Miniaturized Biosensors Based on Lanthanide-Doped Upconversion Polymeric Nanofibers.

Electrospun nanofibers possess a large surface area and a three-dimensional porous network that makes them a perfect material for embedding functional nanoparticles for diverse applications. Herein, we report the trends in embedding upconversion nanoparticles (UCNPs) in polymeric nanofibers for making an advanced miniaturized (bio)analytical device. UCNPs have the benefits of several optical properties, like near-infrared excitation, anti-Stokes emission over a wide range from UV to NIR, narrow emission bands, an extended lifespan, and photostability. The luminescence of UCNPs can be regulated using different lanthanide elements and can be used for sensing and tracking physical processes in biological systems. We foresee that a UCNP-based nanofiber sensing platform will open opportunities in developing cost-effective, miniaturized, portable and user-friendly point-of-care sensing device for monitoring (bio)analytical processes. Major challenges in developing microfluidic (bio)analytical systems based on UCNPs@nanofibers have been reviewed and presented.

Autophagy promotes efficient T cell responses to restrict high-dose Mycobacterium tuberculosis infection in mice.

Although autophagy sequesters Mycobacterium tuberculosis (Mtb) in in vitro cultured macrophages, loss of autophagy in macrophages in vivo does not result in susceptibility to a standard low-dose Mtb infection until late during infection, leaving open questions regarding the protective role of autophagy during Mtb infection. Here we report that loss of autophagy in lung macrophages and dendritic cells results in acute susceptibility of mice to high-dose Mtb infection, a model mimicking active tuberculosis. Rather than observing a role for autophagy in controlling Mtb replication in macrophages, we find that autophagy suppresses macrophage responses to Mtb that otherwise result in accumulation of myeloid-derived suppressor cells and subsequent defects in T cell responses. Our finding that the pathogen-plus-susceptibility gene interaction is dependent on dose has important implications both for understanding how Mtb infections in humans lead to a spectrum of outcomes and for the potential use of autophagy modulators in clinical medicine.

Type I IFN signaling in the absence of IRGM1 promotes M. tuberculosis replication in immune cells by suppressing T cell responses.

Polymorphisms in the IRGM gene are associated with susceptibility to tuberculosis in humans. A murine ortholog of Irgm, Irgm1, is also essential for controlling Mycobacterium tuberculosis (Mtb) infection in mice. Multiple processes have been associated with IRGM1 activity that could impact the host response to Mtb infection, including roles in autophagy-mediated pathogen clearance and expansion of activated T cells. However, what IRGM1-mediated pathway is necessary to control Mtb infection in vivo and the mechanistic basis for this control remains unknown. We dissected the contribution of IRGM1 to immune control of Mtb pathogenesis in vivo and found that Irgm1 deletion leads to higher levels of IRGM3-dependent type I interferon signaling. The increased type I interferon signaling precludes T cell expansion during Mtb infection. The absence of Mtb-specific T cell expansion in Irgm1-/- mice results in uncontrolled Mtb infection in neutrophils and alveolar macrophages, which directly contributes to susceptibility to infection. Together, our studies reveal that IRGM1 is required to promote T cell-mediated control of Mtb infection in neutrophils, which is essential for the survival of Mtb-infected mice. These studies also uncover new ways type I interferon signaling can impact TH1 immune responses.

Estimation of spectroscopic parameters and TL glow curve analysis of Eu3+-activated CaY2O4 phosphor.

