Two pyrrole-derived heteroarylidene donor–π–acceptor (D–π–A) fluorophores were synthesized from pyrrole-2-carboxaldehyde and the active methylene acceptors Meldrum's acid (MAPC) and 1,3-dimethylbarbituric acid (BAPC) as per the reported protocols (Begüm Yılmaz et al., 2025a; Helmy et al., 2014a; Ajayan et al., 2023; Sarma et al., 2021a [1], [2], [3], [4]) and their photophysical properties were investigated in detail. Both compounds are weakly emissive in solution but display intense blue (MAPC, 455 nm) and green (BAPC, 529 nm) fluorescence in the solid state, consistent with aggregation-enhanced emission. Theoretical investigations were performed to elucidate the role of acceptor moiety in the process. It was observed that aggregation influences charge-transfer character and solid-state emission in these pyrrole-based D–π–A fluorophores. DFT and TD-DFT calculations on low-energy aggregates, combined with intrinsic fragment charge-transfer analysis revealed that MAPC aggregates are dominated by local excitation with moderate short-range charge transfer, whereas BAPC aggregates exhibit a much stronger intermolecular charge-transfer. This enhanced charge-transfer contribution in BAPC correlates with its more red-shifted and brighter solid-state emission. Preliminary fluorescence microscopy studies further demonstrated that BAPC is cell-permeable and remains fluorescent in HeLa cells, indicating its potential in bioimaging applications.

Aromatic α-hydroxy-ketones like benzoin, known to undergo oxidation in the presence of NaOH in solvents like dimethyl sulfoxide (DMSO) and ethanol (EtOH) to afford the labile coloured free radical anions which rapidly get transformed to the corresponding diketone. In this study, we observed that the radical anion generated from furoin can be stabilized by carrying out the oxidation using triethanolamine (TEOA) as solvent. The experimental observation of enhanced stabilization of the furil radical anion in TEOA compared to DMSO was confirmed by Electron Paramagnetic Resonance (EPR) Spectroscopy and UV–Vis spectroscopy. Subsequently, this observation was validated by theoretical computational methods.

The matrix metalloproteinases (MMPs) are a class of zinc proteases that aid in breaking most of the extracellular matrix's (ECM) constituents. Additionally, MMPs play a part in processing elements that affect inflammation, cell development and proliferation, and many more. In vivo genetic study of the Drosophila MMPs Mmp1 and Mmp2 reveals they are essential for tissue remodeling but not embryonic development. The canonical and conserved MMP domain organization is present in both fly MMPs. Because Mmp2 appeared to be membrane-anchored and Mmp1 appeared to be released, the pericellular localization of Drosophila MMPs has been used to classify them. This suggests that the protein's localization is the critical distinction in this small MMP family. The signal sequence, the propeptide, the catalytic domain, and the hemopexin-like domain are among the numerous domains found in MMPs. Following secretion from the extracellular environment to the endoplasmic reticulum, the pre-domain, also known as the signal sequence, serves to direct MMP production. MMPs of the secretory and membrane types (MT-MMPs) are two groups of MMPs that have been widely recognized. Subgroups of MMPs are categorized based on their structure and function. While analysis of the intracellular activity of human MMPs is challenging because the human genome contains around 23 distinct MMPs with overlapping functions, only two MMPs, dMMP1 and dMMP2, are encoded by the Drosophila melanogaster genome. On the other hand, the balance between MMPs and the family members are implicated in various pathophysiology/progression of diseases, but whether or not the mechanisms of MMP inhibition are not clearly understood as master regulators. In this review, we outline the role of MMPs as master regulators of tissue morphogenesis.

