Molecular Weights of Polyethyleneimine-Dependent Physicochemical Tuning of Gold Nanoparticles and FRET-Based Turn-On Sensing of Polymyxin B.

Environmental monitoring and the detection of antibiotic contaminants require expensive and time-consuming techniques. To overcome these challenges, gold nanoparticle-mediated fluorometric "turn-on" detection of Polymyxin B (PMB) in an aqueous medium was undertaken. The molecular weight of polyethyleneimine (PEI)-dependent physicochemical tuning of gold nanoparticles (PEI@AuNPs) was achieved and employed for the same. The three variable molecular weights of branched polyethyleneimine (MW 750, 60, and 1.3 kDa) molecules controlled the nano-geometry of the gold nanoparticles along with enhanced stabilization at room temperature. The synthesized gold nanoparticles were characterized through various advanced techniques. The results revealed that polyethyleneimine-stabilized gold nanoparticles (PEI@AuNP-1-3) were 4.5, 7.0, and 52.5 nm in size with spherical shapes, and the zeta potential values were 29.9, 22.5, and 16.6 mV, respectively. Accordingly, the PEI@AuNPs probes demonstrated high sensitivity and selectivity, with a linear relationship curve over a concentration range of 1-6 µM for polymyxin B. The limit of detection (LOD) was calculated as 8.5 nM. This is the first unique report of gold nanoparticle nano-geometry-dependent FRET-based turn-on detection of PMB in an aqueous medium. We believe that this approach would offer a complementary strategy for the development of a highly sophisticated and advanced sensing system for PMB and act as a template for the development of new nanomaterial-based engineered sensors for rapid antibiotic detection in environmental as well as biological samples.

Aggregation-Resistant, Turn-On-Off Fluorometric Sensing of Glutathione and Nickel (II) Using Vancomycin-Conjugated Gold Nanoparticles.

Glutathione (GSH) and nickel (II) cation have an indispensable role in various physiological processes, including preventing the oxidative damage of cells and acting as a cofactor for lipid metabolic enzymes. An imbalance in the physiological level of these species may cause serious health complications. Therefore, sensitive and selective fluorescent probes for the detection of GSH and nickel (II) are of great interest for clinical as well as environmental monitoring. Herein, vancomycin-conjugated gold nanoparticles (PEI-AuNP@Van) were prepared and employed for the detection of GSH and nickel (II) based on a turn-on-off mechanism. The as-synthesized PEI-AuNP@Van was ~7.5 nm in size; it exhibited a spherical shape with face-centered cubic lattice symmetry. As compared to vancomycin unconjugated gold nanoparticles, GSH led to the turn-on state of PEI-AuNP@Van, while Ni2+ acted as a fluorescence quencher (turn-off) without the aggregation of nanoparticles. These phenomena strongly justify the active role of vancomycin conjugation for the detection of GSH and Ni2+. The turn-on-off kinetics was linearly proportional over the concentration range between 0.05-0.8 µM and 0.05-6.4 µM. The detection limits were 205.9 and 90.5 nM for GSH and Ni2+, respectively; these results are excellent in comparison to previous reports. This study demonstrates the active role of vancomycin conjugation for sensing of GSH and Ni2+ along with PEI-AuNP@Van as a promising nanoprobe.

Diagnostic significance of dysregulated miRNAs in T-cell malignancies and their metabolic roles.

T-cell malignancy is a broad term used for a diverse group of disease subtypes representing dysfunctional malignant T cells transformed at various stages of their clonal evolution. Despite having similar clinical manifestations, these disease groups have different disease progressions and diagnostic parameters. The effective diagnosis and prognosis of such a diverse disease group demands testing of molecular entities that capture footprints of the disease physiology in its entirety. MicroRNAs (miRNAs) are a group of noncoding RNA molecules that regulate the expression of genes and, while doing so, leave behind specific miRNA signatures corresponding to cellular expression status in an altered stage of a disease. Using miRNAs as a diagnostic tool is justified, as they can effectively distinguish expressional diversity between various tumors and within subtypes of T-cell malignancies. As global attention for cancer diagnosis shifts toward liquid biopsy, diagnosis using miRNAs is more relevant in blood cancers than in solid tumors. We also lay forward the diagnostic significance of miRNAs that are indicative of subtype, progression, severity, therapy response, and relapse. This review discusses the potential use and the role of miRNAs, miRNA signatures, or classifiers in the diagnosis of major groups of T-cell malignancies like T-cell acute lymphoblastic lymphoma (T-ALL), peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma (ENKTCL), and cutaneous T-cell lymphoma (CTCL). The review also briefly discusses major diagnostic miRNAs having prominent metabolic roles in these malignancies to highlight their importance among other dysregulated miRNAs.

