Lindgrentroelsen2756

This study mapped QTLs associated with kernel-related traits by high-density genetic map. Five new major and stable QTLs for KL, KDR, SN, and KWPS were mapped in multiple environments. In the present study, a recombinant inbred line population including 371 lines derived from the cross of Chuannong18 and T1208 was genotyped using the Wheat55K single nucleotide polymorphism array. A novel high-density genetic map consisting of 11,583 markers spanning 4192.62cM and distributed across 21 wheat chromosomes was constructed. QTLs for important kernel-related traits were mapped in multiple environments. A total of 96 and 151 QTLs were mapped by using the ICIM method and the MET method, respectively. And a total of 114 digenic epistatic QTLs were also detected across 21 chromosomes, and the epistatic effects of each trait were analyzed. BLAST analysis showed that 23QTLs for different kernel-related traits were first time mapped and five of them were major and stable QTLs for kernel diameter ratio (121.34-126.83cM os detected in this study.Different hepatoxic factors cause irreversible liver injury, leading to liver failure, cirrhosis, and cancer in mammals. Liver transplantation is the only effective strategy, which can improve the prognosis of patients with end-stage liver diseases, but it is limited by liver donor shortage, expensive costs, liver graft rejection and dysfunction, and recurring liver failure. Recently, mesenchymal stromal cells (MSCs) isolated from various tissues are regarded as the main stem cell type with therapeutic effects in liver diseases because of their hepatogenic differentiation, anti-inflammatory, immuoregulatory, anti-apoptotic, antifibrotic, and antitumor capacities. To further improve the therapeutic effects of MSCs, multiple studies showed that genetically engineered MSCs have increased regenerative capacities and are able to more effectively inhibit cell death. Moreover, they are able to secrete therapeutic proteins for attenuating liver injury in liver diseases. Cyclopamine In this review, we mainly focus on gene overexpression for reprogramming MSCs to increase their therapeutic effects in treating various liver diseases. We described the potential mechanisms of MSCs with gene overexpression in attenuating liver injury, and we recommend further expansion of experiments to discover more gene targets and optimized gene delivery methods for MSC-based regenerative medicine. We also discussed the potential hurdles in genetic engineering MSCs. In conclusion, we highlight that we need to overcome all scientific hurdles before genetically modified MSC therapy can be translated into clinical practices for patients with liver diseases.NLRP3 inflammasome-driven inflammation represents a key trigger for hepatic fibrogenesis during cholestatic liver injury. However, whether sphingosine 1-phosphate (S1P) plays a role in NLRP3 inflammasome priming and activation remains unknown. Here, we found that the expression of NLRP3 in macrophages and NLRP3 inflammasome activation were significantly elevated in the liver injured by bile duct ligation (BDL). In vitro, S1P promoted the NLRP3 inflammasome priming and activation via S1P receptor 2 (S1PR2) in bone marrow-derived monocyte/macrophages (BMMs). Focusing on BMMs, the gene silencing of Gα12 or Gα13 by specific siRNA suppressed NLRP3 inflammasome priming and pro-inflammatory cytokine (IL-1β and IL-18) secretion, whereas Gα(i/o) and Gαq were not involved in this process. The MAPK signaling pathways (P38, ERK, and JNK) mediated NLRP3 inflammasome priming and IL-1β and IL-18 secretion, whereas blockage of PI3K, ROCK, and Rho family had no such effect. Moreover, JTE-013 (S1PR2 inhibitor) treatment markedly reduced NLRP3 inflammasome priming and activation in BDL-injured liver. Collectively, S1P promotes NLRP3 inflammasome priming and pro-inflammatory cytokines (IL-1β and IL-18) secretion via the S1PR2/Gα(12/13)/MAPK pathway, which may represent an effective therapeutic strategy for liver disease. KEY MESSAGE • Hepatic NLRP3 expression was significantly elevated in BMMs of BDL-injured mouse liver. • S1P promoted NLRP3 inflammasome priming and activation in BMMs, depending on the S1PR2/Gα(12/13)/MAPK pathway. • Blockade of S1PR2 by JTE-013 reduced NLRP3 inflammasome priming and activation inflammasome in vivo.

Urolithiasis is a common diagnosis in urology. New technologies offer a variety of diagnostic and therapy and consequently display a financial burden on healthcare systems. Hence, clinical practice guidelines (CPG) are essential to implement evidence-based medicine and assure a standard of care considering limited resources. To date, there is no evidence of the use and adherence to CPG on urolithiasis.

Therefore, we performed a cross-sectional study to analyze the use of CPG on urolithiasis. Data collection was carried out by a questionnaire given to 400 German urologists. The survey included use and adherence to guidelines, evaluation of the clinical situation, therapy spectrum, and workplace. In total, 150 (37%) questionnaires were received and included in our survey. Statistics were performed by SPSS using Chi-quadrat test/Fisher's exact test.

In our study, urologists were office based, hospital affiliated, non-academic, or academic centers in 53%, 32%, 16% and 5%, respectively. In 74% and 70%, urologists adhere to CPG in diagnostic and therapy. Interestingly, workplace and therapy spectrum determines the use of different CPG (p = 0.01; p = 0.022). Academic urologists were more likely to use international CPG of EAU (40%), while outpatient urologists significantly orientated on national CPG (46%). 86% of urologists with high volume of urolithiasis practice interventions in contrast to 53% in low volume (p = 0.001). More than 80% of urologists use short versions and app version of CPG.

We firstly describe compliance and the use of CPG on urolithiasis. EAU and DGU present the most commonly used CPG. Short version and app version of CPG find frequent clinical utilization.

We firstly describe compliance and the use of CPG on urolithiasis. EAU and DGU present the most commonly used CPG. Short version and app version of CPG find frequent clinical utilization.