Search Results (5,667)

Lymphatic vessels are a kind of heterogeneous and versatile component of the lymphatic system, with a unique ability to respond to environmental changes in different organs. The heterogeneity and plasticity of lymphatic endothelial cells (LECs) and defective lymphatic architecture are critical for organ-specific lymphatic function. Moreover, lymphatic vessels have a dual effect on tumor microenvironment (TME), and lymphangiogenesis, an active and dynamic player, is a hallmark of cancer progression and treatment resistance. Dysregulation of lymphatic vessels and uncontrolled lymphangiogenesis contribute to the pathogenesis of many diseases, including cancer. Increasing evidence has indicated that lymphangiogenesis provides a critical target for inhibiting lymphatic metastasis, in which immune checkpoint inhibitors, either alone or combined with chemotherapy, may have a therapeutic value. This article reviews the current status of tumor-associated lymphangiogenesis and lymphatic remodeling, as well as the crosstalk among LECs, immune cells and cancer cells, which will help to further understand the role of lymphangiogenesis in cancer progression, metastasis, and therapy. Full article

This paper proposes a compact polarimetric CTLR mode calibration method using only two dihedral reflectors. The method leverages the property that the dihedral scattering matrix is unaffected by double-pass Faraday rotation, effectively eliminating the interference of Faraday rotation on distortion parameter estimation. By selecting any two from four dihedral reflectors rotated at 0°, 22.5°, 45°, and 67.5°, the system distortion parameters can be estimated. To resolve the two-fold solution ambiguity inherent in the estimation process, two ambiguity elimination methods are proposed: Method I selects the solution with equivalent crosstalk magnitude less than 0 dB based on the prior knowledge that the transmit antenna is dominated by right-hand circular polarization; Method II employs cross-validation using different dihedral combinations with distinct product constants, applicable when the prior knowledge does not hold. Through simulation analysis, the algorithm’s sensitivity to receive crosstalk levels, signal-to-noise ratio, and polarization orientation angle shift is evaluated. The results demonstrate that to maintain residual receive imbalance amplitude within ±1 dB, phase within ±10°, and residual equivalent crosstalk below −30 dB, the system received crosstalk must be lower than −25 dB, the signal-to-noise ratio must exceed 35 dB, and polarization orientation angle shift should be controlled within ±1°. The effectiveness of the proposed algorithm is validated using fully polarimetric calibrated GaoFen-3 satellite data, achieving root mean square errors of 0.10 dB, 1.13°, and 0.42 dB for amplitude imbalance, phase imbalance, and equivalent crosstalk amplitude, respectively. Comparative analysis demonstrates that the proposed method achieves significantly higher calibration accuracy than existing approaches, with substantial improvements in parameter estimation precision. Full article

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment paradigm for hepatocellular carcinoma (HCC), establishing them as the cornerstone of systemic therapy for advanced stages of the disease. Nonetheless, the response rate remains limited, with only 15% to 20% of HCC patients benefiting from ICIs. Approximately 70% to 80% of cases exhibit resistance to anti-PD1 therapy. Therefore, exploring the biomarkers that can be used to identify the response of patients with HCC to immunotherapy and elucidating the potential mechanisms of immunotherapy resistance contribute to the development of predictive biomarkers and are significant for overcoming resistance and enhancing treatment efficacy. This review synthesizes the current understanding of both primary and acquired resistance mechanisms to ICIs in HCC. Compared with existing reviews, this article uniquely integrates the latest evidence on metabolic reprogramming and tumor immune microenvironment (TIME) remodeling in HCC. It also emphasizes the mechanistic crosstalk between oncogenic signaling, immunosuppression, and metabolic adaptation, providing an updated and more comprehensive framework for understanding ICI resistance. It provides a valuable reference for future research aimed at overcoming therapeutic resistance in this malignancy. Full article

