Evaluation of Antioxidant Capacities and Total Polyphenols in Various Edible Parts of Capparis spinosa L. Collected from Trans-Himalayas

The phytochemical screening, antioxidant capacity, and total polyphenols in the methanolic extract of leaves, flower buds, roots and fruits of Capparis spinosa collected from trans-Himalayan region of Ladakh were assessed in an effort to corroborate its medicinal and culinary potential. Highest DPPH and ABTS radical scavenging activity were observed in the leaves and least in dried fruit samples, even FRAP assay also illustrated the same trend. IC50 values of DPPH assay was highly correlated with that of ABTS (R2=0.9084) and FRAP assay (R2=0.9771). However, IC50 value of ABTS was reasonably correlated with FRAP assay (R2=0.5838). The highest phenolic and flavonoid content was recorded in the leaf samples (24.78 and 5.69 mg GAE/g DW respectively), whereas it was lowest in the dried fruit samples (4.07 mg quercetin equivalent/g DW and nil, respectively). The total phenolic contents were highly correlated with IC50 value of ABTS (R2=0.9084), DPPH (R2=0.9388) and FRAP value (R2=0.9618). But, total flavonoid contents were highly correlated with ABTS (R2=0.7449), DPPH (R2=0.8791) and FRAP values (R2=0.9588). Thus, this study has validated the medicinal potential of all the edible parts of the C. spinosa

Cracking of enigma of Evans: a rare association with Sjogren and systemic lupus erythematosus

Evans syndrome (ES) is characterized by the simultaneous or consecutive occurrence of warm autoimmune hemolytic anemia (AIHA) along with immune thrombocytopenia (ITP), and less commonly, autoimmune neutropenia. It may manifest spontaneously or as a result of autoimmune, malignancy or lymphoproliferative disease. Clinical manifestations may be associated with hemolysis and thrombocytopenia, potentially leading to life-threatening outcomes. ES is a rare diagnosis of exclusion. Due to its infrequency, the treatment is typically empirical, relying largely on intravenous corticosteroids or immunoglobulins. We are presenting case of a 46-year-old- female with bleeding from the mouth and gums and rashes all over the body with no prior diagnosis of rheumatological disorder. This case is pivotal as it highlights a key factor contributing to ES and presents a pragmatic method for addressing the condition

Heat stress tolerance in peas (Pisum sativum L.): Current status and way forward

In the era of climate change, the overall productivity of pea (Pisum sativum L.) is being threatened by several abiotic stresses including heat stress (HS). HS causes severe yield losses by adversely affecting several traits in peas. A reduction in pod yield has been reported from 11.1% to 17.5% when mean daily temperature increase from 1.4 to 2.2°C. High-temperature stress (30.5-33°C) especially during reproductive phase is known to drastically reduce both seed yield and germination. HS during germination and early vegetative stage resulted in poor emergence and stunted plant growth along with detrimental effects on physiological functions of the pea plant. To combat HS and continue its life cycle, plants use various defense strategies including heat escape, avoidance or tolerance mechanisms. Ironically, the threshold temperatures for pea plant and its responses are inconsistent and not yet clearly identified. Trait discovery through traditional breeding such as semi leaflessness (afila), upright growing habit, lodging tolerance, lower canopy temperature and small seeded nature has highlighted their utility for greater adaptation under HS in pea. Screening of crop gene pool and landraces for HS tolerance in a targeted environment is a simple approach to identify HS tolerant genotypes. Thus, precise phenotyping using modern phenomics tools could lead to increased breeding efficiency. The NGS (next generation sequencing) data can be associated to find the candidate genes responsible for the HS tolerance in pea. In addition, genomic selection, genome wide association studies (GWAS) and marker assisted selection (MAS) can be used for the development of HS tolerant pea genotypes. Additionally, development of transgenics could be an alternative strategy for the development of HS tolerant pea genotypes. This review comprehensively covers the various aspects of HS tolerance mechanisms in the pea plant, screening protocols, omic advances, and future challenges for the development of HS tolerant genotypes

Genome-wide association studies for phenological and agronomic traits in mungbean (Vigna radiata L. Wilczek)

