The repeated outbreaks of coronavirus show how hard it is to keep antiviral effectiveness when the virus mutates. Coronaviruses depend on tightly regulated proteolytic processing mediated by the 3-chymotrypsin-like protease (3CLpro), making it a key antiviral target. Most current inhibitors engage the catalytic site, an approach that remains vulnerable to resistance driven by active-site mutations. Here, we investigate an alternative strategy based on allosteric regulation of 3CLpro by targeting a pocket surrounding residue Asn28, previously shown to influence enzymatic activity and dimer stability. Structure-based virtual screening identified novobiocin as a candidate ligand for this region, which lies adjacent to but distinct from the catalytic center. Biophysical experiments showed direct binding of novobiocin to 3CLpro in solution, with sub-micromolar affinity (Kd ∼ 3 × 10-7 M). Protease thermal stability and dimeric assembly were lowered by ligand binding. Enzymatic assays revealed a pronounced reduction in catalytic turnover with minimal effects on substrate binding, consistent with an allosteric mechanism of inhibition, and yielded IC50 values of ∼0.5 μM across independent assays. Molecular docking and simulation analyses supported stable binding at the Asn28-associated pocket and revealed localized changes in conformational dynamics. These findings show that novobiocin allosterically inhibits 3CLpro and identify the Asn28-associated pocket as a relevant target for developing inhibitors with improved resistance to viral evolution.

This study reports the corrosion behavior and cytocompatibility of a newly developed Mg-based non equiatomic medium entropy alloy, Mg60Ti24.24Zn9.66Nb6.1(Mg-MEA). The corrosion behavior of Mg-MEA in physiological environment was evaluated by four different tests i.e., hydrogen evolution reaction (HER), static immersion test, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The corrosion rate of the Mg-MEA was compared against the corrosion rates of pure Mg and AZ31. The developed alloy exhibited a corrosion rate of 0.86 +/- 0.11 mm/year which is significantly lesser than the corrosion rate of AZ31 and pure Mg (10.15 +/- 0.51 mm/year and 6.94 +/- 0.56 mm/year respectively). The corrosion layer formed on the MEA showed multiple oxides and hydroxides. Further, the formation of hydroxyapatite and Ca-3(PO4)(2) over the surface was confirmed by both EDX and XPS which is beneficial for tissue regeneration. The MEA sample at all concentrations (100 %, 75 %, 50 %, 25 % and 10 %) exhibited no toxicity (cell viability>80 %) which led to minimal cell death and can be visualized from live-dead staining images. Further, the hemocompatibility analysis performed on the MEA sample demonstrated a low hemolysis ratio of 1.3 +/- 0.6 %, indicating minimal hemolysis. The absence of fibrin network/pseudopods on the platelets confirmed the antiplatelet adhesion and enhanced hemocompatibility of Mg-MEA.

Vincetoxicum spirale (Forssk.) D.Z.Li, a threatened perennial climber with therapeutic values, belongs to the family Apocynaceae (Subfamily: Asclepiadoideae). Constraints related to seeds and seedling establishment, coupled with wide-spread habitat destruction depleted natural populations of this species. This study presents the first report of an efficient indirect organogenesis protocol using mature leaf-derived callus of V. spirale. Of the four types of explants evaluated (leaf, node, internode and root), leaf explants were found to be the most suitable for culture establishment and de novo organogenesis. Leaf explants cultured on Murashige and Skoog (MS, 1962) medium containing 2.0 mg L−1 of 2,4-dichlorophenoxyacetic acid (2,4-D) showed the highest response (76.7

