Water-Soluble Small Organic Fluorophores for Oncological Theragnostic Applications: Progress and Development.

Cancer is one of the major noncommunicable diseases, responsible for millions of deaths every year worldwide. Though various cancer detection and treatment modalities are available today, many deaths occur owing to its late-stage detection and metastatic nature. Noninvasive detection using luminescence-based imaging tools is considered one of the promising techniques owing to its low cost, high sensitivity, and brightness. Moreover, these tools are unique and valuable as they can detect even the slightest changes in the cellular microenvironment. To achieve this, a fluorescent probe with strong tumor uptake and high spatial and temporal resolution, especially with high water solubility, is highly demanded. Recently, several water-soluble molecules with emission windows in the visible (400-700 nm), first near-infrared (NIR-I, 700-1000 nm), and second near-infrared (NIR-II, 1000-1700 nm) windows have been reported in literature. This review highlights recently reported water-soluble small organic fluorophores/dyes with applications in cancer diagnosis and therapeutics. We systematically highlight and describe the key concepts, structural classes of fluorophores, strategies for imparting water solubility, and applications in cancer therapy and diagnosis, i.e., theragnostics. We discuss examples of water-soluble fluorescent probes based on coumarin, xanthene, boron-dipyrromethene (BODIPY), and cyanine cores. Some other emerging classes of dyes based on carbocyclic and heterocyclic cores are also discussed. Besides, emerging molecular engineering methods to obtain such fluorophores are discussed. Finally, the opportunities and challenges in this research area are also delineated.

Synthesis, Characterization, Cytotoxicity, Cellular Imaging, Molecular Docking, and ADMET Studies of Piperazine-Linked 1,8-Naphthalimide-Arylsulfonyl Derivatives.

To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 µg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.

Synthesis, anticancer activity, molecular docking and molecular dynamics studies of some pyrazole-chalcone hybrids.

Four new hybrid compounds (H1-H4) bearing pyrazole (S1 and S2) and chalcone (P1 and P2) fragments were synthesized and characterized. Compounds were assayed for their ability to inhibit the proliferation of human lung (A549) and colon (Caco-2) cancer cell lines. Besides, toxicity against normal cells was determined using the human umbilical vein endothelial cells (HUVEC). In silico molecular docking, molecular dynamics (MD) simulation and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were carried out to predict the binding modes, protein stability, drug-likeness and toxicity of the reported compounds. The in vitro anticancer activity of the tested compounds revealed dose-dependent cell-specific cytotoxicity. In silico studies revealed that the compounds have a good binding affinity, possess appropriate drug-likeness properties and have low toxicity profiles.Communicated by Ramaswamy H. Sarma.

The characteristics and distribution of emergency medical services in Saudi Arabia.

BACKGROUND: Emergency medical services (EMS) play an essential role in treating and transporting patients to hospitals or between hospitals. EMS providers must be distributed wisely across all regions of the country to meet healthcare needs during normal times and disasters. No previous study has investigated the characteristics and distribution of the EMS workforce in Saudi Arabia. OBJECTIVES: Examine the characteristics and distribution of the EMS workforce in Saudi Arabia to identify gaps and areas in need of improvement. Also, explore the sociodemographic and educational characteristics of licensed EMS providers in Saudi Arabia. DESIGN: Cross-sectional SETTINGS: EMS in Saudi Arabia METHODS: We included all licensed EMS providers in Saudi Arabia as of 23 December 2020 who were registered in the Saudi Commission for Health Specialties (SCFHS) database. Sociodemographics, where they earned certification, and their job affiliations were collected and categorized. MAIN OUTCOME MEASURES: EMS workforce distribution, gender, and EMS provider-to-population ratio. SAMPLE SIZE: 18 336 EMS providers; 8812 (48.1%) with documented job affiliations. RESULTS: The EMS provider-to-population ratio is very low. In Saudi Arabia, in general, the ratio is 1:3871 (based on n=8812 providers), which is low compared to the 1:1400 ratio for Australian EMS provider-to-population, for example. That makes it a challenge for EMS providers to meet the population's needs, especially in times of disaster. The low ratio may have contributed to the delayed response time in Saudi Arabia (13 minutes for critical cases) which does not meet the international standard response time (8 minutes maximum). Also, only 3.5% of the total EMS providers registered were females, and the clear majority of all EMS providers were technicians. CONCLUSIONS: The growth in the EMS workforce, including the recruitment of more females into the workforce and more EMS specialists compared to EMS technicians and health assistants, is critical to reaching a satisfactory EMS provider-to-population ratio. LIMITATIONS: Most noteworthy of the limitations of this research are the insufficient statistics describing EMS distribution in Saudi Arabia, the lack of previous studies on the research topic in Saudi Arabia, and job affiliation not accurately recorded in the SCFHS database. CONFLICT OF INTEREST: None.

