Advances in Ultra-small Fluorescence Nanoprobes for Detection of Metal Ions, Drugs, Pesticides and Biomarkers.

Identification of trace level chemical species (drugs, pesticides, metal ions and biomarkers) plays key role in environmental monitoring. Recently, fluorescence assay has shown significant advances in detecting of trace level drugs, pesticides, metal ions and biomarkers in real samples. Ultra-small nanostructure materials (metal nanoclusters (NCs), quantum dots (QDs) and carbon dots (CDs)) have been integrated with fluorescence spectrometer for sensitive and selective analysis of trace level target analytes in various samples including environmental and biological samples. This review summarizes the properties of metal NCs and ligand chemistry for the fabrication of metal NCs. We also briefly summarized the synthetic routes for the preparation of QDs and CDs. Advances of ultra-small fluorescent nanosensors (NCs, QDs and CDs) for sensing of metal ions, drugs, pesticides and biomarkers in various sample matrices are briefly discussed. Additionally, we discuss the recent challenges and future perspectives of ultra-small materials as fluorescent sensors for assaying of wide variety of target analytes in real samples.

Virtual(ly) no support: Associations between virtual support group participation and peripartum mental health outcomes during the COVID-19 pandemic.

OBJECTIVE: This study examined associations between participation in virtual support groups for peripartum women and mental health outcomes at follow-up approximately 8 months later. METHODS: This cross-sectional online survey study assessed 383 women from the Perinatal Experiences and COVID-19 Effects (PEACE) study. Initial participants (T1) were re-contacted (T2) and self-reported mental health symptoms of depression (CES-D), anxiety (GAD-7), and COVID-related grief were assessed at both time points. Participants reported involvement in virtual support groups and their perception of the effectiveness of social media in addressing feelings of loneliness. RESULTS: The majority (62%) of respondents participated in a virtual support group, 99% of whom used informal social media-based groups (e.g. Facebook groups). At initial evaluation, virtual group participants reported higher levels of depressive symptoms (p=0.008) and COVID grief (p=0.004), but not higher levels of anxiety. Across the cohort, self-reported depressive, anxiety, and grief symptoms did not change significantly at follow-up in paired analysis, and virtual group participants did not demonstrate improvement in mental health symptoms. CONCLUSIONS: Participation in virtual support groups did not seem to improve mental health outcomes for peripartum women, and most women found social media engagement minimally effective at addressing loneliness.

The impact of inhaler technique on clinical outcomes in adolescents and adults with asthma: A systematic review.

BACKGROUND: Many patients with asthma use their inhalers incorrectly, which can lead to sub-optimal asthma control and an increased risk of exacerbations. The Accuhaler/Diskus and Turbuhaler are arguably two of the most commonly used dry powder inhalers worldwide. METHODS: A systematic literature review (SLR) was conducted to assess the impact of inhalation errors with these dry powder inhalers on clinical outcomes in asthma. Database searches were conducted in MEDLINE, Embase and proceedings from scientific conferences. Observational studies in adults and adolescents with asthma, reporting data for Accuhaler/Diskus and Turbuhaler devices and at least one outcome of interest, were included. Dual-independent screening and validation of studies was performed. RESULTS: The search identified 35 studies. A range of inhaler errors was observed across studies and devices. In 8 out of the 9 studies that involved the two devices, the percentage of overall inhaler error rates was numerically (7 studies) or significantly (1 study) higher for Turbuhaler than Diskus, ranging from 3.7% to 71.9% for Diskus and 1.2%-83% for Turbuhaler. Critical errors, reported in three studies using similar definitions, ranged from 20% to 43% for Diskus and 32%-100% for Turbuhaler. Five studies reported a significant association between inhaler errors and worse asthma control, while one showed no difference. CONCLUSIONS: This SLR identified a large range of inhaler errors with both devices. Across devices, a better inhalation technique was associated with better asthma outcomes. This systematic review confirms the importance of patients using their inhalers correctly as an integral part of achieving optimal asthma outcomes.

The electrical pulse application enhances intra-cellular localization and potentiates cytotoxicity of curcumin in breast cancer cells.

Breast cancer is the most common cancer of women, and fifth leading cause of mortality worldwide. Existing breast cancer regimens are costly and produce severe side effects. This highlights a need for the development of efficient novel therapies, which are cost effective and limit side effects. An electrical pulse (EP)-based chemo therapy, known as electrochemotherapy (ECT) using the natural compound curcumin could be an effective alternative. ECT is a non-surgical modality, which produces excellent anti-tumor efficacy at small drug concentrations due to increased uptake of drugs. In clinics, ECT is shown to be effective in treating advanced, recurrent, and metastatic breast cancers, which are refractory to multiple modalities. ECT with curcumin triggers apoptotic cell death in breast cancer cells and could be an effective alternative, due to curcumin's low cost and reduced side-effects. However, there is a lack of studies quantifying the uptake of curcumin in response to EP application. Towards this, we determined the uptake of different curcuminoids (curcumin, desmethoxycurcumin, and bisdemethoxycurcumin) upon EP application and their impact on cell cytotoxicity. Additionally, we studied the combined effect of calcium chloride (CaCl2) and a curcuminoids (Cur) mixture, based on initial studies suggesting calcium electroporation as a potential inexpensive anti-cancer treatment. Our results indicate EP with Cur increases cellular uptake, cell shrinkage, and cytotoxicity. The EP + Cur resulted in the highest uptake of the bisdemethoxycurcumin. Further, EP also potentiated the cytotoxicity of CaCl2 and of the Cur and CaCl2 combination against breast cancer cells and caused apoptosis. Our preliminary data pave the way to further studies on Cur and CaCl2 combination treating breast cancer.

