The aim of this work is the investigation of the surface activity, aggregation behavior of pyridine-based triethanolamine-tailored cationic surfactants (DDNEA, DDNBA, and DDNHA) in water and study of the interaction of surfactants with bovine serum albumin (BSA) using several techniques, such as UV-Vis, XRD, FT-IR, NMR, tensiometry, conductivity measurements, fluorescence spectroscopy, dynamic light scattering measurement, Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM). Tensiometry measurement confirms the self-assembly formation and surface active nature of the amphiphiles. The polarity and fluidity of the microenvironment was investigated using pyrene and 1,6-Diphenyl-1,3,5-hexatriene (DPH) as fluorescence probe molecules. TEM measurement revealed formation of vesicles in aqueous medium. Vitamin B2 was utilized to inspect the permeability of the lamellar structure. The interaction of the cationic amphiphiles with BSA was also investigated due to their applications in the cosmetic, pharmaceutical, and food industries. A multi spectroscopic approach was used to analyze the details of the binding process. Amphiphiles significantly quenched the intrinsic fluorescence of BSA albumin and the quenching was static in nature. Synchronous and 3D fluorescence spectroscopy indicated that the binding interaction led to microenvironmental changes in protein fluorophores. Molecular docking analysis suggests that hydrogen bonding and hydrophobic interactions primarily drive the complexation process.

Abstract Glycine, alanine, and serine are three different amino acids that were used as structural building blocks to synthesize three different cholesterol-based amphiphiles (CAPs). Their gelation behavior was systematically examined in binary solvent systems using a wide range of methods, such as UV–vis spectroscopy, FT-IR spectroscopy, NMR spectroscopy, rheological measurements, SEM, and XRD. It is interesting to note that all composites showed outstanding adsorption behavior toward water-soluble dyes. The CSAP gel matrix achieved a maximum dye adsorption capacity of approximately 272 mg/g for the calcein dye in aqueous solution. The dye separation study indicates that recyclable CAP amphiphiles are effective adsorbents for large-scale environmental remediation. Additionally, the fabricated matrix demonstrates potential for separating oil from an oil–water mixture with >97% separation efficiency. Extensive in vitro studies using the anticancer drug doxorubicin hydrochloride (DOX), fluoroquinolone antibiotic norfloxacin, and a biomolecule vitamin B12 were conducted to evaluate the release profile of the organogels, aiming to assess their potential for versatile biomedical applications in drug delivery systems in acidic pH.

Vulvovaginal candidiasis (VVC) is one of the most common infections caused by Candida albicans. VVC is characterized by an inadequate hyperinflammatory response and clinical symptoms associated with Candida colonization of the vaginal mucosa. Compared to other host niches in which C. albicans can cause infection, the vaginal environment is extremely rich in lactic acid that is produced by the vaginal microbiota. We examined how lactic acid abundance in the vaginal niche impacts the interaction between C. albicans and the human immune system using an in vitro culture in vaginal simulative medium (VSM). The presence of lactic acid in VSM (VSM+LA) increased C. albicans proliferation, hyphal length, and its ability to cause damage during subsequent infection of vaginal epithelial cells. The cell wall of C. albicans cells grown in VSM+LA displayed a robust mannan fibrillar structure, β-glucan exposure, and low chitin content. These cell wall changes were associated with altered immune responses and an increased ability of the fungus to induce trained immunity. Neutrophils were compromised in clearing C. albicans grown in VSM+LA conditions, despite mounting stronger oxidative responses. Collectively, we found that fungal adaptation to lactic acid in a vaginal simulative context increases its immunogenicity favouring a pro-inflammatory state. This potentially contributes to the immune response dysregulation and neutrophil recruitment observed during recurrent VVC.

