A Novel DNA Binding Mechanism for maf Basic Region-Leucine Zipper Factors Inferred from a MafA–DNA Complex Structure and Binding Specificities

MafA is a proto-oncoprotein and is critical for insulin gene expression in pancreatic β-cells. Maf proteins belong to the AP1 superfamily of basic region-leucine zipper (bZIP) transcription factors. Residues in the basic helix and an ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf proteins with unique DNA binding properties: binding a 13 bp consensus site consisting of a core AP1 site (TGACTCA) flanked by TGC sequences and binding DNA stably as monomers. To further characterize maf DNA binding, we determined the structure of a MafA–DNA complex. MafA forms base-specific hydrogen bonds with the flanking G_–5C_–4 and central C₀/G₀ bases, but not with the core-TGA bases. However, in vitro binding studies utilizing a pulse–chase electrophoretic mobility shift assay protocol revealed that mutating either the core-TGA or flanking-TGC bases dramatically increases the binding off rate. Comparing the known maf structures, we propose that DNA binding specificity results from positioning the basic helix through unique phosphate contacts. The EHR does not contact DNA directly but stabilizes DNA binding by contacting the basic helix. Collectively, these results suggest a novel multistep DNA binding process involving a conformational change from contacting the core-TGA to contacting the flanking-TGC bases

Table_1_Sarcopenia increases the risk of early biliary infection after percutaneous transhepatic biliary stent placement.docx

PurposeTo assess the association between sarcopenia and the risk of early biliary infection (EBI) after percutaneous transhepatic biliary stent (PTBS) placement in patients with inoperable biliary tract cancer (BTC).Patients and methodsIn this single center, retrospective observational study, patients diagnosed with inoperable BTC undergoing PTBS placement between January 2013 and July 2021 were enrolled. Preoperative sarcopenia was defined based on skeletal muscle mass measured by computed tomography images on the level of third lumbar vertebra within one month before PTBS placement. Patients were divided into two groups in accordance with the status of sarcopenia. Univariate and further multivariate logistic analyses were performed to determine predictors for EBI. Stratified and interactive analyses were conducted to investigate the stability of results. Further receiver operating characteristic curve was performed to determine the predictive value of sarcopenia on EBI after PTBS placement.ResultsTotally, 134 patients were included in this retrospective study, with 45 (33.6%) patients characterized as sarcopenia. The incidence rate of EBI was 26.9% (36/134). Multivariate analyses demonstrated that sarcopenia [Odds ratio (OR), 2.75; 95%CI: 1.11–6.77; P=0.028], obstruction length (OR, 1.04; 95%CI: 1.00–1.08; P=0.030) and diabetes (OR, 2.46; 95%CI: 1.01–5.96; P=0.047) were significant predictors of EBI. There were no significant interactions in different subgroups (P for interaction > 0.05). Moreover, the areas under the curves (AUC) revealed that the combined index containing sarcopenia, obstruction length, and diabetes showed the better predictive value (AUC= 0.723) than either one alone.ConclusionSarcopenia increased the risk of EBI in patients with inoperable BTC after PTBS placement. Preoperative assessment of sarcopenia may aid in risk stratification. Patients with sarcopenia should be given intensive monitoring.</p

Table4_The predictive value of prognostic nutritional index on early complications after robot-assisted radical cystectomy.docx

ObjectiveThe purpose of the study was to evaluate the predictive value of prognostic nutritional index (PNI) on early complications (within 30-day) after robot-assisted radical cystectomy (RARC) and urinary diversion.Patients and methodsPatients underwent RARC and urinary diversion between November 2018 and December 2021 in our centre were screened in this retrospective study. Baseline characteristics and perioperative data were recorded. Early complications after surgery were classified according to Clavien-Dindo system. Univariate and multivariate logistic analysis were performed to decide the potential factors associated with post-RARC complications. The receiver operating characteristic (ROC) curve was conducted to determine the predictive value of PNI on early overall and major complications after RARC.ResultsOverall 139 men and 13 women with a median age of 69 years and mean BMI of 24.4 kg/m2 were included in this study. As for urinary diversion, most patients (n = 111, 73%) received cutaneous ureterostomy, 36 patients (23.7%) underwent orthotopic neobladder and 5 patients (3.3%) received ileal conduit. The incidence of postoperative complication rate was 44.7%, which included 82.2% minor complications and 17.8% major complications. Further univariate and multivariate logistic analyses demonstrated that hypertension (OR = 2.96, 95% CI: 1.24–7.07, P = 0.015), PNI (OR = 0.73, 95% CI: 0.62–0.86, P ConclusionPNI can be an early alert for RARC patients thus aiding in closer monitoring and postoperative management.</p

