PEI functionalized NaCeF4:Tb3+/Eu3+ for photoluminescence sensing of heavy metal ions and explosive aromatic nitro compounds

This work reports an eco-friendly hydrothermal approach for the synthesis of hexagonal NaCeF₄:Tb³⁺/Eu³⁺ nanophosphors. The phase, morphology and optical properties were characterized by Powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and photoluminescence (PL) spectroscopy respectively. Herein, the as-synthesized nanophosphor was functionalized with amine rich polyethylenimine (PEI) resulting in development of a luminescent nanoprobe bearing dual sensing functions for hazardous nitroaromatics and heavy metal ions. The strong photoluminescence emission of Eu³⁺ ions was selectively quenched upon addition of toxic analytes at concentrations from 10 to 100 ppm due to complex formation between the analytes and PEI functionalized nanostructure. The synthesized nanomaterial shows sharp emission peaks at 493, 594, 624, 657 and 700 nm. Significantly, the peak at 594 nm shows a noticeable quenching effect on addition of toxic analytes to the aqueous solution of the nanocrystals. The nanophosphors are sensitive and efficient for the PA and Fe³⁺ ion detection with an LOD of 1.32 ppm and 1.39 ppm. The Stern–Volmer (SV) quenching constant (K_SV) is found to be 2.25 × 10⁵ M⁻¹ for PA and 3.8 × 10⁴ M⁻¹ for Fe³⁺ ions. The high K_SV value and low LOD suggest high selectivity and sensitivity of the nanosensor towards PA and Fe³⁺ ions over other analytes. Additionally, a reduced graphene oxide and nanophosphor based nanocomposite was also synthesized to investigate the role of energy transfer involving delocalized energy levels of reduced graphene oxide in regulating the luminescence properties of the nanophosphor. It was observed that PEI plays central role in inhibiting the quenching effect of reduced graphene oxide on the nanophosphor.

This work reports an eco-friendly hydrothermal approach for the synthesis of hexagonal NaCeF₄:Tb³⁺/Eu³⁺ nanophosphors.     

Somatic mosaic monosomy 7 and UPD7q in a child with MIRAGE syndrome caused by a novel SAMD9 mutation

MIRAGE syndrome caused by mutations in SAMD9 is associated with potential loss of chromosome 7 (‐7/7q‐) and an increased risk to develop myelodysplastic syndrome (MDS). We report a case of MIRAGE syndrome, caused by a novel SAMD9 mutation p.Leu641Pro, leading to characteristic clinical features as well as to the coexistence of cells with monosomy 7 (20%) and with uniparental disomy of long arm of chromosome 7 (UPD7q). In contrast to previously reported MIRAGE patients with ‐7/7q‐ developing MDS, our patient achieved complete cytogenetic remission of monosomy 7. As UPD7q remained unchanged, it seems to be a protective factor against MDS.     

Moxibustion: A Complementary Therapy among Bot Tribe Inhabiting Padder Valley of Western Himalaya,India

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Complementary and alternative therapies are time tested practices established since the dawn of human...     

Progress and delivery of health care in Bhutan, the Land of the Thunder Dragon and Gross National Happiness

The Himalayan Kingdom of Bhutan is rapidly changing, but it remains relatively isolated, and it tenaciously embraces its rich cultural heritage. Despite very limited resources, Bhutan is making a concerted effort to update its health care and deliver it to all of its citizens. Healthcare services are delivered through 31 hospitals, 178 basic health unit clinics and 654 outreach clinics that provide maternal and child health services in remote communities in the mountains. Physical access to primary health care is now well sustained for more than 90% of the population. Bhutan has made progress in key health indicators. In the past 50 years, life expectancy increased by 18 years and infant mortality dropped from 102.8 to 49.3 per 1000 live births between 1984 and 2008. Bhutan has a rich medical history. One of the ancient names for Bhutan was 'Land of Medicinal Herbs' because of the diverse medicinal plants it exported to neighbouring countries. In 1967, traditional medicine was included in the National Health System, and in 1971, formal training for Drungtshos (traditional doctors) and sMenpas (traditional compounders) began. In 1982, Bhutan established the Pharmaceutical and Research Unit, which manufactures, develops and researches traditional herbal medicines. Despite commendable achievements, considerable challenges lie ahead, but the advances of the past few decades bode well for the future.     

