Search Results (124)

Population aging and widespread sedentary lifestyles have increased the prevalence of chronic non-communicable diseases, many of which are linked to progressive disruptions of cellular homeostasis. Autophagy, a conserved cellular degradation and recycling pathway, plays a central role in maintaining metabolic flexibility, proteostasis, and organ function. However, aging and physical inactivity impair autophagic regulation, thereby contributing to the development of sarcopenia, cardiovascular diseases, metabolic disorders, and neurodegenerative diseases. Physical exercise is a non-pharmacological intervention that can restore autophagic activity and confer systemic health benefits in multiple preclinical and clinical contexts. Increasing evidence indicates that these benefits are mediated not only by local tissue adaptations but also by complex inter-organ communication. Central to this process are exercise-induced bioactive factors, collectively termed exerkines, including myokines, cardiokines, adipokines, hepatokines, osteokines, and circulating miRNAs. Rather than acting independently, exerkines form an integrated signaling network that fine-tunes autophagic flux across multiple tissues. Exerkine-mediated regulation of autophagy involves key pathways such as AMPK/mTOR, FoxO, SIRT1, ULK1, and TFEB, thereby coordinating energy metabolism, mitochondrial quality control, inflammation, and protein turnover in skeletal muscle, heart, liver, adipose tissue, bone, and the central nervous system. This review summarizes current evidence on representative exerkines and their roles in autophagy-dependent inter-organ crosstalk, highlighting the exercise–exerkine–autophagy axis as a promising target for preventing and managing chronic diseases. Full article

Depression and osteoporosis frequently co-occur, presenting a significant and increasing clinical challenge, especially among older adults. Growing research highlights the bone–brain axis, a complex bidirectional communication network connecting the skeletal and central nervous systems, as a central mechanism linking these conditions. This review comprehensively examines the current knowledge of the molecular and cellular pathways within this axis that contribute to depression–osteoporosis interactions. It details how depression promotes bone loss through sustained hypothalamic–pituitary–adrenal axis activation, sympathetic nervous system overactivity, and chronic low-grade inflammation. This review also explores how bone-derived factors, including osteocalcin, lipocalin 2, and extracellular vesicles, cross the blood–brain barrier to influence brain function by regulating hippocampal neurogenesis, serotonin signaling, and neuroinflammation. This bidirectional communication is modulated by circadian rhythms and genetic factors. Understanding these pathways offers critical insights into the shared pathophysiology and reveals promising therapeutic targets. Interventions such as neuromodulation, customized exercise programs, and novel treatments focusing on bone-derived signals show potential for simultaneously addressing both mood disorders and bone health deterioration. This review emphasizes the need for an integrated system-based approach in clinical care that moves beyond traditional specialty-focused treatment to improve overall health outcomes, particularly for vulnerable elderly individuals. Full article

The large-scale deployment of electric power wireless private networks (EPWPNs) has significantly increased the number of base stations in substations, transmission corridors, and distribution terminals, leading to rapidly rising electricity expenditure for continuous wireless coverage and power-grid monitoring services. However, the increasing number of base stations deployed across substations and distribution networks has led to rising electricity expenditure, making cost-effective energy supply a critical challenge. To reduce the operating costs of base station clusters and enhance the economic efficiency of power supply, this paper proposes a multimodal power consumption optimization method that coordinates wind energy, solar energy, and energy storage based on user interaction behavior. First, considering user interaction characteristics and the complementarity of multiple energy sources, a dual-layer cellular network architecture consisting of macro- and micro-base stations is constructed. This architecture incorporates grid power purchases, wind power generation, and photovoltaic energy. An optimization model is then developed, which includes both equipment operation constraints and energy interaction constraints. Second, the key factors influencing energy consumption are analyzed using operational research methods. The existence of an optimal solution for the energy consumption function is demonstrated based on the Weierstrass optimization theorem. An energy-saving strategy for base stations under user group access is then derived using Karush–Kuhn–Tucker (KKT) conditions. Through spatio-temporal (ST) dynamic analysis, the coupling relationships among wind power, solar energy, energy storage, and grid electricity purchases are quantified. Based on this analysis, a multimodal cost optimization scheme utilizing dynamic bandwidth allocation is proposed. Simulation results demonstrate that, compared with traditional single-source power supply models and representative existing optimization schemes, the proposed multimodal energy scheduling framework can significantly reduce the operating cost of base station clusters while maintaining communication performance. Full article

