Genomic insights into cytokinin oxidase/dehydrogenase (CKX) gene family, identification, phylogeny and synteny analysis for its possible role in regulating seed number in Pigeonpea (Cajanus cajan (L.) Millsp.).

Cytokinin oxidase/dehydrogenase (CKX) regulates cytokinin levels in plants which are vital for plant growth and development. However, there is a paucity of evidence regarding their role in controlling embryo/seed development in pigeonpea. This comprehensive study provides information on the identification and characterization of CKX genes in pigeonpea. A genome-wide analysis identified 18 CKX genes, each with distinct structure, expression patterns, and possible diverse functions. Domain analysis revealed the presence of the sequences including FAD and CK-Binding domain, and subcellular localization analysis showed that almost 50 % of them reside within the nucleus. They were observed to be located unevenly on chromosome numbers 2, 4, 6, 7, and 11 with a majority of them present on the scaffolds. The 8 homologous pairs and various orthologous gene pairs provided further insights into their evolution pattern. Further, SNP/Indels variation in CKX genes and haplotype groups among contrasting genotypes for SNPP (seed number per pod) were analyzed. Spatiotemporal expression analysis revealed the significant expression pattern of CcCKX15, CcCKX17, and CcCKX2 in genotypes carrying low SNPP reiterating their possible role as negative regulators. These genes can be potential targets to undertake seed and biomass improvement in pigeonpea.

Metal-free functionalized carbon nitride as a photocatalyst driven by sunlight for acetal synthesis and selective regeneration of NAD(P)H cofactor.

Nicotinamide Adenine Dinucleotide Phosphate (NAD(P)H) plays an important role in numerous biologically significant redox reactions. The photochemical restoration of its oxidized form (NAD(P)+) under physiological conditions is intriguing in the context of integrated photo and catalysis. Herein, we report the functionalized graphitic carbon-based solar light active photocatalyst by doping boron and fluorine in the native graphitic carbon nitride (GCN) (nonfunctionalized) for the regeneration of enzymatically visible light active coenzyme and in photo-acetalization reactions. The metal-free functionalized photocatalyst systems such as BFGCN-x leads to higher yield NADH and NADPH regeneration. They are also capable of catalyzing acetal reactions in the absence of any Lewis and Bronsted acids. The current research endeavor provides the advancement and the application of functionalized GCN-based photocatalysts for NADH (61.89%), NADPH (59.84%) regeneration, and photo-acetalization reactions.

Unique functional neuroimaging signatures of genetic versus clinical high risk for psychosis.

BACKGROUND: 22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped results to biological pathways. METHODS: We analyzed two large multi-site cohorts with resting-state functional MRI (rs-fMRI): 1) 22qDel (n=164, 47% female) and typically developing (TD) controls (n=134, 56% female); 2) CHR individuals (n=244, 41% female) and TD controls (n=151, 46% female) from the North American Prodrome Longitudinal Study-2. We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions, testing case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation. RESULTS: BSV, LC, and GBC are significantly disrupted in 22qDel compared with TD controls (False Discovery Rate q<0.05). Spatial maps of BSV and LC differences are highly correlated with each other, unlike GBC. In CHR, only LC is significantly altered versus controls, with a different spatial pattern compared to 22qDel. Group differences map onto biological gradients, with 22qDel effects strongest in regions with high predicted blood flow and metabolism. CONCLUSION: 22qDel and CHR exhibit divergent effects on fMRI temporal variability and multi-scale functional connectivity. In 22qDel, strong and convergent disruptions in BSV and LC not seen in CHR individuals suggest distinct functional brain alterations.

Zn-MOF@rGO nanocomposite: a versatile tool for highly selective and sensitive detection of Pb2+ and Cu2+ ions in water.

