Search

Tri Ethyl Ammonium Picrate (TEAP) and Yttrium (Y2+) ions doped single crystals were grown by slow evaporation technique at room temperature. The estimated band gap of the pure TEAP, 0.10 mol % and 0.15 mol % of Y2+ ions doped TEAP are 3.76 eV, 3.82 eV and 3.86 eV. Crystallite size of the grown materials was calculated from powder XRD as 1.456 nm for TEAP, 3.2028 nm for 0.10 mol % of Y2+ ions doped TEAP and 6.934 nm for 0.15 mol % of Y2+ ions doped TEAP single crystals. Y–O stretching mode was assigned by FTIR spectral peak at 549 cm−1. The PL excitation wavelength of the grown materials is 350 nm. The EDAX analysis confirmed by the Carbon, Nitrogen, Oxygen and Yttrium were presented in grown crystals.

Ehrlichia chaffeensis (E. chaffeensis) has evolved eukaryotic ligand mimicry to repurpose multiple cellular signaling pathways for immune evasion. In this investigation, we demonstrate that TRP120 has a novel repetitive short linear motif (SLiM) that activates the evolutionarily conserved Hedgehog (Hh) signaling pathway to inhibit apoptosis. In silico analysis revealed that TRP120 has sequence and functional similarity with Hh ligands and a candidate Hh ligand SLiM was identified. siRNA knockdown of Hh signaling and transcriptional components significantly reduced infection. Co-immunoprecipitation and surface plasmon resonance demonstrated that rTRP120-TR interacted directly with Hh receptor Patched-2 (PTCH2). E. chaffeensis infection resulted in early upregulation of Hh transcription factor GLI-1 and regulation of Hh target genes. Moreover, soluble recombinant TRP120 (rTRP120) activated Hh and induced gene expression consistent with the eukaryotic Hh ligand. The TRP120-Hh-SLiM (NPEVLIKD) induced nuclear translocation of GLI-1 in THP-1 cells and primary human monocytes and induced a rapid and expansive activation of Hh pathway target genes. Furthermore, Hh activation was blocked by an α-TRP120-Hh-SLiM antibody. TRP120-Hh-SLiM significantly increased levels of Hh target, anti-apoptotic protein B-cell lymphoma 2 (BCL-2), and siRNA knockdown of BCL-2 dramatically inhibited infection. Blocking Hh signaling with the inhibitor Vismodegib, induced a pro-apoptotic cellular program defined by decreased mitochondria membrane potential, significant reductions in BCL-2, activation of caspase 3 and 9, and increased apoptotic cells. This study reveals a novel E. chaffeensis SLiM ligand mimetic that activates Hh signaling to maintain E. chaffeensis infection by engaging a BCL-2 anti-apoptotic cellular program.

Accountability has frequently been presented as a rational practice that can and should be implemented in all governance structures including civil society, economic institutions and organizations. In accounting, it has been identified as a primary objective of financial reporting. This paper examines two emotional states, i.e. guilt and shame that are likely to influence accountability. The paper argues that (a) accountability through information disclosure is a cultural practice closely associated with the emotional state of guilt that is common in certain cultures, and (b) in cultures where the emotional state of shame is common, accountability is likely to be weak and, people are likely to be negatively inclined towards information disclosure. Studies in psychology have also shown that "typical" shame experiences were common in collectivistic, large power-distance and high uncertainty avoidance cultures; while "typical" guilt experiences were more pronounced in individualistic, small power distance and low uncertainty avoidance cultures. [ABSTRACT FROM AUTHOR]

A thin film of pyroelectric composite with 0–3 connectivity was fabricated from zinc oxide (ZnO) nanopowder and polyvinylidene fluoride (PVDF) with different volume fraction from 0–0.25 wt%. The dielectric and pyroelectric properties of the samples were investigated. It was found that the presence of a small amount of ZnO nanoparticles (0.25 wt%) has significantly increased the pyroelectric coefficient of the PVDF by 25%. Furthermore, the nanocomposite films required lower poling field to form polar-δ phase compared to pure PVDF thin films. Analysis of the complex permittivity in a wide range of frequency was carried out indicating that the dielectric constant and loss of PVDF/ZnO nanocomposite thin films increase when doped with ZnO. Havriliak-Negami (HN) empirical function has been employed to obtain the α-relaxation time of the nanocomposite thin films before and after poling. The α-relaxation time does not vary with the increase of ZnO wt%; however, the effect of poling has lengthened the relaxation time of the thin films. FTIR and XRD results supports the fact that the addition of ZnO nanoparticles into PVDF polymer thin films do not cause any significant effect on the structure of the PVDF thin films. In fact, ZnO nanoparticle has enhanced the overall pyroelectricity of PVDF by facilitating the poling process in the composites and led to phase transformation of PVDF from α- to δ-phase as supported by a marked reduction of (100) x-ray diffraction intensities. [ABSTRACT FROM AUTHOR]

Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL)-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum.

Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, encodes a small hydrophobic (SH) protein of unknown function. Here we show that infection of plasmacytoid dendritic cells (pDCs) with a recombinant virus lacking SH expression (rhMPV-ΔSH) enhanced the secretion of type I interferons (IFNs), which required TLR7 and MyD88 expression. HMPV SH protein inhibited TLR7/MyD88/TRAF6 signaling leading to IFN gene transcription, identifying a novel mechanism by which paramyxovirus SH proteins modulate innate immune responses.

The physicochemical properties of the physiological makeup and the chemical componentof the system make this challenging throughout strenuous procedure. The current review concentrated on in silico modelling of drug disposition, involving absorption process, distribution process, and excretion process and includes thorough knowledge of various database expeditions, the development of a pharmacophore model, molecular docking studies, homology modelling supported sequence similarity and quantitative structure-activity relationships (QSAR)/ quantitative structure-property relationships (QSPR) evaluation along with all information about drug movement and related computational tools for understanding potential chemical and pathophysiological changes. The primary development in ADMET modeling in current times has been the clarification of the function and effective modeling of various transporters. In ADMET modelling, there is still work to be done on including the impact of these transporters into existing models. The present state of modelling different elements of drug disposal at the systemic level will then be discussed, along with recent developments in modelling a wide range of active transporters and their effects on drug pharmacokinetic profiles. A more thorough knowledge of the underlying processes governing different aspects of drug disposition should also lead to an increase in mechanism-based modelling methods that are simple to grasp and put into practice. These developments will hasten the transition of model construction from computational to experimental scientists.

Introduction: Raised intracranial pressure (ICP) can be due to varied etiology. Differentiating among these various etiologies is crucial in making appropriate therapeutic decisions. A patient with a known past history of the primary or secondary headache of any etiology, when presenting with new onset severe headache, needs to be evaluated with imaging to rule out an alternative diagnosis., Discussion: Here, we describe the case details of a young lady who presented with recurrent raised ICP headaches due to three different etiologies. At her third visit, isolated intracranial hypertension (IH) was the only manifestation of cerebral venous sinus thrombosis (CVST), which could have been missed if a repeat magnetic resonance imaging (MRI) brain and venogram were not done., Conclusion: Our case highlights the importance of having a high degree of suspicion for CVST in the clinical setting of raised ICP headache in view of its crucial therapeutic implications., (© Journal of the Association of Physicians of India 2023.)

Despite the successes of immunotherapy, melanoma remains one of the deadliest cancers, therefore, the need for innovation remains high. We previously reported anti-melanoma compounds that work by downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to assess the efficacy of these compounds by testing them in A375 cell-line xenograft in nude athymic mice. Animals were randomized into four groups (n = 12/group): 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 thrice a week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results demonstrate the therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. Given the lack of knowledge about the side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50 mg/kg/day via subcutaneous injections, and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, the effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the body weight, blood cell count, blood chemistry, or organs of the mice following the compound treatment. The results show that our compounds, 2155-14 and 2155-18, are not toxic for the study period of three weeks.

The number of total knee arthroplasties performed in India and the world is increasing exponentially. The valgus cut angle (VCA) of the distal femur decides the final alignment achieved in the coronal plane. Little data are available regarding the ideal value for an Indian population and there is little consensus whether to use a single value for all knees or to individualize the angle for each patient. The parameters that can influence the value of this angle have not been evaluated thoroughly.Standard long leg X-ray (orthoscanogram) was used to calculate the VCA in 302 lower limbs (160 patients). Only Indian patients were included in the study; knees with bowed femurs were excluded. VCA, femoral length, medial hip offset, neck shaft angle, and hip knee ankle angle were measured manually. Demographic data such as gender, height, and weight were extracted from hospital charts. The correlation of VCA with the various parameters was evaluated using Pearson's correlation and its significance assessed using the independent Student's 't' test.The average VCA was 7.4 degrees (range: 4-11 degrees). Age, gender, height, hip knee ankle angle (alignment) and body mass index (BMI) had no influence on the VCA. The neck shaft angle ( r  = -0.520, p  = < 0.0001) and hip medial offset ( r  = 0.223, p  = < 0.0001) were the only two parameters significantly and independently influencing the value of VCA. There is a wide variation in the value of VCA in the Indian population. Choosing a fixed VCA will lead to significant number of knees aligned outside the ideal 0- to 3-degree hip knee ankle angle. The neck shaft angle and the medial hip offset are the only two factors that influence the VCA. The patients' height, preoperative deformity, gender, and BMI had no influence on the VCA., Competing Interests: None declared., (Thieme. All rights reserved.)

Herein, we report morphology controlled growth of layered V 2 O 5 on V 2 C by the oxidation of V-MXenes at different temperatures and used it as a cathode material for Zn-ion batteries (ZIBs). Hence, the V 2 O 5 nanoparticles are uniformly grown on the V 2 C nanosheets with interlinked disordered carbon which provide fast diffusion and high rate performance in aqueous zinc-ion batteries.