Plasminogen activator inhibitor-1 (PAI-1) is a central regulator of the fibrinolytic system and is increasingly recognized for its pivotal roles in a broad spectrum of physiological and pathological processes. In addition to its classical function in fibrinolysis, accumulating evidence highlights the involvement of PAI-1 in cellular senescence, differentiation, fibrosis, thrombosis, and tumorigenesis. This review systematically summarizes recent advances in understanding the multifaceted biological functions of PAI-1, with a particular emphasis on its dual regulatory roles in cellular differentiation and senescence. Through manual curation and analysis of the literature, we constructed a PAI-1-centered signaling network associated with differentiation and further integrated this framework with known senescence-related pathways. This integrative approach aims to elucidate the crosstalk between differentiation and senescence mediated by PAI-1. By providing an in-depth overview of PAI-1 functions across various experimental models, this review offers a theoretical foundation for exploring its potential as a therapeutic target and presents novel perspectives for the development of intervention strategies for complex chronic diseases. Full article

Microinflammation serves as a central mechanism linking metabolic diseases and cancer. This study integrates gene expression profiles from irritable bowel syndrome (IBS), obesity, type 2 diabetes (T2D), colorectal cancer (CRC), renal cell carcinoma (RCC), and pancreatic cancer (PC) to identify shared molecular drivers of inflammation-mediated pathology. Weighted gene co-expression network analysis (WGCNA) revealed three highly preserved modules (blue, brown, turquoise) enriched in RNA processing, spliceosome assembly, ribosome biogenesis, and proteostasis regulation. Key hub genes, along with regulatory miRNAs have interconnected networks that modulate transcription, mRNA maturation, protein synthesis, and inflammatory signaling. Although classical inflammatory pathways were not directly enriched, their activity appears to be indirectly shaped by disruptions in RNA-processing and proteostasis machinery. Additionally, gut microbiota-derived products and altered metabolic states may further reinforce these transcriptional and post-transcriptional imbalances. Collectively, these findings reveal conserved molecular signatures that bridge microinflammation, metabolic disease, and oncogenesis, and highlight potential diagnostic and therapeutic targets centered on RNA regulation, proteostasis, and miRNA-mediated control Full article

In this work, a layout-level design methodology is presented for Low-Noise Amplifiers (LNAs), targeting a wide frequency spectrum from RF to millimeter-wave (mmWave) bands, and implemented using a 22 nmFDSOI CMOS process. A nested inductor structure is introduced at RF frequencies to reduce silicon footprint, with magnetic crosstalk effects characterized through electromagnetic (EM) simulations using Ansys^® RaptorX, Release 2024 R2, ANSYS, Inc. and integrated into the design process. Single-ended LNA architectures are employed for RF bands, while at mmWave frequencies, a differential topology is adopted to enhance linearity and enable simultaneous input and output impedance matching. An EM-based verification flow is applied across all designs to ensure RF/mmWave design flow compatibility, simulation accuracy, and enhanced performance. The proposed designs are evaluated using key metrics including input/output matching, reverse isolation, forward gain, noise figure, linearity ($I{P}_1,I{P}_3$), stability factor, power consumption, and total chip area to quantify the efficiency of the proposed methodology. The simulation results demonstrate that nested inductors are highly effective for area reduction in RF LNAs, while differential topologies are more suitable for mmWave designs, providing a unified framework for area-efficient and high performance LNA implementation. Full article

