Search Results (1,072)

Pleurotus ostreatus is a widely cultivated edible fungus in China, renowned for its rich nutritional composition and diverse medicinal compounds. However, the quality of the currently published P. ostreatus genomes remained suboptimal, which limited in-depth research on its evolution, growth, and development. In this study, we conducted a chromosome-level genome assembly of the monokaryotic basidiospore strain PC80. The assembled genome spanned 40.6 Mb and consisted of 15 scaffolds. Ten of these scaffolds contained complete telomere-to-telomere structures. The scaffold N50 value was 3.6 Mb. Genome annotation revealed 634 carbohydrate-active enzyme (CAZyme) family genes. Through collinearity analysis, we further confirmed that the PC80 genome exhibited higher completeness and greater accuracy compared to the currently published genomes of P. ostreatus. At the matA locus of PC80, three hd1 genes and one hd2 gene were identified. At the matB locus, seven pheromone receptor genes and two pheromone precursor genes were detected. Further phylogenetic analysis indicated that three of these pheromone receptor genes are likely to have mating-specific functions. This complete genome assembly could provide a foundation for future genomic and genetic studies, facilitate the identification of key genes related to growth and developmental regulation, and promote technological innovations in P. ostreatus breeding and efficient utilization. Full article

Foodborne pathogenic bacteria critically threaten public health and food industry sustainability, serving as a predominant trigger of food contamination incidents. To mitigate these risks, the development of rapid, sensitive, and highly specific detection technologies is essential for early warning and effective control of foodborne diseases. In recent years, biosensors have gained prominence as a cutting-edge tool for detecting foodborne pathogens, owing to their operational simplicity, rapid response, high sensitivity, and suitability for on-site applications. This review provides a comprehensive evaluation of critical biorecognition elements, such as antibodies, aptamers, nucleic acids, enzymes, cell receptors, molecularly imprinted polymers (MIPs), and bacteriophages. We highlight their design strategies, recent advancements, and pivotal contributions to improving detection specificity and sensitivity. Additionally, we systematically examine mainstream biosensor-based detection technologies, with a focus on three dominant types: electrochemical biosensors, optical biosensors, and piezoelectric biosensors. For each category, we analyze its fundamental principles, structural features, and practical applications in food safety monitoring. Finally, this review identifies future research priorities, including multiplex target detection, enhanced processing of complex samples, commercialization, and scalable deployment of biosensors. These advancements are expected to bridge the gap between laboratory research and real-world food safety surveillance, fostering more robust and practical solutions. Full article

In this review, we explore the complexities of objectively assessing the response to immunotherapy in mycosis fungoides (MF), a prevalent form of cutaneous T-cell lymphoma. The core challenge lies in distinguishing between reactive and malignant lymphocytes amidst treatment, particularly given the absence of uniform pathological biomarkers for MF. We highlight the vital role of emerging histological technologies, such as multispectral imaging and spatial transcriptomics, in offering a more profound insight into the tumor microenvironment (TME) and its dynamic response to immunomodulatory therapies. Drawing on parallels with melanoma—another immunogenic skin cancer—our review suggests that methodologies and insights from melanoma could be instrumental in refining the approach to MF. We specifically focus on the prognostic implications of various TME cell types, including CD8+ tumor-infiltrating lymphocytes, natural killer (NK) cells, and histiocytes, in predicting therapy responses. The review culminates in a discussion about adapting and evolving treatment response quantification strategies from melanoma research to the distinct context of MF, advocating for the implementation of novel techniques like high-throughput T-cell receptor gene rearrangement analysis. This exploration underscores the urgent need for continued innovation and standardization in evaluating responses to immunotherapies in MF, a field rapidly evolving with new therapeutic strategies. Full article

