Search Results (616)

Apple (Malus domestica) is a deciduous perennial tree that belongs to the family “Rosaceae”. Due to the highly suitable agro-climatic conditions for apple cultivation, it is among the widely cultivated fruits in Gilgit-Baltistan (GB). This study aims to evaluate elite apple genotypes in GB based on morphological and biochemical traits. Five- to six-year-old plants were selected for this study. The research employed a completely randomized design (CRD) with three replications, and mean differences were analyzed using the LSD test. In this study, five genotypes were assessed based on morphological (fruit weight, fruit length, fruit width, and firmness) and biochemical attributes (TSS, TA, ascorbic acid, total phenolic content, and flavonoid content). The results revealed significant variation among apple cultivars in both phytochemical and fruit quality attributes. The cultivar ‘Red Delicious’ exhibited the highest fruit weight (146.18 g), total soluble solids (TSS) (15.4 °Brix), and flavonoid content (105.75 mg 100 g⁻¹ FW). In contrast, ‘Red Full Star’ demonstrated superior firmness (7.19 kg cm⁻²), along with the highest total phenolic content (TPC) (4.00 mg GAE g⁻¹ FW) and ascorbic acid content (26.45 mg 100 g⁻¹ FW). Although the indigenous variety ‘Nus Khushu’ exhibited lower values in commercial traits, it holds substantial potential for conservation due to its unique local adaptation. The findings indicate that the “Red Delicious” and “Red Full Star” cultivars cultivated in GB are enriched with a variety of bioactive compounds that offer notable health benefits and may be utilized for future crop enhancement and breeding initiatives. Full article

Objectives: Fibroblast growth factor 9 (FGF9), a crucial member of the FGF family, functions as an intercellular signaling molecule involved in angiogenesis, embryogenesis, and tissue repair. Our previous study demonstrated that FGF9 expression in chicken hierarchical granulosa cells (Post-GCs) is regulated by LSD1 Ser54 phosphorylation and that FGF9 promotes cell proliferation. This study aims to analyze the expression and regulation of the FGF9 gene in chicken ovarian follicles and its genetic effect on laying traits in hens. Methods: Chicken FGF9 mRNA expression patterns were examined by real-time quantitative PCR (RT-qPCR). Detection of single nucleotide polymorphisms (SNPs) was performed using PCR amplification and Sanger sequencing. Transcription activity was compared using dual-luciferase reporter assay. Results: Following follicle selection, chicken FGF9 expression significantly decreased in granulosa cells (p < 0.05) while it increased in theca cells (p < 0.05). Hormonal treatments revealed differential regulation; estradiol and FSH downregulated FGF9 in both pre-hierarchical and hierarchical granulosa cells (p < 0.05), whereas progesterone exhibited opposing effects, suppressing expression in pre-hierarchical granulosa cells (Pre-GCs) but stimulating its expression in Post-GCs (p < 0.05). In theca cells, estradiol consistently inhibited FGF9 expression (p < 0.05), while FSH only affected FGF9 expression in pre-hierarchical follicles. Six SNPs in the promoter region (g.−1965G>A, g.−2177G>A, g.−2289G>A, g.−3669A>G, g.−3770A>G, g.−3906G>A) were identified, five of which (g.−1965G>A, g.−2177G>A, g.−2289G>A, g.−3669A>G, g.−3906G>A) showed significant associations with egg production traits. Notably, alleles A (g.−2289), G (g.−3669), and A (g.−3906) enhanced the transcription activity of chicken FGF9 in Pre-GCs. Conclusions: These findings provide novel insights into the expression pattern and regulatory mechanisms of chicken FGF9 during follicular development and identify some genetic markers for egg-laying traits in chickens. Full article

