Behavior of Microstrain in Nd3+-Sensitized Near-Infrared Upconverting Core-Shell Nanocrystals for Defect-Induced Tailoring of Luminescence Intensity.

In an attempt to optimize the upconversion luminescence (UCL) output of a Nd3+-sensitized near-infrared (808 nm) upconverting core-shell (CS) nanocrystal through deliberate incorporation of lattice defects, a comprehensive analysis of microstrain both at the CS interface and within the core layer was performed using integral breadth calculation of high-energy synchrotron X-ray (λ = 0.568551 Å) diffraction. An atomic level interpretation of such microstrain was performed using pair distribution function analysis of the high-energy total scattering. The core NC developed compressive microstrain, which gradually transformed into tensile microstrain with the growth of the epitaxial shell. Such a reversal was rationalized in terms of a consistent negative lattice mismatch. Upon introduction of lattice defects into the CS systems upon incorporation of Li+, the corresponding UCL intensity was maximized at some specific Li+ incorporation, where the tensile microstrain of CS, compressive microstrain of the core, and atomic level disorders exhibited their respective extreme values irrespective of the activator ions.

One-Step High-Temperature Electrodeposition of Fe-Based Films as Efficient Water Oxidation Catalysts.

Electrolysis of water to produce hydrogen requires an efficient catalyst preferably made of cheap and abundant metal ions for the improved water oxidation reaction. An Fe-based film has been deposited in a single step by electrochemical deposition at temperatures higher than the room temperature. Until now, the electrodeposition of iron oxide has been carried out at 298 K or at lower temperatures under a controlled atmosphere to prohibit atmospheric oxidation of Fe2+ of the iron precursor. A metal inorganic complex, ferrocene, and non-aqueous electrolyte medium propylene carbonate have been used to achieve electrodeposition of iron oxide without the need of any inert or controlled atmosphere. At 298 K, the amorphous film was formed, whereas at 313 K and at higher temperatures, the hematite film was grown, as confirmed by X-ray diffraction. The transformation of iron of the ferrocene into a higher oxidation state under the experimental conditions used was further confirmed by X-ray photoelectron spectroscopy, ultraviolet-visible, and electron paramagnetic resonance spectroscopic methods. The films deposited at 313 K showed the best performance for water oxidation with remarkable long-term electrocatalytic stability and an impressive turnover frequency of 0.028 s-1 which was 4.5 times higher than that of films deposited at 298 K (0.006 s-1). The observed overpotential to achieve a current density of 10 mA cm-2 was found to be 100 mV less for the film deposited at 313 K compared to room-temperature-derived films under similar experimental conditions. Furthermore, electrochemical impedance data revealed that films obtained at 313 K have the least charge transfer resistance (114 Ω) among all, supporting the most efficient electron transport in the film. To the best of our knowledge, this is the first-ever report where the crystalline iron-based film has been shown to be electrodeposited without any post-deposition additional treatment for alkaline oxygen evolution reaction application.

Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts.

A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a-h and related quaternary ammonium salts 4a-h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series 3 and 4 to be potent cytotoxins with submicromolar CC50 values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure-activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, 3a-h are cytotoxic towards a number of leukemic and colon cancer cells. 4b,c lowered the mitochondrial membrane potential in CEM cells, and 4d induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely 3c,d and 4c-e, were identified as lead molecules that have drug-like properties.

Heat shock proteins and their expression in primary murine cardiac cell populations during ischemia and reperfusion.

A tight quality control system over protein folding, turnover and synthesis, involving molecular chaperones and co-chaperones, maintains the balance of cardiac proteins. Various cardiac pathologies, including myocardial infarction, increase stresses and post-translational modifications favoring misfolding due to an overwhelmed quality control system. The toxic nature of accumulated misfolded proteins further worsens the condition. The important molecular chaperones which act as quality control proteins are involved in protecting the heart, these include heat shock protein70 (HSP70) and HSP90. Here, we review the emerging roles of heat shock proteins in the maintenance of cardiac cell populations in experimental models of ischemia/reperfusion (I/R) injury. Furthermore, we discuss the expression of HSP70 and HSP90 with therapeutic and diagnostic considerations. Although there is only a partial understanding of these important HSPs in I/R injury, there is an immense therapeutic potential of modulating these HSPs to counteract the imbalance between misfolding and endogenous protein quality control systems.

