We classify the strategies for colloidal assembly and review the diverse potential applications of micro‐ and nanoparticle structures in materials and device prototypes. The useful properties of the ...particle assemblies, such as high surface‐to‐volume ratio, periodicity at mesoscale, large packing density, and long‐range ordering, can be harnessed in optical, electronic, and biosensing devices. We discuss the present and future trends in the colloidal‐ assembly field, focusing on the challenges of developing fabrication procedures that are rapid and efficiently controlled. We speculate on how the issues of scalability, control, and precision could be addressed, and how the functionality of the assemblies can be increased to better match the needs of technology.
Colloidal assemblies can be fabricated in a variety of structures, shapes and forms through a variety of physical processes that are still under extensive development. We survey the strategies for producing particle structures of different degrees of ordering and dimensionality, and the limitations and challenges in the practical fabrication of such assemblies.
Antimicrobial resistance (AMR) is caused by inappropriate or excessive antibiotic consumption. Early diagnosis of bacterial infections can greatly curb empirical treatment and thus AMR. Current ...diagnostic procedures are time-consuming as they rely on gene amplification and cell culture techniques that are inherently limited by the doubling rate of the involved species. Further, biochemical methods for species identification and antibiotic susceptibility testing for drug/dose effectiveness take several days and are non-scalable. We report a real-time, label-free approach called DEPIS that combines dielectrophoresis (DEP) for bacterial enrichment and impedance spectroscopy (IS) for cell viability analysis under 60 min. Target bacteria are captured on interdigitated electrodes using DEP (30 min) and their antibiotic-induced stress response is measured using IS (another 30 min). This principle is used to generate minimum bactericidal concentration (MBC) plots by measuring impedance change due to ionic release by dying bacteria in a low conductivity buffer. The results are rapid since they rely on cell death rather than cell growth which is an intrinsically slower process. The results are also highly specific and work across all bactericidal antibiotics studied, irrespective of their cellular target or drug action mechanism. More importantly, preliminary results with clinical isolates show that methicillin-susceptible Staphylococcus aureus (MSSA) can easily be differentiated from methicillin-resistant S. aureus (MRSA) under 1 h. This rapid cell analyses approach can aid in faster diagnosis of bacterial infections and benefit the clinical decision-making process for antibiotic treatment, addressing the critical issue of AMR.
•Real-time antibiotic response study with live bacteria using dielectrophoresis and impedance spectroscopy.•Use of drug-induced cellular ionic release as a proxy biomarker for bacterial cell viability.•Impedance-based minimum bactericidal concentration plots generated in 1 h for rapid drug susceptibility profiling.•Differentiation of methicillin-resistant Staphylococcus aureus (MRSA) from its wild type strain under 1 h.
The aim of this study was to determine the fractal dimension (FD) and radiomorphometric indices (RMIs) in the mandible from orthopantomographic radiographs in patients with oral lesions associated ...with smokeless/smoking tobacco (SLT/ST) and areca nut habits in a North Indian cohort.
A prospective, cross-sectional, observational pilot study was conducted of 120 subjects, including controls and 3 study groups of 30 patients each with oral submucous fibrosis, tobacco pouch keratosis, and oral leukoplakia (OL). Two observers calculated FD and the RMIs of mandibular cortical thickness (MCT), panoramic mandibular index (PMI), and mandibular cortical index (MCI).
Mean FD was significantly reduced compared to controls with all oral lesions (P < .05) and with all habits in 3 of 4 regions of interest (P < .05). MCT was significantly reduced with OL (P < .005) and in ST users (P < .05). PMI did not differ regarding lesion status or habits. Compared to the controls, MCI C2 type was significantly more common in all oral lesions (P ≤ .005) and all types of habit (P < .005). Inter- and intraobserver agreement was strong to excellent.
FD and RMI values were significantly altered compared to controls in oral lesions associated with tobacco and areca nut habits and in the dominant type of habit.
Extra-pulmonary tuberculosis (EPTB) is recognized mainly as a secondary manifestation of a primary tuberculosis (TB) infection in the lungs contributing to a high incidence of morbidity and ...mortality. The TB bacilli upon reactivation maneuver from the primary site disseminating to other organs. Diagnosis and treatment of EPTB remains challenging due to the abstruse positioning of the infected organs and the associated invasiveness of sample acquisition as well as misdiagnosis, associated comorbidities, and the inadequacy of biomarkers. Female genital tuberculosis (FGTB) represents the most perilous form of EPTB leading to poor uterine receptivity (UR), recurrent implantation failure and infertility in females. Although the number of TB cases is reducing, FGTB cases are not getting enough attention because of a lack of clinical awareness, nonspecific symptoms, and inappropriate diagnostic measures. This review provides an overview for EPTB, particularly FGTB diagnostics and treatment challenges. We emphasize the need for new therapeutics and highlight the need for the exaction of biomarkers as a point of care diagnostic. Nuclear receptors have reported role in maintaining UR, immune modulation, and TB modulation; therefore, we postulate their role as a therapeutic drug target and biomarker that should be explored in FGTB.