Glioblastoma multiforme (GBM) is characterized by aggressive growth, extensive vascularization, high metabolic malleability, and a striking capacity for therapy resistance. Current treatments involve surgical resection and concomitant radiation therapy and chemotherapy, prolonging survival times marginally due to the therapy resistance that is built up by the tumor cells. A growing body of research has identified exosomes as critical enablers of therapy resistance. These nanoscale vesicles enable GBM cells to disseminate oncogenic proteins, nucleic acids, and lipids that collectively promote angiogenesis, maintain autophagy under metabolic pressure, and suppress apoptosis. As interest grows in targeting tumor communication networks, exosome-based therapeutic strategies have emerged as promising avenues for improving therapeutic outcomes in GBM. This review integrates current insights into two complementary therapeutic strategies: inhibiting exosome biogenesis and secretion, and engineering exosomes as precision vehicles for the delivery of anti-tumor molecular cargo. Key molecular regulators of exosome formation—including the endosomal sorting complex required for transport (ESCRT) machinery, tumor susceptibility gene 101 (TSG101) protein, ceramide-driven pathways, and Rab GTPases—govern the sorting and release of factors that enhance GBM survival. Targeting these pathways through pharmacological or genetic means has shown promise in suppressing angiogenic signaling, disrupting autophagic flux via modulation of autophagy-related gene (ATG) proteins, and sensitizing tumor cells to apoptosis by destabilizing mitochondria and associated survival networks. In parallel, advances in exosome engineering—encompassing siRNA loading, miRNA enrichment, and small-molecule drug packaging—offer new routes for delivering therapeutic agents across the blood–brain barrier with high cellular specificity. Engineered exosomes carrying anti-angiogenic, autophagy-inhibiting, or pro-apoptotic molecules can reprogram the tumor microenvironment and activate both the intrinsic mitochondrial and extrinsic ligand-mediated apoptotic pathways. Collectively, current evidence underscores the potential of strategically modulating endogenous exosome biogenesis and harnessing exogenous engineered therapeutic exosomes to interrupt the angiogenic and autophagic circuits that underpin therapy resistance, ultimately leading to the induction of apoptotic cell death in GBM. Full article

Multipotent mesenchymal stromal stem cells have captivated the scientific community in recent years due to their ability to differentiate into multiple adult cell types. Central to this potential are many members of the nuclear hormone receptor superfamily, comprising 48 ligand-modulated transcription factors involved in key biological processes such as metabolism, physiology, embryonic development, and reproduction. These transcription factors influence cellular fate by regulating gene expression networks critical for MSC specification, commitment, and differentiation. This review explores the role of nuclear receptors in MSC development, focusing on interactions with chromatin structure, co-regulatory complexes, and responsiveness to extracellular stimuli such as hormones, metabolic cues, and endocrine-disrupting chemicals. We conclude with a discussion of the dangers posed by exogenous and aberrant signaling through nuclear receptors. Full article

Extracellular vesicles (EVs) are emerging as key factors in maintaining cellular homeostasis, critical mediators of intercellular communication, potential biomarkers, and therapeutic tools. While small EVs have been extensively characterized, the molecular signatures of large EVs (including those generated during regulated cell death pathways) remain poorly defined. Here, we investigated the characteristics of large EVs released during apoptosis and pyroptosis by human monocytic cell lines (THP-1 and U937). Apoptosis was induced by staurosporine and blocked using the pan-caspase inhibitor Q-VD-OPh, whereas pyroptosis was triggered by LPS/nigericin and inhibited with a selective NLRP3 inhibitor. We found that both forms of regulated cell death markedly enhanced the release of large EVs. Both apoptotic and pyroptotic large EVs showed increased Annexin V binding and decreased CD9 expression compared with those released by healthy cells. Large EVs derived from apoptotic and pyroptotic cells exhibited distinct proteomic profiles. Pyroptotic large EVs carried interacting protein networks of RNA-binding proteins and chromatin-associated proteins many of which are known damage-associated molecular patterns or alarmins. In contrast, we found that a subpopulation of apoptotic large EVs was characterized by the presence of dsDNA, and active caspase-3/7. Together, our data shed light on the specific protein cargo of large EVs released by cells during apoptosis and pyroptosis. This study identifies candidate markers of large EVs released by dying cells and may enhance our understanding of the role of EVs in regulated cell death. Full article

Cystinosis is a rare lysosomal storage disorder characterized by defective cystine transport and progressive multi-organ damage, with the kidney being the primary site of pathology. In addition to the traditional perspective on lysosomal dysfunction, recent studies have demonstrated that cystinosis exerts a substantial impact on cellular energy metabolism, with a particular emphasis on oxidative pathways. Mitochondria, the central hub of ATP production, exhibit structural abnormalities, impaired oxidative phosphorylation, and increased reactive oxygen species. These factors contribute to proximal tubular cell failure and systemic complications. This review highlights the critical role of energy metabolism in cystinosis and supports the emerging idea of organelle communication. A mounting body of evidence points to a robust functional and physical association between lysosomes and mitochondria, facilitated by membrane contact sites, vesicular trafficking, and signaling networks that modulate nutrient sensing, autophagy, and redox balance. Disruption of these interactions in cystinosis leads to defective mitophagy, accumulation of damaged mitochondria, and exacerbation of oxidative stress, creating a vicious cycle of energy failure and cellular injury. A comprehensive understanding of these mechanisms has the potential to reveal novel therapeutic avenues that extend beyond the scope of cysteamine, encompassing strategies that target mitochondrial health, enhance autophagy, and restore lysosome–mitochondria communication. Full article

