Density Functional Theory Study of Cu6 Nanoclusters as a Phenylalanine Detector.

Research on amino acids is an attractive area because of their application in metabolism, cancer treatment, growth, and repair of body tissue, and RNA and DNA syntheses. Twenty amino acids are primarily responsible for protein synthesis. In our study, we used a Cu6 nanocluster as an amino acid detector. For the investigation, we adsorbed amino acids on the Cu6 nanocluster and studied their UV-visible spectra. It is observed that all of the Cu6-amino acid complexes have peaks at near 380 nm wavelength except the Cu-phenylalanine complex, where two UV-visible peaks are found at wavelengths 351 nm (excitation energy 3.49 eV) and 403 nm (excitation energy 3.02 eV), respectively, which originated from the HOMO - 2 to LUMO (28%) and HOMO - 1 to LUMO (38%) transitions. Due to this unique transition, the Cu6 nanocluster can be used for the detection of the phenylalanine amino acid out of the 20 amino acids.

Amino Acid-Based Molecular and Membranous Chiral Tools for Enantiomeric Recognition.

Given the need, both academic and industrial, for new approaches and technologies for chiral discrimination of enantiomers, the present work demonstrates the development through rational design and integration of two new chiral platforms (molecular and membranous) for enantioselective recognition through visual as well as microscopic observation. The molecular platform (TPT) is based on the tryptophan derivative developed through the condensation of two tryptophan units with terepthaloyl chloride. While TPT based on l-tryptophan recognizes R-mandelic acid over the S-isomer, the host with reverse chirality (TPDT) recognizes S-mandelic acid over R-isomer. The role of chemical functionality in this sensitive recognition process was established experimentally by developing an analogue of TPT and by judiciously using different chiral analytes. Importantly, a detailed theoretical study at the molecular level revealed the U-shaped conformation of TPT, creating a cavity for accommodating a chiral guest with selective functional interaction resulting in the discrimination of enantiomers. Finally, a chiral polymeric mat of poly(methyl methacrylate) (PMMA)/polyacrylonitrile (PAN) (2:3) impregnated with TPT was developed via electrospinning. The resulting fibrous mat was successfully utilized for chiral recognition through microscopic and architectural observation. Hence, the present work reports simple chiral tools for enantiomeric recognition.

Effect of Postmeal Fast-Acting Insulin Aspart Injection on the Frequency of Hypoglycemia among Pre-School Children with Type 1 Diabetes: An Open-Label, Cross-Over, Randomized Control Trial.

OBJECTIVES: To study the effect of postmeal Fast-acting insulin Aspart (Fiasp®) on the frequency of hypoglycemia compared to premeal injection among preschool children with type 1 diabetes. METHODS: A single-center trial was conducted among 65 pre-school children (6 mo to 6 y) with Type 1 diabetes for at least 6 mo, on multiple daily insulin injections. Children were randomized to receive their meal bolus postmeal or premeal for the first 3 mo, followed by cross-over at 3 mo. The two groups were compared at the end of 6 mo for the change in frequency of hypoglycemia and hyperglycemia, HbA1c, glycemic variability, and parental satisfaction. Ten children (5 in each group) underwent pharmacokinetic studies. The trial was approved by Institutional Ethics Committee and registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750. RESULTS: Fifty-four children completed the study, with 27 children in each group. There were no significant differences in the frequency of clinical (p = 0.921), severe (p = 0.167) or serious (p = 0.753) hypoglycemia in the two groups. There were no differences in secondary outcome parameters and pharmacokinetics. CONCLUSIONS: The premeal or postmeal injection of Fiasp® does not affect the frequency of hypoglycemia or other glycemic control parameters among pre-school children with Type 1 diabetes. TRIAL REGISTRATION: The trial is registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750.

Nanotechnology based technological development in biofuel production: Current status and future prospects.