Mungbean (Vigna radiata L. Wilczek) is one of the important warm-season food legumes, contributing substantially to nutritional security and environmental sustainability. The genetic complexity of yield-associated agronomic traits in mungbean is not well understood. To dissect the genetic basis of phenological and agronomic traits, we evaluated 153 diverse mungbean genotypes for two phenological (days to heading and days to maturity) and eight agronomic traits (leaf nitrogen status using SPAD, plant height, number of primary branches, pod length, number of pods per plant, seeds per pod, 100-seed weight, and yield per plant) under two environmental conditions. A wide array of phenotypic variability was apparent among the studied genotypes for all the studied traits. The broad sense of heritability of traits ranged from 0.31 to 0.95 and 0.21 to 0.94 at the Delhi and Ludhiana locations, respectively. A total of 55,634 genome-wide single nucleotide polymorphisms (SNPs) were obtained by the genotyping-by-sequencing method, of which 15,926 SNPs were retained for genome-wide association studies (GWAS). GWAS with Bayesian information and linkage-disequilibrium iteratively nested keyway (BLINK) model identified 50 SNPs significantly associated with phenological and agronomic traits. In total, 12 SNPs were found to be significantly associated with phenological traits across environments, explaining 7%–18.5% of phenotypic variability, and 38 SNPs were significantly associated with agronomic traits, explaining 4.7%–27.6% of the phenotypic variability. The maximum number of SNPs (15) were located on chromosome 1, followed by seven SNPs each on chromosomes 2 and 8. The BLAST search identified 19 putative candidate genes that were involved in light signaling, nitrogen responses, phosphorus (P) transport and remobilization, photosynthesis, respiration, metabolic pathways, and regulating growth and development. Digital expression analysis of 19 genes revealed significantly higher expression of 12 genes, viz. VRADI01G08170, VRADI11G09170, VRADI02G00450, VRADI01G00700, VRADI07G14240, VRADI03G06030, VRADI02G14230, VRADI08G01540, VRADI09G02590, VRADI08G00110, VRADI02G14240, and VRADI02G00430 in the roots, cotyledons, seeds, leaves, shoot apical meristems, and flowers. The identified SNPs and putative candidate genes provide valuable genetic information for fostering genomic studies and marker-assisted breeding programs that improve yield and agronomic traits in mungbean

Genome wide association analysis for grain micronutrients and anti-nutritional traits in mungbean [Vigna radiata (L.) R. Wilczek] using SNP markers

Mungbean is an important food grain legume for human nutrition and nutritional food due to its nutrient-dense seed, liked palatability, and high digestibility. However, anti-nutritional factors pose a significant risk to improving nutritional quality for bio fortification. In the present study, genetic architecture of grain micronutrients (grain iron and zinc concentration) and anti-nutritional factors (grain phytic acid and tannin content) in association mapping panel of 145 diverse mungbean were evaluated. Based on all four parameters genotypes PUSA 1333 and IPM 02-19 were observed as desired genotypes as they had high grain iron and zinc concentration but low grain phytic acid and tannin content. The next generation sequencing (NGS)-based genotyping by sequencing (GBS) identified 14,447 genome-wide SNPs in a diverse selected panel of 127 mungbean genotypes. Population admixture analysis revealed the presence of four different ancestries among the genotypes and LD decay of ∼57.6 kb kb physical distance was noted in mungbean chromosomes. Association mapping analysis revealed that a total of 20 significant SNPs were shared by both GLM and Blink models associated with grain micronutrient and anti-nutritional factor traits, with Blink model identifying 35 putative SNPs. Further, this study identified the 185 putative candidate genes. Including potential candidate genes Vradi07g30190, Vradi01g09630, and Vradi09g05450 were found to be associated with grain iron concentration, Vradi10g04830 with grain zinc concentration, Vradi08g09870 and Vradi01g11110 with grain phytic acid content and Vradi04g11580 and Vradi06g15090 with grain tannin content. Moreover, two genes Vradi07g15310 and Vradi09g05480 showed significant variation in protein structure between native and mutated versions. The identified SNPs and candidate genes are potential powerful tools to provide the essential information for genetic studies and marker-assisted breeding program for nutritional improvement in mungbean

Agro-morphological characterization of lentil germplasm of Indian National Genebank and Development of a core set for efficient utilization in lentil improvement programs

