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In the domain of space science, numerous ground-based and space-borne data of various phenomena have been accumulating rapidly, making analysis and scientific interpretation challenging. However, recent trends in the application of artificial intelligence (AI) have been shown to be promising in the extraction of information or knowledge discovery from these extensive data sets. Coincidentally, preparing these data for use as inputs to the AI algorithms, referred to as AI-readiness, is one of the outstanding challenges in leveraging AI in space science. Preparation of AI-ready data includes, among other aspects: 1) collection (accessing and downloading) of appropriate data representing the various physical parameters associated with the phenomena under study from different repositories; 2) addressing data formats such as conversion from one format to another, data gaps, quality flags and labeling; 3) standardizing metadata and keywords in accordance with NASA archive requirements or other defined standards; 4) processing of raw data such as data normalization, detrending, and data modeling; and 5) documentation of technical aspects such as processing steps, operational assumptions, uncertainties, and instrument profiles. Making all existing data AI-ready within a decade is impractical and data from future missions and investigations exacerbates this. This reveals the urgency to set the standards and start implementing them now. This article presents our perspective on the AI-readiness of space science data and mitigation strategies including definition of AI-readiness for AI applications; prioritization of data sets, storage, and accessibility; and identifying the responsible entity (agencies, private sector, or funded individuals) to undertake the task.

Aim: In this study, we have used enzyme-linked immunosorbent assay (ELISA) as an alternative test to replace the cumbersome rapid fluorescent focus inhibition test (RFFIT) to ascertain the immune status of immunized mice against rabies virus. Materials and Methods: Rabies is a devastating disease worldwide caused by rabies virus. Proper usage of pre- or post-exposure rabies vaccine can prevent the disease transmission. In this study, mice were immunized with Vero cell-adapted inactivated rabies vaccine. RFFIT was used as a test to determine the serum neutralizing titers in infected/vaccinated mice. Seroprofiling of mice sera was done in vitro by ELISA. Results: Twenty-one days post-immunization, both ELISA and RFFIT assays indicated similar antibody levels in mice sera that were immunized with Vero cell-adapted inactivated rabies vaccine. Both the tests were correlated, and the linearity was verified by the regression line (R2=0.979). Conclusion: In this study, we profiled the serological status of Vero cell-adapted inactivated rabies vaccine through ELISA in mice model that correlated well with the OIE gold standard test RFFIT.

The present study deals with detecting seismic anisotropy parameters beneath southeastern Tibet near Namcha Barwa Mountain using the splitting of direct S waves. We employ the reference station technique to remove the effects of source-side anisotropy. Seismic anisotropy parameters, splitting time delays, and fast polarization directions are estimated through analyses of a total of 501 splitting measurements obtained from direct S waves from 25 earthquakes ( ≥ 5.5 magnitude) that were recorded at 42 stations of the Namcha Barwa seismic network. We observe a large variation in time delays ranging from 0.64 to 1.68 s, but in most cases, it is more than 1 s, which suggests a highly anisotropic lithospheric mantle in the region. A comparison between direct S- and SKS-derived splitting parameters shows a close similarity, although some discrepancies exist where null or negligible anisotropy has been reported earlier using SKS. The seismic stations with hitherto null or negligible anisotropy are now supplemented with new measurements with clear anisotropic signatures. Our analyses indicate a sharp change in lateral variations of fast polarization directions (FPDs) from consistent SSW–ENE or W–E to NW–SE direction at the southeastern edge of Tibet. Comparison of the FPDs with Global Positioning System (GPS) measurements, absolute plate motion (APM) directions, and surface geological features indicates that the observed anisotropy and hence inferred deformation patterns are not only due to asthenospheric dynamics but are a combination of lithospheric deformation and sub-lithospheric (asthenospheric) mantle dynamics. Direct S-wave-based station-averaged splitting measurements with increased back-azimuths tend to fill the coverage gaps left in SKS measurements.

Aim: The aim of this study was to generate composite bone graft and investigate the rabbit fetal osteoblasts adhesion, proliferation and penetration on acellular matrices of cancellous bone. Materials and Methods: Acellular cancellous bone was prepared and developed as in the previous study with little modification. These matrices were decellularized by rapid freeze and thaw cycle. To remove the cell debris, they were then treated with hydrogen peroxide (3%) and ethanol to remove antigenic cellular and nuclear materials from the scaffold. Primary osteoblast cells were harvested from 20 to 22 days old rabbit fetal long and calvarial bone. These cells were cultured and characterized using a specific marker. The third passaged fetal osteoblast cells were then seeded on the scaffold and incubated for 14 days. The growth pattern of the cells was observed. Scanning electron microscope and hematoxylin and eosin staining were used to investigate cells proliferation. Results: The cells were found to be growing well on the surface of the scaffold and were also present in good numbers with the matrix filopodial extensions upto inside of the core of the tissue. Conclusion: Thus, a viable composite scaffold of bone could be developed which has a great potential in the field of bone tissue engineering.

Abstract The efficient release of magnetic energy in astrophysical plasmas, such as during solar flares, can in principle be achieved through magnetic diffusion, at a rate determined by the associated electric field. However, attempts at measuring electric fields in the solar atmosphere are scarce, and none exist for sites where the magnetic energy is presumably released. Here, we present observations of an energetic event using the National Science Foundation’s Daniel K. Inouye Solar Telescope, where we detect the polarization signature of electric fields associated with magnetic diffusion. We measure the linear and circular polarization across the hydrogen Hε Balmer line at 397 nm at the site of a brightening event in the solar chromosphere. Our spectro-polarimetric modeling demonstrates that the observed polarization signals can only be explained by the presence of electric fields, providing conclusive evidence of magnetic diffusion, and opening a new window for the quantitative study of this mechanism in space plasmas.