Depleting fossil fuels and net carbon emissions associated with their burning have driven the need to find alternative energy sources. Biofuels are near-perfect candidates for alternative energy sources as they are renewable and account for no net CO2 emissions. However, biofuel production must overcome various challenges to compete with conventional fuels. Conventional methods for bioconversion of biomass to biofuel include chemical, thermochemical, and biological processes. Substrate selection and processing, low yield, and total cost of production are some of the main issues associated with biofuel generation. Recently, the uses of nanotechnology and nanoparticles have been explored to improve the biofuel production processes because of their high adsorption, high reactivity, and catalytic properties. The role of these nanoscale particles and nanocatalysts in biomass conversion and their effect on biofuel production processes and yield are discussed in the present article. The applicability of nanotechnology in production processes of biobutanol, bioethanol, biodiesel, biohydrogen, and biogas under biorefinery approach are presented. Different types of nanoparticles, and their function in the bioprocess, such as electron transfer, pretreatment, hydrolysis, microalgae cultivation, lipid extraction, dark and photo fermentation, immobilization, and suppression of inhibitory compounds, are also highlighted. Finally, the current and potential applications of nanotechnology in biorefineries are also discussed.

A comprehensive ATR-FTIR spectroscopic analysis for the identification and differentiation of lip balms.

Lip balm may be encountered as physical evidence in cases involving sexual assaults, homicides, and kidnappings. Lip balm can be used as corroborative evidence by providing a potential link between the victim, accused, and the crime scene. For lip balms to be used as evidence, it is important to understand the diversity and their aging process under different conditions. Therefore, in this study, ATR-FTIR spectroscopy in conjunction with chemometric tools such as principal component analysis (PCA) and linear discriminant analysis (LDA) has been used for the objective identification and differentiation of 20 brands of lip balms. Moreover, lip balms on different substrates and wearing effects over time were also investigated. The results show that the PCA-LDA training accuracy was 92.5%, whereas the validation accuracy comes out to be 83.33%. A blind study using pristine samples was also performed which resulted in 80% PCA-LDA accuracy. PCA-LDA prediction of samples on various substrates showed a higher chemometric prediction accuracy for nonporous substrates (glass, plastic, and steel), than for porous substrates (cotton cloth, cotton swab stick, dry tissue paper, and white paper) for samples kept in room temperature and under sunlight for 15 days. The substrate study showed that the samples from various substrates could effectively generate respective spectra which can help in brand-level identification even after several days. The present method demonstrates a potential for lip balm samples to be used in forensic casework applications.

Monitoring structural fluctuations of discotic liquid crystal during phase transitions.

The discotic liquid crystal 4-((2, 3, 4-tris (octyloxy) phenyl) diazenyl) benzoic acid, hereafter referred as DLC A8, exhibited in dimeric form has been studied using a combination of quantum chemical approaches and vibrational spectroscopy. This study investigates the structural alteration of DLC A8 associated with phase transition. The phase transitions of DLC A8 are Iso â†’ Discotic nematic â†’ Columnar â†’ Crystalline, which have been investigated using differential scanning calorimetry (DSC) accompanied with polarized optical microscopy (POM). Monotropic columnar mesophase was observed during the cooling cycle while discotic nematic mesophase was observed in both the heating and cooling cycles. Density functional theory (DFT) along with IR and Raman spectroscopic techniques were utilized to study the dynamics of molecules during phase transition. To predict the most stable conformation of the molecule, one-dimensional PES scans have been performed along 31 flexible bonds using DFT/B3LYP/6-311G++(d,p) method. Vibrational normal modes were analyzed in detail, taking potential energy contribution into account. The spectral analysis of FT-IR and FT-Raman was done by deconvoluting the structural sensitive bands. The agreement between the calculated IR and Raman spectra and the observed FT-IR and Raman spectra at room temperature confirms our theoretically predicted molecular model of investigated discotic liquid crystal. Moreover, our studies have unraveled the existence of intact intermolecular H-bonding of dimers throughout the phase transitions.