In this work, a hybrid nanocomposite material (PUC2@rGO) was prepared by integrating our previously developed Zn-MOF (PUC2) with reduced graphene oxide (rGO) through the wet impregnation method. The characterization of PUC2@rGO was performed using various analytical techniques, including FTIR, PXRD, FE-SEM, HR-TEM, XPS, zeta potential, and time-resolved FL spectroscopy. Our investigation primarily focused on assessing the composite's capability to detect water pollutants. Notably, PUC2@rGO demonstrated remarkable selectivity and sensitivity towards Pb2+ and Cu2+ ions via fluorescence quenching, exhibiting low detection limits and high quenching constant values. Spectroscopic analysis revealed that electron transfer from PUC2@rGO (donor) to the metal ions (acceptor) resulted in the observed quenching effect induced by Pb2+ and Cu2+ ions. Time-resolved fluorescence studies of PUC2@rGO before and after adding Pb2+ and Cu2+ ions confirmed dynamic quenching, further affirming strong interactions between PUC2@rGO and the targeted metal ions. These findings highlight PUC2@rGO's potential for efficiently detecting heavy metal pollutants in water.

Green synthesis and multifunctional properties of Cu/NiO nanocomposites using Commelina benghalensis leaf extract.

This study presents the green synthesis and multifunctional properties of Cu/NiO nanocomposites (NCs) fabricated with varying ratios (90:10, 80:20, and 70:30) using Commelina benghalensis leaf extract. X-ray diffraction (XRD) analysis confirmed the polycrystalline nature of the NCs, revealing crystallite sizes of 13.62, 13.22, and 7.14 nm. Scanning electron microscopy (SEM) showed rod-shaped and agglomerated particles with sizes ranging from 17.64 to 22.97 nm. Energy-dispersive X-ray spectroscopy (EDX) verified the elemental composition of copper, nickel, oxygen, and carbon. UV-visible spectroscopy determined the energy band gaps to be in the range of 1.24-1.56 eV. Fourier-transform infrared spectroscopy (FT-IR) indicated the presence of bioactive compounds responsible for the reduction of precursor metal salts. The Cu/NiO NCs exhibited remarkable antimicrobial activity, with the 90:10 ratio showing the highest zones of inhibition at 32.76 ± 0.23 mm, 18.66 ± 0.33 mm, and 14.36 ± 0.32 mm against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, respectively. Additionally, the 70:30 Cu/NiO NCs demonstrated superior antioxidant activity, with a radical scavenging efficiency of 83.22%, closely approaching that of ascorbic acid (96.98%). Photocatalytic evaluations revealed that the NCs were highly effective in degrading environmental pollutants, achieving 97.69% degradation of malachite green and 96.52% of congo red under UV light irradiation. The novelty of this work lies in the use of Commelina benghalensis leaf extract as a sustainable and eco-friendly reducing and stabilizing agent for synthesizing Cu/NiO NCs, offering a green alternative to conventional methods. The synergistic effects between Cu and NiO in the different compositions (90:10, 80:20, and 70:30) enhanced the overall antimicrobial and photocatalytic activities, highlighting their potential for environmental remediation applications.

Investigation of the efficacy of Zn/Ce-CuO nanoparticles for enhanced photocatalytic, antibacterial, and antioxidant activities.

The world is dealing with unprecedented environmental challenges, leading to a growing urgency to limit environmental damage. So, this study focuses on the synthesis of pure CuO, Zn, Ce, and Zn/Ce dual-doped CuO nanoparticles (NPs) using extract of Citrus limon leaves as reductant via simple co-precipitation method. The X-ray diffraction (XRD) characterization was employed to analyze structural characteristics of synthesized samples which confirm influence of Zn or Ce doping on crystallite size, dislocation density, and strain. The role of functional groups, changes in force constant, and bond length on addition of dopants was indicated by FTIR results. The SEM and TEM results showed variation in morphology from irregular to spherical. The zeta-potential and BET analysis confirmed surface potential as well as surface area characteristics. The change in energy gap values from 1.81 to 1.45 eV of Zn/Ce-doped CuO NPs computed from UV-vis analysis elevated its photocatalytic performance and reduced the chances of recombination of electron-hole pair due to presence of trapping levels between valence and conduction bands. The enhanced photo-degradation of Congo red (CR) and rhodamine B (RhB) with 91 and 94%, respectively, for Zn/Ce-doped CuO NPs was observed. The so-obtained samples have also exhibited good antibacterial and antioxidant activities.