Bilateral Masseter and Internal Pterygoid Muscle Hypertrophy: A Diagnostic Challenge.

OBJECTIVE: To describe an unusual case of bilateral masseter and pterygoid muscle hypertrophy. CLINICAL PRESENTATION AND INTERVENTION: A 23-year-old male patient presented with a bilateral, painless swelling of 1 year duration at the parotid areas without improvement after using antibiotics/systemic corticosteroids/non steroidal anti-inflammatory agents. His medical history was not significant. The initial differential diagnosis included salivary gland/jaw bone/masseter pathology, but the MRI revealed only an increase in the size of the masseter and pterygoid muscles. The patient was informed of the benign nature of the swelling and was advised to discontinue the use of non steroidal anti-inflammatory agents. CONCLUSION: The bilateral hypertrophy of masseter muscles should be considered in differential diagnosis in cases of unilateral or bilateral swelling of the parotid or lateral mandible area.

Reduced Expression of Glutathione S-Transferase α 4 Promotes Vascular Neointimal Hyperplasia in CKD.

Neointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)-mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs. Compared with non-CKD controls, mice with CKD had downregulated expression of GSTA4 at the mRNA and protein levels, with concomitant increase in 4-HNE in arteries and veins. This effect was associated with upregulated phosphorylation of MAPK signaling pathway proteins in proliferating SMCs. Overexpressing GSTA4 blocked 4-HNE-induced SMC proliferation. Additionally, inhibitors of MAPK signaling inhibited the 4-HNE-induced responses. Compared with wild-type mice, mice lacking GSTA4 exhibited increased CKD-induced neointima formation in AVF. Transient expression of an activated form of GSTA4, achieved using a combined Tet-On/Cre induction system in mice, lowered levels of 4-HNE and reduced the proliferation of SMCs. Together, these results demonstrate the critical role of GSTA4 in blocking CKD-induced neointima formation and AVF failure.

Interplay between the folding mechanism and binding modes in folding coupled to binding processes.

Proteins that fold upon binding to their partners exhibit complex binding behavior such as induced-fit. But the connections between the folding mechanism and the binding mode remain unknown. Here we focus on the high affinity complex between the physiologically and marginally unstable, fast folder PSBD and the E1 subunit of pyruvate dehydrogenase. Using coarse-grained simulations we investigate the binding to E1 of a partially disordered PSBD under two folding scenarios: two-state and downhill. Our simulations show that induced-fit binding requires that PSBD folds-unfolds in the downhill folding regime. In contrast, a two-state folding PSBD must fold completely before it binds. The reason is that effective coupling between folding and binding involves partially folded conformations, which are only sufficiently populated under the downhill folding regime. Our results establish a direct mechanistic link between complex binding and downhill folding, supporting the idea that PSBD operates functionally as a conformational rheostat.

In silico structural and functional analysis of protein encoded by wheat early salt-stress response gene (WESR3).

Salt stress is one of the major abiotic stresses limiting grain yield in wheat (Triticum aestivum L.). Wheat early salt-stress response gene (WESR3) is one of the major salt stress genes, which is affected in the first phase of salt stress. In this study, sequence and structural analysis of protein coded by WESR3 gene was carried out using various bioinformatics tools. Sequence analysis of WESR3 protein revealed the presence of highly conserved regions of Mlo gene family. Three-dimensional modeling was carried out to elucidate its structure and its active site. The sequence analysis revealed that WESR3 protein might be involved in fungal pathogen attack pathway. Thus, in addition to its involvement in abiotic stresses, it also seemed to play an important part in biotic stress pathways. Out of the three modeled protein structures obtained from I-TASSER, HHPred and QUARK, the I-TASSER protein model was the best model based on high confidence score and lesser number of bad contacts. The Ramchandran plot analysis also showed that all amino acid residues of I-TASSER model lie in the allowed region and thus indicating towards the overall good quality of the predicted model. Seventeen active sites were predicted in the protein bearing resemblance to the Mlo family conserved regions. In conclusion, a detailed analysis of WESR3 protein suggested an important role of WESR3 in biotic and abiotic stress. These results aid to the experimental data and help to build up a complete view of WESR3 proteins and their role in plant stress response.

