Alterations of biaxial viscoelastic properties of the right ventricle in pulmonary hypertension development in rest and acute stress conditions

Introduction: The right ventricle (RV) mechanical property is an important determinant of its function. However, compared to its elasticity, RV viscoelasticity is much less studied, and it remains unclear how pulmonary hypertension (PH) alters RV viscoelasticity. Our goal was to characterize the changes in RV free wall (RVFW) anisotropic viscoelastic properties with PH development and at varied heart rates.Methods: PH was induced in rats by monocrotaline treatment, and the RV function was quantified by echocardiography. After euthanasia, equibiaxial stress relaxation tests were performed on RVFWs from healthy and PH rats at various strain-rates and strain levels, which recapitulate physiological deformations at varied heart rates (at rest and under acute stress) and diastole phases (at early and late filling), respectively.Results and Discussion: We observed that PH increased RVFW viscoelasticity in both longitudinal (outflow tract) and circumferential directions. The tissue anisotropy was pronounced for the diseased RVs, not healthy RVs. We also examined the relative change of viscosity to elasticity by the damping capacity (ratio of dissipated energy to total energy), and we found that PH decreased RVFW damping capacity in both directions. The RV viscoelasticity was also differently altered from resting to acute stress conditions between the groups—the damping capacity was decreased only in the circumferential direction for healthy RVs, but it was reduced in both directions for diseased RVs. Lastly, we found some correlations between the damping capacity and RV function indices and there was no correlation between elasticity or viscosity and RV function. Thus, the RV damping capacity may be a better indicator of RV function than elasticity or viscosity alone. These novel findings on RV dynamic mechanical properties offer deeper insights into the role of RV biomechanics in the adaptation of RV to chronic pressure overload and acute stress

Weak acids produced during anaerobic respiration suppress both photosynthesis and aerobic respiration

peer reviewedWhile photosynthesis transforms sunlight energy into sugar, aerobic and anaerobic respiration (fermentation) catabolizes sugars to fuel cellular activities. These processes take place within one cell across several compartments, however it remains largely unexplored how they interact with one another. Here we report that the weak acids produced during fermentation down-regulate both photosynthesis and aerobic respiration. This effect is mechanistically explained with an "ion trapping" model, in which the lipid bilayer selectively traps protons that effectively acidify subcellular compartments with smaller buffer capacities - such as the thylakoid lumen. Physiologically, we propose that under certain conditions, e.g., dim light at dawn, tuning down the photosynthetic light reaction could mitigate the pressure on its electron transport chains, while suppression of respiration could accelerate the net oxygen evolution, thus speeding up the recovery from hypoxia. Since we show that this effect is conserved across photosynthetic phyla, these results indicate that fermentation metabolites exert widespread feedback control over photosynthesis and aerobic respiration. This likely allows algae to better cope with changing environmental conditions

Excavation of diagnostic biomarkers and construction of prognostic model for clear cell renal cell carcinoma based on urine proteomics

PurposeClear cell renal cell carcinoma (ccRCC) is the most common pathology type in kidney cancer. However, the prognosis of advanced ccRCC is unsatisfactory. Thus, early diagnosis becomes one of the most important research priorities of ccRCC. However, currently available studies about ccRCC lack urine-related further studies. In this study, we applied proteomics to search urinary biomarkers to assist early diagnosis of ccRCC. In addition, we constructed a prognostic model to assist judge patients’ prognosis.Materials and methodsUrine which was used to perform 4D label-free quantitative proteomics was collected from 12 ccRCC patients and 11 non-tumor patients with no urinary system diseases. The urine of 12 patients with ccRCC confirmed by pathological examination after surgery was collected before operatoin. Bioinformatics analysis was used to describe the urinary proteomics landscape of these patients with ccRCC. The top ten proteins with the highest expression content were selected as the basis for subsequent validation. Urine from 46 ccRCC patients and 45 control patients were collected to use for verification by enzyme linked immunosorbent assay (ELISA). In order to assess the prognostic value of urine proteomics, a prognostic model was constructed by COX regression analysis on the intersection of RNA-sequencing data in The Cancer Genome Atlas (TCGA) database and our urine proteomic data.Results133 proteins differentially expressed in the urinary samples were found and 85 proteins (Fold Change, FC>1.5) were identified up-regulated while 48 down-regulated (FC<0.5). Top 10 proteins including S100A14, PKHD1L1, FABP4, ITIH2, C3, C8G, C2, ATF6, ANGPTL6, F13B were performed ELISA to verify. The results showed that PKHD1L1, ANGPTL6, FABP4 and C3 were statistically significant (P<0.05). We performed multivariate logistic regression analysis and plotted a nomogram. Receiver operating characteristic (ROC) curve indicted that the diagnostic efficiency of combined indicators is satisfactory (Aare under curve, AUC=0.835). Furthermore, the prognostic value of the urine proteomics was explored through the intersection between urine proteomics and TCGA RNA-seq data. Thus, COX regression analysis showed that VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 were statistically significant (P<0.05).ConclusionOur study indicated that the application of urine proteomics to explore diagnostic biomarkers and to construct prognostic models of renal clear cell carcinoma is of certain clinical value. PKHD1L1, ANGPTL6, FABP4 and C3 can assist to diagnose ccRCC. The prognostic model constituted of VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 can significantly predict the prognosis of ccRCC patients, but this still needs more clinical trials to verify

