Exploring the gelation and AIE properties of a tripodal acylhydrazone-based probe: turn-on Zn(II) sensing in HEPES buffer.

Two C3-symmetric acylhydrazone-based AIE active probes, TRI-QUI and TRI-NAP, were synthesized with different peripheral substituents. The probe containing a quinoline moiety in the periphery displayed a selective turn-on response towards Zn2+ in HEPES buffer, with a calculated detection limit of 6.45 µM. The probe TRI-QUI was also identified as a supergelator as it formed a gel in DMSO-H2O (2 : 3, v/v) with a minimum gelation concentration of 0.5 mg mL-1. The gelator could interact with various metal ions or anions in the gel phase. Furthermore, the gelator could encapsulate small molecules like methyl orange and bromophenol blue, making the probe a multifunctional smart material.

Inhibition of staphylococcal nuclease by benzimidazole-based Ligand: Implications in DNA-Mediated entrapment and uptake of MRSA by Macrophage-like cells.

The staphylococcal nuclease also referred as micrococcal nuclease (MNase) is a key drug target as the enzyme degrades the neutrophil extracellular trap (NET) and empowers the pathogen to subvert the host innate immune system. To this end, the current study presents a critical evaluation of MNase inhibition rendered by benzimidazole-based ligands (C1 and C2) and probes its therapeutic implications. A nuclease assay indicated that MNase inhibition rendered by C1 and C2 was âˆ¼ 55 % and âˆ¼ 72 %, respectively, at the highest tested concentration of 10 µM. Studies on enzyme kinetics revealed that C2 rendered non-competitive inhibition and significantly reduced MNase turnover number (Kcat) and catalytic efficiency (Kcat/Km) with an IC50 value of âˆ¼ 1122 nM. In CD spectroscopy, a notable perturbation in the ß-sheet content of MNase was observed in presence of C2. Fluorescence-microscope analysis indicated that MNase inhibition by C2 could restore entrapment of methicillin-resistant Staphylococcus aureus (MRSA) in calf-thymus DNA (CT-DNA). Flow cytometry and confocal microscope analysis revealed that uptake of DNA-entrapped MRSA by activated THP-1 cells was reinstated by MNase inhibition rendered by C2. Inhibition of nuclease by the non-toxic ligand C2 holds therapeutic prospect as it has the potential to bolster the DNA-mediated entrapment machinery and mitigate MRSA infections.

Carbazole-Derived Amphiphile-Based AIEgen: Detection of Nitro-Antibiotics and Water-Repelling Surfaces.

We have designed three amphiphilic substituted urea compounds with varying chain lengths. These hydrophobic amphiphiles displayed aggregation-induced emission on solvent switching. The aggregates were further detailed by microscopy. The hydrophobicity of these AIEgens has been used to create water-repelling fluorescent surfaces. The AIEgen via the photoinduced electron transfer-mediated mechanism has been applied in the detection of nitroantibiotics. The analytical utility of the AIEgen is being demonstrated concerning the detection of nitroantibiotics in biofluids.

Surfactant-induced disaggregation of a quinoxaline AIEgen scaffold: aggregation aptitude in the solid and solution states.

We have designed five propellor-shaped molecules based on the quinoxaline scaffold with a functional group variation. They exhibit aggregation-induced emission, and the responses of these congeners regarding good solvents and poor solvents are investigated both spectroscopically and microscopically. Solid- as well as solution-state parallel analysis of the aggregation facet is laid out. Notably, L2 interacts specifically with a cationic surfactant, unlike other congeners where the mechanism proceeds via disaggregation. Real sample analysis was carried out on freshwater samples as well as waste effluent samples from domestic households and industries, thus projecting the analytical and environmental significance.

Exploring the Aggregation and Light-Harvesting Aptitude of Naphthalimide-Based Amphiphile and Non-amphiphile AIEgen.

Herein, we report a comparative study of two naphthalimide-tethered amphiphile and non-amphiphile with their aggregation-induced emission properties. A synthetic modulation of a hydrophobic tail on the framework repressed the ACQ-phoric fluorophore to an AIEgen. L1 and L2 remain in the dispersed form in DMF and exhibits aggregation and intense emission signal in aqueous media. Microscopy detailing of the aggregating process has been analyzed. Not only the AIEgens are emissive in water but also they are emissive in the solid state. The natural light-harvesting process is mimicked by the aggregated state, establishing an energy transfer process between L1 and commercial dye. Disaggregation of the AIEgen has also been utilized in the detection of nitroaromatics. Analytical utility of the AIE-gen is being demonstrated concerning the detection of explosives in aqueous media.

