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40 pages, 1196 KB  
Review
Metabolic Rewiring in MASLD: From Disease Mechanisms to Precision Medicine
by Amedeo Lonardo and Ralf Weiskirchen
Metabolites 2026, 16(8), 529; https://doi.org/10.3390/metabo16080529 - 27 Jul 2026
Viewed by 847
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), a leading cause of chronic liver disease, encompasses a continuum from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. This review aimed to synthesize current evidence on how metabolomic, lipidomic, and spatial [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), a leading cause of chronic liver disease, encompasses a continuum from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. This review aimed to synthesize current evidence on how metabolomic, lipidomic, and spatial multi-omic approaches illuminate MASLD pathogenesis and support precision hepatology. Methods: A structured narrative review was conducted through searches of PubMed, Scopus, and Web of Science, complemented by manual screening of key references. Studies were prioritized when they addressed MASLD biology, metabolic rewiring, lipid remodeling, mitochondrial dysfunction, inflammatory and fibrogenic pathways, gut–liver–adipose crosstalk, biomarker development, or therapeutic monitoring. Results: The reviewed evidence identifies MASLD as a systemic metabolic disorder shaped by excess lipid flux, enhanced de novo lipogenesis, impaired mitochondrial adaptation, oxidative and endoplasmic reticulum stress, sterile inflammation, and hepatic stellate-cell activation. Recurrent metabolomic signatures include altered amino acid, fatty acids, bile acid, and microbial co-metabolite pathways. Lipidomic studies consistently implicate depletion of protective polyunsaturated fatty acids, lysophosphatidylcholines, and phosphatidylcholines, in association with accumulation of diacylglycerols and ceramides, in the transition from steatosis to MASH and fibrosis. Emerging spatial and multi-omic analyses further resolve cell-specific metabolic niches involving hepatocytes, macrophages, endothelial cells, and stellate cells. Conclusions: Metabolomics provides a mechanistic and translational bridge between molecular injury, histological progression, and non-invasive risk stratification in MASLD. Future progress requires standardized analytical workflows, longitudinal validation, causal pathway interrogation, and integration with imaging, genetics, microbiome profiling, and treatment-response phenotyping. Clinical implementation will require standardized platforms, transparent metabolite identification, external validation across diverse populations, cost-effectiveness analyses, and regulatory-grade evidence of clinical utility. Full article
(This article belongs to the Special Issue Metabolomics and MASLD: Pathways, Biomarkers, and Clinical Insights)
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17 pages, 856 KB  
Review
Global Coupling and Phase Locking in Laser Diode Arrays: A Review of Talbot Cavity Research
by Yikun Yang, Chenyao Huang, Jie Chen, Yixian Xie, Yuying Feng, Xi Cao, Zhengjie Guo, Fuyueyang Tan, Chuanjie Xin, Zaijin Li, Yi Qu and Lin Li
Micromachines 2026, 17(8), 896; https://doi.org/10.3390/mi17080896 - 26 Jul 2026
Viewed by 364
Abstract
High-power semiconductor laser diode arrays (LDAs) are pivotal for applications such as optical pumping, industrial manufacturing, and precision measurement, yet they face inherent bottlenecks in balancing high output power, superior beam quality, and stable phase synchronization. The Talbot cavity, leveraging the Talbot self-imaging [...] Read more.