Soil salinity is a major constraint on global crop production, disrupting photosynthesis, ion homeostasis, and growth. Beyond the roles of classic osmoprotectants and antioxidant enzymes, flavonoids have emerged as versatile mediators of salt stress tolerance at the interface of redox control, hormone signaling, and developmental plasticity. This review summarizes current evidence on how salinity remodels flavonoid biosynthesis, regulation, and function from cellular to whole-plant scales. We first outline the phenylpropanoid–flavonoid pathway, with emphasis on transcriptional control by MYB, bHLH, and NAC factors and their integration with ABA, JA, and auxin signaling. We then discussed how post-synthetic modifications such as glycosylation and methylation adjust flavonoid stability, compartmentation, and activity under salt stress. Functional sections highlight roles of flavonoids in ROS scavenging, Na⁺/K⁺ homeostasis, membrane integrity, and the modulation of ABA/MAPK/Ca²⁺ cascades and noncoding RNA networks. Spatial aspects, including root–shoot communication and rhizosphere microbiota recruitment, are also considered. Based on this synthesis, we propose a flavonoid-centered stress network (FCSN), in which specific flavonoids function as key nodes that connect metabolic flux with hormonal crosstalk and stress signaling pathways. We argue that reconceptualizing flavonoids as central stress network regulators, rather than generic antioxidants, provides a basis for metabolic engineering, bio-stimulant design, and breeding strategies aimed at improving crop performance on saline soils. Full article

The paradigm of cellular vehicle-to-everything (C-V2X) communications assisted by unmanned aerial vehicles (UAVs) is poised to revolutionize the future of sixth-generation (6G) intelligent transportation systems, as outlined by the international mobile telecommunication (IMT)-2030 vision. This integration of UAV-assisted C-V2X communications is set to enhance mobility and connectivity, creating a smarter and reliable autonomous transportation landscape. The UAV-assisted C-V2X networks enable hyper-reliable and low-latency vehicular communications for 6G applications including augmented reality, immersive reality and virtual reality, real-time holographic mapping support, and futuristic infotainment services. This paper presents a Markov chain model to study a third-generation partnership project (3GPP)-specified C-V2X network communicating with a flying UAV for task offloading in a Federated Learning (FL) environment. We evaluate the impact of various factors such as model update frequency, queue backlog, and UAV energy consumption on different types of communication latency. Additionally, we examine the end-to-end latency in the FL environment against the latency in conventional data offloading. This is achieved by considering cooperative perception messages (CPMs) that are triggered by random events and basic safety messages (BSMs) that are periodically transmitted. Simulation results demonstrate that optimizing the transmission intervals results in a lower average delay. Also, for both scenarios, the optimal policy aims to optimize the available UAV energy consumption, minimize the cumulative queuing backlog, and maximize the UAV’s available battery power utilization. We also find that the queuing delay can be controlled by adjusting the optimal policy and the value function in the relative value iteration (RVI). Moreover, the communication latency in an FL environment is comparable to that in the gross data offloading environment based on Kullback–Leibler (KL) divergence. Full article

The complexity of adverse responses from radiation injury (RI) followed by physical trauma, namely, radiation combined injury (RCI), is unique and more pronounced than either insult alone due to a poor understanding of the integration of these insults at the molecular/cellular/tissue and/or organ levels. It was shown that mice receiving ⁶⁰Co γ-photon RCI with wounding had a lower LD_50/30 than RI alone. This survival synergism was observed in bone marrow and the gastrointestinal system, as evidenced by an increase in γ-H2AX expression in bone marrow cell DNA, loss of circulatory blood cells, elevation of serum cytokine concentration, and activation of nuclear factor-κB/inducible nitric oxide synthase, and an earlier onset of bacterial infection and sepsis after RCI than after RI was detected. Dysbiosis (imbalance of the gut microbiota) was observed. There remains a pressing need for both prophylactic countermeasures and therapeutic remedies to deal with RCI threats. Investigations of how RCI can affect this important network of communication between the gut microbiota and other organs, including the brain, lung, heart, liver, kidney, and skin, could lead to new and critical interventions and prevention strategies. This review provides an update on new RCI animal models, dynamic changes in cytokine expression, dysbiosis, as well as links between the gut microbiome and other organs after RCI. Full article