Abstract Clean river water is an essential and life-sustaining asset for all living organisms. The upper Ganga and Yamuna river system has shown signs of rejuvenation and tremendous improvement in the water quality following the nationwide lockdown due to the coronavirus pandemic. All the industrial and commercial activity was shut down, and there was negligible wastewater discharge from the industries. This article addresses the water quality assessment from the study area, which is based on the original data of physical parameters, major and trace elements, and stable isotopes (hydrogen and oxygen) systematics during the nationwide lockdown. The impact of the lockdown could be seen in terms of an increase in dissolved oxygen (DO). Water samples were collected from the Upper Ganga and Yamuna river basins (Alaknanda, Bhagirathi, and Tons rivers) during an eight-week lockdown in Uttarakhand, India. We discussed the signs of rejuvenation of riverine based on physical parameters, major ions, trace elements, isotopic ratios, and water pollution index (WPI). Results reveal that the water quality of the entire upper basins of the Ganga has significantly improved by 93%, reflecting the signs of self-rejuvenation of the rivers. Multivariate analysis suggests a negative factor loading for an anthropogenic element ( $${NO}_{3}^{-}$$ NO 3 - ), implying that they contribute little to the river water during the lockdown. Further, bicarbonate ( $${HCO}_{3}^{-}$$ HCO 3 - ) is a dominant element in both river basins. The geochemical facies are mainly characterized by the ( $${{Ca}^{2+} :{Mg}^{2+} : HCO}_{3}^{-}$$ Ca 2 + : Mg 2 + : H C O 3 - ) type of water, suggesting that silicate rock weathering dominates with little influence from carbonate weathering in the area. The positive factor loadings of some cations, like $${HCO}_{3}^{-}$$ HCO 3 - , $${Ca}^{2+}$$ Ca 2 + , and $${Mg}^{2+}$$ Mg 2 + reflect their strong association with the source of origin in the lockdown phases. Stable isotopic reveals that the glaciated region contributed the most to the river basin, as evidenced by the low d-excess in riverine water compared to anthropogenic contributions. Rivers can self-rejuvenate if issues of human influence and anthropogenic activities are adequately resolved and underline our responsibility for purifying the ecosystem. We observed that this improvement in the river water quality will take a shorter time, and quality will deteriorate again when commercial and industrial activity resumes.

Abstract Background Centromere function is highly conserved across eukaryotes, but the underlying centromeric DNA sequences vary dramatically between species. Centromeres often contain a high proportion of repetitive DNA, such as tandem repeats and/or transposable elements (TEs). Einkorn wheat centromeres lack tandem repeat arrays and are instead composed mostly of the two long terminal repeat (LTR) retrotransposon families RLG_Cereba and RLG_Quinta which specifically insert in centromeres. However, it is poorly understood how these two TE families relate to each other and if and how they contribute to centromere function and evolution. Results Based on conservation of diagnostic motifs (LTRs, integrase and primer binding site and polypurine-tract), we propose that RLG_Cereba and RLG_Quinta are a pair of autonomous and non-autonomous partners, in which the autonomous RLG_Cereba contributes all the proteins required for transposition, while the non-autonomous RLG_Quinta contributes GAG protein. Phylogenetic analysis of predicted GAG proteins showed that the RLG_Cereba lineage was present for at least 100 million years in monocotyledon plants. In contrast, RLG_Quinta evolved from RLG_Cereba between 28 and 35 million years ago in the common ancestor of oat and wheat. Interestingly, the integrase of RLG_Cereba is fused to a so-called CR-domain, which is hypothesized to guide the integrase to the functional centromere. Indeed, ChIP-seq data and TE population analysis show only the youngest subfamilies of RLG_Cereba and RLG_Quinta are found in the active centromeres. Importantly, the LTRs of RLG_Quinta and RLG_Cereba are strongly associated with the presence of the centromere-specific CENH3 histone variant. We hypothesize that the LTRs of RLG_Cereba and RLG_Quinta contribute to wheat centromere integrity by phasing and/or placing CENH3 nucleosomes, thus favoring their persistence in the competitive centromere-niche. Conclusion Our data show that RLG_Cereba cross-mobilizes the non-autonomous RLG_Quinta retrotransposons. New copies of both families are specifically integrated into functional centromeres presumably through direct binding of the integrase CR domain to CENH3 histone variants. The LTRs of newly inserted RLG_Cereba and RLG_Quinta elements, in turn, recruit and/or phase new CENH3 deposition. This mutualistic interplay between the two TE families and the plant host dynamically maintains wheat centromeres.

Abstract Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

The general expression of TEM response of large loop source over the layered earth models is not available in the literature for arbitrary source-receiver positions, except for the case of central loop and coincident loop configurations over the homogeneous earth model. In the present study, an attempt is made to present the TEM response of a large loop source over the layered earth model for arbitrary receiver positions. The frequency domain responses of large loop source over the layer earth model for arbitrary receiver positions are converted into the impulse (time derivative of magnetic field) TEM response using Fourier cosine or sine transform. These impulse TEM responses in turn are converted into voltage responses for arbitrary receiver positions, namely, central loop, arbitrary in-loop, and offset-loop TEM responses over the layered earth models. For checking the accuracy of the method, results are compared with the results obtained using analytical expression over a homogeneous earth model. The complete matching of both of the results suggests that the present computational technique is capable of computing TEM response of large loop source over the homogeneous earth model with high accuracy. Thereafter, the technique is applied for computation of TEM response of a large loop source over the layered earth (2-layer, 3-layer, and 4-layer) models for the central loop, in-loop, and offset-loop configurations and the results are presented in voltage decay form. The results depict their characteristic variations. These results would be useful for modeling and inversion of large loop TEM data over the layer earth models for all the possible configurations resulting from a large loop source.

