Synergistic Crystal and Interface Engineering for Efficient and Stable Perovskite Photovoltaics

The presence of bulk and surface defects in perovskite light harvesting materials limits the overall efficiency of perovskite solar cells (PSCs). The formation of such defects is suppressed by adding methylammonium chloride (MACl) as a crystallization aid to the precursor solution to realize high‐quality, large‐grain triple A‐cation perovskite films and that are combined with judicious engineering of the perovskite interface with the electron and hole selective contact materials. A planar SnO₂/TiO₂ double layer oxide is introduced to ascertain fast electron extraction and the surface of the perovskite facing the hole conductor is treated with iodine dissolved in isopropanol to passivate surface trap states resulting in a retardation of radiationless carrier recombination. A maximum solar to electric power conversion efficiency (PCE) of 21.65% and open circuit photovoltage (V_oc) of ≈1.24 V with only ≈370 mV loss in potential with respect to the band gap are achieved, by applying these modifications. Additionally, the defect healing enhances the operational stability of the devices that retain 96%, 90%, and 85% of their initial PCE values after 500 h under continuously light illumination at 20, 50, and 65 °C, respectively, demonstrating one of the most stable planar PSCs reported so far.     

DIVERSITY IN GUT MICROFLORA OF Helicoverpa armigera POPULATIONS FROM DIFFERENT REGIONS IN RELATION TO BIOLOGICAL ACTIVITY OF Bacillus thuringiensis δ‐ENDOTOXIN Cry1Ac

Transgenic crops expressing toxin proteins from Bacillus thuringiensis (Bt) have been deployed on a large scale for management of Helicoverpa armigera. Resistance to Bt toxins has been documented in several papers, and therefore, we examined the role of midgut microflora of H. armigera in its susceptibility to Bt toxins. The susceptibility of H. armigera to Bt toxin Cry1Ac was assessed using Log‐dose‐Probit analysis, and the microbial communities were identified by 16S rRNA sequencing. The H. armigera populations from nine locations harbored diverse microbial communities, and had some unique bacteria, suggesting a wide geographical variation in microbial community in the midgut of the pod borer larvae. Phylotypes belonging to 32 genera were identified in the H. armigera midgut in field populations from nine locations. Bacteria belonging to Enterobacteriaceae (Order Bacillales) were present in all the populations, and these may be the common members of the H. armigera larval midgut microflora. Presence and/or absence of certain species were linked to H. armigera susceptibility to Bt toxins, but there were no clear trends across locations. Variation in susceptibility of F₁ neonates of H. armigera from different locations to the Bt toxin Cry1Ac was found to be 3.4‐fold. These findings support the idea that insect migut microflora may influence the biological activity of Bt toxins.     

Impact of Hyperhomocysteinemia on Breast Cancer Initiation and Progression: Epigenetic Perspective

Our recent study showing association of hyperhomocysteinemia and hypomethioninemia in breast cancer and other studies indicating association of hyperhomocysteinemia with metastasis and development of drug resistance in breast cancer cells treated with homocysteine lead us to hypothesize that homocysteine might modulate the expression of certain tumor suppressors, i.e., RASSF1, RARβ1, CNND1, BRCA1, and p21, and might influence prognostic markers such as BNIP3 by inducing epigenetic alteration. To demonstrate this hypothesis, we have treated MCF-7 and MDA-MB-231 cells with different doses of homocysteine and observed dose-dependent inhibition of BRCA1 and RASSF1, respectively. In breast cancer tissues, we observed the following expression pattern: BNIP3 > BRCA1 > RARβ1 > CCND1 > p21 > RASSF1. Hyperhomocysteinemia was positively associated with BRAC1 hypermethylation both in breast cancer tissue and corresponding peripheral blood. Peripheral blood CpG island methylation of BRCA1 in all types of breast cancer and methylation of RASSF1 in ER/PR-negative breast cancers showed positive correlation with total plasma homocysteine. The methylation of RASSF1 and BRCA1 was associated with breast cancer initiation as well as progression, while BRCA1 methylation was associated with DNA damage. Vitamin B₁₂ showed inverse association with the methylation at both the loci. RFC1 G80A and cSHMT C1420T variants showed positive association with methylation at both the loci. Genetic variants influencing remethylation step were associated positively with BRCA1 methylation and inversely with RASSF1 methylation. GCPII C1561T variant showed inverse association with BRCA1 methylation. We found good correlation of BRAC1 (r = 0.90) and RASSF1 (0.92) methylation pattern between the breast cancer tissue and the corresponding peripheral blood. To conclude, elevated homocysteine influences methionine dependency phenotype of breast cancer cells and is associated with breast cancer progression by epigenetic modulation of RASSF1 and BRCA1 .     

Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase

Fbw7 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction. Genomic deletion or mutation of FBW7 has been frequently found in various types of human cancers; however, little is known about the upstream signaling pathway(s) governing Fbw7 stability and cellular functions. Here we report that Fbw7 protein destruction and tumor suppressor function are negatively regulated by the prolyl isomerase Pin1. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Consequently, overexpressing Pin1 reduces Fbw7 abundance and suppresses Fbw7's ability to inhibit proliferation and transformation. By contrast, depletion of Pin1 in cancer cells leads to elevated Fbw7 expression, which subsequently reduces Mcl-1 abundance, sensitizing cancer cells to Taxol. Thus, Pin1-mediated inhibition of Fbw7 contributes to oncogenesis, and Pin1 may be a promising drug target for anticancer therapy.     