Sesbania grandiflora, a fast-growing shrub from the Fabaceae family, is extensively researched for its therapeutic properties. Despite its highly valued medicinal properties, there have been no reports on exploring the proteome of Sesbania grandiflora. The present study aims to address this gap by investigating the proteomic profile of Sesbania grandiflora seeds with a primary focus on identifying storage proteins. The proteomic data disclosed an abundant vicilin protein from the seeds, which was subsequently purified to homogeneity. Structural analysis revealed the heterotrimeric nature of the purified protein, with an intact molecular weight of approximately 130 kDa and the presence of N-glycosylation. Further, in-gel digested protein bands were analyzed via LC-MS/MS, and partial de novo sequences were deduced through a homology-driven proteomic approach. Circular dichroism spectroscopy revealed that the vicilin is predominantly composed of n-sheet structures, with a melting temperature of 69.3 degrees C. Functional studies demonstrated the protein's chitin-binding capability via chitin affinity chromatography, highlighting its anti-mycotic properties. The antifungal activity was quantified, showing that approximately 15 mu M of the purified protein inhibited 50 % of Fusarium oxysporum growth. A cell permeability assay with propidium iodide staining confirmed the interaction between the protein and the fungal cell wall, highlighting its role in antifungal activity.

Pyomelanogenic P. aeruginosa, frequently isolated from patients with urinary tract infections and cystic fibrosis, possesses the ability to withstand oxidative stress, contributing to virulence and resulting in persistent infections. Whole genome sequence analysis of U804, a pyomelanogenic, multidrug-resistant, clinical isolate, demonstrates the mechanism underlying pyomelanin overproduction. Seven essential oils (EOs) were screened for pyomelanin inhibition. Garlic, cinnamon and thyme EOs were selected for further studies based on their significant anti-virulent properties, like inhibition of pyomelanin production and biofilm formation. Additionally, downregulation of the expression of virulence genes regulated by quorum sensing (QS) and a decrease in levels of the QS signaling molecule, C12-HSL, were also observed. The EO treatment inhibited the survival of U804 in human blood and increased survival of C. elegans, a whole animal model of pathogenesis. EO treatment also resulted in a significant reduction of efflux pump activity, indicative of their effect on antibiotic sensitization. Garlic oil enhanced the permeability of the bacterial membrane, resulting in decreased survival, when combined with sub-MIC concentrations of colistin. This study demonstrates that thyme, cinnamon and garlic EOs can attenuate pyomelanogenic P. aeruginosa virulence traits. Additionally, garlic potentiates drug sensitivity, suggesting its promising therapeutic use in combating pyomelanogenic MDR infections.

Endophytic fungi, residing harmlessly within plant tissues, represent an underexplored, but promising source of bioactive compounds. This study explores the bioactive potential of an endophytic fungus, Penicillium rubens EF 363, isolated from a mangrove plant, Ceriops tagal. The bioactive compound was extracted, purified, characterized and identified as Citrinin. This compound displayed significant antimicrobial activity with a minimum inhibitory concentration (MIC) of 5–20 µg/ml against bacterial pathogens (Bacillus cereus, Escherichia coli, and Staphylococcus aureus), 10 µg/ml against Fusarium solani, and 90

Snakebite remains a significant public health issue in tropical regions, with 4.5 to 5.4 million incidents annually. Trimeresurus popeiorum (Pope's Pit Viper), found in Southeast Asia and northeast India, poses a potential threat, yet its venom's protein composition and toxicity are poorly understood. In this study, we used label-free quantitative proteomics to analyze the venom of T. popeiorum, identifying 106 proteins across 12 venom protein families. Notably, 60 % of the venom consisted of proteolytic enzymes, correlating with its prominent metalloprotease, fibrin(ogen)lytic, procoagulant, and thrombin-like activities. The proteome composition also correlates with the clinical effects such as consumption coagulopathy and local effects, seen in victims of Pit Viper envenomation in northeast India. Our findings suggest that T. popeiorum venom is less toxic than other Viperinae species such as Daboia russelii and Echis carinatus, likely due to isoform-level variations in certain toxin classes, including metalloprotease and serine protease. The venom's lethal dose (LD50) in Swiss albino mice was 1 mg/kg, and it caused haemorrhage, tissue necrosis, edema, myotoxicity, and defibrinogenation. Histopathological examination of the TPV-treated mice showed notable toxic effects, including marked hepatic vacuolation in the liver, damage to cardiac muscle and vascular congestion in the heart, bronchial epithelial hyperplasia with cellular infiltration in the interstitial and peribronchiolar regions of the lungs, as well as tubular necrosis and haemorrhage in the kidneys. This research provides the first comprehensive analysis of T. popeiorum venom, highlighting its pharmacological effects and the need for greater medical attention to this lesser-known species.

