Influenza A virus (IAV) remains a significant public health concern due to its annual epidemics and potential for global pandemics. Despite the availability of countermeasures such as vaccines and antiviral treatments, their effectiveness is often questioned due to the emergence of novel strains with antiviral resistance and the variable efficacy of influenza vaccines compared to other vaccines. Traditionally, influenza vaccination strategies have focused on matrix, neuraminidase, and nucleoproteins. In this study, considering the crucial roles of HA and RdRp (PA, PB1, and PB2) of Influenza A, a reverse vaccinology approach is put forth in designing a possible promising antigenic protein toward the development of vaccines against H1N1 viruses. With the development of immunoinformatics approach, one can design/construct potential candidates for vaccine formulation against IAV with the epitope segments identified based on B- and T-cell recognition linked via adjuvants like EAAAK, GPGPG, and AAY linkers. Computational assessments of physicochemical properties, antigenicity, immunogenicity, allergenicity, and toxicity predictions, conducted to evaluate the potential of designed vaccine construct, indicated high antigenicity and potential interactions with immune receptors. Molecular docking of the vaccine construct with human immune receptors (MHCI, MHCII, TLR4, TLR7, and TLR8) followed by molecular dynamics simulations demonstrated stable dynamics with strong binding affinity. The computational immune response modeling with multiple dosages suggested significant immune activation by this construct against IAV. In essence, these findings highlight the potential immune property of the vaccine construct, and put forth the need of thorough preclinical assessments in transforming this construct as a vaccine against the challenging IAV pathogens.

Inflammation and oxidative stress are key pathological drivers of many chronic and neurodegenerative disorders, prompting increasing interest in natural compounds that can safely modulate inflammatory responses and protect neural cells from oxidative damage. In this study, walnut shell pectin (WSP), extracted from Chilean walnut shells, was evaluated for its anti-inflammatory and neuroprotective potential using in vitro models. The anti-inflammatory effects were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, while the neuroprotective effects were investigated in rotenone-treated SH-SY5Y neuroblastoma cells. WSP significantly reduced LPS-induced inflammation by downregulating the expression of pro-inflammatory cytokine TNF-α and enhancing the anti-inflammatory cytokine IL-10. In rotenone-exposed SH-SY5Y cells, WSP increased the activities of antioxidant enzymes, catalase and superoxide dismutase, thereby reducing oxidative stress and improving neuronal viability. The maximum protective concentration for both cell lines was determined to be 50 µg/ml. Overall, WSP exhibited strong anti-inflammatory and neuroprotective activities in vitro, highlighting its potential as a natural therapeutic compound for preventing and managing inflammation-associated and neurodegenerative disorders.

Monoamine oxidases (MAOs) are FAD-dependent enzymes responsible for the oxidation of neurotransmitter monoamines. In humans, two isoenzymes exist—MAO-A and MAO-B. Altered or elevated MAO-B levels have been associated with neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. This study investigates the impact of non-synonymous single-nucleotide polymorphisms (nsSNPs) on MAO-B structure and function. A combination of sequence-based, structure-based, and evolutionary conservation analyses, including the ConSurf server, was used to identify harmful nsSNPs. The dbSNP database revealed 257 nsSNPs in the MAO-B, which were evaluated using 20 computational tools. Seven nsSNPs (W388C, R38C, A19G, Y60C, I272T, I462T, and V245F) were predicted as the most deleterious, and all are located at highly conserved residues. To assess structural and functional effects, molecular dynamics simulations (MDS) were performed on native and mutant protein models. Results indicated that these mutations could significantly influence MAO-B stability, flexibility, and enzymatic activity, potentially altering its physiological role. Conservation analysis suggested that mutations at conserved sites are more likely to disrupt protein function, aligning with the observed predictions. This in silico approach highlights key nsSNPs that may contribute to the pathogenesis of neurodegenerative diseases by impairing MAO-B function. While computational predictions provide valuable insights, experimental validation through in vitro and in vivo studies is essential to confirm these findings. Overall, the identified deleterious nsSNPs represent important candidates for understanding mutation-driven alterations in MAO-B, offering potential avenues for biomarker development and therapeutic interventions in MAO-B–related neurological disorders.

