Search

Oxidative stress, driven by reactive oxygen, nitrogen, and sulphur species (ROS, RNS, RSS), poses a significant threat to cellular integrity and human health. Generated during mitochondrial respiration, inflammation, UV exposure and pollution, these species damage cells and contribute to pathologies like cardiovascular issues, neurodegeneration, cancer, and metabolic syndromes. Lifestyle factors exert a substantial influence on oxidative stress levels, with mitochondria emerging as pivotal players in ROS generation and cellular equilibrium. Phytochemicals, abundant in plants, such as carotenoids, ascorbic acid, tocopherols and polyphenols, offer diverse antioxidant mechanisms. They scavenge free radicals, chelate metal ions, and modulate cellular signalling pathways to mitigate oxidative damage. Furthermore, plants thriving in high-altitude regions are adapted to extreme conditions, and synthesize secondary metabolites, like flavonoids and phenolic compounds in bulk quantities, which act to form a robust antioxidant defence against oxidative stress, including UV radiation and temperature fluctuations. These plants are promising sources for drug development, offering innovative strategies by which to manage oxidative stress-related ailments and enhance human health. Understanding and harnessing the antioxidant potential of phytochemicals from high-altitude plants represent crucial steps in combating oxidative stress-induced disorders and promoting overall wellbeing. This study offers a comprehensive summary of the production and physio-pathological aspects of lifestyle-induced oxidative stress disorders and explores the potential of phytochemicals as promising antioxidants. Additionally, it presents an appraisal of high-altitude medicinal plants as significant sources of antioxidants, highlighting their potential for drug development and the creation of innovative antioxidant therapeutic approaches.

Green approaches for nanoparticle synthesis have emerged as biocompatible, economical, and environment-friendly alternatives to counteract the menace of microbial drug resistance. Recently, the utilization of honey as a green source to synthesize Fe 2 O 3 -NPs has been introduced, but its antibacterial activity against one of the opportunistic MDR pathogens, Klebsiella pneumoniae , has not been explored. Therefore, this study employed Apis mellifera honey as a reducing and capping agent for the synthesis of iron oxide nanoparticles (Fe 2 O 3 -NPs). Subsequent to the characterization of nanoparticles, their antibacterial, antioxidant, and anti-inflammatory properties were appraised. In UV-Vis spectroscopic analysis, the absorption band ascribed to the SPR peak was observed at 350 nm. XRD analysis confirmed the crystalline nature of Fe 2 O 3 -NPs, and the crystal size was deduced to be 36.2 nm. Elemental analysis by EDX validated the presence of iron coupled with oxygen in the nanoparticle composition. In ICP-MS, the highest concentration was of iron (87.15 ppm), followed by sodium (1.49 ppm) and other trace elements (<1 ppm). VSM analysis revealed weak magnetic properties of Fe 2 O 3 -NPs. Morphological properties of Fe 2 O 3 -NPs revealed by SEM demonstrated that their average size range was 100-150 nm with a non-uniform spherical shape. The antibacterial activity of Fe 2 O 3 -NPs was ascertained against 30 clinical isolates of Klebsiella pneumoniae , with the largest inhibition zone recorded being 10 mm. The MIC value for Fe 2 O 3 -NPs was 30 µg/mL. However, when mingled with three selected antibiotics, Fe 2 O 3 -NPs did not affect any antibacterial activity. Momentous antioxidant (IC 50 = 22 µg/mL) and anti-inflammatory (IC 50 = 70 µg/mL) activities of Fe 2 O 3 -NPs were discerned in comparison with the standard at various concentrations. Consequently, honey-mediated Fe 2 O 3 -NP synthesis may serve as a substitute for orthodox antimicrobial drugs and may be explored for prospective biomedical applications.

Radioresistant microorganisms possess inimitable capabilities enabling them to thrive under extreme radiation. However, the existence of radiosensitive microorganisms inhabiting such an inhospitable environment is still a mystery. The current study examines the potential of radioresistant microorganisms to protect radiosensitive microorganisms in harsh environments. Bacillus subtilis strain ASM-1 was isolated from the Thal desert in Pakistan and evaluated for antioxidative and radioprotective potential after being exposed to UV radiation. The strain exhibited 54.91% survivability under UVB radiation (5.424 × 10 3 J/m 2 for 8 min) and 50.94% to mitomycin-C (4 µg/mL). Extracellular fractions collected from ASM-1 extracts showed significant antioxidant potential, and chemical profiling revealed a pool of bioactive compounds, including pyrrolopyrazines, amides, alcoholics, and phenolics. The E-2 fraction showed the maximum antioxidant potential via DPPH assay (75%), and H 2 O 2 scavenging assay (68%). A combination of ASM-1 supernatant with E-2 fraction (50 µL in a ratio of 2:1) provided substantial protection to radiosensitive cell types, Bacillus altitudinis ASM-9 (MT722073) and E. coli (ATCC 10536), under UVB radiation. Docking studies reveal that the compound supported by literature against the target proteins have strong binding affinities which further inferred its medical uses in health care treatment. This is followed by molecular dynamic simulations where it was observed among trajectories that there were no significant changes in major secondary structure elements, despite the presence of naturally flexible loops. This behavior can be interpreted as a strategy to enhance intermolecular conformational stability as the simulation progresses. Thus, our study concludes that Bacillus subtilis ASM-1 protects radiosensitive strains from radiation-induced injuries via biofilm formation and secretion of antioxidative and radioprotective compounds in the environment.

Among all available antimicrobials, antibiotics hold a prime position in the treatment of infectious diseases. However, the emergence of antimicrobial resistance (AMR) has posed a serious threat to the effectiveness of antibiotics, resulting in increased morbidity, mortality, and escalation in healthcare costs causing a global health crisis. The overuse and misuse of antibiotics in global healthcare setups have accelerated the development and spread of AMR, leading to the emergence of multidrug-resistant (MDR) pathogens, which further limits treatment options. This creates a critical need to explore alternative approaches to combat bacterial infections. Phytochemicals have gained attention as a potential source of alternative medicine to address the challenge of AMR. Phytochemicals are structurally and functionally diverse and have multitarget antimicrobial effects, disrupting essential cellular activities. Given the promising results of plant-based antimicrobials, coupled with the slow discovery of novel antibiotics, it has become highly imperative to explore the vast repository of phytocompounds to overcome the looming catastrophe of AMR. This review summarizes the emergence of AMR towards existing antibiotics and potent phytochemicals having antimicrobial activities, along with a comprehensive overview of 123 Himalayan medicinal plants reported to possess antimicrobial phytocompounds, thus compiling the existing information that will help researchers in the exploration of phytochemicals to combat AMR.