Image1_The predictive value of prognostic nutritional index on early complications after robot-assisted radical cystectomy.tif

ObjectiveThe purpose of the study was to evaluate the predictive value of prognostic nutritional index (PNI) on early complications (within 30-day) after robot-assisted radical cystectomy (RARC) and urinary diversion.Patients and methodsPatients underwent RARC and urinary diversion between November 2018 and December 2021 in our centre were screened in this retrospective study. Baseline characteristics and perioperative data were recorded. Early complications after surgery were classified according to Clavien-Dindo system. Univariate and multivariate logistic analysis were performed to decide the potential factors associated with post-RARC complications. The receiver operating characteristic (ROC) curve was conducted to determine the predictive value of PNI on early overall and major complications after RARC.ResultsOverall 139 men and 13 women with a median age of 69 years and mean BMI of 24.4 kg/m2 were included in this study. As for urinary diversion, most patients (n = 111, 73%) received cutaneous ureterostomy, 36 patients (23.7%) underwent orthotopic neobladder and 5 patients (3.3%) received ileal conduit. The incidence of postoperative complication rate was 44.7%, which included 82.2% minor complications and 17.8% major complications. Further univariate and multivariate logistic analyses demonstrated that hypertension (OR = 2.96, 95% CI: 1.24–7.07, P = 0.015), PNI (OR = 0.73, 95% CI: 0.62–0.86, P ConclusionPNI can be an early alert for RARC patients thus aiding in closer monitoring and postoperative management.</p

Table3_The predictive value of prognostic nutritional index on early complications after robot-assisted radical cystectomy.docx

ObjectiveThe purpose of the study was to evaluate the predictive value of prognostic nutritional index (PNI) on early complications (within 30-day) after robot-assisted radical cystectomy (RARC) and urinary diversion.Patients and methodsPatients underwent RARC and urinary diversion between November 2018 and December 2021 in our centre were screened in this retrospective study. Baseline characteristics and perioperative data were recorded. Early complications after surgery were classified according to Clavien-Dindo system. Univariate and multivariate logistic analysis were performed to decide the potential factors associated with post-RARC complications. The receiver operating characteristic (ROC) curve was conducted to determine the predictive value of PNI on early overall and major complications after RARC.ResultsOverall 139 men and 13 women with a median age of 69 years and mean BMI of 24.4 kg/m2 were included in this study. As for urinary diversion, most patients (n = 111, 73%) received cutaneous ureterostomy, 36 patients (23.7%) underwent orthotopic neobladder and 5 patients (3.3%) received ileal conduit. The incidence of postoperative complication rate was 44.7%, which included 82.2% minor complications and 17.8% major complications. Further univariate and multivariate logistic analyses demonstrated that hypertension (OR = 2.96, 95% CI: 1.24–7.07, P = 0.015), PNI (OR = 0.73, 95% CI: 0.62–0.86, P ConclusionPNI can be an early alert for RARC patients thus aiding in closer monitoring and postoperative management.</p

Image2_The predictive value of prognostic nutritional index on early complications after robot-assisted radical cystectomy.tif

ObjectiveThe purpose of the study was to evaluate the predictive value of prognostic nutritional index (PNI) on early complications (within 30-day) after robot-assisted radical cystectomy (RARC) and urinary diversion.Patients and methodsPatients underwent RARC and urinary diversion between November 2018 and December 2021 in our centre were screened in this retrospective study. Baseline characteristics and perioperative data were recorded. Early complications after surgery were classified according to Clavien-Dindo system. Univariate and multivariate logistic analysis were performed to decide the potential factors associated with post-RARC complications. The receiver operating characteristic (ROC) curve was conducted to determine the predictive value of PNI on early overall and major complications after RARC.ResultsOverall 139 men and 13 women with a median age of 69 years and mean BMI of 24.4 kg/m2 were included in this study. As for urinary diversion, most patients (n = 111, 73%) received cutaneous ureterostomy, 36 patients (23.7%) underwent orthotopic neobladder and 5 patients (3.3%) received ileal conduit. The incidence of postoperative complication rate was 44.7%, which included 82.2% minor complications and 17.8% major complications. Further univariate and multivariate logistic analyses demonstrated that hypertension (OR = 2.96, 95% CI: 1.24–7.07, P = 0.015), PNI (OR = 0.73, 95% CI: 0.62–0.86, P ConclusionPNI can be an early alert for RARC patients thus aiding in closer monitoring and postoperative management.</p