High-power semiconductor laser diode arrays (LDAs) are pivotal for applications such as optical pumping, industrial manufacturing, and precision measurement, yet they face inherent bottlenecks in balancing high output power, superior beam quality, and stable phase synchronization. The Talbot cavity, leveraging the Talbot self-imaging effect, has emerged as a core external cavity technology to address these challenges, enabling global coupling and passive phase locking of LDAs. This paper systematically reviews the research progress of Talbot cavities in phase-locked LDAs under global coupling. It elaborates on the fundamental principle of Talbot-effect-based phase locking, along with the structural characteristics and working mechanisms of three typical Talbot cavity configurations: conventional Talbot cavities, V-shaped Littrow–Talbot cavities, and monolithic integrated Talbot cavities. Furthermore, it summarizes key experimental advancements of LDAs, covering diverse laser media (e.g., near-infrared, blue, terahertz, and mid-infrared antimonide lasers) and array scales ranging from a few to thousands of emitters, with representative performance metrics including far-field visibility up to 99%, narrowed spectral linewidths achieving 20–50 pm for blue LDA, and output power exceeding 200 W. Numerical simulation progress on supermodel stability and parameter optimization is also discussed. Finally, the current challenges, such as thermal crosstalk and integration complexity, are analyzed, and future prospects involving intelligent control and novel physical mechanisms are outlined. This review aims to provide a comprehensive reference for the further development and practical application of high-brightness phase-locked laser sources. Full article
(This article belongs to the Special Issue Advanced Optoelectronic Materials/Devices and Their Applications)
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16 pages, 1346 KB  
Article
Occupant-Centred Acoustic Assessment of Teachers’ Responses to Sound Sources in a Secondary School
by Hang Fu, Jiayi Zhou, Jie Zhang, Rumei Han and Yuan Zhang
Buildings 2026, 16(14), 2894; https://doi.org/10.3390/buildings16142894 - 21 Jul 2026
Viewed by 444
Abstract
The acoustic quality of a school’s indoor environment affects the health, performance and comfort of the teachers who work in it, yet assessment often reduces that environment to a single overall level. In a cross-sectional case study of one secondary school in China, [...] Read more.
The acoustic quality of a school’s indoor environment affects the health, performance and comfort of the teachers who work in it, yet assessment often reduces that environment to a single overall level. In a cross-sectional case study of one secondary school in China, all 148 teachers rated eleven school sound-source categories on audibility, annoyance and interference with teaching and office concentration, and reported perceived noisiness, voice raising, voice strain, fatigue, emotional distress and noise sensitivity, while selected-room acoustic measurements provided site context not matched to individual respondents. Ratings across the eleven sources were dominated by one component, but the resulting composite score was not associated with all teacher responses alike. Source load was associated with emotional distress, voice raising and perceived noisiness but not fatigue, which instead tracked voice strain, whereas emotional distress was associated most strongly with noise sensitivity. In exploratory source-specific models, traffic and other external sources had the largest associations with perceived noisiness, whereas playground activity and student talking had the largest associations with voice raising. No tested subgroup interaction survived false-discovery-rate correction. The selected-room measurements documented conditions compatible with source intrusion and raised vocal effort. The findings support an occupant-centred, source-resolved approach to school indoor acoustics and provide hypotheses for future multi-school testing. Full article
(This article belongs to the Section Building Energy, Physics, Environment, and Systems)
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30 pages, 5179 KB  
Review
Methyl Jasmonate: A Key Regulator of Postharvest Fruit Quality Maintenance and Its Crosstalk with Phytohormones
by Shouhui Wei, Yue Zhong, Qiao Tan, Xiuqiao Wu, Jinlian Yuan, Lijuan Wei and Yiqing Liu
Horticulturae 2026, 12(7), 790; https://doi.org/10.3390/horticulturae12070790 - 28 Jun 2026
Viewed by 780
Abstract
Methyl jasmonate (MeJA) is a volatile phytohormone that regulates diverse physiological processes and mediates plant responses to various external stressors. Recently, MeJA has emerged as a promising postharvest alternative for the improvement of fruit quality. Here, we reviewed the research progress on the [...] Read more.
Methyl jasmonate (MeJA) is a volatile phytohormone that regulates diverse physiological processes and mediates plant responses to various external stressors. Recently, MeJA has emerged as a promising postharvest alternative for the improvement of fruit quality. Here, we reviewed the research progress on the application of exogenous MeJA to postharvest fruits, focusing on its regulatory roles in regulating fruit ripening, improving postharvest fruit quality, alleviating postharvest chilling injury, and controlling postharvest diseases. The potential physiological and biochemical mechanisms mainly include: (1) inducing endogenous JA biosynthesis; (2) mediating JA signaling transduction; (3) enhancing antioxidant capacity; (4) inducing the defense system; (5) regulating sucrose metabolism; and (6) modulating energy metabolism. Additionally, a specific finding is the possible crosstalk of applications of MeJA and various phytohormones during postharvest fruit storage, which provides a new method and insight for the fruit quality industry. Full article
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24 pages, 10002 KB  
Article
A Wireless Analog Interface with Near Frame-Accurate Synchronization for Optical Motion Capture
by Taylor M. Pierce, Emerson Noble, Lucas Davis, Jesus Wilkins and Kenneth J. Loh
Electronics 2026, 15(13), 2787; https://doi.org/10.3390/electronics15132787 - 24 Jun 2026
Viewed by 500
Abstract
Human kinematic analysis is an increasingly important tool in biomechanics, human performance, and wearable sensing research. Many emerging sensing modalities utilize custom sensors requiring accurate temporal alignment with ground-truth biomechanical movement data. Optical motion capture systems provide high-fidelity kinematic measurements but operate as [...] Read more.
