Crystal structure of 2-methylamino-3-nitro-4-p-tolylpyrano[3,2-c]chromen-5(4H)-one

The authors thank Dr Babu Varghese, SAIF, IIT, Chennai, India, for the data collection.Peer reviewedPublisher PD

Wild Sugarcane - Saccharum sp. germplasm collection in the states of Punjab and Haryana, India

The Indian sub-continent harbours a great wealth of diversity of Saccharum and its related genera. Several targeted expeditions were conducted to collect the range of diversity present in Saccharum complex from diverse parts of the country. But the north western states of Punjab and Haryana were hitherto unexplored. A targeted exploration was conducted during 2016 to collect the entire range of variability present in Saccharum complex. Collections were made from a wide range of habitats and altitudes. The Saccharum spontaneum was present mostly along the river banks and river beds and showed considerable variability for morphological characteristics. S. spontaneum was distributed throughout both the states and collections could be made from all the districts and union territory of Chandigarh. A total of 104 accessions comprising of 100 Saccharum spontaneum and four Erinathus sp. have been collected. They were occurring mostly as small population except in the canal bunds where larger population was noticed. Plant height ranged from 0.46 m to 4.5 m. Variation for leaf and stem characters were observed from the collections. Statistical analysis of altitude of the collection sites with plant characters showed no significant association. Correlation analysis among plant characters showed the highest correlation coefficient between plant height and internode thickness. Clustering of Haryana, Chandigarh and Punjab Saccharum spontaneum collections through complete linkage clustering resulted in five clear clusters among the collections. Geographic distance and environmental factors including local climates interplay in the formation of the genetic structure and geographic patterns of the native S. spontaneum populations. Haryana and Punjab state were not much explored during earlier period and hence the collection would add more diversity to the germplasm maintained. In addition to the 100 S. spontaneum, four Erianthus sp. were collected during the exploration which will enrich the gene pool

Nanocomposite Scaffolds for Monitoring of Drug Diffusion in Three-Dimensional Cell Environments by Surface-Enhanced Raman Spectroscopy

[EN]Monitoring dynamic processes in complex cellular environments requires the integration of uniformly distributed detectors within such three-dimensional (3D) networks, to an extent that the sensor could provide real-time information on nearby perturbations in a non-invasive manner. In this context, the development of 3D-printed structures that can function as both sensors and cell culture platforms emerges as a promising strategy, not only for mimicking a specific cell niche but also toward identifying its characteristic physicochemical conditions, such as concentration gradients. We present herein a 3D cancer model that incorporates a hydrogel-based scaffold containing gold nanorods. In addition to sustaining cell growth, the printed nanocomposite inks display the ability to uncover drug diffusion profiles by surface-enhanced Raman scattering, with high spatiotemporal resolution. We additionally demonstrate that the acquired information could pave the way to designing novel strategies for drug discovery in cancer therapy, through correlation of drug diffusion with cell death.J.P. acknowledges an FPU fellowship from the Spanish Ministry of Science, Innovation and Universities. L.M.L.-M. acknowledges funding from the European Research Council (Grants ERC AdG 787510, 4DbioSERS) and the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (Grant MDM-2017-0720). A.C. was funded by MICINN (Grant PID2019-108787RB-I00 (FEDER/EU)) and the European Research Council (ERC Consolidator Grant 819242)

Development of Next-Generation Fluorescent Turn-On Sensor to Simultaneously Detect and Detoxify Mercury in Living Samples

Strategies for simultaneous detection and detoxification of Hg^(2+) using a single sensor from biological and environmental samples are limited and have not been realized in living organisms so far. We report a highly selective, small molecule “turn-on” fluorescent sensor, PYDMSA, based on the cationic dye Pyronin Y (PY) and chelating agent meso-2,3-dimercaptosuccinic acid (DMSA) for the simultaneous detection and detoxification of inorganic mercury (Hg^(2+)). After Hg^(2+) detection, concomitant detoxification was carried out with sufficient efficacy in living samples, which makes the sensor unique. PYDMSA exhibits high selectivity for Hg^(2+) over other competing metal ions with an experimental detection limit of ∼300 pM in aqueous buffer solution. When PYDMSA reacts with Hg2+, the CS–C^9 bond in the sensor gets cleaved. This results in the “turn-on” response of the fluorescence probe with a concomitant release of one equivalent of water-soluble Hg^(2+)–DMSA complex which leads to a synchronous detoxifying effect. The sensor by itself is nontoxic to cells in culture and has been used to monitor the real-time uptake of Hg^(2+) in live cells and zebrafish larvae. Thus, PYDMSA is a unique sensor which can be used to detect and detoxify mercury at the same time in living samples

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Raziskava hidrodinamičnih lastnosti toka v cevni kači z ovalnostjo in gubami

The forming of helical coils using a rolling process results in geometrical irregularities (wrinkles and ovality) that are likely to influence the hydrodynamic behaviour of the flow field inside the coil in applications such as air generators. In this study, the above behaviour was investigated by experimental and numerical analyses considering the heat exchanger used in dry air generators. In experimental analysis, a three-turn copper helical coil with wrinkles and ovality was investigated to estimate the global hydrodynamic characteristics inside the helical coil. The results were compared with that of the ideal geometry of a coil without wrinkles and ovality. The effect of wrinkles was assessed through friction factor, and the corresponding equivalent surface roughness was found to increase by 5.7 times, owing to the presence of wrinkles in the helical coil. Numerical simulation was conducted to determine the pressure distribution, velocity distribution, and secondary flow inside the helical coilthe results were validated with experimental data. A critical portion of the helical coil with multiple wrinkles was considered for numerical simulation to investigate the localized effects of wrinkles on the flow field behaviour. The analysis in the vicinity of wrinkles revealed negative pressure development during flow, which in turn would cause re-circulation and cavitation that are undesirable