Fluorescent Sensors for Tetracycline Detection in Aqueous Medium: A Mini-Review.

Tetracycline (TC) is a commonly used antibiotic in human therapy and animal husbandry. Public concerns about TC residues inflated due to their negative impact on the environment, food, and human health concerns. To ensure human health and safety, there is a need for fluorogenic chemosensors that can easily detect TC antibiotics with high selectivity and sensitivity in the aqueous medium. This mini-review discusses the progress and achievements in several fluorometric antibiotic tetracycline detection methods. Fluorogenic chemosensors for tetracycline antibiotics with easy-to-use, high selectivity, and sensitivity have been essentially required to regulate food safety and secure human health and safety. Moreover, we gave more attention to the practical applicability of chemosensors for tetracycline antibiotics in food and water quality assessment. This article starts with a section that constitutes an overview of the problems of antibiotics and the typical features of traditional techniques of antibiotic detection. It then goes on to describe up-to-date optical methods for the selective detection and efficient removal of TC. These methods involve a variety of platforms, like tetraphenylethylene polymers, metal complexes, self-assembled CuNCs, and hydrogel. The article also discusses the practical applicability of chemosensors for tetracycline antibiotics in food and water quality.

Luminogenic and Bactericidal Studies of an Acrylonitrile-Based AIEgen.

We have synthesized an aggregation-induced emissive molecule that exhibits promising photophysical characteristics. The aggregating aptitude is demonstrated by binary solvent mixture and it is emissive in both solution and solid state. The luminogenic characteristics are employed in creating fluorescent inks as well as for the detection of nitro antibiotics in biofluids and in solid support. Moreover, the acrylonitrile-based compound is bactericidal tested on E. coli and B. subtilis.

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.

Amphiphilic polyphenol incorporated hydrogel derived from mucoadhesive of Dillenia indica: Potential antioxidant and adsorbent.

In this work, the mucoadhesive substances from the fruits and seeds of Dillenia indica (DI), a plant present abundantly in India, have been extracted and utilised to prepare a hydrogel. A synthetically prepared amphiphilic polyphenol (L) has been incorporated within the hydrogel network to enhance the hydrogelation property. Moreover, the DI-L hydrogel's total phenolic content and radical scavenging prospects have been investigated. The DI-L hydrogel has shown good, sensitive, and efficient adsorptive removal of Fe(III) from the aqueous medium with an adsorption capacity of 6.157 mg/g for an initial concentration of 10 mg/L of Fe(III) solution. As a result, these findings elucidate the most innovative application of transforming fruit mucoadhesive into sustainable environmental solutions.

Naphthalimide-based AIE-active receptor: HSO4-/SO42- sensing and detection of Pb2+ by receptor-anion ensemble in aqueous medium.

Herein we report a naphthalimide-chromophore based blue light emitting Aggregation-Induced Emission (AIE) active fluorescent chemo-sensor for the selective turn-on fluorescent sensing of HSO4-/SO42- ions in the aqueous medium through in-depth spectroscopic and microscopic analysis. HSO4-/SO42-sensing in aqueous environment is quite challenging due to its high hydration energy, however Nap-1 showed a detection limit down to the micromolar range without any interference from the other tested competitive anions. The sensing mechanism has been discussed thoroughly. Nap-1 was further applied in detection of HSO4-/SO42- ions in real water as well as in fabrication of an economical paper strip model. The receptor-anion ensemble was further used for the sensing of heavy metal ions such as Pb2+ in the micromolar range. Nap-1 was used for the construction of two inputs INHIBIT type molecular logic gate.

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.

Fluorescent Probes for Detection of Environmental Contaminants (NACs & VOCs): Probe Design from a Supramolecular Perspective.