Human kinematic analysis is an increasingly important tool in biomechanics, human performance, and wearable sensing research. Many emerging sensing modalities utilize custom sensors requiring accurate temporal alignment with ground-truth biomechanical movement data. Optical motion capture systems provide high-fidelity kinematic measurements but operate as closed, self-contained systems, making time synchronization with external sensor data non-trivial, particularly in wireless and mobile contexts. This work presents a wireless analog interface system built using commercially available components that enables alignment between analog sensor data (e.g., from custom wearables and Internet-of-Things devices) and a commercial motion capture system. The proposed architecture consists of a wearable data acquisition node and a receiver node interfaced directly with an optical motion capture system, allowing synchronized recording of analog sensor signals alongside kinematic data. Notably, the system reconstructs signals into the commercial hardware interface rather than relying on triggers or sync outputs, resulting in a single data file containing kinematics and sensor readings. Benchtop testing demonstrated a mean end-to-end frame delay of ~6 ms, with 95% of the sample exhibiting delay within 15 ms. Accounting for the typical offset, this leaves a standard deviation of 4 ms, within one motion capture frame of the true timestamp (at 100 Hz). Voltage reconstruction accuracy was within 30 mV across the tested conditions, with gain compression below 2.7%. Adjacent channel crosstalk remained below −83 dB across all test conditions. The use of commercial off-the-shelf components supports replication and adaptation by other research groups and integration with different optical motion capture systems. Full article
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8 pages, 2101 KB  
Article
Microwave Near Field Imaging of Externally Injected Signals in an Encapsulated Electronic Device
by Qiang Zhu, Yangfan Zhang, Xin Li, Huanfei Wen, Jun Tang and Jun Liu
Micromachines 2026, 17(6), 711; https://doi.org/10.3390/mi17060711 - 10 Jun 2026
Viewed by 362
Abstract
Addressing the challenges of electromagnetic compatibility testing and non-destructive inspection of internal structures in miniaturized electronic devices. This paper reports a non-destructive testing method based on wide-field imaging using diamond nitrogen-vacancy (NV) centers, and systematically demonstrates its application on a black-epoxy-encapsulated Universal Serial [...] Read more.
Addressing the challenges of electromagnetic compatibility testing and non-destructive inspection of internal structures in miniaturized electronic devices. This paper reports a non-destructive testing method based on wide-field imaging using diamond nitrogen-vacancy (NV) centers, and systematically demonstrates its application on a black-epoxy-encapsulated Universal Serial Bus (USB) flash drive. In the experiment, a swept microwave signal from 2.82 GHz to 2.97 GHz was sequentially injected into the four external interface pins of the USB drive. A bulk diamond served as the quantum sensing layer, and optically detected magnetic resonance (ODMR) was employed to perform wide-field imaging of the microwave field distribution on the surface of the signal lines within a 1 × 1 mm2 region of interest. The experimental results show that the microwave field distributions corresponding to different interface channels are significantly different. Based on these differences, the connection relationship between each signal line and its corresponding interface pin can be clearly identified, and the differences in field distribution as well as crosstalk characteristics among channels can be revealed. The method established in this work provides an effective technical pathway for non-destructive electromagnetic testing and functional verification of electronic products. Full article
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28 pages, 2022 KB  
Review
Terrestrial Plant- and Algal-Derived Biostimulants as Modulators of ROS and Hormone Networks in Crop Abiotic Stress Resilience
by Pavel Minkov, Tsanko S. Gechev and Aakansha Kanojia
Plants 2026, 15(7), 992; https://doi.org/10.3390/plants15070992 - 24 Mar 2026
Viewed by 1341
Abstract
Abiotic stresses severely constrain crop productivity by disrupting cellular redox homeostasis and hormone signaling. Although individual stresses differ in origin, plant responses converge on a conserved regulatory system centered on reactive oxygen species (ROS) and phytohormone crosstalk. Controlled ROS production in chloroplasts, mitochondria [...] Read more.