Walnut shell is widely generated agricultural waste which offers immense opportunities for high-value biovalorisation, transforming a significant environmental burden into a valuable resource. This sustainable approach converts walnut shell into various valuable products, fostering a circular bioeconomy through diverse pathways. This review explores various bioconversion strategies, viz., generation of bioenergy and biofuels through pyrolysis, biodiesel production and biogas generation. Additionally, it covers the chemical and material applications including activated carbon, biocomposites and natural dyes, replacing synthetic alternatives. This review covers pharmaceutical and cosmeceutical applications, food and feed uses, and agricultural and environmental solutions, highlighting their roles in promoting health, enhancing nutrition, and supporting sustainability. Economic and life cycle assessments are evaluated to ensure the viability and scalability of walnut shell biovalorisation. By leveraging technological advancements, life cycle assessments, and sustainability analyses, walnut shell biovalorisation ensures efficiency, environmental viability and economic benefits. This approach reduces waste disposal costs, creates new revenue streams, promotes rural development, enhances environmental sustainability and improves human health through value-added products, presenting a compelling solution for industry stakeholders and researchers.

Oxalyldihydrazide (ODH) and coffee extracted fuel (CEF) were used to synthesize Ceria (CeO2) nanoparticles by solution combustion synthesis route. The cubic fluorite structure, crystalline nature, crystallite size and particle size of ceria nanoparticles were confirmed using the powder X-ray diffraction (PXRD) and High-Resolution Transmission Electron Microscope patterns respectively. Field Emission Scanning Electron Microscope (FESEM) images were used to understand the Surface morphology of the synthesized samples. Based on XRD results the volume of coffee husk extract for the optimum phase formation is found to be 40 mL. The fluorite structure of the samples and the presence of oxygen vacancies in the samples were confirmed from the Raman spectral analysis. ESR (Electron Spin Resonance) studies confirmed formation of relatively more intrinsic defects in CEF-ceria nanoparticles compared to ODH-ceria nanoparticles. The semiconducting nature of the synthesized samples was confirmed by analysing UV-visible absorbance spectra. The functional group confirmation was obtained by analysing Fourier Transform Infrared (FTIR) spectra of both the samples. AC conductivity and dielectric relaxation studies of the samples in pellet form were carried out over a wide frequency (20Hz-10 MHz) and temperature (200-640 degrees C) range using a precision impedance analyser. A higher value of dielectric constant was observed for CEF-ceria nanoparticles.

Grapes are rich in phenolic compounds with potent antioxidant properties that mitigate risks associated with cardiovascular and neurodegenerative diseases. However, postharvest storage often leads to microbial infestations, significantly deteriorating fruit quality. This study investigated the effects of two composite edible coatings i.e., Coffee Husk Pectin-Clove Oil (CHP-CO) and Freeze-Dried Coffee Husk Pectin-Clove Oil (FD-CHP-CO) on prolonging the shelf life of grapes. Coated and uncoated grapes were evaluated for their physicochemical (weight loss, colour, pH, total soluble solids and titratable acidity), bioactive compounds (total phenolics and total flavonoids), in vitro antioxidant and antimicrobial properties during 14 d of storage at ambient (RT, 25 ± 1 °C) and cold (4 ± 1 °C) storage conditions. Coated grapes maintained better quality compared to uncoated grapes, with FD-CHP-CO reducing weight loss by up to 76

Coffee husk, an agricultural waste abundant in carbohydrates and nutrients, is typically discarded through landfills, mixed with animal fodder, or incinerated. However, in alignment with sustainable development principles, researchers worldwide are exploring innovative methods to harness the value of coffee husk, transforming it into profitable products. One such avenue is the biotechnological approach to bioethanol production from agricultural wastes, offering an eco-friendly alternative to mitigate the adverse effects of fossil fuels. This study delves into the feasibility of utilizing coffee husk as a substrate for bioethanol production, employing and comparing various hydrolysis methods. The enzymatic hydrolysis method outshone thermochemical and thermal approaches, yielding 1.84 and 3.07 times more reducing sugars in the hydrolysate, respectively. In examining bioethanol production, a comparison between free and encapsulated cells in enzyme hydrolysate revealed that free-cell fermentation faced challenges due to cell viability issues. Under specific fermentation conditions, bioethanol yield (0.59 and 0.83 g of bioethanol/g of reducing sugar) and productivity (0.1 and 0.12 g/L h) were achieved for free and encapsulated cells, respectively. However, it was noted that bioethanol production by encapsulated cells was more significantly influenced by internal mass transfer effects, as indicated by the Thiele modulus and effectiveness factor. In conclusion, our findings underscore the potential of coffee husk as a valuable substrate for bioethanol production, showcasing its viability in contributing to sustainable and eco-friendly practices.

