Search Results (6,055)

Dengue fever remains a significant public health concern in tropical regions, including Central India, where outbreaks are frequent and associated with high morbidity and mortality. This study investigated the dynamics of dengue virus transmission and evolution in Central India from 2019 to 2023, focusing on the emergence of new strains and their impact on outbreak patterns. For this, 40 mosquito pools and 300 patient samples were recruited for the study. Phylogenetic and Bayesian evolutionary analyses performed on CPrM region and whole genome sequences generated by Sanger and Illumina sequencing, respectively, revealed the emergence and predominance of a novel DENV-2 genotype IV lineage III strain in the 2019 and 2023 outbreaks, which displaced the previously circulating DENV-1 genotype responsible for the 2016–2017 outbreak. Despite pre-existing DENV-1 neutralizing antibodies in the community (67 healthy volunteers), the novel DENV-2 strain exhibited higher viral loads and a greater reproduction number (R0), contributing to rapid disease spread. Molecular clock and Shannon entropy analyses suggest that DENV evolution occurred within the mosquito vector, driven by natural selection. Our findings highlight the importance of continuous DENV surveillance, including genetic characterization in both vectors and hosts, to understand viral evolution and predict future outbreaks. Rapid urbanization and inadequate sanitation in densely populated regions like India create ideal breeding grounds for mosquitoes, facilitating the introduction and establishment of novel DENV strains. Interrupting the vector–DENV–host cycle through targeted interventions is crucial for effective dengue control. Full article

The diversity of anaerobic ciliates is greatly underestimated owing to the limitation in sampling and cultivation when compared with their aerobic counterparts. In this study, four anaerobic ciliates, viz. Brachonella abnormalis sp. nov., Brachonella contorta (Levander, 1894) Jankowski, 1964, Metopus contortus (Quennerstedt, 1867) Kahl, 1932, and Metopus major Kahl, 1932, were investigated by live observation, protargol staining and 18S rRNA gene sequencing. B. abnormalis sp. nov. can be separated from its congeners by a combination of the following features: bullet-shaped cell with a life size of about 130–190 × 90–120 μm, dikinetids distributed along dorsal dome kineties, highly developed adoral zone comprised of 87–107 polykinetids, making about 450° spiralization around the long axis. The present work demonstrates that two known species, M. contortus and M. major, have a special trait never previously reported, viz. short, regularly arranged preoral dome dikinetids. Species with short, regularly arranged dome dikinetids appear in divergent clades in SSU rRNA gene trees, which may infer that this trait evolved several times. Phylogenetic analyses based on SSU rRNA gene sequence data also support the monophyly of the genus Brachonella and the paraphyly of the order Metopida, respectively. Full article

Chronic pain and mental health disorders, such as depression and anxiety, frequently co-occur and share underlying mechanisms involving neuronal excitability and synaptic transmission. The inwardly rectifying potassium channel 4.1 (Kir4.1), predominantly expressed in glial cells, is crucial for maintaining extracellular potassium and glutamate homeostasis. Dysregulation of Kir4.1 leads to altered neuronal activity, contributing to both chronic pain and mental health disorders. In chronic pain, downregulation of Kir4.1 impairs potassium buffering and glutamate clearance, increasing neuronal excitability and enhancing pain signaling through peripheral and central sensitization. In mental health disorders, impaired Kir4.1 function disrupts neurotrophic factor secretion and neuroinflammatory pathways, leading to mood disturbances. This review primarily summarizes findings from preclinical studies to examine the relationship between Kir4.1 and the pathogenesis of chronic pain and mental health disorders, discussing its molecular structure, expression patterns, and functional roles. Furthermore, we explore therapeutic strategies targeting Kir4.1, including pharmacological modulators and gene therapy approaches, emphasizing its potential as a novel therapeutic target. Full article