Lentil (Lens culinaris Medik.) is one of the major cool-season pulse crops worldwide. Its increasing demand as a staple pulse has led to the unlocking of diverse germplasm collections conserved in the genebanks to develop its superior varieties. The Indian National Genebank, housed at the Indian Council of Agricultural Research (ICAR)-National Bureau of Plant Genetic Resources, New Delhi, India, currently has 2,324 accessions comprising 1,796 indigenous and 528 exotic collections. This study was conducted to unveil the potential of lentil germplasm by assessing its agro-morphological characteristics and diversity, identifying trait-specific germplasm, and developing a core set. The complete germplasm set was characterized for two years, i.e., 2017-2018 and 2018-2019, and data were recorded on 26 agro-morphological traits. High phenotypic variability was observed for nine quantitative and 17 qualitative traits. A core set comprising 170 accessions (137 Indian and 33 exotic) was derived based on the characterization data as well as geographical origin using a heuristic method and PowerCore software. This core set was found to be sufficiently diverse and representative of the entire collection based on the comparison made using Shannon-Weaver diversity indices and χ2 test. These results were further validated by summary statistics. The core set displayed high genetic diversity as evident from a higher coefficient of variance in comparison to the entire set for individual traits and overall Shannon-Weaver diversity indices (entire: 1.054; core: 1.361). In addition, the total variation explained by the first three principal components was higher in the core set (70.69%) than in the entire collection (68.03%). Further, the conservation of pairwise correlation values among descriptors in the entire and core set reflected the maintenance of the structure of the whole set. Based on the results, this core set is believed to represent the entire collection, completely. Therefore, it constitutes a potential set of germplasm that can be used in the genetic enhancement of lentils

Strategies for identifying stable lentil cultivars (Lens culinaris Medik) for combating hidden hunger, malnourishment, and climate variability

Iron and zinc malnutrition is a global humanitarian concern that mostly affects newborns, children, and women in low- and middle-income countries where plant-based diets are regularly consumed. This kind of malnutrition has the potential to result in a number of immediate and long-term implications, including stunted growth, an elevated risk of infectious diseases, and poor development, all of which may ultimately cause children to not develop to the fullest extent possible. A determination of the contributions from genotype, environment, and genotype by environment interactions is necessary for the production of nutrient-dense lentil varieties that offer greater availability of iron and zinc with a high level of trait stability. Understanding the genotype and environmental parameters that affect G x E (Genotype x Environment) interactions is essential for plant breeding. We used GGE(Genotype, Genotype x Environment interactions) and AMMI (Additive Main effects and Multiplicative Interaction) models to study genetic stability and GE(Genotype x Environment interactions) for grain Fe, Zn, Al, and anti-nutritional factors like phytic acid content in sixteen commercially produced lentil cultivars over several different six geographical locations across India. Significant genetic variability was evident in the Fe and Zn levels of different genotypes of lentils. The amounts of grain iron, zinc, and phytic acid varied from 114.10 to 49.90 mg/kg, 74.62 to 21.90 mg/kg, and 0.76 to 2.84 g/100g (dw) respectively. The environment and GE (Genotype x Environment interactions) had an impact on the concentration of grain Fe, Zn, and phytic acid (PA). Heritability estimations ranged from low to high (53.18% to 99.48%). The study indicated strong correlation between the contents of Fe and Zn, a strategy for simultaneously increasing Fe and Zn in lentils may be recommended. In addition, our research revealed that the stable and ideal lentil varieties L4076 (Pusa Shivalik) for Fe concentration and L4717 (Pusa Ageti) for Zn content, which have lower phytic acid contents, will not only play an essential role as stable donors in the lentil bio-fortification but will also enable the expansion of the growing area of bio-fortified crops for the security of health and nutrition

Combinatorial polymeric conjugated micelles with dual cytotoxic and antiangiogenic effects for the treatment of ovarian cancer

Emerging treatment paradigms like targeting the tumor microenvironment and/or dosing as part of a metronomic regimen are anticipated to produce better outcomes in ovarian cancer, but current drug delivery systems are lacking. We have designed and evaluated paclitaxel (PTX) and rapamycin (RAP) micellar systems that can be tailored for various dosing regimens and target tumor microenvironment. Individual and mixed PTX/RAP (MIX-M) micelles are prepared by conjugating drugs to a poly­(ethylene glycol)-<i>block</i>-poly­(β-benzyl l-aspartate) using a pH-sensitive linker. The micelles release the drug(s) at pH 5.5 indicating preferential release in the acidic endosomal/lysosomal environment. Micelles exhibit antiproliferative effects in ovarian cell cancer lines (SKOV-3 (human caucasian ovarian adenocarcinoma) and ES2 (human ovarian clear cell carcinoma)) and an endothelial cell line (HUVEC; human umbilical vein endothelial cells) with the MIX-M being synergistic. The micelles also inhibited endothelial migration and tube formation. In healthy mice, micelles at 60 mg/kg/drug demonstrated no acute toxicity over 21 days. ES2 xenograft model efficacy studies at 20 mg/kg/drug dosed every 4 days and evaluated at 21 days indicate that the individual micelles exhibit antiangiogenic effects, while the MIX-M exhibited both antiangiogenic and apoptotic induction that results in significant tumor volume reduction. On the basis of our results, MIX-M micelles can be utilized to achieve synergistic apoptotic and antiangiogenic effects when treated at frequent low doses

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