Fashionable Co-operative Sensing of Bivalent Zn2+ and Cd2+ in Attendance of OAc- by Use of Simple Sensor: Exploration of Molecular Logic Gate and Docking Studies.

The Schiff-base probe H2VL [6,6'-((1E,1'E)-hydrazine-1,2 diylidenebis(methanylylidene))bis(2-methoxyphenol)] is synthesized and structurally characterized by single crystal X-ray diffraction (SCXRD). H2VL is able to detect selectively acetate ion (OAc-) colorimetrically over other anions with 1:1 co-ordination. The detection limit is found to be 4.93 µM. On the other hand, fluorescence intensity of the receptor is drastically enhanced with Zn2+ and Cd2+ in the presence of acetate as counter anion. N, N-Dimethyl formamide (DMF) or Dimethylsulphoxide (DMSO) and acetate (OAc-) was the best solvent and counter anion for Zn2+/Cd2+ -sensing compared with other solvents and anions, respectively. Detection limit for Zn2+ and Cd2+ are calculated to be 1.94 µM and 1.99 µM, respectively. The strong selective emissive behavior could be attributed to the CHEF (chelation-enhanced fluorescence) process. According to the changes in output emission intensity in DMSO in response to the set of ions (Zn2+, Cd2+ and OAc¯) as input variables, the function of 3-input multifunctional molecular logic circuits has been demonstrated. The molecular docking studies of H2VL with DNA and BSA are also performed to confirm its possible bioactivity.

Risk factors for severe rhino-orbital mucormycosis during its epidemic post-COVID-19 pandemic.

Postsecond wave of COVID-19 pandemic in the year 2021, rhino-orbital mucormycosis (ROM) was seen as an epidemic in the Indian community. Severe ROM disease has poor prognosis and requires a multidisciplinary approach for treatment. Hence, its prevention is better than cure. Studies done during the epidemic assessed predisposing factors, but this was a novel study which focused on assessing risk factors for severe disease of ROM. Ninety-four consecutive patients of ROM admitted at our designated nodal tertiary hospital of North India were enrolled, and data were collected and analyzed. Facial edema was the most common presenting complaint. Subclinical and mild COVID-19 infection was associated with severe ROM. Uncontrolled diabetes mellitus and prophylactic zinc supplementation were other significant risk factors for severe ROM. Public awareness among the general population for the above risk factors can prevent a debilitating disease like severe ROM.

Nailfold capillary changes in newly diagnosed hypertensive patients: An observational analytical study.

INTRODUCTION: Nail Fold capillaroscopy (NFC) is used to evaluate microvascular changes in the horizontally lying capillaries in the proximal nail fold. Arterial hypertension affects the microvascular beds producing structural changes. Our objective was to evaluate qualitative and quantitative NFC changes in newly diagnosed hypertensives as compared to age and sex matched normotensive controls and to determine association, if any, with microvascular changes visualized on fundoscopy. MATERIALS AND METHODS: This observational, analytical study involved 41 newly diagnosed hypertensives (18-60 years) with 41 normotensive age and sex matched normotensive controls. The mean capillary density (MCD) and morphological changes were assessed for all, while fundoscopy was done for study group participants. The collected data was statistically analyzed. RESULTS: The MCD in newly diagnosed hypertensives (5.21 ± 0.90 capillaries/mm) was significantly lower than normotensive controls (6.50 ± 0.65 capillaries/mm) (p < 0.001) in our study. Qualitative morphologic changes were more common in hypertensive patients including meandering capillaries, capillary dilation, avascular areas, bushy capillaries, and microhemorrhages (p value <0.001). Capillary disarray (73.17%) was a unique morphologic change seen significantly more commonly in study group (p < 0.001). Among hypertensives, MCD was lesser in patients with retinopathy (p = 0.125) and with microalbuminuria, while avascular areas and dilated capillaries were significantly more common. CONCLUSION: Our study supports the role of NFC with USB dermatoscope in detecting unique microvascular morphological alterations in hypertensives, which were more frequent as well as distinctive, as compared to healthy controls. A good correlation with fundoscopic features and microalbuminuria suggests that it could be useful in predicting/detecting cardiovascular, or renal complications early, with an advantage of easy accessibility and repeatability.