Termitomyces mushrooms, known for their symbiotic relationship with termites and their high nutritional and medicinal value, are challenging to cultivate artificially due to their specific growth requirements. This study investigates the impact of arginine on the mycelial growth, development, and lignocellulolytic capabilities of Termitomyces. We found that arginine significantly promoted conidia formation, altered mycelial morphology, and enhanced biomass and polysaccharide content. The addition of arginine also upregulated the expression of the enzymes related to lignocellulose decomposition, leading to increased activities of cellulase, hemicellulase, and laccase, which accelerated the decomposition and utilization of corn straw. A transcriptome analysis revealed differential expression patterns of carbohydrate-active enzyme genes in arginine-supplemented Termitomyces mycelia, providing insights into the molecular mechanisms underlying these enhancements. The GO enrichment analysis and KEGG pathway analysis highlighted the role of arginine in transmembrane transport, fatty acid oxidation, and carbohydrate metabolism. This study offers a molecular basis for the observed phenotypic changes and valuable insights for developing optimal culture strategies for Termitomyces, potentially enhancing its artificial cultivation and application in the bioconversion of lignocellulosic waste. Full article

The rising incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) necessitates advancements in risk stratification to optimize treatment outcomes and improve the quality of life for patients. Despite its favorable prognosis compared to HPV-negative OPSCC, current clinical staging and biomarkers, such as p16 status, are limited in their ability to distinguish between high- and low-risk patients within HPV-associated OPSCC. This limitation results in the overtreatment of low-risk patients, exposing them to unnecessary toxicity, and the undertreatment of high-risk patients who require more aggressive interventions. This review critically evaluates current stratification methods, including clinical assessments, de-escalation trials, and candidate molecular biomarkers for risk stratification. Emerging approaches such as immune markers, viral genomic integration patterns, and other molecular markers offer promising avenues for enhanced prognostic accuracy. By integrating advanced risk stratification methods, tailored treatment approaches may one day be developed to balance oncologic efficacy with reduced treatment-related morbidity. This review underscores the need for continued research into predictive biomarkers and adaptive treatment strategies to better address the diverse risk profiles of HPV-associated OPSCC patients. Full article

MYB (myeloblastosis) is one of the most abundant transcription factors in plants which regulates various biological processes. The molecular characteristics and function of R2R3-MYB transcription factors in amaranth remain unclear. In this study, 73 R2R3-MYB members were identified from the amaranth genome database and we further analyzed their chromosome position, conserved motifs, physiological and biochemical features, collinearity relationships, gene structure, phylogeny and cis-acting element. Based on the phylogenetic and expression pattern analysis, 14 candidate R2R3-MYB genes might be involved in the betalain synthesis. Amongst the 14 candidate R2R3-MYB genes, the expression level of AtrMYB72 was higher in ‘Suxian No.1’ than ‘Suxian No.2’, and also higher in the red section than in the green section of the same leaf in Amaranthus. The overexpression vector pCambia1301-AtrMYB72-GUS and VIGS (virus-induced gene silencing) vector pTRV2- AtrMYB72 were transferred into leaves of ‘Suxian No.1’ via an Agrobacterium-mediated method. The results showed that AtrMYB72 overexpression could promote betalain synthesis. A yeast one-hybrid assay and dual luciferase reporter gene assay demonstrated that AtrMYB72 could bind to the AtrCYP76AD1 promoter to promote betalain synthesis. These results indicated that AtrMYB72 promoted betalain biosynthesis in amaranth by activating the AtrCYP76AD1 transcription. Our results could provide new insights into the betalain biosynthesis in amaranth. Full article

Puya raimondii Harms is a charismatic species discovered in the Cordillera Blanca (now Huascarán National Park, Peru) in 1867 by the great Italian-born Peruvian geographer and naturalist Antonio Raimondi. The importance of this plant is due to its imposing size, the rare and extreme ecosystem that depends on it, and the fact that it is linked to the name Antonio Raimondi. Four studies on its genetic diversity revealed a range of patterns, with a fixation index of 0.740 as weighted mean and gene flow as low as 0.02–0.03. In fact, the vast majority of the total genetic variation was documented between populations, with very low genetic variation found within populations (weighted mean genetic diversity as low as Hs = 0.072 and mean genetic similarity very high, ranging from 96% up to 99%). We hypothesize that the narrow genetic base of P. raimondii populations may be due to a combination of factors: (i) an inbreeding-based reproductive strategy (i.e., mating between individuals related by common ancestry), which leads to homozygosity and genomic uniformity; (ii) strong environmental selective pressure (e.g., day–night temperature excursion, long dry period, etc.), which favors only the highest fitness individual genotypes; and (iii) a long life cycle, which hampers recombination events and reduces genetic diversity. Overall, these factors suggest that P. raimondii is a genetically fragile, fragmented, and endangered species. Full article