Drug repurposing is preferred over de-novo drug discovery to unveil the therapeutic applications of existing drug candidates before investing considerable resources in unexplored novel chemical entities. This study demonstrated multifaceted stratagems to reconnoiter promising repurposable candidates against Hepatocellular Carcinoma (HCC) by amalgamating Real-World-Data (RWD) with bioinformatics algorithms corroborated with in-silico and in-vitro studies. At the outset, the RWD from the Food and Drug Administration Adverse Event Reporting System (FAERS) was explored to navigate signals to retrieve repurposable drugs that are inversely associated with HCC via Disproportionality Analysis. Further, transcriptomic analysis was used to capture the potential targets of HCC. Following this, the interactions between repurposable drugs and HCC targets were virtually demonstrated via molecular docking and Molecular Dynamics Simulations (MDS). Furthermore, additional cytotoxicity and gene expression experiments were conducted to corroborate the results. Overall, 64 drugs with Drug Event >5 were shortlisted as prospective repurposable drugs as per the RWD obtained from FAERS. The transcriptomic analysis highlighted significant upregulation of Cyclin A2 (CCNA2) in HCC, which activates Cyclin Dependent Kinase 2 (CDK2). Further, in-silico studies identified Losartan and Allopurinol, with docking scores of -7.11 and -6.219, respectively, as potential repurposable drugs. The selected drugs underwent further scrutiny through in-vitro studies. The treatment of HepG2 cells with Allopurinol resulted in significant downregulation of CCNA2/CDK2 expression with an elevation in reactive oxygen species levels, uncovering Allopurinol's anticancer mechanism through cellular apoptosis. This study suggests the importance of RWD in drug repurposing and the potential of Allopurinol as a repurposable drug against HCC.

The Dopa Decarboxylase (DDC) gene plays an important role in the synthesis of biogenic amines such as dopamine, serotonin, and histamine. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the DDC gene have been linked with various neurodegenerative disorders. In this study, a comprehensive in silico analysis of nsSNPs in the DDC gene was conducted to assess their potential functional consequences and associations with disease outcomes. Using publicly available databases, a complete list of nsSNPs in the DDC gene was obtained. 29 computational tools and algorithms were used to characterise the effects of these nsSNPs on protein structure, function, and stability. In addition, the population-based association studies were performed to investigate possible associations between specific nsSNPs and arthritis. Our research identified four novel DDC gene nsSNPs that have a major impact on the structure and function of proteins. Through molecular dynamics simulations (MDS), we observed changes in the stability of the DDC protein induced by specific nsSNPs. Furthermore, population-based association studies have revealed potential associations between certain DDC nsSNPs and various neurological disorders, including Parkinson's disease and dementia. The in silico approach used in this study offers insightful information about the functional effects of nsSNPs in the DDC gene. These discoveries provide insight into the cellular processes that underlie cognitive disorders. Furthermore, the detection of disease-associated nsSNPs in the DDC gene may facilitate the development of tailored and targeted therapy approaches.Communicated by Ramaswamy H. Sarma