The most common cause of mortality and disability globally right now is cholangiocarcinoma, one of the worst forms of cancer that may affect people. When cholangiocarcinoma develops, the DNA of the bile duct cells is altered. Cholangiocarcinoma claims the lives of about 7000 individuals annually. Women pass away less often than men. Asians have the greatest fatality rate. Following Whites (20%) and Asians (22%), African Americans (45%) saw the greatest increase in cholangiocarcinoma mortality between 2021 and 2022. For instance, 60-70% of cholangiocarcinoma patients have local infiltration or distant metastases, which makes them unable to receive a curative surgical procedure. Across the board, the median survival time is less than a year. Many researchers work hard to detect cholangiocarcinoma, but this is after the appearance of symptoms, which is late detection. If cholangiocarcinoma progression is detected at an earlier stage, then it will help doctors and patients in treatment. Therefore, an ensemble deep learning model (EDLM), which consists of three deep learning algorithms-long short-term model (LSTM), gated recurrent units (GRUs), and bi-directional LSTM (BLSTM)-is developed for the early identification of cholangiocarcinoma. Several tests are presented, such as a 10-fold cross-validation test (10-FCVT), an independent set test (IST), and a self-consistency test (SCT). Several statistical techniques are used to evaluate the proposed model, such as accuracy (Acc), sensitivity (Sn), specificity (Sp), and Matthew's correlation coefficient (MCC). There are 672 mutations in 45 distinct cholangiocarcinoma genes among the 516 human samples included in the proposed study. The IST has the highest Acc at 98%, outperforming all other validation approaches.

To cope with environmental pollution caused by toxic emissions into water streams, high-performance photocatalysts based on ZnO semiconductor materials are urgently needed. In this study, ZnO nanostructures are synthesized using leafy spinach extract using a biogenic approach. By using phytochemicals contained in spinach, ZnO nanorods are transformed into large clusters assembled with nanosheets with visible porous structures. Through X-ray diffraction, it has been demonstrated that leafy spinach extract prepared with ZnO is hexagonal in structure. Surface properties of ZnO were altered by using 10 mL, 20 mL, 30 mL, and 40 mL quantities of leafy spinach extract. The size of ZnO crystallites is typically 14 nanometers. In the presence of sunlight, ZnO nanostructures mineralized methylene blue. Studies investigated photocatalyst doses, dye concentrations, pH effects on dye solutions, and scavengers. The ZnO nanostructures prepared with 40 mL of leafy spinach extract outperformed the degradation efficiency of 99.9% for the MB since hydroxyl radicals were primarily responsible for degradation. During degradation, first-order kinetics were observed. Leafy spinach extract could be used to develop novel photocatalysts for the production of solar hydrogen and environmental hydrogen.

To determine urea accurately in clinical samples, food samples, dairy products, and agricultural samples, a new analytical method is required, and non-enzymatic methods are preferred due to their low cost and ease of use. In this study, bitter gourd peel biomass waste is utilized to modify and structurally transform nickel oxide (NiO) nanostructures during the low-temperature aqueous chemical growth method. As a result of the high concentration of phytochemicals, the surface was highly sensitive to urea oxidation under alkaline conditions of 0.1 M NaOH. We investigated the structure and shape of NiO nanostructures using powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). In spite of their flake-like morphology and excellent crystal quality, NiO nanostructures exhibited cubic phases. An investigation of the effects of bitter gourd juice demonstrated that a large volume of juice produced thin flakes measuring 100 to 200 nanometers in diameter. We are able to detect urea concentrations between 1-9 mM with a detection limit of 0.02 mM using our urea sensor. Additionally, the stability, reproducibility, repeatability, and selectivity of the sensor were examined. A variety of real samples, including milk, blood, urine, wheat flour, and curd, were used to test the non-enzymatic urea sensors. These real samples demonstrated the potential of the electrode device for measuring urea in a routine manner. It is noteworthy that bitter gourd contains phytochemicals that are capable of altering surfaces and activating catalytic reactions. In this way, new materials can be developed for a wide range of applications, including biomedicine, energy production, and environmental protection.

Background and Objective : Mutations in the CYB5R3 gene cause reduced NADH-dependent cytochrome b5 reductase enzyme function and consequently lead to recessive congenital methemoglobinemia (RCM). RCM exists as RCM type I (RCM1) and RCM type II (RCM2). RCM1 leads to higher methemoglobin levels causing only cyanosis, while in RCM2, neurological complications are also present along with cyanosis. Materials and Methods : In the current study, a consanguineous Pakistani family with three individuals showing clinical manifestations of cyanosis, chest pain radiating to the left arm, dyspnea, orthopnea, and hemoptysis was studied. Following clinical assessment, a search for the causative gene was performed using whole exome sequencing (WES) and Sanger sequencing. Various variant effect prediction tools and ACMG criteria were applied to interpret the pathogenicity of the prioritized variants. Molecular dynamic simulation studies of wild and mutant systems were performed to determine the stability of the mutant CYB5R3 protein. Results : Data analysis of WES revealed a novel homozygous missense variant NM&#95;001171660.2: c.670A > T: NP&#95;001165131.1: p.(Ile224Phe) in exon 8 of the CYB5R3 gene located on chromosome 22q13.2. Sanger sequencing validated the segregation of the identified variant with the disease phenotype within the family. Bioinformatics prediction tools and ACMG guidelines predicted the identified variant p.(Ile224Phe) as disease-causing and likely pathogenic, respectively. Molecular dynamics study revealed that the variant p.(Ile224Phe) in the CYB5R3 resides in the NADH domain of the protein, the aberrant function of which is detrimental. Conclusions : The present study expanded the variant spectrum of the CYB5R3 gene. This will facilitate genetic counselling of the same and other similar families carrying mutations in the CYB5R3 gene.

