Search Results (377)

Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by persistent hyperglycemia, hyperinsulinemia, and long-term cardiovascular complications. Another hallmark of T2D is disrupted hormonal homeostasis—marked by elevated levels of insulin and leptin and reduced adiponectin—which plays a crucial role in modulating immune cell function. Individuals with T2D exhibit a skewed immune profile, with an elevated secretion of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL17, and IL6, which are well-established drivers of vascular inflammation and dysfunction. Moreover, dysregulated metabolic hormones in T2D promote the acquisition of a pro-inflammatory phenotype in immune cells, suggesting that these hormones not only regulate energy balance but also serve as potent immune activators. Their dysregulation likely plays a significant—and perhaps underappreciated—role in the onset and progression of diabetic cardiovascular complications. Full article

Genomic islands (GIs) including integrative and conjugative elements (ICEs), prophages, and integrative plasmids are central drivers of horizontal gene transfer in bacterial plant pathogens. These elements often carry cargo genes encoding virulence factors, antibiotic and metal resistance determinants, and metabolic functions that enhance environmental adaptability. In plant-pathogenic species such as Pseudomonas syringae, GIs contribute to host specificity, immune evasion, and the emergence of novel pathogenic variants. ICEclc and its homologs represent integrative and mobilizable elements whose tightly regulated excision and transfer are driven by a specialized transcriptional cascade, while ICEs in P. syringae highlight the ecological impact of cargo genes on pathogen virulence and fitness. Pathogenicity islands further modulate virulence gene expression in response to in planta stimuli. Beyond P. syringae, GIs in genera such as Erwinia, Pectobacterium, and Ralstonia underpin critical traits like toxin biosynthesis, secretion system acquisition, and topoisomerase-mediated stability. Leveraging high-throughput genomics and structural biology will be essential to dissect GI regulation and develop targeted interventions to curb disease spread. This review synthesizes the current understanding of GIs in plant-pathogenic gammaproteobacteria and outlines future research priorities for translating mechanistic insights into sustainable disease control strategies. Full article

The soil-borne fungal pathogen Verticillium dahliae causes devastating vascular wilt disease in numerous crops, including cotton. In this study, we reveal that VdSOX1, a highly conserved sarcosine oxidase gene, is significantly upregulated during host infection and plays a multifaceted role in fungal physiology and pathogenicity. Functional deletion of VdSOX1 leads to increased fungal virulence, accompanied by enhanced microsclerotia formation, elevated carbon source utilization, and pronounced upregulation of effector genes, including over 50 predicted secreted proteins genes. Moreover, the VdSOX1 knockout strains suppress the expression of key defense-related transcription factors in cotton, such as WRKY, MYB, AP2/ERF, and GRAS families, thereby impairing host immune responses. Transcriptomic analyses confirm that VdSOX1 orchestrates a broad metabolic reprogramming that links nutrient acquisition to immune evasion. Our findings identify VdSOX1 as a central regulator that promotes V. dahliae virulence by upregulating effector gene expression and suppressing host immune responses, offering novel insights into the molecular basis of host–pathogen interactions and highlighting potential targets for disease management. Full article

Background/Objectives: Oral leukoplakia (OL) is a prevalent oral potentially malignant disorder. Despite its clinical relevance, the molecular basis of its progression to malignancy is not yet fully elucidated. This scoping review of systematic reviews and meta-analyses aimed to synthesize current knowledge and evidence gaps regarding the implications of hallmarks of cancer expression in OL malignant transformation. Methods: A systematic search was conducted in MEDLINE, Embase, DARE, and the Cochrane Library to identify systematic reviews (with or without meta-analysis) published up to April-2025. Results: Twenty-two systematic reviews were included. The most frequently explored hallmark was activation of invasion and metastasis (n = 12; 32.40%), followed by tumor-promoting inflammation (n = 10; 27.03%), evasion of growth suppressors (n = 8; 21.60%), sustained proliferative signaling (n = 3; 8.10%), energy metabolism reprogramming (n = 2; 5.40%), replicative immortality (n = 1; 2.70%), and resistance to cell death (n = 1; 2.70%). No evidence was found for angiogenesis or immune evasion in OL. Conclusions: Available evidence indicates that OL may develop oncogenic mechanisms in early stages of oral oncogenesis, especially those related to sustained proliferation, evasion of growth suppressor signals, and cellular migration and invasion. Chronic inflammation also may facilitate the acquisition of other hallmarks throughout the multistep process of oral carcinogenesis. These findings also reveal evidence gaps in underexplored hallmarks of cancer, which highlights the need to expand future primary- and secondary-level investigations to better define the molecular mechanisms underlying OL malignant transformation. Full article