Background/Objectives: Lumpy skin disease (LSD) is a notifiable disease due to a marked potency for rapid spread and a significant negative economic impact on agriculture worldwide. As such, vaccination is considered the most effective way to control the disease in endemic countries, and the serological response to homologous LSDV-based vaccines is widely investigated. However, less is known about the seroconversion and duration of the immune response that is elicited by live attenuated heterologous vaccines based on the Sheeppox virus (SPPV) used for LSD prevention. This study aimed to investigate the humoral immune response in cattle immunized with a heterologous SPPV-based vaccine in the field. Methods: Commercial ELISA, based on P32 protein, as well as immunoblotting, were used to assess the antibody response in 6-month-old, 17-month-old, and older animals before and after the first immunization and revaccination. Results: Only a secondary immune response was detected when using commercial ELISA in revaccinated animals in each of the groups (83.3% and 30%, respectively). A comparative bioinformatic analysis proved a marked polymorphism of P32, derived from LSDV/SPPV/GTPV, which potentially resulted in negative responses in the ELISA. However, immunoblotting revealed a 100% seroconversion in vaccinated animals after the first vaccination and revaccination. Notably, specific antibodies were found in the sera of 80% of 6-month-old calves before the first vaccination, which had probably been passively transferred from their mothers, who were multiply vaccinated with SPPV-based vaccines. Conclusions: Several immunodominant antigens were able to induce a humoral immune response in cattle to the SPPV-based vaccine after passive and active immunization, serving as promising markers for a humoral immune response to heterologous vaccines. Full article

Lysosomal storage disorders (LSDs) represent a diverse group of inherited metabolic diseases in which impaired lysosomal function leads to progressive accumulation of undegraded substrates and widespread cellular dysfunction. Although traditionally classified according to the type of stored macromolecule, this substrate-based approach often fails to reflect the underlying molecular mechanisms. Recent advances in genetics and cell biology have prompted a shift toward functional classifications that group disorders by the lysosomal pathway disrupted—namely, enzymatic hydrolytic defects, transporter-related defects, biogenesis and signaling defects, and cross-organelle interaction abnormalities. This framework better captures disease complexity and provides a translational roadmap for precision medicine. The neurological system, with its high metabolic demands and vulnerability to impaired clearance mechanisms, is particularly affected, leading to clinical phenotypes ranging from developmental delay to severe neurodegeneration. Genomic technologies and multi-omics platforms have facilitated earlier diagnoses, revealed atypical variants, and informed the development of tailored therapies such as enzyme replacement, substrate reduction, chaperone-based approaches, and gene therapy. The current review proposes a cellular-pathway-oriented framework for classifying LSDs with neurological features and underscores how such an approach can assist in the development of personalized therapeutic strategies. Full article

Background/Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established therapy for a range of hereditary disorders, including hemoglobinopathies, primary immunodeficiencies, and lysosomal storage diseases. Despite its long-standing use, rapid developments in donor availability, conditioning strategies, and supportive care have significantly broadened and refined its clinical application. This review combines recent evidence to clarify how these advances redefine current indications and therapeutic expectations. Methods: We critically analyze contemporary clinical data with a focus on elements that have undergone meaningful evolution—donor selection algorithms, conditioning intensity, graft manipulation, and post-transplant management. Comparative outcomes across major hereditary disease groups were examined to identify emerging trends in efficacy and safety. Results: The analysis highlights several novel shifts: expanding eligibility due to improved donor options, increasing reliance on reduced-toxicity regimens, and enhanced understanding of the mechanistic basis for hematologic, immunologic, and metabolic correction. These developments collectively improve survival and functional outcomes across diverse hereditary disorders. Conclusions: allo-HSCT remains a key therapeutic strategy for selected hereditary diseases, offering durable hematologic and metabolic correction. The prospective development of gene-addition and genome-editing therapies creates opportunities to complement—or in some cases replace—allo-HSCT, supporting the emergence of more personalized treatment approaches. Full article

Livestock is the backbone of the economy in an agricultural country like Pakistan, with cattle serving as a milk and protein source. In 2021/22, Pakistan was hit by the first major outbreak of lumpy skin disease (LSD) in cattle, in all four provinces. LSD is characterized by the development of skin nodules, leading to severe illness, decreased milk production, and mortality, causing huge economic losses. This study aimed to analyze and classify the lumpy skin disease virus (LSDV) strains involved in the outbreak in the Punjab province at the molecular and phylogenetic levels to develop effective control strategies. A combination of different real-time PCRs was used for the identification and differentiation between vaccine, wild-type, and recombinant LSDV strains. This was mented with the sequence determination and phylogenetic analysis of ten genomic loci from two selected isolates from the 2021/22 Pakistan outbreak. The combined data showed that these isolates belonged to LSDV clade 1.2 and were clearly different from the vaccine clade 1.1 (Neethling-like), as well as from the recombinant clade 2 strains. In addition, using a fit-for-purpose gel-based PCR, the isolates from the outbreak were also shown to be different from KSGP0240-based vaccines. Full article