Introduction: MicroRNAs (miRNAs) are small non-coding RNAs that play a key role in post-transcriptional modulation of individual genes' expression. Several miRNA variants from different populations are known to be associated with an increased risk of rheumatoid arthritis (RA)., Aim: This study was undertaken with the aim to investigate the association of single nucleotide variants; namely, rs2292832, rs3746444, rs11614913, rs1044165, and rs767649 of MIR149, MIR499, MIR196, MIR223, and MIR155, respectively, with RA in the Pakistani population., Methods: A case-control study was performed by recruiting and genotyping a total of 600 individuals (300 cases and 300 controls) for these five variants using a TaqMan single-nucleotide polymorphism (SNP) genotyping assay. The resultant genotypic data was statistically analyzed through a chi-squared test for its association with RA under different inheritance models., Results: We found a significant association of rs2292832 with RA at genotypic (co-dominant ( p < 0.0001), dominant (CC vs. TT + CT: OR 2.063 (1.437-2.962); p = 0.0001), recessive (TT vs. CT + CC: OR 0.376 (0.259-0.548); p < 0.0001)), and allelic (allele C) levels ((OR 0.506 (0.402-0637); p < 0.0001)). Similarly, the rs3746444 showed a significant association with RA under co-dominant ( p = 0.0001), dominant (GG vs. AA + AG: OR 5.246 (3.414-8.061); p < 0.0001), recessive (AA vs. GG + AG: OR 0.653 (0.466-0.916); p = 0.014), and additive models (G vs. A; OR 0.779 (0.620-0.978); p = 0.03). However, we did not observe any significant association of rs11614913, rs1044165, or rs767649 with RA in our subjects., Conclusion: To our knowledge, this was the first study that investigated and found an association between functional polymorphisms in miRNAs and RA in the Pakistani population.

Nickel-supported hierarchical zeolite catalysts were prepared through a desilication reassembly process under optimized conditions and applied in one-pot menthol synthesis. In this work, the hierarchical zeolite-supported metal bifunctional catalysts were prepared with the help of desilication re-assembly and wetness impregnation techniques and applied in menthol synthesis via citral hydrogenation. The prepared catalysts were characterized using PXRD, BET, FE-TEM, NH 3 -TPD, H 2 -TPR, pyridine adsorption, and ICP-OES techniques. As a result, the physicochemical and acidic properties, such as mesopore surface area, metal dispersion, acidity, catalytic activity, and strong Lewis acid sites of pure microporous ZSM-5/USY zeolites, were significantly improved. Consequently, with the occurrence of superior physicochemical and acidic properties, the Ni/HZ-0.5 M catalyst exhibited outstanding catalytic activity (100% conversion, TOF 7.12 h -1 ) and menthol selectivity (83%, 4 h) with uniform stability at 100 °C, 1.0 MPa hydrogen. Similarly, the cracking rate decreased with the decrease in Bronsted acid sites.

In this study, chloride (Cl−) ions were successfully doped into ZnO nanostructures by the solvothermal method. The effect of various Cl− concentrations on the photocatalytic activity of ZnO towards the photodegradation of methylene blue (MB) under the illumination of ultraviolet light was studied. The as-prepared Cl−-doped ZnO nanostructures were analyzed in terms of morphology, structure, composition and optical properties. XRD data revealed an average crystallite size of 23 nm, and the XRD patterns were assigned to the wurtzite structure of ZnO even after doping with Cl−. Importantly, the optical band gap of various Cl ion-doped ZnO nanostructures was successively reduced from 3.42 to 3.16 eV. The photodegradation efficiency of various Cl− ion-doped ZnO nanostructures was studied for MB in aqueous solution, and the relative performance of each Cl ion-doped ZnO sample was as follows: 20% Cl−-doped ZnO > 15% Cl−-doped ZnO > 10% Cl−-doped ZnO > 5% Cl−-doped ZnO > pristine ZnO. Furthermore, the correlation of the pH of the MB solution and each Cl ion dopant concentration was also investigated. The combined results of varying dopant levels and the effect of the pH of the MB solution on the photodegradation process verified the crucial role of Cl− ions in activating the degradation kinetics of MB. Therefore, these newly developed photocatalysts could be considered as alternative materials for practical applications such as wastewater treatment.

Soil nematodes contribute to nutrient cycling. This year-long study aimed to investigate the changes in the diversity of soil nematodes during the spring, summer, and winter seasons in rice fields at 24 sites and to determine the indicator nematode genera that inhibit the roots of rice plants. A total of 216 soil samples were collected during three seasons, and the collection of 72 root samples was carried out during rice cropping. Forty-four soil nematode genera were identified. They exhibited significant changers in their abundance, which were dependent on the seasons and on soil characteristics. In particular, the abundance of plant-parasitic nematodes (PPNs) and free-living soil nematodes was 49% and 15% higher during the summer than during the spring and winter seasons, respectively. Soil characteristics, such as soil nitrogen (N) contents, carbon (C) contents, and soil moisture were significantly higher during the summer than in the spring and winter seasons, but soil pH was significantly lower during the summer than in the spring and winter seasons. Moreover, Hirschmanniella, Meloidogyne, and Heterodera emerged as good indicators for rice root inhibition, corroborating the frequency, density, and prominence value of PPNs of the sampled soil and rice roots. This study also indicated that free-living nematode genera, such as Rhabdolaimus , Diplogaster, and Rhabditis , might function as ecological indicators for soil health.

