Y-switch: a spring-loaded synthetic gene switch for robust DNA/RNA signal amplification and detection.

Nucleic acid tests (NATs) are essential for biomedical diagnostics. Traditional NATs, often complex and expensive, have prompted the exploration of toehold-mediated strand displacement (TMSD) circuits as an economical alternative. However, the wide application of TMSD-based reactions is limited by 'leakage'-the spurious activation of the reaction leading to high background signals and false positives. Here, we introduce the Y-Switch, a new TMSD cascade design that recognizes a custom nucleic acid input and generates an amplified output. The Y-Switch is based on a pair of thermodynamically spring-loaded DNA modules. The binding of a predefined nucleic acid target triggers an intermolecular reaction that activates a T7 promoter, leading to the perpetual transcription of a fluorescent aptamer that can be detected by a smartphone camera. The system is designed to permit the selective depletion of leakage byproducts to achieve high sensitivity and zero-background signal in the absence of the correct trigger. Using Zika virus (ZIKV)- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived nucleic acid sequences, we show that the assay generates a reliable target-specific readout. Y-Switches detect native RNA under isothermal conditions without reverse transcription or pre-amplification, with a detection threshold as low as ∼200 attomole. The modularity of the assay allows easy re-programming for the detection of other targets by exchanging a single sequence domain. This work provides a low-complexity and high-fidelity synthetic biology tool for point-of-care diagnostics and for the construction of more complex biomolecular computations.

Formulation and Skin Permeation of Active-Loaded Lipid Nanoparticles: Evaluation and Screening by Synergizing Molecular Dynamics Simulations and Experiments.

Encapsulation into nanoparticles (NPs) is a potential method to deliver pharmaceutical/cosmetic actives deep into the skin. However, understanding the NP formulations and underlying mechanism of active delivery to skin has scarcely been studied. We report a simulation platform that screens, evaluates, formulates, and provides atomic-resolution interpretation of NP-based formulations, and reveals the active permeation mechanism from NPs to skin. First, three actives, namely, ferulic acid (FA), clotrimazole (CZE), and tretinoin (TTN), and five lipid excipients' (Compritol, Precirol, Geleol, Gelot, Gelucire) combinations were screened by MD simulations for the best pairs. For each suggested pair, the actual active and lipid compositions for the synthesis of stable NP formulations were then obtained by experiments. MD simulations demonstrate that in NP formulations, FA and CZE actives are present at the surface of the NPs, whereas TTN actives are present at both the surface and interior of the NP core. The NP shapes obtained by simulation perfectly match with experiments. For each NP, separate MD simulations illustrate that active-loaded NPs approach the skin surface quickly, and then actives translocate from NP surface to skin surface followed by penetration of NPs through skin. The driving force for the translocation which initiates during the penetration process, is the stronger active-skin interaction compared to active-NP interaction. Permeation free energy indicates spontaneous transfer of actives from solution phase to the surface of the skin bilayer. The free energy barriers are increased in the order of FA < TTN < CZE. Significantly lower diffusions of actives are obtained in the main barrier region compared to bulk, and the average diffusion coefficients of actives are in the same order of magnitude (∼10-6 cm2/s). The estimated permeability coefficients (log P) of actives are mainly governed by free energy barriers. The study would facilitate the development of novel lipid-based NP formulations for personal-care/pharmaceutical applications.

Cu(II)/PTABS-Promoted, Regioselective SNAr Amination of Polychlorinated Pyrimidines with Mechanistic Understanding.

Regioselective amination of polyhalogenated heteroarenes (especially pyrimidines) has extensive synthetic and commercial relevance for drug synthesis applications but is plagued by the lack of effective synthetic strategies. Herein, we report the Cu(II)/PTABS-promoted highly regioselective nucleophilic aromatic substitution (SNAr) of polychlorinated pyrimidines assisted by DFT predictions of the bond dissociation energies of different C-Cl bonds. The unique reactivity of Cu(II)-PTABS has been attributed to the coordination/activation mechanism that has been known to operate in these reactions, but further insights into the catalytic species have also been provided.

In silico identification of a promising inhibitor of Fusarium oxysporum f. sp. Lycopersici, Secreted in Xylem 1 protein.

Fusarium oxysporum f. sp. Lycopersici (FOL) is a soilborne pathogen that infects tomato plants and inflicts severe damage, resulting in heavy yield losses worldwide, causing Fusarium wilt disease. FOL encodes several pathogenicity factors necessary for colonizing and invading the host plants. Secreted in Xylem (SIX), a pathogenicity factor, is a small cysteine-rich fungal protein found in the xylem sap of FOL-infected tomato plants, which plays a major role in determining host specificity and in contributing to pathogenicity/virulence. However, the structure of SIX1 has not been modeled yet. Therefore, this study aimed to elucidate the structure of SIX1 by comparative modeling using Robetta server. The best possible structures obtained were then refined, validated, and utilized for subsequent analysis. An antifungal library comprising 16,824 compounds was screened to determine small molecules that can interact with SIX1. Five antifungal compounds were identified from the library. Further analyses revealed that, of the five ligands, 4-[(2-(3-methoxyphenoxy)acetyl)amino] benzamide exhibited the capacity to stably interact with SIX1. This shows that 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide can be used as a potential candidate in the prevention of FOL infection. In summary, small-molecule inhibitors such as 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide could be highly effective in combating FOL infection, along with biocontrol methods and strategies that use transgenic plants overexpressing resistance genes.

Heavy and less common metals in rainwater and the kinetics of the oxidation of hydrogen sulfide by oxygen in rainwater medium.

As a sequel to our recent study on the oxidation by O2, i. e., autoxidation of dissolved hydrogen sulfide, H2S, in aqueous medium, we present here the results of a similar study in rain water medium. The rainwater sampling was done sequentially for four years (2016-2019). In all 67 samples of rainwater were collected on event basis during monsoon period (June-October) in and around the Campus of University of Rajasthan, Jaipur (26°50̛ N-75°52̛ E), which is situated in a semi-arid region adjacent to the Thar Desert in the North-Western part of the India having an annual average rainfall of 54 cm. ICP-MS technique was used in the analysis of rainwater and more than 30 metals were detected, which included transition metals, rare earths, less common metals. Beryllium, vanadium, silver, selenium, manganese, cerium, gallium, yttrium, barium, cesium, copper, rubidium, arsenic, lanthanum, cadmium, lead, uranium and bismuth were common to all rain water samples.H2S oxidation by dissolved oxygen was studied in rainwater as well as in laboratory water media for comparison. The kinetics rate law was: -d[O2]/dt = k1K1[H+][S][O2]t/( [H+]2 + K1[H+] + K1K2), where K1 is first dissociation constant of H2S and k1 is the rate constant for the dominant reaction step:HS- + O2 → products.

Catalytic amino acid production from biomass-derived intermediates.

Amino acids are the building blocks for protein biosynthesis and find use in myriad industrial applications including in food for humans, in animal feed, and as precursors for bio-based plastics, among others. However, the development of efficient chemical methods to convert abundant and renewable feedstocks into amino acids has been largely unsuccessful to date. To that end, here we report a heterogeneous catalyst that directly transforms lignocellulosic biomass-derived α-hydroxyl acids into α-amino acids, including alanine, leucine, valine, aspartic acid, and phenylalanine in high yields. The reaction follows a dehydrogenation-reductive amination pathway, with dehydrogenation as the rate-determining step. Ruthenium nanoparticles supported on carbon nanotubes (Ru/CNT) exhibit exceptional efficiency compared with catalysts based on other metals, due to the unique, reversible enhancement effect of NH3 on Ru in dehydrogenation. Based on the catalytic system, a two-step chemical process was designed to convert glucose into alanine in 43% yield, comparable with the well-established microbial cultivation process, and therefore, the present strategy enables a route for the production of amino acids from renewable feedstocks. Moreover, a conceptual process design employing membrane distillation to facilitate product purification is proposed and validated. Overall, this study offers a rapid and potentially more efficient chemical method to produce amino acids from woody biomass components.

Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome.

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above-mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early-onset end-stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.

In vitro and in silico molecular interaction of multiphase nanoparticles containing inositol hexaphosphate and jacalin: Therapeutic potential against colon cancer cells (HCT-15).

Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer.

Cdk5: A main culprit in neurodegeneration.

Objectives: Neurodegenerative diseases (NDs) such as Alzheimer Diseases (AD), Parkinson Diseases (PD) are a huge public health problem. The elucidation of their pathophysiological mechanism is one of our greatest challenges. Hyperactive immune system contributes to the pathophysiology of neurological disorders. Methods: In this review article, we have highlighted the neurodegenerative role of CDK5 and its involvement in Amyloid precursor pathway via Beta secretase enzyme. Results:All the landmark research reports for CDK5 were considered for this review and its involvement in disrupted autophagy and hyper immune response is the key cause for neurodegeneration. Conclusion: In conclusion, the present review focus on the pathways associated with Cdk5 and its role in causing neurodegeneration.

Optimization of Inositol Hexaphosphate Colon Targeted Formulation for Anticarcinogenic Marker Modulation.

Colorectal cancer has become the third most frequent reason of cancer death in men and women. Currently, natural compounds are being looked up to, for subversion and deterrence of cancers. Inositol hexaphosphate (IP6) is one such naturally occurring phosphorylated carbohydrate present in most legumes and cereals which acts as a potential antineoplastic agent and can be used effectively to prevent and treat colon carcinomas. Despite the immense potential, due to the prevalence of high charge and ability to form salts and chelates with various divalent metals, it gets excreted out quickly from the body. On reaching the colon in its original form, it can serve as an effective anticancer agent. Therefore, a suitable dosage form that can prevent the drugs from being absorbed from the upper gastrointestinal tract is required to be prepared, to target it to the colon. Thus, microspheres of IP6 using a biodegradable polymer that degrades in the colon were attempted using the solvent evaporation method. The formulation was investigated for percentage yield, encapsulation efficiency, particle size distribution modification, and release rate. Optimized formulation showed particle size of 92 ± 0.76 µm, entrapment efficiency of 67.26% ± 0.75, percent drug loading of 15.74%, and in vitro drug release 82.36 ± 0.51. The results of the in vivo study divulged that IP6 loaded pectin microspheres showed significant positive modulation of biomarker levels and restoration of colonic architecture to almost normal as observed through histopathology and scanning electron microscopy studies in DMH-induced colon tumors in Albino Wistar rats.

Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model.

Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC50 value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p < 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P < 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation.

Molecular docking and simulation studies of gustatory receptor of Aedes aegypti: A potent drug target to distract host-seeking behaviour in mosquitoes.

BACKGROUND & OBJECTIVES: It is well reported that exhaled CO 2 and skin odour from human being assist female mosquitoes to locate human host. Basically, the receptors for this activity are expressed in cpA neurons. In both Aedes aegypti and Anopheles gambiae, this CO 2-sensitive olfactory neuron detects myriad number of chemicals present in human skin. Therefore, manipulation of gustatory receptors housing these neurons may serve as important targets for behavioural intervention. The study was aimed towards virtual screening of small molecules in the analyzed conserved active site residues of gustatory receptor and molecular dynamics simulation study of optimum protein-ligand complex to identify a suitable lead molecule for distracting host-seeking behaviour of mosquitoes. METHODS: The conserved residue analysis of gustatory receptor (GR) of Ae. aegypti and An. gambiae was performed. The structure of GR protein from Ae. aegypti was modeled and validated, and then molecular docking was performed to screen 2903 small molecules against the predicted active residues of GR. Further, simulation studies were also carried out to prove protein-ligand stability. RESULTS: The glutamine 154 residue of GR was found to be highly conserved in Ae. aegypti and An. gambiae. Docking results indicated that the dodecanoic acid, 1,2,3-propanetriyl ester (dynasan 112) was interacting with this residue, as it showed better LibDock score than previously reported ethyl acetate used as mosquito repellant. Simulation studies indicated the structural instability of GR protein in docked form with dynasan 112 suggesting its involvement in structural changes. Based on the interaction energies and stability, this compound has been proposed to be used in mosquitoes' repellant. INTERPRETATION & CONCLUSION: A novel effective odorant acting as inhibitor of GR is proposed based on its stability, docking score, interactions and RMSD, considering ethyl pyruvate as a standard inhibitor. Host preference and host-seeking ability of mosquito vectors play key roles in disease transmission, a clear understanding of these aspects is essential for preventing the spread of the disease.

Dosimetric analysis of Co-60 source based high dose rate (HDR) brachytherapy: A case series of ten patients with carcinoma of the uterine cervix.

AIM: To analyse the dosimetric parameters of Co-60 based high dose rate (HDR) brachytherapy plans for patients of carcinoma uterine cervix. BACKGROUND: Co-60 high dose rate (HDR) brachytherapy unit has been introduced in past few years and is gaining importance owing to its long half life, economical benefits and comparable clinical outcome compared to Ir-192 HDR brachytherapy. MATERIALS AND METHODS: A study was conducted on ten patients with locally advanced carcinoma of the uterine cervix (Ca Cx). Computed tomography (CT) images were taken after three channel applicator insertions. The planning for 7 Gray per fraction (7 Gy/#) was done for Co-60 HDR brachytherapy unit following the American Brachytherapy Society (ABS) guidelines. All the patients were treated with 3# with one week interval between fractions. RESULTS: The mean dose to high risk clinical target volumes (HRCTV) for D90 (dose to 90% volume) was found to be 102.05% (Standard Deviation (SD): 3.07). The mean D2cc (dose to 2 cubic centimeter volume) of the bladder, rectum and sigmoid were found to be 15.9 Gy (SD: 0.58), 11.5 Gy (SD: 0.91) and 4.1 Gy (SD: 1.52), respectively. CONCLUSION: The target coverage and doses to organs at risk (OARs) were achieved as per the ABS guidelines. Hence, it can be concluded that the Co-60 HDR brachytherapy unit is a good choice especially for the centers with a small number of brachytherapy procedures as no frequent source replacement is required like in an Ir-192 HDR unit.

Water Desalination through Zeolitic Imidazolate Framework Membranes: Significant Role of Functional Groups.

A molecular simulation study is reported for water desalination through five zeolitic imidazolate framework (ZIF) membranes, namely ZIF-25, -71, -93, -96, and -97. The five ZIFs possess identical rho-topology but differ in functional groups. The rejection of salt (NaCl) is found to be around 97% in ZIF-25, and 100% in the other four ZIFs. The permeance ranges from 27 to 710 kg/(m(2)·h·bar), about one∼two orders of magnitude higher compared with commercial reverse osmosis membranes. Due to a larger aperture size da, ZIF-25, -71, and -96 exhibit a much higher water flux than ZIF-93 and -97; however, the flux in ZIF-25, -71, and -96 is governed by the polarity of functional group rather than da. With the hydrophobic CH3 group, ZIF-25 has the highest flux despite the smallest da among ZIF-25, -71, and -96. The lifetime of hydrogen bonding in ZIF-25 is shorter than that in ZIF-71 and -96. Furthermore, water molecules undergo a fast flushing motion in ZIF-25, but frequent jumping in ZIF-96 and particularly in ZIF-97. An Arrhenius-type relationship is found between water flux in ZIF-25 and temperature, and the activation energy is predicted to be 6.5 kJ/mol. This simulation study provides a microscopic insight into water desalination in a series of ZIFs, reveals the key factors (aperture size and polarity of functional group) governing water flux, and suggests that ZIF-25 might be an interesting reverse osmosis membrane for high-performance water desalination.

Modulation of miR-203 and its regulators as a function of time during the development of 7, 12 dimethylbenz [a] anthracene induced mouse skin tumors in presence or absence of the antitumor agents.

We investigated the chemopreventive effects of naturally occurring compounds like butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) individually or in combination in 7, 12-dimethylbenz [a] anthracene (DMBA) treated mouse skin at 4 and 16 weeks, the time before and after the tumor development. DMBA application did not show any skin tumors at 4 weeks but well defined tumors appeared at 16 weeks. BA, NA or CAG prevented the tumor development significantly but the protection was highly enhanced when all these compounds were given together. In order to see the molecular changes progressing with tumors, we showed the downregulation of tumor suppressor miR-203 at 16 weeks and upregulation of histone deacetylases (HDAC), DNA methyltransferase, promoter methylation of miR-203 at 4 or 16 weeks. Regulators of micro RNA biogenesis such as DICER1 and Ago2 were also deregulated by DMBA. Proto-oncogene c-myc and BMI1 were upregulated and tumor suppressor gene p16 was downregulated by DMBA as a function of time. Effects of BA, NA or CAG were more pronounced after 16 weeks as compared to 4 weeks in preventing the tumor development and altered gene expression. Concomitant administration of BA, NA and CAG tried to prevent these alterations more effectively than that of individual compound possibly by regulating miR-203 status through epigenetic or biogenetic modulations before and after the tumor development. Study provides a rationale for chemoprevention by combination of different compounds targeting miR-203.

Involvement of EZH2, SUV39H1, G9a and associated molecules in pathogenesis of urethane induced mouse lung tumors: potential targets for cancer control.

In the present study, we showed the correlation of EZH2, SUV39H1 or G9a expression and histone modifications with the urethane induced mouse lung tumorigenesis in the presence or absence of antitumor agent, inositol hexaphosphate (IP6). Tumorigenesis and the molecular events involved therein were studied at 1, 4, 12 or 36 weeks after the exposure. There were no tumors at 1 or 4 weeks but tumors started appearing at 12 weeks and grew further till 36 weeks after urethane exposure. Among the molecular events, upregulation of EZH2 and SUV39H1 expressions appeared to be time dependent, but G9a expression was altered significantly only at later stages of 12 or 36 weeks. Alteration in miR-138 expression supports the upregulation of its target, EZH2. H3K9me2, H3K27me3 or H4K20me3 was found to be altered at 12 or 36 weeks. However, ChIP analysis of p16 and MLH1 promoters showed their binding with H3K9me2 and H3K27me3 which was maximum at 36 weeks. Thus, histone modification and their interactions with gene promoter resulted in the reduced expression of p16 and MLH1. IP6 prevented the incidence and the size of urethane induced lung tumors. IP6 also prevented the urethane induced alterations in EZH2, SUV39H1, G9a expressions and histone modifications. Our results suggest that the alterations in the histone modification pathways involving EZH2 and SUV39H1 expressions are among the early events in urethane induced mouse lung tumorigenesis and could be exploited for cancer control.

Involvement of epigenetics and microRNA-29b in the urethane induced inception and establishment of mouse lung tumors.

Epigenetic changes are correlated with tumor development showing aberrations in DNA methylation and histone modifications. To find the early changes, we evaluated the epigenetic events from early to late stage of the urethane induced lung tumor development in mouse model and tried to correlate the molecular events with the progression of tumor. We addressed the hypothesis by examining the tumor development, status of DNMTs, HDACs and MBDs, DNA methylation and expression of microRNA-29b during 1 to 36 weeks after urethane exposure that included the period before and after the tumor appearance. Tumors did not appear after 1 or 4 weeks but well defined tumors appeared after 12 weeks and larger tumors appeared at 36 weeks which was prevented by IP6. DNMT1, DNMT3a and DNMT3b were upregulated after urethane exposure at the time of no tumor till the tumor developed and showed its upregulated functional activity. DNMTs are shown to be the targets of microRNA-29b and we showed that microRNA-29b was downregulated in the line of DNMT upregulation. HDAC, the histone modifier, also showed progressive upregulation. Periodic increase in methyl binding proteins, MBD2, supported the expression of gene silencing pathways in terms of the downregulation of tumor suppressor genes, p16 and MLH1. All these molecular alterations were protected in the presence of IP6. Our results showed that the key steps of epigenetics, DNMTs, mir29b, and HDAC1, are altered both before and after the development of tumors.

Evaluation of polymer-preservative interactions for preservation efficacy: molecular dynamics simulation and QSAR approaches.

Preservatives are critical ingredients in various pharmaceutical and consumer products. In particular, a high efficacy preservative system is essential in enhancing the shelf-life and safety of these products. However, the development of such a preservative system heavily relies on experimental approaches. In this study, molecular dynamics (MD) simulation was complemented with quantitative structure-activity relationship (QSAR) modelling to comprehensively evaluate polymer-preservative interactions between three different polymers (polyethylene terephthalate, PET; polypropylene, PP; and cellulose) and a series of preservatives from the classes of aliphatic, aromatic, and organic acids. First, adsorption of preservatives onto polymer surfaces was simulated in an aqueous environment. The preservatives did not adhere to hydrophilic cellulose, but most preservatives were adsorbed by PET and PP in distinct configurations. Interaction energies (IEs) between the preservatives and the polymers generally increase from cellulose to PP and PET. The diffusion coefficients of preservatives are dependent on polymer nature, preservative structure, and their resulting molecular interactions. Linear and low molecular weight preservatives exhibit higher diffusion coefficients in polymers. For a particular preservative, diffusion coefficients increased in the order of cellulose < PET < PP. Finally, using MD properties and molecular descriptors of preservatives, QSAR models were developed to identify key descriptors of preservatives and predict their IEs and diffusion coefficients in polymers. This study demonstrates a computational approach for identifying critical materials properties, and predicting polymer-preservative molecular interactions in water. Such an approach streamlines the rational selection and design of high efficacy preservative systems for various pharmaceutical, food and cosmetic products. Furthermore, the integrated computational strategy also reduces trial-and-error experimental efforts, thereby accelerating the development of high efficacy preservative systems.

Lid wiper epitheliopathy: Topical review of current identification strategies and future perspectives.

Lid Wiper Epitheliopathy (LWE) is a recognized ocular condition affecting visual quality and ocular comfort, characterized by the damage of the marginal conjunctiva of the upper eyelid. This review critically examines the current strategies for LWE identification and explores the multifactorial etiology of LWE and its association with various ocular surface diseases. A literature review conducted on PubMed identified 67 relevant studies, which were analyzed to enhance understanding of LWE's diagnostic criteria and its clinical implications, offering future perspectives on improving diagnostic accuracy and patient outcomes. The association between LWE and contact lens-related discomfort is examined, with studies reporting conflicting findings regarding its prevalence and severity among soft contact lens wearers. Moreover, LWE has been linked to tear film abnormalities, altered tear composition, and eyelid margin abnormalities in non-contact lens wearers, further complicating diagnosis and management. Current LWE grading systems, including subjective methods and semi-objective approaches, are reviewed, highlighting challenges such as subjectivity, complexity, and variability. Recent advances in LWE grading, including semi-automated methods and photographic scales, show promise but face implementation challenges in clinical settings. The review concludes by proposing areas for further research, including investigating factors contributing to LWE onset and development, developing more sensitive diagnostic tools, and exploring the impact of LWE on ocular surface health and visual function. Standardization, validation, and innovation in grading systems are emphasized to enhance diagnostic accuracy and improve clinical outcomes for patients with LWE. Ongoing research in LWE grading is essential for addressing diagnostic challenges and optimizing assessment methodologies in clinical practice.