4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway.

4-Hydroxynonenal (HNE) has been widely implicated in the mechanisms of oxidant-induced toxicity, but the detrimental effects of HNE associated with DNA damage or cell cycle arrest have not been thoroughly studied. Here we demonstrate for the first time that HNE caused G2/M cell cycle arrest of hepatocellular carcinoma HepG2 (p53 wild type) and Hep3B (p53 null) cells that was accompanied with decreased expression of CDK1 and cyclin B1 and activation of p21 in a p53-independent manner. HNE treatment suppressed the Cdc25C level, which led to inactivation of CDK1. HNE-induced phosphorylation of Cdc25C at Ser-216 resulted in its translocation from nucleus to cytoplasm, thereby facilitating its degradation via the ubiquitin-mediated proteasomal pathway. This phosphorylation of Cdc25C was regulated by activation of the ataxia telangiectasia and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) pathway. The role of HNE in the DNA double strand break was strongly suggested by a remarkable increase in comet tail formation and H2A.X phosphorylation in HNE-treated cells in vitro. This was supported by increased in vivo phosphorylation of H2A.X in mGsta4 null mice that have impaired HNE metabolism and increased HNE levels in tissues. HNE-mediated ATR/Chk1 signaling was inhibited by ATR kinase inhibitor (caffeine). Additionally, most of the signaling effects of HNE on cell cycle arrest were attenuated in hGSTA4 transfected cells, thereby indicating the involvement of HNE in these events. A novel role of GSTA4-4 in the maintenance of genomic integrity is also suggested.

Altered expression of calcineurin, calpain, calpastatin and HMWCaMBP in cardiac cells following ischemia and reperfusion.

A rise in intracellular myocardial Ca(2+) during cardiac ischemia activates calpain (Calpn) thereby causing damage to myocardial proteins, which leads to myocyte death and consequently to loss of myocardial structure and function. Calcineurin (CaN) interacts with Calpn and causes cellular damage eventually leading to cell death. Calpastatin (Calp) and high molecular weight calmodulin-binding protein (HMWCaMBP) (homolog of Calp), inhibit Calpn activity and thus prevent cell death. CaN stimulation can also result in self-repair of damaged cardiomyocytes. The present study attempts to elucidate the expression of these proteins in cells under pre-ischemic condition (control), following ischemia induction and also reperfusion subsequent to ischemia. For the first time, flow cytometric analysis (FACS) has been used for analyzing protein expression concurrently with viability. We induced ischemia and subsequently reperfusion in 80% confluent cultures of neonatal murine cardiomyocytes (NMCC). Viability following induction was assessed with 7-AAD staining and the cells were simultaneously checked for protein expression by FACS. We observed that ischemia induction results in increased expression of CaN, Calp and Calpn. HMWCaMBP expression was reduced in live cells following ischemia which suggests that there is a poor survival outcome of cells expressing HMWCaMBP thereby making it a potential biomarker for such cells. Most live cells following ischemia expressed CaN pointing towards self-repair and favorable survival outcomes.

Lens specific RLIP76 transgenic mice show a phenotype similar to microphthalmia.