Fresh air and clean water are essential constituents for the human population as well as for fauna and flora. Owing to the extreme toxicity of NACs and VOCs in physiological systems and their widespread presence in the environment, serious mitigation is required. The innovation of chemosensors for these two types of harmful organic contaminants (NACs i. e., nitroaromatics, and VOCs i. e., volatile organic compounds) have unfolded as a key research topic in recent decades, garnering a lot of attention due to their environmental, industrial and biological importance. In recent years, there has been a significant amount of research on both NACs and VOCs chemosensors. This Review article has recapitulated the latest development of fluorescent chemosensors especially small molecular frameworks from 2015 to 2022, for NACs and VOCs which has been discussed individually. In addition, the detection of NACs and VOCs on multiple platforms with a special focus on their mechanistic exploration, as well as their probable applications in natural water body specimens, vapor phase detection, and paper strip analysis have also been discussed.

Anthraquinone-Based Ligands as MNase Inhibitors: Insights from Inhibition Studies and Generation of a Payload Nanocarrier for Potential Anti-MRSA Therapy.

The present study highlights the prospect of an anthraquinone-based ligand (C1) as an inhibitor of micrococcal nuclease (MNase) enzyme secreted by Staphylococcus aureus. MNase inhibition rendered by 5.0 µM C1 was ∼96 % and the ligand could significantly distort the ß-sheet conformation present in MNase. Mechanistic studies revealed that C1 rendered non-competitive inhibition, reduced the turnover (Kcat ) and catalytic efficiency (Km /Kcat ) of MNase with an IC50 value of 323 nM. C1 could also inhibit nuclease present in the cell-free supernatant (CFS) of a methicillin-resistant Staphylococcus aureus (MRSA) strain. A C1-loaded human serum albumin (HSA)-based nanocarrier (C1-HNC) was developed, which was amicable to protease-triggered release of payload in presence of the CFS of an MRSA strain. Eluates from C1-HNC could effectively reduce the rate of MNase-catalyzed DNA cleavage. The non-toxic nature of C1-HNC in conjunction with the non-competitive mode of MNase inhibition rendered by C1 offers interesting therapeutic prospect in alleviation of MRSA infections.

Quinoxaline-based membrane-targeting therapeutic material: Implications in rejuvenating antibiotic and curb MRSA invasion in an in vitro bone cell infection model.

Manifestation of resistance in methicillin-resistant Staphylococcus aureus (MRSA) against multiple antibiotics demands an effective strategy to counter the menace of the pathogen. To address this challenge, the current study explores quinoxaline-based synthetic ligands as an adjuvant material to target MRSA in a combination therapy regimen. Amongst the tested ligands (C1-C4), only C2 was bactericidal against the MRSA strain S. aureus 4 s, with a minimum inhibitory concentration (MIC) of 32 µM. C2 displayed a membrane-directed activity and could effectively hinder MRSA biofilm formation. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that C2 downregulated expression of the regulator gene agrC and reduced the fold change in the expression of adhesin genes fnbA and cnbA in MRSA in a dose-dependent manner. C2 enabled a 4-fold reduction in the MIC of ciprofloxacin (CPX) and in presence of 10 µM C2 and 8.0 µM CPX, growth of MRSA was arrested. Furthermore, a combination of 10 µM C2 and 12 µM CPX could strongly inhibit MRSA biofilm formation and reduce biofilm metabolic activity. The minimum biofilm inhibitory concentration (MBIC) of CPX against S. aureus 4 s biofilm was reduced and a synergy resulted between C2 and CPX. In a combinatorial treatment regimen, C2 could prevent emergence of CPX resistance and arrest growth of MRSA till 360 generations. C2 could also be leveraged in combination treatment (12 µM CPX and 10 µM C2) to target MRSA in an in vitro bone cell infection model, wherein MRSA cell adhesion and invasion onto cultured MG-63 cells was only ~17 % and ~ 0.37 %, respectively. The combinatorial treatment regimen was also biocompatible as the viability of MG-63 cells was high (~ 91 %). Thus, C2 is a promising adjuvant material to counter antibiotic-refractory therapy and mitigate MRSA-mediated bone cell infection.

