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Abstract Linseed, also known as flax is an important oilseed crop with many potential uses in paint, textile, food and pharmaceutical industries. Susceptibility to bud fly (Dasyneura lini Barnes) infestation is a serious biotic concern leading to severe yield penalty in linseed. Protease inhibitors (PIs) are potential candidates that activate during the insect-pest attack and modulate the resistance. In the present study, we explored the PI candidates in the linseed genome and a total of 100 LuPI genes were identified and grouped into five distinct subgroups. The analysis of cis-acting elements revealed that almost all LuPI promoters contain several regulatory elementary related to growth and development, hormonal regulation and stress responses. Across the subfamilies of PIs, the specific domains are consistently found conserved in all protein sequences. The tissue-specific in-silico expression pattern via RNA-seq revealed that all the genes were regulated during different stress. The expression through qRT-PCR of 15 genes revealed the significant up-regulation of LuPI-24, LuPI-40, LuPI-49, LuPI-53, and LuPI-63 upon bud fly infestation in resistant genotype EC0099001 and resistant check variety Neela. This study establishes a foundation resource for comprehending the structural, functional, and evolutionary dimensions of protease inhibitors in linseed.

Species within the primitive genus Magnolia may often produce specialized floral traits and behaviour to grab the attention of potential pollinators from their surroundings. These reproductive traits in plants undergo various selection pressures and frequently bring forth variations to adapt to the new habitat that may result in speciation. We have aimed to understand the floral traits, the functional role of floral parts, and the variable response of visitors in Magnolia grandiflora belonging to an ancient order Magnoliales. Our observations reveal that the floral traits of M. grandiflora resemble those of basal angiosperms, conforming to the primitive existence of the genus Magnolia. The inconsistency in floral form reflected that M. grandiflora has been experiencing various selection pressures from biotic and abiotic factors. Inconsistency in floral equations and diagrams reflect the structural variability in flowers, which can directly impact pollination and reproductive output. SEM images of pollen grains reveal that the pollen grains were monocolpate and boat-shaped in structure. GC-MS analysis showed that VOCs in stigmatic exudation of the flower were largely composed of terpene hydrocarbons such as Perthenine, β-Elemene, β-Caryophyllene, α-Humulene, Bicyclogermacrene, Germacrene A and D, etc. Beyond pollinators attraction, VOCs play a major role in repelling unwanted visitors and in improving the defensive mechanisms in Magnolia. Beetles, bees, and flies were found to be the active pollinators and the behaviour of bees indicates that bees were trying to replace the role of beetles in pollinating M. grandiflora. In summary, floral whorls were diversely functionalized to ensure maximum reproduction in M. grandiflora.

Abstract Purpose The aim of this study is to evaluate the outcomes of retrograde intra renal surgery (RIRS) in the setting of large or multiple stones in children (15 mm, or both. Outcomes included stone free rate (SFR) and complications within 30 days. Results In total, 344 patients were included with 197 and 147 in Groups 1 and 2, respectively. Ureteric access sheaths were more frequently used in Group 2 (39.5% vs. 56.8%, p = 0.021). The operation time was significantly longer in Group 2 (p

Globally, excess deaths during 2020-21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 deaths from other changes in mortality related to pandemic control measures using medically-certified death registrations from Madurai, India-an urban center with well-functioning vital surveillance. Between March, 2020 and July, 2021, all-cause deaths in Madurai exceeded expected levels by 30% (95% confidence interval: 27-33%). Although driven by deaths attributed to cardiovascular or cerebrovascular conditions, diabetes, senility, and other uncategorized causes, increases in these attributions were restricted to medically-unsupervised deaths, and aligned with surges in confirmed or attributed COVID-19 mortality, likely reflecting mortality among unconfirmed COVID-19 cases. Implementation of lockdown measures was associated with a 7% (0-13%) reduction in all-cause mortality, driven by reductions in deaths attributed to injuries, infectious diseases and maternal conditions, and cirrhosis and other liver conditions, respectively, but offset by a doubling in cancer deaths. Our findings help to account for gaps between documented COVID-19 mortality and excess all-cause mortality during the pandemic in an LMIC setting.