Walnuts, known for their high nutritional value, generate significant waste in the form of husks and shells, the disposal of which contributes to environmental pollution. The utilization of this walnut waste for the production of beneficial compounds remains underexplored. In the current study, extraction time, temperature, microwave power, and solid-to-solvent ratio were optimized using response surface methodology. This technique significantly reduced the extraction time, yielding pectin at 34.13 +/- 3.83 % under optimal conditions: temperature (74 degrees C), microwave power (400 W), irradiation time (16 min), and solid-solvent ratio (1:25). XRD characterization revealed the crystalline nature of the extracted pectin, while FTIR confirmed the presence of major functional groups. The extracted pectin exhibited an equivalent weight of 576.99 +/- 7.63 g/ mol with a degree of esterification of 59.88 +/- 0.28 %, making it suitable for food, pharmaceutical, and cosmetic applications. Further, the extracted pectin demonstrated significant antioxidant activity with IC50 values of 5.08 +/- 0.08 mg/ml for DPPH and 2.87 +/- 0.023 mg/ml for ABTS assays. It also showed antibacterial activity against both gram-positive Staphylococcus aureus MTCC 96 and gram-negative Pseudomonas aeruginosa MTCC 424, with zones of inhibition measuring 25.33 +/- 0.58 mm and 28.33 +/- 0.58 mm, respectively. SEM analysis revealed changes in cell morphology of S. aureus and P. aeruginosa when treated with the extracted pectin. These findings suggest that microwave-assisted extraction offers a rapid, eco-friendly, and cost-effective method for pectin extraction from walnut shells, promoting sustainable utilization of this waste resource and providing a potential pectin source with enhanced biological activity.

In recent years, the use of fermented fruit juices to offer protection against mental illness has been increasing enormously. The present study, aimed at formulating a synbiotic fruit beverage for mental well-being using fructo-oligosaccharide (FOS), Gamma-aminobutyric acid (GABA) and Lactobacillus rhamnosus. Guava extract (abbreviated as fruit extract, FE; 10%) supplemented with FOS (1%) fermented for 48 h using L. rhamnosus, was then fortified with 0.05% GABA (FE + FOS + GABA). This GABA-fortified fermented guava beverage exhibited significant in-vitro antioxidant activity as measured by using 2,2-diphenyl-1-picrylhydrazyl (IC50 value of 0.451 ± 0.05 mg/ml) and ferrous reducing antioxidant capacity (A700 nm value of 0.68 ± 0.06) assays. Fermentation also enhanced total phenolics and flavonoids by 27.63% and 27.41%, respectively. Furthermore, GABA-fortified fermented guava beverage showed a significant neuroprotective effect by negatively modulating oxidative stress and upregulating activity of antioxidant enzymes (superoxide dismutase and catalase) in rotenone treated neuronal cell lines. Taken together, our research findings clearly indicate the propensity of GABA-fortified fermented guava beverage to protect against rotenone mediated neuronal cell damage. Even though the underlying molecular mechanisms need further research, in conclusion, our study demonstrates that the GABA-fortified fermented guava beverage effectively confers neuroprotective effects in vitro, suggesting its potential as a functional beverage for promoting brain health. Graphical Abstract

Biochar is a carbon-rich material obtained through the thermal decomposition of lignocellulosic percussor in the absence of oxygen. Biochar is widely utilized as a sustainable and potential adsorbent for the removal of pollutants owing to its unique physicochemical properties. This chapter aims to review the importance of utilizing lignocellulosic waste in the development of biochar-based adsorbents. The influence of process parameters that affect the properties of biochar is also provided. The comprehensive review of modification methods of biochar properties is explained along with adsorption characteristics, and sorption abilities of biochar in the amputation of organic and inorganic pollutants.

Tyrosine Kinase beta (TRKβ), is a type I membrane receptor which plays a major role in various signalling pathways. TRKβ was found to be upregulated in various cancers and contrastingly downregulated in various neurodegenerative disorders. Hitherto, contemporary drug research is oriented towards discovery of TRKβ inhibitors, thus neglecting the development of TRKβ agonists. This research is aimed at identifying FDA approved drugs exhibiting repurposable potential as TRKβ agonists by mapping them with fingerprints of the BDNF/TRKβ interaction interface. Initially, crucial interacting residues were retrieved and a receptor grid was generated around it. TRKβ agonists were retrieved from literature search and a drug library was created for each agonist based on its structural and side effect similarities. Subsequently, molecular docking and dynamics were performed for each library to identify the drugs possessing affinity towards the binding pocket of TRKβ. The study revealed molecular interactions of Perospirone, Droperidol, Urapidil, and Clobenzorex with the crucial amino acids lining the active binding pocket of TRKβ. Subsequent network pharmacological analysis of the above drugs revealed their interactions with key proteins involved in neurotransmitter signalling pathways. Clobenzorex displayed high stability in dynamics simulation and therefore this drug is recommended for further experimental evaluations to attain better mechanistic insights and predict its implications in correcting neuropathological aberrations. This study's focus on the interaction interface between TRKβ and BDNF, combined with the utilization of fingerprint analysis for drug repurposing, contributes to our understanding of neurotrophic signalling and holds potential for identifying new therapeutic options for neurological disorders.

