Boothsosa8629
By annotating genes relevant to top SNPs, we have distinguished 18 potential candidate genes comprising HNF4beta, CKMT1B, TBC1D22A, RPL8, CACNA2D1, FZD4, SGMS1, IRF8, OPTN, LOC420362, TRABD, OvoDA1, DAD1, USP6, RBM12B, MIR1772, MIR1709 and MIR6696 and also 89 putative gene-gene combinations responsible for plumage color variation in chickens. Furthermore, several KEGG pathways including metabolic pathway, cytokine-cytokine receptor interaction, focal adhesion, melanogenesis, glycosaminoglycan biosynthesis-keratan sulfate and sphingolipid metabolism were enriched in the gene-set analysis. The results indicated that plumage color is a highly polygenic trait which, in turn, can be affected by multiple coding genes, regulatory genes and gene-gene epistasis interactions. In addition to genes with additive effects, epistatic genes with tiny individual effect sizes but significant effects in a pair have the potential to control plumage coloration in chickens.
Decellularized extracellular matrixs (dECMs) derived from organs and tissues have emerged as a promising tool, as they encompass the characteristics of an ideal tissue scaffold complex composition, vascular networks and unique tissue-specific architecture. Consequently, their use has propagated throughout tissue engineering and regenerative medicine. dECM can be easily obtained from various tissues/organs by appropriate decellularization protocolsand is entitled to provide necessary cues to cells homing.
In this review, we describe the decellularization and sterilization methods that are commonly used in recent research, the effects of these methods upon biologic scaffold material are discussed. Also, we summarize the recent developments of recellularization and vascularization techniques in regeneration medicine. Additionally, dECM preservation methods is mentioned, which provides the basis for the establishment of organ bank.
Biomedical applications and the status of current research developments relating to dECM biomaterials are outlined, including transplantation in vivo, disease models and drug screening, organoid, 3D bioprinting, tissue reconstruction and rehabilitation and cell transplantation and culture. Finally, critical challenges and future developing technologies are discussed.
With the development of tissue engineering and regenerative medicine, dECM will have broader applications in the field of biomedicine in the near future.
With the development of tissue engineering and regenerative medicine, dECM will have broader applications in the field of biomedicine in the near future.
Sudden cardiac death (SCD) caused by acute myocardial ischaemia and ventricular fibrillation (VF) is an unmet therapeutic need. Lidocaine suppresses ischaemia-induced VF, but its utility is limited by side effects and a narrow therapeutic index. Here, we characterise OCT2013, a putative ischaemia-activated prodrug of lidocaine.
The rat Langendorff-perfused isolated heart, anaesthetised rat and rat ventricular myocyte preparations were utilised in a series of blinded and randomised studies to investigate the antiarrhythmic effectiveness, adverse effects and mechanism of action of OCT2013, compared with lidocaine.
In isolated hearts, OCT2013 and lidocaine prevented ischaemia-induced VF equi-effectively, but OCT2013 did not share lidocaine's adverse effects (PR widening, bradycardia and negative inotropy). In anaesthetised rats, i.v. OCT2013 and lidocaine suppressed VF and increased survival equi-effectively; OCT2013 had no effect on cardiac output even at 64 mg·kg
i.v., whereas lidocaine reduced it even at 1 mg·kg
. In adult rat ventricular myocytes, OCT2013 had no effect on Ca
handling, whereas lidocaine impaired it. In paced isolated hearts, lidocaine caused rate-dependent conduction slowing and block, whereas OCT2013 was inactive. However, during regional ischaemia, OCT2013 and lidocaine equi-effectively hastened conduction block. Chromatography and MS analysis revealed that OCT2013, detectable in normoxic OCT2013-perfused hearts, became undetectable during global ischaemia, with lidocaine becoming detectable.
OCT2013 is inactive but is bio-reduced locally in ischaemic myocardium to lidocaine, acting as an ischaemia-activated and ischaemia-selective antiarrhythmic prodrug with a large therapeutic index, mimicking lidocaine's benefit without adversity.
OCT2013 is inactive but is bio-reduced locally in ischaemic myocardium to lidocaine, acting as an ischaemia-activated and ischaemia-selective antiarrhythmic prodrug with a large therapeutic index, mimicking lidocaine's benefit without adversity.The recovery and maintenance of plant homeostasis under stressful environments are complex processes involving organelle crosstalk for a coordinated cellular response. Here, we revealed through nuclear and chloroplast subcellular proteomics, biochemical cell profiles and targeted transcriptomics how chloroplasts and nuclei developed their responses under increased temperatures in a long-lived species (Pinus radiata). Parallel to photosynthetic impairment and reactive oxygen species production in the chloroplast, a DNA damage response was triggered in the nucleus followed by an altered chromatin conformation. In addition, in the nuclei, we found several proteins, such as HEMERA or WHIRLY, which change their locations from the chloroplasts to the nuclei carrying the stress message. Additionally, our data showed a deep rearrangement of RNA metabolism in both organelles, revealing microRNAs and AGO1 as potential regulators of the acclimation mechanisms. Altogether, our study highlights the synchronisation among the different stages required for thermotolerance acquisition in P. radiata, pointing out the role of chromatin conformation and posttranscriptional gene regulation in overcoming heat stress and assuring plant survival for the following years.