Acute gastroenteritis is the major cause of morbidity and mortality among infants and children around the globe. Along with other enteropathogens, human adenovirus (HadV) is a major etiological agent associated with diarrhea in young children. However, information about the epidemiology of Adenoviruses in Pakistan is limited or has not been reported. A total of 1082 stool samples were collected from patients with acute gastroenteritis under the age of five years with symptoms of diarrhea, vomiting, nausea, and abdominal cramps who visited Benazir Bhutto Hospital Rawalpindi and Children's hospital in Lahore of Punjab Province in Pakistan. Of this, 384 cases with no blood in their stool, negative for Rotavirus, and under the age of five years were recruited in this study. Human Adenoviruses were isolated in the human epithelial HEp-2 cell line. Furthermore, adenovirus antigen detection was carried out by an enzyme-linked immunosorbent assay (ELISA), and then all positive and negative samples were confirmed by nested PCR. After inoculating a clear stool supernatant on HEp-2 cell lines, we observed a positive cytopathic effect in 65 (16%) cases. Using an enzyme-linked immunosorbent assay, HAdV antigens were detected in 54 (14.06%) of the clear supernatant from gastroenteritis cases. However, HAdV hexon coding regions were amplified in 57 (14.80%) fecal samples, mainly from patients ≤24 months of age. The findings of this study suggest that adenovirus circulates significantly in the children population under the age of five years and may be the potential etiological factor of acute gastroenteritis in the mentioned cities. This study provides baseline data about the possible role of adenovirus in causing viral diarrhea in children. Further large-scale epidemiological surveys are recommended to better understand disease burden, etiological agents, and its clinical impact across the country.

Genes are composed of DNA and each gene has a specific sequence. Recombination or replication within the gene base ends in a permanent change in the nucleotide collection in a DNA called mutation and some mutations can lead to cancer. Breast adenocarcinoma starts in secretary cells. Breast adenocarcinoma is the most common of all cancers that occur in women. According to a survey within the United States of America, there are more than 282,000 breast adenocarcinoma patients registered each 12 months, and most of them are women. Recognition of cancer in its early stages saves many lives. A proposed framework is developed for the early detection of breast adenocarcinoma using an ensemble learning technique with multiple deep learning algorithms, specifically: Long Short-Term Memory (LSTM), Gated Recurrent Units (GRU), and Bi-directional LSTM. There are 99 types of driver genes involved in breast adenocarcinoma. This study uses a dataset of 4127 samples including men and women taken from more than 12 cohorts of cancer detection institutes. The dataset encompasses a total of 6170 mutations that occur in 99 genes. On these gene sequences, different algorithms are applied for feature extraction. Three types of testing techniques including independent set testing, self-consistency testing, and a 10-fold cross-validation test is applied to validate and test the learning approaches. Subsequently, multiple deep learning approaches such as LSTM, GRU, and bi-directional LSTM algorithms are applied. Several evaluation metrics are enumerated for the validation of results including accuracy, sensitivity, specificity, Mathew's correlation coefficient, area under the curve, training loss, precision, recall, F1 score, and Cohen's kappa while the values obtained are 99.57, 99.50, 99.63, 0.99, 1.0, 0.2027, 99.57, 99.57, 99.57, and 99.14 respectively.

The importance of traditional and indigenous knowledge is acknowledged on a worldwide scale for its coexistence principles and sustainable use techniques. In view of this, the present study is an attempt to document the ethno-veterinary plants used by the tribal communities of Western Himalaya. This study also provides the scientific validation of herbal medicines used in ethno-veterinary practices through a reverse pharmacological approach. A total of 59 informants were selected through a non-probability sampling method. Detailed information on the medicinal plants used in ethno-veterinary practices along with their habits and habitats, part/s used, remedy preparation methods, additives/ingredients used during preparation and administration, dosages administered, and route of administration was collected. Data was analyzed for the Relative Frequency of Citations (RFC), Use Values (UV), Informant Consensus Factor (ICF), and Jaccard Index (JI). Further, a reverse pharmacological approach was used for scientific validations of the documented herbal knowledge of plant species. During the study, 56 plant species belonging to 54 genera and 39 families were documented. Asteraceae was the dominant family followed by Lamiaceae, Amaranthaceae and Fabaceae. Life forms were dominated by herbaceous species and leaves were the most common plant parts used. The highest Relative Frequency of Citations (RFC) and Use Values (UV) were recorded for Brassica rapa L. (Brassicaceae). The Pearson correlation coefficient between RFC and UV shows a strong positive correlation between the proportion of uses of a plant species within a sample of informants and the number of times that a particular use of a plant species was mentioned by the informant. Studies of the biological activity of ethno-veterinary plants can provide clues of promising leads for the isolation and identification of useful compounds that may be developed into pharmaceuticals for human welfare.

The GluN2B subunit of N-methyl-D-aspartate receptors plays an important role in the physiology of different neurodevelopmental diseases. Genetic variations in the GluN2B coding gene ( GRIN2B ) have consistently been linked to West syndrome, intellectual impairment with focal epilepsy, developmental delay, macrocephaly, corticogenesis, brain plasticity, as well as infantile spasms and Lennox-Gastaut syndrome. It is unknown, however, how GRIN2B genetic variation impacts protein function. We determined the cumulative pathogenic impact of GRIN2B variations on healthy participants using a computational approach. We looked at all of the known mutations and calculated the impact of single nucleotide polymorphisms on GRIN2B , which encodes the GluN2B protein. The pathogenic effect, functional impact, conservation analysis, post-translation alterations, their driving residues, and dynamic behaviors of deleterious nsSNPs on protein models were then examined. Four polymorphisms were identified as phylogenetically conserved PTM drivers and were related to structural and functional impact: rs869312669 (p.Thr685Pro), rs387906636 (p.Arg682Cys), rs672601377 (p.Asn615Ile), and rs1131691702 (p.Ser526Pro). The combined impact of protein function is accounted for by the calculated stability, compactness, and total globularity score. GluN2B hydrogen occupancy was positively associated with protein stability, and solvent-accessible surface area was positively related to globularity. Furthermore, there was a link between GluN2B protein folding, movement, and function, indicating that both putative high and low local movements were linked to protein function. Multiple GRIN2B genetic variations are linked to gene expression, phylogenetic conservation, PTMs, and protein instability behavior in neurodevelopmental diseases. These findings suggest the relevance of GRIN2B genetic variations in neurodevelopmental problems., Competing Interests: The authors declare no conflict of interest.