Using bonding agent prior to pits and fissure sealant application enhances the microtensile bond strength and the interface morphology.

BACKGROUND: A pits and fissures sealant is an effective method for preventing dental caries. Using a bonding agent before applying the sealant may increase its retention. This study aimed to compare the microtensile strength (µTBS) of a fissure sealant with and without a bonding agent and to characterize the enamel-sealant interface using confocal laser scanning microscopy (CLSM). The null hypothesis was that the use of a bonding agent before fissure sealant application would not change the microtensile strength or the enamel-sealant interface. MATERIALS AND METHODS: Twenty caries-free premolars were used. Each tooth was divided into four parts. The first two parts were assigned to the bonded group, where a bonding system was used before sealant application. The remaining two parts were treated only with a fissure sealant (i.e., the nonbonded group). In each group, the µTBS was examined after 24 h (n = 20) and after a 3-month aging period (n = 20). Five other caries-free extracted premolars were used to assess the enamel-sealant interface using CLSM. Two-way analysis of variance (ANOVA) and Pearson chi-square statistical analysis tests were used to analyze the µTBS and the enamel-sealant interface, respectively. RESULTS: The mean µTBS for the bonded group was significantly higher (p = 0.001) in the immediate group (36.87 ± 14.95 MPa) and the aged group (31.08 ± 15.88 MPa) than in the respective nonbonded groups (19.77 ± 9.67 MPa and 19.52 ± 14.14 MPa). The µTBS was not significantly different in either group after aging (p = 0.46 [bonded group] and p = 0.98 [nonbonded group]). In addition, using a dental adhesive, before applying a fissure sealant resulted in a significantly higher (53%) resin penetration into the enamel with the continuous integrity of the resin. CONCLUSION: The use of a bonding agent before the application of fissure sealant resulted in superior microtensile bond strength immediately and after aging. In addition, the enamel-sealant interface characteristics were improved.

Bacillus-Mediated Silver Nanoparticle Synthesis and Its Antagonistic Activity against Bacterial and Fungal Pathogens.

In this article, the supernatant of the soil-borne pathogen Bacillus mn14 was used as the catalyst for the synthesis of AgNPs. The antibacterial and antifungal activity of Bs-AgNPs was evaluated, in which S. viridans and R. solani showed susceptibility at 70 µL and 100 µL concentrations. Enzyme properties of the isolates, according to minimal inhibitory action and a growth-enhancing hormone-indole acetic acid (IAA) study of the isolates, were expressed in TLC as a purple color with an Rf value of 0.7. UV/Vis spectroscopy revealed the presence of small-sized AgNPs, with a surface plasmon resonance (SPR) peak at 450 nm. The particle size analyzer identified the average diameter of the particles as 40.2 nm. The X-ray diffraction study confirmed the crystalline nature and face-centered cubic type of the silver nanoparticle. Scanning electron microscopy characterized the globular, small, round shape of the silver nanoparticle. AFM revealed the two-dimensional topology of the silver nanoparticle with a characteristic size ranging around 50 nm. Confocal microscopy showed the cell-wall disruption of S. viridans treated with Bs-AgNPs. High-content screening and compound microscopy revealed the destruction of mycelia of R. solani after exposure to Bs-AgNPs. Furthermore, the Bs-AgNPs cured sheath blight disease by reducing lesion length and enhancing root and shoot length in Oryza sativa seeds. This soil-borne pathogen Bacillus-mediated synthesis approach of AgNPs appears to be cost-efficient, ecofriendly, and farmer-friendly, representing an easy way of providing valuable nutritious edibles in the future.

Fabrication of Reproducible and Selective Ammonia Vapor Sensor-Pellet of Polypyrrole/Cerium Oxide Nanocomposite for Prompt Detection at Room Temperature.