Animal venoms are complex biochemical secretions rich in highly potent and selective bioactive molecules, including peptides, enzymes, and small organic compounds. Once associated primarily with toxicity, these venoms are now recognized as a promising source of therapeutic agents for a wide range of medical conditions. This review provides a comprehensive analysis of the pharmacological potential of venom-derived compounds, highlighting their mechanisms of action, such as ion channel modulation, receptor targeting, and enzyme inhibition. Successful venom-derived drugs like captopril and ziconotide exemplify the translational potential of this biological arsenal. We discuss therapeutic applications in cardiovascular diseases, chronic pain, cancer, thrombosis, and infectious diseases, as well as emerging peptide candidates in clinical development. Technological advancements in omics, structural biology, and synthetic peptide engineering have significantly enhanced the discovery and optimization of venom-based therapeutics. Despite challenges related to stability, immunogenicity, and ecological sustainability, the integration of AI-driven drug discovery and personalized medicine is expected to accelerate progress in this field. By synthesizing current findings and future directions, this review underscores the transformative potential of animal venoms in modern pharmacotherapy and drug development. We also discuss current therapeutic limitations and how venom-derived compounds may address unmet needs in specific disorders. Full article

The serotonergic system, originating in the raphe nuclei, differentially modulates the dorsal and ventral hippocampus, which are implicated in cognition and emotion, respectively. Emerging evidence from rodent models (e.g., neonatal ventral hippocampal lesion, pharmacological NMDA receptor antagonist exposure) and human postmortem studies indicates dorsoventral serotonergic alterations in schizophrenia. These data include elevated 5-HT1A receptor expression in the dorsal hippocampus, linking serotonergic hypofunction to cognitive deficits, and hyperactive 5-HT2A/3 receptor signaling and denser serotonergic innervation in the ventral hippocampus driving local hyperexcitability associated with psychosis and stress responsivity. These dorsoventral serotonergic alterations are shown to disrupt the excitation–inhibition balance, impair synaptic plasticity, and disturb network oscillations, as established by in vivo electrophysiology and functional imaging. Synthesizing these multi-level findings, we propose a novel “dorsoventral serotonin imbalance” model of schizophrenia, in which ventral hyperactivation predominantly contributes to psychotic symptoms and dorsal hypoactivity underlies cognitive deficits. We further highlight promising preclinical evidence that selective targeting of region- and receptor-specific targeting, using both pharmacological agents and emerging delivery technologies, may offer novel therapeutic opportunities enabling symptom-specific strategies in schizophrenia. Full article

Bacteriophages (phages), the most abundant biological entities on Earth, have long served as both model systems and therapeutic tools. Recent advances in synthetic biology and genetic engineering have revolutionized the capacity to tailor phages with enhanced functionality beyond their natural capabilities. This review outlines the current landscape of synthetic and functional engineering of phages, encompassing both in-vivo and in-vitro strategies. We describe in-vivo approaches such as phage recombineering systems, CRISPR-Cas-assisted editing, and bacterial retron-based methods, as well as synthetic assembly platforms including yeast-based artificial chromosomes, Gibson, Golden Gate, and iPac assemblies. In addition, we explore in-vitro rebooting using TXTL (transcription–translation) systems, which offer a flexible alternative to cell-based rebooting but are less effective for large genomes or structurally complex phages. Special focus is given to the design of customized phages for targeted applications, including host range expansion via receptor-binding protein modifications, delivery of antimicrobial proteins or CRISPR payloads, and the construction of biocontained, non-replicative capsid systems for safe clinical use. Through illustrative examples, we highlight how these technologies enable the transformation of phages into programmable bactericidal agents, precision diagnostic tools, and drug delivery vehicles. Together, these advances establish a powerful foundation for next-generation antimicrobial platforms and synthetic microbiology. Full article

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and suppressing graft-versus-host disease (GvHD). Methods: A systematic review following PROSPERO guidelines (CRD420251073207) was conducted across PubMed, Scopus, and Web of Science for studies published from 2015 to 2024. After screening 105 articles, 17 studies involving CAR-Tregs in preclinical or in vivo transplant or GvHD models were included. Results: CAR-Tregs exhibited superior graft-protective properties compared to unmodified or polyclonal Tregs. HLA-A2-specific CAR-Tregs consistently improved graft survival, reduced inflammatory cytokines, and suppressed immune cell infiltration across skin, heart, and pancreatic islet transplant models. The inclusion of CD28 as a co-stimulatory domain enhanced Treg function and FOXP3 expression. However, challenges such as Treg exhaustion, tonic signaling, and reduced in vivo persistence were noted. Some studies reported synergistic effects when CAR-Tregs were combined with immunosuppressants like rapamycin or tacrolimus. Conclusions: CAR-Tregs offer a promising strategy for inducing targeted immunosuppression in allogeneic transplantation. While preclinical findings are encouraging, further work is needed to optimize CAR design, ensure in vivo stability, and establish clinical-scale manufacturing before translation to human trials. Full article