RALBP1/RLIP76 is a ubiquitously expressed protein, involved in promotion and regulation of functions initiated by Ral and R-Ras small GTPases. Presence of multiple domains in its structure enables RLIP76 to be involved in a number of physiological processes such as endocytosis, exocytosis, mitochondrial fission, actin cytoskeleton remodeling, and transport of exogenous and endogenous toxicants. Previously, we have established that RLIP76 provides protection to ocular tissues against oxidative stress by transporting the glutathione-conjugates of the toxic, electrophilic products of lipid peroxidation generated during oxidative stress. Therefore, we developed lens specific RLIP76 transgenic mice (lensRLIP76 Tg) to elucidate the role of RLIP76 in protection against oxidative stress, but these transgenic mice showed impaired lens development and a phenotype with small eyes similar to that observed in microphthalmia. These findings prompted us to investigate the mechanisms via which RLIP76 affects lens and eye development. In the present study, we report engineering of lensRLIP76 Tg mice, characterization of the associated phenotype, and the possible molecular mechanisms that lead to the impaired development of eye and lens in these mice. The results of microarray array analysis indicate that the genes involved in pathways for G-Protein signaling, actin cytoskeleton reorganization, endocytosis, and apoptosis are affected in these transgenic mice. The expression of transcription factors, Pax6, Hsf1, and Hsf4b known to be involved in lens development is down regulated in the lens of these Tg mice. However, the expression of heat shock proteins (Hsps), the downstream targets of Hsfs, is differentially affected in the lens showing down regulation of Hsp27, Hsp40, up regulation of Hsp60, and no effect on Hsp70 and Hsp90 expression. The disruption in the organization of actin cytoskeleton of these Tg mice was associated with the inhibition of the activation of Cdc42 and down regulation of cofilin phosphorylation. These mice may provide useful animal model for elucidating the mechanisms of lens development, and etiology of microphthalmia.

An improved method and cost effective strategy for soluble expression and purification of human N-myristoyltransferase 1 in E. coli.

N-myristoyltransferase (NMT) is an indispensible enzyme, which exists as two isoforms (NMT1 and NMT2) in humans and has proven roles in development of cancerous states. It is thus a target for novel anti-cancer drug design, but understanding of the biochemical and functional differences of these isozymes is not fully deciphered. A soluble expression under the T7 promoter for human NMT1 was achieved in E. coli BL21 (DE3) cells, devoid of any isopropyl ß-D-1-thiogalactopyranoside-based induction. The identity of expressed protein was confirmed by matrix-assisted laser desorption ionization mass spectrometry peptide-fingerprint analysis and a two-step purification protocol yielded homogeneous enzyme. The intact mass of the purified protein was verified by electrospray ionization mass spectrometry and found to be in agreement with the theoretical mass (48.141 vs. 48.140 kDa). The fluorescence spectrophotometric analyses of the ligand binding and enzyme activity demonstrated that the recombinant form is functional. The yield of purified protein was ~8-10 mg/L culture (batch to batch variation) with a specific activity value of 18,500 ± 513 U/mg of protein under the experimental conditions used. The final verification of the myristoylation was demonstrated by mass spectrometry analysis of reaction product. The described approach could be readily adapted for production of human NMT1, with high yields of pure enzyme preparations, which should aid in downstream applications involving inhibitor design and structure-function studies of NMT's.

Comparison of intra-articular glucocorticoid injections with DMARDs versus DMARDs alone in rheumatoid arthritis.

BACKGROUND: Intra-articular triamcinolone in combination with DMARDs may be able to achieve faster and tighter control of disease activity in early rheumatoid arthritis that may be the key to preventing or minimizing later deformities. OBJECTIVE: To compare the efficacy of a combination of Disease Modifying Anti-Rheumatoid Drugs (DMARDs) with Intra-articular Glucocorticoids versus only DMARDs in a group of patients with early Rheumatoid Arthritis (RA). METHODS: Fifty patients diagnosed as Rheumatoid Arthritis (RA) by American Rheumatology Association (ARA) criteria (1987) with disease duration less than two years were randomized into two groups. The Control group received a combination of Methotrexate 15 mg daily with Sulfasalazine 2 gm daily for 3 months and the Study group received the above combination along with Intra-articular injections of Triamcinolone acetate (40 mg per ml) in each of the swollen joints at the start of the study. Outcome was assessed in terms of Disease Activity Score (DAS-28), American College of Rheumatology (ACR) 20/50/70 criteria and number of rescue medications used at the end of 3 months. RESULTS: The study group had significant reductions in DAS 28 scores (3.39 versus 4.99 in control group) and significantly more subjects achieved the ACR 20/50/70 criteria at the end of 3 months (100/60/36% versus 84/20/0%) Secondary end-points like tender and swollen joint count, ESR, early morning stiffness, health assessment questionnaire (HAQ) scores and general health status were significantly reduced in the study group. Also, significantly lesser rescue medications were needed in the study group. CONCLUSION: Combination of DMARDs with Intra-articular corticosteroids is significantly better than DMARDs alone in early RA.