Simple hydrothermal approach for synthesis of fluorescent molybdenum disulfide quantum dots: Sensing of Cr3+ ion and cellular imaging.

Nowadays, fluorescent molybdenum disulfide quantum dots (MoS2 QDs) have proven to be potential candidates in the sensing and bioimaging areas owing to their exceptional intrinsic characteristics. Here, a simple hydrothermal strategy was explored for the preparation of MoS2 QDs using ammonium heptamolybdate and 6-mercaptopurine (6-MP) as precursors. The emission peak of MoS2 QDs was significantly quenched in the presence Cr3+ ion due to the selective surface chemistry on the surfaces of MoS2 QDs. The designed fluorescent MoS2 QDs showed a linear fluorescence quenching response with increasing concentration of Cr3+ ion (0.1-10 µM), allowing to detect Cr3+ ion even at 0.08 µM. This fluorescent MoS2 QDs were utilized for the quantification of Cr3+ ion in real samples (water and biological samples). Interestingly, the synthesized MoS2 QDs exhibited negligible cytotoxicity on NRK cells and acted as good candidates for imaging of Trichoderma viride fungal cells.

Acid Oxidation of Muskmelon Fruit for the Fabrication of Carbon Dots with Specific Emission Colors for Recognition of Hg2+ Ions and Cell Imaging.

In this study, water-soluble emissive carbon dots (CDs) are effectively fabricated with specific optical properties and colors by acid oxidation of muskmelon (Cucumis melo) fruit, which are termed as C. melo CDs (CMCDs). The fluorescence properties of CMCDs were tuned by controlling the experimental conditions that allow them to emit different colors, that is, blue (B-), green (G-), and yellow (Y-) CMCDs, with different emission wavelengths at 432, 515, and 554 nm when excited at 342, 415, and 425 nm, respectively. The fabricated multicolor-emissive CDs were confirmed by various analytical techniques. The sizes of B-, G-, and Y-CMCDs were found to be ∼3.5, ∼4.3, and ∼5.8 nm, respectively. The as-prepared CMCDs display stable emissions with quantum yields of 7.07, 26.9, and 14.3% for the three CMCDs, which could act as a promising probe for the selective detection of Hg2+ ions. Upon the addition of Hg2+ ions, the fluorescence intensity of G-CMCDs at 515 nm was quenched largely than that of B- and Y-CMCDs. The spectroscopic results display that the G-CMCDs acted as a sensor for the detection of Hg2+ ions with a wide linear range from 1.0 to 25 µM (R 2 = 0.9855) with a detection limit of 0.33 µM. This method was successfully applied to detect Hg2+ ions in biological and water samples. The fabricated multicolor-emissive CMCDs possess the cell (Cunninghamella elegans, Aspergillus flavus, and Rhizoctonia solani) imaging property, suggesting the biocompatible nature for multicolor imaging of various cells.

Influence of doping ion, capping agent and pH on the fluorescence properties of zinc sulfide quantum dots: Sensing of Cu2+ and Hg2+ ions and their biocompatibility with cancer and fungal cells.

Herein, a facile one-pot synthetic method was explored for the fabrication of glutathione capped Mn2+ doped­zinc sulphide quantum dots (GSH-Mn2+-ZnS QDs) for both fluorescent detection of Cu2+ and Hg2+ ions and for fluorescence imaging of two cancer (RIN5F and MDAMB231) and fungal (Rhizopus oryzae) cells. Particularly, doping of Mn2+ into ZnS QDs nanocrystal structure resulted a great improvement in the fluorescence properties of ZnS QDs. The emission peak of undoped ZnS QDs was found at 447 nm, which is due to the large number of surface defects in the ZnS QDs nanostructures. Under identical conditions, there is a good linear relationship between the quenching of fluorescence intensity and analytes (Cu2+ and Hg2+ ions) concentration in the range of 0.005 to 0.2 mM and of 0.025 to 0.4 mM for Cu2+ and Hg2+ ions, respectively. The GSH-Mn2+-ZnS QDs exhibit least cytotoxicity against RIN5F and MDAMB231 cells, demonstrating the multifunctional applications in sensing of metal ions and biocompatibility towards cancer (RIN5F and MDAMB231) and fungal (Rhizopus oryzae) cells.