Aim: This study was undertaken to assess the differential expression levels of toll-like receptors (TLRs) 2, 3 and 7 in peripheral blood mononuclear cells (PBMCs) isolated from Tharparkar and Crossbred cattle belonging to different regions of India. Materials and Methods: PBMCs were isolated from blood samples of Tharparkar cattle from Indian Veterinary Research Institute (IVRI) farm (n=30); Suratgarh farm (n=61); Jaipur farm (n=8) and cross breed cattle from Jaipur (n=47). RNA was isolated from PBMCs and cDNA was synthesized using random hexamers. The expression profiles of TLR 2, 3 and 7 were estimated by real-time PCR and normalized to the expression of β-actin. Results: PBMCs of Tharparkar cattle from Suratgarh, exhibited a significantly higher (p

Abstract Identifying faces requires configural processing of visual information. We previously proposed that the poor visual acuity experienced by newborns in their first year of life lays the groundwork for such configural processing by forcing integration over larger spatial fields. This hypothesis predicts that children treated for congenital cataracts late in life will exhibit persistent impairments in face- but not object-identification, because they begin their visual journey with higher than newborn acuity. This would not be the case for patients whose pretreatment condition has allowed for initial low acuity vision, like that of a newborn. Here, we test this prediction by assessing the development of facial identification skill in three groups: patients treated for congenital cataracts whose pretreatment visual acuity was worse than that of a newborn, patients whose pretreatment acuity was better than that of a newborn, and age-matched controls. We find that while both patient groups show significant gains in object-identification, the emergence of face identification is determined by pretreatment acuity: patients with pre-operative acuity worse than a newborn did not show any improvements on face-identification tasks despite years of visual experience, whereas those with pretreatment acuity comparable to a newborn improved on both the object- and face-identification tasks. These findings not only answer our research question but also provide new insights into the role of early visual acuity in facial identification development. We discuss these results in the context of both typical and atypical visual development.

Abstract Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.

Abstract Objective Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2‐item scale polygenic score with anxiety in MS. Methods Using a case–control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview‐diagnosed, and lifetime self‐report physician‐diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome‐wide association study and was tested using regression. Results A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta‐analyses identified that in MS, each 1‐SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09–1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. Interpretation Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

Abstract Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms (CAA) in KD despite intravenous gamma globulin (IVIG) treatment is not known. We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z ≥ 2.5 and large coronary aneurysm (CAA/L) (N = 92) as z ≥ 5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p

Abstract Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

Abstract Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by extensive intratumoral heterogeneity, high metastasis, and chemoresistance, leading to poor clinical outcomes. Despite progress, the mechanistic basis of these aggressive behaviors remains poorly understood. Using single-cell and spatial transcriptome analysis, here we discovered basal epithelial subpopulations located within the stroma that exhibit chemoresistance characteristics. The subpopulations are defined by distinct signature genes that show a frequent gain in copy number and exhibit an activated epithelial-to-mesenchymal transition program. A subset of these genes can accurately predict chemotherapy response and are associated with poor prognosis. Interestingly, among these genes, elevated ITGB1 participates in enhancing intercellular signaling while ACTN1 confers a survival advantage to foster chemoresistance. Furthermore, by subjecting the transcriptional signatures to drug repurposing analysis, we find that chemoresistant tumors may benefit from distinct inhibitors in treatment-naive versus post-NAC patients. These findings shed light on the mechanistic basis of chemoresistance while providing the best-in-class biomarker to predict chemotherapy response and alternate therapeutic avenues for improved management of TNBC patients resistant to chemotherapy.

Abstract Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype characterised by extensive intratumoral heterogeneity, high rates of metastasis and chemoresistance, leading to poor clinical outcomes. Despite progress, the mechanistic basis of chemotherapy resistance in TNBC patients remains poorly understood. Here, leveraging single-cell transcriptome datasets of matched longitudinal TNBC chemoresponsive and chemoresistant patient cohorts, we unravel distinct cell subpopulations intricately associated with chemoresistance and the signature genes defining these populations. Notably, using genome-wide mapping of the H3K27ac mark, we show that the expression of these chemoresistance genes is driven via a set of TNBC super-enhancers and associated transcription factor networks across TNBC subtypes. Furthermore, genetic screens reveal that a subset of these transcription factors is essential for the survival of TNBC cells, and their loss increases sensitivity to chemotherapeutic agents. Overall, our study has revealed epigenetic and transcription factor networks underlying chemoresistance and suggests novel avenues to stratify and improve the treatment of patients with a high risk of developing resistance.

Abstract Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

Assessing the dynamics and patterns of Land Use and Land Cover (LULC) and its transformation is an important practice of urban planners and environmentalists for a variety of applications, including land management, urban climate modeling, and sustainability of any urban region. Monitoring changes in LULC using geospatial techniques can help to identify areas at risk for indefensible land use, low-grade environment, and especially for sustainable urban planning. This study aims to analyze the changing pattern, dynamics, and alteration of LULC using Google Earth Engine (GEE) and Machine Learning Applications for the years 1991, 2001, 2011, and 2022 in the Varanasi City Development Region (VCDR). The LULC classification was divided into seven classes using random forest classification, and Landsat-5(TM) and 9(OLI-2) satellite data were used. Saga GIS has been utilized for the detection of LULC change during the 1991-2022 period. For validation of classification results, accuracy assessment was estimated using error matrices and through user, producer, and overall accuracy estimation. The Kappa statistics were applied for the reliability of the accuracy assessment result. As a result, the built-up area increased by 507.8 percent, and other classes like agricultural, barren, fallow land, and vegetation cover rapidly declined and altered into concrete areas over the period. Water bodies and river sand classes have been slightly converted into different classes. The finding explains that 114.8 km2 of fertile agricultural land, 14.81 km2 barren land, and 12.93 km2 of vegetation cover transformed into impervious surface, which is unsustainable and causes various problems like food scarcity, environmental degradation, and low quality of urban life. This study can be a useful guide for urban planners, academicians, and policymakers by providing a scientific background for sustainable urban planning and management of VCDR and other cities as well.