Regulation of N-myristoyltransferase by the calpain and caspase systems.

N-myristoyltransferase (NMT) is an essential eukaryotic enzyme which catalyzes the transfer of the myristoyl group to the terminal glycine residue of a number of proteins including those involved in signal transduction and apoptotic pathways. In higher eukaryotes, two isoforms of NMT have been identified (NMT1 and NMT2) which share about 76% amino acid sequence identity in humans. Protein-protein interactions of NMTs reveal that m-calpain interacts with NMT1 whereas caspase-3 interacts with NMT2. These findings reveal differential interactions of both isoforms of NMT with various signaling molecules. This minireview provides an overview of the regulation of N-myristoyltransferase by calpain and caspase systems.

Antibacterial activity of bark extracts of Moringa oleifera Lam. against some selected bacteria.

The methanol, chloroform, ethyl acetate and aqueous bark extracts of Moringa oleifera were evaluated for their antibacterial activity against four bacteria viz. Staphylococcus aureus, Citrobacter freundii, Bacillus megaterium and Pseudomonas fluorescens using erythromycin as positive control. The activity was analyzed using paper disc diffusion method at different concentration of the extract. The study revealed that all the bark extracts irrespective of their types, in different concentrations inhibited growth of the test pathogens to varying degrees. Ethyl acetate extract showed maximum activity against all the bacterial strains followed in descending order by chloroform, methanol and aqueous extracts. The activity decreased with decrease in concentration of the extract. Staphylococcus aureus was found to be the most sensitive test organism to different extracts of Moringa oleifera. Looking to these results it may be concluded that M. oleifera may be a potential source for the treatment of different infections caused by the resistant microbes.

Product development and characterization of a lipid-based Ayurvedic polyherbal formulation: Kalyanaka Ghrita.

BACKGROUND: Kalyanaka Ghrita (KG) is polyherbal oleaginous medicament consisting of extracts from twenty-eight different plants, indicated for management of psychosomatic disorders like Unmada (Schizophrenia), Apasmara (Epilepsy) and numerous other ailments. OBJECTIVE: To develop and validate standard manufacturing procedure of KG by following Ayurvedic principles in three batches to ensure process uniformity and standards. MATERIALS AND METHODS: Three batches of KG were prepared by adopting principles of Ashtanga Hrudya and Ayurvedic Formulary of India to ensure consistency in manufacturing process. Observations during process such as temperature, duration were recorded. KG was subjected to chief desired characteristics, organoleptic (color, odour, taste, texture, touch), physicochemical (acid value, peroxide value, iodine value, saponification value, loss on drying, refractive index, specific gravity, mineral oil, rancidity test, viscosity) as per pharmacopeial standard. Chromatographic screening and fingerprinting of KG were conducted through GCMS whereas quantification of curcumin and chebulagic acid biomarkers were assessed through HPLC. RESULTS: Average yield of KG was 83.41%, with average intermittent heating duration of 20.35 h subsequently divided into three days. Temperature throughout preparation ranged from 66 °C to 101 °C. KG was pale olive in colour, exhibiting pleasant taste, characteristic smell, and soft texture. Organoleptic and physicochemical characters were comparable for three batches of KG while safety parameters were found within permissible limits. CONCLUSION: Pharmaceutical standardization of Kalyanaka Ghrita is necessary for establishing biological and chemical profile of formulations. Present study recommends use of coarse powdered ingredients for optimal yield during pharmaceutical process, and heating up to Madhyama Paka stage calibrated over three days with average temperature of 85 °C. The data obtained from this study may contribute to future research and development activities, serving as a basis for manufacturing standards of KG.

Interfacial Engineering over Pt-Calcium Ferrite/2D Carbon Nitride Nanosheet p-n Heterojunctions for Superior Photocatalytic Properties.