The solid-state reaction method was utilised to create a down-conversion phosphor in an air environment in CaY2O4:Eu3+ nanocrystalline material. The calcination temperature was set at 1000 °C, and the sintering temperature was set at 1300 °C. Following annealing, confirmation of the crystallinity quality of the phosphor was accomplished by the use of X-ray diffraction analysis. The particle size was predicted to be 43.113 nm using Scherrer's formula. To produce down-conversion luminescence spectra, an excitation wavelength of 247 nm was applied with a fluorescence spectrophotometer. The PL got increasingly intense as the concentration of the dopant increased. The maximum intensity was measured at 2.0 mol% of Eu3+ ion, which gradually decreased as the concentration increased because of concentration quenching. To analyse spectrophotometric peak determinations, the approach developed by the Commission Internationale de l'Éclairage (CIE) was used. Thermoluminescence (TL) glow curve analysis of the CaY2O4:Eu3+-doped phosphor manufactured here revealed a wide TL centred at 225 °C, which comprised of so many peaks that may be extracted by the computerised glow curve deconvolution (CGCD) approach using glow-fit software. The associated kinetic parameters were then determined. The prepared phosphor may be useful for application in various display devices upon excitation by 247 nm; the prominent 613 nm peak of the Eu3+ ion (5D0 → 7F2) electric dipole transition features a red component. CaY2O4:Eu3+ phosphors show promise as materials for potential use in phosphor-converted white LEDs in the field of solid-state lighting technology. The linear connection that the TL glow curve has with UV dose provides evidence for its possible use in dosimetry.

Optimizing the luminescence efficiency of an europium (Eu3+) doped SrY2O4 phosphor for flexible display and lighting applications.

This research paper reports the synthesis and luminescence study of an Eu3+ activated SrY2O4 phosphor prepared by a modified solid-state reaction method with varying concentrations of Eu3+ ions (0.1-2.5 mol%). X-ray diffraction (XRD) revealed the orthorhombic structure and Fourier transform infrared spectroscopy (FTIR) methods were used to analyse the produced phosphors. Photoluminescence emission and excitation spectra were recorded for varying concentrations of Eu3+ ions, and an optimum concentration of 2.0 mol% was found to produce the highest intensity. Under 254 nm excitation the emission peaks were found to be at 580 nm, 590 nm, 611 nm and 619 nm, corresponding to transitions at 5D0 → 7F0, 5D0 → 7F1, and 5D0 → 7F2 respectively. Because of Eu3+ inherent luminosity, these emission peaks indicate radiative transitions between excited states of ions, making them useful for developing white light-emitting phosphors for optoelectronic and flexible display applications. The 1931 CIE (x, y) chromaticity coordinates were calculated from the photoluminescence emission spectra and found to be near white light emission, indicating the potential application of the prepared phosphor for light emitting diodes (white component). TL glow curve analysis was also performed for various concentrations of doping ions and UV exposure times, and a single broad peak was observed at 187 °C. Using the computerised glow curve deconvolution (CGCD) method, kinetic parameters were computed.

Intense green light emission and thermoluminescence glow curve analysis of Tb3+ -activated CaY2 O4 phosphor.

Here, the synthesis and luminescence analysis of the Tb3+ -activated phosphor were reported. The CaY2 O4 phosphors were synthesized using a modified solid-state reaction method with a variable doping concentration of Tb3+ ion (0.1-2.5 mol%). As synthesized, the phosphor was characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction analysis techniques for the optimized concentration of doping ions. The prepared phosphor showed a cubic structure, and FTIR analysis confirmed functional group analysis. It was discovered that the intensity of 1.5 mol% was higher than at other concentrations after the photoluminescence (PL) excitation and emission spectra were recorded for different concentrations of doping ions. The excitation was monitored at 542 nm, and the emission was monitored at 237 nm. At 237 nm excitation, the emission peaks were found at 620 nm (5 D4 →7 F3 ), 582 nm (5 D4 →7 F4 ), 542 nm (5 D4 →7 F5 ), and 484 nm (5 D4 →7 F6 ). The 1931 CIE (x, y) chromaticity coordinates showed the distribution of the spectral region calculated from the PL emission spectra. The values of (x = 0.34 and y = 0.60) were very close to dark green emission. Therefore, the produced phosphor would be very useful for light-emitting diode (green component) applications. Thermoluminescence glow curve analysis for various concentrations of doping ions and various ultraviolet (UV) exposure times was carried out, and a single broad peak was found at 252°C. The computerized glow curve deconvolution method was used to obtain the related kinetic parameters. The prepared phosphor exhibited an excellent response to UV dose and could be useful for UV ray dosimetry.

Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir.