Abiotic stresses severely constrain crop productivity by disrupting cellular redox homeostasis and hormone signaling. Although individual stresses differ in origin, plant responses converge on a conserved regulatory system centered on reactive oxygen species (ROS) and phytohormone crosstalk. Controlled ROS production in chloroplasts, mitochondria and the apoplast functions as a signaling mechanism that interacts dynamically with abscisic acid, auxin, ethylene, jasmonate and cytokinin pathways through shared regulatory nodes, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and redox-sensitive transcriptional cascades. Endogenous metabolites, including phenolics, terpenoids, carotenoids, alkaloids, polyamines, glutathione and signaling peptides, are embedded within this network and modulate its amplitude and sensitivity. In parallel, non-microbial biostimulants derived from seaweeds, higher plants, protein hydrolysates and humic substances have been widely reported to enhance crop performance under abiotic stress. However, mechanistic integration between biostimulant research and plant stress signaling remains limited. In this review, we propose that terrestrial plant- and algal-derived biostimulants act not as external substitutes for hormones or antioxidants but as modulators of endogenous ROS–hormone signaling hubs. We first synthesize the current understanding of redox–hormone integration under abiotic stress, then examine endogenous metabolites as intrinsic regulators of this network, followed by an analysis of biostimulants in relation to shared regulatory nodes. By positioning biostimulant action within the established redox–hormone network, we provide a mechanistic framework that links stress biology with agronomic application and supports rational strategies to enhance crop resilience. Full article
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34 pages, 2385 KB  
Review
New Insight into Endophytic Fungi–Plant Symbioses Under Climate Change: Molecular Crosstalk, Nutrient Exchange, and Ecosystem Resilience
by Ayaz Ahmad, Mian Muhammad Ahmed, Aadab Akhtar, Chen Shuihong, Zeeshan Zafar, Rehmat Ullah, Muhammad Asim, Zhenli He and Muhammad Bilal Khan
Appl. Microbiol. 2026, 6(3), 47; https://doi.org/10.3390/applmicrobiol6030047 - 17 Mar 2026
Cited by 8 | Viewed by 2966
Abstract
Fungal endophytes are microorganisms that inhabit plant tissues without causing disease and emerge as critical mediators of plant stress tolerance, nutrient acquisition, and ecosystem resilience under diverse climate change scenarios. Their unique position within the host allows them to modulate physiological responses more [...] Read more.
Fungal endophytes are microorganisms that inhabit plant tissues without causing disease and emerge as critical mediators of plant stress tolerance, nutrient acquisition, and ecosystem resilience under diverse climate change scenarios. Their unique position within the host allows them to modulate physiological responses more closely than external microbiota. This review explores how endophytic fungi contribute to plant adaptation under climate-induced stresses such as heat, salinity, drought, pollution, and nutrient limitation, with a focus on molecular crosstalk, functional trait modules, and metabolic trade-offs. Key findings emphasize multilayered signaling systems, including MAMP/DAMP recognition, phytohormone regulation, immune tuning, ROS dynamics, and effector deployment, while emerging mechanisms such as cross-kingdom RNA and extracellular vesicle (EV)-mediated exchange are discussed as promising but currently limited in empirical validation within many endophytic systems. Endophytes also enhance nutrient exchange through conditional carbon-for-benefit trade and may shape rhizosphere microbiota and soil activities through plant-mediated inputs. Integrative multi-omics approaches provide predominantly correlational insights into the mechanistic basis of these effects, linking molecular function to ecosystem and community outcomes. These insights have potential applications in climate-resilient agriculture, phytoremediation, and ecosystem restoration; however, their large-scale implementation requires further field-based validation and context-specific assessment. Future priorities should focus on trait-based selection, ecological modeling, and biosafety evaluation to translate microbial functions into reliable field-level strategies that support sustainable crop performance under accelerating environmental stress. Full article
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20 pages, 5298 KB  
Article
Bioinformatics Profiling of a Paeoniflorin-Associated “Macrophage–Lactylation” Axis in Hepatocellular Carcinoma: An LDHA-Based Prognostic Model and Structural Computational Evidence
by Kongli Fan, Ruiqi Zhao, Jialing Sun, Jing Li, Minling Lv, Mengqing Ma, Jiesheng Guo and Xiaozhou Zhou
Int. J. Mol. Sci. 2026, 27(5), 2495; https://doi.org/10.3390/ijms27052495 - 9 Mar 2026
Cited by 1 | Viewed by 1188
Abstract
Hepatocellular carcinoma (HCC) progression is shaped by crosstalk between the tumor immune microenvironment (TME) and metabolic reprogramming. This study aims to characterize a macrophage–lactylation molecular axis in HCC and to develop a quantitative prognostic stratification model. Using the TCGA-LIHC cohort, differentially expressed genes [...] Read more.