Synthesis of vancomycin functionalized fluorescent gold nanoparticles and selective sensing of mercury (II).

Mercury ions (Hg2+) are widely found in the environment; it is considered a major pollutant. Therefore, the rapid and reliable detection of Hg2+ is of great technical interest. In this study, a highly fluorescent, sensitive, and selective fluorometric assay for detecting Hg2+ ions was developed using vancomycin functionalized and polyethyleneimine stabilized gold nanoparticles (PEI-f-AuNPs@Van). The as-made gold nanoparticles were highly fluorescent, with excitation and emission maxima occurring at 320 and 418 nm, respectively. The size of nanoparticles was ~7 nm; a zeta potential of ~38.8 mV was determined. The XRD analysis confirmed that the nanoparticles possessed crystalline structure with face centerd cubic symmetry. Using the PEI-f-AuNP@Van probe, the detection limit of Hg2+ ion was achieved up to 0.988 nM (within a linear range) by calculating the KSV. However, the detection limit in a natural environmental sample was shown to be 12.5 nM. Furthermore, the selectivity tests confirmed that the designed probe was highly selective to mercury (II) cations among tested other divalent cations. Owing to its sensitivity and selectivity, this approach for Hg2+ ions detection can be utilized for the analysis of real water samples.

Performance of qSOFA Score as a Screening Tool for Sepsis in the Emergency Department.

Introduction: Sepsis is the leading cause of mortality, and various scoring systems have been developed for its early identification and treatment. The objective was to test the ability of quick sequential organ failure assessment (qSOFA) score to identify sepsis and predict sepsis-related mortality in the emergency department (ED). Methods: We conducted a prospective study from July 2018 to April 2020. Consecutive patients with age ≥18 years who presented to the ED with a clinical suspicion of infection were included. Sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and odds ratio (OR) for sepsis related mortality on day 7 and 28 were measured. Results: A total of 1200 patients were recruited; of which 48 patients were excluded and 17 patients were lost to follow-up. 54 (45.4%) of 119 patients with positive qSOFA (qSOFA >2) died at 7 days and 76 (63.9%) died at 28 days. A total of 103 (10.1%) of 1016 patients with negative qSOFA (qSOFA score <2) died at 7 days and 207 (20.4%) died at 28 days. Patients with positive qSOFA score were at higher odds of dying at 7 days (OR: 3.9, 95% confidence interval [CI]: 3.1-5.2, P < 0.001) and 28 days (OR: 6.9, 95% CI: 4.6-10.3, P < 0.001). The PPV and NPV with positive qSOFA score to predict 7- and 28-day mortality were 45.4%, 89.9% and 63.9%, 79.6%, respectively. Conclusion: The qSOFA score can be used as a risk stratification tool in a resource-limited setting to identify infected patients at an increased risk of death.

Diagnostic Accuracy of Ocular Ultrasonography in Identifying Raised Intracranial Pressure among Pediatric Population.