Lumpy Skin Disease (LSD) is a transboundary viral disease of wild and domesticated ruminants, and notifiable to the World Organisation for Animal Health (WOAH). LSD has spread rapidly in the cattle population across the African, European and Asian continents since 1929. Following recent outbreaks in the Southeast Asia region, Singapore observed its first occurrence of LSD in a local dairy cattle farm in March 2022. LSD was confirmed in dairy cattle exhibiting clinical signs with quantitative real-time PCR and sequencing with MinION Nanopore. Analyses of the assembled whole viral genomes also revealed high phylogenetic relatedness to LSD recombinant strains. It remains unclear how the virus was introduced into Singapore, given the absence of known vectors and strict import regulations in place. This highlights the importance of biosurveillance, and laboratory diagnostic readiness to manage outbreaks and prevent the spread of transboundary diseases. Full article

The employment of linear features to enhance the positioning precision and robustness of point-based VIO (visual-inertial odometry) has attracted mounting attention, especially for UAV (unmanned aerial vehicle) applications where reliable 6-DoF pose estimation is critical for autonomous navigation, mission execution, and safety. This paper presents GPLVINS—GNSS (global navigation satellite system)-point-line-visual-inertial navigation system—a UAV-tailored enhancement of the nonlinear optimization-based GVINS (GNSS-visual-inertial navigation system). Unlike GVINS, which struggles with feature extraction in weak-texture environments and depends entirely on point features, GPLVINS innovatively integrates line features into its state optimization framework to enhance robustness and accuracy. While existing studies adopt the LSD (line segment detector) algorithm for line feature extraction, this approach often generates numerous short line segments in real-world scenes. Such an outcome not only increases computational costs but also degrades pose estimation performance. In order to address this issue, the present study proposes an NMS (non-maximum suppression) strategy for the refinement of LSD. The line reprojection residual is then formulated as the distance between point and line, which is incorporated into the nonlinear optimization process. Experimental validations on open-source datasets and self-collected UAV datasets across indoor, outdoor, and indoor–outdoor transition scenarios demonstrate that GPLVINS exhibits superior positioning performance and enhanced robustness for UAVs in environments with feature degradation or drastic lighting intensity variations. Full article

Serotonergic psychedelics, particularly psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), are increasingly recognised as powerful tools to advance the understanding of consciousness and its relation to brain activity. Psychedelic research has informed neuroscientific theories that attempt to map neural observations of network connectivity and signal diversity to phenomenological qualities like psychological flexibility. Thus far, however, there have been relatively limited efforts to bridge the gap between psychedelic-informed theory and the experiential differences observed in neurodevelopmental conditions such as autism. In this narrative review and conceptual synthesis, we compare the psychedelic state and autism in adults from a neurophenomenological perspective. Predictive processing is invoked as a unifying framework. This procedure highlights both phenomena as involving a shift towards sensory information relative to prior knowledge, but potentially implicating alterations at opposite ends of the cortical hierarchy. This contrastive approach also reveals opportunities for refining concepts—including psychological flexibility—as well as interpretations of results across fields. However, neurobiological findings, especially in autism, are heterogeneous and there are inherent restrictions in comparing transient state and lifelong trait phenomena. Conclusions of this comparison are primarily conceptual and offer testable hypotheses for the neurophenomenology of the psychedelic state, autism, and their interaction. Full article