Understanding the role of P-type ATPases in regulating pollen fertility and development in pigeonpea.

The P-type ATPase superfamily genes are the cation and phospholipid pumps that transport ions across the membranes by hydrolyzing ATP. They are involved in a diverse range of functions, including fundamental cellular events that occur during the growth of plants, especially in the reproductive organs. The present work has been undertaken to understand and characterize the P-type ATPases in the pigeonpea genome and their potential role in anther development and pollen fertility. A total of 59 P-type ATPases were predicted in the pigeonpea genome. The phylogenetic analysis classified the ATPases into five subfamilies: eleven P1B, eighteen P2A/B, fourteen P3A, fifteen P4, and one P5. Twenty-three pairs of P-type ATPases were tandemly duplicated, resulting in their expansion in the pigeonpea genome during evolution. The orthologs of the reported anther development-related genes were searched in the pigeonpea genome, and the expression profiling studies of specific genes via qRT-PCR in the pre- and post-meiotic anther stages of AKCMS11A (male sterile), AKCMS11B (maintainer) and AKPR303 (fertility restorer) lines of pigeonpea was done. Compared to the restorer and maintainer lines, the down-regulation of CcP-typeATPase22 in the post-meiotic anthers of the male sterile line might have played a role in pollen sterility. Furthermore, the strong expression of CcP-typeATPase2 in the post-meiotic anthers of restorer line and CcP-typeATPase46, CcP-typeATPase51, and CcP-typeATPase52 in the maintainer lines, respectively, compared to the male sterile line, clearly indicates their potential role in developing male reproductive organs in pigeonpea.

Nitric oxide brings innate immune resistance to M. tuberculosis infection among high-risk household contacts of pulmonary tuberculosis patients.

Nitric oxide (NO) and iNOS are crucial host factors in innate immunity against intracellular pathogens. However, the role of NO in Mycobacterium tuberculosis (M. tb) infection in humans remains controversial, unlike in the murine model of TB. To investigate this, levels of NO, iNOS, and L-arginine, as well as the NOS2A gene polymorphism rs57234985 at the promoter region of NOS2A, were evaluated in pulmonary TB (PTB) patients and their household contacts (HHCs). Increased levels of NO and iNOS expression in HHCs indicated exposure to M. tb infection which was confirmed by higher levels of iNOS and NO in Mantouxpositive individuals. Furthermore, higher levels of arginine were detected in HHCs, suggesting its potential role in promoting optimal NO synthesis. PTB patients had higher levels of these analytes due to ongoing active infection. Interestingly, iNOS and NO levels were inversely related to bacterial burden, suggesting their antimicrobial role. NOS2A gene polymorphism was found to be associated with disease susceptibility, with the TT genotype linked to increased iNOS expression. To conclude, iNOS plays a crucial role in controlling early M. tb infection in HHCs by inducing optimal NO production with help of L-arginine. Further longitudinal studies are needed to better understand the role of these host factors upon disease activation.

Beneficial effect of lupeol and metformin in mouse model of intracerebroventricular streptozotocin induced dementia.