In this study, we identify cortical molecular biomarkers potentially associated with learning in mice using artificial intelligence (AI), inclusive of established and novel feature selection combined with supervised learning technologies. We applied multiple machine learning (ML) algorithms, using public domain ML software, to a public domain dataset, in order to support reproducible findings. We developed technologies tasked with predicting whether a given mouse was shocked to learn, based on protein expression levels extracted from their cortices. Results indicate that it is possible to predict whether a mouse has been shocked to learn or not based only on the following cortical molecular biomarkers: brain-derived neurotrophic factor (BDNF), NR2A subunit of N-methyl-D-aspartate receptor, B-cell lymphoma 2 (BCL2), histone H3 acetylation at lysine 18 (H3AcK18), protein kinase R-like endoplasmic reticulum kinase (pERK), and superoxide dismutase 1 (SOD1). These results were obtained with a novel redundancy-aware feature selection method. Five out of six protein expression biomarkers (BDNF, NR2A, H3AcK18, pERK, SOD1) identified have previously been associated with aspects of learning in the literature. Three of the proteins (BDNF, NR2A, and BCL2) have previously been associated with pruning, and one has previously been associated with apoptosis (BCL2), implying a potential connection between learning and both cortical pruning and apoptosis. The results imply that these six protein expression profiles (BDNF, NR2A, BCL2, H3AcK18, pERK, SOD1) are highly predictive of whether or not a mouse has been shocked to learn. Full article

Ischemic stroke ranks among the top global causes of disability and mortality, with a highly dynamic pathological process. Post-stroke neuroinflammation, mediated by microglia, demonstrates a dual role in both injury and repair. The CX3CR1/CX3CL1 signaling axis, highly expressed in microglia, acts as a key regulator. This review examines the spatiotemporal dynamics of the axis across the stroke process and its involvement in neural repair. Crucially, this signaling pathway demonstrates stage-dependent functional duality: its cellular sources, receptor expression profiles, and functional consequences undergo temporally orchestrated shifts, manifesting coexisting or interconverting protective and damaging properties. Ignoring this dynamism compromises the therapeutic efficacy of targeted interventions. Thus, we propose a triple precision strategy of “stroke phase—biomarker—targeted intervention”. It uses specific biomarkers for precise staging and designs interventions based on each phase’s signaling characteristics. Despite challenges like biomarker validation, mechanistic exploration, and cross-species differences, integrating cutting-edge technologies such as spatial metabolomics and AI-driven dynamic modeling promises to shift stroke therapy toward personalized spatiotemporal programming. Temporally targeting CX3CR1 signaling may offer a key basis for developing next-generation precision neural repair strategies for stroke. Full article

Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease (ESKD) globally. Despite advances in our understanding of its pathophysiology, current therapies are often insufficient to stop its progression. In recent years, microRNAs (miRNAs)—small, non-coding RNA molecules involved in post-transcriptional gene regulation—have emerged as critical modulators of key pathogenic mechanisms in DKD, including fibrosis, inflammation, oxidative stress, and apoptosis. Numerous studies have identified specific miRNAs that either exacerbate or mitigate renal injury in DKD. Among them, miR-21, miR-192, miR-155, and miR-34a are associated with disease progression, while miR-126-3p, miR-29, miR-146a, and miR-215 demonstrate protective effects. These molecules are also detectable in plasma, urine, and renal tissue, making them attractive candidates for diagnostic and prognostic biomarkers. Advances in therapeutic technologies such as antagomiRs, mimics, locked nucleic acids, and nanoparticle-based delivery systems have opened new possibilities for targeting miRNAs in DKD. Additionally, conventional drugs, including SGLT2 inhibitors, metformin, and GLP-1 receptor agonists, as well as dietary compounds like polyphenols and sulforaphane, may exert nephroprotective effects by modulating miRNA expression. Recent evidence also highlights the role of gut microbiota in regulating miRNA activity, linking metabolic and immune pathways relevant to DKD progression. Further research is needed to define stage-specific miRNA signatures, improve delivery systems, and develop personalized therapeutic approaches. Modulation of miRNA expression represents a promising strategy to slow DKD progression and improve patient outcomes. Full article