Supramolecular self-assembly of a nitro-incorporating quinoxaline framework: insights into the origin of fluorescence turn-on response towards the benzene group of VOCs.

Hazardous volatile organic compounds (VOCs) can significantly impact human health and the environment. Hence, the detection of VOCs is of foremost importance. A quinoxaline-based fluorimetric probe (1) unveils a notable "turn-on" fluorescence response towards mesitylene in the presence of other VOCs and common interfering ions in aqueous media. The sensing phenomenon involves specific 1 : 1 stoichiometric binding of the probe with mesitylene with a ∼2.66 ppm detection limit. Furthermore, the probe experiences morphological transformations from a fibril-network to a stone-shaped hetero-structure upon treatment with mesitylene, indicating mesitylene induced self-assembly. The detection induced self-assembly of the probe was further corroborated by dynamic-light-scattering (DLS) and fluorescence microscopy study. Importantly, this proposed approach is applicable to detect mesitylene in natural water sources and in the vapor phase using portable, low-cost filter paper strips.

Pandemics and marketing: insights, impacts, and research opportunities.

Pandemics have been an unfortunate but consistent facet of human existence over centuries, threatening lives as well as livelihoods globally. Disconcertingly, their frequency persists, with four "major" pandemics disrupting the planet in the last 65 years and more expected in the future. While many of the economic and health consequences of pandemics are well-documented, their marketing implications are less understood. Addressing this gap, we develop a broad, conceptual framework to highlight the characteristics and impacts of pandemics as they relate to marketing. We first identify four macro-level forces that characterize pandemics and highlight their marketing implications. Next, using the 7P marketing mix model as the organizing structure, we discuss these implications at a micro-level and identify a set of research questions to stimulate further inquiry, not only to generate deeper insights pertaining to pandemics' marketing implications but also to envision new developments in these areas. Finally, we identify pandemics' disproportionate impacts on and implications for some industry sectors, including healthcare, retail, education, hospitality, and tourism.

Interplay between Supramolecular and Coordination Interactions in Synthetic Amphiphiles: Triggering Metal Starvation and Anchorage onto MRSA Cell Surface.

The present work highlights the implications of supramolecular interaction and metal coordination on the self-assembly behavior and bactericidal potential of salicaldehyde-(C1) and napthaldehyde-based (C2) amphiphiles against methicillin-resistant Staphylococcus aureus (MRSA). LB trough and atomic force microscope (AFM) analysis indicated the propensity of the amphiphiles to form a monolayer as well as spherical aggregates, with the critical micelle concentration (CMC) for C2 (7.0 µM) being lower than C1 (18.5 µM) in water. Formation of an amphiphile-metal complex was evidenced by ESI-MS, FTIR, FETEM-EDX, and ITC analysis. Growth of S. aureus MRSA 100 cells was remarkably impaired in the presence of 5.0 µM C1 or 20 µM C2 as compared to free cells or cells grown in the presence of equivalent levels of amphiphile-metal complexes, suggesting that the amphiphiles perhaps sequester metal and induce metal starvation in MRSA. C1 and C2 rendered superior membrane damage in MRSA and were less toxic to human embryonic kidney (HEK 293) cells as compared to their metal complexes. C1 and C2 rendered a dose-dependent inhibition of S. aureus biofilm formation, while revival of biofilm upon Zn(II) addition suggested that zinc starvation rendered by the amphiphiles may induce biofilm inhibition. C1 imposed a concentration-dependent metal starvation response in MRSA as there was an upregulation of the cntL gene and downregulation of cntA gene, which are involved in synthesis of the zincophore staphylopine (Stp) and transport of the Stp-Zn complex, respectively. ITC analysis revealed that binding of C1 and C2 to staphylococcal lipoteichoic acid (LTA) was stronger than the corresponding Zn(II) complexes, which perhaps accounted for the higher bactericidal potency of the amphiphiles. The study provides a fundamental understanding on how the chemistry-driven multimodal interaction of the amphiphile translates into growth inhibition and metal starvation in MRSA and advances the idea of combating drug resistance in pathogenic bacteria through amphiphiles, which are pluri-active.

"Turn-on" Pb2+ sensing and rapid detection of biothiols in aqueous medium and real samples.