The present study was designed and conducted to evaluate the influence of methoxyfenozide on the reproductive potential of 1st, 2nd, 3rd and 4th instars larvae, as a safe and suitable alternative for the conventional organic insecticide. Results showed that the highest concentration i.e. 15 ppm of methoxyfenozide caused maximum reduction in fecundity i.e. 118.43 ± 6.08 eggs laid/ female and hatchability i.e. 31.52 ± 1.18% when both males and females were crossed emerged from treated culture in case of 1st instar exposed larvae. Such pairs showed maximum sterility also when emerged from 15 ppm concentration of food in 1st instar exposure. Fecundity, fertility and sterility comparatively decreased in 2nd, 3rd and 4thinstar larvae due to their comparatively poor exposure duration. Such knowledge may offcourse be beneficial for the effective control of rice-moth in particular and lepidopterous pest in general in eco-friendly way.

The hyetograph represents the temporal spread of rainfall intensity occurring at a point or over a watershed during a storm. The importance of regionally derived/developed hyetographs and the pooled sets of categorical seasonal curves on intensity-duration, intensity-depth, and depth-duration are of multifarious conveniences and importance. Twenty-one years of daily and sub-daily rainfall records (2000–2020) regained via satellite-observed precipitation products were examined and used to retrieve a valid understanding towards annual, monthly, daily, and hourly based variability of rainfall across six different stations. An attempt was made to compare the shapes of synthesized seasonal rain mass curves with that of the historic Soil Conservation Service (SCS) mass curve. The results indicate that the location-specific patterns and trends of curves do not align closely with any historical SCS curves or theoretical curves prevalent in the literature and commonly adopted. It has been observed that region-specific rainfall and its temporal distributions exhibit unique trends, not necessarily conforming to the standard SCS-based curves categorized as Types I, Ia, II, and III. This emphasizes the need to rely more on region-specific curves rather than instinctively adopting a standard set of curves. HIGHLIGHTS Region-specific hyetographs reveal distinct rainfall intensity patterns.; Historical Soil Conservation Service curve shapes do not align with regional trends.; Emphasizes the need for region-specific curves over standardized ones.; Advocates for site-specific mass curves and hyetographs.;

Abstract Schizophrenia is a severe mental illness and a major risk factor for suicide, with approximately 50% of schizophrenia patients attempting and 10% dying from suicide. Although genetic components play a significant role in schizophrenia risk, the underlying genetic risk factors for suicide are poorly understood. The complement component C4 gene, an immune gene involved in the innate immune system and located in the major histocompatibility complex (MHC) region, has been identified to be strongly associated with schizophrenia risk. In addition, recent findings have also suggested that the MHC region has been associated with suicide risk across disorders, making C4 a potential candidate of interest for studying suicidality in schizophrenia patients. Despite growing interest in investigating the association between the C4 gene and schizophrenia, to our knowledge, no work has been done to examine the potential of C4 variants as suicide risk factors in patients with schizophrenia. In this study, we investigated the association between different C4 copy number variants and predicted C4 brain expression with suicidal outcomes (suicide attempts/suicidal ideation). We directly genotyped 434 schizophrenia patients to determine their C4A and C4B copy number variants. We found the C4AS copy number to be marginally and negatively associated with suicide risk, potentially being protective against suicide attempts (OR = 0.49; p = 0.05) and suicidal ideation (OR = 0.65; p = 0.07). Furthermore, sex-stratified analyses revealed that there are no significant differences between males and females. Our preliminary findings encourage additional studies of C4 and potential immune dysregulation in suicide.

Abstract Background African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. Methods Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. Results We observed genome-wide significant (P-value < 5.0E−8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E−6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E−6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E−6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. Conclusions Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke’s risk prediction and development of new targeted interventions to prevent or treat stroke.

The article introduces a cost-effective and user-friendly alternative to traditional pyrolysis techniques, obviating the necessity for intricate tube furnaces and inert gas environments. This novel approach employs materials capable of reacting with and sequestering oxygen to establish an oxygen-depleted atmosphere. The experimental setup entails positioning a crucible containing the sample inside a ceramic pot, enveloped by varying sizes of wood coal particles, and subsequently subjecting the ceramic pot to furnace conditions. Utilizing this oxygen-limited strategy, a biochar sample, derived via hydrothermal processing, underwent carbonization at 650°C for 6.5 hours, with outcomes compared against ambient condition carbonization under identical temperature and duration parameters. Gravimetric analysis revealed that wood coal effectively curtails oxygen availability, augmenting biochar yield from 1.53 % to 19.50 %. Fourier-transform infrared spectroscopy (FTIR) indicates diminished oxygen functional groups, while X-ray diffraction (XRD) and field-emission scanning electron microscopy (FESEM) affirmed a denser, compact carbon structure in biochar produced under oxygen-restricted conditions versus ambient conditions. The carbon content percentage in biochar samples treated at 650°C for 6.5 hours under both conditions was assessed via energy-dispersive X-ray spectroscopy (EDX) data. The emergence of a novel carbon nanomaterial, derived from biomass waste through our oxygen-limiting method, may exhibits applications in energy storage and water purification. Our approach offers simplicity, cost-efficiency, and straightforward implementation while upholding the integrity of pyrolysis/thermal treatment within inert conditions, ensuring the robustness of the procedure.