Objective Neonatal jaundice is the most common cause of neonatal morbidity and rehospitalisation in the first week of life, affecting approximately 60% of term and 80% of preterm neonates, with 10% requiring phototherapy to prevent bilirubin-induced neurological dysfunction. Enterohepatic circulation contributes 10%–20% of the body’s bilirubin load, and oral calcium-phosphate can inhibit this process by binding to unconjugated bilirubin and acting as a bilirubin-trapping agent in the gut. This study aimed to evaluate the efficacy of oral calcium phosphate as an adjunct to phototherapy in reducing phototherapy duration, improving bilirubin decline rate and lowering rebound hyperbilirubinaemia incidence.Methods This double-blind, placebo-controlled randomised controlled trial with a 1:1 allocation ratio was conducted in the neonatal intensive care unit of a tertiary care hospital in Eastern India. The investigator and the analyst were blinded to the treatment assignments. Eligible neonates with neonatal jaundice requiring phototherapy as per the ‘American Academy of Pediatrics or ‘National Institute for Health and Care Excellence’ guidelines were enrolled and randomly assigned to receive either oral calcium phosphate or placebo.Results The total duration of phototherapy was significantly lower in the intervention group compared with placebo (18.8±5.63 hours vs 24.3±4.50 hours; mean difference=−5.55 (95% CI −7.82 to −3.28), p

Tomato is a widely cultivated crop significant for its economic and nutritional benefits. The South American tomato pinworm, Tuta absoluta, originated in Peru South America and has invaded many nations, causing up to 100% yield loss in tomatoes. The pest was classified as a quarantine pest by the European Plant Protection Organization, before invading the Spain region. Later, this quarantine pest also invaded other regions of Europe, Africa and Asian countries. Invasive insect pests cause global economic losses of 70 billion dollars annually. Among the several management measures suggested against pests, insecticides are the primary method in practice among growers due to significant results, easier operations, and other crucial advantages. Anyhow, repeated application of insecticides has caused the pest to evolve resistance against most of the insecticides in vogue, resulting in a chain of events like management failures, using increased doses of insecticides, intensified chemical residues in the food chain, and irreparable environmental contamination. Major insecticides globally used to control T. absoluta belong to organophosphates, synthetic pyrethroids, neonicotinoids, diamides, avermectins, spinosyns, and oxadizines. Understanding the baseline susceptibility of pests to insecticides helps for better pest management options and is the same for T. absoluta populations to insecticides. The current review paper discusses the T. absoluta distribution, biology, spread, host range, baseline insecticide susceptibility, global insecticide resistance status, and possible management inputs based on our understanding of insecticide susceptibility. The pest can be managed with integrated insecticide resistance management including molecular approaches.

Abstract Background Neuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE’s pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can also activate neurotoxic glial cells the brain. A prior pre-clinical study demonstrated that IL-6 can acutely induce a loss of sucrose preference; the present study sought to assess the necessity of chronic IL-6 exposure in the NPSLE-like disease of MRL/lpr lupus mice. Methods We quantified 1308 proteins in individual serum or pooled CSF samples from MRL/lpr and control MRL/mpj mice using protein microarrays. Serum IL-6 levels were plotted against characteristic NPSLE neurobehavioral deficits. Next, IL-6 knockout MRL/lpr (IL-6 KO; n = 15) and IL-6 wildtype MRL/lpr mice (IL-6 WT; n = 15) underwent behavioral testing, focusing on murine correlates of learning and memory deficits, depression, and anxiety. Using qPCR, we quantified the expression of inflammatory genes in the cortex and hippocampus of MRL/lpr IL-6 KO and WT mice. Immunofluorescent staining was performed to quantify numbers of microglia (Iba1 +) and astrocytes (GFAP +) in multiple cortical regions, the hippocampus, and the amygdala. Results MRL/lpr CSF analyses revealed increases in IL-17, MCP-1, TNF-α, and IL-6 (a priori p-value

Interfacial solar steam generation is considered as economical and more effective implementation of Solar steam generation (SSG) where solar energy is concentrated at the liquid surface via the utilization of heat localization materials (HLM). Herein we report the fabrication of an HLM constituted of a nanocomposite absorber of graphitic carbon nitride (g-C3N4) and covellite copper sulfide (CuS) supported on a mixed cellulose ester membrane, with a substrate of air laid paper-wrapped polystyrene foam. This structure allowed for strong broad-spectrum absorbance, increased hydrophilic character and minimal thermal losses. The HLM system absorbed 98% of the material and had an evaporation rate of 2.58 kgs per square meter per hour. This is twice the evaporation rate of water tested under the same conditions. Moreover, as fabricated HLM was also incorporated in a solar still in order to assess its practical performance in solar distillation. Initial studies proved that HLM modified solar still was more effective than conventional solar stills.