Fibrosis is one of the major outcomes following injury in the heart. Immune response in the injury niche modulates fibrosis, yet little is known about how cell-autonomous immune signaling in adult cardiac fibroblasts regulates fibrosis. Using FACS, single-cell sequencing of cardiac fibroblasts from Collagen1-α1GFP mice and human heart failure patients, we demonstrate that TLR4 is the major immune sensor expressed in cardiac fibroblasts. Inhibition of TLR4 signaling reduces TGF-β induced fibrotic changes such as contractibility and migration of adult human cardiac fibroblasts in TGF-β treated fibrotic conditions. TGF-β treated cardiac fibroblastss show enhanced cytokine expression, and inhibition of TLR4 signaling reduces the expression of cytokines, thereby reducing TGF-β targets such as extracellular matrix genes. Thus, our data demonstrate that TLR4 and other signaling molecules downstream of TLR4 are expressed in cardiac fibroblast, and inhibition of TLR4 modulates fibrotic changes in vitro.

Background: The constant increase in global onion production escalates the generation of onion peel waste. For instance, globally, >50 lakh tons of onion waste are generated annually. Methods: Its objectionable odor precludes its use in agriculture or disposal as landfilling presents environmental issues. Previous studies show that two major flavonoids, quercetin and its glycosides (spiraeoside), have been identified in abundance in onion waste. By utilizing the spiraeoside (quercetin-4ʹ-glucoside), a rapid synthesis of pachypodol (quercetin-3,3′,7-trimethyl ether, and a rare flavonol), an essential Ayurvedic product, has been developed and achieved. Pachypodol and analogs were studied for their ability to inhibit matrix metalloproteinase-2 and -9 (MMP-2 & 9) activity. Amongst the compounds tested, pachypodol significantly inhibited MMP-2 activity. Results: In-silico docking studies suggest that, unlike most known MMP inhibitors, pachypodol interacts selectively with MMP-2 through the residues Ile222, Tyr223, and Thr227 in a zincindependent manner. Conclusion: The experimental studies also prove that pachypodol inhibits the MMP-2 enzyme in a zinc-independent way.

Approximately 40-50% of municipal solid waste is organic and causing biogenic malodor and infections, due to inefficient treatment methods. Biorefinery-based bioremediation and valorization is in vogue against these conventional strategies since it combines unit operations for better efficiency and productivity. Deriving inspiration, the proposed strategy puts together a unique and compatible combination of processes. This novel two-step valorization workflow involves the extraction of small molecules using organic solvents, and fermentation of resulting denatured residues (increased biodegradability or decreased recalcitrance) of reduced microbial load. The extraction step also doubles up as a sterilization event, with different solvents (petroleum ether, chloroform, ethyl methyl ketone and methanol) exhibiting varied efficiency, methanol and ethyl methyl ketone being the most effective. Different recalcitrant plant organic wastes resulting from four plants (Cocos nucifera, Allium cepa, Artocarpus hirsutus and Swietenia mahagoni) were used as feedstocks in the preliminary exploratory study using chosen pathogenic bacteria. Onion peel (Allium cepa) ethyl methyl ketone extract was chosen for further studies, as it inhibits Salmonella enterica, which is associated with infection and malodour (due to biogenic H2S) in wastewater. Further, fractionation of the extract yielded quercetin and its glycoside. The onion peel residue, after solvent extraction was fortified with peptone and essential minerals to promote the growth of Bacillus clausii. Fortified post-extraction residue supported the growth better than the pre-extraction residue. The residue resultant after solvent extraction was fermented with Bacillus clausii and with release of bioactive supernatants. The concentrated supernatant showed significant inhibition of Salmonella enterica and Shigella dysenteriae. Additionally, all the exudates showed considerable inhibition in H2S production, respectively.