Tri Ethyl Ammonium Picrate (TEAP) and Yttrium (Y 2+ ) ions doped single crystals were grown by slow evaporation technique at room temperature. The estimated band gap of the pure TEAP, 0.10 mol % and 0.15 mol % of Y 2+ ions doped TEAP are 3.76 eV, 3.82 eV and 3.86 eV. Crystallite size of the grown materials was calculated from powder XRD as 1.456 nm for TEAP, 3.2028 nm for 0.10 mol % of Y 2+ ions doped TEAP and 6.934 nm for 0.15 mol % of Y 2+ ions doped TEAP single crystals. Y-O stretching mode was assigned by FTIR spectral peak at 549 cm -1 . The PL excitation wavelength of the grown materials is 350 nm. The EDAX analysis confirmed by the Carbon, Nitrogen, Oxygen and Yttrium were presented in grown crystals.

Background: Repellents such as coils, vaporizers, mats and creams can be used to reduce the risk of malaria and other infectious diseases. Although evidence for their effectiveness is limited, they are advertised as providing an additional approach to mosquito control in combination with other strategies, e.g. insecticide-treated nets. We examined the use of repellents in India in an urban setting in Chennai (mainly Plasmodium vivax malaria), a peri-urban setting in Nadiad (both P. vivax and P. falciparum malaria), and a more rural setting in Raurkela (mainly P. falciparum malaria)., Methods: The use of repellents was examined at the household level during a census, and at the individual level in cross-sectional surveys and among patients visiting a clinic with fever or other symptoms. Factors associated with their use were examined in a multivariate analysis, and the association between malaria and the use of repellents was assessed among survey- and clinic participants., Results: Characteristics of participants differed by region, with more people of higher education present in Chennai. Use of repellents varied between 56-77 % at the household level and between 32-78 % at the individual level. Vaporizers were the main repellents used in Chennai, whereas coils were more common in Nadiad and Raurkela. In Chennai and Nadiad, vaporizers were more likely to be used in households with young male children. Vaporizer use was associated with higher socio-economic status (SES) in households in Chennai and Nadiad, whereas use of coils was greater in the lower SES strata. In Raurkela, there was a higher use of coils among the higher SES strata. Education was associated with the use of a repellent among survey participants in Chennai and clinic study participants in Chennai and Nadiad. Repellent use was associated with less malaria in the clinic study in Chennai and Raurkela, but not in the surveys, with the exception of the use of coils in Nadiad., Conclusions: Repellents are widely used in India. Their use is influenced by the level of education and SES. Information on effectiveness and guidance on choices may improve rational use.

Objective: To evaluate the antiulcer activity of Samanea saman (Jacq) Merr bark on ethanol and stress induced gastric lesions in albino rats., Materials and Methods: Gastric lesions were induced in rats by oral administration of absolute ethanol (5 ml/kg) and stress induced by water immersion. The antiulcer activity of methanolic extract of Samanea saman (Jacq) Merr bark (100 mg/kg, 200 mg/kg, 400 mg/kg) was compared with standard drugs. The parameters studied were ulcer index, gastric juice volume, pH, free acidity and total acidity., Result: Samanea saman (Jacq) Merr showed a dose dependent curative ratio compared to ulcer control groups. The extract at 400 mg/kg showed significant anti ulcer activity which is almost equal to that of the standard drug in both models. The volume of acid secretion, total and free acidity was decreased and pH of the gastric juice was increased compared to ulcer control group., Conclusions: The present study indicates that Samanea saman (Jacq) Merr bark extracts have potential anti ulcer activity.

Prostate cancer is the most common malignancy and the second leading cause of cancer death in the male population in developing countries. Ukrain is a reaction product of different alkaloids from Chelidoniummajus L. (celandine) conjugated with thiophosphoric acid, which has cytotoxic effects on various malignant cells. In the present study, cell viability was assessed using the dimethyl thiazolyl tetrazolium bromide (MTT)method in PC-3 cells after treatment with Ukrain. The IC(50) value was observed in 10 μg concentration of Ukrain. Bax, Bad, and FasL mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction, and protein expressions of p-Akt, Bcl-2, and caspase 10 were determined by western-blot analysis. Nuclei were stained with 4’,6-diamidino-2-phenylindole, dihydrochloride (DAPI). Ukrain significantly increased the pro-apoptotic mRNA expression of Bad, Bax, and FasL; decreased the cell survival protein p-Akt and the anti-apoptotic protein Bcl-2; and increased the protein levels of cleaved poly(ADP)-ribose polymerase (PARP) and caspase-10.The results of this study suggest that Ukrain decreases the cell survival of androgen-independent prostate cancer cells and induces their apoptosis, thus supporting its use as a therapeutic drug for the treatment of prostate cancer