Genetic variants in microRNA genes have a detrimental effect on miRNA-mediated regulation of gene expression and may contribute to coronary artery disease (CAD). CAD is the primary cause of mortality worldwide. Several environmental, genetic, and epigenetic factors are responsible for CAD susceptibility. The contribution of protein-coding genes is extensively studied. However, the role of microRNA genes in CAD is at infancy. The study is aimed to investigate the impact of rs895819, rs11614913, and rs2168518 variants in MIR27A , MIR196A2 , and MIR4513 , respectively, in CAD using allele-specific PCR. Results: For variant rs11614913, significant distribution of the genotypes among the cases and controls was determined by co-dominant [χ 2 = 54.4; p value ≤ 0.0001], dominant (C/C vs. C/T + T/T) [OR = 0.257 (0.133-0.496); p value ≤ 0.0001], recessive (T/T vs. C/T + C/C) [OR = 1.56 (0.677-0.632); p value = 0.398], and additive models [OR = 0.421 (0.262-0.675); p value = 0.0004]. Similarly, a significant association of rs895819 was determined by co-dominant [χ 2 = 9.669; p value ≤ 0.008], dominant (A/A vs. A/G + G/G) [OR = 0.285 (0.1242-0.6575); p value ≤ 0.0034], recessive (G/G vs. A/G + A/A) [OR = 0.900 (0.3202-3.519); p value = 1.000], and additive models [OR = 0.604 (0.3640-1.002); p value = 0.05] while no significant association of rs2168518 with CAD was found. Conclusion: The variants rs895819 and rs11614913 are the susceptibility factors for CAD.

The potato is one of the most important and valuable crops in terms of consumption worldwide. However, abiotic stressors are the critical delimiters for the growth and productivity of potato. Invertase genes play key roles in carbon metabolism, plant development, and responses to stress stimuli. Therefore, a comprehensive genome-wide identification, characterization and expression analysis of invertase genes was performed in the potato. The current study identified 19 invertase genes, randomly distributed throughout the potato genome. To further elucidate their evolutionary, functional and structural relationship within family and with other plant species, we performed sequence and phylogenetic analysis, which segregated invertase genes into two main groups based on their sequence homology. A total of 11 genes are included in acidic invertases and 8 genes are in neutral or alkaline invertases, elucidating their functional divergence. Tissue specific expression analyses (RNA sequencing and qRT-PCR) of different plant tissues showed differential expression pattern. Invertase genes have higher expression in flower, leaf, root and shoot tissues, while under abiotic stress conditions, the expression of the invertase gene is significantly upregulated. Results of this study revealed that vacuolar and cell wall destined invertases are mainly the functional member genes of the invertase family. This study provides comprehensive data and knowledge about StINV genes in Solanum tuberosum for future genetic and epigenetic studies.

Most of the food packaging materials used in the market are petroleum-based plastics; such materials are neither biodegradable nor environmentally friendly and require years to decompose. To overcome these problems, biodegradable and edible materials are encouraged to be used because such materials degrade quickly due to the actions of bacteria, fungi, and other environmental effects. In this work, commonly available household materials such as gelatin, soy protein, corn starch, and papaya were used to prepare cost-effective lab-scale biodegradable and edible packaging film as an effective alternative to commercial plastics to reduce waste generation. Prepared films were characterized in terms of Fourier transform infrared spectroscopy (FTIR), water vapor transmission rate (WVTR), optical transparency, and tensile strength. FTIR confirmed the addition of papaya and soy protein to the gelatin backbone. WVTR of the gelatin-papaya films was recorded to be less than 50 g/m 2 /day. This water vapor barrier was five times better than films of pristine gelatin. The gelatin, papaya, and soy protein films exhibited transparencies of around 70% in the visible region. The tensile strength of the film was 2.44 MPa, which improved by a factor of 1.5 for the films containing papaya and soy protein. The barrier qualities of the gelatin and gelatin-papaya films maintained the properties even after going through 2000 bending cycles. From the results, it is inferred that the prepared films are ideally suitable for food encapsulation and their production on a larger scale can considerably cut down the plastic wastage.

Silica is one of the most efficient gas barrier materials, and hence is widely used as an encapsulating material for electronic devices. In general, the processing of silica is carried out at high temperatures, i.e., around 1000 °C. Recently, processing of silica has been carried out from a polymer called Perhydropolysilazane (PHPS). The PHPS reacts with environmental moisture or oxygen and yields pure silica. This material has attracted many researchers and has been widely used in many applications such as encapsulation of organic light-emitting diodes (OLED) displays, semiconductor industries, and organic solar cells. In this paper, we have demonstrated the process optimization of the conversion of the PHPS into silica in terms of curing methods as well as curing the environment. Various curing methods including exposure to dry heat, damp heat, deep UV, and their combination under different environments were used to cure PHPS. FTIR analysis suggested that the quickest conversion method is the irradiation of PHPS with deep UV and simultaneous heating at 100 °C. Curing with this method yields a water permeation rate of 10 -3 g/(m 2 ⋅day) and oxygen permeation rate of less than 10 -1 cm 3 /(m 2 ·day·bar). Rapid curing at low-temperature processing along with barrier properties makes PHPS an ideal encapsulating material for organic solar cell devices and a variety of similar applications., Competing Interests: The authors declare no conflict of interest.

A large number of smart devices in Internet of Things (IoT) environments communicate via different messaging protocols. Message Queuing Telemetry Transport (MQTT) is a widely used publish-subscribe-based protocol for the communication of sensor or event data. The publish-subscribe strategy makes it more attractive for intruders and thus increases the number of possible attacks over MQTT. In this paper, we proposed a Deep Neural Network (DNN) for intrusion detection in the MQTT-based protocol and also compared its performance with other traditional machine learning (ML) algorithms, such as a Naive Bayes (NB), Random Forest (RF), k-Nearest Neighbour (kNN), Decision Tree (DT), Long Short-Term Memory (LSTM), and Gated Recurrent Units (GRUs). The performance is proved using two different publicly available datasets, including (1) MQTT-IoT-IDS2020 and (2) a dataset with three different types of attacks, such as Man in the Middle (MitM), Intrusion in the network, and Denial of Services (DoS). The MQTT-IoT-IDS2020 contains three abstract-level features, including Uni-Flow, Bi-Flow, and Packet-Flow. The results for the first dataset and binary classification show that the DNN-based model achieved 99.92%, 99.75%, and 94.94% accuracies for Uni-flow, Bi-flow, and Packet-flow, respectively. However, in the case of multi-label classification, these accuracies reduced to 97.08%, 98.12%, and 90.79%, respectively. On the other hand, the proposed DNN model attains the highest accuracy of 97.13% against LSTM and GRUs for the second dataset.