INTRODUCTION: Role of CT scan, MRI, ophthalmoscopy, direct monitoring by a transducer probe in identifying raised intracranial pressure (ICP) in emergency department is limited. There are few studies correlating elevated optic nerve sheath diameter (ONSD) measured by point of care ultrasound (POCUS) with raised ICP in pediatrics emergencies. We studied the diagnostic accuracy of ONSD, crescent sign, and optic disc elevation in identifying increased ICP in pediatrics. METHODS: Prospective observational study was done between April 2018 and August 2019 after ethics approval. Out of 125 subjects, 40 patients without clinical features of raised ICP were recruited as external controls and 85 with clinical features of raised ICP as study subjects. Their demographic profile, clinical examination, and ocular ultrasound findings were noted. This was followed by CT scan. Out of 85 patients, 43 had raised ICP (cases) and 42 had normal ICP (disease controls). Diagnostic accuracy of ONSD in identifying raised ICP was evaluated using STATA. RESULTS: The mean ONSD in case group was 5.5 ± 0.6 mm, 4.9 ± 0.5 mm in disease control group and external control group was 4.8 ± 0.3 mm. Cut-off of ONSD for raised ICP at ≥4.5 mm had a sensitivity and specificity of 97.67% and 10.98%, while ≥5.0 mm showed a sensitivity and specificity of 86.05% and 71.95%. Crescent sign and optic disc elevation had good correlation with increased ICP. CONCLUSION: ONSD ≥5 mm by POCUS identified raised ICP in pediatric population. Crescent sign and optic disc elevation may function as additional POCUS signs in identifying raised ICP.

A whole cell fluorescence quenching-based approach for the investigation of polyethyleneimine functionalized silver nanoparticles interaction with Candida albicans.

The antimicrobial activity of metal nanoparticles can be considered a two-step process. In the first step, nanoparticles interact with the cell surface; the second step involves the implementation of the microbicidal processes. Silver nanoparticles have been widely explored for their antimicrobial activity against many pathogens. The interaction dynamics of functionalized silver nanoparticles at the biological interface must be better understood to develop surface-tuned biocompatible nanomaterial-containing formulations with selective antimicrobial activity. Herein, this study used the intrinsic fluorescence of whole C. albicans cells as a molecular probe to understand the cell surface interaction dynamics of polyethyleneimine-functionalized silver nanoparticles and antifungal mechanism of the same. The results demonstrated that synthesized PEI-f-Ag-NPs were ~ 5.6 ± 1.2 nm in size and exhibited a crystalline structure. Furthermore, the recorded zeta potential (+18.2 mV) was associated with the stability of NPS and shown a strong electrostatic interaction tendency between the negatively charged cell surface. Thus, rapid killing kinetics was observed, with a remarkably low MIC value of 5 µg/mL. PEI-f-Ag-NPs quenched the intrinsic fluorescence of C. albicans cells with increasing incubation time and concentration and have shown saturation effect within 120 min. The calculated binding constant (Kb = 1 × 105 M-1, n = 1.01) indicated strong binding tendency of PEI-f-Ag-NPs with C. albicans surface. It should also be noted that the silver nanoparticles interacted more selectively with the tyrosine-rich proteins in the fungal cell. However, calcofluor white fluorescence quenching showed non-specific binding on the cell surface. Thus, the antifungal mechanisms of PEI-f-Ag-NPs were observed as reactive oxygen species (ROS) overproduction and cell wall pit formation. This study demonstrated the utility of fluorescence spectroscopy for qualitative analysis of polyethyleneimine-functionalized silver nanoparticle interaction/binding with C. albicans cell surface biomolecules. Although, a quantitative approach is needed to better understand the interaction dynamics in order to formulate selective surface tuned nanoparticle for selective antifungal activity.

Size and Zeta Potential Clicked Germination Attenuation and Anti-Sporangiospores Activity of PEI-Functionalized Silver Nanoparticles against COVID-19 Associated Mucorales (Rhizopus arrhizus).