The Psychological Impact of Rhino-Orbital Mucormycosis During the Second Wave of COVID-19 Pandemic From South East Asian Country.

AIM: The present study addressed overcoming the lacunae in the literature of psychiatric manifestations associated with rhino-orbital mucormycosis. The current study aimed to assess the symptoms of depression, anxiety, stress, coping measures, suicidal intent, and visual disability in patients of rhino-orbital mucormycosis (ROM) during the epidemic of the disease at the nodal tertiary care center in North India. METHODS: Fifty-four inpatients of laboratory-proven rhino-orbital mucor-mycosis (ROM) were included for an observational, cross-sectional study at nodal, designated COVID-19, and mucormycosis treating tertiary care hospital. Patients with Hindi Mini-Mental State Examination score <24, prior psychiatric illness, and severely ill requiring ventilator support were excluded. The psychological variables were assessed using Depression, Anxiety, and Stress Scale 21 (DASS 21), Beck's Suicide intent Scale, Coping Scale Questionnaire, and Visual disability scale (IND-VFQ33). Their socioeconomic status was assessed using the Modified Kuppuswamy Scale. RESULTS: Ninety percent of patients with ROM had diabetes mellitus. The majority (44%) of patients belonged to lower socioeconomic strata. Higher frequencies of severe depression (28%), extremely severe anxiety (26%), and mild stress (17%) were noted in the study participants. On the Tukey test, depression score was higher in patients of ROM compared to COVID (with ROM) (p-value= 0.016). On Tukey analysis, anxiety score was significantly higher in ROM patients compared to COVID (with ROM) patients (p-value = 0.018). Coping scores were significantly higher in COVID (with ROM) patients compared to ROM patients (p value = 0.035). Mild to moderate visual disability was noted in the study participants.  Conclusion: The current study reflects the association of higher depression and anxiety scores in cases with ROM that indicated higher mental health needs. Early assessment, early detection, and early intervention for psychological help, along with the multidisciplinary team, helped to improve the overall psychological outcome of the affected patients.

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.

Quinoxaline-probe embedded injectable fluorogenic hydrogels: Comparative detection of mesitylene in guar gum and i-carrageenan hydrogels.

The innovation of novel chemosensor probes for the recognition of trace volatile organic compounds is critical due to their hazardous effect on the environment and human health. A nitro-group integrated quinoxaline probe with a profound discriminative fluorescence 'turn-on' response to mesitylene was fabricated into guar gum and i-carrageenan, two biopolymer-based hydrogel matrices, to develop compact, portable fluorogenic hydrogel sensors and assess their fluorescence properties. A comparative characterization-based analysis of native, probe-associated, and probe-analyte-associated hydrogels, (comprising of FT-IR, XRD, TGA) was investigated to ascertain the overall compatibility of the hydrogel-based sensors for use as a smart rapid detection tool. Dynamic rheological measurements also validated the mechanical stability and robustness of the developed hydrogel matrices. Fluorescence spectroscopic investigations yielded promising results of 0.15 ppm limit of detection (LOD) in guar gum and 0.29 ppm LOD in i-carrageenan hydrogels respectively. FESEM and Fluorescence microscopy studies represented the morphological variations of the hydrogel sensors on interaction with mesitylene. The practical feasibility of the chemosensor in hydrogel form for mesitylene detection in the vapor phase was also explored. Probe-embedded hydrogels with injectable property was shown, depicting its use as security ink for information encryption functions. This approach of incorporating chemosensors into biobased hydrogel networks has the potential to broaden its opportunities in the field of chemical, biomedical, and environmental sensing sectors.

Low Dose Atropine in Preventing the Progression of Childhood Myopia: A Randomised Controlled Trial.

PURPOSE: To study the efficacy of low dose atropine (0.01%) eye drops in preventing myopia progression in children by comparing the mean change in spherical equivalent (diopter) and axial length (mm) over a period of one year to a control group and study its effect on near vision, pupil size, keratometry and pachymetry. METHODS: 200 eyes of 100 myopic children were randomized into two groups based on a computer-generated random number table. The treatment group was administered 0.01% atropine eye drop once at bedtime and control group was administered a placebo. The follow up was done 3-monthly for 12 months by assessing the mean change in spherical equivalent and mean change in axial length. Other parameters like near vision, pupil size, keratometry and pachymetry were assessed at each follow up. RESULT: The study was age and sex matched. The mean change in spherical equivalent refraction and axial length was significantly lower in the treatment group (0.31 ± 0.55 D; 0.11 ± 0.22 mm) than the placebo group (0.80 ± 1.65 D; 0.23 ± 0.44 D) (p-value: 0.003). Less steepening of the corneal curvature was observed in the treatment group (0.16 ± 0.28 D vs 0.29 ± 0.3 D; p < 0.001) and the mean change in pachymetry was comparable between the groups (0.00 ± 0.01) (p-value 0.489). No significant change was seen in near vision (96% of the eyes with atropine had no change in near vision; 2% of the eyes had a change of near vision by one line (p-value 0.500); 2% had a change by 3 lines (p-value: 0.07) or pupil size following treatment. CONCLUSION: The use of 0.01% atropine eye drop reduced the progression of myopia over the study period of one year with no significant changes in near vision, pupil size. No patient reported any systemic and local side effects with administration of 0.01% atropine eye drop.

Retrospective analysis of the role of retrobulbar amphotericin-B injection in the management of COVID-19 associated rhino-orbito-cerebral-mucormycosis.

Introduction: Rhino-orbito-cerebral-mucormycosis (ROCM) is the most common form of mucormycosis observed during the second wave of COVID-19 where a steep rise in the number of cases was seen. The orbital form is almost always associated with fungal sinusitis. Among the various treatment modalities available, the role of retrobulbar Amphotericin-B injections is under-reported. This study is conducted to determine the role of transcutaneous retrobulbar amphotericin-B (TRAMB) in the management of COVID-19 associated ROCM. Methods: a retrospective analysis of 61 patients of COVID-19 associated ROCM was done, who met the inclusion criteria and presented to a tertiary care center, between May to August 2021. These patients were administered TRAMB (deoxycholate/emulsion form) along-with systemic amphotericin B. All the patients were evaluated for clinical improvement. Results: out of 61 patients, 58 (95.08%) showed overall improvement. 40 patients (65.57%) stabilized or improved clinically and 3 patients succumbed to the illness due to advanced systemic mucormycosis and acute kidney failure. Sixteen out of 58 patients underwent orbital exenteration. Out of remaining 43 patients, 35 showed complete recovery of orbital and ocular disease and the disease stabilized in eight patients. Seven patients demonstrated TRAMB associated ocular complications which however completely resolved in six patients. Conclusion: to the best of the author´s knowledge, regression of orbital mucormycosis with improvement in ptosis, proptosis, ocular motility and stabilization of visual acuity are scarcely reported in literature. Further TRAMB as a globe non-deforming treatment modality is an option available for ROCM.

Spectral Domain Optical Coherence Tomography Findings in Vision-Threatening Rhino-Orbital Cerebral Mucor Mycosis-A Prospective Analysis.

