Manganese contamination in drinking water poses a significant environmental and public health concern, particularly in regions impacted by industrial discharges and geogenic leaching. This study investigates the potential of activated biochar derived from Pinus roxburghii pinecones (PCB), an abundant forestry residue, as a sustainable and cost-effective adsorbent for the removal of Mn(II) from aqueous systems. The biochar was chemically activated using potassium hydroxide to enhance its adsorption properties. Comprehensive characterization using Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) confirmed the development of a highly porous structure and the presence of oxygen-containing functional groups responsible for metal binding. To optimize the adsorption process, Response Surface Methodology (RSM) based on a Box–Behnken Design (BBD) was employed, considering key operational parameters such as pH, adsorbent dosage, stirring speed, and contact time. The optimal conditions were determined to be pH 8.0, adsorbent dosage of 5 g/L, stirring speed of 230 rpm, and contact time of 45.6 min. Under these conditions, a maximum Mn(II) removal efficiency of 83.59
Biosurfactants (BSs) are surface-active compounds synthesized by several microbes, serving as a sustainable substitute for chemical surfactants due to their non-toxicity, biodegradability and environmental-friendliness. They have garnered considerable attention owing to their broad applications in the agricultural, environmental, food, pharmaceutical, and cosmetic industries. Their wide applications in industries have been hindered due to the higher cost of production and low yield. Though the yield and production efficiency of BSs have significantly improved through the advancement and optimisation of diverse process parameters. Efforts have been made to reduce production costs by using byproducts of agricultural, food, and animal industries. This approach not only reduces production costs but also supports waste valorization and promotes the circular-bioeconomy. Further, specific statistical tools were employed to optimize the production parameters, such as substrate concentration, pH, temperature, etc., which significantly improve the yield and reduce the cost of production. This review discusses utilizing low-cost, waste raw substrates and statistical approaches used in optimizing BS production processes.
Diabetic nephropathy (DN) is a diabetic complication that leads to the progressive deterioration of kidney function. Oxidative stress and inflammation play crucial roles in the pathogenesis of DN. Oral hypoglycemic agents such as sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors show renal protective effects and help in slowing the progression of the disease. Emerging therapeutic targets, including phosphodiesterase inhibitors, Vitamin D analogues, and others, are being explored for treating DN. The development of newer biomarkers needs more attention and clinical acceptance for the timely diagnosis and management of DN. The present review attempts to discuss the different stages of DN, the pathophysiological mechanisms involved in DN development and progression, and potential biomarkers (Neutrophil Gelatinase-Associated Lipocalin, β2-microglobulin, Kidney Injury Molecule-1, Serum homocysteine, β-trace protein, Angiotensinogen, Osteopontin, Urinary exosomes, MicroRNAs) and therapeutic approaches for the effective management of DN.
Covalent inhibition has emerged as an effective strategy for targeting oncogenic proteins, yet successful covalent engagement depends not only on binding affinity but also on the dynamic preservation of productive electrophile–thiol geometry. Motivated by the clinical success of acrylamide-based KRAS G12C inhibitors such as sotorasib, we performed a structure-based and molecular dynamics investigation of acrylamide-containing KRAS G12C ligands. Although several ligands initially achieved near-reactive proximity to Cys12, production molecular dynamics simulations revealed rapid relaxation of the pre-reactive geometry and loss of productive electrophile–thiol alignment. Similar geometric relaxation was observed for noncovalent sotorasib simulations, whereas covalent KRAS G12C complexes preserved stable sulfur–carbon distances and chemically consistent bond geometries throughout explicit-solvent molecular dynamics. These findings suggest that covalent feasibility in KRAS G12C is governed by stringent dynamic geometric constraints and emphasize the importance of reactive-state preorganization in covalent inhibitor design.