Genetic differences and aberrant methylation in the apelin system predict the risk of high-altitude pulmonary edema

Hypoxia-inducible factor stimulates the expression of apelin, a potent vasodilator, in response to reduced blood arterial oxygen saturation. However, aberrations in the apelin system impair pulmonary vascular function, potentially resulting in the development of high-altitude (HA)-related disorders. This study aimed to elucidate the genetic and epigenetic regulation of apelin, apelin receptor (APLNR), and endothelial nitric oxide synthase (NOS3) in HA adaptation and HA pulmonary edema (HAPE). A genome-wide association study and sequencing identified variants of apelin, APLNR, and NOS3 that were validated in a larger sample size of HAPE-patients (HAPE-p), HAPE-free controls (HAPE-f), and healthy highland natives (HLs). Apelin-13 and nitrite levels and apelin and NOS3 expression were down-regulated in HAPE-p (P < 0.001). Among the several studied polymorphisms, apelin rs3761581, rs2235312, and rs3115757; APLNR rs11544374 and rs2282623; and NOS3 4b/4a, rs1799983, and rs7830 were associated with HAPE (P < 0.03). The risk allele rs3761581G was associated with a 58.6% reduction in gene expression (P = 0.017), and the risk alleles rs3761581G and rs2235312T were associated with low levels of apelin-13 and nitrite (P < 0.05). The latter two levels decreased further when both of these risk alleles were present in the patients (P < 0.05). Methylation of the apelin CpG island was significantly higher in HAPE-p at 11.92% than in HAPE-f and HLs at ≤7.1% (P < 0.05). Moreover, the methylation effect was 9% stronger in the 5′ UTR and was associated with decreased apelin expression and apelin-13 levels. The rs3761581 and rs2235312 polymorphisms and methylation of the CpG island influence the expression of apelin in HAPE.Apelin plays a crucial role in the adaptive and nonadaptive physiological responses of the vascular endothelium and smooth muscles (1). It is a potent regulator of vascular and oxygen homeostasis, which are pertinent to the high-altitude (HA) physiology. Therefore, elucidating apelin function under hypobaric hypoxia is of significant importance. Hypobaric hypoxia of HA lowers the blood arterial oxygen saturation (SaO₂) in the body. To restore this cellular O₂ content, an array of adaptive responses occurs that are mediated through hypoxia-inducible factor (HIF) (2–4). Stimulation of the apelin signaling system is one of these responses, and any aberration in this response impairs pulmonary vascular function, which may result in the development of HA-related disorders (5, 6).Apelin induces endothelium-dependent vasodilation by activating endothelial nitric oxide synthase (NOS3) via the AKT pathway (7). The release of nitric oxide (NO) by NOS3 activates soluble guanylate cyclase in vascular smooth muscle cells (VSMCs), resulting in an increased level of cyclic guanosine monophosphate (8). These events enhance vasodilation, an important phenomenon required for increasing blood circulation, which in turn improves tissue oxygenation in the body (9). However, in an impaired endothelium, apelin binds to its receptor, apelin receptor (APLNR), which is present in VSMCs, to induce VSMC-dependent vasoconstriction (1). Thus, apelin, APLNR and NOS3 may contribute to pathophysiological manifestations associated with various HA disorders (10, 11). HA pulmonary edema (HAPE) is one such HA disorder, characterized by pulmonary vasoconstriction, endothelial dysfunction, and intravascular fluid retention, which develops in otherwise healthy individuals upon rapid ascent to altitudes above 2,500 m (12).In addition to the local environment, physiological regulatory mechanisms are also governed by genetics (12), and the loci of several genes that are associated with HA adaptation and disease susceptibility have been identified (13–18). However, the genetic and epigenetic regulations of apelin signaling have not been investigated in HAPE and HA adaptation, even though variants of the genes involved in this signaling have been extensively investigated in several disease conditions (17–24). Our previous reports on NOS3 revealed a selection of polymorphisms in both HA adaptation and HAPE (17, 18). Epigenetic regulatory mechanisms help elucidate the complex interactions between the genome and the hypobaric hypoxia environment (25). Among these epigenetic mechanisms, DNA methylation plays a crucial role in regulating the genes and therefore the physiology (26). Alterations in the DNA methylation of the CpG islands of several genes have been found in various cancers and other diseases (26, 27). A CpG island is a short stretch of DNA that is enriched with CpG sites in the 5′ end of a gene; although it remains unmethylated, it tends to undergo aberrant methylation upon exposure to certain environmental conditions (28). Thus, it may explain the physiological consequences of the complex interactions among aberrant DNA methylation, the genome, and the hypobaric hypoxia environment.To elucidate the apelin signaling system at HA, we used a genome-wide association study (GWAS) and sequencing to identify novel and known variants of apelin, APLNR, and NOS3 in HAPE-patients (HAPE-p), HAPE-free controls (HAPE-f), and healthy highland natives (HLs). The identified variants were further validated in a larger sample size and through luciferase activity assays. Additionally, the plasma levels of apelin-13 and nitrite, the expression levels of the three genes and the CpG island methylation status were also assessed in these subjects. The functional consequences of associated SNPs and methylated CpG islands were determined by performing several association, correlation, and regression analyses.