Colorectal cancer, the second prime catastrophic cause of cancer-related mortality worldwide, manifests resistance to standard chemotherapy leading to poor patient outcomes. Mono-terpenoid alcohol geraniol, a cardinal ingredient of many essential oils, is active against various cancers and can induce apoptotic events and trigger oxidative assault in striving against cancer. However, its clinical application is restricted due to its indigent bioavailability and non-specific biodistribution. To address these issues, the present study focuses on the fabrication and characterizations of folate receptor-targeted and pH-tunable dextran-modified geraniol protein nano-scaffold (GER-BSA-DEX-F NPs) to instigate oxidative stress and apoptotic effectiveness against HCT-116 colorectal cancer cells. The formulated spherical nano-structure was 117.8 nm in diameter with high encapsulation efficiency and better drug loading capacity. Adequate uptake of GER-BSA-DEX-F NPs in HCT-116 cells and pH-tunable intracellular release of geraniol prompted enhanced cytoplasmatic reactive oxygen species generation that effectuating oxidative stress persuaded apoptosis in HCT-116 cells. GER-BSA-DEX-F NPs caused the decline in mitochondrial membrane potential and executed loss of micro-tubular organization in HCT-116 cells. This ultimately impelled apoptosis-inducing cell death by arresting the cell cycle at the G2/M phase. In conclusion, these findings divulge that GER-BSA-DEX-F NPs may be a striking therapeutic strategy against colorectal cancer therapy.

Oil spills in the ocean and textile dyes have a catastrophic impact on the environment, economy, and ecosystem. Phase-selective organic gelator dye sorption and oil separation for oil adsorption should meet certain criteria such as facile synthesis, low cost, effective gelation, and recyclability. This study has discovered that an aliphatic chain synthetic amphiphile based on cholesterol can produce organogels in a variety of organic solvents. Numerous methods, such as X-ray diffraction, Fourier-transform infrared spectroscopy, high-resolution scanning electron microscopy, and rheology, have been used extensively to examine and describe these organogels. An environmentally acceptable technique for achieving hazardous dye separation is presented here. For the sustainable filtration of dye-contaminated water, a new, straightforward, one-step method driven by gravitational force has been employed by using a gel column. This approach has shown excellent stability and reusability with repeated use, and it is easily scalable for the effective removal of a wide range of hazardous dyes. Furthermore, because the oil fraction was absorbed in the gel, the study showed how well it might be used to apply phase selectivity to separate the oil-water mixture from marine accidents. Furthermore, a straightforward distillation method can be used to quantitatively recover the oils contained in the gel and gelator molecules in phase-selective gelation. This low-tech, ecofriendly, and highly effective method also offers valuable insights into the development of advanced materials for separating toxic dyes and oil from water.

Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of breast cancer due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance to standard current treatments. Hesperetin (HSP), a natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but its hydrophobicity limits its clinical development. The present study reports the fabrication of a biocompatible and pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic-co-glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) and the exploration of its in vitro and in vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs were synthesized and characterized by DLS, FTIR, FE-SEM, and 1H NMR spectroscopy. The stability and in vitro release profile of nanoparticles were inspected, and anticancer efficacy was scrutinized in terms of in vitro cytotoxicity, oxidative stress and apoptosis biomarkers, and cell cycle arrest. In vivo tumor regression and host survival studies were executed in Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. The drug uptake of highly stable PLGA-HSP-TF NPs was accomplished effectively in MDA-MB-231 cells and showed the pH-dependent intracellular release of HSP, which generated excessive intracellular reactive oxygen species (ROS) that led to oxidative assault to the TNBC cells. This elevated ROS dropped the mitochondrial membrane potential and triggered apoptosis-mediated cell death by arresting the cell cycle at the G0/G1 phase. Furthermore, PLGA-HSP-TF NPs unveiled significant in vivo Ehrlich ascites carcinoma regression and host survival compared to free HSP with minimum toxicity at a minimum dose of 20 mg/kg body weight. The study divulges that PLGA-HSP-TF NPs may be an astounding anticancer nanocandidate for aggressive triple-negative breast cancer therapy.

Over the last few decades, scientists have been working hard to produce edible structural agents those can be used in food, cosmetics, agriculture, pharmaceuticals, and biotechnology. The supramolecular assembly of simple amphiphiles in presence of edible oil is the most ideal system for this purpose because the system has no harmful health consequences. We have attempted to address the aforementioned implications in this article by synthesizing a novel class of structuring agents 2-alkyl amino pyrimidine-4-carboxylic acid amphiphiles named 2-decylamino-pyrimidine-4-carboxylic acid (DPCA), 2-dodecylamino- pyrimidine-4-carboxylic acid (DDPCA) and 2-tetradecylamino-pyrimidine-4-carboxylic acid (TDPCA), using simple procedure. To our delight, the prepared amphiphiles self-assemble to a gel matrix in various vegetable oils and mineral oils. Microscopic analyses were used to investigate the nanostructured morphology of molecular gels. Rheological studies revealed that oleogels are mechanically processable and viscoelastic. Temperature dependent and concentration dependent proton nuclear magnetic resonance (1H-NMR) studies were performed to analyze the hydrogen bonding and pi-pi interactions. The study discovered that gelators act as reusable phase selective gelators (PSG) of oil in water-oil mixture. The (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay has proven that the synthetic oleogelators are nontoxic.