The human microbiome is a complex ecosystem that produces a diverse repertoire of bioactive molecules essential for maintaining physiological homeostasis. Growing evidence indicates that microbiome-derived metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), polyamines, vitamins, tryptophan-derived metabolites and microbial bioactive compounds, play vital roles not only in modulating immune responses and metabolic pathways but also in maintaining epithelial integrity and regulating systemic inflammation. Through their effects on host signaling pathways, these molecules act as key mediators in the development and progression of metabolic diseases and cancer. This review discusses how such molecules influence the tumor microenvironment, regulate epigenetic processes, such as histone deacetylase inhibition, and modulate metabolic pathways, including lipid homeostasis, adipogenesis, and insulin sensitivity. Emerging therapeutic approaches, including probiotics, postbiotics, and fecal microbiota transplantation, highlight the translational potential of microbiome-targeted interventions. Postbiotics comprise preparations of inanimate microorganisms and/or their components that confer health benefits and should be distinguished from purified microbial metabolites. Despite advancements in this field, challenges remain, including the standardization of metabolites and inter-individual variability in the microbiome, which can hinder widespread application. Future perspectives emphasize not only multi-omics technology but also the significant impact of personalized microbiome medicine, bioprospecting for novel metabolites, and computational modeling. Collectively, these findings highlight the therapeutic landscape of microbiome-derived molecules and their potential to transform interventional strategies for metabolic diseases and even cancer. This review synthesizes current knowledge on major classes of microbiome-derived metabolites, emphasizing their origins, mechanisms of action, and roles in disease modulation.
Abstract Fluorine-containing xenobiotics including per- and polyfluoroalkyl substances (PFAS), fluorinated pharmaceuticals, agrochemicals, and industrial compounds, pose significant analytical challenges due to their persistence, low environmental concentrations, and structural diversity. Detection and monitoring of these compounds require highly sensitive and selective methods capable of resolving complex mixtures at trace levels. Analytical strategies increasingly employ chromatographic techniques such as high- and ultra-high-performance liquid chromatography (HPLC, UHPLC) and gas chromatography (GC), coupled with tandem and high-resolution mass spectrometry (LC–MS/MS, GC–MS/MS, Orbitrap, TOF) for both targeted and non-targeted analyses. Ion chromatography (IC) enables measurement of ionic species, while 19F nuclear magnetic resonance (NMR) enables direct, quantitative fluorine-specific detection for structure and pathway elucidation. Complementary spectroscopic methods, including X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FTIR), and Raman spectroscopy, provide further insights into C–F bonding environments. Total fluorine determination by combustion ion chromatography (CIC) and particle-induced gamma-ray emission (PIGE) spectroscopy offers a comprehensive assessment of fluorine content, while the total oxidisable precursor (TOP) assay and fluoride ion-selective electrodes (ISE) aid in precursor and degradation analysis. Integration of passive sampling, isotope-labelled standards, and biomonitoring enhances environmental and biological relevance. Beyond analytical advances, this review critically examines how emerging targeted, suspect-screening, and non-targeted approaches improve source tracking, exposure assessment, environmental monitoring, and regulatory surveillance of fluorinated contaminants. The review further discusses current knowledge gaps, the challenges associated with emerging fluorinated compounds, and the need for integrated analytical and monitoring frameworks to support future risk assessment, remediation strategies, and evidence-based environmental management.
