Search Results (2,232)

Black spot is currently one of the most widespread diseases affecting Yanbian Pingguoli pears (Pyrus pyrifolia cv. ‘Pingguoli’), resulting in significant economic losses for fruit farmers. It is mainly caused by infestation by the fungal group of Alternaria species. To date, no research has reported the presence of Alternaria species and the pathogen of black spot disease on Yanbian Pingguoli pears in China. This study isolated, identified, and performed molecular profiling of 124 Alternaria strains collected from 15 major growing areas of Yanbian Pingguoli pear (more than 5000 trees). Moreover, the study evaluated the ability of Artemisia capillaris essential oil (AcEO) to suppress the mycelial expansion of Alternaria pathogens and conducted comprehensive chemical profiling. Overall, 124 pathogenic fungi were identified as Alternaria tenuissima (67 isolates, 54.0%) and A. alternate (57 isolates, 46.0%). AcEO showed a strong inhibitory effect on the two Alternaria species, with a minimal inhibitory concentration (MIC) value equivalent to 5.0 μL/mL. Eucalyptol, 2,2-Dimethyl-3-methylenebicyclo [2.2.1] heptane, (-)-alcanfor, and β-copaene were identified as the predominant bioactive components of AcEO. AcEO demonstrated concentration-dependent inhibition of the mycelial growth of A. tenuissima and A. alternata. These findings position AcEO as a promising candidate for developing sustainable fungicides to combat Alternaria-induced crop losses. Full article

Basic helix-loop-helix (bHLH) transcription factors represent one of the largest transcriptional regulator families in cereal crops such as rice, maize, and wheat. They play crucial and diverse roles in regulating key agronomic traits and essential physiological processes. This review provides a systematic synthesis of the functionally characterized bHLH genes across the three major cereals, offering a comparative perspective on their roles in growth, development, and stress responses. We comprehensively summarize their documented functions, highlighting specific regulators such as TaPGS1 for grain size, rice ILI subfamily for leaf angle, OsbHLH004 for seed dormancy and maize “Ms23-Ms32-bHLH122-bHLH51” cascade for the anther development. Their conserved and species-specific functions in iron homeostasis (e.g., IRO2) and in responses to drought, cold, salinity, and pathogens are also detailed. Additionally, we discuss the underlying molecular mechanisms, including specific binding to E-box/G-box cis-elements, protein dimerization, and integration with hormone signaling pathways. By integrating the current knowledge, this review serves as a consolidated and up-to-date reference that highlights the strategic potential of bHLH transcription factors in molecular breeding programs for improving yield, quality, and stress tolerance in cereals. Full article

Acute myeloid leukemia (AML) accounts for 15–20% of childhood leukemia cases; however, it is characterized by very high aggressiveness and has the highest mortality rate among leukemias, with relapse rates ranging from 34% to 38%. It is a disease characterized by high molecular diversity, and the frequency of specific genetic alterations in children is different from that in adults. Furthermore, mutations and rearrangements vary with age within the pediatric population. To date, a wide spectrum of genetic alterations has already been studied, but the molecular landscape of each patient is unique. An analysis of rearrangements and mutations specific to children of different ages appears to be crucial in order to individualize diagnosis and therapy appropriately. The aim of the following review is to analyze the molecular landscape of pediatric AML by age in detail in order to prioritize therapeutic strategies dedicated to specific age groups. Full article

Selective and potent inhibitors of the NAD⁺-dependent deacetylase Sirt2 represent a valuable epigenetic strategy for the treatment of currently incurable diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis. Guided by molecular docking and MM/GBSA validation studies, a lead structure-based hybridization strategy was developed, resulting in a series of very effective Sirt2 inhibitors. With RW-93, we present a highly potent and subtype selective Sirt2 inhibitor (IC₅₀ = 16 nM), which as a next generation SirReal-type inhibitor significantly surpasses established Sirt2 inhibitors and contributes to the extension of the current SAR profile. The structural modification strategy employed in this study proved to be highly promising, resulting in the identification of the most potent low-molecular-weight Sirt2 inhibitor reported to date, providing a promising target for further medicinal chemistry-driven SAR studies. Full article

Ischemic stroke is now widely recognized as a disease with a strong inflammatory profile. Cerebral vascular damage is both preceded and followed by a chain of molecular events involving immune cells and inflammatory markers, irrespective of the etiology of the ischemic injury. Over time, an increasingly comprehensive understanding of these markers has led to a better insight into the mechanisms behind the vascular event and recovery following ischemic stroke. However, to date, there are still no available circulating or tissue biomarkers for early diagnosis or prognostic stratification, making ischemic stroke diagnosis contingent on clinical and instrumental investigations. However, neurological and internal medicine research is progressing in identifying markers that could potentially take on this role. This manuscript, therefore, aims to review the most recent and innovative results of medical advances, summarising the current state of the art and future perspectives. If ischaemic stroke is an inflammatory disease, it is also true that it is not just a singular condition, but a group of entities with their own neuroinflammatory features. Thus, given that, in ischemic cerebral vascular damage, “time is brain,” tracking increasingly accurate markers in the diagnosis of ischemic stroke is a valuable tool that will potentially enable earlier recognition of this disease and, hopefully, make it less disabling and more widely treated. Full article