MXene/Ag 2 CrO 4 nanocomposite was synthesized effectively by means of superficial low-cost co-precipitation technique in order to inspect its capacitive storage potential for supercapacitors. MXene was etched from MAX powder and Ag 2 CrO 4 spinel was synthesized by an easy sol-gel scheme. X-Ray diffraction (XRD) revealed an addition in inter-planar spacing from 4.7 Å to 6.2 Å while Ag 2 CrO 4 nanoparticles diffused in form of clusters over MXene layers that had been explored by scanning electron microscopy (SEM). Energy dispersive X-Ray (EDX) demonstrated the elemental analysis. Raman spectroscopy opens the gap between bonding structure of as-synthesized nanocomposite. From photoluminence (PL) spectra the energy band gap value 3.86 eV was estimated. Electrode properties were characterized by applying electrochemical observations such as cyclic voltammetry along with electrochemical impedance spectroscopy (EIS) for understanding redox mechanism and electron transfer rate constant K app . Additionally, this novel work will be an assessment to analyze the capacitive behavior of electrode in different electrolytes such as in acidic of 0.1 M H 2 SO 4 has specific capacitance C sp = 525 F/g at 10 mVs -1 and much low value in basic of 1 M KOH electrolyte. This paper reflects the novel synthesis and applications of MXene/Ag 2 CrO 4 nanocomposite electrode fabrication in energy storage devices such as supercapacitors.

Although recent studies have explored the potential of multidomain brain health programs, there is a dearth of literature on operationalizing this research to create a clinical treatment program specifically for subjective cognitive decline (SCD). Patients seen by geriatricians in primary care and by behavioral neurology services at our institution presenting with SCD were recruited via a patient-appropriate flyer. After all participants had a 1-h brain health consultation with a neuropsychologist and were provided with program materials, they were randomized to attend a 10-week intervention designed to support program implementation (N = 10) or the control group of implementing the program on their own (N = 11). The program included (1) a calendar-based executive and memory support system for compensatory training and (2) training in healthy lifestyle. There were no significant differences between groups for any outcomes. Participants across both groups showed significant improvements with moderate effect sizes in compensatory strategy use, anxiety symptoms, and daily functioning, which were sustained through 6-month follow-up. They also increased physical activity by the end of the intervention period but did not sustain this through 6-month follow-up. Our pilot study demonstrates preliminary feasibility of a cognitive compensatory and lifestyle-based brain health program. Additional research is recommended to further develop two potentially scalable implementation strategies-coaching and self-implementation after brief consultation.

Myxobacteria are unicellular, Gram-negative, soil-dwelling, gliding bacteria that belong to class δ-proteobacteria and order Myxococcales. They grow and proliferate by transverse fission under normal conditions, but form fruiting bodies which contain myxospores during unfavorable conditions. In view of the escalating problem of antibiotic resistance among disease-causing pathogens, it becomes mandatory to search for new antibiotics effective against such pathogens from natural sources. Among the different approaches, Myxobacteria, having a rich armor of secondary metabolites, preferably derivatives of polyketide synthases (PKSs) along with non-ribosomal peptide synthases (NRPSs) and their hybrids, are currently being explored as producers of new antibiotics. The Myxobacterial species are functionally characterized to assess their ability to produce antibacterial, antifungal, anticancer, antimalarial, immunosuppressive, cytotoxic and antioxidative bioactive compounds. In our study, we have found their compounds to be effective against a wide range of pathogens associated with the concurrence of different infectious diseases.

Pseudomonas aeruginosa and Sphingobacterium sp. are well known for their ability to decontaminate many environmental pollutants while Geobacillus sp. have been exploited for their thermostable enzymes. This study reports the annotation of genomes of P. aeruginosa S3 , Sphingobacterium S2 and Geobacillus EC-3 that were isolated from compost, based on their ability to degrade poly(lactic acid), PLA. Draft genomes of the strains were assembled from Illumina reads, annotated and viewed with the aim of gaining insight into the genetic elements involved in degradation of PLA. The draft genome of Sphinogobacterium strain S2 (435 contigs) was estimated at 5,604,691 bp and the draft genome of P. aeruginosa strain S3 (303 contigs) was estimated at 6,631,638 bp. The draft genome of the thermophile Geobacillus strain EC-3 (111 contigs) was estimated at 3,397,712 bp. A total of 5385 (60% with annotation), 6437 (80% with annotation) and 3790 (74% with annotation) protein-coding genes were predicted for strains S2, S3 and EC-3, respectively. Catabolic genes for the biodegradation of xenobiotics, aromatic compounds and lactic acid as well as the genes attributable to the establishment and regulation of biofilm were identified in all three draft genomes. Our results reveal essential genetic elements that facilitate PLA metabolism at mesophilic and thermophilic temperatures in these three isolates.