BACKGROUND:Exosomes are extracellular vesicles released by cells that mediate intercellular communication and actively participate in cancer progression, metastasis, and regulation of immune response within the tumour microenvironment. Inhibiting exosome release from cancer cells could be employed as a therapeutic against cancer. METHODS AND RESULTS:In the present study, we have studied the effects of Acorus calamus in inhibiting exosome secretion via targetting Rab27a and neutral sphingomyelinase 2 (nSMase2) in HER2-positive (MDA-MB-453), hormone receptor-positive (MCF-7) and triple-negative breast cancer (MDA-MB-231) cells. We observed that treatment with A. calamus significantly downregulated the expression of Rab27a and nSMase2 in all tested cells. NTA analysis showed that inhibition of Rab27a and nSMase2 reduced exosome secretion from breast cancer cells. We conducted metabolic profiling of A. calamus extract to reveal the phytochemicals present and docked them on Rab27a and nSMase2 to decipher the compounds responsible for protein inhibition. Molecular dynamic simulations were conducted on lead compounds, and we observed that calcitriol lactone showed the most stable binding interactions with nSMase2. Treatment of breast cancer cells with calcitriol lactone significantly downregulated nSMase2 expression. CONCLUSIONS:Our study demonstrates that A. calamus significantly inhibits exosome secretion in HER2-positive, hormone receptor-positive, and triple-negative breast cancer cells by targeting key regulatory proteins Rab27a and neutral sphingomyelinase 2 (nSMase2). These findings suggest that A. calamus holds therapeutic potential in inhibiting exosome-mediated cancer progression by targeting the exosome secretion pathway. Further investigations are warranted to explore the clinical applications of these findings in breast cancer treatment.

In this study, Fe-xMg60Ti24.24Zn9.66Nb6.1 medium entropy alloy (x= 0, 5, 10, 15 volume percent) sample were fabricated using additive manufacturing and microwave sintering. The incorporation of Mg60Ti24.24Zn9.66Nb6.1 MEA in the Fe matrix reduced the compressive yield strength. The potentiodynamic polarization test showed a gradual increase in corrosion rate with the addition of MEA reinforcement. Despite the increased corrosion rate, Fe-10MEA and Fe-15MEA samples demonstrated cell viability values greater than 80% indicating non-cytotoxicity. Based on mechanical, corrosion and biological assessment, Fe-10MEA was selected for the fabrication of bone scaffolds. A computational scheme for designing graded scaffolds was proposed, which employed normal distribution function to determine feature position and size. The graded design demonstrated a progressive reduction in strength whereas the uniform design showed a rapid decrease in strength after reaching peak value. Further, the graded scaffolds exhibited higher energy absorption per unit volume than uniform scaffolds irrespective of material.

Plant-derived exosome-like nanoparticles represent a novel class of plant-based therapeutics with potential anti-cancer applications. The present study aims to isolate, characterize, and evaluate the Acorus calamus-derived exosome-like nanoparticles (ACENPs) for their cytotoxic and apoptotic effects on breast cancer cells. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) revealed that ACENPs exhibited a mean hydrodynamic diameter of 122.4 ± 5.0 nm and a particle concentration of 1.58 × 1011 particles/mL. Cellular uptake studies confirmed the efficient internalization of ACENPs in MCF-7, MDA-MB-453, and MDA-MB-231 breast cancer cells. Cytotoxicity assay demonstrated a significant reduction in cell viability by 17.6

An efficient micropropagation method has been defined utilizing meta-topolin (mT) for the first time in Momordica balsamina L., an underutilized cucurbit with high nutraceutical and therapeutic potential. Centpercent nodal explants exhibited bud-breaking on Murashige and Skoog's (MS, 1962) medium containing 1.0 mg L-1 mT and 0.1 mg L-1 Indole-3-acetic acid (IAA) and produced 4.65 f 0.30 shoots measuring 4.60 f 0.37 cm in length. During multiplication, MS medium supplemented with 0.5 mg L-1 mT, 0.1 mg L-1 IAA, and additives resulted in the maximum shoot number (44.20 f 1.21) with 6.54 f 0.13 cm shoot length per culture vessel, after 4 weeks of the fourth subculture. The types of cytokinins [mT or 6-benzylaminopurine (BAP)] influenced the development of foliar micromorphological characteristics. The leaves developed on mT and IAA containing medium exhibited superior foliar micromorphological parameters such as stomatal index, stomatal density, druse density, well-developed veins/veinlets in comparison to leaves developed on BAP and IAA containing medium. Ex vitro rooting and concurrent acclimatization (EVRCA) were achieved in greenhouse by pulse-treating the shoot-base with 250 mg L-1 indole-3-butyric acid (IBA) for 5 min. About 81 % shoots rooted ex vitro and developed 7.85 f 0.32 roots per shoot measuring 6.31 f 0.34 cm root length, after 4 weeks. Around 86 % of ex vitro rooted plantlets survived in the nursery and sets fruits. To ensure genetic homogeneity of the protocol, Start Codon Targeted (SCoT) and Inter Simple Sequence Repeats (ISSR) markers were utilized and the monomorphic banding profiles confirmed the clonal nature of the regenerants. Therefore, the defined protocol appears to be simple, robust and consistent for the large-scale production of genetically identical plants of M. balsamina. (c) 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

