TGFβƒ1 Promotes Gemcitabine Resistance Through Regulating the LncRNA-LET/NF90/miR-145 Signaling Axis in Bladder Cancer

High tumor recurrence is frequently observed in patients with urinary bladder cancers (UBCs), with the need for biomarkers of prognosis and drug response. Chemoresistance and subsequent recurrence of cancers are driven by a subpopulation of tumor initiating cells, namely cancer stem-like cells (CSCs). However, the underlying molecular mechanism in chemotherapy-induced CSCs enrichment remains largely unclear. In this study, we found that during gemcitabine treatment lncRNA-Low Expression in Tumor (lncRNA-LET) was downregulated in chemoresistant UBC, accompanied with the enrichment of CSC population. Knockdown of lncRNA-LET increased UBC cell stemness, whereas forced expression of lncRNA-LET delayed gemcitabine-induced tumor recurrence. Furthermore, lncRNA-LET was directly repressed by gemcitabine treatment-induced overactivation of TGFβ/SMAD signaling through SMAD binding element (SBE) in the lncRNA-LET promoter. Consequently, reduced lncRNA-LET increased the NF90 protein stability, which in turn repressed biogenesis of miR-145 and subsequently resulted in accumulation of CSCs evidenced by the elevated levels of stemness markers HMGA2 and KLF4. Treatment of gemcitabine resistant xenografts with LY2157299, a clinically relevant specific inhibitor of TGFβRI, sensitized them to gemcitabine and significantly reduced tumorigenecity in vivo. Notably, overexpression of TGFβ1, combined with decreased levels of lncRNA-LET and miR-145 predicted poor prognosis in UBC patients. Collectively, we proved that the dysregulated lncRNA-LET/NF90/miR-145 axis by gemcitabine-induced TGFβ1 promotes UBC chemoresistance through enhancing cancer cell stemness. The combined changes in TGFβ1/lncRNA-LET/miR-145 provide novel molecular prognostic markers in UBC outcome. Therefore, targeting this axis could be a promising therapeutic approach in treating UBC patients

High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting

Purpose: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. Methods: We developed 3D ViSTa-MRF, which combined Visualization of Short Transverse relaxation time component (ViSTa) technique with MR Fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multi-compartment fitting that could introduce bias and/or noise from additional assumptions or priors. Results: The in-vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in-vivo results of 1mm- and 0.66mm-iso datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30x slower with lower SNR. Furthermore, we applied the proposed method to enable 5-minute whole-brain 1mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. Conclusions: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1mm and 0.66mm isotropic resolution in 5 and 15 minutes, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.Comment: 38 pages, 12 figures and 1 tabl

The complete chloroplast genome of Tulipa gesneriana (Liliaceae) and its phylogenetic analysis

The complete chloroplast genome sequence of Tulipa gesneriana L. was determined to investigate its phylogenetic position. This plastome is 151,958 base pairs (bp) in length, and comprises two inverted repeat (IRa and IRb) regions of 26,352 bp, a small single-copy region of 17,123 bp and a large single-copy region of 82,131 bp. The GC contents of the cp genome were 36.6%. In total, we annotated 126 genes including 81 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on nine chloroplast genomes indicates that T. gesneriana is closely related to T. iliensis and T. thianschanica

Effects of high temperature and high relative humidity drying on moisture distribution, starch microstructure and cooking characteristics of extruded whole buckwheat noodles

ABSTRACT: Drying is a key step in starch noodle production. The effects of high temperature (60, 70, 80°C) and high relative humidity (65%, 75%, 85%) drying (HTHD) on the moisture distribution, starch microstructure and cooking characteristics of extruded whole buckwheat noodles were investigated. Compared to the conventional hot-air drying (CHAD) at 40°C, the increase in drying temperature (60–80°C) and the decrease in relative humidity (85%–65%) significantly improved drying efficiency of the extruded noodles. By adjusting drying temperature and relative humidity, the rate of moisture migration in noodles and phase transition of starch could be appropriately controlled. The optimum drying parameters (T70H75, 70°C drying temperature and 75% relative humidity) showed smooth and dense network structure, resulting in the lowest cooking loss (6.61%), broken rate (0%), highest hardness (1 695.17 g) and springiness (0.92). However, the total flavonoid content (TFC) and the total phenolic content (TPC) reduced by 6.81%–28.50% and 7.19%–53.23% in contrast to CHAD, and the color of buckwheat noodles became darker through HTHD. These findings showed the potential of HTHD for increasing drying efficiency and improving buckwheat noodle quality. The appropriate drying parameters could maintain a balanced relationship between moisture migration in noodles and phase transition of starch, which resulted in better cooking quality for extruded whole buckwheat noodles. Such a study is valuable for regulating the process conditions of buckwheat-based foods and promoting its commercial utilization

Recent advances in hypertrophic scar

Hypertrophic scars (HTS) are predominant diseases after burn and trauma, which cause severe physiological and psychological problems. HTS have been researched for decades, and our knowledge about the mechanisms of HTS formation process has been increasing. However, the effects of currently available prevention and treatment strategies are limited. In this review, we summarize currently known mechanisms and recent studies of HTS, including extracellular matrix, matrix metalloproteinases, fibroblasts, myofibroblasts and their contraction ability, keratinocytes, growth factors, inflammatory and immune response, and stem cell treatment, hoping for a better understanding of HTS generation, development and effective translation to treatment strategies