Insulin resistance develops when skeletal muscle (SM), adipose tissue (AT), and the liver fail to respond adequately to insulin, a dysfunction closely intertwined with chronic low-grade inflammation. This combination leads to compensatory hyperinsulinemia, dysglycemia, and metabolic stress, driving major disorders such as type 2 diabetes, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disease. Both adipokines and myokines are central modulators of this metabolic–inflammatory axis. In obesity, diabetes, MASLD, and thyroid dysfunction, alterations in myokines such as myostatin, irisin, fibroblast growth factor 21 (FGF-21), apelin, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-15 (IL-15) influence glucose uptake, lipid oxidation, mitochondrial function, and systemic inflammation. Exercise-induced myokines exert insulin-sensitizing and anti-inflammatory effects, whereas myostatin and tumor necrosis factor-alpha (TNF-α) promote metabolic impairment. These pathways reveal extensive crosstalk between SM and key metabolic organs—including the liver, pancreas, AT, intestine, heart, and thyroid gland. In metabolic disease, inflammation-driven changes in deiodinase activity and triiodothyronine (T3) availability further link muscle dysfunction with thyroid imbalance. The aim of this narrative review was to elucidate the complex interplay between myokines, adipokines, inflammation, and insulin resistance, and to clarify their clinical relevance in metabolic and thyroid disorders. Given this integrative role of SM, sarcopenia should be recognized as a clinical marker of metabolic or thyroid dysregulation, and preserving muscle mass through structured physical activity should be a core therapeutic target. Full article

Oxidative stress (OS) reflects a pathologic imbalance between excessive production of reactive oxygen species (ROS) and insufficient antioxidant defenses. Growing evidence indicates that a healthy gut microbiota (GM) is essential for regulating redox homeostasis, whereas gut dysbiosis contributes to elevated ROS levels and oxidative damage in DNA, lipids, and proteins. This redox disequilibrium initiates a cascade of cellular disturbances—including synaptic dysfunction, altered receptor activity, excitotoxicity, mitochondrial disruption, and chronic neuroinflammation—that can, in turn, impair cognitive and social functioning in metabolic and neuropsychiatric disorders via epigenetic mechanisms. In this review, we synthesize current knowledge on (1) how OS contributes to cognitive and social deficits through epigenetic dysregulation; (2) the role of disrupted one-carbon metabolism in epigenetically mediated neurological dysfunction; and (3) mechanistic links between leaky gut, OS, altered GM composition, and GM-derived epigenetic metabolites. We also highlight emerging microbiota-based therapeutic strategies capable of mitigating epigenetic abnormalities and improving cognitive and social outcomes. Understanding the OS–microbiota–epigenetic interplay may uncover new targetable pathways for therapies aimed at restoring brain and behavioral health. Full article

The plant plasma membrane serves as the primary interface for perceiving extracellular signals, a function largely mediated by plasma membrane receptors (PMRs). In wheat (Triticum aestivum), the functional characterization of these receptors is impeded by the species’ large, hexaploid genome, which results in extensive gene duplication and functional redundancy. This review synthesizes current knowledge on wheat PMRs, covering their diversity, classification, and signaling mechanisms, with a particular emphasis on their central role in plant immunity. We highlight the remarkable structural and functional diversification of PMR families, which range in size from 10 members, as seen in the case of wheat leaf rust kinase (WLRK), to over 3424 members in the receptor-like kinase (RLK) family. Furthermore, we reviewed the role of PMRs in being critical for detecting a wide array of biotic stimuli, including pathogen-associated molecular patterns (PAMPs), herbivore-associated molecular patterns (HAMPs), and symbiotic signals. Upon perception, PMRs initiate downstream signaling cascades that orchestrate defense responses, including transcriptional reprogramming, cell wall reinforcement, and metabolic changes. The review also examines the complex cross-talk between immune receptors and other signaling pathways, such as those mediated by brassinosteroid and jasmonic acid receptors, which underpin the delicate balance between growth and defense. Finally, we bridge these fundamental insights to applications in crop improvement, delineating strategies like marker-assisted selection, gene stacking, and receptor engineering to enhance disease resistance. After identifying key obstacles such as genetic redundancy and pleiotropic effects, we propose future research directions that leverage multi-omics, systems biology, and synthetic biology to fully unlock the potential of wheat PMRs for sustainable agriculture. Full article