The gut microbiome possesses a diverse range of biological properties that play a role in maintaining host health and preventing disease. Gut microbial metabolites, including short-chain fatty acids, natural purine nucleosides, ellagic acid derivatives, and tryptophan metabolites, have been observed to have complex and multifaceted roles in the gut and in wider body systems in the management of disease, including cancer. Triple-negative breast cancer is the most aggressive subtype of breast cancer, with restricted treatment options and poor prognoses. Recently, preclinical research has investigated the antiproliferative potential of gut microbial metabolites against this type of breast cancer with promising results. However, little is understood about the mechanisms of action and molecular pathways driving this antiproliferative potential. Understanding the complex mechanisms of action of gut microbial metabolites on triple-negative breast cancer will be instrumental in the investigation of the combined administration with standard chemotherapeutic drugs. To date, there is a paucity of research studies investigating the potential synergistic interactions between gut microbial metabolites and standard chemotherapeutic drugs. The identification of synergistic potential between these compounds may provide alternate and more effective therapeutic options in the treatment and management of triple-negative breast cancer. Further investigation into the mechanistic action of gut microbial metabolites against this breast cancer subtype may support the administration of more cost-effective treatment options for breast cancer, with an aim to reduce side effects associated with standard treatments. Additionally, future research will aim to identify more potent metabolite–drug combinations in the mitigation of triple-negative breast cancer progression and metastasis. Full article

The grassland caterpillar Gynaephora qinghaiensis (Lepidoptera: Lymantriidae) is a dominant pest species in the alpine meadows of the Tibetan Plateau. Elucidating changes in key gene expression patterns will provide molecular insights into the adaptive evolutionary mechanisms of insects. Quantitative real-time PCR (qRT-PCR) is currently the predominant analytical methodology for assessing gene expression levels. However, variability among samples can compromise result reliability. Thus, selecting stably expressed reference genes for target gene normalization under diverse scenarios is critical. To date, suitable reference genes for G. qinghaiensis under varying experimental conditions have remained unidentified. In this study, the transcriptome data of G. qinghaiensis were obtained using the RNA-seq technique, and 13 candidate reference genes were selected. Four independent algorithms—ΔCt, geNorm, NormFinder, and BestKeeper—as well as a comprehensive online platform, RefFinder, were employed to evaluate the stability under six experimental conditions (tissues, developmental stages, sexes, temperatures, starvation, and insecticide treatments). Our findings identified the following optimal reference gene combinations for each experimental condition: RPS18, RPS15, and RPL19 for tissue samples; RPL19, RPS15, and RPL17 across developmental stages; RPS18 and RPS15 for different sexes; RPS8 and EF1-α under varying temperature conditions; RPL17 and RPL15 during starvation; and RPL19 and RPL17 following insecticide treatments. To validate the feasibility of the reference genes, we examined the expression of the target gene HSP60 in different tissues and under different temperatures. Our results established essential reference standards for qRT-PCR with G. qinghaiensis samples, laying the foundation for precise gene expression quantification in the future. Full article

To date, Philaenus spumarius (Linnaeus, 1758), Philaenus italosignus Drosopoulos & Remane, 2000, and Neophilaenus campestris (Fallén, 1805) are proven vectors of the phytopathogenic bacterium Xylella fastidiosa Wells et al., 1987 in Europe. Currently, the identification of these three species relies on the well-documented status of morphological and taxonomical characters, making the discrimination of vector adult males possible by genitalia comparison. This study updates the biomolecular diagnostic tests with a rapid identification tool for P. italosignus, using locked nucleic acid (LNA) probe technology. The test also overcomes the difficulties associated with the morphological identification of females and juveniles. The morphological α-taxonomic identification of the male, achieved through comparison with the type of the species, retains its primary role in specimen identification for probe building. Later, the proposed assay can contribute to the rapid identification of P. italosignus by the secondary (molecular) identification step. The new LNA qPCR test offers high reliability and reproducibility in the identification of P. italosignus instars, thus improving targeted surveys of X. fastidiosa vector populations and allowing discrimination between species collected in the field. The accurate identification and census of vector individuals, regardless of their gender and instar, enhances the efficacy of Xylella IPM-DSS (Integrated Pest Management Decision Support System) strategies. Full article