Many countries around the world are facing severe challenges due to the recently emerging variants of SARS-CoV-2. Over the last few months, scientists have been developing treatments, drugs, and vaccines to subdue the virus and prevent its transmission. In this context, a peptide-based vaccine construct containing pathogenic proteins of the virus known to elicit an immune response was constructed. An analysis of the spike protein-based epitopes allowed us to design an “epitope-based subunit vaccine” against coronavirus using the approaches of “reverse vaccinology” and “immunoinformatics.” Computational experimentation and a systematic, comprehensive protocol were followed with an aim to develop and design a multi-epitope-based peptide (MEBP) vaccine candidate. Our study attempted to predict an MEBP vaccine by introducing mutations of SARS-CoV-2 (Delta, Lambda, Iota, Omicron, and Kappa) in Spike glycoprotein and predicting dual-purpose epitopes (B-cell and T-cell). This was followed by screening the selected epitopes based on antigenicity, allergenicity, and population coverage and constructing them into a vaccine by using linkers and adjuvants. The vaccine construct was analyzed for its physicochemical properties and secondary structure prediction, and a 3D structure was built, refined, and validated. Furthermore, the peptide-protein interaction of the vaccine construct with Toll-like receptor (TLR) molecules was performed. Immune profiling was performed to check the immune response. Codon optimization of the vaccine construct was performed to obtain the GC content before cloning it into the E. coli genome, facilitating its progression it into a vector. Finally, an in-silico simulation of the vaccine–protein complex was performed to comprehend its stability and conformational behavior.

Several well-known neuropsychological tests of working memory performance, hitherto thought to be unrelated, in fact share a common structure termed here the self-ordered selection paradigm. Examples include the subject-ordered pointing task, variants of the Corsi blocks test, the multiple-location search task, and the letter-recitation task. The defining features of the paradigm are outlined. A statistical framework for assessing and testing hypotheses about working memory capacity in the self-ordered selection paradigm is described. To enable neuropsychologists to conduct a rapid statistical analysis of working memory performance, a computer program is presented along with detailed practical examples of three useful statistical procedures for both single-case and group-based analysis. The program may be accessed and executed online over the Internet.

The viral disease dengue is transmitted by the Aedes mosquito and is commonly seen to occur in the tropical and subtropical regions of the world. It is a growing public health concern. To date, other than supportive treatments, there are no specific antiviral treatments to combat the infection. Therefore, finding potential compounds that have antiviral activity against the dengue virus is essential. The NS2B-NS3 dengue protease plays a vital role in the replication and viral assembly. If the functioning of this protease were to be obstructed then viral replication would be halted. As a result, this NS2B-NS3 proves to be a promising target in the process of anti-viral drug design. Through this study, we aim to provide suggestions for compounds that may serve as potent inhibitors of the dengue NS2B-NS3 protein. Here, a ligand-based pharmacophore model was generated and the ZINC database was screened through ZINCPharmer to identify molecules with similar features. 2D QSAR model was developed and validated using reported 4-Benzyloxy Phenyl Glycine derivatives and was utilized to predict the IC50 values of unknown compounds. Further, the study is extended to molecular docking to investigate interactions at the active pocket of the target protein. ZINC36596404 and ZINC22973642 showed a predicted pIC50 of 6.477 and 7.872, respectively. They also showed excellent binding with NS3 protease as is evident from their binding energy of -8.3and -8.1 kcal/mol, respectively. ADMET predictionsofcompounds have shown high drug-likeness. Finally, the molecular dynamic simulations integrated with MM-PBSA binding energy calculations confirmedboth identified ZINC compounds as potential hit moleculeswith good stability.