Chronic liver congestion reflecting right-sided heart failure (RHF), Budd-Chiari syndrome, or Fontan-associated liver disease (FALD) is involved in liver fibrosis and HCC. However, molecular mechanisms of fibrosis and HCC in chronic liver congestion remain poorly understood.
Here, we first demonstrated that chronic liver congestion promoted HCC and metastatic liver tumor growth using murine model of chronic liver congestion by partial inferior vena cava ligation (pIVCL). As the initial step triggering HCC promotion and fibrosis, gut-derived lipopolysaccharide (LPS) appeared to induce LSECs capillarization in mice and in vitro. LSEC capillarization was also confirmed in patients with FALD. Mitogenic factor, sphingosine-1-phosphate (S1P), was increased in congestive liver and expression of sphingosine kinase 1, a major synthetase of S1P, was increased in capillarized LSECs after pIVCL. Inhibition of S1P receptor (S1PR) 1 (Ex26) and S1PR2 (JTE013) mitigated HCC development and liver fibrosis, respectively. Antimicrobial treatment lowered portal blood LPS concentration, LSEC capillarization, and liver S1P concentration accompanied by reduction of HCC development and fibrosis in the congestive liver.
In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS-induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for patients with RHF with primary or metastatic liver cancer.
In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS-induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for patients with RHF with primary or metastatic liver cancer.Long noncoding RNAs (lncRNAs) have been considered to be important regulators of gene expression in a range of biological processes in plants. A large number of lncRNAs have been identified in plants. However, most of their biological functions still remain to be determined. Here, we identified a total of 3004 lncRNAs in cassava under normal or cold-treated conditions from Iso-seq data. We further characterized a cold-responsive intergenic lncRNA 1 (CRIR1) as a novel positive regulator of the plant response to cold stress. CRIR1 can be significantly induced by cold treatment. Ectopic expression of CRIR1 in cassava enhanced the cold tolerance of transgenic plants. Transcriptome analysis demonstrated that CRIR1 regulated a range of cold stress-related genes in a CBF-independent pathway. We further found that CRIR1 RNA can interact with cassava cold shock protein 5 (MeCSP5), which acts as an RNA chaperone, indicating that CRIR1 may recruit MeCSP5 to improve the translation efficiency of messenger RNA. In summary, our study extends the repertoire of lncRNAs in plants as well as their role in cold stress responses. Moreover, it reveals a mechanism by which CRIR1 affected cold stress response by modulating the expression of stress-responsive genes and increasing their translational yield.
Convolution/superposition algorithms used in megavoltage (MV) photon radiotherapy model radiation transport in water, yielding dose to water-in-water (D
). Advanced algorithms constitute a step forward, but their dose distributions in terms of dose to medium-in-medium (D
) or dose to water-in-medium (D
) can be problematic when used in plan optimization due to their different dose responses to some atomic composition heterogeneities. Failure to take this into account can lead to undesired overcorrections and thus to unnoticed suboptimal and unrobust plans. Dose to reference-like medium (D
) was recently introduced to overcome these limitations while ensuring accurate transport. This work evaluates and compares the performance of these four dose quantities in planning target volume (PTV)-based optimization.
We considered three cases with heterogeneities inside the PTV virtual phantom with water surrounded by bone; head and neck; and lung. These cases were planned with volumetric modulated arc theraeasily implemented as a built-in feature of the TPS and can facilitate and simplify the treatment planning process when using advanced algorithms. Final reporting can be kept in Dm,m or Dw,m for clinical correlations.It is difficult to conceive of a re-imagination of "us" by focusing solely on the state, especially where the intended objective is to trouble the prevailing national project. KRpep2d If national projects, like racial projects, must be laboured at to be sustained, then in the case of Britishness we find a rich vein of contestation by those left out of its formal narration. It is on this point that the discussion will focus, beginning with a preliminary but unstated question that warrants explicit attention, namely why re-make national projects at all?Videolaryngoscopes are thought to improve glottic view and facilitate tracheal intubation compared with the Macintosh direct laryngoscope. However, we currently do not know which one would be the best choice in most patients undergoing anaesthesia. We designed this systematic review with network meta-analyses to rank the different videolaryngoscopes and the Macintosh direct laryngoscope. We conducted searches in PubMed and a further five databases on 11 January 2021. We included randomised clinical trials with patients aged ≥16 years, comparing different videolaryngoscopes, or videolaryngoscopes with the Macintosh direct laryngoscope for the outcomes failed intubation; failed first intubation attempt; failed intubation within two attempts; difficult intubation; percentage of glottic opening seen; difficult laryngoscopy; and time needed for intubation. We assessed the quality of evidence according to GRADE recommendations and included 179 studies in the meta-analyses. The C-MAC and C-MAC D-Blade were top ranked for avoiding failed intubation, but we did not find statistically significant differences between any two distinct videolaryngoscopes for this outcome.