This review covers issues related to the characteristics, diagnosis, and treatment of colorectal cancer (CRC). It discusses traditional methods of treating colorectal cancer, including surgery, chemotherapy, and radiotherapy, as well as modern approaches, including targeted therapies, immunotherapy, and innovative gene therapy strategies. Particular attention is paid to the identification of molecular subtypes of CRC, which has revolutionized treatment in advanced stages of the disease and contributed to improved patient survival. The role of biomarkers, including liquid biopsy, in diagnosis, therapy monitoring, and treatment response assessment is emphasized. The potential of artificial intelligence in planning and optimizing surgical procedures is also discussed, opening up new possibilities in personalized therapy. This article provides up-to-date knowledge on the molecular mechanisms of CRC, diagnostic prospects, and directions for the development of precision therapies, serving as a valuable source of information for both clinicians involved in the treatment of CRC and patients wishing to deepen their knowledge of the disease and modern therapeutic options. Full article

Monoclonal antibodies (mAbs) have revolutionized the treatment landscape for neurological diseases, providing targeted, mechanism-based therapies for conditions ranging from autoimmune demyelinating disorders to neurodegenerative diseases. In multiple sclerosis (MS), mAbs against CD20, CD52, and α4-integrins offer disease-modifying efficacy by altering immune responses, depleting B cells, or blocking leukocyte migration into the central nervous system (CNS). Similarly, novel agents under investigation, such as frexalimab and foralumab, modulate T and B cell interactions and regulatory immunity. In neuromyelitis optica spectrum disorder (NMOSD), mAbs targeting IL-6, the complement cascade, and B cell lineage have demonstrated significant clinical benefit in preventing relapses and disability. In Alzheimer’s disease (AD), several anti-amyloid mAbs have gained regulatory approval. Anti-tau and anti-α-synuclein antibodies, though promising, have shown limited efficacy to date in AD and parkinson’s disease (PD), respectively. The evolving armamentarium of mAbs reflects a paradigm shift toward personalized neuroimmunology and neurodegeneration-targeted treatments, based on ongoing clarification of molecular and neuroinflammatory mechanisms. In this context, the present review summarizes current evidence on mAbs used in CNS disorders, with an emphasis on their pathophysiological targets, molecular mechanisms, clinical efficacy, and safety. Full article

Onychophora (velvet worms) are rare, soil-dwelling invertebrates with a fragile body structure that limits their fossil record. Their current distribution across the Neotropics has long been shaped by vicariance and dispersal events. Here, we evaluate the hypothesis that the Cretaceous–Paleogene (K–Pg) asteroid impact played a role in shaping the modern biogeography of Onychophora by eliminating lineages within the affected zone. Using published molecular phylogenies and geological data on the Chicxulub impact, we assess whether extant clades are congruent with a post-impact recolonization scenario. We find that several clades have divergence dates incompatible with extinction at the K–Pg boundary and that current distributions do not show a clear biogeographic signature consistent with impact-induced extirpation. Our hypothesis test supports the survival of onychophoran lineages through the K–Pg event and calls for caution in attributing modern distributions to a single extinction event without integrating molecular, stratigraphic, and ecological data. Full article

Background/Objectives: The role of the molecular chaperone heat shock protein 90 (Hsp90) in pain and analgesia has been recognized; however, no study to date has investigated its role in facial allodynia during headache. In the current study, we examined the role of Hsp90 and its possible connection to the endocannabinoid system utilizing a rodent model of cortical spreading depression (CSD). Methods: CSD, a physiological phenomenon associated with headache disorders, was induced by cortical injection of KCl in female Sprague Dawley rats. To selectively inhibit Hsp90, 17-AAG was applied on the dura mater 24 h before CSD induction. Periorbital allodynia was assessed by von Frey filaments, while tissue samples were subjected to LC-MS, qPCR, Western immunoblotting, and the GTPγS coupling assay. Results: Increased expression of Hsp90 was selectively observed in the periaqueductal gray (PAG) harvested 90 min after cortical KCl injection, suggesting increased cellular stress from CSD induction. Application of 17-AAG (0.5 nmol) on dura mater 24 h before CSD induction significantly prevented facial allodynia as measured by von Frey filaments. This effect was blocked by injection of the CB₁R antagonist rimonabant (1 mg/kg, ip). The pretreatment with 17-AAG significantly increased the level of anandamide (AEA) in PAG 90 min after cortical insult, as measured by LC-MS. This effect was accompanied by reduced expression of FAAH and increased expression of NAPE-PLD in the same nuclei. Conclusions: These results suggest that Hsp90 inhibition positively modulates the endocannabinoid system, causing pain relief through descending pain modulation in PAG post-CSD. Full article