NS3-4A, a serine protease, is a primary target for drug development against Hepatitis C Virus (HCV). However, the effectiveness of potent next-generation protease inhibitors is limited by the emergence of mutations and resulting drug resistance. To address this, in this study a structure-based drug design approach is employed to screen a large library of 7320 natural compounds against both wild-type and mutant variants of NS3-4A protease. Telaprevir, a widely used protease inhibitor, was recruited as the control drug. The top 10 compounds with favorable binding affinities underwent drug-likeness evaluation. Based on ADMET studies, complexes of NP_024762 and NP_006776 were selected for molecular dynamic simulations. Principal component analysis (PCA) was employed to explore the conformational space and protein dynamics of the protein-ligand complex using a Free Energy Landscape (FEL) approach. The cosine values obtained from FEL analysis ranged from 0 to 1, and eigenvectors with cosine values below 0.2 were chosen for further analysis. To forecast binding free energies and evaluate energy contributions per residue, the MM-PBSA method was employed. The results highlighted the crucial role of amino acids in the catalytic domain for the binding of the protease with phytochemicals. Stable associations between the top compounds and the target protease were confirmed by the formation of hydrogen bonds in the binding pocket involving residues: His1057, Gly1137, Ser1139, and Ala1157. These findings suggest the potential of these compounds for further validation through biological evaluation.Communicated by Ramaswamy H. Sarma

Quinonoid dihydropteridine reductase (QDPR) is an enzyme that regulates tetrahydrobiopterin (BH4), a cofactor for enzymes involved in neurotransmitter synthesis and blood pressure regulation. Reduced QDPR activity can cause dihydrobiopterin (BH2) accumulation and BH4 depletion, leading to impaired neurotransmitter synthesis, oxidative stress, and increased risk of Parkinson’s disease. A total of 10,236 SNPs were identified in the QDPR gene, with 217 being missense SNPs. Over 18 different sequence-based and structure-based tools were employed to assess the protein’s biological activity, with several computational tools identifying deleterious SNPs. Additionally, the article provides detailed information about the QDPR gene and protein structure and conservation analysis. The results showed that 10 mutations were harmful and linked to brain and central nervous system disorders, and were predicted to be oncogenic by Dr. Cancer and CScape. Following conservation analysis, the HOPE server was used to analyse the effect of six selected mutations (L14P, V15G, G23S, V54G, M107K, G151S) on the protein structure. Overall, the study provides insights into the biological and functional impact of nsSNPs on QDPR activity and the potential induced pathogenicity and oncogenicity. In the future, research can be conducted to systematically evaluate QDPR gene variation through clinical studies, investigate mutation prevalence across different geographical regions, and validate computational results with conclusive experiments. Communicated by Ramaswamy H. Sarma

The dry method of coffee processing generates a significant amount of coffee husk, an agricultural waste for which currently there is a lack of profitable use, and their disposal constitutes a major environmental problem. Pectin was extracted from coffee husk using citric acid solution (pH 1.5) by microwave-assisted extraction method, followed by using ice-cold ethanol. The coffee husk pectin (CHP) with a yield of 40.2% was characterized using SEM, FT-IR, and XRD techniques. The CHP exhibited significant in-vitro antioxidant activity as measured by using 2,2-diphenyl-1-picrylhydrazyl; (IC50 value of 395.1 +/- 0.42 mu g/mL), ferrous reducing antioxidant capacity (A700 nm = 0.55 +/- 0.08), 2,2 '-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging (42.02 +/- 0.38%) and ascorbic acid auto-oxidation inhibition (92.01 +/- 0.28%) assays. CHP demonstrated antibacterial activity against Escherichia coli and Bacillus cereus with an inhibition diameter of 20 +/- 1.01 mm and 18 +/- 0.84 mm, respectively. Interestingly, CHP showed a significant antiinflammatory effect by negatively modulating the expressions of TNF-alpha and TGF- beta in LPSstimulated macrophage cell lines. Collectively, our findings suggest that the coffee husk is a potential source of commercial pectin, microwave-assisted extraction has a great potency on the commercial pectin extraction from the coffee husk and CHP demonstrates significant biological activity.