Probing the selective separation of potassium ion from sodium ion with cyclopentadienyl anion as receptor: a computational study.

A systematic computational study has been carried out using post-Hartree-Fock and density functional theory methods on half sandwich (M-Cp), sandwich (Cp-M-Cp), inversed sandwich (M-Cp-M), and multi-decker chain complexes of alkali metal ions (Na(+), and K(+)). The binding affinity of cyclopentadienyl anion (Cp) with K(+) and Na(+) ions has been studied in half sandwich, sandwich, inversed sandwich, and multi-decker chain complexes. These complexes have been examined in the aqueous phase. The calculated results show that Cp anion can preferentially bind with Na(+) ion over K(+) ion in aqueous phase. The results obtained from DFT calculations have been compared with the crystal structures of Cp-Na and Cp-K complexes. The Bader's atoms in molecule (AIM) analysis were performed to characterize the non-covalent cation-π interactions in the Cp-M complexes. The calculated electron density at cage critical point indicates the strength of the Cp-M complexes. Energy decomposition analysis (EDA) has also been performed to investigate the origins of these interactions. The electrostatic interaction contributes significantly to the total interaction energy in Cp-M complexes. The relative stability difference of cyclopentadienyl anion (Cp) with K(+) and Na(+) ions in aqueous phase can be exploited for the separations from mixture such as sea bittern. The lower stability of K-Cp complex can induce to precipitate the K(+) ions more easily than the corresponding Na(+) ions. Graphical Abstract Potassium ion from sodium ion with cyclopentadienyl anion as receptor.

Mutagenic response of the endogenous hprt gene and lacI transgene in benzo[a]pyrene-treated Big Blue B6C3F1 mice.

Big Blue (BB) and generic B6C3F1 mice were given one to three i.p. injections of 50 mg/kg benzo[a]pyrene (B[a]P) in DMSO every other day to achieve cumulative doses of 50 to 150 mg/kg. Three weeks after treatment, the mutation frequency at the endogenous hprt gene and lacI transgene was measured in splenic T cells. Generic mice given 50, 100, and 150 mg/kg B[a]P displayed induced hprt frequencies (observed hprt frequency minus control frequency) of 5.5 +/- 1.0, 11 +/- 2.0, and 19 +/- 2.6 x 10(-6), respectively (average +/- SEM). In contrast, BB mice given 50 and 150 mg/kg B[a]P displayed induced hprt frequencies of 0.9 +/- 0.6 and 9.1 +/- 1.5 x 10(-6). 32P postlabelling revealed that the lower hprt response in BB mice correlated with lower amounts of BP-DNA adducts in spleen, liver, and lung 24 hours after B[a]P exposure. Western blot analysis of liver samples from B[a]P-treated mice suggests that the reduced adduct load in turn may be due to lower P450 1A1 levels in BB mice. The frequency of induced, nonsectored blue plaques (observed blue plaque frequency minus control frequency) in BB mice receiving 50 and 150 mg/kg B[a]P was 41 +/- 9 and 134 +/- 10 x 10(-6) (15- to 40-fold higher than the induced hprt frequency in the same treated animals). Sectored plaques were observed in both control and B[a]P groups but their frequency showed no relationship to dose (sectored frequency in all groups was approximately 20 x 10(-6)). To test whether persistent DNA adducts in the packaged lambda vector were contributing to the observed blue plaque frequency, purified lambda-LIZ DNA was treated in vitro with B[a]P diol epoxide (BPDE), packaged, and plated on E. coli lawn cells. Treatment with BPDE did not produce significant increases in homogeneous blue plaques, suggesting that the majority of mutants obtained from B[a]P-treated BB mice occurred in vivo. These results indicate that B[a]P exposure produces many more mutations at the lacI transgene than at the endogenous hprt locus.

Generation of a primitive erythroid cell line and promotion of its growth by basic fibroblast growth factor.

An immortalized cell line representing the primitive erythroid (EryP) lineage was established from in vitro-differentiated progeny (embryoid bodies [EBs]) of embryonic stem (ES) cells using a retroviral insertional mutation, and has been termed EB-PE for embryoid body-derived primitive erythroid. Even though EB-PE cells are immortalized, they show characteristics of normal EryP cells, such as gene expression and growth factor dependency. In addition, EB-PE cells can differentiate further in culture. Investigation of growth factor requirements of EB-PE cells showed that basic fibroblast growth factor (bFGF) and erythropoietin (Epo) play unique roles in EB-PE proliferation and differentiation. While bFGF was a strong mitogen, Epo was required for both proliferation and differentiation. The unique proliferative response to bFGF coincided with upregulation of its receptor, fibroblast growth factor receptor (fgfr-1), and downregulation of erythropoietin receptor (EpoR) gene expression. Studies of primary EryP cells derived from early EBs, when tested in a colony-formation assay, also provided evidence for the mitogenic role of bFGF in concert with Epo.