This study examines the effectiveness of lupeol and metformin in a mouse model of dementia generated by intracerebroventricular streptozotocin (i.c.v., STZ). Dementia was induced in Swiss mice with the i.c.v. administration of STZ at a dosage of 3 mg/kg on the first and third day. The assessment of dementia involved an examination of the Morris Water Maze (MWM) performance, as well as a number of biochemical and histological studies. STZ treatment resulted in significant decrease in MWM performance; various biochemical alterations (increase in brain acetyl cholinesterase (AChE) activity, thiobarbituric acid reactive species (TBARS), nitrite/nitrate, and reduction in nuclear factor erythroid 2 related factor-2 (Nrf-2), reduced glutathione (GSH) levels) and neuroinflammation [increased myeloperoxidase (MPO) activity & neutrophil infiltration]. The administration of Lupeol (50 mg/kg & 100 mg/kg; p.o.) and Metformin (150 mg/kg & 300 mg/kg; p.o.) demonstrated a considerable reduction in the behavioral, biochemical, and histological alterations produced by STZ. Low dose combination of lupeol (50 mg/kg; p.o.) and Metformin (150 mg/kg; p.o.) produced more pronounced effect than that of high doses of either agent alone. It is concluded that Lupeol and Metformin has shown efficacy in dementia with possible synergism between the two and can be explored as potential therapeutic agents for managing dementia of Alzheimer's disease (AD) type.

Amplification of Cardioprotective Response of Remote Ischemic Preconditioning in Rats by Quercetin: Potential Role of Activation of mTOR-dependent Autophagy and Nrf2.

OBJECTIVES: Noninvasive remote ischemic preconditioning (RIPC) is a practical, acceptable, and feasible conditioning technique reported to provide cardioprotection in myocardial ischemia-reperfusion injury (MIRI). It has been well-reported that quercetin possesses antioxidant and anti-inflammatory properties. This study investigates the modification of the cardioprotective response of RIPC by quercetin. METHODS: Adult Wistar rats were randomized into 12 groups of six animals each. MIRI was induced by subjecting the isolated hearts of Wistar rats to global ischemia for 30 min, succeeded by reperfusion of 120 min after mounting on the Langendorff PowerLab apparatus. Hind limb RIPC was applied in four alternate cycles of ischemia and reperfusion of 5 min each by tying the pressure cuff before isolation of hearts. RESULTS: MIRI was reflected by significantly increased infarct size, LDH-1, and CK-MB, TNF-α, TBARS, and decreased GSH, catalase, and hemodynamic index, and modulated Nrf2. Pretreatment of quercetin (25 and 50 mg/kg; i.p.) significantly attenuated the MIRI-induced cardiac damage and potentiated the cardioprotective response of RIPC at the low dose. Pretreatment of ketamine (10 mg/kg; i.p.), an mTOR-dependent autophagy inhibitor, significantly abolished the cardioprotective effects of quercetin and RIPC. CONCLUSIONS: The findings highlight the modification of the cardioprotective effect of RIPC by quercetin and that quercetin protects the heart against MIRI through multiple mechanisms, including mTOR-dependent activation of autophagy and Nrf-2 activation.

High-effect gene-coding variants impact cognition, mental well-being, and neighborhood safety substrates in brain morphology.

Our genetic makeup, together with environmental and social influences, shape our brain's development. Yet, the imaging genetics field has struggled to integrate all these modalities to investigate the interplay between genetic blueprint, environment, human health, daily living skills and outcomes. Hence, we interrogated the Adolescent Brain Cognitive Development (ABCD) cohort to outline the effects of rare high-effect genetic variants on brain architecture and corresponding implications on cognitive, behavioral, psychosocial, and socioeconomic traits. Specifically, we designed a holistic pattern-learning algorithm that quantitatively dissects the impacts of copy number variations (CNVs) on brain structure and 962 behavioral variables spanning 20 categories in 7,657 adolescents. Our results reveal associations between genetic alterations, higher-order brain networks, and specific parameters of the family well-being (increased parental and child stress, anxiety and depression) or neighborhood dynamics (decreased safety); effects extending beyond the impairment of cognitive ability or language capacity, dominantly reported in the CNV literature. Our investigation thus spotlights a far-reaching interplay between genetic variation and subjective life quality in adolescents and their families.

Identification of superior haplotypes for flowering time in pigeonpea through candidate gene-based association study of a diverse minicore collection.