N-acetyl-D-glucosamine (GlcNAc) is a major component of bacterial cell walls. Many organisms recycle GlcNAc from the cell wall or metabolize environmental GlcNAc. The first step in GlcNAc metabolism is phosphorylation to GlcNAc-6-phosphate. In bacteria, the ROK family kinase N-acetylglu-cosamine kinase (NagK) performs this activity. Although ROK kinases have been studied extensively, no ternary complex showing the two substrates has yet been observed. Here, we solved the structure of NagK from the human pathogen Ple-siomonas shigelloides in complex with GlcNAc and the ATP analog AMP-PNP. Surprisingly, PsNagK showed distinct conformational changes associated with the binding of each substrate. Consistent with this, the enzyme showed a sequential random enzyme mechanism. This indicates that the enzyme acts as a coordinated unit responding to each interaction. Our molecular dynamics modeling of catalytic ion binding confirmed the location of the essential catalytic metal. Addi-tionally, site-directed mutagenesis confirmed the catalytic base and that the metal-coordinating residue is essential. Together, this study provides the most comprehensive insight into the activity of a ROK kinase.

In this work, the gelation ability of a series of novel pyridine-based glucose tailored gelators (DPHAEN, DPHABN, and DPHAHN) with a flexible alkyl chain has been examined in binary solvent mixtures using a number of techniques, for example, UV spectroscopy, FT-IR spectroscopy, NMR spectroscopy, rheology measurement, SEM, XRD, and computational study. Proposed herein is an environment-friendly method to realize toxic dye separation and oil/water separation. It has been found that gels in a selective binary solvent mixture are efficient reusable absorbers of toxic dye molecules. A new gravitational force-driven, simple one-step, toxic dye removal and oil-water separation method is presented for sustainable filtration of waste water and simultaneous collection of oil. The gel column also showed high stability and reusability over repeated use and can be easily scaled for efficient clean-up of a large number of toxic dyes and oil spills present in water. Studies also exposed that the gel column can simultaneously separate dye molecules and mineral oils from water. This simple, green, and efficient method overcomes a nontrivial hurdle for environmentally safe separation of toxic dyes as well as oil/water mixtures and offers insights into the design of advanced materials for practical oil/water separation.

The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role. ### Competing Interest Statement The authors have declared no competing interest.

In this work, four pyridine-based gemini and hetero-gemini gelator molecules have been designed which demonstrated aggregate-induced enhanced emission (AIEE) after gel formation in a DMSO/DMF:H2O mixture. This AIEE effect was brought down after the addition of 0.01 M NaOH solution, but the AIEE intensity was regained after the addition of 0.01 M HCl solution. This occurrence makes an organogel to act as a hydroxyl ion sensor. The different characteristics of organogels were studied by numerous methods, for example, spectroscopy, rheology, X-ray diffraction, theoretical study, and SEM. These organogels have the ability to detect the toxic metal ions Pb(II) and Cd(II). The detection limit of the organogels has been found to be lesser than the permitted limit of Pb(II) and Cd(II) in water. In addition to the detection ability studied, organogels showed the absorbing and elution capacities of Pb(II) and Cd(II) ions. This efficacy implied that organogels can be utilized to detect and eliminate toxic metal ions from contaminated water. Besides this property, gelator molecules exhibit catecholase-type activity. The high rate of catalytic efficacy of the studied compounds was confirmed by high Kcat values. In this study, we first proposed that without the presence of any transition-metal atom, pyridine-based gelator molecules showed efficient catechol oxidase activity.