SCOBY is a symbiotic consortium of bacteria and yeasts that forms a cellulose-rich pellicle during kombucha fermentation. Our aim was to study different bleaching processes to produce bacterial cellulose (BC) leather with improved properties. The fermentation process was carried out for 6 days and the SCOBY layer was removed and submitted to a sanitization using NaOCl (48 h) followed by a bleaching process using two H2O2 concentrations (23
Research has shown that oxidative stress is a key factor in the progression of a range of human illnesses, such as cancer and neurodegenerative diseases. Extensive research is underway to explore new management strategies due to the significant impact of these diseases on public health. Phytochemicals found in plants, particularly phenolic compounds, have demonstrated significant potential in the treatment and prevention of diseases associated with oxidative stress. Therefore, this review delves into the chemistry of plant phenolic compounds, examining their antioxidant activity and potential for disease prevention from a critical standpoint. Additionally, it highlights recent advancements in their absorption within the body. Phenolic compounds can act as antioxidant agents, providing protection against oxidative stress. They achieve this by modulating various cellular processes such as apoptosis, redox balance signaling, differentiation, and proliferation. It is intriguing that, despite obstacles within the body, phenols can reach peripheral organs such as the brain. Further research is needed to explore the relationship between phenolic compounds and gut microbiota, as well as the dose-response relationship. These fields of research hold immense potential to revolutionize our understanding of the physiological benefits of consuming phenolic compounds.
Scanning tunneling microscopy-based single-molecule junction techniques, such as break junction (STM-BJ) and fixed junction (STM-FJ), have been widely used to study molecular electronic properties and transient events. However, their application to monitoring chemical reactions remains challenging, because each molecular species involved needs to be chemically modified in order to form stable single-molecule junctions with electrodes. Here, using our previously developed macrocycle-assisted, anchor-free STM-FJ platform, we demonstrate the real-time monitoring of a cucurbit[6]uril (CB6)-catalyzed azide-alkyne cycloaddition reaction in aqueous solution. By modifying one gold electrode with CB6, anchor-free reactants and products can be captured within the macrocyclic cavity and incorporated into stable single-molecule junctions, thereby converting molecular events into electrical readouts with sub-millisecond temporal resolution. Current-time traces reveal a clear evolution of conductance states corresponding to different molecular species. A short-lived high-conductance state was observed at the early stage of the reaction and is attributed to a ternary precursor complex in which both reactants are simultaneously encapsulated. This state gradually disappeared as the conductance signature of the CB6-triazole product becomes dominant, indicating the completion of the reaction. These results show the macrocycle-modified STM-FJ junction is a powerful platform for monitoring chemical reactions and biological systems in aqueous environments.
Prolonged hyperglycemia exacerbates diabetes through the formation of early Amadori-glycoxidation, intermediate reactive dicarbonyl species and advanced cross-linked aggregates. The study utilizes multi-spectroscopies based biophysical analyses to encompass an early to advanced stage inhibition of fructose (Fru) and methylglyoxal mediated bovine serum albumin (BSA) glycation (Fru-gBSA and methylglyoxal-gBSA) by introducing dansyl labelled molecular probe in the privileged scaffold pseudo C2‒symmetric transoid aldazines (bis-aldimine) framework. The study thus explores the pharmacophoric role of aldazine moiety through the conformational-binding selection of s-trans dansylated-bis-vanillin aldimines (DVBA-1) to investigate the inhibition mechanism of BSA glycation from early Amadori-glycoxidation to advanced cross-linking. Conformational studies in association with molecular docking and dynamic simulation reflects a distinctive binding between IIA and IIIA sub-domain of BSA of a specific rotameric transoid conformation of DVBA-1, among all transoid conformers, which causes secondary structural perturbation and glycation micro-environment alteration. This strategy supports the primary interactions of aldazine pharmacophore of DVBA-1 near sugar-binding domain of BSA resulting inhibition of glycation.