The SARS-CoV-2 infections in Indian people have been associated with a mucormycotic fungal infection caused by the filamentous fungi Rhizopus arrhizus. The sporangiospores of R. arrhizus are omnipresent in the environment and cause infection through inhalation or ingestion of contaminated air and foods. Therefore, the anti-sporangiospore activity of polyethyleneimine functionalized silver nanoparticles (PEI-f-Ag-NPs) with variable size and surface charge as a function of the molecular weight of PEI was explored. The results showed that both PEI-f-AgNP-1 and PEI-f-AgNP-2, potentially, attenuated the germination and reduced the viability of sporangiospores. Furthermore, the results showed that the minimum inhibitory concentration (MIC) values of both PEI-f-AgNP-1 and PEI-f-AgNP-2 (1.65 and 6.50 µg/mL, respectively) were dependent on the nanoparticle size and surface ζ potentials. Similarly, the sporangiospore germination inhibition at MIC values was recorded, showing 97.33% and 94% germination inhibition, respectively, by PEI-f-AgNP-1 and 2 within 24 h, respectively. The confocal laser scanning microscopy, SEM-EDS, and confocal Raman spectroscopy investigation of PEI-f-Ag-NPs treated sporangiospores confirmed size and surface charge-dependent killing dynamics in sporangiospores. To the best of our knowledge, this is the first investigation of the polyethyleneimine functionalized silver nanoparticle-mediated size and surface charge-dependent anti-sporangiospore activity against R. arrhizus, along with a possible antifungal mechanism.

Amine-Functionalized Silver Nanoparticles: A Potential Antiviral-Coating Material with Trap and Kill Efficiency to Combat Viral Dissemination (COVID-19).

The outbreak of COVID-19 has drastically affected the daily lifestyles of people globally where specific Coronavirus-2 transmits primarily by respiratory droplets. Structurally, the SARS-CoV-2 virus is made up of four types of proteins in which S-protein is indispensable among them, as it causes rapid replication in the host body. Therefore, the glycine and alanine composed of HR1 of S-protein is the ideal target for antiviral action. Different forms of surface-active PPEs can efficiently prevent this transmission in this circumstance. However, the virus can survive on the conventional PPEs for a long time. Hence, the nanotechnological approaches based on engineered nanomaterials coating on medical equipments can potentially prevent the dissemination of infections in public. Silver nanoparticles with tuneable physicochemical properties and versatile chemical functionalization provide an excellent platform to combat the disease. The coating of amine-functionalized silver nanoparticle (especially amine linked to aliphatic chain and trialkoxysilane) in its nanostructured form enables cloths trap and kill efficient. PPEs are a primary and reliable preventive measure, although they are not 100% effective against viral infections. So, developing and commercializing surface-active PPEs with trap and kill efficacy is highly needed to cope with current and future viral infections. This review article discusses the COVID-19 morphology, antiviral mechanism of Ag-NPs against SARS-CoV-2 virus, surface factors that influence viral persistence on fomites, the necessity of antiviral PPEs, and the potential application of amine-functionalized silver nanoparticles as a coating material for the development of trap and kill-efficient face masks and PPE kits.

Synthetic incorporation of palladium-nickel bimetallic nanoparticles within mesoporous silica/silica nanoparticles as efficient and cheaper catalyst for both cationic and anionic dyes degradation.

Nickel-palladium bimetallic nanocrystallite supported mesoporous silica/silica nanoparticles (MSPs/MSNPs) made at a controlled ratio of Pd/Ni via organotrialkoxysilane mediated reduction of palladium cations are reported. The organotrialkoxysilane serve as a template for the stabilization and formation of bimetallic Pd-Ni nanocrystallite within MSPs/MSNPs that are characterized by TEM, EDX, HR-SEM, HR-MS, XRD, BET and Elemental mapping analysis, kinetic analysis for degradation of both cationic and anionic dyes, i.e., rhodamine B and congo red, respectively. The nanocrystallite inserted MSNPs of particle diameter 200 nm justify faster degradation with rate constant to the order of 6.9 x10-2s-1 as compared to that for MSPs of 50 µm to the order of 3.2 x10-2 s-1 for 15 ppm Rh B within 50 s as compared to that for mesoporous silica of 50 µm within 110 s under similar conditions with analogous observation for the degradation of congo red. Heterogeneous support is fully recyclable and shows 100% catalytic activity even after five subsequent applications. The degradation dynamics have further been evaluated based on fluorescent spectra and HR-MS analysis.

Interplay of Nutrition and Psychoneuroendocrineimmune Modulation: Relevance for COVID-19 in BRICS Nations.