Per- and polyfluoroalkyl substances (PFASs) comprise a diverse array of synthetic chemicals that resist environmental degradation. They are increasingly recognised as endocrine-disrupting compounds (EDCs). These chemicals, found in non-stick cookware, food packaging, and industrial waste, accumulate in human tissues and fluids, raising substantial concerns regarding their impact on female reproductive health. Epidemiological studies have demonstrated associations between PFAS exposure and reduced fertility; nevertheless, the underlying molecular pathways remain inadequately understood. This narrative review investigates the multifaceted effects of PFASs on ovarian physiology, including its disruption of the hypothalamic–pituitary–ovarian (HPO) axis, alteration of anti-Müllerian hormone (AMH) levels, folliculogenesis, and gonadotropin receptor signalling. Significant attention is directed towards the emerging association between PFASs and polycystic ovarian syndrome (PCOS), wherein PFAS-induced hormonal disruption may exacerbate metabolic issues and elevated androgen levels. Furthermore, we analyse the current data regarding PFAS exposure in women undergoing treatment based on assisted reproductive technologies (ARTs), specifically in vitro fertilisation (IVF), highlighting possible associations with diminished oocyte quality, suboptimal embryo development, and implantation failure. We examine potential epigenetic and transgenerational alterations that may influence women’s reproductive capabilities over time. This study underscores the urgent need for further research and regulatory actions to tackle PFAS-related reproductive toxicity, particularly in vulnerable populations, such as women of reproductive age and those receiving fertility treatments. Full article

Avian leukosis virus subgroup J (ALV-J), an α-retrovirus, mediates infection by binding to the host-specific receptor chNHE1 (chicken sodium–hydrogen exchanger type 1), leading to immunosuppression and tumorigenesis, which severely threatens the sustainable development of the poultry industry. Studies have shown that the tryptophan residue at position 38 (W38) of the chNHE1 protein is the critical site for ALV-J infection. In this study, we employed the CRISPR/Cas9 system to construct a lentiviral vector targeting the W38 site of chNHE1, transfected it into chicken primordial germ cells (PGCs), and validated its antiviral efficacy through ALV-J infection assays, successfully establishing an in vitro gene-editing system for chicken PGCs. The constructed dual lentiviral vector efficiently targeted the W38 site. PGCs isolated from 5.5- to 7-day-old chicken embryos were suitable for in vitro gene editing. Stable fluorescence expression was observed within 24–72 h post-transfection, confirming high transfection efficiency. ALV-J challenge tests demonstrated that no viral env gene expression was detected in transfected PGCs at 48 h or 72 h post-infection, while high env expression was observed in control groups. After 7 days of infection, p27 antigen ELISA tests were negative in transfected groups but positive in controls, indicating that W38-deleted PGCs exhibited strong resistance to ALV-J. This study successfully generated ALV-J-resistant gene-edited PGCs using CRISPR/Cas9 technology, providing a novel strategy for disease-resistant poultry breeding and advancing avian gene-editing applications. Full article

Sweet taste plays a pivotal role in human dietary behavior and metabolic regulation. With the increasing incidence of metabolic disorders linked to excessive sugar intake, the development and accurate evaluation of new sweeteners have become critical topics in food science and public health. However, the structural diversity of sweeteners and their complex interactions with sweet taste receptors present major challenges for standardized sweetness detection. This review offers a comprehensive and up-to-date overview of sweet taste transmission mechanisms and current detection methods. It outlines the classification and sensory characteristics of both conventional and emerging sweeteners, and explains the multi-level signaling pathway from receptor binding to neural encoding. Key detection techniques, including sensory evaluation, electronic tongues, and biosensors, are systematically compared in terms of their working principles, application scope, and limitations. Special emphasis is placed on advanced biosensing technologies utilizing receptor–ligand interactions and nanomaterials for highly sensitive and specific detection. Furthermore, an intelligent detection framework integrating molecular recognition, multi-source data fusion, and artificial intelligence is proposed. This interdisciplinary approach provides new insights and technical solutions to support precise sweetness evaluation and the future development of healthier food systems. Full article