The present study aims at investigating the application of ultrasound assisted choline chloride (ChCl) – formic acid (FA) deep eutectic solvent (DES) pretreatment of Barley straw. In addition, the efficiency of a wet grinding followed by high intensity ultrasound (HIUS) treatment for production of cellulose nanofibers (CNF) has been evaluated. The DES (using ChCl: FA at 1:9 M ratio) treatment at 45 kHz ultrasound frequency and 3 h of treatment duration resulted in 84.68 ± 1.02 % and 82.96 ± 0.79 % of lignin and hemicellulose solubilisation, respectively. The purification of DES treated solid residue resulted in cellulose with more than 90 % purity. Further, 10 min of wet grinding followed by 40 min of HIUS treatment resulted in more than 80 % nano-fibrillation efficiency. The produced CNF had diameters less than 100 nm in number size distribution and type I cellulose structure. This study confirmed that the developed process offers a sustainable method for producing nanocellulose from agricultural waste.

Multiwalled carbon nanotubes (MWCNTs) are at the forefront of nanotechnology-based advancements in cancer therapy, particularly in the field of targeted drug delivery. The nanotubes are characterized by their concentric graphene layers, which give them outstanding structural strength. They can deliver substantial doses of therapeutic agents, potentially reducing treatment frequency and improving patient compliance. MWCNTs’ diminutive size and modifiable surface enable them to have a high drug loading capacity and penetrate biological barriers. As a result of the extensive research on these nanomaterials, they have been studied extensively as synthetic and chemically functionalized molecules, which can be combined with various ligands (such as folic acid, antibodies, peptides, mannose, galactose, polymers) and linkers, and to deliver anticancer drugs, including but not limited to paclitaxel, docetaxel, cisplatin, doxorubicin, tamoxifen, methotrexate, quercetin and others, to cancer cells. This functionalization facilitates selective targeting of cancer cells, as these ligands bind to specific receptors overexpressed in tumor cells. By sparing non-cancerous cells and delivering the therapeutic payload precisely to cancer cells, this therapeutic payload delivery ability reduces chemotherapy systemic toxicity. There is great potential for MWCNTs to be used as targeted delivery systems for drugs. In this review, we discuss techniques for functionalizing and conjugating MWCNTs to drugs using natural and biomacromolecular linkers, which can bind to the cancer cells’ receptors/biomolecules. Using MWCNTs to administer cancer drugs is a transformative approach to cancer treatment that combines nanotechnology and pharmacotherapy. It is an exciting and rich field of research to explore and optimize MWCNTs for drug delivery purposes, which could result in significant benefits for cancer patients.

Abstract Background Glioblastomas are characterized by aggressive behavior. Surgery, radiotherapy, and alkylating agents, including temozolomide are the most common treatment options for glioblastoma. Often, conventional therapies fail to treat these tumors since they develop drug resistance. There is a need for newer agents to combat this deadly tumor. Natural products such as gedunin have shown efficacy in several human diseases. A comprehensive study of gedunin, an heat shock protein (HSP)90 inhibitor, has not been thoroughly investigated in glioblastoma cell lines with different genetic modifications. Aims A key objective of this study was to determine how gedunin affects the biological and signaling mechanisms in glioblastoma cells, and to determine how those mechanisms affect the proliferation and apoptosis of glioblastoma cells. Methods The viability potentials of gedunin were tested using MTT, cell counts, and wound healing assays. Gedunin's effects on glioma cells were further validated using LDH and colony formation assays. In addition, we investigated the survival and apoptotic molecular signaling targets perturbed by gedunin using Western blot analysis and flow cytometry. Results Our results show that there was a reduction in cell viability and inhibition of wound healing in the cells tested. Western blot analysis of the gene expression data revealed genes such as EGFR and mTOR/Akt/NF kappa B to be associated with gedunin sensitivity. Gedunin treatment induced apoptosis by cleaving poly ADP‐ribose polymerase, activating caspases, and downregulating BCL‐xL. Based on these results, gedunin suppressed cell growth and HSP client proteins, resulting in apoptosis in glioblastoma cell lines. Conclusion Our data provide in vitro support for the anticancer activity of gedunin in glioma cells by downregulating cancer survival proteins.

Acoustic cavitation, an intriguing phenomenon resulting from the interaction of sound waves with a liquid medium, has emerged as a promising avenue in agri-food processing, offering opportunities to enhance established processes improving primary production of ingredients and further food processing. This comprehensive review provides an in-depth analysis of the mechanisms, design considerations, challenges and scale-up strategies associated with acoustic cavitation for agri-food applications. The paper starts by elucidating the fundamental principles of acoustic cavitation and its measurement, delving then into the diverse effects of different parameters associated with, the acoustic wave, mechanical design and operation of the ultrasonic system, along with those related to the food matrix. The technological advancements achieved in the design and set-up of ultrasonic reactors addressing limitations during scale up are also discussed. The design, engineering and mathematical modelling of ultrasonic equipment tailored for agri-food applications are explored, along with strategies to maximize cavitation intensity and efficiency in the application of brining, freezing, drying, emulsification, filtration and extraction. Advanced US equipment, such as multi-transducers (tubular resonator, FLOW:WAVE®) and larger processing surface areas through innovative designing (Barbell horn, CascatrodesTM), are one of the most promising strategies to ensure consistency of US operations at industrial scale. This review paper aims to provide valuable insights into harnessing acoustic cavitation's potential for up-scaling applications in food processing via critical examination of current research and advancements, while identifying future directions and opportunities for further research and innovation.