Spectroscopic and quantum chemical investigations to explore the effect of intermolecular interactions in a diuretic drug: Hydrochlorothiazide.

Hydrochlorothiazide (HCTZ) being a diuretic drug widely used in anti-hypertensive therapy as it lowers the blood pressure by reducing the reabsorption of electrolytes in kidney resulting an increment of urine output and lowering the blood pressure. The purpose of the present work is to study the structural, vibrational and chemical properties of HCTZ based on its monomeric, dimeric and trimeric models by utilizing computational methods and experimental techniques. Density functional theory (DFT) with functional B3LYP and 6-311++G (d, p) basis set was used for a detailed computational study. Monomeric, dimeric and trimeric models of HCTZ have been studied for a better understanding of inter- and intramolecular hydrogen bonding. FT-IR (400-3800 cm-1) and FT-Raman (100-3600 cm-1) spectroscopy have been utilized for the characterization of HCTZ. The shifting in wavenumber of NH2 and OSO group were observed in dimer and trimer due to the formation of intermolecular hydrogen bonding. Quantum theory of atoms in molecules (QTAIM) along with natural bond orbital (NBO) analysis were performed to examine the nature and strength of hydrogen bonding which showed that all the interactions were medium and partially covalent in nature; transition from LP(3)O15 â†’ σ*(H46 â†’ N32) and LP(3)O39 â†’ σ*(H74 â†’ N51) were responsible for the formation of O15•••H46 and O39•••H74 H-bonds, respectively. HOMO-LUMO energies predicted the chemical reactivity and stability of the molecule and the energy gap for dimer (4.6240 eV) and trimer (4.0493 eV) was found to be lesser than the monomer (5.0888 eV) which showed that the dimer and trimer have predicted more chemical reactivity in comparison to monomer. The most electronegative electrostatic potential was observed around the OSO group and the most electropositive potential around the amide group from MEPS analysis. Global as well as local reactivity descriptors have predicted the reactivity and hence, stability of the title molecule.

Neonatal diabetes with a rare LRBA mutation.

Neonatal diabetes mellitus (NDM) is characterised by onset of persistent hyperglycaemia within the first 6 months of life. NDM is frequently caused by a mutation in a single gene affecting pancreatic beta cell function. We report an infant, born to a non-consanguineous couple, who presented with osmotic symptoms and diabetic ketoacidosis. The genetic analysis showed a mutation in LRBA (lipopolysaccharide-responsive and beige-like anchor protein) gene. We highlight the importance of considering genetic analysis in every infant with NDM, to understand the nature of genetic mutation, associated comorbidities, response to glibenclamide and future prognosis.

Graphene Synthesis Techniques and Environmental Applications.

Graphene is fundamentally a two-dimensional material with extraordinary optical, thermal, mechanical, and electrical characteristics. It has a versatile surface chemistry and large surface area. It is a carbon nanomaterial, which comprises sp2 hybridized carbon atoms placed in a hexagonal lattice with one-atom thickness, giving it a two-dimensional structure. A large number of synthesis techniques including epitaxial growth, liquid phase exfoliation, electrochemical exfoliation, mechanical exfoliation, and chemical vapor deposition are used for the synthesis of graphene. Graphene prepared using different techniques can have a number of benefits and deficiencies depending on its application. This study provides a summary of graphene preparation techniques and critically assesses the use of graphene, its derivates, and composites in environmental applications. These applications include the use of graphene as membrane material for the detoxication and purification of water, active material for gas sensing, heavy metal ions detection, and CO2 conversion. Furthermore, a trend analysis of both synthesis techniques and environmental applications of graphene has been performed by extracting and analyzing Scopus data from the past ten years. Finally, conclusions and outlook are provided to address the residual challenges related to the synthesis of the material and its use for environmental applications.

Glycaemic control and factors affecting it in type 1 diabetes in children: experience from a tertiary care centre in India.