Tonsils are secondary lymphoid organs that play a crucial role in the immunological response, with B cells being a major component involved in both innate and adaptive immunity. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and obstructive sleep apnea syndrome (OSAS) are both common pediatric conditions involving tonsillar pathology. In both syndromes, the molecular pathways dysregulated in tonsillar B cells are still to be understood. The study aimed to unravel and compare the proteomic profiles of tonsillar CD19+ B cells isolated from pediatric patients with PFAPA (n = 6) and OSAS (n = 6) to identify disease-specific molecular signatures. B cells were isolated from the tonsillar tissue using magnetic microbeads (with a purity of 93.50%). Proteomic analysis was performed by nanoLC-MS/MS with both data-dependent (DDA) and data-independent acquisition (DIA) methods, followed by comprehensive bioinformatic analysis. By merging DDA and DIA datasets, a total of 18.078 unique proteins were identified. Differential expression analysis revealed 83 proteins increased and 49 proteins decreased in OSAS B cells compared to PFAPA B cells (fold change ≥ 1.5 or ≤0.6, p < 0.05). Distinct pathway enrichments were highlighted, including alterations in the regulation of PTEN gene transcription, circadian gene expression, inflammasome pathways (IPAF and AIM2), and the metabolism of angiotensinogen to angiotensin. Specific proteins such as p53, Hdac3, RPTOR, MED1, Caspase-1, Cathepsin D, Chymase, and TLR2 (validated by WB) were shown to be differentially expressed. These findings reveal distinct proteomic signatures in tonsillar B cells from patients with PFAPA and OSAS, offering novel insights into the pathophysiology and potential avenues for biomarker discovery. Full article

Helicobacter pylori is a Gram-negative bacterium that infects almost half of the global population and is linked to gastric conditions like peptic ulcers and gastric cancer, as well as other diseases such as neurological disorders, cardiovascular problems, and iron deficiency anemia. Its survival in the acidic stomach environment is due to virulence factors like urease, flagella, and adhesion proteins (BabA, SabA). Current treatments involve a combination of antibiotics (clarithromycin, metronidazole, amoxicillin, tetracycline) and proton pump inhibitors, but increasing antibiotic resistance, especially to clarithromycin and metronidazole, poses a major challenge. Resistance mechanisms include mutations in drug targets, efflux pump overexpression, and enzymatic degradation of antibiotics. This has prompted exploration of alternative therapies targeting bacterial processes like urease activity, biofilm formation, and metabolic pathways (energy production, amino acid synthesis, iron acquisition). Natural compounds, such as chitosan and plant extracts, show promise in combating H. pylori growth and virulence. Vaccine development is also ongoing, with DNA vaccines showing potential for broad immune responses. However, no vaccine is yet close to widespread clinical use. Full article