KEY MESSAGE: In current study candidate gene (261 genes) based association mapping on 144 pigeonpea accessions for flowering time and related traits and 29 MTAs producing eight superior haplotypes were identified. In the current study, we have conducted an association analysis for flowering-associated traits in a diverse pigeonpea mini-core collection comprising 144 accessions using the SNP data of 261 flowering-related genes. In total, 13,449 SNPs were detected in the current study, which ranged from 743 (ICP10228) to 1469 (ICP6668) among the individuals. The nucleotide diversity (0.28) and Watterson estimates (0.34) reflected substantial diversity, while Tajima's D (-0.70) indicated the abundance of rare alleles in the collection. A total of 29 marker trait associations (MTAs) were identified, among which 19 were unique to days to first flowering (DOF) and/or days to fifty percent flowering (DFF), 9 to plant height (PH), and 1 to determinate (Det) growth habit using 3 years of phenotypic data. Among these MTAs, six were common to DOF and/or DFF, and four were common to DOF/DFF along with the PH, reflecting their pleiotropic action. These 29 MTAs spanned 25 genes, among which 10 genes clustered in the protein-protein network analysis, indicating their concerted involvement in floral induction. Furthermore, we identified eight haplotypes, four of which regulate late flowering, while the remaining four regulate early flowering using the MTAs. Interestingly, haplotypes conferring late flowering (H001, H002, and H008) were found to be taller, while those involved in early flowering (H003) were shorter in height. The expression pattern of these genes, as inferred from the transcriptome data, also underpinned their involvement in floral induction. The haplotypes identified will be highly useful to the pigeonpea breeding community for haplotype-based breeding.

Unique genetic architecture of prolificacy in 'Sikkim Primitive' maize unraveled through whole-genome resequencing-based DNA polymorphism.

KEY MESSAGE: 'Sikkim Primitive' maize landrace, unique for prolificacy (7-9 ears per plant) possesses unique genomic architecture in branching and inflorescence-related gene(s), and locus Zm00001eb365210 encoding glycosyltransferases was identified as the putative candidate gene underlying QTL (qProl-SP-8.05) for prolificacy. The genotype possesses immense usage in breeding high-yielding baby-corn genotypes. 'Sikkim Primitive' is a native landrace of North Eastern Himalayas, and is characterized by having 7-9 ears per plant compared to 1-2 ears in normal maize. Though 'Sikkim Primitive' was identified in the 1960s, it has not been characterized at a whole-genome scale. Here, we sequenced the entire genome of an inbred (MGUSP101) derived from 'Sikkim Primitive' along with three non-prolific (HKI1128, UMI1200, and HKI1105) and three prolific (CM150Q, CM151Q and HKI323) inbreds. A total of 942,417 SNPs, 24,160 insertions, and 27,600 deletions were identified in 'Sikkim Primitive'. The gene-specific functional mutations in 'Sikkim Primitive' were classified as 10,847 missense (54.36%), 402 non-sense (2.015%), and 8,705 silent (43.625%) mutations. The number of transitions and transversions specific to 'Sikkim Primitive' were 666,021 and 279,950, respectively. Among all base changes, (G to A) was the most frequent (215,772), while (C to G) was the rarest (22,520). Polygalacturonate 4-α-galacturonosyltransferase enzyme involved in pectin biosynthesis, cell-wall organization, nucleotide sugar, and amino-sugar metabolism was found to have unique alleles in 'Sikkim Primitive'. The analysis further revealed the Zm00001eb365210 gene encoding glycosyltransferases as the putative candidate underlying QTL (qProl-SP-8.05) for prolificacy in 'Sikkim Primitive'. High-impact nucleotide variations were found in ramosa3 (Zm00001eb327910) and zeaxanthin epoxidase1 (Zm00001eb081460) genes having a role in branching and inflorescence development in 'Sikkim Primitive'. The information generated unraveled the genetic architecture and identified key genes/alleles unique to the 'Sikkim Primitive' genome. This is the first report of whole-genome characterization of the 'Sikkim Primitive' landrace unique for its high prolificacy.