Abstract Monitoring changes in Land Use/Land Cover (LULC), spectral indices, and Land Surface Temperature (LST) can help to identify the areas at risk for indefensible land use, a low-grade environment, and especially urban heat islands (UHI). This study aims to examine the changing pattern of LULC, the dynamics of geospatial indices (Normalised Difference Vegetation Index (NDVI), Normalised Difference Built-up Index (NDBI), Normalised Difference Water Index (NDWI), Normalised Difference Bareness Index (NDBaI), and Normalised Difference Latent-heat Index (NDLI)), and LST patterns with the relationship among them between 1991 and 2021 in the Varanasi City Development Region (VCDR). The LULC classification was done into seven classes (using the maximum likelihood method), the LST has been retrieved, and the above spectral indices have been calculated using Landsat 5 and 8 data. Pearson’s correlation method was used to analyse the relationship between LST and spectral indices. As per result, built-up area was increased by 507.8 per cent consequently, water bodies, agricultural, barren, fallow land and vegetation cover were declined by 4.84, 18.68, 82.41, 26.18 and 22.16 per cent respectively during 1991–2021. The maximum, minimum, and mean LST increased by 6.18, 2.28, and 2.24 °C, respectively, throughout the period. A positive relationship has been observed among NDBI, NDBaI, NDLI, and LST, whereas NDVI, NDWI, and LST have an inverse relationship. The finding explains the high number of water bodies, healthy vegetation cover, sufficient open space, and less concrete surface are necessary to maintain the LST and its related problems. So, an SPURS plan has been proposed to maintain the thermal environment of VCDR. This study can be a useful guide for planners and policymakers by providing a scientific background as well as the suggestions for sustainable urban management and development in VCDR and other cities as well.

Abstract Currently, space-coiling acoustic metamaterials are static, requiring manual reconfiguration for sound-field modulation. Here, we introduce an approach to enable active reconfiguration, using standalone dynamic space-coiling unit cells called dynamic meta-bricks. Unlike their static counterparts, these meta-bricks, house an actuatable soft robotic-inspired magnetorheological elastomeric flap. This flap operates like a switch to directly control the transmitted ultrasound. For scalability, we present a hybrid stacking method, which vertically combines static and dynamic meta-bricks. This allows us to form a surface-integrated metasurface through concatenating variations of either fully static or hybrid stacks. By actuating dynamic metasurface sections, we experimentally demonstrate accurate modulation of λ/4 (≈2 mm) between two acoustic twin traps. We shift a levitated bead between the traps, validating that full-array operational dynamicity is achievable with partial, localised actuation. This work showcases the synergy between active and passive reconfigurability, opening possibilities to develop multifunctional metamaterials with additional degrees of freedom in design and control.

Abstract With methane emissions from ruminant agriculture contributing 17% of total methane emissions worldwide, there is increasing urgency to develop strategies to reduce greenhouse gas emissions in this sector. One of the proposed strategies is ruminant feed intervention studies focused on the inclusion of anti-methanogenic compounds which are those capable of interacting with the rumen microbiome, reducing the capacity of ruminal microorganisms to produce methane. Recently, seaweeds have been investigated for their ability to reduce methane in ruminants in vitro and in vivo, with the greatest methane abatement reported when using the red seaweed Asparagopsis taxiformis (attributed to the bromoform content of this species). From the literature analysis in this study, levels of up to 99% reduction in ruminant methane emissions have been reported from inclusion of this seaweed in animal feed, although further in vivo and microbiome studies are required to confirm these results as other reports showed no effect on methane emission resulting from the inclusion of seaweed to basal feed. This review explores the current state of research aiming to integrate seaweeds as anti-methanogenic feed additives, as well as examining the specific bioactive compounds within seaweeds that are likely to be related to these effects. The effects of the inclusion of seaweeds on the ruminal microbiome are also reviewed, as well as the future challenges when considering the large-scale inclusion of seaweeds into ruminant diets as anti-methanogenic agents.

Abstract Microbial electrosynthesis (MES) presents a versatile approach for efficiently converting carbon dioxide (CO2) into valuable products. However, poor electron uptake by the microorganisms from the cathode severely limits the performance of MES. In this study, a graphitic carbon nitride (g-C3N4)-metal–organic framework (MOF) i.e. HKUST-1 composite was newly designed and synthesized as the cathode catalyst for MES operations. The physiochemical analysis such as X-ray diffraction, scanning electron microscopy (SEM), and X-ray fluorescence spectroscopy showed the successful synthesis of g-C3N4-HKUST-1, whereas electrochemical assessments revealed its enhanced kinetics for redox reactions. The g-C3N4-HKUST-1 composite displayed excellent biocompatibility to develop electroactive biohybrid catalyst for CO2 reduction. The MES with g-C3N4-HKUST-1 biohybrid demonstrated an excellent current uptake of 1.7 mA/cm2, which was noted higher as compared to the MES using g-C3N4 biohybrid (1.1 mA/cm2). Both the MESs could convert CO2 into acetic and isobutyric acid with a significantly higher yield of 0.46 g/L.d and 0.14 g/L.d respectively in MES with g-C3N4-HKUST-1 biohybrid and 0.27 g/L.d and 0.06 g/L.d, respectively in MES with g-C3N4 biohybrid. The findings of this study suggest that g-C3N4-HKUST-1 is a highly efficient catalytic material for biocathodes in MESs to significantly enhance the CO2 conversion.