Hydrodynamic slamming loads during water landing are one of the main concerns for the structural design and wave resistance performance of large amphibious aircraft. However, current existing sensors are not used for full-scale hydrodynamic load flight tests on complex models due to their large size, fragility, intrusiveness, limited range, frequency response limitations, accuracy issues, and low sampling frequency. Fibre-optic sensors’ small size, immunity to electromagnetic interference, and reduced susceptibility to environmental disturbances have led to their progressive development in maritime and aeronautic fields. This research proposes a novel hydrodynamic profile encapsulation method using ultra-thin surface-mounted micro-electromechanical system (MEMS) fibre-optic Fabry–Pérot pressure sensors (total thickness of 1 mm). The proposed sensor exhibits an exceptional linear response and low-temperature sensitivity in hydrostatic calibration tests and shows superior response and detection accuracy in water-entry tests of wedge-shaped bodies. This work exhibits significant potential for the in situ monitoring of hydrodynamic loads during water landing, contributing to the research of large amphibious aircraft. Furthermore, this research demonstrates, for the first time, the proposed surface-mounted pressure sensor in conjunction with a high-speed acquisition system for the in situ monitoring of hydrodynamic pressure on the hull of a large amphibious prototype. Following flight tests, the sensors remained intact throughout multiple high-speed hydrodynamic taxiing events and 12 full water landings, successfully acquiring the complete dataset. The flight test results show that this proposed pressure sensor exhibits superior robustness in extreme environments compared to traditional invasive electrical sensors and can be used for full-scale hydrodynamic load flight tests. Full article

(1) Background: CRISPR-Cas systems provide adaptive immunity against mobile genetic elements (MGEs) carrying antimicrobial resistance (AMR) genes. Carbapenem-resistant (CR) Klebsiella pneumoniae is a major public health concern, and the role of CRISPR-Cas in its resistance is understudied. This study explored CRISPR-Cas associations with multidrug resistance in clinical K. pneumoniae. (2) Methods: 400 K. pneumoniae isolates (200 CR and 200 carbapenem susceptible (CS)) were analyzed. Carbapenemase genes (bla_OXA-48, bla_NDM-1, bla_KPC-2), cas1, rpoB, and CRISPR1-3 loci were identified by PCR, while only CRISPR loci were sequenced. Genetic relatedness was assessed via PFGE, MLST, and spacer analysis. Statistical analysis utilized chi-squared and Fisher’s exact tests. (3) Results: CRISPR-Cas was present in 15.8% of isolates, mainly subtypes I-E and I-E* (93.3%), with CRISPR3 loci showing the greatest spacer diversity. Clonal complexes ST14/15/101 (CR) and ST35 (CS) were identified. bla_OXA-48 was linked to CRISPR-Cas-negative strains, while bla_NDM-1 and bla_KPC-2 were more frequent in CRISPR-Cas-positive strains (p < 0.0001). Imipenem/relebactam resistance was higher in CRISPR-Cas-negative isolates. (4) Conclusions: K. pneumoniae CRISPR-Cas systems correlate with specific carbapenemase profiles, suggesting pressure against bla_OXA-48 acquisition. The coexistence of I-E and I-E* subtypes highlight synergies in targeting MGEs. CRISPR loci could be tools for subtyping organisms following MLST. Full article

Infants born to HIV-positive mothers remain at significant risk of HIV acquisition despite maternal adherence to antiretroviral therapy, cesarean delivery, and formula feeding. Our previous study reported that initiating early antiretroviral treatment at three days post-SIV infection resulted in approximately eighty percent of pediatric virologic remission. In this study, we investigated treatment outcomes in postnatally SHIV-exposed infant macaques when early intervention was delayed by two days, as well as the mechanisms underlying virologic control. The results showed that, although initiating treatment at five days post-exposure effectively suppressed viral replication, only one of the three infant macaques achieved a sustained state of virologic remission following analytical treatment interruption. Notably, this virus-controlled infant lacked detectable virus-specific immunity, including neutralizing antibodies, cytotoxic T cell responses, and antibody-dependent cellular cytotoxicity. These findings highlight the critical importance of early treatment initiation as a key determinant of virologic control in HIV-exposed, infected infants. This study provides valuable insights for guiding early pediatric HIV intervention strategies in clinical settings. Full article