This study explores the factors influencing luxury fashion brands' information adoption and purchase intention. Using the information acceptance model (IACM), a double-layered conceptual model was developed to investigate the relationship between various dimensions of information from electronic word of mouth (eWOM) customers receive from social media and information adoption and purchase intention. A survey instrument was used to collect data online from 452 social media users who have purchased luxury fashion brands in India. The hypotheses were tested using AMOS software for structural equation modeling and Hayes PROCESS macros. The results indicate that information credibility, information quality, attitude towards information (ATI), information usefulness, and information needs were positive predictors of consumer information adoption. Results also show that information adoption is positively related to purchase intention. Furthermore, this study has found a significant moderating role of perceived risk (PR) in the relationship between information adoption and purchase intention. Contrary to what has been hypothesized, the three-way interaction between information adoption, PR, and information credibility on purchase intention was not supported. This study focused on the information-adoption-purchase intention of luxury fashion brands, particularly in the context of a developing country, India.

Recently, the metal Additive Manufacturing (AM) process has seen a substantial surge in its usage than other processes, especially indirect routes to obtain metal parts, including Rapid Sand Casting (RSC) using Selective Laser Sintering (SLS) and Binder Jetting (BJ). Further, it is observed that the SLS process has lost importance due to the dominance of the BJ. Thus, literature and commercial AM systems are investigated to determine the causes. This study comprises a Systematic Literature Review (SLR) and Bibliometrix using the Biblioshiny web application for patternless sand mold and core production using RSC. This article aims to obtain research articles via SLR for the SLS and BJ AM process, followed by the Bibliometrix using the Biblioshiny web application. The SLR divided the RSC domain into the AM and the Sand Casting (SC). The authors considered three databases, Scopus, Web of Science (WoS), and EBSCO, and applied the SLR, resulting in 148 articles. Subsequently, the authors analyzed 131 relevant articles via Biblioshiny, which led to valuable insights for future research. The bibliometrix and content analysis revealed seven clusters: RSC processes, its optimization, comparison, multi-material compatibility, environmental impact, mold coating, and applications. The RSC via BJ exhibited dominance in the research and commercial market over SLS, one reason SLS lost its importance. The authors proposed the revival of the SLS AM process by employing affordable CO2 laser and linear motor flying optics coupled with recent advancements, including incorporating a hybrid AM approach, adaptive slicing, and mold design for AM (DfAM).

This dataset provides a comprehensive phytochemical profile of Saraswata Ghrita, a classical Ayurvedic formulation traditionally used for cognitive enhancement. To capture its diverse bioactive constituents, three different extracts-methanol, hexane, and hexane-ethanol-were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS/MS) and High-Resolution Liquid Chromatography-Mass Spectrometry-Quadrupole Time-of-Flight (HR-LCMS/MS-QTOF). The dataset includes volatile and semi-volatile compounds identified through GC-MS/MS, while HR-LCMS/MS-QTOF facilitates the characterization of non-volatile and polar metabolites. Advanced chromatographic and spectrometric techniques were employed, integrating mass spectrometric detection, retention time analysis, and cheminformatics-based compound classification. Spectral data were processed using multiple databases, ensuring accurate compound annotation. Additionally, key parameters such as molecular weight, chemical structure, base peak intensity, and ion fragmentation patterns were recorded to aid in structural elucidation. This dataset is structured for comparative metabolomics, quality control, and pharmacological exploration, offering a valuable reference for researchers investigating the phytochemical complexity of Ayurvedic formulations. The compiled raw data, including chromatograms, peak intensities, spectral fingerprints, and molecular fragmentations, are publicly available for further computational modeling and validation. The dataset can also support future drug discovery efforts, network pharmacology studies, and Ayurvedic formulation standardization, ensuring reproducibility and facilitating integrative research on traditional medicine.