INTRODUCTION: Optimal glycaemic control is essential for the prevention of future micro- and macrovascular complications in type 1 diabetes (T1D). The type of insulin, the type of insulin delivery device, the caregiver's knowledge, the patient's age, duration of diabetes, and self-monitoring of blood glucose affect glycaemic control in type 1 diabetes. In the present study, we analysed glycaemic control and factors affecting it at a tertiary care centre in northern India. MATERIAL AND METHODS: A retrospective review of records of patients registered between 2015 and 2018 was done. The data on demographic and disease-related factors were collected from the records. The different groups were compared with the t-test, one-way ANOVA, or Kruskal-Wallis test. RESULTS: The mean age at the time of evaluation was 10.43 ±4.04 years (2-21 years), and the mean disease duration was 46.61 ±28.49 months (16-141 months). Most of the patients were prepubertal and using a basal-bolus regimen. The mean glycated haemoglobin (HbA1c ) was 7.96 ±1.46%, but only 24% had HbA1c below the International Society of Paediatric and Adolescent Diabetes (ISPAD) recommended desirable level of below 7%. Forty-six patients suffered one or more micro-macrovascular complications, and dyslipidaemia was the most common complication. Children with a longer duration of disease (8.39 ±1.42% vs. 7.59 ±1.65%), an episode of DKA (diabetes ketoacidosis) within a year of evaluation (9.19 ±2.54% vs. 7.93 ±1.39%), lower maternal (8.22 ±1.37% vs. 7.56 ±1.45%) and paternal education (8.26 ±1.67% vs. 7.78 ±1.30%), and hyperthyroid state (9.43 ±2.28% vs. 7.91 ±1.45%) had higher HbA1c. CONCLUSIONS: Better diabetes education focusing on parents with lower education strata and children with longer disease duration and poor compliance can help improve glycaemic control in developing countries like India.

Trichotillomania in a child with nephrotic syndrome: An unusual steroid induced psychiatric manifestation.

Steroid-induced psychosis is a known serious adverse effect seen commonly in adults but less commonly in children. We present a seven-year-old girl with steroid-dependent nephrotic syndrome who developed abnormal behaviour, trichotillomania, alopecia and mood changes. She was investigated to rule out other causes and treated with tapering steroids, fluoxetine and olanzapine. A marked improvement was noted after two months. Patients on long term or high dose steroids should be monitored for adverse psychological effects of steroids, as early recognition and intervention can improve the outcome.

Mauriac syndrome: A failure of parent or physician.

Mauriac syndrome is rare; we share our experience of nine patients who presented at a young age with malnutrition, short stature, abdominal distention and deranged liver function.

Frequency spectrum of rare and clinically relevant markers in multiethnic Indian populations (ClinIndb): A resource for genomic medicine in India.

There have been concerted efforts toward cataloging rare and deleterious variants in different world populations using high-throughput genotyping and sequencing-based methods. The Indian population is underrepresented or its information with respect to clinically relevant variants is sparse in public data sets. The aim of this study was to estimate the burden of monogenic disease-causing variants in Indian populations. Toward this, we have assessed the frequency profile of monogenic phenotype-associated ClinVar variants. The study utilized a genotype data set (global screening array, Illumina) from 2795 individuals (multiple in-house genomics cohorts) representing diverse ethnic and geographically distinct Indian populations. Of the analyzed variants from Global Screening Array, ~9% were found to be informative and were either not known earlier or underrepresented in public databases in terms of their frequencies. These variants were linked to disorders, namely inborn errors of metabolism, monogenic diabetes, hereditary cancers, and various other hereditary conditions. We have also shown that our study cohort is genetically a better representative of the Indian population than its representation in the 1000 Genome Project (South Asians). We have created a database, ClinIndb, linked to the Leiden Open Variation Database, to help clinicians and researchers in diagnosis, counseling, and development of appropriate genetic screening tools relevant to the Indian populations and Indians living abroad.

Identification, Characterization and Evaluation of Multifaceted Traits of Plant Growth Promoting Rhizobacteria from Soil for Sustainable Approach to Agriculture.