Zileuton is a leukotriene inhibitor used to treat asthma. As a BCS class II drug it exhibits challenges with solubility which likely impact its absorption. As patient gender significantly impacts the pharmacokinetics of many drugs, this study aimed to investigate potential gender-based pharmacokinetic differences after oral zileuton administration in rats. Male and female Sprague Dawley rats received single oral gavage doses of pure zileuton as an active pharmaceutical ingredient (30 mg/kg body weight (bw)), physical mixture (PM; at 30 mg/kg bw of the formulation contains zileuton, kollidon VA64 fine, dowfax2A1 and trehalose), and nanocrystalline formulation of zileuton (NfZ; at 30 mg/kg bw of the formulation). Plasma, tissue, and urine concentrations were quantified using high performance liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis showed higher zileuton levels in the plasma of female versus male rats across all evaluated forms of zileuton (API, PM, and NfZ). Female rats demonstrated higher peak plasma concentrations (Cmax) and increased area under the plasma concentration-time curve (AUC) relative to males, regardless of formulation. These findings reveal substantial gender disparities in the pharmacokinetics of zileuton in the rat model. This study emphasizes the critical need to evaluate gender differences during preclinical drug development to enable gender-based precision dosing strategies for equivalent efficacy/safety outcomes in male and female patients. Additional studies are warranted to investigate underlying mechanisms of such pharmacokinetic gender divergences.

Objective Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder with no reliable serum biomarkers currently available other than autoantibodies.Methods In the present study, isobaric tags for relative and absolute quantitation-based mass spectrometry was used to screen the sera of patients with SLE to uncover potential disease biomarkers.Results 85 common proteins were identified, with 16 being elevated (≥1.3) and 23 being decreased (≤0.7) in SLE. Of the 16 elevated proteins, serum alpha-1-microglobulin/bikunin precursor (AMBP), zinc alpha-2 glycoprotein (AZGP) and retinol-binding protein 4 (RBP4) were validated in independent cross-sectional cohorts (Cohort I, N=52; Cohort II, N=117) using an orthogonal platform, ELISA. Serum AMBP, AZGP and RBP4 were validated to be significantly elevated in both patients with inactive SLE and patients with active SLE compared with healthy controls (HCs) (p2.5) in Cohort I. All three proteins exhibited good discriminatory power for distinguishing active SLE and inactive SLE (area under the curve=0.82–0.96), from HCs. Serum AMBP exhibited the largest fold change in active SLE (5.96) compared with HCs and correlated with renal disease activity. The elevation in serum AMBP was validated in a second cohort of patients with SLE of different ethnic origins, correlating with serum creatinine (r=0.60, p

A woman with recent personalized external aortic root support implant presented in cardiogenic shock with bilateral coronary ostial occlusion and aortic inflammation requiring emergency coronary angioplasty. Subsequent computed tomography with positron emission tomography scanning demonstrated aortitis with extensive inflammation adjacent to the personalized external aortic root support mesh, the first report of this important complication.