Hepatocellular carcinoma (HCC) progression is shaped by crosstalk between the tumor immune microenvironment (TME) and metabolic reprogramming. This study aims to characterize a macrophage–lactylation molecular axis in HCC and to develop a quantitative prognostic stratification model. Using the TCGA-LIHC cohort, differentially expressed genes were intersected with Paeoniflorin (PF)-related targets, HCC disease targets, and macrophage-/lactylation-related genes to identify candidate genes. Prognostic genes were selected through Cox and LASSO-Cox analyses to construct a risk score model, followed by survival analysis and ROC curve evaluation. Immune infiltration was assessed using ESTIMATE and ssGSEA algorithms, and PF–protein binding interactions were explored via molecular docking and molecular dynamics simulations. Intersection analysis identified eight key genes, and prognostic model genes (HNRNPU, LDHA, and NPM1) were used to construct the prognostic model. High-risk patients exhibited significantly poorer overall survival (p < 0.001), with 1- and 3-year AUC values ranging from 0.70 to 0.90. HNRNPU was positively correlated with activated CD4 T cells (r = 0.385) and negatively correlated with eosinophils (r = −0.498). Molecular docking indicated favorable binding of PF to the model proteins, with the highest predicted affinity observed for LDHA (Vina score = −8.9 kcal/mol), and molecular dynamics simulations suggested the formation of a stable LDHA–PF complex during the later stage of the simulation. We propose a prognostic risk model for HCC constructed using three prognostic model genes and provide computational evidence linking PF to key molecular nodes such as LDHA. External cohort validation and experimental studies are warranted. Full article
(This article belongs to the Section Molecular Informatics)
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35 pages, 1095 KB  
Review
Cerebral Ischemia–Reperfusion Injury: Unraveling the Mitophagy–Oxidative Stress Axis for Neuroprotective Strategies
by Yanling Zhou, Baochun Luo, Tong Shang, Zengrong Wei and Wei Zou
Int. J. Mol. Sci. 2026, 27(5), 2448; https://doi.org/10.3390/ijms27052448 - 6 Mar 2026
Cited by 6 | Viewed by 1777
Abstract
Cerebral ischemia–reperfusion (I/R) injury is a major pathological contributor to neurological deterioration following ischemic stroke (IS) and remains a critical barrier to effective neuroprotection. Accumulating evidence indicates that cerebral I/R injury is driven not by isolated stress responses but by coordinated and dynamic [...] Read more.