Abstract A large body of evidence has shown a direct link between arsenic exposure and drug resistance to Leishmania parasites against antimonial preparations in visceral leishmaniasis (VL) hyper-endemic regions, especially in India and its sub-continent. However, the implicated roles of arsenic on the VL host, pathophysiological changes, and immune function have not yet been clarified, particularly at the reported concentration of arsenic in the VL hyper-endemic area of Bihar, India. Herein, we exposed the mouse VL model to arsenic (0.5 mg/L to 2 mg/L) through their drinking water and analyzed its effect on T cells proliferation, Th1/Th2-mediators, MAPK signaling cascade, and parasite load in preclinical models. Coherently, the parasite count in Giemsa stained spleen imprint has been investigated and found significant positive associations with levels of arsenic exposure. The liver and kidney function tests (AST, ALT, ALP, BUN, Creatinine, Urea, etc.) are apparent to hepatonephric toxicity in arsenic exposed VL mice compared to unexposed. This observation appears to be consistent with the up-regulated expression of immune regulatory Th2 mediators (IL-4, IL-10, TGF-β) and down-regulated expression of Th1 mediators (IL-12, IFN-γ, TNF-α) with a suppressed leishmanicidal function of macrophage (ROS, NO, iNOS). We also established that arsenic exposure modulated the host ERK-1/2 and p38 MAPK signaling cascade, limited T lymphocyte proliferation, and a lower IgG2a/IgG1 ratio to favor the Leishmania parasite survival inside the host. This study suggests that the contorted Th1-subtype and exacerbated Th2-subtype immune responses are involved in the increased susceptibility and pathogenesis of Leishmania parasite among subjects/individuals regularly exposed to arsenic.

The tumor microenvironment (TME) is crucial in cancer development and therapeutic response. Immunotherapy is increasingly recognized as a critical component of cancer treatment. While immunotherapies have shown efficacy in various cancers, including breast cancer, patient responses vary widely. Some patients receive significant benefits, while others experience minimal or no improvement. This disparity underscores the complexity and diversity of the immune system. In this study, we investigated the immune landscape and cell–cell communication within the TME of breast cancer through integrated analysis of bulk and single-cell RNA sequencing data. We established profiles of tumor immune infiltration that span across a broad spectrum of adaptive and innate immune cells. Our clustering analysis of immune infiltration identified three distinct patient groups: high T cell abundance, moderate infiltration, and low infiltration. Patients with low immune infiltration exhibited the poorest survival rates, while those in the moderate infiltration group showed better outcomes than those with high T cell abundance. Moreover, the high cell abundance group was associated with a greater tumor burden and higher rates of TP53 mutations, whereas the moderate infiltration group was characterized by a lower tumor burden and elevated PIK3CA mutations. Analysis of an independent single-cell RNA-seq breast cancer dataset confirmed the presence of similar infiltration patterns. Further investigation into ligand–receptor interactions within the TME unveiled significant variations in cell–cell communication patterns among these groups. Notably, we found that the signaling pathways SPP1 and EGF were exclusively active in the low immune infiltration group, suggesting their involvement in immune suppression. This work comprehensively characterizes the composition and dynamic interplay in the breast cancer TME. Our findings reveal associations between the extent of immune infiltration and clinical outcomes, providing valuable prognostic information for patient stratification. The unique mutations and signaling pathways associated with different patient groups offer insights into the mechanisms underlying diverse tumor immune infiltration and the formation of an immunosuppressive tumor microenvironment.

Abstract Background Iatrogenesis is an inevitable global threat to healthcare that drastically increases morbidity and mortality. Cancer is a fatal pathological condition that affects people of different ages, sexes, and races around the world. In addition to the detrimental cancer pathology, one of the most common contraindications and challenges observed in cancer patients is severe adverse drug effects and hypersensitivity reactions induced by chemotherapy. Chemotherapy‐induced cognitive neurotoxicity is clinically referred to as Chemotherapy‐induced cognitive impairment (CICI), chemobrain, or chemofog. In addition to CICI, chemotherapy also causes neuropsychiatric issues, mental disorders, hyperarousal states, and movement disorders. A synergistic chemotherapy regimen of Doxorubicin (Anthracycline‐DOX) and Cyclophosphamide (Alkylating Cytophosphane‐CPS) is indicated for the management of various cancers (breast cancer, lymphoma, and leukemia). Nevertheless, there are limited research studies on Doxorubicin and Cyclophosphamide's pharmacodynamic and toxicological effects on dopaminergic neuronal function. Aim This study evaluated the dopaminergic neurotoxic effects of Doxorubicin and Cyclophosphamide. Methods and Results Doxorubicin and Cyclophosphamide were incubated with dopaminergic (N27) neurons. Neuronal viability was assessed using an MTT assay. The effect of Doxorubicin and Cyclophosphamide on various prooxidants, antioxidants, mitochondrial Complex‐I & IV activities, and BAX expression were evaluated by Spectroscopic, Fluorometric, and RT‐PCR methods, respectively. Prism‐V software (La Jolla, CA, USA) was used for statistical analysis. Chemotherapeutics dose‐dependently inhibited the proliferation of the dopaminergic neurons. The dopaminergic neurotoxic mechanism of Doxorubicin and Cyclophosphamide was attributed to a significant increase in prooxidants, a decrease in antioxidants, and augmented apoptosis without affecting mitochondrial function. Conclusion This is one of the first reports that reveal Doxorubicin and Cyclophosphamide induce significant dopaminergic neurotoxicity. Thus, Chemotherapy‐induced adverse drug reaction issues substantially persist during and after treatment and sometimes never be completely resolved clinically. Consequently, failure to adopt adequate patient care measures for cancer patients treated with certain chemotherapeutics might substantially raise the incidence of numerous movement disorders.

