
Relapsed pediatric ALL patients with TP53 alterations had inferior 5‐year EFS and OS. TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The prevalence of Restless legs syndrome (RLS) in End Stage Renal Disease (ESRD) patients is higher than that in the general population. However, the associations of RLS within the ESRD population ...are inconsistent and RLS is usually neglected in dialysis centers, although it impairs the life quality among ESRD patients. We aim to investigate the prevalence of RLS in patients with ESRD undergoing maintenance hemodialysis and evaluate the risk factors of developing RLS and the effect of RLS on quality of life among ESRD patients.
ESRD patients undergoing maintenance hemodialysis in Shanghai General Hospital dialysis unit from July 2016 to October 2016 were enrolled in the study. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). IRLSSG Severity Scale was used to evaluate the severity of RLS. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and Hospital Anxiety and Depression Scale (HADS) was used to estimate anxiety and depression. Serologic and historic variables were analyzed to determine predictors of RLS in the ESRD population.
A total of 137 ESRD patients were enrolled. The prevalence of RLS among the ESRD patients was 20.44%. The risk of RLS was increased significantly in females (OR = 2.729, p = 0.032) and daily alcohol drinkers (OR = 4.716, p = 0.022). RLS increased the risks of sleep disorders (25/28, 89.3% vs 73/109, 67.0%, p = 0.02) and sedative hypnotics intake (7/28, 25.0% vs 10/109, 9.2%, p = 0.047) and impaired the sleep quality (7/109 vs 11/28, p = 0.001) according to PSQI sum scores.
A high RLS prevalence among the ESRD patients undergoing hemodialysis was confirmed. ESRD patients who are women and drinking alcohol have a higher risk of RLS. The sleep quality was significantly impaired and sleeping medication use was more common among the ESRD patients with RLS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Post-stroke depression is a major neuropsychiatric complication after stroke.•IL-10 levels are significantly lower in PSD patients compared to those without.•IL-10 levels were significantly ...correlated with HAMD scores.•IL-10 levels can be used as an independent predictor of PSD.
Interleukin-10 (IL-10) is a pathophysiological factor in acute ischaemic stroke (AIS) and is relevant to mood disorders after stroke. We evaluated the predictive value of IL-10 in patients with post-stroke depression (PSD).
A total of 350 stroke patients were recruited at baseline, and 151 AIS patients were screened and completed a 1-month follow-up. Serum IL-10 levels were measured within 24 h of admission. We used the 17-item Hamilton Depression Scale (HAMD-17) to evaluate depression symptoms; PSD was defined as an HAMD score ≥ 7.
Fifty-one (33.8%) patients showed a more serious stroke degree, larger infarction volume, and poorer daily life activities and prognosis (P < 0.05) and were diagnosed with PSD at the 1-month follow-up. Their IL-10 level decreased significantly compared to the non-PSD group (P < 0.001). After adjusting for confounders, IL-10 could be used as an independent predictor for PSD with an adjusted odds ratio (OR) of 0.615 (95% CI 0.410–0.923, P = 0.019). In addition, the optimal cut-off value of IL-10 was 0.615 pg/mL based on an area under the receiver operating characteristic curve of 0.692 (95% CI 0.604–0.781, P < 0.001), demonstrating that IL-10 could predict the occurrence of PSD. Moreover, IL-10 was an indicator of stroke severity, living ability, and functional outcomes (P < 0.05).
IL-10 was only measured upon admission; dynamic changes need to be further monitored. This was also a single-centre study with a relatively small sample.
Lower IL-10 levels may be used to predict PSD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Interleukin (IL)− 33, a nuclear factor and pleiotropic cytokine of the IL-1 family, is gaining attention owing to its important role in chronic inflammatory and autoimmune diseases. This review ...extends our knowledge of the effects exerted by IL-33 on target cells by binding to its specific receptor serum stimulation-2 (ST2). Depending on the tissue context, IL-33 performs multiple functions encompassing host defence, immune response, initiation and amplification of inflammation, tissue repair, and homeostasis. The levels and activity of IL-33 in the body are controlled by complex IL-33-targeting regulatory pathways. The unique temporal and spatial expression patterns of IL-33 are associated with host homeostasis and the development of immune and inflammatory disorders. Therefore, understanding the origin, function, and processes of IL-33 under various conditions is crucial. This review summarises the regulatory mechanisms underlying the IL-33/ST2 signalling axis and its potential role and clinical significance in immune and inflammatory diseases, and discusses the current complex and conflicting findings related to IL-33 in host responses.
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•IL-33 is a dual identity alarmin with abundant roles and wide tissue distribution.•Host exists a complex and sophisticated regulatory mechanism targeting the IL-33-ST2 signalling axis.•Immunomodulation, tissue homeostasis, and metabolic regulation are the main roles of the IL-33-ST2 signalling axis.•IL-33 involves in many diseases pathophysiological process and has clinical implications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Herein, we report a facile and efficient synthetic method to construct azepino1,2-aindoles through a novel gold(I)-catalyzed intramolecular hydroarylation of alkynylindoles. A wide range of ...functional groups can be well tolerated in this transformation, and the corresponding highly functionalized azepino1,2-aindole skeletons were obtained in moderate to excellent yields. Subsequent oxidation of the products gave the interesting and valuable polycyclic carbazoles, which were widely used as the key building blocks in materials science.
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IJS, KILJ, NUK, PNG, UL, UM
A metal-free inactive C(sp
3
)-H bond functionalization of thioethers with styrenes using TBHP as an initiator and DBU as a base has been developed. This transformation has broken through the low ...activity of thioethers and realized moderate yields. Herein extended experiments were conducted to confirm the radical relay process, reaction energy and intermediate transformations.
Overcoming the low reactivity of thioethers, a C(sp
3
)-H bond functionalization of thioethers with styrenes using TBHP and DBU involving a radical relay process in metal-free conditions with theoretical questions elaborated is described.
Objectives There are increasing numbers of studies of pleural tags (PTs). The purpose of this case series was to classify the PTs in patients with peripheral pulmonary adenocarcinoma based on ...radiologic-pathologic comparison and to study the prognosis. Methods The clinical, imaging, pathological and prognostic data of 161 patients with peripheral pulmonary adenocarcinoma in three hospitals were analyzed retrospectively. We classified PTs using computed tomography (CT) for pathologic comparison. Results According to the relationship between tumors and pleural on CT images, PTs were classified into four types: type 1, one or more linear pleural tag; type 2, one or more linear pleural tag with soft tissue component at the pleural end; type 3, one soft tissue cord-like pleural tag; type 4, directly abutting the visceral pleura, pulling or pushing the visceral pleura. In these PTs, the incidence of visceral pleural invasion (VPI) was high in type 2 (46.88%) and type 3 (56.41%) of PTs. Our prognostic analysis showed that micropapillary or solid histological subtype (HR = 5.766, 95% CI: 1.435-23.159, P = 0.014) and type 3 of PTs (HR = 11.058, 95% CI: 1.349-90.623, P = 0.025) were two independent risk factors for tumor progression. Conclusions PT is a risk factor for poor prognosis in patients with peripheral pulmonary adenocarcinoma, the presence of which on CT images can remind us to provide patients with a more reasonable treatment. Keywords: Visceral pleural invasion, Pleural tag, Computed tomography, Pathology, Prognosis
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK