Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.

Gestational Serum Retinol Deficiency Is Associated with Enamel Hypoplasia.

Enamel hypoplasia (EH) is a prevalent developmental defect of teeth that can result from various insults, including prenatal nutrient deficiencies. This study aimed to evaluate the association between prenatal serum retinol deficiency and EH in the deciduous teeth of offspring at 2-y of age. A cohort of 1,450 pregnant women was enrolled, and their prenatal nutritional status was assessed between 12 and 14 wk of gestation. Maternal serum retinol, serum 25-hydroxyvitamin D (25OHD), hemoglobin, body mass index, and birth outcomes, infant feeding practices, family socioeconomic status, and demographic information were recorded. Oral health examinations were conducted for the children semiannually, and EH was diagnosed using the Modified DDE index on all the surfaces of erupted teeth. A modified Poisson regression analysis was used to assess the cumulative risk of EH over a period of 2-y. A total of 920 (63.4%) mother-child pairs completed the study, and the cumulative EH prevalence among offspring after 2-y of follow-up was 16.5% (N = 152; 87/1,114 children in the first year and 132/920 in the second year, with 20/920 having EH only in the first year). After adjusting for potential confounders, maternal serum retinol deficiency significantly increased the risk of deciduous EH (risk ratio [RR], 2.0; 95% confidence interval [CI], 1.1-3.7). In addition, deficient serum 25OHD (RR, 6.5; 95% CI, 4.0-10.7), caesarean delivery (RR, 1.6; 95% CI, 1.0-2.4), Muslim (RR, 2.9; 95% CI, 2.0-4.1) and Christian (RR, 2.4; 95% CI, 1.6-3.5) versus Hindu religions, and very preterm birth (RR, 1.7; 95% CI, 1.1-2.9) increased the risk of EH. Children presenting with EH had 2 or more teeth affected, and the maxillary incisors were the most frequently affected, followed by the first primary molars and canines. In conclusion, maternal serum retinol deficiency during the 12 to 14 wk of gestation may increase the risk of deciduous EH, besides the well-established 25OHD deficiency.

Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil's semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARS-CoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied.

Efficacy of marine algal extracts against oral pathogens - A systematic review.

Introduction: Marine algae possess a plethora of secondary active metabolites which has many biomedical applications. Anti-bacterial activity against oral cariogenic bacteria is reported in literature, however there is no comprehensive review available. Hence, this review is attempted to collate all the evidence available regarding the marine algal extracts and its constituents against oral cariogenic bacteria. Methods: Electronic search was conducted in the Google scholar, the Pubmed database and various clinical trial registries. Included studies were clinical, in-vitro studies assessing DMFT, DMFS, minimum inhibitory concentration or colony forming unit counts. Result: A total of 19 trials were obtained out of which only 7 were eligible for this review. Quality assessment was done by Higgins and Greens (2011) method. Results showed all the studies where they used crude algal extracts or its active constituents were showing anti-bacterial activity. Conclusion: Thus, this review showed that marine algal extracts and other constituents are having anti-microbial properties, making them potential anti-microbial agents for oral hygiene maintenance without adverse effects of currently available chemical based oral care products.

Algal biomass as a source for novel oral nano-antimicrobial agent.

In the present study, sulphated polysaccharide Ulvan from Ulva lactuca was used for the synthesis of biogenic Selenium Nanoparticles (SeNPs) conjugate and Mouth rinse was prepared using this conjugate. The synthesis of nanoparticles was confirmed by UV-Visible spectrophotometry and characterized using Fourier transform infrared spectroscopy (FTIR), transmission electron microscope (TEM) and X-ray diffraction (XRD). TEM showed that the average size of the nanoparticle was 85 nm and spherical in shape. Furthermore, nanoparticle conjugates were evaluated for cell viability using MTT assay 3T3-L1 cell line and at 30 µl/ml showed 34% cell viability. The antimicrobial activity of SeNPs mouth rinse was tested against oral pathogens such as Streptococcus mutans, Staphylococcus aureus, Lactobacillus, and Candida albicans and it was effective against all tested microorganism at the concentration of 100 µl/ml. The present study has shown that Ulvan from algal biomass can be a safe and effective source for the development of oral nano-antimicrobial agents.

Acceptability of silver diamine fluoride as interim measure towards untreated dental caries and its impact on ohrqol among children with HIV: Pilot study.

BACKGROUND: Children with HIV are a special group with limited access to care and high prevalence of dental caries. Silver Diamine Fluoride (SDF) is approved universally for the management of asymptomatic carious lesions but research on the psychological impact of black staining is scarce. AIMS: Effect of silver diamine fluoride (SDF) application as an interim caries management on the child's oral health-related quality of life of children with HIV over a period of 4 months until definitive care was provided. SETTINGS AND DESIGN: A pilot study conducted among children with HIV in a care home. It was a pilot trial to check the acceptability of SDF among these children. METHODS AND MATERIAL: Forty-two children (12.3 ± 3.5 years) participated in this pilot study. Prevalence of caries (DMFT), candidiasis, gingival inflammation, and cervical lymphadenitis was evaluated. OHRQoL inventory (COHIP-SF) was completed by the students at baseline, immediately, 4 months after SDF application. STATISTICAL ANALYSIS USED: One-way ANOVA with post hoc Tukey HSD test. RESULTS AND CONCLUSION: Poor oral hygiene was universal and mean DMFT was 3.2 ± 2.5. OHRQoL was not significantly affected at baseline (26.2 ± 6.4), but immediately following SDF application, OHRQoL was significantly poor (48.7 ± 8.2), remained poor even after 4 months (42.6 ± 6.1). Emotional wellbeing was significantly impacted negatively following SDF application (p < 0.001); whereas oral health, functional wellbeing dimensions were not impacted. SDF should be used with caution among special children as the black discoloration of the teeth can cause emotional trauma and negatively impacting their OHRQoL while trying to improve the same.

Evaluation of adhesion of Streptococcus mutans, plaque accumulation on zirconia and stainless steel crowns, and surrounding gingival inflammation in primary molars: randomized controlled trial.

OBJECTIVE: To evaluate the adhesion of Streptococcus mutans to preformed zirconia and stainless steel crowns and compare plaque accumulation and gingival inflammation over a period of 1 year. MATERIALS AND METHODS: Thirty children between 6 to 9 years with pulpectomised bilateral mandibular primary second molars were randomly divided into zirconia/stainless steel groups. Plaque was collected from the crowns using swabs at 3, 6, 9, and 12 months. Gingival and plaque index were recorded at all follow-ups. S. mutans was cultured on tryptone-yeast-cysteine-sucrose-bacitracin agar, and organisms were expressed as colony-forming units. Within-group analysis was performed using repeated measures ANOVA and between-groups using the independent T test. RESULTS: S. mutans were found in significantly higher numbers on the stainless steel crowns as compared with zirconia crowns at all the follow-ups. Gingival inflammation and plaque index scores were also significantly higher around the stainless steel crowns as compared with zirconia at the end of 12 months follow-up. CONCLUSION: Adhesion of S. mutans to stainless steel crowns was significantly greater when compared with zirconia, and minimal gingival inflammation and plaque accumulation was found in the tooth restored with zirconia crowns as compared with stainless steel crowns. CLINICAL RELEVANCE: Preformed zirconia crowns prevents adhesion of S. mutans onto its surface, and reduces plaque accumulation around the crown, inflammation of surrounding gingiva compared to conventional stainless-steel crowns. Pediatric zirconia crowns could help in reducing the overall microbial density and prevalence in the oral cavity, thus reducing the caries risk in the long term.

Bioconjugated graphene oxide-based Raman probe for selective identification of SKBR3 breast cancer cells.

In this article, we demonstrate the use of bio-conjugated 2D graphene oxide (bio-GO) nanostructure to probe breast cancer cell (SKBR3) with excellent discrimination over other types of circulating tumor cells. We distinctly observed that bio-GO nanostructure targets and bind SKBR3 cell selectively in the cell mixture. Longer incubation of SKBR3 cell with bio-GO causes Raman signal "turn off" when excited with 532 nm laser. This is attributed to penetration of the bio-GO through the plasma membrane of the cell by generating transient hole. Extraction of GO after cell digestion also support the internalization rubric of 2D graphene through cell membrane. Our experimental data with the HaCaT healthy cell line, as well as with LNCaP prostate cancer cell line clearly demonstrated that this Raman scattering assay is highly selective to SKBR3. The mechanism of selectivity and the assay's response change have been verified and discussed utilizing fluorescence properties of GO and various other techniques. The experimental results open up a possibility of new label free Raman scattering assay, for reliable diagnosis of cancer cell lines by monitoring "turn-off" of the Raman signal from Bio-GO nanostructure.

Alizarin Dye based ultrasensitive plasmonic SERS probe for trace level Cadmium detection in drinking water.

Alizarin functionalized on plasmonic gold nanoparticle displays strong surface enhanced Raman scattering from the various Raman modes of Alizarin, which can be exploited in multiple ways for heavy metal sensing purposes. The present article reports a surface enhanced Raman spectroscopy (SERS) probe for trace level Cadmium in water samples. Alizarin, a highly Raman active dye was functionalized on plasmonic gold surface as a Raman reporter, and then 3-mercaptopropionic acid, 2,6-Pyridinedicarboxylic acid at pH 8.5 was immobilized on the surface of the nanoparticle for the selective coordination of the Cd (II). Upon addition of Cadmium, gold nanoparticle provide an excellent hotspot for Alizarin dye and Raman signal enhancement. This plasmonic SERS assay provided an excellent sensitivity for Cadmium detection from the drinking water samples. We achieved as low as 10 ppt sensitivity from various drinking water sources against other Alkali and heavy metal ions. The developed SERS probe is quite simple and rapid with excellent repeatability and has great potential for prototype scale up for field application.

Effect of ozone to remineralize initial enamel caries: in situ study.

OBJECTIVES: Effect of ozonated water in remineralizing artificially created initial enamel caries was investigated using laser fluorescence and polarized light microscopy in an in situ study. MATERIALS AND METHODS: Teeth specimens (buccal sections) were immersed in 5-ml solution of 2 mM CaCl2, 2 mM NaH2P04, and 50 mM CH3COOH at pH of 4.55 for 5 h in an incubator at 37° to create subsurface demineralization. After which, they were randomly allocated into one of the following remineralization regimens: ozone (ozonated water 0.1 mg/l and 10 % nano-hydroxyapatite paste, Aclaim(TM)), without ozone (only 10 % nano-hydroxyapatite paste, Aclaim(TM)), and control (subjects' saliva alone). Specimens were embedded in acrylic retainers worn by orthodontic patients throughout the 21-day study duration and constantly exposed to their saliva. Laser fluorescence was recorded for all the specimens at baseline, after demineralization, and remineralization using DIAGNOdent, and the results were validated using polarized microscopic examination. The results were analyzed using repeated measures, one-way ANOVA with post hoc multiple comparisons. RESULTS: Reduced DIAGNOdent scores and greater depth of remineralization following application of ozonated water and nano-hydroxyapatite were found compared to those of the without ozone and control groups (P < 0.001), and the ozone-treated group exhibited maximum remineralization under the polarized light microscopy. CONCLUSION: Ozonated water can be considered an effective agent in reversing the initial enamel caries alongside with nano-hydroxyapatite compared to nano-hydroxyapatite alone and saliva. CLINICAL RELEVANCE: Ozone water can be used to remineralize incipient carious lesions, and it enhances the remineralizing potential of nano-hydroxyapatite thereby preventing the tooth from entering into the repetitive restorative cycle.

MEISENHEIMER COMPLEX BETWEEN 2,4,6-TRINITROTOLUENE AND 3-AMINOPROPYLTRIETHOXYSILANE AND ITS USE FOR A PAPER-BASED SENSOR.

2,4,6-Trinitrotoluene (TNT) forms a red-colored Meisenheimer complex with 3-aminopropyltrenthoxysilane (APTES) both in solution and on solid phase. The TNT-APTES complex is unique since it forms yellow-colored complexes with 2,4,6-trinitrophenol and 4-nitrophenol, and no complex with 2,4-dinitrotoluene. The absorption spectrum of TNT-APTES has two absorption bands at 530 and 650 nm, while APTES complexes with 2,4,6-trinitrophenol and 4-nitrophenol have absorption maxima at around 420 nm, and no absorption change for 2,4-dinitrotoluene. The TNT-APTES complex facilitates the exchange of the TNT-CH3 proton/deuteron with solvent molecules. The red color of TNT-APTES is immediately visible at 1 µM of TNT.

Evaluation of instant desensitization after a single topical application over 30 days: a randomized trial.

BACKGROUND: The aim of this study was to evaluate the efficacy of ProArgin(™) (8% arginine), Gluma(®) and NovaMin(®) (5% calcium phosphosilicate) in relieving dentinal hypersensitivity immediately and over 30 days following a single topical application. METHODS: A three-cell, parallel group randomized trial was conducted among 56 patients exhibiting dentinal hypersensitivity with tooth as the unit of study. ProArgin(™) paste, Gluma(®) Desensitizer and NovaMin(®) paste were applied on randomly assigned teeth in each participant. Three stimuli were tested: tactile stimulated by running an explorer and measured using VAS (1-10 scale); air blast and cold water stimulated hypersensitivity measured using the Schiff Sensitivity Scale at baseline, immediately, 15 days and 30 days after application. Friedman test and Wilcoxon test were used for within group comparisons. Kruskal-Wallis test and Mann-Whitney U test were used for between group comparisons. RESULTS: All three groups showed significant reductions in hypersensitivity from baseline at all time points (p < 0.05). ProArgin(™) paste elicited a significantly higher reduction in hypersensitivity (p < 0.016) compared to Gluma(®) and NovaMin(®) for all stimuli at the end of 30 days. CONCLUSIONS: A single topical application of ProArgin(™) paste is significantly more effective than both a single topical application of Gluma(®) and NovaMin(®) paste in relieving dentinal hypersensitivity immediately and over 30 days.

A surface enhanced Raman scattering probe for highly selective and ultra sensitive detection of iodide in water and salt samples.

Iodine is a biophilic and essential trace element for all life and especially for vertebrates, which require it to produce indispensable thyroid hormones in their thyroid glands. As a result, the adequate measurement of iodine in water and food samples is crucial to lead a healthy life. Motivated by its importance, this is the first time in the literature that the highly selective and ultra sensitive (30 ppt limit) surface enhanced Raman scattering (SERS)-based detection of iodide ions (I(-)) from environmental and food samples has been reported. The desired sensitivity and selectivity has been achieved by measuring the change in the SERS intensity originating from Rh6G-adsorbed 30 nm gold nanoparticles (GNPs) upon the addition of I(-). The strong chemical affinity offered by I(-) towards the gold surface results in extra negative charge being deposited on it. As a result, the GNP surface attracts a greater number of positively charged Rh6G molecules and induces a marked increase in the number of hot spots through aggregation, providing a significant enhancement of the Raman signal intensity. The oxidation of I(-) to molecular iodine (I(2)) by hydrogen peroxide (H(2)O(2)) is employed for the successful screening of the bromide ion (Br(-)) which shows substantial interference at higher concentrations.

Sensitive and selective detection of trivalent chromium using Hyper Rayleigh Scattering with 5,5'-dithio-bis-(2-nitrobenzoic acid)-modified gold nanoparticles.

Hyper Rayleigh Scattering (HRS) and absorption spectral assays using surface-modified gold nanoparticles (AuNP) have been developed for sensitive and selective detection of trivalent chromium (Cr3+) from other metal ions including hexavalent chromium (as Cr2O72-). Gold nanoparticles of 13 nm, covalently attached with 5,5'-dithio-bis-(2-nitrobenzoic acid) (AuNP-DTNBA), is used as a probe for both the absorption and HRS assays. AuNP-DTNBA is able to detect Cr3+ at 20 ppb level at pH 6.0 using absorption spectral change of the AuNP-DTNBA. Visible color change can be observed when mixed with 250 ppb of Cr3+, while there is no color change when mixed with 2 ppm level of some of the most common metal ions such as Cr2O72-, Hg2+, Ba2+, Fe3+, Pb2+, Na+, Zn2+, Cd2+, Co2+, Mn2+, Ca2+, and Ni2+. However, a color change is observed when mixed with Ni2+, Zn2+, and Cd2+ at a concentration higher than 2 ppm. The detection limit for the HRS assay is on a remarkable 25 ppt level, and there is no detectable HRS signal at 2 ppm level for Cr2O72-, Hg2+, Ba2+, Fe3+, Pb2+, Na+, Zn2+, Cd2+, Co2+, Mn2+, Ca2+, and Ni2+.

Chloridodiphen-yl{[1-(1,3-thia-zol-2-yl-κN)ethyl-idene]-4-phenyl-thio-semicarbazidato-κN,S}tin(IV) methanol monosolvate.

The title compound, [Sn(C(6)H(5))(2)(C(12)H(11)N(4)S(2))Cl]·CH(4)O, is formed during the reaction between 2-acetyl-thia-zole 4-phenyl-thio-semicarbazone (Hacthptsc) and diphenyl-tin(IV) dichloride in methanol. In the crystal structure, the Sn atom exhibits an octa-hedral geometry with the [N(2)S] anionic tridentate thio-semicarbazone ligand having chloride trans to the central N and the two phenyl groups trans to each other. The Sn-Cl distance is 2.5929 (6), Sn-S is 2.4896 (6) and Sn-N to the central N is 2.3220 (16) Å. The MeOH mol-ecules link the Sn complexes into one-dimensional chains via N-H⋯O and O-H⋯Cl hydrogen bonds.

A label-free gold-nanoparticle-based SERS assay for direct cyanide detection at the parts-per-trillion level.

Cyanide is an extremely toxic lethal poison known to humankind. Developing rapid, highly sensitive, and selective detection of cyanide from water samples is extremely essential for human life safety. Driven by the need, here we report a gold-nanoparticle-based label-free surface-enhanced Raman spectroscopy (SERS) system for highly toxic cyanide ion recognition in parts-per-trillion level and to examine gold-nanoparticle-cyanide interaction. We have shown that the SERS assay can be used to probe the gold nanoparticle dissociation process in the presence of cyanide ions. Our experimental data indicates that gold-nanoparticle-based SERS can detect cyanide from a water sample at the 110 ppt level with excellent discrimination against other common anions and cations. The results also show that the SERS probe can be used to detect cyanide from environmental samples.

Iodido{4-phenyl-1-[1-(1,3-thia-zol-2-yl-κN)ethyl-idene]thio-semicarbazidato-κN',S}{4-phenyl-1-[1-(1,3-thia-zol-2-yl)ethyl-idene]thio-semicarbazide-κS}mercury(II).

In the title compound, [Hg(C(12)H(11)N(4)S(2))I(C(12)H(12)N(4)S(2))], the Hg atom is in a distorted square-pyramidal coordination, defined by the iodide ligand, by the S atom of the neutral ligand in the apical position, and by the N atom of the thia-zole ring, the thio-ureido N and the S atom of the deprotonated ligand. The deprotonated ligand intra-molecularly hydrogen bonds to the thia-zole ring N atom, while the deprotonated ligand forms an inter-molecular hydrogen bond to the thiol-ate S atom. The deprotonation of the tridentate ligand and its coordination to Hg via the S atom strikingly affects the C-S bond lengths. In the free ligand, the C-S bond distance is 1.685 (7) Å, whereas it is 1.749 (7) Šin the deprotonated ligand. Similarly, the Hg-S bond distance is slightly longer to the neutral ligand [2.6682 (18) Å] than to the deprotonated ligand [2.5202 (19) Å]. The Hg-I distance is 2.7505 (8) Å.

Photodegradation of selected PCBs in the presence of Nano-TiO2 as catalyst and H2O2 as an oxidant.

Photodegradation of five strategically selected PCBs was carried out in acetonitrile/water 80:20. Quantum chemical calculations reveal that PCBs without any chlorine on ortho-positions are closer to be planar, while PCBs with at least one chlorine atoms at the ortho-positions causes the two benzene rings to be nearly perpendicular. Light-induced degradation of planar PCBs is much slower than the perpendicular ones. The use of nano-TiO(2) speeds up the degradation of the planar PCBs, but slows down the degradation of the non-planar ones. The use of H(2)O(2) speeds up the degradation of planar PCBs greatly (by >20 times), but has little effect on non-planar ones except 2,3,5,6-TCB. The relative photodegradation rate is: 2,2',4,4'-TCB > 2,3,5,6-TCB > 2,6-DCB ≈ 3,3',4,4'-TCB > 3,4',5-TCB. The use of H(2)O(2) in combination with sunlight irradiation could be an efficient and "green" technology for PCB remediation.

Highly sensitive and selective dynamic light-scattering assay for TNT detection using p-ATP attached gold nanoparticle.

TNT is one of the most commonly used nitro aromatic explosives for landmines of military and terrorist activities. As a result, there is an urgent need for rapid and reliable methods for the detection of trace amount of TNT for screenings in airport, analysis of forensic samples, and environmental analysis. Driven by the need to detect trace amounts of TNT from environmental samples, this article demonstrates a label-free, highly selective, and ultrasensitive para-aminothiophenol (p-ATP) modified gold nanoparticle based dynamic light scattering (DLS) probe for TNT recognition in 100 pico molar (pM) level from ethanol:acetonitile mixture solution. Because of the formation of strong π-donor-acceptor interaction between TNT and p-ATP, para-aminothiophenol attached gold nanoparticles undergo aggregation in the presence of TNT, which changes the DLS intensity tremendously. A detailed mechanism for significant DLS intensity change has been discussed. Our experimental results show that TNT can be detected quickly and accurately without any dye tagging in 100 pM level with excellent discrimination against other nitro compounds.