Finger millet (Eleusine coracana L.), ragi or mandua, is one of essential minor millets extensively grown in the Indian and African subcontinents. It is a staple food in India, particularly for people belonging to low-socioeconomic groups. Finger millet is highly valued for its content of macro- and micronutrients. It is rich in carbohydrates, protein, and fat. Its micronutrients include calcium (0.38%), dietary fiber (18%), and phenolic compounds (0.3–3%), such as catechin, epicatechin, as well as ferulic, salicylic, protocatechuic, cinnamic, and hydroxybenzoic acids, etc. Finger millet is also recognized as a source of vital amino acids, including isoleucine, leucine, methionine, and phenylalanine, which are otherwise deficient in starchy meals. In addition, finger millet is well appreciated for its pharmacological properties such as anti-diabetic, anti-tumorigenic, anti-atherosclerogenic, antioxidant, and antimicrobial effects. To improve its nutritional and sensory properties, this grain can be processed by various traditional and advanced methods (soaking, malting, cooking, fermentation, popping, and radiation). These processing techniques equally assist in the reduction of anti-nutritional factors (tannins, phytic acid, oxalic acid, protein inhibitors, glucans) and their inhibitory effects. In this review, we highlighted the nutritional composition, health attributes, and uses of finger millet for the development of functional food products. Researchers and producers can further explore the opportunities and scope for utilizing finger millet and develop more products in the same line to solve the current issues of food and nutrition security.

Abstract Background The molecular content of urine is defined by filtration in the kidneys and by local release from tissues lining the urinary tract. Pathological processes and different therapies change the molecular composition of urine and a variety of markers have been analyzed in patients with bladder cancer. The response to BCG immunotherapy and chemotherapy has been extensively studied and elevated urine concentrations of IL‐1RA, IFN‐α, IFN‐γ TNF‐α, and IL‐17 have been associated with improved outcome. Methods In this study, the host response to intravesical alpha 1‐oleate treatment was characterized in patients with non‐muscle invasive bladder cancer by proteomic and transcriptomic analysis. Results Proteomic profiling detected a significant increase in multiple cytokines in the treatment group compared to placebo. The innate immune response was strongly activated, including IL‐1RA and pro‐inflammatory cytokines in the IL‐1 family (IL‐1α, IL‐1β, IL‐33), chemokines (MIP‐1α, IL‐8), and interferons (IFN‐α2, IFN‐γ). Adaptive immune mediators included IL‐12, Granzyme B, CD40, PD‐L1, and IL‐17D, suggesting broad effects of alpha 1‐oleate treatment on the tumor tissues. Conclusions The cytokine response profile in alpha 1‐oleate treated patients was similar to that reported in BCG treated patients, suggesting a significant overlap. A reduction in protein levels at the end of treatment coincided with inhibition of cancer‐related gene expression in tissue biopsies, consistent with a positive treatment effect. Thus, in addition to killing tumor cells and inducing cell detachment, alpha 1‐oleate is shown to activate a broad immune response with a protective potential.

Abstract Introduction Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children. Methods This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics. Results This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p

IntroductionSystemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). The complexity and heterogeneity of clinical presentations of NPSLE impede direct investigation of disease etiology in patients. The limitations of existing mouse models developed for NPSLE obstruct a comprehensive understanding of this disease. Hence, the identification of a robust mouse model of NPSLE is desirable.MethodsC57BL/6 mice transgenic for human MeCP2 (B6.Mecp2Tg1) were phenotyped, including autoantibody profiling through antigen array, analysis of cellularity and activation of splenic immune cells through flow cytometry, and measurement of proteinuria. Behavioral tests were conducted to explore their neuropsychiatric functions. Immunofluorescence analyses were used to reveal altered neurogenesis and brain inflammation. Various signaling molecules implicated in lupus pathogenesis were examined using western blotting.ResultsB6.Mecp2Tg1 exhibits elevated proteinuria and an overall increase in autoantibodies, particularly in female B6.Mecp2Tg1 mice. An increase in CD3+CD4+ T cells in the transgenic mice was observed, along with activated germinal center cells and activated CD11b+F4/80+ macrophages. Moreover, the transgenic mice displayed reduced locomotor activity, heightened anxiety and depression, and impaired short-term memory. Immunofluorescence analysis revealed IgG deposition and immune cell infiltration in the kidneys and brains of transgenic mice, as well as altered neurogenesis, activated microglia, and compromised blood-brain barrier (BBB). Additionally, protein levels of various key signaling molecules were found to be differentially modulated upon MeCP2 overexpression, including GFAP, BDNF, Albumin, NCoR1, mTOR, and NLRP3.DiscussionCollectively, this work demonstrates that B6.Mecp2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting its utility as a new animal model for NPSLE.