Background/Objectives: Pancreatic adenocarcinoma (PDAC) remains one of the most lethal cancers, with limited advancements in treatment efficacy due to high rates of chemoresistance. Circulating tumor cells (CTCs) derived from liquid biopsies offer a non-invasive approach to monitoring tumor evolution and identifying molecular mechanisms of resistance. This study aims to longitudinally collect, culture, and characterize CTCs from PDAC patients to elucidate resistance mechanisms and tumor-specific gene expression profiles. Methods: Blood samples from 10 PDAC patients were collected across different treatment stages, yielding 16 CTC cultures. Differential gene expression, pathway dysregulation, and protein–protein interaction studies were utilized, highlighting patient-specific and disease progression-associated changes. Longitudinal comparisons within five patients provided further insights into dynamic molecular changes associated with therapeutic resistance. Results: CTC cultures exhibited the activation of key pathways implicated in PDAC progression and resistance, including TNFα/NF-kB, hedgehog signaling, and the epithelial-to-mesenchymal transition. Longitudinal samples revealed dynamic changes in signaling pathways, highlighting upregulated mechanisms of chemoresistance, including PI3K/Akt/mTOR and TGF-β pathways. Additionally, protein–protein interaction analysis emphasized the role of the immune system in PDAC progression and therapy response. Patient-specific gene expression patterns therefore suggest potential applications for precision medicine. Conclusions: This proof-of-concept study demonstrates the feasibility of longitudinally capturing and analyzing CTCs from PDAC patients. The findings provide critical insights into molecular drivers of chemoresistance and highlight the potential of CTC profiling to inform personalized therapeutic strategies. Future large-scale studies are warranted to validate these findings and further explore CTC-based approaches in PDAC management. Full article

Background: As the global population ages, the prevalence of neurodegenerative conditions, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies, and frontotemporal dementia, continues to rise. Understanding the impact of aging on striatal glucose metabolism is pivotal in identifying potential biomarkers for the early detection of these disorders. Methods: We investigated age-related changes in striatal glucose metabolism using both region of interest (ROI)-based and voxel-wise correlation analyses. Additionally, we employed a normative modeling approach to establish age-related metabolic trajectories and assess individual deviations from these normative patterns. In vivo cerebral glucose metabolism was quantified using a molecular neuroimaging technique, ¹⁸F-FDG PET. Results: Our results revealed significant negative correlations between age and glucose metabolism in the bilateral caudate. Furthermore, the normative modeling demonstrated a clear, progressive decline in caudate metabolism with advancing age, and the most pronounced reductions were observed in older individuals. Conclusions: These findings suggest that metabolic reductions in the caudate may serve as a sensitive biomarker for normal aging and offer valuable insights into the early stages of neurodegenerative diseases. Moreover, by establishing age-specific reference values for caudate glucose metabolism, the normative model provides a framework for detecting deviations from expected metabolic patterns, which may facilitate the early identification of metabolic alterations that could precede clinical symptoms of neurodegenerative processes. Full article