Bioactive peptides used in foods and nutraceuticals are frequently exposed to oxidizing environments that reshape their structure, function, and safety profile. Beyond acting as radical scavengers, peptides can undergo extensive modification by reactive oxygen species (ROS) and by oxidized lipid and sugar products that co-occur in complex food matrices. Mechanistic studies reveal that hydroxyl radicals, peroxyl radicals, and metal‑catalyzed H2O2 systems generate peptide hydroperoxides, carbonyls, backbone fragments, and covalent dimers in a sequence‑dependent manner, particularly at proline, tryptophan, tyrosine, and histidine residues. Parallel reactions with oxidized lipids, including lipid hydroperoxides and electrophilic aldehydes such as malondialdehyde and hydroxynonenal, drive additional layers of modification through trans‑oxidation, Schiff base formation, and Michael addition, yielding diverse adducts whose structures and stabilities differ markedly from classical ROS products. Glycation and glycoxidation further contribute carbonyl‑derived cross‑links and fluorophores in sugar‑rich systems. While the biological consequences of protein oxidation are well described, the functional and toxicological implications of oxidized bioactive peptides remain largely unexplored. Emerging evidence indicates that peptide hydroperoxides, lipid‑derived aldehyde adducts, and advanced glycoxidation/lipoxidation products can alter peptide bioavailability, immunoreactivity, redox behaviour, and cellular functions in cell and animal models. This review integrates current knowledge on the chemistry, analytical detection, and structural diversity of peptide oxidation products, highlights sequence‑specific reactivity patterns, and outlines safety considerations and research priorities for peptide‑based functional ingredients.
The global crisis of multidrug-resistant (MDR) bacteria, driven by the overuse and misuse of antibiotics, demands the urgent exploration of effective alternatives. In response, biotics, encompassing probiotics, prebiotics, postbiotics, synbiotics, and bacteriophages—demonstrating 37–40
Medicinal plants have been commonly used in traditional medicine for many centuries to cure various ailments because of their phytocompounds, especially the secondary metabolites. Capparis zeylanica Linn., plant of family Capparaceae is used in ‘Rasayana’ of Ayurvedic medicines to cure indigestion and as an antidote to snake bites and to treat inflammation of testicles, smallpox, boils, cholera, colic, hemiplegia, neuralgia, sores, pneumonia and pleurisy. Many studies have indicated that different parts of Capparis zeylanica, which are stem, roots, seeds, and fruit, have many activities, such as antioxidant, anticancer, antiparasitic, antimicrobial, etc. However, there is a lack of exploration of the flower of Capparis zeylanica. Thus, the aim of this study is to identify the phytochemistry and some pharmacological properties of the Capparis zeylanica flower. The qualitative screening of flower methanolic extract revealed the phytochemical compounds such as flavonoids, saponins, terpenoids, anthraquinones, steroids, phlobatannins and carbohydrates, and the total polyphenol content had been exhibited as 79.70 mg GAE/g of dry extract, and the surface functional groups are identified by FTIR. A total of 27 compounds were obtained from the GC-MS/MS analysis, and 61 metabolites were obtained tentatively belonging to the categories of flavonoids, coumarins, carboxylic acids, herbicides, glycosides, alkaloids, terpenoids, antibiotics, fatty acids, carbohydrates, amino acids, phenols, aldehydes, and esters by LC-ESI-QTOF-MS/MS analysis. The antioxidant activity of the flower methanolic extract showed an IC50 value of 57.87 µg mL⁻¹, and the antivibriocidal activity revealed the minimum inhibitory concentration of 62.5 µg mL⁻¹ of the flower methanolic extract against V. parahaemolyticus and V. harveyi. Therefore, the present study revealed the importance of various analytical methods in the determination of the phytochemistry of the flower Capparis zeylanica.
Naloxone is an important opioid antagonist often used for the rapid reversal of opioid-induced respiratory depression and life-threatening opioid overdose. It has become more essential globally because of the rising opioid crisis and its application in emergency medicine as well as community harm-reduction efforts. This review offers an in-depth introduction to naloxone, encompassing the history, synthetic protocols, and molecular mechanism of action as a competitive antagonist primarily at µ-opioid receptors. The structure-activity relationship (SAR) features of naloxone that influence receptor affinity and antagonistic activity are discussed. Further, the molecular docking demonstrated the naloxone-receptor interactions at the binding site. The pharmacokinetic and pharmacodynamic profile of naloxone, which includes a rapid onset and short duration of action, is critically examined in relation to clinical outcomes. Additionally, the discussion covers emerging therapeutic roles, current clinical applications, limitations, and adverse effects, including withdrawal precipitation and opioid renarcotization. A comparative examination with similar opioid antagonists, i.e., naltrexone and nalmefene, highlighted the disparities in duration, clinical utility, and bioavailability. Finally, the future perspectives to develop the next-generation opioid antagonists are provided, focusing on enhanced formulations, longer-acting analogs, and advanced computational approaches.