This study assessed potential of plant growth promoting rhizobacteria (PGPR) found in 34 soil samples collected from Sirmaur, Himachal Pradesh. Out of 238 rhizobacterial isolates, 48 rhizobacterial isolates exhibited multiple PGP (plant growth promoting) traits. Out of the 48 isolates, nine isolates exhibiting most promising PGP traits were evaluated. CSRS12 isolate showed maximum solubilization of phosphate and potassium up to 530.71 and 30.44 mg l-1, respectively. Maximum zinc solubilizing efficiency (ZSE) was also observed in case of isolate CSRS12. The maximum IAA production was observed by isolate PPRS17 with 37.34 mg l-1 followed by PCRS24 with 34.44 mg l-1 after 120 h. Maximum siderophore unit production was observed upto 92.29% by isolate CSRS12 followed by 65.54% with isolate TA1PS. The selected PGPR isolates were identified through 16S rDNA sequencing. The identified PGPRs were Burkholderia arboris (isolate CSRS12), Pseudomonas aeruginosa (isolate PPRS17) and Acinetobacter baumannii (isolate TA1PS). B. arboris CSRS12 isolate showed multiple PGP traits as mineral solubilization of phosphate, potassium and zinc, production of siderophore and ammonia. Among all three PGPR treatment, B. arboris CSRS12 isolate showed significant increment in lateral root number, root and shoot length, fresh and dry weight of root and shoot of mung bean (Vigna radiata) in pot experiments. The results showed that CSRS12 isolate could be used for exploitation as bio-inoculant, which can facilitate better productivity and ecological dynamics for both domesticated crops as well as wild varieties.

Genetic relationship, population structure analysis and allelic characterization of flowering and maturity genes E1, E2, E3 and E4 among 90 Indian soybean landraces.

A set of 90 Indian soybean landraces were analysed for polymorphism at 43 SSRs and five allele specific markers of four major genes involved in regulating flowering and photoperiod response. A total of 42 polymorphic SSRs had amplified 126 alleles which served as raw data for estimation of genetic relationship and population structure among 90 accessions. Rare alleles of four and three SSRs were detected in accessions IC18768 and IC15089, respectively. Gene diversity in the population ranges from 0.065 to 0.717 with a mean value of 0.411. The polymorphism information content of 42 SSRs varied from 0.063 to 0.668. Hierarchical clustering based on neighbour-joining method identified three major clusters among 90 soybean accessions. Model based population structure analysis divided the 90 soybean accessions into four populations (K = 4). Mean value of Fst for different populations ranged between 0.4143 and 0.7239. Genotyping of 90 accessions with allele specific markers had identified accession IC15089 as triple recessive mutant of flowering genes E1, E2 and photoperiod sensitivity gene E3. The triple mutant IC15089 (e1, e3, e3) had been characterized phenotypically and identified as early maturing (88 days) and photoperiod insensitive genotype under extended photoperiod. The present study characterized genetic relationship among 90 Indian soybean landraces and had identified a few diverse and unique genotypes for utilization in soybean breeding programmes targeting development of short duration and photoperiod insensitive varieties through marker assisted selection.

Controlled Growth of Highly Aligned Cu Nanowires by Pulse Electrodeposition in Nanoporous Alumina.

Metallic nanowire networks are emerging as potential replacements for transparent conducting oxide coatings because of their high conductivity, flexibility and relative transparency. However, a cheap, reliable and controlled manufacturing process is required to exploit this and the surface of the copper nanowire needs to be protected if high conductivity is to be retained. In this study a fabrication method for highly aligned and densely packed copper nanowires with controlled length using pulse-electrodeposition and a nanoporous alumina template has been developed. Nanoporous alumina was obtained by anodisation of pure aluminum in oxalic acid using a two-step anodisation process. In order to provide the conductivity at the bottom of the pores, a dendritic structure at the interface was created through the stepwise voltage reduction method with a voltage reduction rate of 15 V/s followed by mild chemical etching. Highly repeatable near 100% filling of copper is achieved. Copper nanowire length was highly controllable from 100 nm to 2 µm with a fixed diameter of 60 ± 5 nm by monitoring current density during the deposition. Such controlled growth of Cu nanowires could lead towards transparent conducting layer applications but the protection of the material against oxidation remains an issue.