Cell migration is fundamental to both development and adult physiology, including gastrulation, brain development, angiogenesis, wound healing, bone remodeling, tissue homeostasis, and the immune response. Additionally, misguided cellular migration is implicated in disease pathologies such as cancer metastasis and fibrosis. The microenvironment influences cell migration modes such as mesenchymal, amoeboid, lobopodial, and collective, and these are governed through local signaling by affecting the gene expression and epigenetic alteration of migration-related genes. Plasticity in switching between migration modes is essential for key cellular processes across various contexts. Understanding the mechanisms of cell migration modes and its plasticity is essential for unraveling the complexities of this process and revealing its implications in physiological and pathological contexts. This review focuses on different modes of cell migration, including their aberrant migration in disease pathologies and how they can be therapeutically targeted in disease conditions such as cancer.

Summary: Superhydrophobic surfaces face challenges in comprehensive durability when used in extreme outdoor environments. Here, we present a protocol for preparing nanocomposite bulks with hierarchical structures using the template technique. We describe steps for using hybrid nanoparticles of polytetrafluoroethylene and multi-walled carbon nanotube to fill inside and dip on the polyurethane (PU) foam. We then detail procedures for its removal by sintering treatment. The extra accretion layer on the PU foam surface was highlighted to construct hierarchical porous structures.For complete details on the use and execution of this protocol, please refer to Wu et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Pharmaceuticals, recognized for their life-saving potential, have emerged as a concerning class of micropollutants in the environment. Even at minute concentrations, chronic exposure poses a significant threat to ecosystems. Various pharmaceutically active micropollutants (PhAMP), including antibiotics, analgesics, and hormones, have been detected in underground waters, surface waters, seawater, sewage treatment plants, soils, and activated sludges due to the absence of standardized regulations on pharmaceutical discharge. Prolonged exposureof hospital waste and sewage treatment facilities is linked to the presence of antibiotic-resistant bacteria. Conventional water treatment methods prove ineffective, prompting the use of alternative techniques like photolysis, reverse osmosis, UV-degradation, bio-degradation, and nano-filtration. However, commercial implementation faces challenges such as incomplete removal, toxic sludge generation, high costs, and the need for skilled personnel. Research gaps include the need to comprehensively identify and understand various types of pharmaceutically active micropollutants, investigate their long-term ecological impact, develop more sensitive monitoring techniques, and explore integrated treatment approaches. Additionally, there is a gap in understanding the socio-economic implications of pharmaceutical pollution and the efficacy of public awareness campaigns. Future research should delve into alternative strategies like phagotherapy, vaccines, and natural substance substitutes to address the escalating threat of pharmaceutical pollution.

Among the various loose flower crops, marigold (Tagetes erecta L.) holds a prominent place among commercial crops. Its vibrant blooms are in high demand, but flowers are perishable, rendering them susceptible to significant post-harvest losses. Efforts to mitigate these losses will enhance the overall flower production, distribution to maximize its economic potential and to sustain valuable contribution for the industry. So, the present experiment on storage of marigold flowers was conducted during 2021 and 2022 at the ICAR- Indian Agricultural Research Institute, New Delhi with an objective to improve the shelf life of flowers by using different packaging materials. The results revealed that in marigold var. Pusa Basanti Gainda, maximum shelf life, high carotenoid content, minimum ion leakage, physiological loss in weight and enzyme activity were achieved in flowers packed in shrink-wrap and stored under low-temperature (6±20C) conditions.

IntroductionPeanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models.MethodsCompounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP.ResultsXPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) is a hybrid of the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets, and its association with renal outcomes remains unclear. In the REasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort, diet data were collected at baseline using food frequency questionnaires. Modified Poisson regression was used to examine the association of MIND diet with incident chronic kidney disease (CKD). In the REGARDS stroke case-cohort, 357 metabolites were measured in baseline plasma. Weighted linear regression was used to test associations between MIND diet and metabolites. Weighted logistic regression was used to test associations between MIND-associated metabolites and incident CKD. Mediation analyses were conducted to determine whether metabolites mediated the relationship between MIND diet and CKD. A higher MIND diet score was associated with a decreased risk of incident CKD (risk ratio 0.90, 95% CI (0.86–0.94); p = 2.03 × 10−7). Fifty-seven metabolites were associated with MIND diet (p < 3 × 10−4). Guanosine was found to mediate the relationship between MIND diet and incident CKD (odds ratio for indirect effects 0.93, 95% CI (0.88–0.97); p < 0.05). These findings suggest a role of the MIND diet in renal outcomes.

Utilization of fish rest raw material for fish oil extraction has received interest with the increasing demand for sustainable food sources. Enzymatic hydrolysis is an efficient method for the extraction of value-added compounds, but its effectiveness may be enhanced by high-pressure processing (HPP). However, HPP can induce lipid oxidation, affecting the quality of the oil. This study aimed to evaluate the quality of fish oil obtained after enzymatic hydrolysis of a mixture of rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) rest raw material pretreated by HPP. Six pretreatments were tested prior to enzymatic hydrolysis; 200 MPa × 4 min, 200 MPa × 8 min, 400 MPa × 4 min, 400 MPa × 8 min, 600 MPa × 4 min, and 600 MPa × 8 min. The oil samples were analyzed for lipid oxidation parameters, free fatty acid content, fatty acid composition, and color changes over 8 weeks. The results confirmed that HPP may induce lipid oxidation and revealed significant influence of HPP parameters on lipid oxidation, with higher pressures leading to increased oxidation. Fatty acid composition varied among samples, but it was not substantially affected by HPP.

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle’s proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.

Dedicated to Dr. Rama P. Tripathi, Former Chief Scientist at CSIR-Central Drug Research Institute, Lucknow, India, for his extraordinary contribution to “Drug development against Tuberculosis”