Polypyrrole (PPy) and polypyrrole/cerium oxide nanocomposite (PPy/CeO2) were prepared by the chemical oxidative method in an aqueous medium using anhydrous ferric chloride (FeCl3) as an oxidant. The successful formulation of materials was confirmed by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and transmittance electron microscopy (TEM). A four-in-line probe device was used for studying DC electrical conductivity and ammonia vapor sensing properties of PPy and PPy/CeO2. The significant improvement in both the conductivity and sensing parameters of PPy/CeO2 compared to pristine PPy reveals some synergistic/electronic interaction between PPy and cerium oxide nanoparticles (CeO2 NPs) working at molecular levels. The initial conductivity (i.e., conductivity at room temperature) was found to be 0.152 Scm-1 and 1.295 Scm-1 for PPy and PPy/CeO2, respectively. Also, PPy/CeO2 showed much better conductivity retention than pristine PPy under both the isothermal and cyclic ageing conditions. Ammonia vapor sensing was carried out at different concentration (0.01, 0.03, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 vol %). The sensing response of PPy/CeO2 varied with varying concentrations. At 0.5 vol % ammonia concentration, the % sensing response of PPy and PPy/CeO2 sensor was found to be 39.1% and 93.4%, respectively. The sensing efficiency of the PPy/CeO2 sensor was also evaluated at 0.4. 0.3, 0.2, 0.1, 0.05, 0.03, and 0.01 vol % ammonia concentration in terms of % sensing response, response/recovery time, reversibility, selectivity as well as stability at room temperature.

Enhanced Photocatalytic Activity of Cu2O Cabbage/RGO Nanocomposites under Visible Light Irradiation.

Towards the utilization of Cu2O nanomaterial for the degradation of industrial dye pollutants such as methylene blue and methyl orange, the graphene-incorporated Cu2O nanocomposites (GCC) were developed via a precipitation method. Using Hummers method, the grapheme oxide (GO) was initially synthesized. The varying weight percentages (1-4 wt %) of GO was incorporated along with the precipitation of Cu2O catalyst. Various characterization techniques such as Fourier-transform infra-red (FT-IR), X-ray diffraction (XRD), UV-visible diffused reflectance (UV-DRS), Raman spectroscopy, thermo gravimetric analysis (TGA), energy-dispersive X-ray analysis (EDX), and electro chemical impedance (EIS) were followed for characterization. The cabbage-like morphology of the developed Cu2O and its composites were ascertained from field-emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HR-TEM). In addition, the growth mechanism was also proposed. The results infer that 2 wt % GO-incorporated Cu2O composites shows the highest value of degradation efficiency (97.9% and 96.1%) for MB and MO at 160 and 220 min, respectively. Further, its catalytic performance over visible region (red shift) was also enhanced to an appreciable extent, when compared with that of other samples.

Comparison of the Effectiveness and Comfort Level of Two Commonly Used Mask Ventilation Techniques in a Model.

BACKGROUND: Mask ventilation is an important rescue airway skill for providing oxygenation and ventilation. Maintaining a good face mask seal is a fundamental factor for successful ventilation. Therefore, the aim of this study was to compare the effectiveness and comfortability of 2 commonly used mask ventilation techniques. METHODS: A randomized crossover study was performed to compare the 2-handed C-E and 2-handed V-E techniques on a simulation model. Respiratory therapists were recruited by convenience sampling to hold the mask during mechanical ventilation with a fixed tidal volume (VT) of 500 mL, a rate of 12 breaths/min and a PEEP of zero were provided. Each participant performed a 2-min ventilation session, with a total of 24 breaths for each technique. For each technique, we recorded the median VT and the number of successful breaths (≥300 mL). Provider comfort was assessed by using a 5-point Likert scale at the end of the 2 techniques. Subgroup analyses were conducted for sex, experience, and height of the participants. RESULTS: Of the 75 respiratory therapists recruited, 74 participants were included in the analysis. There was no statistically significant difference in the median VT between the V-E (417 mL [interquartile range, 396-427] mL) and C-E techniques (410 [interquartile range, 391-423] mL) (P = .82). Approximately 74% of breaths delivered by the C-E technique were effective, whereas only 68% of those delivered by the V-E technique were effective (P < .001). Most of the participants reported that using the 2-handed C-E technique was more comfortable. CONCLUSIONS: In our study, the median VT did not differ significantly between the 2 techniques. However, the C-E technique seemed to be superior to the V-E technique in terms of the number of effectively delivered breaths and comfortability. Further studies are recommended for basic airway management techniques.

Glycation and Oxidative Stress Increase Autoantibodies in the Elderly.