The ability of a virus to be propagated within a host cell is dependent on a multitude of dynamic virus–host interactions. Live-cell imaging is an invaluable approach in the study of virus replication cycles and virus–host interactions as it can allow for the direct visualisation of key events and interactions in real time. These details can provide unique insights into many aspects of viral infections including the cellular pathways that are exploited by viruses, the evasion of host immune defences, and viral pathogenesis. This review summarises the live-cell fluorescence imaging approaches that have been developed and applied to study Flaviviridae virus family members that are responsible for significant public health burdens and outbreaks which, in many instances, are increasing in frequency and severity. We discuss how these approaches have expanded our understanding of fundamental stages of viral replication cycles by enabling the direct visualisation of the localisation, trafficking, and interactions of virus particles, proteins, and genomes at distinct stages. The strategies that can be employed to enhance the biological relevance of live-cell fluorescence imaging acquisitions are discussed, along with how live-cell imaging approaches can be further developed to increase resolution, enable multi-colour imaging, and support the long-term visualisation of multiple stages of a viral replication cycle. Full article

Single-cell RNA sequencing (scRNA-seq) has revolutionized neuroscience by enabling the analysis of cellular heterogeneity and dynamic molecular processes at the single-cell resolution. In spinal cord research, scRNA-seq provides critical insights into cell type diversity, developmental trajectories, and pathological mechanisms. This review summarizes recent progress in the application of scRNA-seq to spinal cord development, injury, and neurodegenerative diseases and discusses the current challenges and future directions. Relevant studies focusing on the key applications of scRNA-seq, including advances in spatial transcriptomics and multi-omics integration, were retrieved from PubMed and the Web of Science. scRNA-seq has enabled the identification of distinct spinal cord cell populations and revealed the gene regulatory networks driving development. Injury models have revealed the temporal dynamics of immune and glial responses, alongside potential regenerative processes. In neurodegenerative conditions, scRNA-seq highlights cell-specific vulnerabilities and molecular changes. The integration of spatial transcriptomics and computational tools, such as machine learning, has further improved the resolution of spinal cord biology. However, challenges remain in terms of data complexity, sample acquisition, and clinical translation. Single-cell transcriptomics is a powerful approach for understanding spinal cord biology. Its integration with emerging technologies will advance both basic research and clinical applications, supporting personalized and regenerative therapy. Addressing these technical and analytical barriers is essential to fully realize the potential of scRNA-seq in spinal cord science. Full article

The CRISPR-Cas system represents an adaptive immune mechanism found across diverse Archaea and Bacteria, allowing them to defend against invading genetic elements such as viruses and plasmids. Despite its broad distribution, the prevalence and complexity of CRISPR-Cas systems differ significantly between these domains. This study aimed to characterize and compare the genomic distribution, structural features, and functional implications of CRISPR-Cas systems and associated antibiotic resistance genes in 30 archaeal and 30 bacterial genomes. Through bioinformatic analyses of CRISPR arrays, cas gene architectures, direct repeats (DRs), and thermodynamic properties, we observed that Archaea exhibit a higher number and greater complexity of CRISPR loci, with more diverse cas gene subtypes exclusively of Class 1. Bacteria, in contrast, showed fewer CRISPR loci, comprising a mix of Class 1 and Class 2 systems, with Class 1 representing the majority (~75%) of the detected systems. Notably, Bacteria lacking CRISPR-Cas systems displayed a higher prevalence of antibiotic resistance genes, suggesting a possible inverse correlation between the presence of these immune systems and the acquisition of such genes. Phylogenetic and thermodynamic analyses further highlighted domain-specific adaptations and conservation patterns. These findings support the hypothesis that CRISPR-Cas systems play a dual role: first, as a defense mechanism preventing the integration of foreign genetic material—reflected in the higher complexity and diversity of CRISPR loci in Archaea—and second, as a regulator of horizontal gene transfer, evidenced by the lower frequency of antibiotic resistance genes in organisms with active CRISPR-Cas systems. Together, these results underscore the evolutionary and functional diversification of CRISPR-Cas systems in response to environmental and selective pressures. Full article