Abstract Biomolecular condensates formed by liquid–liquid phase separation (LLPS) have emerged as fundamental components of intracellular organization. While their biophysical mechanisms are increasingly well understood, much less is known about how the ability to phase-separate is subject to natural selection. In this article, we argue that phase separation should be treated as an evolvable molecular phenotype. We review how classical sequence-based molecular evolution, motif-level modeling, and comparative trait-evolution frameworks collectively offer powerful tools for dissecting how natural selection shapes the condensate-forming capacity of proteins, and we outline promising directions for future investigation. Using examples from well-aligned proteins such as members of the FET family and from motif-rich intrinsically disordered regions (IDRs), we illustrate how selection acts on residues, motif number and spacing, domain architecture, and emergent biophysical properties. Recent advances in artificial intelligence make it possible to predict latent molecular traits—including disorder propensity, interaction valency, and phase-separation potential—directly from sequence, enabling these properties to be embedded within evolutionary models. Together, these approaches lay the foundation for the emerging field of evolutionary condensate biology, spanning residue-level constraints, motif organization, and biophysical trait dynamics. This synthesis opens new opportunities for comparative and predictive studies of LLPS across the tree of life and for the rational design of proteins capable of controlled phase separation.
Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are caused largely by protein fibril misfoldings, their aggregation, mitochondrial dysfunction and irregularity in cell signalling pathways. Due to the presence of the blood brain barrier and poor target specificity, the traditional therapeutics showed limited success. In recent times, with the progress in computational biology and artificial intelligence a structurally precise, highly stable de novo microproteins with tunable binding affinity have been designed to treat such deleterious diseases. These engineered small proteins through selective binding with the amyloid protein fibrils as well as by enhancing mitochondrial function and proteostasis prevent the onset and progression of neural disorders. This review highlights de novo design of microproteins, their mechanisms of action, challenges and future prospects in neurodegenerative pathologies. Collectively, de novo designed microproteins represent a promising candidate in curing of neural diseases.
The emergence of room-temperature phosphorescence (RTP) has opened a new era in material science, offering metal-free alternatives for efficient triplet exciton utilization. Key advances, such as the incorporation of non-metallic heavy atoms (S, Se, B), rigid conjugated scaffolds, and intramolecular locking strategies, have enabled efficient inter-system crossing (ISC), spin-orbit coupling (SOC), and the stabilization of triplet states, leading to efficient RTP. Alongside RTP, thermally activated delayed fluorescence (TADF) emitters have emerged as another breakthrough in purely organic triplet harvesting. Both classes of materials share design synergies, such as rigid polycyclic frameworks and precise electronic control, yet differ fundamentally in their excited-state dynamics: RTP relies on triplet phosphorescence, while TADF relies on reverse inter-system crossing. Interestingly, recent studies reveal that certain TADF molecules can also exhibit RTP, owing to their structural modulation. This duality suggests exciting opportunities to design multifunctional emitters that selectively access TADF and RTP, thereby broadening the application landscape. This review critically surveys and classifies the state-of-the-art in organic RTP molecules showing TADF, outlining molecular design strategies, photo physical principles and their potential applications in OLEDs, bio imaging, information encryption, X-Ray imaging, time-gated bioassay, photodynamic therapy, flexible wearable optoelectronic devices and circularly polarized room-temperature phosphorescence. Finally, the challenges and opportunities are identified for expanding these classes of organic triplet-harvesting molecules.