Cerebral ischemia–reperfusion (I/R) injury is a major pathological contributor to neurological deterioration following ischemic stroke (IS) and remains a critical barrier to effective neuroprotection. Accumulating evidence indicates that cerebral I/R injury is driven not by isolated stress responses but by coordinated and dynamic interactions among multiple cellular pathways. Among these, the bidirectional crosstalk between mitophagy and oxidative stress has emerged as a central regulatory axis. Moderate oxidative stress can function as an adaptive signal, activating protective mitophagy through key pathways such as AMPK/ULK1 signaling and cardiolipin externalization, thereby facilitating mitochondrial quality control and maintaining cellular homeostasis. Conversely, appropriately regulated mitophagy limits excessive reactive oxygen species (ROS) production by removing dysfunctional mitochondria, forming a negative feedback mechanism. However, dysregulation or excessive activation of either process disrupts this balance, leading to a self-amplifying cycle of mitochondrial dysfunction and oxidative damage that exacerbates neuronal injury. This review systematically summarizes the molecular mechanisms governing the oxidative stress–mitophagy crosstalk in cerebral I/R injury, highlighting key signaling nodes and regulatory pathways that determine protective versus detrimental outcomes. Furthermore, we discuss emerging therapeutic strategies aimed at precisely modulating this axis in a spatiotemporal- and intensity-dependent manner. By integrating mechanistic insights with translational perspectives, this review provides a conceptual framework for developing targeted neuroprotective interventions based on coordinated regulation of mitochondrial quality control and redox homeostasis. Full article
(This article belongs to the Special Issue Molecular Diagnosis and Targeted Therapies in Ischemic Stroke)
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13 pages, 11722 KB  
Article
A 3D-Printed Pump-Free Multi-Organ-on-a-Chip Platform for Modeling the Intestine–Liver–Muscle Axis
by Rodi Kado Abdalkader and Takuya Fujita
Micromachines 2026, 17(2), 180; https://doi.org/10.3390/mi17020180 - 28 Jan 2026
Cited by 2 | Viewed by 1560
Abstract
The intestine–liver–muscle axis plays an essential role in drug and nutrient absorption, metabolism, and energy balance. Yet in vitro models capable of recapitulating this inter-organ communication remain limited. Here, we present a pump-free, 3D-printed multi-organ-on-a-chip device that enables dynamic co-culture of Caco-2 intestinal [...] Read more.
The intestine–liver–muscle axis plays an essential role in drug and nutrient absorption, metabolism, and energy balance. Yet in vitro models capable of recapitulating this inter-organ communication remain limited. Here, we present a pump-free, 3D-printed multi-organ-on-a-chip device that enables dynamic co-culture of Caco-2 intestinal epithelial cells, HepG2 hepatocytes, and primary human skeletal myoblasts (HSkMs) under gravity-driven oscillatory flow. The device consists of five interconnected chambers designed to accommodate Transwell cell culture inserts for intestine and muscle compartments and hydrogel-embedded hepatocyte spheroids in the central hepatic compartment. The device was fabricated by low-cost fused deposition modeling (FDM) using acrylonitrile butadiene styrene (ABS) polymers. Under dynamic rocking, oscillatory perfusion promoted inter-organ communication without the need for external pumps or complex tubing. Biological assessments revealed that dynamic co-culture significantly enhanced the characteristics of skeletal muscle, as indicated by increased myosin heavy chain expression and elevated lactate production, while HepG2 spheroids exhibited improved hepatic function with higher albumin expression compared with monoculture. Additionally, Caco-2 cells maintained stable tight junctions and transepithelial electrical resistance, demonstrating preserved intestinal barrier integrity under dynamic flow. These results establish the device as a versatile, accessible 3D-printed platform for modeling the intestine–liver–muscle axis and investigating metabolic cross-talk in drug discovery and disease modeling. Full article
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30 pages, 2436 KB  
Review
Advances in the Pathophysiology and Management of Cancer Pain: A Scoping Review
by Giustino Varrassi, Antonella Paladini, Y Van Tran, Van Phong Pham, Ameen A. Al Alwany, Giacomo Farì, Annalisa Caruso, Marco Mercieri, Joseph V. Pergolizzi, Alan D. Kaye, Frank Breve, Alberto Corriero, Christopher Gharibo and Matteo Luigi Giuseppe Leoni
Cancers 2026, 18(2), 259; https://doi.org/10.3390/cancers18020259 - 14 Jan 2026
Cited by 7 | Viewed by 4342
Abstract
Background/Objectives: Cancer pain affects 55–95% of patients with advanced malignancy, representing a complex syndrome involving nociceptive, neuropathic and nociplastic mechanisms. Despite therapeutic advances, two-thirds of patients with metastatic cancer experience inadequate pain control. This scoping review synthesizes recent advances in cancer pain pathophysiology [...] Read more.