Virus-like nanoparticles (VNPs) based on Moloney murine leukemia virus represent a well-established platform for the expression of heterologous molecules such as cytokines, cytokine receptors, peptide MHC (pMHC) and major allergens, but their application for inducing protective anti-viral immunity has remained understudied as of yet. Here, we variably fused the wildtype SARS-CoV-2 spike, its receptor-binding domain (RBD) and nucleocapsid (NC) to the minimal CD16b-GPI anchor acceptor sequence for expression on the surface of VNP. Moreover, a CD16b-GPI-anchored single-chain version of IL-12 was tested for its adjuvanticity. VNPs expressing RBD::CD16b-GPI alone or in combination with IL-12::CD16b-GPI were used to immunize BALB/c mice intramuscularly and subsequently to investigate virus-specific humoral and cellular immune responses. CD16b-GPI-anchored viral molecules and IL-12-GPI were well-expressed on HEK-293T-producer cells and purified VNPs. After the immunization of mice with VNPs, RBD-specific antibodies were only induced with RBD-expressing VNPs, but not with empty control VNPs or VNPs solely expressing IL-12. Mice immunized with RBD VNPs produced RBD-specific IgM, IgG_2a and IgG₁ after the first immunization, whereas RBD-specific IgA only appeared after a booster immunization. Protein/peptide microarray and ELISA analyses confirmed exclusive IgG reactivity with folded but not unfolded RBD and showed no specific IgG reactivity with linear RBD peptides. Notably, booster injections gradually increased long-term IgG antibody avidity as measured by ELISA. Interestingly, the final immunization with RBD–Omicron VNPs mainly enhanced preexisting RBD Wuhan Hu-1-specific antibodies. Furthermore, the induced antibodies significantly neutralized SARS-CoV-2 and specifically enhanced cellular cytotoxicity (ADCC) against RBD protein-expressing target cells. In summary, VNPs expressing viral proteins, even in the absence of adjuvants, efficiently induce functional SARS-CoV-2-specific antibodies of all three major classes, making this technology very interesting for future vaccine development and boosting strategies with low reactogenicity. Full article

In B-cell chronic lymphocytic leukemia (B-CLL), hypodiploidy is a rare but aggressive subtype of the disease with a very bad prognosis. Hypodiploidy, in contrast to normal B-CLL chromosomal aberrations, is marked by widespread genomic instability, which promotes treatment resistance and quick illness development. Its persistence after treatment implies that chromosomal loss gives cancerous clones a selection edge, which is made worse by telomere malfunction and epigenetic changes. Since thorough genetic profiling has a major impact on patient outcomes, advanced diagnostic methods are crucial for early detection. Treatment approaches must advance beyond accepted practices because of its resistance to traditional medicines. Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor (CAR) T-cell therapy are two potential new therapeutic modalities. Relapse and treatment-related morbidity continue to be limiting concerns, despite the noteworthy improvements in outcomes in high-risk CLL patients receiving HSCT. Although more research is required, CAR T-cell treatment is effective in treating recurrent B-ALL and may also be used to treat B-CLL with hypodiploidy. Novel approaches are essential for enhancing patient outcomes and redefining therapeutic success when hypodiploidy challenges established treatment paradigms. Hypodiploidy is an uncommon yet aggressive form of B-CLL that has a very bad prognosis. Hypodiploidy represents significant chromosomal loss and structural imbalance, which contributes to a disordered genomic environment, in contrast to more prevalent cytogenetic changes. This instability promotes resistance to certain new drugs as well as chemoimmunotherapy and speeds up clonal evolution. Its persistence after treatment implies that hypodiploid clones have benefits in survival, which are probably strengthened by chromosomal segregation issues and damaged DNA repair pathways. Malignant progression and treatment failure are further exacerbated by telomere erosion and epigenetic dysregulation. The need for more sensitive molecular diagnostics is highlighted by the fact that standard karyotyping frequently overlooks hypodiploid clones, particularly those concealed by endoreduplication, despite the fact that these complications make early and correct diagnosis crucial. Hypodiploidy requires a move toward individualized treatment because of their link to high-risk genetic traits and resistance to conventional regimens. Although treatments like hematopoietic stem cell transplantation and CAR T-cells show promise, long-term management is still elusive. To improve long-term results and avoid early relapse, addressing this cytogenetic population necessitates combining high-resolution genomic technologies with changing therapy approaches. Full article