Pediatric neurological disorders include neurodegenerative diseases causing cognitive impairment and vision loss. They are one of the important causes of morbidity and mortality in children with diverse etiologies. Diagnosis is difficult despite genetic work, and a final diagnosis can be achieved in only 60

Arsenic contamination of soil and water is a major environmental issue. Bioremediation through plant growth-promoting bacteria is viable, cost-effective, and sustainable. Along with arsenic removal, it also improves plant productivity under stressful conditions. A crucial aspect of such a strategy is the selection of bacterial inoculum. The described study demonstrates that the indigenous wastewater isolate, ASBT-KP1, could be a promising candidate. Identified as Klebsiella pneumoniae, ASBT-KP1 harbors genes associated with heavy metal and oxidative stress resistance, production of antimicrobial compounds and growth-promotion activity. The isolate efficiently accumulated 30 μg/g bacterial dry mass of arsenic. Tolerance toward arsenate and arsenite was 120 mM and 70 mM, respectively. Plant biomass content of Vigna radiata improved by 13% when grown in arsenic-free soil under laboratory conditions in the presence of the isolate. The increase became even more significant under the same conditions in the presence of arsenic, recording a 37% increase. The phylogenetic analysis assigned ASBT-KP1 to the clade of Klebsiella strains that promote plant growth. Similar results were also observed in Oryza sativa, employed to assess the ability of the strain to promote growth, in plants other than V. radiata. This study identifies a prospective candidate in ASBT-KP1 that could be employed as a plant growth-promoting rhizoinoculant in agricultural practices.

Metatranscriptomic analyses offer unprecedented insights into the interplay between SARS-CoV-2 and human hosts, shedding light on distinct differentially expressed genes (DEGs) and their implications. The global significance of wastewater as a resource underscores its potential for disease surveillance and public health. Leveraging wastewater-based epidemiology (WBE) and advanced sequencing technologies, this study aims to elucidate DEGs between SARS-CoV-2 and human hosts. The introduction of high-throughput sequencing techniques has revolutionized our ability to detect and monitor viral pathogens in wastewater, presenting a cost-effective and comprehensive approach to epidemiological surveillance. By employing both, short-read Illumina whole transcriptome shotgun sequencing (WTSS) and long-read Oxford Nanopore Technologies (ONT), this study reveals DEGs associated with SARS-CoV-2 pathogenesis, providing valuable insights into viral-host interactions. The analysis identifies distinct alpha diversity clades between WBE and clinical microbiomes, offering potential clues to concurrent infections and underlying pathways. Host transcriptional signatures associated with COVID-19, such as those observed in MCP signal and ABC transporters, hold promise for elucidating the role of DEGs in the infectious cycle. This pioneering metatranscriptome analysis represents a significant step towards understanding the molecular basis of SARS-CoV-2 pathogenesis and highlights the potential of wastewater-based surveillance in combating infectious diseasesFunding: This work was partially funded under the SERB special project grant CVD/2022/000021 titled "Early Detection, Surveillance, and prevention of Communicable Viral diseases in Jaipur city: a Wastewater-Based Epidemiological study for COVID-19 (DISCOVER-WBE)".Declaration of Interest: None.Ethical Approval: All experimental protocols were approved by the institutional ethics Committee with informed consents taken from all the patients.

Background:: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples. We identified 76 miRNAs that were differentially expressed in DCIS and IDC. Methods:: Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in early-stage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples. Results:: Higher expression of miR-301a-3p is associated with poor overall survival in The Can-cer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation. Conclusion:: We also analyzed competing endogenous networks associated with differentially expressed miRNAs and identified LRRC75A-AS1 and MAGI2-AS3 as lncRNAs that potentially play an important role in early-stage breast cancers.