Purified Recombinant VP2 Protein Can Provide Complete Protection to very Virulent Infectious Bursal Disease Virus Challenge as a Subunit Vaccine

Background: The very virulent infectious bursal disease virus has become the dominant path type that damage lymphoid tissues with high mortality in young chickens in China. Current commercial vaccines are modified live vaccines originated from classic form of virulent virus and cannot provide complete protection as they cause bursal atrophy and immunosuppression. There is an urgent call to more effective and safer vaccines.Methods: In this study, we successfully expressed the soluble VP2 protein in E.coli and purified recombinant protein by using ion-exchange chromatography. The recombinant protein was subsequently used on chickens as a subunit vaccine. Result: The purified recombinant VP2 protein can generate high agar gel diffusion recipitation antibodies and provide complete protection to a very virulent filed infectious bursal disease virus challenge as shown by results of clinical manifestations and histopathological examination. By contrast,commercial vaccines can only provide 60% protection as compared with recombinant VP2 protein.Conclusion: The subunit vaccine based on recombinant VP2 protein could be a promising vaccine candidate to be used on chickens.</p

Additive-Modulated Evolution of HC(NH₂)₂PbI₃ Black Polymorph for Mesoscopic Perovskite Solar Cells

Formamidinium lead triiodide (HC­(NH₂)₂PbI₃ or FAPbI₃) is gaining increasing interest in the field of mesoscopic perovskite solar cells (PSCs) for its broader light absorption compared with the more widely studied CH₃NH₃PbI₃ (MAPbI₃). Because FAPbI₃ has two polymorphs (“black” α-FAPbI₃ and “yellow” δ-FAPbI₃) at ambient temperature, where α-FAPbI₃ is the desirable photoactive perovskite phase, it becomes particularly important to suppress the formation of the nonperovskite δ-FAPbI₃ for achieving high efficiency in FAPbI₃-based mesoscopic PSCs. In this study, we demonstrate that the judicious use of low-volatility additives in the precursor solution assists in the evolution of α-FAPbI₃ through the formation of non-δ-FAPbI₃ intermediate phases, which then convert to α-FAPbI₃ during thermal annealing. The underlying mechanism involved in the additive-modulated evolution of α-FAPbI₃ upon mesoporous TiO₂ substrates is elucidated, which suggests guidelines for developing protocols for the fabrication efficient FAPbI₃-based mesoscopic PSCs

The mPlrp2 and mClps genes are involved in the hydrolysis of retinyl esters in the mouse liver[S]

Retinyl esters are the major chemical forms of vitamin A stored in the liver, and can be delivered to peripheral tissues for conversion into biologically active forms. The function and regulation of the hepatic genes that are potentially involved in catalyzing the hydrolysis of retinyl esters remain unclear. Here we show that two lipid hydrolytic genes, pancreatic-related protein 2 (mPlrp2) and procolipase (mClps), expressed specifically in the mouse pancreas, are associated with the ratio of S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy). Light illumination deficiency or administration of 5′-AMP elevated the ratio of AdoMet to AdoHcy and induced the expression in the liver of mPlrp2 and mClps, which was blocked by all-trans retinoic acid. Mice fed a vitamin A-free diet exhibited increased activation of hepatic mPlrp2 and mClps expression, which was associated with increased methylation of histone H3K4 residues located near the mPlrp2 and mClps promoters. Inhibition of hepatic mPlrp2 and mClps expression by a methylase inhibitor, methylthioadenosine, markedly decreased plasma retinol levels in these mice. The activated hepatic stellate cell (HSC)-T6 cell line specifically expressed mClps and mPlrp2. Inhibition of mClps gene expressions by short hairpin RNA (shRNA) decreased hydrolysis of retinyl esters in the HSC-T6 cell line. These data suggest that the conditional expression of mPlrp2 and mClps is involved in the hydrolysis of retinyl esters in the mouse liver