Abstract Conventional CCSD(T) calculations are widely considered as the gold standard for electronic structure theory. However, they become computationally prohibitive for medium- and large-sized molecular systems even with the high-end hardware. In this study, we evaluate the effectiveness of the Grafting-assisted Molecular Tailoring Approach (GMTA) in calculating the energies at the CCSD(T) level of theory. Benchmark calculations are performed on ammonia and water clusters as well as on covalent compounds, utilizing correlation-consistent basis sets. Later, GMTA-CCSD(T) results are compared with conventional (when available) and recently reported FMO2-CCSD(T) calculations. GMTA is found to reproduce energies precisely, with deviations generally in a sub-milli-Hartree range. These findings confirm GMTA as a reliable and computationally efficient alternative for conventional CCSD(T) in the study of medium- and large-molecular systems. Further, such calculations are possible for cases when conventional calculations are not feasible due to hardware limitations.
Hydroxytyrosol (HTY), a phenolic compound mainly found in olive oil, has garnered significant interest in recent years due to its diverse pharmacological properties influenced by specific metabolic pathways. This review provides an in-depth analysis of the current research on HTY, with a specific focus on elucidating the key signaling pathways that underlie its antioxidant, anti-inflammatory, antidiabetic, anticancer, antiatherosclerotic, and wound healing properties. The key signaling pathways investigated include the nuclear factor erthriod 2 related factor 2 (Nrf2) activation cascade which leads to the upregulation of phase 2 detoxification genes heme oxygenase (HO1), superoxide dismutase and catalase (CAT), inhibition of the inflammatory signaling pathway of nuclear kappa B (NF-κB), modulation of PI3K/Akt/mTOR pathways in cancer cells and activation of the adenosine monophosphate activated protein kinase (AMPK) for metabolic regulation. Furthermore, HTY’s iron chelation ability not only inhibits ferroptosis cell death but also influences miRNA expression profiles, regulating various downstream targets and impacting crucial cellular processes. This review highlights the interconnected therapeutic potential of biochemical networks in addressing a spectrum of health issues, including cardiovascular diseases, neurological disorders, metabolic dysfunction, and cancer. Despite existing preclinical and clinical evidence indicating that HTY possesses pathway-specific mechanisms, further investigation is required to comprehensively elucidate its interactions with multiple targets, validate its efficacy in specific disease contexts, and ensure its safe and effective application in clinical environments. To make a significant impact on human health and well-being, it is crucial to focus on addressing the identified research gaps in validating biochemical pathways and translating research findings into clinical applications.
Abstract Microencapsulation stands as a cornerstone strategy for controlled delivery and stabilization of functional biomolecules, unlocking potential in biomedical, pharmaceutical, and tissue engineering fields. Unlike prior reviews that catalogue general biomaterials and techniques, this work uniquely adopts a bioinspired perspective to compare natural polymers such as alginate, chitosan, gelatin, cellulose, and collagen based on their biomimetic attributes, including hierarchical structures that enhance biocompatibility, biodegradability, mechanical resilience, and biomolecular activity preservation. This review evaluate key selection criteria alongside major encapsulation methods such as spray/freeze drying, electrospinning, and supercritical fluids, detailing their advantages, limitations, and biomolecule-specific suitability. Furthermore, the characterization strategies for physical, chemical, biological performance, release kinetics, stability, and bioactivity are critically analysed to pinpoint parameters driving encapsulation efficiency and therapeutic outcomes. Therapeutic applications in cancer therapy, wound healing, and regenerative medicine are emphasized through application-driven design principles that prioritize biomimetic mimicry for targeted delivery. Current challenges like scalability, long-term stability, and regulatory hurdles are addressed, alongside emerging directions in smart biomaterials, 3D bioprinting, and in vivo monitoring. This review advances the field by introducing a biomimetic comparison framework absent in existing literature, guiding the rational design of next-generation encapsulation systems that boost clinical translation via enhanced stability, precision targeting, and superior safety-efficacy profiles. Graphical abstract