Acinetobacter baumannii causes severe infections in humans, resists multiple antibiotics, and survives in stressful environmental conditions due to modulations of its complex transcriptional regulatory network (TRN). Unfortunately, our global understanding of the TRN in this emerging opportunistic pathogen is limited. Here, we apply independent component analysis, an unsupervised machine learning method, to a compendium of 139 RNA-seq data sets of three multidrug-resistant A. baumannii international clonal complex I strains (AB5075, AYE, and AB0057). This analysis allows us to define 49 independently modulated gene sets, which we call iModulons. Analysis of the identified A. baumannii iModulons reveals validating parallels to previously defined biological operons/regulons and provides a framework for defining unknown regulons. By utilizing the iModulons, we uncover potential mechanisms for a RpoS-independent general stress response, define global stress-virulence trade-offs, and identify conditions that may induce plasmid-borne multidrug resistance. The iModulons provide a model of the TRN that emphasizes the importance of transcriptional regulation of virulence phenotypes in A. baumannii. Furthermore, they suggest the possibility of future interventions to guide gene expression toward diminished pathogenic potential.IMPORTANCEThe rise in hospital outbreaks of multidrug-resistant Acinetobacter baumannii infections underscores the urgent need for alternatives to traditional broad-spectrum antibiotic therapies. The success of A. baumannii as a significant nosocomial pathogen is largely attributed to its ability to resist antibiotics and survive environmental stressors. However, there is limited literature available on the global, complex regulatory circuitry that shapes these phenotypes. Computational tools that can assist in the elucidation of A. baumannii's transcriptional regulatory network architecture can provide much-needed context for a comprehensive understanding of pathogenesis and virulence, as well as for the development of targeted therapies that modulate these pathways.

Background Snake venom is a complex mixture of organic and inorganic constituents, including proteins and peptides. Several studies showed that antivenom efficacy differs due to intra- and inter-species venom variation.Methods In the current study, comparative functional characterization of major enzymatic proteins present in Craspedocephalus malabaricus and Daboia russelii venom was investigated through various in vitro and immunological cross-reactivity assays.Results The enzymatic assays revealed that hyaluronidase and phospholipase A2 activities were markedly higher in D. russelii. By contrast, fibrinogenolytic, fibrin clotting and L-amino acid oxidase activities were higher in C. malabaricus venom. ELISA results suggested that all the antivenoms had lower binding potential towards C. malabaricus venom. For D. russelii venom, the endpoint titration value was observed at 1:72 900 for all the antivenoms. In the case of C. malabaricus venom, the endpoint titration value was 1:2700, except for Biological E (1:8100). All these results, along with the avidity assays, indicate the strength of venom-antivenom interactions. Similarly, the western blot results suggest that all the antivenoms showed varied efficacies in binding and detecting the venom antigenic epitopes in both species.Conclusions The results highlight the need for species-specific antivenom to better manage snakebite victims.

The intricate combination of organic and inorganic compounds found in snake venom includes proteins, peptides, lipids, carbohydrates, nucleotides, and metal ions. These components work together to immobilise and consume prey through processes such as paralysis and hypotension. Proteins, both enzymatic and non-enzymatic, form the primary components of the venom. Based on the effects they produce, venom can be classified as neurotoxic, hemotoxic, and cytotoxic. Studies have shown that, after envenomation, proteins in snake venom also contribute significantly to the induction of inflammatory responses which can either have systemic or localized consequences. This review delves into the mechanisms by which snake venom proteins trigger inflammatory responses, focusing on key families such as phospholipase A2, metalloproteinases, serine proteases, C-type lectins, cysteine-rich secretory proteins, and L-amino acid oxidase. In addition, the role of venom proteins in activating various inflammatory pathways, including the complement system, inflammasomes, and sterile inflammation are also summarized. The available therapeutic options are examined, with a focus on antivenom therapy and its side effects. In general, this review offers a comprehensive understanding of the inflammatory mechanisms that are triggered by snake venom proteins and the side effects of antivenom treatment. All these emphasize the need for effective strategies to mitigate these detrimental effects.

The gut microbiota, amounting to approximately 100 trillion (1014) microbes represents a genetic repertoire that is bigger than the human genome itself. Evidence on bidirectional interplay between human and microbial genes is mounting. Microbiota probably play vital roles in diverse aspects of normal human metabolism, such as digestion, immune modulation, and gut endocrine function, as well as in the genesis and progression of many human diseases. Indeed, the gut microbiota has been most closely linked to various chronic ailments affecting the liver, although concrete scientific data are sparse. In this narrative review, we initially discuss the basic epidemiology of gut microbiota and the factors influencing their initial formation in the gut. Subsequently, we delve into the gut-liver axis and the evidence regarding the link between gut microbiota and the genesis or progression of various liver diseases. Finally, we summarise the recent research on plausible ways to modulate the gut microbiota to alter the natural history of liver disease.