Myelodysplastic neoplasms (MDS) are a group of hematological malignancies originating from hematopoietic stem cells (HSCs), characterized by distinct clinical and/or molecular heterogeneity across different MDS subtypes. This review elucidates the pathogenesis of MDS from two main perspectives: the bone marrow microenvironment and recurrent genetic abnormalities. Abnormal bone marrow microenvironment initiates aberrant innate immune response in HSCs, with quantitative and/or functional alterations of immune cells that collectively establish an immunosuppressive microenvironment, and abnormal bone marrow mesenchymal stromal cells that support and promote the progression of MDS. In addition, this review synthesizes current evidence on the biological functions and pathogenic mechanisms of frequently mutated genes in MDS. Furthermore, emerging therapies based on the pathogenesis of MDS are evaluated and summarized. In summary, aberrant innate immune responses promote pyroptosis of HSCs and acquisition of recurrent genetic abnormalities, resulting in the transformation of HSCs into MDS blasts; the immunosuppressive milieu (especially in higher-risk MDS) facilitates immune evasion of MDS blasts, ultimately leading to disease progression. Future research should focus on the interplay between different genetic abnormalities and immune dysregulation, coupled with the development of novel therapies targeting multiple nodes of the pathogenic network, to overcome current challenges in the treatment of MDS. Full article

Mueller matrix polarimetry has great potential for tissue detection and clinical diagnosis due to its ability to provide rich microstructural information accurately. However, in practical in vivo tissue imaging based on backscattering Mueller matrix polarimetry, specular reflection is often inevitable, leading to overexposed regions and the following inaccurate polarization information acquisition of tissues. In this study, we probe the influence of specular reflection and overexposure on backscattering Mueller matrix polarimetry for tissue imaging and sensing. We investigate in detail the differentiation of polarization behaviors between the specular reflection and non-specular reflection tissue regions using a 3 × 3 backscattering Mueller matrix measurement. Then, we obtain the vertical projection profiles to further quantify the Mueller matrix elements of porcine liver tissue in different specular reflection regions. Finally, we calculate the polarization feature parameters derived from a 3 × 3 Mueller matrix and analyze their behavior in overexposed regions. Based on the quantitative analysis and comparisons, we obtain a group of polarization feature parameters with strong immunity to the specular reflection process. This study offers a strategy for selecting the polarization parameters during in vivo polarimetric imaging applications, provides valuable references for further eliminating the characterization errors induced by specular reflection, and may contribute to the advancement of quantitative tissue polarimetric imaging and sensing. Full article

This study proposes a novel virus propagation model designed explicitly for SCADA(supervisory Control and Data Acquisition) industrial networks. It addresses a critical limitation in existing models applied to the Internet and Industrial Internet of Things (IIoT)—their failure to account for inter-node information exchange processes. The model is inspired by the phenomenon that “immune” nodes in real-world and biological systems inhibit the spread of viruses by exchanging information. This model incorporates isolation strategies to curb virus transmission, considering the uncertainty of vulnerable device behavior. Central to this research are the assumptions of a nonlinear infection rate and dual delays, which better mirror the real-world conditions of industrial control networks. This approach diverges significantly from prior studies that relied on bilinear infection rate assumptions. This study constructed an SMIQR model through theoretical derivation and experimental validation. The model enables nodes to autonomously enhance their defenses after receiving risk information while accounting for the impact of inter-node information exchange. Experiments based on real-world data demonstrated the model’s effectiveness in simulating virus propagation and evaluating defense strategies, overcoming the limitations of traditional bilinear infection rate assumptions. Comparative experiments show that the SMIQR model significantly reduces the number of infected nodes in SCADA industrial networks, demonstrating its superior effectiveness in curbing virus spread. Furthermore, the research proposed dynamic isolation tactics that balance industrial operational continuity, providing SCADA industrial networks with a theoretical framework (incorporating nonlinear infection rates and dual delay characteristics) and practical defense solutions to curb malware spread without disrupting production. Full article