Anthropometric and metabolic characteristics of the study groups.

<p>Anthropometric and metabolic characteristics of the study groups.</p

Table2_The predictive value of prognostic nutritional index on early complications after robot-assisted radical cystectomy.docx

ObjectiveThe purpose of the study was to evaluate the predictive value of prognostic nutritional index (PNI) on early complications (within 30-day) after robot-assisted radical cystectomy (RARC) and urinary diversion.Patients and methodsPatients underwent RARC and urinary diversion between November 2018 and December 2021 in our centre were screened in this retrospective study. Baseline characteristics and perioperative data were recorded. Early complications after surgery were classified according to Clavien-Dindo system. Univariate and multivariate logistic analysis were performed to decide the potential factors associated with post-RARC complications. The receiver operating characteristic (ROC) curve was conducted to determine the predictive value of PNI on early overall and major complications after RARC.ResultsOverall 139 men and 13 women with a median age of 69 years and mean BMI of 24.4 kg/m2 were included in this study. As for urinary diversion, most patients (n = 111, 73%) received cutaneous ureterostomy, 36 patients (23.7%) underwent orthotopic neobladder and 5 patients (3.3%) received ileal conduit. The incidence of postoperative complication rate was 44.7%, which included 82.2% minor complications and 17.8% major complications. Further univariate and multivariate logistic analyses demonstrated that hypertension (OR = 2.96, 95% CI: 1.24–7.07, P = 0.015), PNI (OR = 0.73, 95% CI: 0.62–0.86, P ConclusionPNI can be an early alert for RARC patients thus aiding in closer monitoring and postoperative management.</p

Browning of mammary fat cells from breast tumors and benign lesions.

<p>Human adipose SVF cells were harvested from the mammary fat of breast tumors and benign lesions. SVF cells were then cultured and induced to mature (Day 14). Quantitative RT-PCR analysis of mRNA expression of fat browning-related genes: UCP1, PRDM16, CIDEA, COX7A1, PGC1α, TMEM26 and TBX1 (mean ± SEM; n = 6; *<i>P</i><0.05, **<i>P</i><0.01). (Cancer associated adipocytes, CAA; control adipocytes, CON).</p

Table5_The predictive value of prognostic nutritional index on early complications after robot-assisted radical cystectomy.docx

ObjectiveThe purpose of the study was to evaluate the predictive value of prognostic nutritional index (PNI) on early complications (within 30-day) after robot-assisted radical cystectomy (RARC) and urinary diversion.Patients and methodsPatients underwent RARC and urinary diversion between November 2018 and December 2021 in our centre were screened in this retrospective study. Baseline characteristics and perioperative data were recorded. Early complications after surgery were classified according to Clavien-Dindo system. Univariate and multivariate logistic analysis were performed to decide the potential factors associated with post-RARC complications. The receiver operating characteristic (ROC) curve was conducted to determine the predictive value of PNI on early overall and major complications after RARC.ResultsOverall 139 men and 13 women with a median age of 69 years and mean BMI of 24.4 kg/m2 were included in this study. As for urinary diversion, most patients (n = 111, 73%) received cutaneous ureterostomy, 36 patients (23.7%) underwent orthotopic neobladder and 5 patients (3.3%) received ileal conduit. The incidence of postoperative complication rate was 44.7%, which included 82.2% minor complications and 17.8% major complications. Further univariate and multivariate logistic analyses demonstrated that hypertension (OR = 2.96, 95% CI: 1.24–7.07, P = 0.015), PNI (OR = 0.73, 95% CI: 0.62–0.86, P ConclusionPNI can be an early alert for RARC patients thus aiding in closer monitoring and postoperative management.</p