As dengue expands globally and many vaccines are under trials, there is a growing recognition of the need for assessing T cell immunity in addition to assessing the functions of neutralizing antibodies during these endeavors. While several dengue-specific experimentally validated T cell epitopes are known, less is understood about which of these epitopes are conserved among circulating dengue viruses and also shared by potential vaccine candidates. As India emerges as the epicenter of the dengue disease burden and vaccine trials commence in this region, we have here aligned known dengue specific T cell epitopes, reported from other parts of the world with published polyprotein sequences of 107 dengue virus isolates available from India. Of the 1305 CD4 and 584 CD8 epitopes, we found that 24% and 41%, respectively, were conserved universally, whereas 27% and 13% were absent in any viral isolates. With these data, we catalogued epitopes conserved in circulating dengue viruses from India and matched them with each of the six vaccine candidates under consideration (TV003, TDEN, DPIV, CYD-TDV, DENVax and TVDV). Similar analyses with viruses from Thailand, Brazil and Mexico revealed regional overlaps and variations in these patterns. Thus, our study provides detailed and nuanced insights into regional variation that should be considered for itemization of T cell responses during dengue natural infection and vaccine design, testing and evaluation.

Cucumis collosus (Rottl.) Cogn., a wild ancestor of melon cultivars, is an underutilized cucurbit of arid horticulture having nutraceutical and therapeutic significance. C. collosus has great potential for enhancing the genetic base of cultivated melon and other cucurbits. This investigation is the first report on a robust and reliable micropropagation system for C. collosus (var. AHK-119) using nodal explants, followed by micromorphological and genetic stability assessment. More than 95% explants showed axillary shoot-bud induction on MS (Murashige and Skoog, 1962) medium containing 0.5 mg L-1 BAP and developed a maximum of 3.2 +/- 0.6 shoots measuring 3.2 +/- 0.1 cm length. After evaluating the various parameters, the best shoot multiplication (Shoot Number 34.9 +/- 1.7, Shoot Length 6.7 +/- 0.9 cm) was achieved on MS medium having half-strength of nitrates (825 mg L-1 NH4NO3 and 950 mg L-1 KNO3) + 0.25 mg L-1 6-benzylaminopurine (BAP) + 0.1 mg L-1 Kinetin (Kin) + 0.1 mg L-1 Indole-3-acetic acid (IAA) + additives (50 mg L-1 ascorbic acid and 25 mg L-1 each of adenine sulfate, L-arginine and citric acid), after 4 weeks. Micro-shoots were rooted using three approaches: In Vitro Continuous Treatment (IVCT), In Vitro Pulse-Treatment (IVPT) and Ex Vitro Pulse Treatment (EVPT). Of these, EVPT approach proved to be most successful in terms of rooting response (80%), root number (6.4 +/- 0.9) and root length (5.7 +/- 0.7 cm). The foliar micro-morphology analysis of in vitro leaves (IVL), ex vitro leaves (EVL) and mother plant leaves (MPL) demonstrated notable adaptive alterations during the transitional stages and produced structurally stable plants similar to the mother plant. Furthermore, the validation of genetic homogeneity using Start Codon Targeted (SCoT) and Inter Simple Sequence Repeats (ISSR) markers revealed monomorphic banding patterns among the micropropagated and the mother plant. The discussed method can be applied for large-scale commercial production of C. collosus for arid horticulture, urban/vertical farming, breeding purposes and improvement of other cucurbits.