Heat shock transcription factors (HSFs) have long been recognized for their essential role in mediating thermotolerance via the activation of heat shock proteins (HSPs). Recent studies, however, have significantly broadened this view, revealing that HSFs function as versatile transcriptional regulators orchestrating plant adaptation to a wide range of abiotic and biotic stresses. This review synthesizes current knowledge of HSF structure, activation, and canonical roles in the heat shock response, while emphasizing emerging insights into their diverse functions beyond heat stress. Evidence from both model and crop species demonstrates that many HSFs confer tolerance to a broad range of stresses, including drought, cold, salinity, oxidative stress, and pathogen attack, through intricate crosstalk with hormonal (e.g., ABA, SA, JA) and redox signaling pathways, as well as MAPK-mediated phosphorylation. We also discuss biotechnological strategies such as CRISPR/Cas-mediated genome editing, stress-inducible promoter engineering, and synthetic transcriptional circuits that offer promising avenues for fine-tuning HSF expression and enhancing multi-stress resilience in crops. A deeper understanding of HSF multifunctionality not only advances our comprehension of plant stress biology but also provides a foundation for engineering resilient crops in the context of global climate change. Full article

T cells and B cells are central components of the adaptive immune system, orchestrating immune responses through a complex network of interactions. This review explores the dynamic interplay between T and B cells, focusing on their development, activation, and functional coordination in immune defense. T cells provide essential help to B cells through cytokine signaling and direct cell–cell interactions, facilitating antibody production and affinity maturation in germinal centers. Conversely, B cells contribute to antigen presentation and cytokine modulation, influencing T cell differentiation and function. The regulation of these interactions is critical for maintaining immune homeostasis, preventing autoimmunity, and enhancing vaccine efficacy. Dysregulation of T-B cell crosstalk is implicated in various immune disorders, including autoimmune diseases and immunodeficiencies. Recent advances in immunotherapy have targeted these pathways to modulate immune responses in conditions such as cancer, infections, and inflammatory diseases. This review synthesizes current knowledge on T and B cell physiology, highlighting emerging research on their cooperative mechanisms. Full article

Crosstalk between elements in ultrasonic transducer arrays significantly degrades image quality in medical ultrasound systems by introducing noise and reducing spatial resolution. This review provides a comprehensive overview of the origins of crosstalk—acoustic, mechanical, and electrical—and the main characterization methods used to analyze it, including direct measurements, impedance analysis, finite element modeling, and equivalent circuit approaches. Emphasis is placed on recent advances in passive and active mitigation strategies, such as material coatings, structural decoupling, phononic crystals, adaptive filtering, and impedance matching. A key finding is that the optimal crosstalk reduction method depends strongly on the transducer technology employed—whether CMUT, PMUT, or bulk PZT. The review highlights the importance of tailoring mitigation techniques to the physical properties and operating conditions of each technology. By synthesizing current knowledge and identifying remaining challenges—particularly the role of filler material losses—this work offers a solid foundation for the development of next-generation ultrasound arrays with enhanced imaging performance. Full article

Valine-glutamine motif proteins (VQ), plant-specific transcriptional co-regulators harboring the conserved FxxhVQxhTG motif, play pivotal roles in coordinating plant stress adaptation through dynamic interactions with WRKY transcription factors (WRKY), mitogen-activated protein kinases (MAPKs) cascades, and hormone signaling pathways. Evolutionary analyses reveal the characteristics of their evolutionary protection and ancient origin, with lineage-specific expansion via genome duplication events. Structurally, compact genes lacking introns and the presence of intrinsic disordered regions (IDRs) facilitate rapid stress responses and versatile protein interactions. Functionally, VQ proteins orchestrate abiotic stress tolerance (e.g., drought, salinity, temperature extremes) by modulating reactive oxygen species (ROS) homeostasis, osmotic balance, and abscisic acid/salicylic acid (ABA/SA)-mediated signaling. Concurrently, they enhance biotic stress resistance via pathogen-responsive WRKY-VQ modules that regulate defense gene expression and hormone crosstalk. Despite advances, challenges persist in deciphering post-translational modifications, tissue-specific functions, and cross-stress integration mechanisms. Harnessing CRISPR-based editing and multi-omics approaches will accelerate the exploitation of VQ genes for developing climate-resilient crops. This review synthesizes the molecular architecture, evolutionary dynamics, and multifunctional regulatory networks of VQ proteins, providing a roadmap for their utilization in sustainable agriculture. Full article