Rhino-orbital cerebral mucor mycosis is a rare disease entity, where retinal involvement is described in the literature mostly as CRAO. However, pathological studies have shown mucor invading the choroid and retina with a neutrophilic reaction. So, it is pertinent that retinal inflammation secondary to invading mucor has some role in microstructural changes seen in the vitreous and retina of these patients. This novel study aims to describe the vitreal and retinal features of patients with vision-threatening rhino-orbital cerebral mucor mycosis and how they evolve on spectral domain optical coherence tomography (SD-OCT). This study shall also provide insight into the pathophysiology of these vitreoretinal manifestations by in vitro analysis of the exenterated orbital content. Fifteen eyes of fifteen patients with vision-threatening ROCM treated with standard care were enrolled in this study and underwent complete ophthalmic examination, serial colour fundus photography, and SD-OCT for both qualitative and quantitative analysis, at baseline and follow-up visits. SD-OCT on serial follow-up revealed thickening and increased inner-retinal reflectivity at presentation followed by thinning of both, other features such as the loss of the inner-retinal organized layer structure, external limiting membrane (ELM) disruption, necrotic spaces in the outer retina, and hyperreflective foci. Vitreous cells with vitreous haze were also seen. There was a significant reduction in CMT, inner and outer retinal thickness, total retinal thickness (all p < 0.05) with time, the quantum of reduction concentrated primarily to the inner retina. In summary, in vivo and in vitro analysis revealed that early microstructural changes were primarily a result of retinal infarctions secondary to thrombotic angioinvasion. With the late microstructural changes, there was possible sequelae of retinal infarction with some contribution from the inflammation, resulting from mucor invading the choroid and retina.

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.

Amine-incorporated quinoxaline based fluorescent sensor for detection of trace water: Solvent influenced self-assembly.

Polarity is a complex parameter, with important effect in chemistry and biology. In recent years, polarity exploration attracted more and more attention hence, it's of great importance to exploit new methods for polarity determination. A novel class of long, coplanar, and amine incorporated electron-rich quinoxaline scaffold(L1) furnished maximum solvatochromic effect and large Stokes shift and was chosen to determine water content in organic solvents e.g. acetonitrile, THF, DMF, and methanol through fluorescence spectroscopy. Moreover, the probe was found to perform as an effective fluorescent sensor for the quantitative detection of low-level moisture content in four commonly-used organic solvents with low detection limits (0.018%, 0.027%, 0.012%, and 0.43% respectively). This study also describes the morphological transformation of L1 form a fibrous network to spherical aggregates upon increasing water content in several organic solvents. Real-life implementation of the probe was successfully employed for the detection of moisture content in commercial food products and building materials such as cement, sand, limestone, salt, wheat, and detergent powder. Furthermore, probe L1-immersed easy-to-prepare test strips provide a reliable approach for qualitative monitoring of water content in organic solvents by a simple color-changing method under UV irradiation via smartphone-assisted RGB analysis.

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.

Urea-Based Ligand as an Efflux Pump Inhibitor: Warhead to Counter Ciprofloxacin Resistance and Inhibit Collagen Adhesion by MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frontline human pathogen in which efflux pump activity confers high levels of antibiotic-resistance and poses a therapeutic challenge in the clinics. The present study illustrates the potential of urea-based ligand as an efflux pump inhibitor (EPI) in order to restore the efficacy of ciprofloxacin (CPX) against MRSA. Among eight structurally varying urea-based ligands, the ligand C8 could significantly inhibit efflux pump activity in the clinical MRSA strain S. aureus 4s and was superior to the known EPI reserpine. In combinatorial treatment, C8 enhanced cellular accumulation of CPX, rendered a 16× decrease in the MIC of CPX, and restored the susceptibility of S. aureus 4s to CPX. Notably, C8 downregulated the expression of norA gene coding for the efflux pump in MRSA and treatment with 10 µM C8 and 2.0 µM CPX prevented emergence of the CPX resistance trait and suppressed MRSA cell growth till 120 generations. For potential anti-MRSA therapy, C8-loaded poly(d,l-lactide-co-glycolide) nanocarrier (C8-PNC) was generated, which facilitated facile release of C8 in physiologically relevant fluid. C8-PNC (loaded with 50 µM C8) rendered efflux pump inhibition and eliminated MRSA in combination with only 2.0 µM CPX. Treatment with the non-toxic C8-PNC (loaded with 50 µM C8) and CPX (2.0 µM) also hindered MRSA adhesion on collagen manifold higher as compared to cells treated with 32 µM CPX and significantly downregulated norA gene expression in non-adhered MRSA cells. The urea-based ligand presented herein is a promising biocompatible therapeutic material for effective mitigation of MRSA infections.