Organic photovoltaics (OPVs) die due to their interactions with environmental gases, i.e., moisture and oxygen, the latter being the most dangerous, especially under illumination, due to the fact that most of the active layers used in OPVs are extremely sensitive to oxygen. In this work we demonstrate solution-based effective barrier coatings based on composite of poly(vinyl butyral) (PVB) and mica flakes for the protection of poly (3-hexylthiophene) (P3HT)-based organic solar cells (OSCs) against photobleaching under illumination conditions. In the first step we developed a protective layer with cost effective and environmentally friendly methods and optimized its properties in terms of transparency, barrier improvement factor, and bendability. The developed protective layer maintained a high transparency in the visible region and improved oxygen and moisture barrier quality by the factor of ~7. The resultant protective layers showed ultra-flexibility, as no significant degradation in protective characteristics were observed after 10 K bending cycles. In the second step, a PVB/mica composite layer was applied on top of the P3HT film and subjected to photo-degradation. The P3HT films coated with PVB/mica composite showed improved stability under constant light irradiation and exhibited a loss of <20% of the initial optical density over the period of 150 h. Finally, optimized barrier layers were used as encapsulation for organic solar cell (OSC) devices. The lifetime results confirmed that the stability of the OSCs was extended from few hours to over 240 h in a sun test (65 °C, ambient RH%) which corresponds to an enhanced lifetime by a factor of 9 compared to devices encapsulated with pristine PVB.

MicroRNAs (miRNAs) are small non-coding RNA molecules that control the post-transcriptional gene expression. They play a pivotal role in the regulation of important physiological processes. Variations in miRNA genes coding for mature miRNA sequences have been implicated in several diseases. However, the association of variants in miRNAs genes with Type 2 Diabetes Mellitus (T2DM) in the Pakistani population is rarely reported. Therefore, the current study was designed to investigate the association of rs11614913 T/C ( MIR196A2 ), rs2910164 G/C ( MIR146A ), and rs6505162 C/A ( MIR423 ) in clinicopathological proven T2DM patients and gender-matched healthy controls. The tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR) reaction method was used to determine the genotypes and to establish the association of each variant with T2DM through inherited models. In conclusion, the present study showed that variants rs11614913 T/C and rs2910164 G/C were linked with the risk of T2DM. The data suggested that rs11614913 T/C and rs2910164 G/C could be considered as novel risk factors in the pathogenesis of T2DM in the Pakistani population.

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (M pro ) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia , commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 M pro . Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>-10 kcal/mol) in the SARS-CoV-2 M pro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<-4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 M pro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 M pro antagonist with higher affinity and drug-likeness.

Marine rhodophyte polysaccharides have a wide range of described biological properties with nontoxic characteristics, and show great potential in prebiotics and the functional foods industries. However, there is a virtual lack of Gracilaria blodgettii polysaccharides (GBP) profiling and their bioactivities. This study was designed while keeping in view the lack of physical and chemical characterization of GBP. This polysaccharide was also not previously tested for any bioactivities. A linear random coil conformation was observed for GBP, which was found to be a polysaccharide. A significant sulfate ( w/w , 9.16%) and 3,6-anhydrogalactose (AHG, w/w , 17.97%) content was found in GBP. The significant difference in its setting (27.33 °C) and melting (64.33 °C) points makes it resistant to increasing heat. This, in turn, points to its utility in industrial scale processing and in enhancing the shelf-life of products under high temperatures. A radical scavenging activity of 19.80%, 25.42% and 8.80% was noted for GBP (3 mg/mL) in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (ABTS) and hydroxyl radical (HO) scavenging assays, respectively. Therefore, the findings suggest that Gracilaria blodgettii polysaccharides display a good antioxidant potential and may have potential applications in the functional food industry.

Due to the feasibility of an electrically rechargeable zinc/air cell made of a zinc foil as active material, an aqueous choline acetate (ChAcO) mixture as an electrolyte and a spinel MnCo 2 O 4 (MCO) and NiCo 2 O 4 (NCO) as a bi-functional oxygen catalyst was investigated in this work. The 30 wt.% water-containing aqueous ChAcO solution showed high contact angles close to those of KOH favoring triple-phase boundary formation in the gas diffusion electrode. Conductivity and pH value of 30 wt.% H 2 O/ChAcO amounted to 5.9 mS cm -1 and 10.8, respectively. Best results in terms of reversible capacity and longevity of zinc/air cell were yielded during 100 h charge/discharge with the MnCo 2 O 4 (MCO) air electrode polarization procedure at 100 µA cm -2 (2.8 mA g -1 zinc ). The corresponding reversible capacity amounted to 25.4 mAh (28% depth of discharge (DOD)) and the energy efficiency ranged from 29-54% during the first and seventh cycle within a 1500 h polarization period. Maximum active material utilization of zinc foil at 100 µA cm -2 was determined to 38.1 mAh (42% DOD) whereas a further charging step was not possible due to irreversible passivation of the zinc foil surface. A special side-by-side optical cell was used to identify reaction products of the zinc/air system during a single discharge step in aqueous ChAcO that were identified as Zn(OH) 2 and ZnO by Raman analysis while no carbonate was detected.

Conducting polymers and carbon-based materials such as graphene oxide (GO) and activated carbon (AC) are the most promising capacitive materials, though both offer charge storage through different mechanisms. However, their combination can lead to some unusual results, offering improvement in certain properties in comparison with the individual materials. Cycling stability of supercapacitors devices is often a matter of concern, and extensive research is underway to improve this phenomena of supercapacitive devices. Herein, a high-performance asymmetric supercapacitor device was fabricated using graphene oxide-polyaniline (GO@PANI) nanocomposite as positive electrode and activated carbon (AC) as negative electrode. The device showed 142 F g -1 specific capacitance at 1 A g -1 current density with capacitance retention of 73.94% at higher current density (10 A g -1 ). Most importantly, the device exhibited very high electrochemical cycling stability. It retained 118.6% specific capacitance of the starting value after 10,000 cycles at 3 Ag -1 and with coulombic efficiency of 98.06 %, indicating great potential for practical applications. Very small solution resistance (Rs, 0.640 Ω) and charge transfer resistance (Rct, 0.200 Ω) were observed hinting efficient charge transfer and fast ion diffusion. Due to asymmetric combination, potential window was extended to 1.2 V in aqueous electrolyte, as a result higher energy density (28.5 Wh kg -1 ) and power density of 2503 W kg -1 were achieved at the current density 1 Ag -1 . It also showed an aerial capacitance of 57 mF cm -2 at current 3.2 mA cm -2 . At this current density, its energy density was maximum (0.92 mWh cm -2 ) with power density (10.47 W cm -2 )., Competing Interests: The authors declare no conflict of interest.