Cadaba fruticosa (L.) Druce (Capparaceae) is a pharmaceutically valuable woody shrub. Reproductive constraints (poor seed-setting, low seed germination, viability, and seedling survival) coupled with habitat disruption have caused decline in populations of this now endangered species. This paper reports an improved de novo shoot organogenesis using mature leaf–derived callus for the first time. Influence of plant growth regulators (PGRs), incorporation of additives, amending salts, and re-culturing of differentiated callus on shoot multiplication in C. fruticosa were studied. About 77

PurposeThis study focuses on Aaker's Brand Equity Model, to check the effect of brand equity determinants on booking intention (BI) for ridesharing in India. The study also explores the moderation of ecologically conscious consumer behavior (ECCB) on the multiplicative effect of brand awareness (BAw), brand association (BA) and perceived quality (PQ) in influencing the BI.Design/methodology/approachResponses from 393 Indian ridesharing users were collected using judgmental sampling and were analyzed using Hayes Process macro.FindingsThe study found a direct relationship between BAw and BI, BAw and BA, BAw and PQ, BA and PQ, PQ and BI, and BA and BI. Findings revealed mediation of BA in BAw and BI relationship and PQ in BAw and BI relationship. Results revealed that BA and PQ serially mediate BAw and BI relationship. ECCB moderates PQ and BI relationship but not BAw and BI relationship.Research limitations/implicationsSerial mediation and moderated-mediation results draw various theoretical implications for determinants of Aaker's Brand Equity model and ECCB.Practical implicationsThe research has several implications for managers in view of brand equity determinants and ECCB. The study also contributes to policy implications.Originality/valueStudy's novel contributions are mediation, serial mediation between brand equity determinants, and moderation of ECCB between BAw and BI for ridesharing.

Purpose Integrating additive manufacturing (AM) tools in traditional mold-making provides complex yet affordable sand molds and cores. AM processes such as selective laser sintering (SLS) and Binder jetting three-dimensional printing (BJ3DP) are widely used for patternless sand mold and core production. This study aims to perform an in-depth literature review to understand the current status, determine research gaps and propose future research directions. In addition, obtain valuable insights into authors, organizations, countries, keywords, documents, sources and cited references, sources and authors. Design/methodology/approach This study followed the systematic literature review (SLR) to gather relevant rapid sand casting (RSC) documents via Scopus, Web of Science and EBSCO databases. Furthermore, bibliometrics was performed via the Visualization of Similarities (VOSviewer) software. Findings An evaluation of 116 documents focused primarily on commercial AM setups and process optimization of the SLS. Process optimization studies the effects of AM processes, their input parameters, scanning approaches, sand types and the integration of computer-aided design in AM on the properties of sample. The authors performed detailed bibliometrics of 80 out of 120 documents via VOSviewer software. Research limitations/implications This review focuses primarily on the SLS AM process. Originality/value A SLR and bibliometrics using VOSviewer software for patternless sand mold and core production via the AM process.

HMGB1 is the most abundant nonhistone nuclear protein, which has been widely studied for its roles in the cytoplasm as an autophagy mediator and in the extracellular matrix as an inflammatory molecule. Studies concerning HMGB1's actual role and its binding within the nucleus are inadequate. Through this in vitro study, we aimed to discern the binding parameters of HMGB1 with various types of DNA, nucleosomes, and chromatin. HMGB1 binds differentially to different DNA, with a high affinity for altered DNA structures such as triplex and bulge DNA. Remodelling of nucleosome by CHD7 remodeller was negatively impacted by the binding of HMGB1. We also found that HMGB1 binds to the linker DNA of chromatin. Findings from this study shed light on the diverse roles HMGB1 may play in transcription, gene expression, viral replication, CHARGE syndrome and so forth.