The sugars streptose and dihydrohydroxystreptose (DHHS) are unique to the bacteria Streptomyces griseus and Coxiella burnetii, respectively. Streptose forms the central moiety of the antibiotic streptomycin, while DHHS is found in the O-antigen of the zoonotic pathogen C. burnetii. Biosynthesis of these sugars has been proposed to follow a similar path to that of TDP-rhamnose, catalyzed by the enzymes RmlA, RmlB, RmlC, and RmlD, but the exact mechanism is unclear. Streptose and DHHS biosynthesis unusually requires a ring contraction step that could be performed by orthologs of RmlC or RmlD. Genome sequencing of S. griseus and C. burnetii has identified StrM and CBU1838 proteins as RmlC orthologs in these respective species. Here, we demonstrate that both enzymes can perform the RmlC 3’’,5’’ double epimerization activity necessary to support TDP-rhamnose biosynthesis in vivo. This is consistent with the ring contraction step being performed on a double epimerized substrate. We further demonstrate that proton exchange is faster at the 3’’-position than the 5’’-position, in contrast to a previously studied ortholog. We additionally solved the crystal structures of CBU1838 and StrM in complex with TDP and show that they form an active site highly similar to those of the previously characterized enzymes RmlC, EvaD, and ChmJ. These results support the hypothesis that streptose and DHHS are biosynthesized using the TDP pathway and that an RmlD paralog most likely performs ring contraction following double epimerization. This work will support the elucidation of the full pathways for biosynthesis of these unique sugars.

The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.

Boronic acid based amphiphiles are new generation green surfactant materials because they degrade to produce environmentally friendly boric acid. This study describes the interfacial property as well as aggregation behaviour of two pyridine based boronic acid amphiphiles containing amide linkage in hydrocarbon chain named sodium salt of 2-amidodecyl pyridine-5-boronic acid (SADPB) and sodium salt of 2-amidododecyl pyridine-5-boronic acid (SADDPB). Tensiometry study was executed for investigation of interfacial properties of pyiridine based boronic acid derivatives. Polarity and viscosity of the microenvironment of aggregates was investigated using fluorescence technique. DLS measurement suggested size of the assemblies of SADDPB is larger than SADPB in solutions. XRD technique was employed to examine arrangement of the hydrophobic tails in the bilayer aggregates. TEM technique was utilised to scrutinize aggregate morphology in solutions. The findings showed prospect of these amphiphiles to be applicable as drug carrier in pharmaceutical industries.

N -acetyl-D-glucosamine (GlcNAc) is a major component of bacterial cell walls. Many organisms recycle GlcNAc from the cell wall or metabolise environmental GlcNAc. The first step in GlcNAc metabolism is phosphorylation to GlcNAc-6-phosphate. In bacteria, the ROK family kinase NagK performs this activity. Although ROK kinases have been studied extensively, no ternary complex showing the two substrates has yet been observed. Here, we solved the structure of NagK from the human pathogen Plesiomonas shigelloides in complex with GlcNAc and the ATP analogue AMP-PNP. Surprisingly, Ps NagK showed two conformational changes associated with the binding of each substrate. Consistent with this, the enzyme showed a sequential random enzyme mechanism. This indicates that the enzyme acts as a coordinated unit responding to each interaction. Molecular dynamics modelling of catalytic ion binding confirmed the location of the essential catalytic metal. Site-directed mutagenesis confirmed the catalytic base, and that the metal coordinating residue is essential. Together, this study provides the most comprehensive insight into the activity of a ROK kinase. ### Competing Interest Statement The authors have declared no competing interest.

Gelation performances of three synthesized short tripeptide based amphiphiles [11-(2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-undecanoylamino]-acetic acid TBMBUA (A), [11-(2-tert-Butoxycarbonylamino-3-methyl-pentanoylamino)-undecanoylamino]-acetic acid TBMPUA (B) and [11-(2-tertButoxycarbonylamino-3-phenyl-propionylamino)-undecanoylamino]-acetic acid TBPPUA (C) have been investigated. The results recommended that these can act as good hydrogelators. Various instrumental techniques like Field Emission Scanning Electron Microscopic (FE-SEM) and high resolution Transmission Electron Microscopic (HR-TEM) imaging for morphological analyses of hydrogel, X-ray Diffraction analyses to know packing pattern of gelators in the assembled state, Fourier Transformed Infrared Spectroscopic (FT-IR) measurements to execute role of hydrogen bonding in the gel morphology and rheological experiments for investigation of mechanical stability were carried out to characterize the hydrogels. Prepared hydrogels were employed for entrapment and release of Vitamin B12 and Doxorubicin, an anticancer drug molecule. The study revealed that the release capacity is dependent on pH of the medium. Synthesized hydrogelators (TBMBUA, TBMPUA and TBPPUA) showed anticancer activity by exhibiting in vitro cytotoxicity against the human breast cancer cell line (MCF-7 cell) as well as in-vivo cancer cell line (EAC cell) using MTT assay. The gelators did not exhibit any notable lethality towards normal human lymphocytes up to the concentration of 25 ?g/ml. These results propose that the utilization of hydrogelators for localized breast cancer therapy may have a high therapeutic potential.