Protective Role of Vitamin D Against Development of Active Tuberculosis in Close Household Contacts of Pulmonary Tuberculosis Patients: A Prospective Cohort Study.

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment.

Comparative analysis of soil quality and enzymatic activities under different tillage based nutrient management practices in soybean-wheat cropping sequence in Vertisols.

In the modern era, intensive agricultural practices such as agrochemicals are applied in excessive amounts to enhance agricultural production. However, imbalanced adoption of these chemicals has arisen in the dwindling of agriculture factor productivity and soil quality. To maintain soil fertility and production, these chemical fertilizers must be supplemented with organic inputs. Keeping this in the backdrop, a research trail was established during 2018-19 and 2019-20 years at Research Farm of Agriculture University, Kota, India. The treatment setup was comprised of 5 treatment modules viz., conservation tillage + organic management (CAOM), conservation tillage + chemical management (CACM), conventional tillage + chemical management (CTCM), conventional tillage + organic management (CTOM) and the package of practices (PoPs) with four replications. Results indicated that the highest organic carbon (0.68%), bacterial (29.11 × 107 cfu g-1), fungal (4.77 × 104 cfu g-1), actinomycetes populations (5.67 × 104 cfu g-1), acid phosphatase (44.1 µg g-1 h-1), urease (45.3 µg g-1 h-1) and dehydrogenase (23.3 µg triphenylformazan [TPF] g-1 h-1) activity in soil were found in the treatment of conservation organic system during both the years of study at each soil depth. In contrast to other parameters, the highest system productivity was observed with conservation chemical crop management approaches, with a soybean equivalent yield of 4615 kg ha-1 in a soybean-wheat system of production. Furthermore, the soil quality index (SQI) significantly varied from the lowest score (0.30) at 45-60 cm layer of soil in the package of practices to the highest score (0.92) at 0-15 cm layer of soil with regards to the conservation organic which shows, 206.67 percent enhancement through the soil profile of various crop management practices. The SQI variation from 0-15 to 45-60 cm soil depth was 130.0, 81.08, 60.0, 175.0 and 83.33 percent, respectively, for CAOM, CACM, CTCM, CTOM and PoPs. Amongst, different systems, the highest mean performance was noticed under the conservation organic systems for physical and biological properties. Hence, in line with the salient outcome, we may propose that the conservation chemical system needs to be followed to improve crop productivity, whereas, conservation organic seems a good option for soil health with long-term viability.

Using rare genetic mutations to revisit structural brain asymmetry.

Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We designed a pattern-learning approach to dissect the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior data fusion highlights the consequences of genetically controlled brain lateralization on uniquely human cognitive capacities.

Effect of Benidipine Alone and in Combination With Bosentan and Sildenafil in Amelioration of Pulmonary Arterial Hypertension in Experimental Model in Rats.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a persistent condition affecting the pulmonary arteries' endothelium. Benidipine, a calcium channel blocker, possesses vasodilatory, anti-inflammatory activity, reduces oxidative stress, and inhibits the activity of Transforming growth factor-ß (TGF-ß) and α-smooth muscle actin (α-SMA). The present study was designed to investigate the effect of benidipine alone and in combination with bosentan and sildenafil on monocrotaline (MCT)-induced pulmonary hypertension in a rat model. PAH was induced by a single-dose administration of MCT in rats. Animals were randomized into different groups and treated with benidipine alone and in combination with bosentan or sildenafil. Various parameters such as hemodynamic parameters, Fulton's index and oxidative stress parameters were performed. Additionally, histopathology of lung and right ventricular of heart tissue, immunohistochemistry, expression of α-SMA, endothelial nitric oxide synthase (eNOS), TGF-ß, and RT-PCR, and an in vitro study using human umbilical vein endothelial cells (HUVECs) was also carried out. Treatment of benidipine and its combination exhibited better prevention in the elevated right ventricular systolic pressure, right ventricular hypertrophy, rise in oxidative stress, and increase in expression of α-SMA and TGF-ß receptor 1 compared with MCT control group rats. In HUVECs, the expression of α-SMA was increased, whereas that of eNOS decreased after TGF-ß exposure and was substantially reversed after pretreatment with benidipine. We concluded that benidipine and its combination with bosentan and sildenafil exhibit beneficial effects in MCT-induced PAH through the eNOS/TGF-ß/α-SMA signaling pathway.