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the abnormal proliferation of B-lineage lymphocytes in the bone marrow (BM). The roles of immune cells within the BM microenvironment remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) provides the potential for groundbreaking insights into the pathogenesis of B-ALL. In this study, scRNA-seq was conducted on BM samples from 17 B-ALL patients (B-ALL cohorts) and 13 healthy controls (HCs). Bioinformatics analyses, including clustering, differential expression, pathway analysis, and gene set variation analysis, systematically identified immune cell types and assessed T-cell prognostic and metabolic heterogeneity. A metabolic-feature-based machine learning model was developed for B-ALL subtyping. Furthermore, T-cell–monocyte interactions, transcription factor (TF) activity, and drug enrichment analyses were performed to identify therapeutic targets. The results indicated significant increases in Pro-B cells, alongside decreases in B cells, NK cells, monocytes, and plasmacytoid dendritic cells (pDCs) among B-ALL patients, suggesting immune dysfunction. Clinical prognosis correlated significantly with the distribution of T-cell subsets. Metabolic heterogeneity categorized patients into four distinct groups (A–D), all exhibiting enhanced major histocompatibility class I (MHC-I)-mediated intercellular communication. The metabolic-based machine learning model achieved precise classification of B-ALL groups. Analysis of TF activity underscored the critical roles of MYC, STAT3, and TCF7 within the B-ALL immunometabolic network. Drug targeting studies revealed that dorlimomab aritox and palbociclib specifically target dysregulation in ribosomal and CDK4/6 pathways, offering novel therapeutic avenues. This study elucidates immunometabolic dysregulation in B-ALL, characterized by altered cellular composition, metabolic disturbances, and abnormal cellular interactions. Key TFs were identified, and targeted drug profiles were established, demonstrating the significant clinical potential of integrating immunological mechanisms with metabolic regulation for the treatment of B-ALL. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3⁺ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3⁺/CD44⁺ cells in femoral and tibial cartilage and meniscus. Ki67⁺ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44⁺. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA. 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

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive cartilage disorder caused by biallelic variants in CCN6, which encodes the matricellular protein WISP3. Although WISP3 is thought to contribute to extracellular matrix (ECM) homeostasis, its precise molecular role in PPD remains unclear. To elucidate how disease-associated CCN6 variants affect chondrocyte function, we overexpressed four variants—p.Cys52*, p.Tyr109*, p.Gly83Glu, and p.Cys114Trp—all located within the IGFBP domain, and evaluated their impact on parameters including redox balance, ER stress, ECM remodeling, gene expression, and protein–protein interactions. The p.Cys52* variant resulted in rapid degradation of WISP3, indicating a complete loss-of-function. The p.Tyr109* variant disrupted ECM regulation, markedly reducing protein interaction capacity, which was correlated with elevated mitochondrial ROS (mtROS) levels and triggered a strong response that led to programmed cell death. Although both missense variants yielded full-length proteins, their effects diverged significantly: p.Gly83Glu induced minor cellular alterations, whereas p.Cys114Trp caused severe protein destabilization, increased ROS accumulation, and high levels of ER stress. Proteomic analysis revealed that p.Cys114Trp acquired novel interaction partners, suggesting a potential gain-of-function mechanism. Collectively, these findings demonstrate that the functional consequences of CCN6 variants depend not only on variant type or domain location but also on their positional and structural context. The distinct cellular responses elicited by each variant underscore the importance of functional validation in modeling PPD pathogenesis and offer valuable biological and therapeutic perspectives. Full article

Waveforms define the shape, structure, and frequency characteristics of signals, whereas modulation schemes determine how information symbols are mapped onto these waveforms for transmission. Their appropriate selection plays a critical role in determining the efficiency, robustness, and reliability of data transmission. In wireless communications, the choice of waveform influences key factors, such as network capacity, coverage, performance, power consumption, battery life, spectral efficiency (SE), bandwidth utilization, and the system’s resistance to noise and electromagnetic interference. This paper provides a comprehensive analysis of the waveforms and modulation schemes used across successive generations of mobile cellular networks, exploring their fundamental differences, structural characteristics, and trade-offs for various communication scenarios. It also situates this analysis within the historical evolution of mobile standards, highlighting how advances in modulation and waveform technologies have shaped the development and proliferation of cellular networks. It further examines criteria for waveform selection—such as SE, bit error rate (BER), throughput, and latency—and discusses methods for assessing waveform performance. Finally, this study presents a comparative evaluation of modulation schemes across multiple mobile generations, focusing on key performance metrics, with the BER analysis conducted through MATLAB simulations. Full article