Background/Objectives: Cancer pain affects 55–95% of patients with advanced malignancy, representing a complex syndrome involving nociceptive, neuropathic and nociplastic mechanisms. Despite therapeutic advances, two-thirds of patients with metastatic cancer experience inadequate pain control. This scoping review synthesizes recent advances in cancer pain pathophysiology and management, focusing on molecular and cellular mechanisms, emerging pharmacological, interventional and technological therapies and key evidence gaps to inform future precision-based pain management strategies. Methods: Following PRISMA-ScR methodology, we searched PubMed, Embase, Scopus, and Web of Science for studies published between January 2022 and September 2025. After screening 3412 records, 278 studies were included and analyzed across different domains: biological mechanisms, pharmacological management, interventional and neuromodulatory approaches, radiotherapy developments, and digital health innovations. Results: Recent mechanistic research reveals cancer pain arises from tumor–neuron–immune crosstalk, with malignant cells secreting neurotrophic factors that promote axonal sprouting and nociceptor sensitization. Genetic polymorphisms and epigenetic modifications contribute to inter-individual pain variability. Management strategies are evolving toward multimodal precision medicine: NSAIDs and opioids remain foundational, complemented by adjuvant agents and interventional procedures including nerve blocks, intrathecal delivery, and neuromodulation (spinal cord and dorsal root ganglion stimulation). Stereotactic body radiotherapy demonstrates superior analgesic durability versus conventional approaches. Digital health innovations, such as mobile applications, remote monitoring, wearables, and AI-enabled predictive models, enable continuous assessment and personalized treatment optimization. Conclusions: Cancer pain management is transitioning toward mechanism-based precision medicine integrating biological insights, advanced interventional techniques, and digital technologies. However, implementation challenges persist, including limited randomized trials for interventional approaches, the incomplete external validation of AI tools, and digital health equity concerns. Future research must prioritize prospective controlled studies and equitable integration into routine care. Full article
(This article belongs to the Special Issue Cancer Pain: Advances in Pathophysiology and Management)
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13 pages, 733 KB  
Review
G Protein-Coupled Receptors in Irritable Bowel Syndrome: Mechanisms and Therapeutic Opportunities
by Zhenya Zhu, Ziyu Liu, Yate He, Xiaorui He, Wei Zheng and Mizu Jiang
Int. J. Mol. Sci. 2026, 27(2), 752; https://doi.org/10.3390/ijms27020752 - 12 Jan 2026
Viewed by 1550
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, altered motility, and visceral hypersensitivity. Emerging evidence implicates G protein-coupled receptors (GPCRs) as key integrators of microbial, immune, endocrine, and neural signals in IBS pathophysiology. This review summarizes recent advances [...] Read more.
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, altered motility, and visceral hypersensitivity. Emerging evidence implicates G protein-coupled receptors (GPCRs) as key integrators of microbial, immune, endocrine, and neural signals in IBS pathophysiology. This review summarizes recent advances in understanding how GPCRs mediate gut immune regulation, microbiota–host crosstalk, metabolic signaling, and pain processing in IBS. Recent studies show that microbial metabolites (e.g., short-chain fatty acids, biogenic amines, and lipid mediators) signal through GPCRs on immune cells, epithelia, and neurons to influence intestinal homeostasis. On immune cells and neurons, GPCRs also mediate signals from external substances (such as fats, sugars, histamine, etc.) to regulate immune and neural functions. And there are challenges and future directions in targeting GPCRs for IBS, including patient heterogeneity and the complexity of host–microbiome interactions. This review provides a mechanistic framework for GPCR-based therapies in IBS. Full article
(This article belongs to the Special Issue Emerging Roles of the Gut-Brain Axis (GBA) in Health and Disease)
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13 pages, 22217 KB  
Article
Crosstalk Effects in a Dual ToF-Based Tactile–Proximity Sensing Platform Integrated in a Flat PMMA Light Guide
by Andrejs Ogurcovs, Ilze Aulika, Sergio Cartiel, Jorge Garcia-Pueyo and Adolfo Muñoz
Sensors 2025, 25(23), 7319; https://doi.org/10.3390/s25237319 - 2 Dec 2025
Viewed by 1169
Abstract
We investigate crosstalk effects in a dual-modality tactile–proximity sensing system based on Time-of-Flight (ToF) technology integrated within a flat poly(methyl methacrylate) (PMMA) light guide. Building on the OptoSkin framework, we employ two commercially available TMF8828 multi-zone ToF sensors, one configured for tactile detection [...] Read more.