Aging causes gradual changes in free radicals, antioxidants, and immune-imbalance in the elderly. This study aims to understand links among aging, gluco-oxidative stress, and autoantibodies in asymptomatic individuals. In vitro glycation of human serum albumin (Gly-HSA) induces appreciable biochemical changes. Significant inhibition of advanced glycation end products (AGEs) formation was achieved using garlic extract (53.75%) and epigallocatechin-3-gallate from green tea (72.5%). Increased amounts of serum carbonyl content (2.42 ± 0.5) and pentosidine (0.0321 ± 0.0029) were detected in IV-S (S represent smokers) vs. IV group individuals. Direct binding ELISA results exhibited significantly high autoantibodies against Gly-HSA in group IV-S (0.55 ± 0.054; p < 0.001) and III-S (0.40 ± 0.044; p < 0.01) individuals as compared to the age matched subjects who were non-smokers (group IV and III). Moreover, high average percent inhibition (51.3 ± 4.1%) was obtained against Gly-HSA in IV-S group individuals. Apparent association constant was found to be high for serum immunoglobulin-G (IgG) from group IV-S (1.18 × 10-6 M) vs. serum IgG from IV group (3.32 × 10-7 M). Aging induced gluco-oxidative stress and AGEs formation may generate neo-epitopes on blood-proteins, contributing to production of autoantibodies in the elderly, especially smokers. Use of anti-glycation natural products may reduce age-related pathophysiological changes.

Biofloc Technology: Emerging Microbial Biotechnology for the Improvement of Aquaculture Productivity.

With the significant increases in the human population, global aquaculture has undergone a great increase during the last decade. The management of optimum conditions for fish production, which are entirely based on the physicochemical and biological qualities of water, plays a vital role in the prompt aquaculture growth. Therefore, focusing on research that highlights the understanding of water quality and breeding systems' stability is very important. The biofloc technology (BFT) is a system that maximizes aquaculture productivity by using microbial biotechnology to increase the efficacy and utilization of fish feeds, where toxic materials such as nitrogen components are treated and converted to a useful product, like a protein for using as supplementary feeds to the fish and crustaceans. Thus, biofloc is an excellent technology used to develop the aquaculture system under limited or zero water exchange with high fish stocking density, strong aeration, and biota. This review is highlighted on biofloc composition and mechanism of system work, especially the optimization of water quality and treatment of ammonium wastes. In addition, the advantages and disadvantages of the BFT system have been explained. Finally, the importance of contemporary research on biofloc systems as a figure of microbial biotechnology has been emphasized with arguments for developing this system for better production of aquaculture with limited natural resources of water.

Discrepant Antibody Testing Results: Which One to Believe?

The impact of solid-phase immunoassay for HLA antibody detection on the field of transplantation has been extremely significant by providing the most sensitive and precise method for characterization of HLA antibodies. However, despite all the benefits, technical limitations and inherent artifacts represent significant challenges, particularly with Luminex-based single-antigen bead (SAB) assay. Discordant results between antibody detection (screening assay) and identification (SAB) is not uncommon. Positive SAB assay in the context of negative screening testing is well documented and attributed to altered tertiary structure of HLA molecules exposing new epitopes or detection of naturally occurring antibodies. However, there are few reports that addressed the opposite scenario when negative SAB appeared in the context of positive screening assay. In such discrepant results, unmissed HLA antibody has to be excluded with certainty by other tests; however, with the availability of variable assays it may be difficult to choose the best combinations that clarify discrepancy without adding more confusion. Here we describe the results of correlation between 2 antibody screening solid-phase immunoassays (LABScreen Mixed using Luminex and FlowPRA Screen) on conventional flow cytometry and compare their outcomes with SAB and crossmatch results.

A methanol and protic ionic liquid Ugi multicomponent reaction path to cytotoxic α-phenylacetamido amides.

The Ugi four component reaction of an aldehyde, amine, isocyanide and an ethanoic acid was effected smoothly in protic ionic liquids ethylammonium nitrate (EAN) and propylammonium nitrate (PAN) to afford analogues of α-phenylacetamido amides in good to excellent isolated yields. The corresponding reactions in [BMIM][PF6] and the protic ionic liquid ethanolammonium nitrate (ETAN) failed. Microwave irradiation in EAN facilitated rapid access to three focused libraries, based on the parent isocyanide: cyclohexyl isocyanide, benzyl isocyanide and ethyl isocyanoacetate. Analysis of the structure activity relationship data suggested the presence of a bulky moiety originating from the isocyanide (cyclohexyl and benzyl) enhanced cytotoxicity. Removal of the acetylenic H-atom from the ethanoic acid moiety was detrimental to cytotoxicity. The most active analogues produced, N-(2-cyclohexylamino)-1-(4-methoxyphenyl)-2-oxoethyl-N-(3,5-dimethoxyphenyl)propiolamide, returned average GI50 values of ≤1 µM across the cancer cell lines evaluated. Combined, these data suggest that analogues of this nature are interesting potential anti-cancer development leads.