Background Alzheimer's disease (AD) is a progressive neurodegenerative disorder that impairs memory, language, and cognitive functions and currently has no definitive cure. Saraswata Ghrita (SG), a traditional Ayurvedic remedy administered nasally, offers a holistic approach and is believed to directly affect brain functions through its unique delivery route. Objective This study aimed to evaluate the effectiveness of SG in improving cognitive function and neurochemical biomarkers in a patient with AD. Key outcomes included electroencephalography-based excitation/inhibition (fE/I) ratio, and levels of phosphorylated Tau-181 (pTau-181), serotonin, dopamine, acetylcholine, and dehydroepiandrosterone (DHEA). Methods A 90-day proof-of-concept clinical trial was conducted with one AD patient. Nasal administration of SG was performed twice daily. Measurements included EEG spectral power analysis across 1–48 Hz, cognitive function assessed by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Quality of Life in Alzheimer's Disease (QoL-AD) scales, and biochemical analyses of pTau-181, serotonin, dopamine, acetylcholine, and DHEA. Results Notable improvements were observed: ADAS-Cog score decreased from 40 to 36, QoL-AD score increased from 23 to 31, MMSE score improved from 13 to 18, and MoCA score increased from 8 to 13. Biochemical markers showed a decrease in pTau-181 (12.50 pg/ml to 6.28 pg/ml), an increase in acetylcholine (13.73 pg/ml to 31.83 pg/ml), while serotonin and DHEA levels rose, and dopamine levels decreased (39.14 pg/ml to 36.21 pg/ml). Conclusions SG demonstrated potential in enhancing cognitive functions and neurochemical markers in AD, with the nasal route proving safe and effective. These findings suggest the value of traditional Ayurvedic treatments in contemporary AD management.

Purpose This study aims to improve the acceleration in the additive manufacturing (AM) process. AM tools, such as extrusion heads, jets, electric arcs, lasers and electron beams (EB), experience negligible forces. However, their speeds are limited by the positioning systems. In addition, a thin tool must travel several kilometers in tiny motions with several turns while realizing the AM part. Hence, acceleration is a more significant limiting factor than the velocity or precision for all except EB. Design/methodology/approach The sawtooth (ST) scanning strategy presented in this paper minimizes the time by combining three motion features: zigzag scan, 45º or 135º rotation for successive layers in G00 to avoid the CNC interpolation, and modifying these movements along 45º or 135º into sawtooth to halve the turns. Findings Sawtooth effectiveness is tested using an in-house developed Sand AM (SaAM) apparatus based on the laser–powder bed fusion AM technique. For a simple rectangle layer, the sawtooth achieved a path length reduction of 0.19%–1.49% and reduced the overall time by 3.508–4.889 times, proving that sawtooth uses increased acceleration more effectively than the other three scans. The complex layer study reduced calculated time by 69.80%–139.96% and manufacturing time by 47.35%–86.85%. Sawtooth samples also exhibited less dimensional variation (0.88%) than zigzag 45° (12.94%) along the build direction. Research limitations/implications Sawtooth is limited to flying optics AM process. Originality/value Development of scanning strategy for flying optics AM process to reduce the warpage by improving the acceleration.

Plants have a history of being employed in managing breast cancer. However, no scientific evidence supports the idea that these plants can effectively reduce the level of HER2 expression. In this study, extracts from 10 medicinal plants were evaluated for their anticancer properties against HER2-positive breast cancer cells through various methods, including the SRB assay, comet assay, annexin V-FITC dual staining, and immunoblotting. All extracts exerted antiproliferative activity against HER2-positive breast cancer cells. Furthermore, Terminalia chebula (T. chebula), Berberis aristata (B. aristata), and Mucuna pruriens (M. pruriens) reduced HER2 expression in tested cell lines. In addition, an increased Bax/Bcl-2 ratio was observed after the treatment. A comparative proteomics study showed modulation in the proteome profile of breast cancer cells after treatment with T. chebula, B. aristata, Punica granatum, M. pruriens, and Acorus calamus. Metabolic profiling of lead plants revealed the existence of multiple anticancer compounds. Our study demonstrates the considerable potential of the mentioned plants as innovative therapies for HER2-positive breast cancer.