Understanding hormonal and molecular changes during the transition from preterm to near-term gestation is essential for investigating how pregnancy complications impact fetal heart development and contribute to long-term cardiovascular risks for offspring. This study examines these cardiac changes in fetal sheep, focusing on the changes between 116 days (preterm) and 140 days (near term) of gestation (dG, term = 150) using Western blotting, LC-MS/MS, and histological techniques. We observed a strong correlation between cortisol and T₃ (Triiodothyronine) in heart tissue in near-term fetuses, highlighting the role of glucocorticoid signalling in fetal heart maturation. Protein expression patterns in the heart revealed a decrease in multiple glucocorticoid receptor isoforms (GRα-A, GR-P, GR-A, GRα-D2, and GRα-D3), alongside a decrease in IGF-1R (a marker of cardiac proliferative capacity) and p-FOXO1(Thr24) but an increase in PCNA (a marker of DNA replication), indicating a shift towards cardiomyocyte maturation from preterm to near term. The increased expression of proteins regulating mitochondrial biogenesis and OXPHOS complex 4 reflects the known transition from glycolysis to oxidative phosphorylation, essential for meeting the energy demands of the postnatal heart. We also found altered glucose transporter expression, with increased pIRS-1(ser789) and GLUT-4 but decreased GLUT-1 expression, suggesting improved insulin responsiveness as the heart approaches term. Notably, the reduced protein abundance of SIRT-1 and SERCA2, along with increased phosphorylation of cardiac Troponin I(Ser23/24), indicates adaptations for more energy-efficient contraction in the near-term heart. In conclusion, these findings show the complex interplay of hormonal, metabolic, and growth changes that regulate fetal heart development, providing new insights into heart development that are crucial for understanding pathological conditions at birth and throughout life. Full article

Active cancer targeting consists of the selective recognition of overexpressed biomarkers on cancer cell surfaces or within the tumor microenvironment, enabled by ligands conjugated to drug carriers. Nanoparticle (NP)-based systems are highly relevant for such an approach due to their large surface area which is amenable to a variety of chemical modifications. Over the past decades, several studies have debated the efficiency of passive targeting, highlighting active targeting as a more specific and selective approach. The choice of conjugation chemistry for attaching ligands to nanocarriers is critical to ensure a stable and robust system. Among the panel of cancer biomarkers, the epidermal growth factor receptor (EGFR) stands as one of the most frequently overexpressed receptors in different cancer types. The design and development of nanocarriers with surface-bound anti-EGFR ligands are vital for targeted therapy, relying on their facilitated capture by EGFR-overexpressing tumor cells and enabling receptor-mediated endocytosis to improve drug accumulation within the tumor microenvironment. In this review, we examine several examples of the most recent and significant anti-EGFR nanocarriers and explore the various conjugation strategies for NP functionalization with anti-EGFR biomolecules and small molecular ligands. In addition, we also describe some of the most common characterization techniques to confirm and analyze the conjugation patterns. Full article

Ammopiptanthus nanus, a Tertiary-era endangered plant, is of great scientific value. In this research, we focus on A. nanus population dynamics in an effort to bridge the divide between micro genetic variation and a macroscopic ecological pattern of distribution. The population structure of 129 wild specimens of A. nanus from eight populations was analyzed using EST-SSR molecular markers in this research. The Mantel test and RDA analysis have been used in this research to investigate the factors that influence the genetic diversity of A. nanus. Using 15 pairs of SSR primers, a total of 227 alleles were detected in 129 samples from 8 populations. The mean number of alleles was 17, and the average expected heterozygosity was 0.405. It is shown that wild A. nanus is divided into six individual populations. A. nanus are significantly affected by wind speed in terms of the variation of genetics. It is suggested that a nature conservation area for A. nanus be established as soon as possible, based on our results and the current natural distribution of the species. It is necessary to focus on the issue of pests and diseases while simultaneously preventing the continuation of anthropogenic woodcutting and disaster. Manual seedling collection should be employed in regions where the environment permits. Through making use of manual breeding techniques, this will contribute to the growth of the natural population of A. nanus. Full article