Isoniazid induces apoptosis: Role of oxidative stress and inhibition of nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2).

AIMS: Long-term treatment of Isoniazid (INH) in tuberculosis (TB) patients can lead to anti-tuberculosis drug-induced hepatotoxicity. To understand the mechanism of hepatotoxicity, an attempt has been made to elucidate the role of Nrf2, a transcription factor induced by oxidative stress, in INH induced apoptosis liver cancer cell lines. MATERIALS AND METHODS: Cytotoxicity was evaluated by MTT assay. Apoptosis and reactive oxygen species (ROS) generation was performed by flow cytometry. mRNA and protein expression of various genes involves in INH induced toxicity was evaluated via Real-time PCR and western blot analysis respectively. Differential protein expression was performed by two-dimensional gel electrophoresis followed by identification using MALDI TOF/TOF. KEY FINDINGS: INH induced ROS and apoptosis in HepG2 as well as THLE-2 cells. Nuclear damage was also observed by INH treatment in HepG2 cells. Expression of apoptotic (Cytochrome C and Caspase 9) and antioxidative (Keap1 and Nrf2) genes were observed to increase. INH induced PKCδ phosphorylation and released Nrf2 from its inhibitor Keap1 in the cytoplasm of HepG2 cells. However, over-expression of Nrf2 did not affect nuclear Nrf2 protein level as well as its downstream target NQO1. Nrf2 importer, Karyopherin ß1 level was observed to decrease in HepG2 as well as THLE-2 cells following INH treatment. SIGNIFICANCE: These findings suggest that INH prevented Nrf2 translocation into the nucleus by inhibiting its importer Karyopherin ß1. Therefore Nrf2 might not able to bind ARE sequences from inducing antioxidative response for protecting the cells undergoing apoptosis.

Bazedoxifene enhances the anti-tumor effects of cisplatin and radiation treatment by blocking IL-6 signaling in head and neck cancer.

Recent studies have shown that IL-6 signaling plays an important role in the aggressive and metastatic phenotype of head and neck squamous cell carcinoma (HNSCC). Therefore, we hypothesized that targeting of IL-6 signaling in HNSCC could enhance the therapeutic efficacy of standard chemoradiation treatment. We used both in vitro and in vivo models to test the efficacy of Bazedoxifene (BZA), a drug that was originally developed as a newer-generation selective estrogen receptor modulator (SERM) for the treatment of postmenopausal osteoporosis. Recently, BZA was also shown to exhibit potent anti-cancer effects that were both estrogen receptor (ER)-dependent and ER-independent. Our results suggest that BZA inhibits IL-6 signaling by disrupting IL-6R/gp130 protein-protein interactions. BZA treatment of CAL27-IL-6 (IL-6 overexpressing cells) or UM-SCC-74A (naturally expressing high levels of IL-6) significantly inhibited cell proliferation, migration and colony formation ability in a dose-dependent manner. In addition, BZA significantly decreased IL-6-mediated tumorsphere formation by markedly reducing nanog expression. BZA treatment also markedly reduced chemo and radioresistance in head and neck cancer cells by downregulating ERCC-1, XRCC-1 and survivin expression. In a SCID mouse xenograft model, BZA significantly enhanced the anti-tumor effects of cisplatin and radiation treatment with no added systemic toxicity. Furthermore, combination treatments significantly decreased tumor metastasis, pSTAT3 expression and nanog expression, in vivo. Taken together, our results suggest that targeting IL-6 signaling with bazedoxifene could be an effective treatment strategy for the treatment of HNSCC patients.