The consequences of COVID-19 are not limited to physical health deterioration; the impact on neuropsychological well-being is also substantially reported. The inter-regulation of physical health and psychological well-being through the psychoneuroendocrineimmune (PNEI) axis has enduring consequences in susceptibility, treatment outcome as well as recuperation. The pandemic effects are upsetting the lifestyle, social interaction, and financial security; and also pose a threat through perceived fear. These consequences of COVID-19 also influence the PNEI system and wreck the prognosis. The nutritional status of individuals is also reported to have a determinative role in COVID-19 severity and convalescence. In addition to energetic demand, diet also provides precursor substances [amino acids (AAs), vitamins, etc.] for regulators of the PNEI axis such as neurotransmitters (NTs) and immunomodulators. Moreover, exaggerated immune response and recovery phase of COVID-19 demand additional nutrient intake; widening the gap of pre-existing undernourishment. Mushrooms, fresh fruits and vegetables, herbs and spices, and legumes are few of such readily available food ingredients which are rich in protein and also have medicinal benefits. BRICS nations have their influences on global development and are highly impacted by a large number of confirmed COVID-19 cases and deaths. The adequacy and access to healthcare are also low in BRICS nations as compared to the rest of the world. Attempt to combat the COVID-19 pandemic are praiseworthy in BRICS nations. However, large population sizes, high prevalence of undernourishment (PoU), and high incidence of mental health ailments in BRICS nations provide a suitable landscape for jeopardy of COVID-19. Therefore, appraising the interplay of nutrition and PNEI modulation especially in BRICS countries will provide better understanding; and will aid in combat COVID-19. It can be suggested that the monitoring will assist in designing adjunctive interventions through medical nutrition therapy and psychopsychiatric management.

Curcumin, a traditional spice component, can hold the promise against COVID-19?

The severity of the recent pandemic and the absence of any specific medication impelled the identification of existing drugs with potential in the treatment of Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Curcumin, known for its pharmacological abilities especially as an anti-inflammatory agent, can be hypothesized as a potential candidate in the therapeutic regimen. COVID-19 has an assorted range of pathophysiological consequences, including pulmonary damage, elevated inflammatory response, coagulopathy, and multi-organ damage. This review summarizes the several evidences for the pharmacological benefits of curcumin in COVID-19-associated clinical manifestations. Curcumin can be appraised to hinder cellular entry, replication of SARS-CoV-2, and to prevent and repair COVID-19-associated damage of pneumocytes, renal cells, cardiomyocytes, hematopoietic stem cells, etc. The modulation and protective effect of curcumin on cytokine storm-related disorders are also discussed. Collectively, this review provides grounds for its clinical evaluation in the therapeutic management of SARS-CoV-2 infection.

Molecular weight of polyethylenimine-dependent transfusion and selective antimicrobial activity of functional silver nanoparticles.

Synthetic cationic polymer-mediated synthesis of silver nanoparticles and selective antimicrobial activity of the same were demonstrated. Polyethyleneimine (PEI)-coated silver nanoparticles showed antimicrobial activity against Acinetobacter baumannii as a function of the polymeric molecular weight (MW) of PEI. Silver nanoparticles were coated with PEI of three different MWs: Ag-NP-1 with PEI exhibiting a MW of 750,000, Ag-NP-2 with PEI exhibiting a MW of 1300, and Ag-NP-3 with PEI exhibiting a MW of 60,000. These nanoparticles showed a particle size distribution of 4-20 nm. The nanoparticles exhibited potent antimicrobial activity against A. baumannii, with the minimum inhibitory concentration of Ag-NP-1, Ag-NP-2, and Ag-NP-3 on the order of 5, 10, and 5 µg/mL, respectively, and minimum bactericidal concentration of Ag-NP-1, Ag-NP-2, and Ag-NP-3 on the order of 10, 20, and 10 µg/mL, respectively. Fluorescence imaging of Ag-NPs revealed selective transfusion of Ag-NPs across the cell membrane as a function of the polymeric MW; differential interaction of the cytoplasmic proteins during antimicrobial activity was observed.