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Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction
Identification of novel 7-hydroxycoumarin derivatives as ELOC binders with potential to modulate CRL2 complex formation
Abstract The VHL-containing cullin-RING E3 ubiquitin ligase (CRL2 VHL ) complex is an E3 ligase commonly used in targeted protein degradation (TPD). Hydroxyproline-based ligands that mimic VHL substrates have been developed as anchor molecules for proteolysis-targeting chimeras (PROTACs) in TPD. To expand the chemical space for VHL ligands, we conducted fragment screening using VHL–ELOB–ELOC (VBC) proteins. We found that certain 7-hydroxycoumarin derivatives (7HCs), rather than VHL, would bind to the ELOC component of the VBC complex. The 7HC binding site overlapped with the CUL2 binding interface on ELOC but did not overlap with the CUL5 binding interface, suggesting that 7HCs may influence the formation of CRL2 but not CRL5. Although the binding affinities of these 7HCs to the VBC complex were relatively low, they represent novel and promising foundational agents for the development of chemical probes or inhibitors that target ELOC-containing CRLs.
Enhanced recovery after surgery society’s recommendations for liver surgery reduces non surgical complications
Abstract Enhanced Recovery after Surgery (ERAS) is a multimodal approach to improve surgical outcome and has been implemented in many fields of surgery in an international scale. The aim of this study was to evaluate the effect of the Enhanced Recovery after Surgery (ERAS) society recommendations in liver surgery and the impact on general and surgery-related complications. 1049 patients who underwent liver surgery from July 2018 to October 2023 were included. The ERAS program strictly followed the official ERAS society recommendations. As a control group (Non-ERAS) 90 patients were treated according to the clinic standard, while 959 patients were treated according within the ERAS measures. After propensity score (PSM) matching 87 Non-ERAS and 258 ERAS patients were analyzed by complications and cumulative sum analysis (CUSUM). ERAS implementation resulted in a significant decrease in general complications (control 27.6% vs. ERAS 16.3%, p = 0.033), largely attributed to a reduction in infection-related complications (control 20.7% vs. ERAS 9.7%, p = 0.007). When examining surgery-related complications no significant disparities were observed (control 17.2% vs. ERAS 17.1%, p = 0.968). The CUSUM analysis of general and non-surgical complications showed that the full effect of the ERAS program only became apparent after several years. Moreover, adherence increased over time consecutively from 62.5 to 72.5% in 4 years. The ERAS society recommendations for liver surgery reduced general complications but did not have any effect on surgery related complications. The effect of the ERAS program progressively improved over the years, highlighting the need for continuous effort to maintain and further enhance outcomes.
Unexpected species diversity in the understanding of selenium-containing soil invertebrates
Experimental and computational approach on the corrosion inhibition properties of two newly pyrazole derivatives on carbon steel in acid medium
Author Correction: Impact of standard and long-lasting ivermectin formulations in cattle and buffalo on wild Anopheles survival on Sumba Island, Indonesia
Mitochondrial dysfunction-driven AMPK-p53 axis activation underpins the anti-hepatocellular carcinoma effects of sulfane sulfur
Resistance-breaking strains of tomato spotted wilt virus hamper photosynthesis and protein synthesis pathways in a virus accumulation-dependent manner in Sw5-carrying tomatoes
Abstract Tomato spotted wilt virus (TSWV; Orthotospovirus tomatomaculae) is one of the major horticultural threats due to its worldwide distribution and broad host range. In Italy, TSWV is widely spread in tomato (Solanum lycopersicum) crops and causes severe yield losses. In the last decades, several tomato varieties carrying the Sw-5b gene for resistance to TSWV have been released. We investigated the interaction between Sw-5b-carrying tomatoes and Sw5-Resistance-Breaking (SRB) TSWV to elucidate the molecular mechanisms underlying resistance breakage. Transcriptome sequencing (RNA-Seq) was used to analyze 18 tomato leaf samples collected from a field crop naturally infected by SRB TSWV in Italy. An increase in virus accumulation level in leaf tissues (titer) resulted in a higher number of differentially expressed genes (DEGs), ranging from 33 to 44% of the whole transcriptome, when the samples with the lowest and the highest virus titer were compared to the asymptomatic sample, respectively. Photosynthesis and protein biosynthesis were the main down-regulated biological processes, while enzyme families such as oxidoreductases and transferases, genes related to the response to biotic stimuli, solute transport, and vesicle trafficking were overall up-regulated. Remarkably, the expression of around 45% of genes (ca. 14000) of the whole transcriptome was significantly (P < 0.05) correlated (positively or negatively) to the virus titer, and in 6% of cases (about 2000 genes) the correlation was high (i.e., absolute value of R2 > 0.85). This phenomenon was also verified on 15 genes by a quantitative reverse transcription PCR assay on a greenhouse experiment with a different Sw-5b-tomato variety artificially inoculated with another SRB TSWV strain. In conclusion, the tomato transcriptome was considerably rearranged upon TSWV infection, with deregulation of photosynthesis, protein biosynthesis, and induction of defense pathways. Finally, this research demonstrated that the magnitude of transcriptional changes was proportional to the virus accumulation level in the leaves.