The emergence of Plasmodium falciparum resistance raises an urgent need to find new antimalarial drugs. Here, we report the rational repurposing of the anti-hepatitis C virus drug, alisporivir, a nonimmunosuppressive analog of cyclosporin A, against artemisinin-resistant strains of P. falciparum. In silico docking studies and molecular dynamic simulation predicted strong interaction of alisporivir with PfCyclophilin 19B, confirmed through biophysical assays with a Kd value of 354.3 nM. Alisporivir showed potent antimalarial activity against chloroquine-resistant (PfRKL-9 with resistance index [Ri] 2.14 ± 0.23) and artemisinin-resistant (PfKelch13R539T with Ri 1.15 ± 0.04) parasites. The Ri is defined as the ratio between the IC50 values of the resistant line to that of the sensitive line. To further investigate the mechanism involved, we analyzed the expression level of PfCyclophilin 19B in artemisinin-resistant P. falciparum (PfKelch13R539T). Semiquantitative real-time transcript, Western blot, and immunofluorescence analyses confirmed the overexpression of PfCyclophilin 19B in PfKelch13R539T. A 50% inhibitory concentration in the nanomolar range, together with the targeting of PfCyclophilin 19B, suggests that alisporivir can be used in combination with artemisinin. Since artemisinin resistance slows the clearance of ring-stage parasites, we performed a ring survival assay on artemisinin-resistant strain PfKelch13R539T and found significant decrease in parasite survival with alisporivir. Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity in vivo. Altogether, with the rational target-based Repurposing of alisporivir against malaria, our results support the hypothesis that targeting resistance mechanisms is a viable approach toward dealing with drug-resistant parasite.

Role of Workplace Spirituality, Empathic Concern and Organizational Politics in Employee Wellbeing: A Study on Police Personnel.

Employee wellbeing as a central aspect of organizational growth has been widely regarded and accepted. Therefore, a considerable growth in the number of researches focusing on employee wellbeing has been comprehended in recent years. Employee wellbeing characterizes the individual's own cognitive interpretation of his/her life at work. The present study made an attempt to examine how workplace spirituality, empathic concern and organizational politics influences employee wellbeing. It was hypothesized that empathic concern mediates the relationship between workplace spirituality and employee wellbeing while organizational politics act as a moderator in this relationship. A survey was conducted on 253 employees working in Uttar Pradesh Police department (Uttar Pradesh, India). The results obtained revealed that workplace spirituality, empathic concern and employee wellbeing carries a positive association among them whereas these variables were found to be negatively correlated with organizational politics. Results also depicted that empathic concern significantly mediates between workplace spirituality and employee wellbeing. Further, moderated mediation analysis confirmed employee wellbeing as a function of workplace spirituality, empathic concern and organizational politics. The present study has put forward several practical implications for business practitioners and research directions for academicians, emphasizing upon the need to investigate the comprehensive impact of employee wellbeing in organization and the society as a whole.

Effects of Meditation on Structural Changes of the Brain in Patients With Mild Cognitive Impairment or Alzheimer's Disease Dementia.

Previous cross-sectional studies reported positive effects of meditation on the brain areas related to attention and executive function in the healthy elderly population. Effects of long-term regular meditation in persons with mild cognitive impairment (MCI) and Alzheimer's disease dementia (AD) have rarely been studied. In this study, we explored changes in cortical thickness and gray matter volume in meditation-naïve persons with MCI or mild AD after long-term meditation intervention. MCI or mild AD patients underwent detailed clinical and neuropsychological assessment and were assigned into meditation or non-meditation groups. High resolution T1-weighted magnetic resonance images (MRI) were acquired at baseline and after 6 months. Longitudinal symmetrized percentage changes (SPC) in cortical thickness and gray matter volume were estimated. Left caudal middle frontal, left rostral middle frontal, left superior parietal, right lateral orbitofrontal, and right superior frontal cortices showed changes in both cortical thickness and gray matter volume; the left paracentral cortex showed changes in cortical thickness; the left lateral occipital, left superior frontal, left banks of the superior temporal sulcus (bankssts), and left medial orbitofrontal cortices showed changes in gray matter volume. All these areas exhibited significantly higher SPC values in meditators as compared to non-meditators. Conversely, the left lateral occipital, and right posterior cingulate cortices showed significantly lower SPC values for cortical thickness in the meditators. In hippocampal subfields analysis, we observed significantly higher SPC in gray matter volume of the left CA1, molecular layer HP, and CA3 with a trend for increased gray matter volume in most other areas. No significant changes were found for the hippocampal subfields in the right hemisphere. Analysis of the subcortical structures revealed significantly increased volume in the right thalamus in the meditation group. The results of the study point out that long-term meditation practice in persons with MCI or mild AD leads to salutary changes in cortical thickness and gray matter volumes. Most of these changes were observed in the brain areas related to executive control and memory that are prominently at risk in neurodegenerative diseases.