Objective: Evaluating the in vitro marginal adaptation of conventional, flowable and restorative bulk-fill resin composites placed in large class II cavities with supra- and sub-gingival margins, using a bulk-fill or layering approach, before and after thermo-mechanical loading (TML) simulating parafunctional forces. A total of 40 prepared teeth were divided and assigned to each of the five experimental groups. In group 1, restorations were made of layered high-viscosity conventional composite (Tetric EvoCeram); in groups 2 and 3 restorations were made of a high-viscosity bulk-fill composite (Tetric Powerfill) applied in one (group 2) or three layers (group 3); in groups 4 and 5 restorations were made of a flowable bulk-fill composite (SDRflow) applied in one (group 4) or two layers (group 5), underneath a layer of high-viscosity composite (Ceram-X Spectra ST). The same adhesive (OptiBond FL) was used in all groups. All specimens were submitted to a TML comprising a loading phase of 250,000 cycles at 100 N combined to 1675 thermal cycles (5 to 55 °C). The proximal tooth-restoration interfaces were analyzed quantitatively by SEM, prior and after TML. Results: Repeated measures ANOVA followed by Fisher’s LSD (Least Significant Difference) post hoc tests served for comparing inter-group marginal adaptation percentages between the pre- (T0) and post- (T1) loading conditions and intra-group marginal adaptation percentages. The lowest pre-loading values were for the cervical dentin adaptation ranging from 94.79% (SDRflow layered) to 66.06% (Tetric Powerfill layered) while the post-loading values of continuous cervical dentin adaptation varied from 61.20% (SDRflow layered) to 33.36% (SDRflow Monolayer). TML with higher axial forces led to a marked reduction in continuous adaptation at enamel or dentin margins in all groups. Overall, the low-viscosity bulk-fill SDRflow layers showed the best behavior while other products showed varying levels of degradation. Conclusions–Clinical significance: Simulated bruxism loading conditions induced severe marginal adaptions of class II composite restorations, which could potentially impact their lifespan. Full article

Background: The E26 transformation-specific (ETS) transcription factor Friend Leukemia Integration 1 (FLI1) has been linked to breast cancer aggressiveness, stromal remodeling, and immune modulation, yet the regulatory mechanisms governing its activity remain poorly defined. Of note, various studies have shown that EWS-FLI1-mediated transcription programs are facilitated via direct recruitment and binding of the NuRD-LSD1 complex, regulating its associated gene targets. Furthermore, LSD1 inhibition exhibited reverse transcriptional profiles driven by ETS-FLI and reduced in vivo tumorigenesis in cancers. Methods: We evaluated FLI1 expression across multiple invasive breast carcinoma (IBC) cohorts to determine its prognostic significance and associations with stromal features. In parallel, we investigated FLI1 regulation in humanized breast cancer mouse models treated with an LSD1 inhibitor. Results: High FLI1 expression was associated with advanced histological grade in IBC, consistent with an oncogenic function. FLI1-high tumors also exhibited elevated stromal and immune scores, indicating a role in remodeling the tumor microenvironment. Additionally, LSD1 inhibition downregulated FLI1 target genes involving angiogenesis and invasion. Conclusions: These findings highlight the dual role of FLI1: tumor-intrinsic FLI1 promotes proliferation and invasion, whereas its transcriptional regulation in tumor and endothelial compartments likely reflects LSD1 dependence. Collectively, our results support a mechanistic model in which LSD1–FLI1 crosstalk is involved in immune and stromal remodeling, positioning FLI1 as both a marker of tumor aggressiveness and a potential predictor of response to epigenetic therapies in breast cancer. Full article

The global sparkling wine market continues to grow steadily, reaching approximately 24 million hectoliters in 2023, with an annual increase of around 4% despite a general decline in overall alcoholic beverage consumption. This growth highlights the importance of employing diverse yeast strains to improve product variety and quality. Flor yeasts are specialized strains of Saccharomyces cerevisiae that develop a biofilm on the surface of certain wines during biological ageing. They possess unique physiological properties, including high ethanol tolerance and the capacity to adhere, which supports wine clarification. They also have the ability to contribute unique volatile compounds and aroma profiles, making them promising candidates for sparkling wine production. This study evaluated two flor yeast strains (G1 and N62), which were isolated from the Pérez Barquero winery during the second fermentation process using the traditional method. Sparkling wines were produced by inoculating base wine (BW) with each strain, and the wines were monitored at 3 bar CO₂ pressure and after 9 months of ageing on lees. Comprehensive metabolomic analysis was performed using GC-MS for volatile compounds and HPLC for nitrogen compounds, with statistical analysis including PCA, ANOVA, Fisher’s LSD, and correction FDR tests. Strain N62 demonstrated faster fermentation kinetics and higher cellular concentration, reaching 3 bar pressure in 27 days compared to 52 days for strain G1. Both strains achieved similar final pressures, 5.1–5.4 bars. Metabolomic profiling revealed significant differences in the profiles of volatile and nitrogen compounds between the two strains. G1 produced higher concentrations of 3-methyl-1-butanol, 2-methyl-1-butanol, and acetaldehyde, while N62 generated elevated levels of glycerol, ethyl esters, and amino acids, including glutamic acid, aspartic acid, and alanine. These findings demonstrate that both flor yeast strains successfully complete sparkling wine fermentation while producing distinct metabolic signatures that could contribute to unique sensory characteristics. This supports their potential as alternatives to conventional sparkling wine yeasts for enhanced product diversification. Full article