Symbiotic nitrogen fixation, recognized as the most efficient nitrogen assimilation system in ecosystems, is essential for soybean growth, as nodulation provides critical nitrogen to host cells. Soybeans thrive in warm and moist environments. However, they are highly susceptible to low temperatures, which impede the formation and development of root nodules. The genetic basis and molecular mechanism underlying the inhibition of nodulation induced by low temperatures remain unclear. In this study, we conducted a comparative transcriptomic analysis of soybean roots inoculated with rhizobium at 1 DPI (Day Post Inoculation) under normal or cold treatments. We identified 39 up-regulated and 35 down-regulated genes associated with nodulation and nitrogen fixation. Notably, cold-responsive genes including three FRI (Frigida) family genes were identified among differentially expressed genes (DEGs). Further expression pattern analysis of GmFRI-1 demonstrated it being significantly responsive to rhizobium inoculation and its highest expression in nodules. Further investigation revealed that overexpression of GmFRI-1 led to an increase in the nodule number, while RNA interference (RNAi)-mediated gene editing of GmFRI-1 suppressed nodule formation. Additionally, GmFRI-1 overexpression may regulate soybean nodulation by modulating the expression of GmNIN (NODULE INCEPTION), GmNSP1 (nodulation signaling pathway 1), and GmHAP2-2 (histone- or haem-associated protein domain) in the nod factor signaling pathway. This study offers new insights into the genetic basis of nodulation regulation under cold stress in legumes and indicates that GmFRI-1 may serve as a key regulator of nodule formation under cold stress. Full article

Migraine with aura (MwA) is a common and severely disabling neurological disorder, characterised by transient yet recurrent visual disturbances, including scintillating scotomas, flickering photopsias, and complex geometric patterns. These episodic visual phenomena significantly compromise daily functioning, productivity, and overall quality of life. Despite extensive research, the underlying pathophysiological mechanisms remain only partially understood. Cortical spreading depression (CSD), a propagating wave of neuronal and glial depolarisation, has been identified as a central process in MwA. This phenomenon is triggered by ion channel dysfunction, leading to elevated intracellular calcium levels and excessive glutamate release, which contribute to widespread cortical hyperexcitability. Genetic studies, particularly involving the CACNA gene family, further implicate dysregulation of calcium channels in the pathogenesis of MwA. Recent advances in neuroimaging, particularly functional magnetic resonance imaging (fMRI), have provided critical insights into the neurophysiology of MwA. These results support the central role of CSD as a basic mechanism behind MwA and imply that cortical dysfunction endures beyond brief episodes, possibly due to chronic neuronal dysregulation or hyperexcitability. The visual cortex of MwA patients exhibits activation patterns in comparison to other neuroimaging studies, supporting the possibility that it is a disease-specific biomarker. Its distinctive sensory and cognitive characteristics are influenced by a complex interplay of cortical, vascular, and genetic factors, demonstrating the multifactorial nature of MwA. We now know much more about the pathophysiology of MwA thanks to the combination of molecular and genetic research with sophisticated neuroimaging techniques like arterial spin labelling (ASL) and fMRI. This review aims to synthesize current knowledge and analyse molecular and neurophysiological targets, providing a foundation for developing targeted therapies to modulate cortical excitability, restore neural network stability, and alleviate the burden of migraine with aura. The most important and impactful research in our field has been the focus of this review, which highlights important developments and their contributions to the knowledge and treatment of migraine with aura. Full article

The treatment of metastasized gastroesophageal adenocarcinoma largely depends on molecular profiling based on immunohistochemical procedures. Therefore, the examination of HER2, PD-L1, and dMMR/MSI is recommended by the majority of clinical practice guidelines, as positive expression leads to different treatment approaches. Data from large phase-III trials and consequent approvals in various countries enable physicians to offer their patients several therapy options including immunotherapy, targeted therapy, or both combined with chemotherapy. The introduction of novel therapeutic targets such as CLDN18.2 leads to a more complex decision-making process as a significant number of patients show positive results for the co-expression of other biomarkers besides CLDN18.2. The aim of this review is to summarize the current biomarker landscape of patients with metastatic gastroesophageal tumors, its direct clinical impact on daily decision-making, and to evaluate current findings on biomarker co-expression. Furthermore, possible treatment strategies with multiple biomarker expression are discussed. Full article