In silico analysis of Single Nucleotide Polymorphisms (SNPs) in human BRAF gene

BRAF gene mutations are frequently seen in both inherited and somatic diseases. However, the harmful mutations for BRAF gene have not been predicted in silico. Owing to the importance of BRAF gene in cell division, differentiation and secretion processes, the functional analysis was carried out to explore the possible association between genetic mutations and phenotypic variations. Genomic analysis of BRAF was initiated with SIFT followed by PolyPhen and SNPs&GO servers to retrieve the 85 deleterious non-synonymous SNPs (nsSNPs) from dbSNP. A total of 5 mutations i.e. c.406T>G (S136A), c.1446G>T (R462I), c.1556 A>G (K499E), c.1860 T>A (V600E) and c.2352 C>T (P764L) that are found to exert benign effects on the BRAF protein structure and function were chosen for further analysis. Protein structural analysis with these amino acid variants was performed by using I-Mutant, FOLD-X, HOPE, NetSurfP, Swiss PDB viewer, Chimera and NOMAD-Ref servers to check their solvent accessibility, molecular dynamics and energy minimization calculations. Our in silico analysis suggested that S136A and P764L variants of BRAF could directly or indirectly destabilize the amino acid interactions and hydrogen bond networks thus explain the functional deviations of protein to some extent. Screening for BRAF, S136A and P764Lvariants may be useful for disease molecular diagnosis and also to design the molecular inhibitors of BRAF pathways.     

Emerging roles of the FBW7 tumour suppressor in stem cell differentiation

FBW7 is a ubiquitin E3 ligase substrate adaptor that targets many important oncoproteins-such as Notch, c-Myc, cyclin E and c-Jun-for ubiquitin-dependent proteolysis. By doing so, it plays crucial roles in many cellular processes, including cell cycle progression, cell growth, cellular metabolism, differentiation and apoptosis. Loss of FBW7 has been observed in many types of human cancer, and its role as a tumour suppressor was confirmed by genetic ablation of FBW7 in mice, which leads to the induction of tumorigenesis. How FBW7 exerts its tumour suppression function, and whether loss of FBW7 leads to de-differentiation or acquisition of stemness-a process frequently seen in human carcinomas-remains unclear. Emerging evidence shows that FBW7 controls stem cell self-renewal, differentiation, survival and multipotency in various stem cells, including those of the haematopoietic and nervous systems, liver and intestine. Here, we focus on the function of FBW7 in stem cell differentiation, and its potential relevance to human disease and therapeutics.     

A New Heteroleptic Ruthenium Sensitizer for Transparent Dye‐Sensitized Solar Cells

A new heteroleptic ruthenium complex, coded CYC‐B19 , incorporating an ancillary ligand endowed with hexylthio‐bithiophene segments and a conjugated anchoring ligand with vinyl groups was prepared. This new sensitizer exhibits a lower energy MLCT band centred at 562 nm with a remarkably high molar absorption coefficient of 2.97 × 10⁴ M^?1 cm^?1. DFT‐TDDFT theoretical calculation revealed that insertion a vinyl group in the anchoring ligand pushes the LUMO electron locating more on the anchoring ligand. This will benefit the electron transfer from dye to TiO₂ when the dye molecules were excited by light. Physicochemical measurements and the optimization of electrolyte were done to investigate the potential of CYC‐B19 in TiO₂ scattering‐layer free dye‐sensitized solar cells. Not only is a good photovoltaic efficiency of 8.4% reached, but the transparent device sensitized by CYC‐B19 also presents a superior spectral response to its predecessor CYC‐B11 .     

The intrinsic axial ligand effect on propene oxidation by horseradish peroxidase versus cytochrome P450 enzymes

The axial ligand effect on reactivity of heme enzymes is explored by means of density functional theoretical calculations of the oxidation reactions of propene by a model compound I species of horseradish peroxidase (HRP). The results are assessed vis-à-vis those of cytochrome P450 compound I. It is shown that the two enzymatic species perform C=C epoxidation and C–H hydroxylation in a multistate reactivity scenario with Fe^III and Fe^IV electromeric situations and two different spin states, doublet and quartet. However, while the HRP species preferentially keeps the iron in a low oxidation state (Fe^III), the cytochrome P450 species prefers the higher oxidation state (Fe^IV). It is found that HRP compound I has somewhat lower barriers than those obtained by the cytochrome P450 species. Furthermore, in agreement with experimental observations and studies on model systems, HRP prefers C=C epoxidation, whereas cytochrome P450 prefers C–H hydroxylation. Thus, had the compound I species of HRP been by itself, it would have been an epoxidizing agent, and at least as reactive as cytochrome P450. In the enzyme, HRP is much less reactive than cytochrome P450, presumably because HRP reactivity is limited by the access of the substrate to compound I.Electronic Supplementary Material Supplementary material is available for this article at .The paper is dedicated to D. K. Bohme on the occasion of his forthcoming 65th birthday.