White light emission and thermoluminescence studies of Dy3+ -activated hardystonite (Ca2 ZnSi2 O7 ) phosphor.

Here, we report the photoluminescence and thermoluminescent properties of Dy-activated Ca2 ZnSi2 O7 phosphors synthesized using the solid-state method. The synthesized phosphors showed hardystonite type structure, and had micron-sized particles. Fourier transform infrared spectroscopy (FTIR) showed the existence of the functional groups and confirmed the formation of phosphor and photoluminescence techniques. The phosphors under excitation at 239 nm exhibited green-yellow emission spectra in the region 481-575 nm corresponding to the 4 F9/2 →6 H15/2 and 4 F9/2 →6 H13/2 transitions of Dy3+ ions. The Commission Internationale de l'Eclairage (CIE) coordinates were achieved to be (0.25, 0.27), which was narrowly close to the white region. Thermoluminescence (TL) glow curve analysis of prepared Dy3+ -activated Ca2 ZnSi2 O7 phosphors were recorded for different ultraviolet (UV) light exposure times and found to have a linear response with dose. The TL glow curves, recorded with various UV exposure times ranging from 5 to 25 min, showed a linear response with dosage. The corresponding kinetic parameters were also calculated using a computerized glow curve deconvolution (CGCD) technique. Activation energy was observed to enhance the increase in the peak temperature and its value was substantially higher for the third peak fitted using CGCD. The obtained results indicated that the synthesized pristine phosphors could be potentially used for lighting, displays, and dosimetric applications.

Mycobacterium tuberculosis Peptidyl Prolyl Isomerase A Interacts With Host Integrin Receptor to Exacerbate Disease Progression.

Attenuated intracellular survival of Mycobacterium tuberculosis (Mtb) secretory gene mutants exemplifies their role as virulence factors. Mtb peptidyl prolyl isomerase A (PPiA) assists in protein folding through cis/trans isomerization of prolyl bonds. Here, we show that PPiA abets Mtb survival and aids in disease progression by exploiting host-associated factors. While the deletion of PPiA has no discernable effect on bacillary survival in a murine infection model, it compromises the formation of granuloma-like lesions and promotes host cell death through ferroptosis. Overexpression of PPiA enhances the bacillary load and exacerbates pathology in mice lungs. Importantly, PPiA interacts with the integrin α5ß1 receptor through a conserved surface-exposed RGD motif. The secretion of PPiA as well as interaction with integrin contributes to disease progression by upregulating multiple host matrix metalloproteinases. Collectively, we identified a novel nonchaperone role of PPiA that is critical in facilitating host-pathogen interaction and ensuing disease progression.

Knowledge of COVID-19 and Its Influence on Mindfulness, Cognitive Emotion Regulation and Psychological Flexibility in the Indian Community.