Detection of lead has continued to be of immense interest in the present industrial as well as environmental diaspora. To this end, we report a prudent Schiff base which enables the sensitive detection of Pb2+ ions in mixed aqueous medium. The probe is afforded by simple synthetic and purification processes. Further, the probe employs simple mechanistic detection of Pb2+ and also successively detects a host of biothiols. The sensor is also used to detect Pb2+ ions in real water samples and consecutive detection of a variety of biothiols, including functionalized thiouracils, in onion and garlic extract. The fact that the Pb2+-L ensemble is 'non-selective' towards any particular thiol substituted analyte in real samples could as well prove to be an interesting contribution for chemical and biological detoxification processes.

Exploring the potential of a urea derivative: an AIE-luminogen and its interaction with human serum albumin in aqueous medium.

A urea derivative L1 exhibits Aggregation-Induced Emission (AIE) activity in an acetonitrile-water mixed solvent. The aggregation phenomenon has been corroborated by microscopy and light scattering studies. The ligand (L1) also displays a selective turn-on fluorescence response towards human serum albumin (HSA) in 100% aqueous medium over various other comparable proteins (even bovine serum albumin (BSA)) and enzymes. The weakly emissive probe L1 showed a substantial increase in emission intensity upon binding with HSA through electrostatic interactions. The good linear relationship between the fluorescence enhancement (I/I0 - 1) and the concentration of HSA provided the scope to attain an impressive detection limit as low as 5 µg mL-1. A drug displacement experiment and molecular docking study were employed to ascertain the likely protein (HSA)-ligand binding interactions.

Twisted-Intramolecular-Charge-Transfer-Based Turn-On Fluorogenic Nanoprobe for Real-Time Detection of Serum Albumin in Physiological Conditions.

Two cyanine-based fluorescent probes, ( E)-2-(4-(diethylamino)-2-hydroxystyryl)-3-ethyl-1,1-dimethyl-1 H-benzo[ e]indol-3-ium iodide (L) and ( E)-3-ethyl-1,1-dimethyl-2-(4-nitrostyryl)-1 H-benzo[ e]indol-3-ium iodide (L1), have been designed and synthesized. Of these two probes, the twisted-intramolecular-charge-transfer (TICT)-based probe, L, can preferentially self-assemble to form nanoaggregates. L displayed a selective turn-on fluorescence response toward human and bovine serum albumin (HSA and BSA) in ∼100% aqueous PBS medium, which is noticeable with the naked eye, whereas L1 failed to sense these albumin proteins. The selective turn-on fluorescence response of L toward HSA and BSA can be attributed to the selective binding of probe L with HSA and BSA without its interfering with known drug-binding sites. The specific binding of L with HSA led to the disassembly of the self-assembled nanoaggregates of L, which was corroborated by dynamic-light-scattering (DLS) and transmission-electron-microscopy (TEM) analysis. Probe L has a limit of detection as low as ∼6.5 nM. The sensing aptitude of probe L to detect HSA in body fluid and an artificial-urine sample has been demonstrated.

Potential of Pyridine Amphiphiles as Staphylococcal Nuclease Inhibitor.

The present study explores the potential of pyridine-based synthetic amphiphiles C1 and C2 having 4-carbon and 12-carbon hydrophobic tails, respectively, as staphylococcal nuclease inhibitors. UV-visible titration with calf-thymus DNA (CT-DNA) revealed a hypochromic shift in the absorbance bands of C1 and C2, whereas fluorescence titration indicated a reduction in the emission intensity of the monomer bands of the amphiphiles. Interaction of deoxyribonuclease I (DNase 1) and micrococcal nuclease (MNase) with C1 or C2 led to a decrease in the emission intensity of tryptophan at λ=345 nm along with an increase in the monomer emission intensity of C1 and C2 at λ=375 nm for DNase I and excimer emission intensity at λ=470 nm for both DNase I and MNase. Scatchard's analysis indicated superior interaction of C2 with DNase I. Circular dichroism spectroscopy revealed major changes in the secondary structures of both DNase I and MNase upon interaction with the amphiphiles. A solution-based nuclease assay in conjunction with gel electrophoresis indicated amphiphile-mediated protection against nuclease-directed DNA cleavage. Interestingly, C2 could render inhibition of nuclease present in the culture supernatant of Staphylococcus aureus MTCC 96, which highlights the therapeutic prospect of the amphiphile against S. aureus.

Heavy metal removal from aqueous solution using sodium alginate immobilized sulfate reducing bacteria: Mechanism and process optimization.