To date, more than 170 chemical modifications have been identified in RNA. m⁶A (N⁶-methyladenine) RNA methylation is the most abundant form of mRNA modification in eukaryotes, playing an important role in RNA post-transcriptional processes. To investigate the function of m⁶A methylation modification in the development and lactation of dairy goat mammary glands, mammary gland tissue samples were collected in the early (20 days postpartum), peak (90 days postpartum), and late period (210 days postpartum) of three dairy goats. MeRIP-seq and RNA-seq were used to explore m⁶A methylation modification events. We identified 1638 differential peaks in the MeRIP-seq data across 1539 differentially methylated genes, which were enriched in ribosome biogenesis in eukaryotes, Toll-like receptor signaling pathway, TNF signaling pathway, MAPK, and other pathways related to mammary gland development and lactation. A conjoint analysis revealed that 179 common differential expressed genes were obtained, of which 150 were negatively regulated by their m⁶A modifications, while 5 common differentially expressed genes—PPARG, HSPA2, CDK5, ACTB and NOTCH3, were screened out in the two groups. In conclusion, m⁶A modification involves the pathways related to mammary gland development and lactation by modifying gene expression. This studyprovides new insights into m⁶A epigenetic regulation, mammary epithelial gene networks, and actionable molecular targets for high-value dairy product production and the breeding of new varieties. Full article

Background/Objectives: Autosomal recessive primary microcephaly is a rare and genetically heterogeneous disorder characterized by congenital non-syndromic microcephaly, with at least 28 causative genes identified to date. Biallelic variants in the CDK5RAP2 gene, an ultra-rare cause of autosomal recessive primary microcephaly, lead to Primary Autosomal Recessive Microcephaly 3 (MCPH3). Methods: We present seven patients from six families diagnosed with MCPH3 in light of clinical and molecular findings using whole-exome sequencing (WES). Furthermore, we investigated the effects of the identified intronic variants on splicing through RNA analysis. Results: Almost all patients had severe microcephaly, mild to moderate intellectual disability, speech delay, and cutaneous pigmentary abnormalities. Four patients presented with postnatal short stature, and two showed weight deficiency. Dysmorphic evaluation revealed that the most prominent features included brachycephaly, hypertelorism, epicanthus, high-arched eyebrows, prominent nasal bridge, and micrognathia. We identified five distinct homozygous CDK5RAP2 variants in our patients, including four novel variants. Segregation analysis verified that the parents were carriers. Two of these variants were intronic (c.3148+5G>C and c.383+4dupA), two were frameshift (c.3168del), and one was a nonsense variant (c.1591C>T). Both intronic variants disrupted splicing, generating a premature stop codon and resulting in a truncated protein. Conclusions: This study broadens the mutational landscape of CDK5RAP2. We also sought to demonstrate the functional consequences of the CDK5RAP2 intronic variants on gene function using RNA analysis. The identification of four novel variants underscores the importance of molecular diagnostics in patients with primary microcephaly and provides valuable data for genetic counseling and future functional studies. Full article

Detection of cancer biomarkers at the earliest stages of disease progression is commonly assumed to extend the overall quality of life for cancer patients as the result of earlier clinical management of the disease. Therefore, there is an urgent need for the development of standardized, sensitive, robust, and commonly available screening and diagnostic tools for detecting the earliest signals of neoplastic pathology progression. Recently, a new paradigm of cancer control, known as multi-cancer detection (MCD), evolved, which measures the composition of cancer-related molecular analytes in the patient’s fluids using minimally invasive techniques. In this respect, the “Holy Grail” of cancer researchers and bioengineers for decades has been composing a repertoire or molecular sensing probes that would allow for the diagnosis, prognosis, and monitoring of cancer diseases via their interaction with cell-secreted and cell-associated cancer antigens and biomarkers. Therefore, the current trend in screening and detection of cancer-related pathologies is the development of portable biosensors for mobile laboratories and individual use. Phage display, since its conception by George Smith 40 years ago, has emerged as a premier tool for molecular evolution in molecular biology with widespread applications including identification and screening of cancer biomarkers, such as Circulating Cellular Communication Network Factor 1 (CCN1), an extracellular matrix-associated signaling protein responsible for a variety of cellular functions and has been shown to be overexpressed as part of the response to various pathologies including cancer. We hypothesize that CCN1 protein can be used as a soluble marker for the early detection of breast cancer in a multi-cancer detection (MCD) platform. However, validated probes have not been identified to date. Here, we screened the multi-billion clone landscape phage display library for phages interacting specifically with immobilized CCN1 protein. Through our study, we discovered a panel of 26 different phage-fused peptides interacting selectively with CCN1 protein that can serve for development of a novel phage-based diagnostic platform to monitor changes in CCN1 serum concentration by liquid biopsy. Full article