The present antibiotic susceptibility testing (AST) techniques based on bacterial culture, gene amplification and mass spectrometry are highly time consuming, labour intensive or expensive. Impedance ...spectroscopy is an emerging tool for rapid bacterial analysis as it is label-free, real-time, affordable and high-throughput. The over-reliance of this technique on complex chip designs and cell enrichment strategies has, however, slowed its foray into clinical AST. We demonstrate a label-free approach in which a low conductivity zwitterionic buffer is used for boosting impedance sensitivity in simple interdigitated electrodes (IDEs) allowing rapid AST in just 20 min without any liquid flow, biofunctionalization or cell enrichment steps. The detection principle relies on measuring changes in solution resistance due to antibiotic-induced bacterial cell death or growth. While the death-based approach is faster (20 min), it's restricted to surface-acting bactericidal antibiotics. The cell growth approach is longer (60–80 min) but more versatile as it applies to all drug types. Results for antibiotic sensitivity analysis and minimum inhibitory concentration (MIC) determination are illustrated for Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus against a wide class of antibiotics (penicillins, cephalosporins, polymyxins, carbapenems etc.).
•Antimicrobial susceptibility testing via impedance in low conductivity buffers.•Direct detection without cell enrichment, bioreceptor immobilization or liquid flow.•Principle of measurement: antibiotic-induced ionic changes due to cell death/growth.•Resistant bacteria identified in clinical samples as early as 20 min.•Results demonstrated for different combinations of 3 bacteria and 11 antibiotics.
Noninvasive, affordable circulating biomarkers for difficult-to-diagnose mild traumatic brain injury (mTBI) are an unmet medical need. Although blood microRNA (miRNA) levels are reportedly altered ...after traumatic brain injury (TBI), their diagnostic potential for mTBI remains inconclusive. We hypothesized that acutely altered plasma miRNAs could serve as diagnostic biomarkers both in the lateral fluid percussion injury (FPI) model and clinical mTBI. We performed plasma small RNA-sequencing from adult male Sprague-Dawley rats (
= 31) at 2 days post-TBI, followed by polymerase chain reaction (PCR)-based validation of selected candidates. miR-9a-3p, miR-136-3p, and miR-434-3p were identified as the most promising candidates at 2 days after lateral FPI. Digital droplet PCR (ddPCR) revealed 4.2-, 2.8-, and 4.6-fold elevations in miR-9a-3p, miR-136-3p, and miR-434-3p levels (
< 0.01 for all), respectively, distinguishing rats with mTBI from naïve rats with 100% sensitivity and specificity. DdPCR further identified a subpopulation of mTBI patients with plasma miR-9-3p (
= 7/15) and miR-136-3p (
= 5/15) levels higher than one standard deviation above the control mean at <2 days postinjury. In sTBI patients, plasma miR-9-3p levels were 6.5- and 9.2-fold in comparison to the mTBI and control groups, respectively. Thus, plasma miR-9-3p and miR-136-3p were identified as promising biomarker candidates for mTBI requiring further evaluation in a larger patient population.
The present study intends to investigate COVID-19 by targeting their main proteins with 17 selected drugs used for treating Oral Lichen Planus (OLP) which is a chronic muco-cutaneous disorder. Here, ...an attempt is made to gain better insight into the structure of various drugs targeting specific proteins which will be helpful in developing drugs useful for therapeutic and preventive measures.
In silico studies, molecular docking and molecular dynamic simulations were performed to repurpose the therapeutic drugs (n = 17) which were used to treat OLP against COVID-19. In addition, the maximum binding affinities of the key protein spike glycoprotein, main-protease (Mpro) of coronavirus, and Angiotensin-Converting Enzyme-2 (ACE-2) in the human body were evaluated with the selected drugs.
Epigallocatechin-3-gallate (EGCG) showed the highest docking values among the drugs selected for repurposing. Among the target proteins, EGCG has shown maximum binding affinity with ACE-2 receptor. Further, according to the molecular dynamic simulation studies, EGCG has shown the least conformational fluctuations with Mpro.