Background: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by impaired differentiation, apoptosis resistance, and metabolic reprogramming, which collectively contribute to therapeutic resistance and poor clinical outcomes. While targeted agents—such as LSD1 inhibitors, the BCL-2 inhibitor venetoclax, and IDH1 inhibitors—have provided clinical benefit, their efficacy is often limited by compensatory signaling and clonal evolution. This study aimed to identify FDA-approved compounds with multitarget potential to simultaneously modulate key epigenetic, apoptotic, and metabolic pathways in AML. Methods: Structure-based virtual screening of 3957 FDA-approved molecules was performed against three AML-relevant targets: lysine-specific demethylase 1 (LSD1), BCL-2, and mutant IDH1 (R132H). Top-ranked hits were evaluated using ADMET prediction and molecular dynamics (MD) simulations to assess pharmacokinetic properties, toxicity, and ligand–protein complex stability over 100 ns trajectories. Results: Three compounds—DB16703, DB08512, and DB16047—exhibited high binding affinities across all three targets with favorable pharmacokinetic and safety profiles. MD simulations confirmed the structural stability of the ligand–protein complexes, revealing persistent hydrogen bonding and minimal conformational deviation. These findings suggest that these repurposed drugs possess a promising multitarget profile capable of addressing AML’s multifactorial pathophysiology. Conclusions: This computational study supports the feasibility of a polypharmacology-based strategy for AML therapy by integrating epigenetic modulation, apoptotic reactivation, and metabolic correction within single molecular scaffolds. However, the identified compounds (Belumosudil, DB08512, and Elraglusib) have not yet demonstrated efficacy in AML models; further preclinical validation is warranted to substantiate these predictions and advance translational development. Full article

Objectives: This study investigates psychedelic drugs to treat substance use disorder (SUD). Researchers have recently begun conducting clinical trials of psychedelic treatment for SUD. The current meta-analysis investigates the extent of efficacy in alleviating SM behaviours (P) using psychedelic therapy (I), concurrent with determining which psychedelic enables the greatest effect (C) as a treatment tool for reducing SUD (O). Methods: The inclusion criteria in this study include evaluating the efficacy of LSD, psilocybin, ketamine, or ibogaine in human beings with an SUD. The exclusion criteria include studies on rodents, patients with schizophrenia, case studies, incomplete or ongoing trials, and studies with insufficient quantitative data. The search criteria obtained 1278 articles, acquired through PubMed and PsycINFO. After excluding literature, 30 papers were kept in the final meta-analysis. A random-effects model analysis was applied to investigate individual psychedelic interventions, with a corresponding combined psychedelic intervention analysis. Results: The results favoured psychedelics as an SM treatment, with ibogaine evidencing the most prominent. We also found a non-significant difference between the effectiveness of psychedelic treatment paired with psychotherapy and psychedelic treatment alone. This study aims to contribute knowledge to future clinical research on the psychedelic treatment of SUD. Full article

Cellular components and inflammatory mediators involved in the transmigration of HTLV-1-infected cells across the blood–brain barrier (BBB) are not fully understood. This study proposes a BBB model to identify the immunological mechanisms associated with HTLV-1 pathogenesis. PBMCs from individuals with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (n = 4) or HTLV-1-infected individuals without HAM/TSP (n = 4) were isolated. An indirect cell co-culture was performed between human brain microvascular endothelial (hBMEC) cells and neuroblastoma (SH-SY5Y) cells. PBMCs from healthy individuals (n = 4) were used as a negative control, and MT-2 cells were used as a positive control. Supernatants and cells were collected to quantify inflammatory cytokines and assess cell death after 24, 48, and 72 h. Multiple comparisons were performed using the Kruskal–Wallis test, followed by Fisher’s LSD post hoc analysis. We observed that the production of cytokines IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, as well as the rate of neuronal death, was higher in co-cultures mimicking HAM/TSP carriers compared to HTLV-1-infected individuals without HAM/TSP and controls. Our results suggest that the HAM/TSP condition induces the release of IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, along with the infiltration of mononuclear cells, which may lead to neuronal death. Full article