Equilibrium of Dietary Patterns Between Alzheimer's Disease Patients and Healthy People: A Comprehensive Analysis Using Multiple Factor Analysis and Classification Modeling.

BACKGROUND: Alzheimer's disease (AD) is a particular type of dementia that currently lacks a definitive treatment and cure. It is possible to reduce the risk of developing AD and mitigate its severity through modifications to one's lifestyle, regular diet, and alcohol-drinking habits. OBJECTIVE: The objective of this study is to examine the daily dietary patterns of individuals with AD compared to healthy controls, with a focus on nutritional balance and its impact on AD. METHODS: This study incorporated multiple-factor analysis (MFA) to evaluate dietary patterns and employed Random Forest (RF) classifier and Sparse Logistic Regression (SLR) for Variable Importance analysis to identify food items significantly associated with AD. RESULTS: MFA revealed trends in the data and a strong correlation (Lg = 0.92, RV = 0.65) between the daily consumption of processed food and meat items in AD patients. In contrast, no significant relationship was found for any daily consumed food categories within the healthy control (HC) group. Food items such as meat pie, hamburger, ham, sausages, beef, capsicum, and cabbage were identified as important variables associated with AD in RF and SLR analyses. CONCLUSIONS: The findings from MFA indicated that the diversity or equilibrium of daily diet might play a potential role in AD development. RF and SLR classifications exhibit among the processed foods, especially deli meats and food made with meat items, are associated with AD.

Whole chloroplast genome-specific non-synonymous SNPs reveal the presence of substantial diversity in the pigeonpea mini-core collection.

To unravel the plastid genome diversity among the cultivated groups of the pigeonpea germplasm, we characterized the SNP occurrence and distribution of 142 pigeonpea mini-core collections based on their reference-based assembly of the chloroplast genome. A total of 8921 SNPs were found, which were again filtered and finally 3871 non-synonymous SNPs were detected and used for diversity estimates. These 3871 SNPs were classified into 12 groups and were present in only 44 of the 125 genes, demonstrating the presence of a precise mechanism for maintaining the whole chloroplast genome throughout evolution. The Acetyl-CoA carboxylase D gene possesses the maximum number of SNPs (12.29%), but the Adenosine Tri-Phosphate synthatase cluster genes (atpA, atpB, atpE, atpF, atpH, and atpI) altogether bear 43.34% of the SNPs making them most diverse. Various diversity estimates, such as the number of effective alleles (1.013), Watterson's estimate (0.19), Tajima's D ( - 3.15), Shannon's information index (0.036), suggest the presence of less diversity in the cultivated gene pool of chloroplast genomes. The genetic relatedness estimates based on pairwise correlations were also in congruence with these diversity descriptors and indicate the prevalence of rare alleles in the accessions. Interestingly, no stratification was observed either through STRUCTURE, PCoA, or phylogenetic analysis, indicating the common origin of the chloroplast in all the accessions used, irrespective of their geographical distribution. Further 6194 Cleaved Amplified Polymorphic Sequences (CAPS) markers for 531 SNPs were developed and validated in a selected set of germplasm. Based on these results, we inferred that all of the cultivated gene pools of pigeonpea have a common origin for the chloroplast genome and they possess less diversity in protein-coding regions, indicating a stable and evolved plastid genome. At the same time, all diversity analysis indicates the occurrence of rare alleles, suggesting the suitability of the mini-core collection in future pigeonpea improvement programs. In addition, the development of chloroplast genome-based CAPS markers would have utility in pigeonpea breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03785-8.