Patients with multiple traumas, particularly those with traumatic brain injury (TBI), are among the most challenging cases in intensive care medicine. Although early orotracheal intubation and invasive mechanical ventilation (IMV) are essential for airway protection and neurological treatment, they significantly increase the risk of lower respiratory tract infection (LRTI), including ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). These complications are particularly prevalent among neurocritical patients due to the distinctive interaction between the brain, lungs and immune system. This narrative review examines the current evidence on the mechanisms underlying the brain–lung–immune axis; the diagnostic challenges in identifying respiratory infections in mechanically ventilated TBI patients; and optimal approaches to empirical or quasi-targeted antimicrobial therapy based on diagnostic algorithms and rapid molecular techniques. Severe TBI induces neurogenic inflammation, autonomic dysregulation, and immunosuppression, thereby increasing susceptibility to pulmonary infections. The ‘triple hit hypothesis’ best explains this cascade: sympathetic hyperactivity (first hit), iatrogenic ventilatory injury (second hit), and intestinal dysbiosis with systemic immune dysregulation (third hit). VAP diagnosis remains challenging due to the lack of universal criteria, the overlap with systemic inflammatory response syndrome, and the low specificity of radiological and clinical signs. VAT may represent an intermediate stage within a continuum of ventilator-associated infection. Recent evidence supports the selective use of nebulized antibiotics for VAT, advocating an individualized, locally adapted empirical approach to VAP treatment. Syndromic molecular panels can accelerate the identification of pathogens, enabling the earlier and more appropriate selection of antimicrobials and improving outcomes while preserving stewardship. Understanding the brain–lung–immune axis and improving diagnostic accuracy are essential to enhancing the treatment of respiratory infections in neurocritical care. Integrating clinical assessment, biomarkers and rapid microbiological testing enables timely, targeted therapy and reduces the misuse of antimicrobials. Full article

Pancreatic β-cells are metabolically active endocrine cells with a high oxygen demand to sustain glucose-stimulated insulin secretion (GSIS). Hypoxia, arising from vascular disruption, islet isolation, or pathological states such as type 2 diabetes (T2D) and obstructive sleep apnoea (OSA), is a potent metabolic stressor that impairs β-cell function, survival, and differentiation. At the molecular level, hypoxia-inducible factors (HIF-1α and HIF-2α) orchestrate transcriptional programs that shift β-cell metabolism from oxidative phosphorylation to glycolysis, modulate mitochondrial function, and regulate survival pathways such as autophagy and mitophagy. Crosstalk with nutrient-sensing mechanisms, redox regulation, growth factor signaling, and protein synthesis control further shapes adaptive or maladaptive outcomes. Hypoxia alters glucose, lipid, and amino acid metabolism, while mitochondrial dysfunction, oxidative stress, and inflammatory signaling contribute to progressive β-cell failure. Therapeutic strategies including incretin hormones, GABAergic signaling, erythropoietin, ChREBP inhibition, and activation of calcineurin–NFAT or oxygen-binding globins—offer potential to preserve β-cell viability under hypoxia. In islet transplantation, oxygen delivery technologies, ischemic preconditioning, mesenchymal stem cell–derived exosomes, and encapsulation systems show promise in mitigating hypoxic injury and improving graft survival. This review synthesizes current knowledge on β-cell responses to hypoxic stress, with emphasis on metabolic reprogramming, molecular signaling, and translational interventions, underscoring that targeted modulation of β-cell metabolism and oxygen handling can enhance resilience to hypoxia and improve outcomes in diabetes therapy and islet transplantation. Full article