EGCG can be a potential inhibitor drug which can bind with ACE-2 receptor thus inhibiting the interaction of mainly Mpro protein and spike glycoprotein of SARS-CoV-2.
Relevance for patients: EGCG, a natural compound shows antiviral potential having considerably high affinity and stability with SARS-CoV-2. It might be further employed as a lead drug against selective inhibitors of SARS-CoV-2 for the therapeutic management of COVID-19 patients after necessary clinical trials.
Bacterial drug resistance has emerged as a serious global threat mandating the development of novel methodologies that allow facile modulation of antimicrobial action in a controlled fashion. ...Conjugating antibiotics to nanoparticles helps to meet this goal by increasing the drug's overall avidity, bioavailability and easier internalisation into mammalian cells, targeting bacteria that otherwise escape antibacterial action by host cell-localisation. We used polymyxin B sulfate (PMB) and sushi peptide as model drugs against Gram-negative bacteria and established their enhanced antimicrobial activity on Escherichia coli (E. coli) cells after conjugation to gold nanoparticles (AuNPs). The efficacy of the bioconjugates was also tested on Salmonella typhi (S. typhi) bacteria infected into cervical cancer cells (HeLa) and further improved through specific targeting via folate receptors. Our results demonstrate significantly lower inhibitory concentration values for sushi-NP assemblies as compared to free drug, especially at optimal drug loading levels. No major cytotoxicity was observed in mammalian cells alone.
Tissue hypoxia in oral submucous fibrosis (OSMF) induces hypoxia-inducible factor (HIF)-1 α and vascular endothelial growth factor (VEGF), causing angiogenesis. Single nucleotide polymorphisms (SNPs) ...may predict susceptibility to environmental carcinogens and to development of OSMF, as well as its severity and malignant transformation. This study aimed to determine the serologic levels and frequencies of SNPs of HIF-1 α and VEGF in OSMF.
In this prospective pilot study, the frequencies of SNPs of HIF-1 α (C1772 T, G1790 A); VEGF-A 936 C/T; and VEGF-C (rs7664413, rs1485766) in patients with OSMF or oral squamous cell carcinoma (OSCC) and in healthy controls were determined by using polymerase chain reaction (PCR) (n = 100 each), and serologic levels were determined by using enzyme-linked immunosorbent assay (ELISA (n = 50 each), in a North Indian population.
Heterozygous forms of HIF-1 α C1772 T (CT: odds ratio OR 5.0; 95% confidence interval CI 2.24–11.16; P < .001); HIF-1 α G1790 A (GA: OR 2.8; 95% CI 1.62–5.16; P < .001); and VEGF-C rs1485766 (AC: OR 2.18; 95% CI 1.19–3.99; P < .05) were associated with OSMF. The mean serologic levels of HIF-1 α, VEGF-A, and VEGF-C were significantly raised in patients with OSMF compared with healthy controls (P < .001).
The SNPs of HIF-1 α, VEGF-A, and VEGF-C and their serologic levels can act as prognostic biomarkers and aid in the development of specialized anti-HIF-1 α or anti-VEGF drugs for the management and prevention of OSCC in patients with OSMF.
We present a tyrosinase-conjugated zinc oxide-reduced graphene oxide (Tyr/ZnO-rGO) nanocomposite system as a biosensing test-bed for rapid and sensitive detection of dopamine (DA). The bioelectrodes ...(Tyr/ZnO-rGO/ITO) were designed by covalently immobilizing tyrosinase enzyme on spin-coated films of ZnO-rGO nanocomposite prepared via self-assembly approach. The cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) showed fast electron transfer kinetics of ZnO-rGO/ITO electrode. The response studies of the Tyr/ZnO-rGO/ITO bioelectrode revealed ultrafast (0.34 ± 0.09 s) detection of DA in a wide linear dynamic range of 0.1–1500 pM. The significant performance of the biosensor in terms of low detection limit (8.75 ± 0.64 pM) and high sensitivity (39.56 ± 0.41 μA nM−1) values is attributed to the fast and unhindered electron transfer mechanism of ZnO-rGO matrix having low electrochemical band gap. The nanoplatform exhibited high selectivity toward DA in human sera, and remained stable up to 3 months at 4 °C, representing its suitability for clinical applications.
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•Tyrosinase immobilized ZnO-rGO nanocomposite films as electrochemical biosensing probes for dopamine detection.•Reduced electrochemical bandgap of ZnO-rGO facilitates rapid electron transfer.•Fabricated sensor allows dopamine detection in clinically significant ranges (0.1–1500 pM).
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