The surface of an Au-disc electrode was modified through electro polymerization of aniline, in the presence of dodecyl benzene sulphonic acid (DBSA) and sulphuric acid (H 2 SO 4 ) solution. The polymerization conditions were pre-optimized so that micelle formation and solution coagulation could be minimized and surfactant doped polyaniline film could be obtained through a quick, simple and one step polymerization route. The synthesized material was characterized via Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and cyclic voltammetry (CV). The effective surface area of the Au-disc, calculated through cyclic voltammetry, was immensely increased through a polyaniline (PANI) coating (0.04 and 0.11 cm 2 for bare and PANI coated gold respectively). The modified electrode was utilized for ascorbic acid (AA) sensing. The changing pH of electrolyte and scan rate influenced the PANI electrode response towards AA. The modified electrode was highly selective towards AA oxidation and showed a very low limit of detection i.e. 0.0267 μmol·L -1 . Moreover, the PANI coating greatly reduced the sensing potential for AA by a value of around 140 mV when compared to that on a bare gold electrode.

An eco-friendly solid-state symmetric ultracapacitor (Uc) device was fabricated using a polyaniline graphene oxide composite co-doped with sulfuric acid (H 2 SO 4 ) and dodecyl benzene sulfonic acid (DBSA) or camphor sulfonic acid (CSA), as electrode material utilizing gold sheets as current collectors. The device showed specific capacitance value of 150 F/g at 1 A/g current density, with a capacitance retention value of 93.33% at higher current density (10 A/g), indicating a high rate capability. An energy density of 15.30 Whkg -1 with a power density of 1716 Wkg -1 was obtained at the current density of 1 A/g. The values of areal capacitance, power density, and energy density, achieved at the current density of 5 mAcm -2 , were 97.38 mFcm -2 , 9.93 mWhcm -2 , and 1.1 Wcm -2 , respectively. Additionally, the device showed very low solution and charge transfer resistance (0.885 Ω and 0.475 Ω, respectively). A device was also fabricated utilizing copper as current collector; however, a lower value of specific capacitance (82 F/g) was observed in this case., Competing Interests: The authors declare no conflict of interest.

Fabrication of composites by developing simple techniques can be an effective way to modify some properties of individual materials. The present study relates to facile synthesis of sodium nitrate (NaNO 3 ) and potassium nitrate (KNO 3 ) contaminated polyaniline (PANI) and poly (ethylene oxide) (PEO) composites without using any additives, plasticizers, or fibers. The physic-chemical and rheological properties of synthesized composites were analyzed. The composites showed enhancement in both storage and loss modules in comparison with the polymer matrices. The dynamic viscosity of the synthesized materials has inverse relation with that of temperature and shear stress. Rheological analysis reveals a continuous drop off in viscosity by increasing shear stress. The flow behavior was affected little by temperature. However, the overall results showed a shear thinning effect suggesting that polymer composites show non-Newtonian behavior. The addition of NaNO 3 and KNO 3 had a profound effect on shear viscosity of the materials, although the overall shear thinning behavior prevails. The PANI-PEO composite follows, as the first approximation models, both Bingham and modified Bingham models, while the salt contaminated system follows only the Bingham model. Both show shear stress values. The greater values of storage (G') and loss (G″) modulus of composites than PANI-PEO blend suggests excellent elasticity, better stiffness, and good mechanical strength of the composites. Furthermore, the composites were more thermally stable than pure polymers.

Owing to its exciting physicochemical properties and doping-dedoping chemistry, polyaniline (PANI) has emerged as a potential adsorbent for removal of dyes and heavy metals from aqueous solution. Herein, we report on the synthesis of PANI composites with magnetic oxide (Fe 3 O 4 ) for efficient removal of Basic Blue 3 (BB3) dye from aqueous solution. PANI, Fe 3 O 4 , and their composites were characterized with several techniques and subsequently applied for adsorption of BB3. Effect of contact time, initial concentration of dye, pH, and ionic strength on adsorption behavior were systematically investigated. The data obtained were fitted into Langmuir, Frundlich, Dubbanin-Rudiskavich (D-R), and Tempkin adsorption isotherm models for evaluation of adsorption parameters. Langmuir isotherm fits closely to the adsorption data with R 2 values of 0.9788, 0.9849, and 0.9985 for Fe 3 O 4 , PANI, and PANI/Fe 3 O 4 composites, respectively. The maximum amount of dye adsorbed was 7.474, 47.977, and 78.13 mg/g for Fe 3 O 4 , PANI, and PANI/Fe 3 O 4 composites, respectively. The enhanced adsorption capability of the composites is attributed to increase in surface area and pore volume of the hybrid materials. The adsorption followed pseudo second order kinetics with R 2 values of 0.873, 0.979, and 0.999 for Fe 3 O 4 , PANI, and PANI/Fe 3 O 4 composites, respectively. The activation energy, enthalpy, Gibbs free energy changes, and entropy changes were found to be 11.14, -32.84, -04.05, and -0.095 kJ/mol for Fe 3 O 4 , 11.97, -62.93, -07.78, and -0.18 kJ/mol for PANI and 09.94, -74.26, -10.63, and -0.210 kJ/mol for PANI/Fe 3 O 4 respectively, which indicate the spontaneous and exothermic nature of the adsorption process.

The cost effective synthesis of electroactive polyaniline (PANI) while retaining its desirable properties is one of the most debatable and challenging tasks for researchers in the field. Herein, we report a cost effective inverse emulsion polymerization pathway for the synthesis of soluble and processable PANI salt by using diesel as a novel dispersion medium. Different reaction parameters and their effects on the properties and yield of polyaniline were optimized. The polymer exhibited a highly porous morphology and was found to be stable up to 417 °C. The PANI salt showed good solubility in common solvents, such as chloroform, N -Methyl- 2 -pyrrolidone (NMP), dimethyl sulphoxide (DMSO) and in a 1:3 mixtures by volume of 2-propanol and toluene. The coating of the synthesized PANI salt on stainless steel has shown good corrosion resistant behavior in marine water by reducing the corrosion rate to 67.9% as compared to uncoated stainless steel.