We investigate crosstalk effects in a dual-modality tactile–proximity sensing system based on Time-of-Flight (ToF) technology integrated within a flat poly(methyl methacrylate) (PMMA) light guide. Building on the OptoSkin framework, we employ two commercially available TMF8828 multi-zone ToF sensors, one configured for tactile detection via frustrated total internal reflection (FTIR) and the other for external proximity measurements through the same transparent substrate. Controlled experiments were conducted using a 2 cm2 silicone pad for tactile interaction and an A4-sized diffuse white target for proximity detection. Additional measurements with a movable PMMA sheet were performed to quantify signal attenuation, peak broadening, and confidence degradation under transparent-substrate conditions. The results demonstrate that the TMF8828 can simultaneously resolve both contact-induced scattering and distant reflections, but that localized interference zones occur when sensor fields of view overlap within the substrate. Histogram analysis reveals the underlying multi-path contributions, providing diagnostic insight not available from black-box ToF devices. These findings highlight both the opportunities and limitations of integrating multiple ToF sensors into transparent waveguides and inform design strategies for scalable robotic skins, wearable interfaces, and multi-modal human–machine interaction systems. Full article
(This article belongs to the Section Optical Sensors)
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25 pages, 5047 KB  
Article
Integrative Single-Cell and Machine Learning Analysis Develops a Glutamine Metabolism–Based Prognostic Model and Identifies MSMO1 as a Therapeutic Target in Osteosarcoma
by Hui Ma, Haiyang Zhang, Johny Bajgai, Md. Habibur Rahman, Thu Thao Pham, Chaodeng Mo, Buchan Cao, Yeong-eun Choi, Cheol-Su Kim and Kyu-Jae Lee
Biomolecules 2025, 15(12), 1664; https://doi.org/10.3390/biom15121664 - 28 Nov 2025
Cited by 1 | Viewed by 1378
Abstract
Although metabolic pathways profoundly influence disease behavior, osteosarcoma (OS) still lacks a glutamine metabolism–based framework for patient stratification. By integrating single-cell RNA sequencing with bulk cohorts, we delineated a glutamine-associated transcriptional program and translated it into an externally validated, clinically oriented risk model. [...] Read more.
Although metabolic pathways profoundly influence disease behavior, osteosarcoma (OS) still lacks a glutamine metabolism–based framework for patient stratification. By integrating single-cell RNA sequencing with bulk cohorts, we delineated a glutamine-associated transcriptional program and translated it into an externally validated, clinically oriented risk model. After rigorous quality control and doublet removal, 19 clusters were annotated into 10 cell types. Glutamine metabolism–related gene (GRG) scores, quantified by five orthogonal algorithms (AUCell, UCell, singscore, ssGSEA, and AddModuleScore), revealed pronounced intratumoral heterogeneity, particularly within osteoblastic cells. A composite GRG score correlated with 641 genes, defining 188 differentially expressed genes; intersecting positively correlated and up-regulated genes yielded 91 candidates. Through a 10-fold cross-validated benchmark of 10 machine-learning algorithms and 101 combinations, Step-Cox [forward] + Ridge emerged as the optimal pipeline, producing a five-gene prognostic model (GPX7, COL11A2, CPE, MSMO1, SGMS2) with moderate yet reproducible performance in independent cohorts. Functionally, stable MSMO1 knockdown in U2OS cells suppressed proliferation, migration, and invasion; increased apoptosis; altered GS, GLS, and α-ketoglutarate; and dampened Wnt/β-catenin signaling. Clinically, the model stratifies OS patients into molecular risk subgroups with distinct outcomes, supporting identification of high-risk individuals and informing personalized glutamine-targeted or combination therapies. Mechanistically, glutamine metabolism shapes the OS tumor microenvironment by modulating immune-evasion and angiogenic cues, underscoring its dual role in metabolic adaptation and immune–metabolic crosstalk. Collectively, this study establishes a single-cell–anchored, glutamine-coupled state in OS, introduces an externally validated prognostic tool with translational promise but modest discriminative power, and positions MSMO1 as a metabolic–signaling node warranting further mechanistic and in-vivo investigation. Full article
(This article belongs to the Special Issue Cancer Biology: Machine Learning and Bioinformatics)
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