Polaron states of the full-configuration defects in metal halide perovskites.

The systematical analysis for varieties of defects with different depths and lattice relaxation strengths in metal halide perovskites (MHPs) is a challenging task. Here, we study the energy shifts of the full-configuration defects due to the polaron effect based on the all-coupling variational method in MHPs, where these polaron states are formed stemming from different defect species coupling with the longitudinal optical phonon modes via Fro¨hlich mechanism. We find that the polaron effect results in defect levels varying from tens to several hundreds of meV, which are very close to the correction of defect levels due to the defect-polaron effect, especially for these defects migration proved in the recent experiments in MHPs. These results provide the significant enlightenment not only for analyzing the radiation and non-radiation processes of carriers mediated by defects, but also for optimizing defect effect in the photovoltaic and photoelectric devices based on MHPs materials.

Dysregulation and imbalance of innate and adaptive immunity are involved in the cardiomyopathy progression.

Background: Cardiomyopathy is known to be a heterogeneous disease with numerous etiologies. They all have varying degrees and types of myocardial pathological changes, resulting in impaired contractility, ventricle relaxation, and heart failure. The purpose of this study was to determine the pathogenesis, immune-related pathways and important biomarkers engaged in the progression of cardiomyopathy from various etiologies. Methods: We downloaded the gene microarray data from the Gene Expression Omnibus (GEO). The hub genes between cardiomyopathy and non-cardiomyopathy control groups were identified using differential expression analysis, least absolute shrinkage and selection operator (LASSO) regression and weighted gene co-expression network analysis (WGCNA). To assess the diagnostic precision of hub genes, receiver-operating characteristic (ROC) curves as well as the area under the ROC curve (AUC) were utilized. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis and Gene Ontology (GO) analysis were conducted on the obtained differential genes. Finally, single-sample GSEA (ssGSEA) and Gene Set Enrichment Analysis (GSEA) were utilized to analyze the infiltration level of 28 immune cells and their relationship with hub genes based on gene expression profile data and all differential gene files. Results: A total of 82 differentially expressed genes (DEGs) were screened after the training datasets were merged and intersected. The WGCNA analysis clustered the expression profile data into four co-expression modules, The turquoise module exhibited the strongest relationship with clinical traits, and nine candidate key genes were obtained from the module. Then we intersected DEGs with nine candidate genes. LASSO regression analysis identified the last three hub genes as promising biomarkers to distinguish the cardiomyopathy group from the non-cardiomyopathy control group. ROC curve analysis in the validation dataset revealed the sensitivity and accuracy of three hub genes as marker genes. The majority of the functional enrichment analysis results were concentrated on immunological and inflammatory pathways. Immune infiltration analysis revealed a significant correlation between regulatory T cells, type I helper T cells, macrophages, myeloid-derived suppressor cells, natural killer cells, activated dendritic cells and the abundance of immune infiltration in hub genes. Conclusion: The hub genes (CD14, CCL2, and SERPINA3) can be used as markers to distinguish cardiomyopathy from non-cardiomyopathy individuals. Among them, SERPINA3 has the best diagnostic performance. T cell immunity (adaptive immune response) is closely linked to cardiomyopathy progression. Hub genes may protect the myocardium from injury through myeloid-derived suppressor cells, regulatory T cells, helper T cells, monocytes/macrophages, natural killer cells and activated dendritic cells. The innate immune response is crucial to this process. Dysregulation and imbalance of innate immune cells or activation of adaptive immune responses are involved in cardiomyopathy disease progression in patients.

Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction.

Descending vasa recta (DVR) are 12- to 15-µm microvessels that supply the renal medulla with blood flow. We examined the ability of intrinsic nitric oxide (NO) and reactive oxygen species (ROS) generation to regulate their vasoactivity. Nitric oxide synthase (NOS) inhibition with N(ω)-nitro-l-arginine methyl ester (l-NAME; 100 µmol/l), or asymmetric N(G),N(G)-dimethyl-l-arginine (ADMA; 100 µmol/l), constricted isolated microperfused DVR by 48.82 ± 4.34 and 27.91 ± 2.91%, respectively. Restoring NO with sodium nitroprusside (SNP; 1 mmol/l) or application of 8-Br-cGMP (100 µmol/l) reversed DVR vasoconstriction by l-NAME. The superoxide dismutase mimetic Tempol (1 mmol/l) and the NAD(P)H inhibitor apocynin (100, 1,000 µmol/l) also blunted ADMA- or l-NAME-induced vasoconstriction, implicating a role for concomitant generation of ROS. A role for ROS generation was also supported by an l-NAME-associated rise in oxidation of dihydroethidium that was prevented by Tempol or apocynin. To test whether H(2)O(2) might play a role, we examined its direct effects. From 1 to 100 µmol/l, H(2)O(2) contracted DVR whereas at 1 mmol/l it was vasodilatory. The H(2)O(2) scavenger polyethylene glycol-catalase reversed H(2)O(2) (10 µmol/l)-induced vasoconstriction; however, it did not affect l-NAME-induced contraction. Finally, the previously known rise in DVR permeability to (22)Na and [(3)H]raffinose that occurs with luminal perfusion was not prevented by NOS blockade. We conclude that intrinsic production of NO and ROS can modulate DVR vasoactivity and that l-NAME-induced vasoconstriction occurs, in part, by modulating superoxide concentration and not through H(2)O(2) generation. Intrinsic NO production does not affect DVR permeability to hydrophilic solutes.

Effect of dendroaspis natriuretic peptide (DNP) on L-type calcium channel current and its pathway.

Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, relaxes gastrointestinal smooth muscle. L-type calcium channel currents play an important role in regulating smooth muscle contraction. The effect of DNP on L-type calcium channel currents in gastrointestinal tract is still unclear. This study was designed to investigate the effect of DNP on barium current (I(Ba)) through the L-type calcium channel in gastric antral myocytes of guinea pigs and cGMP-pathway mechanism. The whole-cell patch-clamp technique was used to record L-type calcium channel currents. The content of cGMP in guinea pig gastric antral smooth muscle and perfusion solution was measured using radioimmunoassay. DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in perfusion medium. DNP concentration-dependently inhibited I(Ba) in freshly isolated guinea pig gastric antral circular smooth muscle cells (SMCs) of guinea pigs. DNP-induced inhibition of I(Ba) was partially blocked by LY83583, an inhibitor of guanylate cyclase. KT5823, a cGMP-dependent protein kinase (PKG) inhibitor, almost completely blocked DNP-induced inhibition of I(Ba). However, DNP-induced inhibition of I(Ba) was potentiated by zaprinast, an inhibitor of cGMP-sensitive phosphodiesterase. Taken together, DNP inhibits L-type calcium channel currents via pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs.

Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through the cGMP/cGMP-dependent protein kinase pathway.

AIM: To systematically investigate if cGMP/cGMP-dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca(2+)-activated K(+) currents (I(K(Ca))) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastric antral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased I(K(Ca)). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates I(K(Ca)) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/PKA pathway.