Low molecular weight organic gelators (LMOGs) have received great attention for their tremendous applications in multiple fields in the past few decades. Therefore, nowadays, synthesis of new type of LMOGs is a demanding field of research. In this work, the effect of hydrophobic moiety on gelation behavior of three synthesized pyridyl boronic acid-derived amphiphiles named sodium, 2-decylpyridine-5-boronate (SDPB), sodium, 2-oxydecylpyridine-5-boronate (SODPB) and sodium, 2-oxydodecylpyridine-5-boronate (SODDPB) has been investigated. The results confirmed that these amphiphiles are good gelators in common organic solvents in the presence of 60 μl of buffer solution and the gelation capability diminished in case of oxygen atom present in the alkyl chain. Further distortion of gelation process was observed with increase of chain length in oxy-alkyl chain. Rheological measurements established that the gel emulsion of SDPB is most stable towards external forces with highest elasticity value. XRD study was performed to analyze the orientation of the alkyl chain in the 3D network structure in the gel emulsions. The morphological changes with respect to concentration were investigated by FE-SEM study of the gel emulsions. The prepared gel emulsions with these amphiphiles are capable to entrap and release the biomolecule vitamin B12 at room temperature keeping the structure and activity unchanged which is indicative that the amphiphiles can be successfully utilized in pharmaceutical industries as drug delivery vehicles.

In this work, we reported hydrogen bonding-induced gelation performance of three benzenesulphonamido-based anionic amphiphiles. The self-assembled gel forms well-defined morphology which typically entrap and release vitamin B 12 with retention of activity at room temperature. The studied sulphonamido-based amphiphiles successfully form gel emulsion in several organic solvents when a critical amount of water is present. FT-IR, 1 H-NMR and computational studies revealed hydrogen bonding between sulphonamide and amide groups are the prime factors to form and preserve the gel-network structures. The mechanical strength, elasticity and gelation property of the gel emulsion are enriched by increasing hydrogen bonding site and hydrophobicity of the head group. XRD study exhibited ordered non-interdigited lamellar arrangement in the gel state. The outcomes of this study are a new addition in the field of sulphonamido-based low-molecular-mass gelators having attractive gelation abilities. Graphic abstract

Formation of nanofibers and nanovesicles in the self-assembled state of small amphiphilic molecules has applications in versatile fields such as tissue engineering, controlled delivery of drug molecules, etc. This paper demonstrated the self-aggregation behavior of three synthesized 6-acylamino nicotinic acid amphiphiles named 6-octanoylamino-nicotinic acid (OANA), 6-decanoylamino-nicotinic acid (DANA) and 6-dodecanoylamino-nicotinic acid (DDANA) in water and basic aqueous solution. The result showed that the amphiphiles successfully self-organize into vesicles and twisted ribbons in water. FT-IR study revealed existence of mixtures of handedness in the fibrous structures. CD spectroscopy and TEM study elucidated formation of chiral structures through aggregation. Results showed that DDANA forms thermoreversible hydrogel in aqueous solutions of NaOH and Na 2 CO 3 , whereas other two amphiphiles form hydrogel only in the presence of NaOH. Morphological investigation revealed that the hydrogel is formed due to self-assembly of fibrils of micron length. The elastic fibrillar networks are quite stable to external forces. Existence of bilayer columnar square packing arrangement in the self-assembled state was recognized by XRD measurement. Spectroscopy and theoretical studies established that hydrogen bonding interactions are responsible to self-assemble the amphiphilic molecules. The amphiphiles are efficient phase selective gelators of mineral oils in water–mineral oil mixtures and excellent remover of rhodamine 6G, eosin Y and rose bengal from water. The amphiphiles successfully create reproducible fiber mat applicable in tissue engineering field. Graphic abstract