The present study discloses the fabrication of efficient p-n heterojunctions using n-type polymeric bulk carbon nitride (b-CN, E g = 2.7 eV) or exfoliated nanosheets of carbon nitride (NSCN, E g = 2.9 eV) with p-type spinel ferrite CaFe2O4 (CFO, E g = 1.9 eV) for photocatalytic hydrogen generation. A series of p-n combinations were fabricated and characterized by various techniques. The oxide-carbon nitride interactions, light absorption, band alignment at the interface, and water/H3O+ adsorption capability were elucidated over heterojunctions and correlated with the photocatalytic hydrogen yield. The main developments in the present study are as follows: (1) All heterojunctions were more active than pure phases. (2) The photocatalytic activity trend validated an increase in the lifetime of charge carriers from TRPL. Pt(1 wt %)-CFO(1 wt %)/NSCN (481.5 µmol/h/g under ultraviolet (UV)-visible-simulated light, 147.5 µmol/h/g under CFL illumination for 20 h, τavg = 10.33 ns) > Pt-NSCN > Pt-CFO/b-CN > CFO/NSCN > CFO/b-CN > NSCN > Pt/b-CN > mechanical mixture (MM) of 1 wt %CFO + NSCN-MM > 1 wt %CFO + b-CN-MM > CFO > b-CN (τavg = 4.5 ns). (3) Pt-CFO/NSCN was most active and exhibited 250 times enhanced photocatalytic activity as compared to parent bulk carbon nitride, 6.5 times more active than CFO/NSCN, and twice more active than Pt-NSCN. Thus, enhanced activity is attributed to the smooth channelizing of electrons across p-n junctions. (4) NSCN evidently offered improved characteristics as a support and photocatalyst over b-CN. The exfoliated NSCN occupied a superior few-layer morphology with 0.35 nm width as compared to parent b-CN. NSCN allowed 57% dispersion of 6 nm-sized CFO, while b-CN supported 14% dispersion of 7.8 nm-sized CFO particles, as revealed by small-angle X-ray scattering spectroscopy (SAXS). Sizes of 2-4 nm were observed for Pt nanoparticles in the 1 wt %Pt/1 wt % CFO/NSCN sample. A binding energy shift and an increase in the FWHM of X-ray photoelectron spectroscopy (XPS) core level peaks established charge transfer and enhanced band bending on p-n contact in Pt-CFO/NSCN. FsTAS revealed the decay of photogenerated electrons via trapping in shallow traps (τ1, τ2) and deep traps (τ3). Lifetimes τ1 (3.19 ps, 42%) and τ2 (187 ps, 31%) were higher in NSCN than those in b-CN (τ1 = 2.2 ps, 42%, τ2 = 30 ps, 31%), which verified that the recombination reaction rate was suppressed by 6 times in NSCN (k 2 = 0.53 × 1010 s-1) as compared to b-CN (k 2 = 3.33 × 1010 s-1). Deep traps lie below the H+/H2 reduction potential; thus, electrons in deep traps are not available for photocatalytic H2 generation. (5) The role of CFO in enhancing water adsorption capability was modeled by molecular dynamics. NSCN or b-CN both showed very poor interaction with water molecules; however, the CFO cluster adsorbed H3O+ ions very strongly through the electrostatic interaction between calcium and oxygen (of H3O+). Pt also showed a strong affinity for H2O but not for H3O+. Thus, both CFO and Pt facilitated NSCN to access water molecules, and CFO further sustained the adsorption of H3O+ molecules, crucial for the photocatalytic reduction of water molecules. (6) Band potentials of CFO and NSCN aligned suitably at the interface of CFO/NSCN, resulting in a type-II band structure. Valence band offset (VBO, ΔE VB) and conduction band offset (CBO, ΔE CB) were calculated at the interface, resulting in an effective band gap of 1.41 eV (2.9 - ΔE VB = 1.9 - ΔE CB), much lower than parent compounds. The interfacial band structure was efficient in driving photogenerated electrons from the CB of CFO to the CB of NSCN and holes from the VB of NSCN to the VB of CFO, thus successfully separating charge carriers, as supported by the increased lifetime of charge carriers and favorable photocatalytic H2 yield.

Loss of glutathione S-transferase A4 accelerates obstruction-induced tubule damage and renal fibrosis.