Heavy metal removal was evaluated using sodium alginate immobilized sulfate reducing bacteria (SRB) under batch and continuous mode. Under batch conditions, more than 95% metal removal was achieved due to formation of insoluble metal sulfides exterior to the bead surface. Best heavy metal removal results were obtained at 48 h hydraulic retention time (HRT). Metal loading rate values upto 2.20 mg/L∙h for Fe(III), Zn(II), Cd(II), Pb(II) and Ni(II) and upto 4.29 mg/L∙h for Cu(II) were proved to be favorable for their removal using the continuous downflow column reactor packed with the immobilized SRB beads. Continuous metal removal from a mixture of the heavy metals showed that Cu(II) removal was maximum (99%), followed by Zn(II) (95.8%) and other metals at their respective low inlet concentrations. However, the removal values were reduced at a high inlet concentration of these metals, which matched well with low COD and sulfate reduction values.

A Nonbactericidal Zinc-Complexing Ligand as a Biofilm Inhibitor: Structure-Guided Contrasting Effects on Staphylococcus aureus Biofilm.

Zinc-complexing ligands are prospective anti-biofilm agents because of the pivotal role of zinc in the formation of Staphylococcus aureus biofilm. Accordingly, the potential of a thiosemicarbazone (compound C1) and a benzothiazole-based ligand (compound C4) in the prevention of S. aureus biofilm formation was assessed. Compound C1 displayed a bimodal activity, hindering biofilm formation only at low concentrations and promoting biofilm growth at higher concentrations. In the case of C4, a dose-dependent inhibition of S. aureus biofilm growth was observed. Atomic force microscopy analysis suggested that at higher concentrations C1 formed globular aggregates, which perhaps formed a substratum that favored adhesion of cells and biofilm formation. In the case of C4, zinc supplementation experiments validated zinc complexation as a plausible mechanism of inhibition of S. aureus biofilm. Interestingly, C4 was nontoxic to cultured HeLa cells and thus has promise as a therapeutic anti-biofilm agent. The essential understanding of the structure-driven implications of zinc-complexing ligands acquired in this study might assist future screening regimes for identification of potent anti-biofilm agents.

A ratiometric fluorogenic probe for the real-time detection of SO32- in aqueous medium: application in a cellulose paper based device and potential to sense SO32- in mitochondria.

A new water soluble and fluorogenic probe (L) that can demonstrate a specific ratiometric detection of a SO2 derivative (SO32-) in 100% aqueous medium and live cells has been designed and synthesized. The detection process can be visualized by the naked eye, as the orange-red fluorescence of L turns into a strong blue fluorescence upon interaction with SO32-. L displayed several beneficial attributes such as detection in complete aqueous medium, extremely fast response time along with high selectivity and sensitivity. The ratiometric sensing was attributed to the selective nucleophilic addition reaction of SO32- with L. The probe was further used to develop a low cost microfluidic sensor device (µPAD). The probe was biocompatible and its potential to sense SO32- in mitochondria was captured in live HeLa cells.

A multi-responsive turn-on flurogenic probe to sense Zn(2+), Cd(2+) and Pb(2+): left-right-center emission signal swing.

A versatile new fluorogenic Schiff base probe (L) has been synthesized by the reaction of quinoline-2-carbohydrazide (which acts as the chelating site) and 4-dimethylamino cinnamaldehyde (which acts as the signaling unit). L can sense three of the most biologically and environmentally important metal ions, Zn(2+), Cd(2+) and Pb(2+), among various tested metal ions through selective TURN-ON fluorescence responses in physiological pH. Interestingly, L can not only sense Zn(2+), Cd(2+) and Pb(2+) fluorometrically in physiological conditions but can also distinguish one from another by exhibiting individual intrinsic left-right-center TURN-ON emission signal swings. These selective fluorescence responses were explained by a chelation-enhanced fluorescence (CHEF) mechanism. Theoretical calculations were carried out to ascertain the preferred L-metal ion binding mode.

Colorimetric and fluorometric discrimination of geometrical isomers (maleic acid vs fumaric acid) with real-time detection of maleic acid in solution and food additives.

Heterobis imine Schiff base probe L is able to discriminate geometrical isomers (maleic acid vs fumaric acid) through sharp colorimetric as well as fluorogenic responses even conspicuous with the naked eye. Colorimetric as well as fluorogenic sensing of maleic acid among various carboxylic acids was also demonstrated in ethanol-buffer medium. Sensing behavior of L was corroborated by (1)H NMR spectra, mass spectrometry, and theoretical calculations. Subsequently sensing behavior of L was used to probe maleic acid in starch rich food samples.