The current global pandemic caused by COVID-19 has brought about an immense effect on the mental health of the general public. Considering the escalation in number of cases, mankind is facing a myriad of psychological problems, ranging from those related to taking precautions and maintaining safety to the ones caused by separation and bereavement. The current study aims to explore whether there is a significant difference between individuals with excellent, good, fair and vague knowledge of COVID-19 with respect to depression, anxiety, stress, level of mindfulness, specific cognitive emotion regulation strategies and psychological flexibility; to find out whether there is any significant relationship among these variables; and to determine whether knowledge of COVID-19, level of mindfulness, specific cognitive emotion regulation strategies and psychological flexibility are significant predictors of depression, anxiety and stress in the sample of the current study. The sample consisted of 402 individuals selected from the community following the research criteria. Data was collected using digital consent form, information schedule and questionnaires, from 3rd May to 13th May, 2020. The questionnaires consisted of a semi-structured interview schedule to assess knowledge of COVID-19, Depression, Anxiety and Stress Scale - 21, Five Facet Mindfulness Questionnaire-Short Form, Cognitive Emotion Regulation Questionnaire-Short version and Acceptance and Action Questionnaire-II. The data was statistically analyzed using analysis of variance test, correlational analysis and linear regression. The findings show that significant differences were present among individuals having varying degrees of knowledge of COVID-19 with respect to anxiety, level of mindfulness and psychological flexibility. Significant relationships were found to be present among the variables of the present study, having differing trends brought forward by the COVID-19 crisis. Certain socio-demographic characteristics and study variables were found to significantly predict the existing levels of depression, anxiety and stress in the current sample. The study suggests the necessity to formulate and implement appropriate mindfulness-based therapeutic interventions to address the mental health concerns arising as a result of the pandemic.

Thermoluminescence Studies of ß and γ-Irradiated Geological Materials for Environment Monitoring.

In the present report, thermally stimulated luminescence (TSL) of quartz and limestone samples irradiated with ß and γ-rays has been investigated. Herein the formation of trap depths and calculation of kinetic parameters of ß and γ - irradiated quartz and limestone samples were studied through thermoluminescence (TL) glow curve analyses. The quartz and limestone samples were collected from various sites of Chhattisgarh (Patharia and Dalli-Rajhara mines). The collected raw samples were annealed at 400 °C. The phase formation of collected samples is confirmed by X-ray diffraction studies. The grain sizes of the samples are determined by using Debye-Scherrer formula. TL glow curves of the collected samples were recorded for various doses of ß and γ-rays. Kinetic parameters such as order of kinetics frequency factor and trap depth were calculated by employing CGCD methods. A comparative study on the TL properties of the geological materials under ß and γ-irradiation was done. The trap model analysis was executed to determine the nature of traps responsible for dominant TL peaks of ß and γ-irradiated limestone and quartz samples.

Impact of early childhood caries on quality of life: Child and parent perspectives.

BACKGROUND: The aim of present study was to examine early childhood caries' impact on oral health-related quality of life from children's self report and parental perception. METHODS: 200 healthy children in the age group of 3-5 years and their parents/guardians were enrolled in the study. 100 children diagnosed with early childhood caries (interventional group) and 100 children without caries (control group) along with their parents/guardians participated in face to face interview and responded to Michigan oral health related quality of life scale - child and parent version. Four weeks after full mouth rehabilitation children with ECC and their parents responded to a survey for a follow-up assessment. Data was analyzed and evaluated using Statistical Package for Social Sciences Version 21.0 statistical software and Chi square test. RESULTS: In our study we have found that ECC subjects had poorer oral health-related quality of life compared to caries free subjects. Further one month follow up after complete treatment, the oral health-related QoL improved significantly in ECC children. CONCLUSIONS: Early childhood caries has a definite negative impact on the OHRQoL of children. At one month follow up after complete oral rehabilitation, the quality of life improved significanty as assessed by children's self reports as well as parental perceptions of their child's OHRQoL.

Chemical Peels in Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

Melasma is a notorious dermatosis, often resistant to treatment. Chemical peeling constitutes an acceptable option of management of melasma (of any type and duration). In this article, as a group of experts from Pigmentary Disorders Society (PDS) in collaboration with South Asian Pigmentary Forum (SPF), we have tried to elaborate the various chemical peeling agents for the treatment of melasma. Besides, we have reviewed the indications, mechanism of action, rationality and the detailed procedure of peeling. The evidence in favor of various peeling agents have been summarized as well.

Bacterial Virulence Factors: Secreted for Survival.