Glutathione transferase isozyme A4 (GSTA4) exhibits high catalytic efficiency to metabolize 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product that has been implicated in the pathogenesis of various chronic diseases. We investigated the role of 4-HNE in the mechanisms of unilateral ureteral obstruction (UUO)-induced fibrosis and its modulation by GSTA4-4 in a mouse model. Our data indicate that after UUO, accumulation of 4-HNE and its adducts were increased in renal tissues, with a concomitant decrease in the expression of GSTA4-4 in mice. As compared to wild-type (WT) mice, UUO caused an increased expression of fibroblast markers in the interstitium of GSTA4 KO mice. Additionally, increased autophagy and tubular cell damage were more severe in UUO-treated GSTA4 KO mice than in WT mice. Furthermore, GSK-3ß phosphorylation and expression of Snail, a regulator of E-cadherin and Occludin, was found to be significantly higher in UUO-inflicted GSTA4 KO mice. GSTA4 over-expression prevented 4-HNE-induced autophagy activation, tubular cell damage and Snail nuclear translocation in vitro. The effects of long-term expression of GSTA4 in restoration of UUO-induced damage in mice with the GSTA4 inducible transposon system indicated that release of obstruction after 3 days of UUO resulted in the attenuation of interstitial SMAα and collagen I expression. This transposon-delivered GSTA4 expression also suppressed UUO-induced loss of tubular cell junction markers and autophagy activation. Together, these results indicate that 4-HNE significantly contributes to the mechanisms of tubule injury and fibrosis and that these effects can be inhibited by the enhanced expression of GSTA4-4.

Cardiomyocyte culture - an update on the in vitro cardiovascular model and future challenges.

The success of any work with isolated cardiomyocytes depends on the reproducibility of cell isolation, because the cells do not divide. To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells and induced pluripotent stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is low. Isolation and expansion of human cardiomyocyte progenitor cells from cardiac surgical waste or, alternatively, from fetal heart tissue is another option. However, to overcome various issues related to human tissue usage, especially ethical concerns, researchers use large- and small-animal models to study cardiac pathophysiology. A simple model to study the changes at the cellular level is cultures of cardiomyocytes. Although primary murine cardiomyocyte cultures have their own advantages and drawbacks, alternative strategies have been developed in the last two decades to minimise animal usage and interspecies differences. This review discusses the use of freshly isolated murine cardiomyocytes and cardiomyocyte alternatives for use in cardiac disease models and other related studies.

Severity and Outcome of Post-Vaccine COVID-19 among Healthcare Workers in a University Hospital in India.

Healthcare workers (HCWs) are at high risk of COVID-19 infection despite vaccination. Limited data exist on COVID-19 cases among vaccinated HCWs. This study aimed to describe the clinical characteristics and outcomes of RT PCR-confirmed COVID-19 cases in vaccinated HCWs, at a COVID clinic in a medical college hospital. This single-center, prospective cohort study included HCWs who received at least one dose of the COVID-19 vaccine and tested positive for COVID-19 within 6 months. Data on demographics, symptoms, work category, COVID-19 vaccination interval, and infection severity were collected. Of 2381 vaccinated HCWs, 105 tested positive and were categorized as mild, moderate, or severe cases. Among vaccinated HCWs, 4.41% had post-vaccine COVID-19 infections. All 105 cases received the first dose, and 79 received the second dose. Of the cases, 47.6% were partially vaccinated, and 53.3% were breakthrough cases. The mean age was 30.90±8.69 years, with 63.8% male and 36.2% female cases. Most cases (85.7%) acquired infection in the hospital, and 47.6% had direct contact with COVID-19 patients. Common symptoms included fatigue (85.7%), fever (82.9%), and cough (64.8%). Among cases, 93.3% were mild, 5.7% were moderate, and 0.9% were severe. Hospital admission and supplemental oxygen therapy were required for moderate and severe cases. No mortality was reported. Certain variables were associated with age, preventive measures, workplace type, symptoms, and comorbidities. Breakthrough infections can occur among fully vaccinated HCWs but with reduced severity and mortality. Monitoring and infection control measures remain crucial even in vaccinated individuals. This study provides insights into clinical presentations, oxygen therapy requirements, and outcomes of post-vaccine COVID-19 cases among HCWs. The data will inform strategies for booster doses to prevent COVID-19.