Virulence is described as an ability of an organism to infect the host and cause a disease. Virulence factors are the molecules that assist the bacterium colonize the host at the cellular level. These factors are either secretory, membrane associated or cytosolic in nature. The cytosolic factors facilitate the bacterium to undergo quick adaptive-metabolic, physiological and morphological shifts. The membrane associated virulence factors aid the bacterium in adhesion and evasion of the host cell. The secretory factors are important components of bacterial armoury which help the bacterium wade through the innate and adaptive immune response mounted within the host. In extracellular pathogens, the secretory virulence factors act synergistically to kill the host cells. In this review, we revisit the role of some of the secreted virulence factors of two human pathogens: Mycobacterium tuberculosis-an intracellular pathogen and Bacillus anthracis-an extracellular pathogen. The advances in research on the role of secretory factors of these pathogens during infection are discussed.

Steps per Day, Daily Peak Stepping Cadence, and Walking Performance in Older Adults.

We tested the hypothesis that the intensity of daily ambulation would relate with functional walking capacity in older adults. Forty-three women (n = 25) and men (n = 18) between the ages of 60-78 years wore an accelerometer for measurement of average daily steps and 30-min peak stepping cadence. A 400-m walk test was used to measure walking speed. No sex difference was found for average daily steps (p = .76), average peak cadence (p = .96), or walking speed (p = .89). Daily steps (women: r = .68, p < .01; men: r = .04) and peak cadence (women: r = .81, p < .01; men: r = -.16) were positively correlated with walking speed in women but not in men. After controlling for daily steps, peak cadence remained significantly associated with walking speed in women (partial r = .61, p < .01). Walking intensity during daily ambulation is independently related to functional walking capacity in older adults, albeit this relation may be more significant for women than men.

Mycobacterium tuberculosis cyclophilin A uses novel signal sequence for secretion and mimics eukaryotic cyclophilins for interaction with host protein repertoire.

Cyclophilins are prolyl isomerases with multitude of functions in different cellular processes and pathological conditions. Cyclophilin A (PpiA) of Mycobacterium tuberculosis is secreted during infection in intraphagosomal niche. However, our understanding about the evolutionary origin, secretory mechanism or the interactome of M. tuberculosis PpiA is limited. This study demonstrates through phylogenetic and structural analyses that PpiA has more proximity to human cyclophilins than the prokaryotic counterparts. We report a unique N-terminal sequence (MADCDSVTNSP) present in pathogenic mycobacterial PpiA and absent in non-pathogenic strains. This sequence stretch was shown to be essential for PpiA secretion. The overexpression of full-length PpiA from M. tuberculosis in non-pathogenic Mycobacterium smegmatis resulted in PpiA secretion while truncation of the N-terminal stretch obstructed the secretion. In addition, presence of an ESX pathway substrate motif in M. tuberculosis PpiA suggested possible involvement of Type VII secretion system. Site-directed mutagenesis of key residues in this motif in full-length PpiA also hindered the secretion in M. smegmatis. Bacterial two-hybrid screens with human lung cDNA library as target were utilized to identify interaction partners of PpiA from host repertoire, and a number of substrates with functional representation in iron storage, signal transduction and immune responses were detected. The extensive host interactome coupled with the sequence and structural similarity to human cyclophilins is strongly suggestive of PpiA being deployed by M. tuberculosis as an effector mimic against the host cyclophilins.

Evaluation of silymarin as a promising radioprotector.

Silymarin, a purified extract of seeds of Silybum marianum L. and well known for its hepatoprotective abilities, has been evaluated for inherent utility as a radioprotective agent. A fraction (INM-7035) was authenticated by characterizing the percentage composition of silybin A and B (39.9% and 57.4%). Free radical scavenging activities of INM-7035 against superoxide radicals (>68%), hydroxyl radicals (>33.75%), DPPH (67.2%), and ABTS (32.4%) were also evaluated. The fraction chelated (>30%) ferrous ions, thereby able to restrict amplification. INM-7035 exhibited >50% peroxyl radical scavenging activity in the lipid phase along with dose-dependent (R2 = 0.990) reducing power in the aqueous phase. Radiation-induced free radical flux can lead to disruption of biomolecules like membrane lipids. INM-7035 completely inhibited lipid peroxidative stress in case of membranes against supralethal radiation stress in the liposomal system. The ability of INM-7035 to modulate the levels of NF-kappaB, indicated its inherent potential as a radioprotective bioactive constituent.