Search Results (3,154)

Background: Addictive disorders are highly heterogeneous and frequently comorbid, limiting the clinical utility of categorical diagnoses. Transdiagnostic pharmacology seeks to address these limitations by targeting symptom dimensions and shared neurobiological processes across addictions. Methods: We conducted a theory-driven narrative review of studies indexed in MEDLINE, PubMed, LILACS, and Web of Science (October–November 2025), integrating clinical, mechanistic, and dimensional evidence. Findings were organized using the Dysregulation Phenomena of the Three Main Modes of the Predostatic Mind and the Advanced Cognitive Emotional Regulation Therapy (DREXI3/ACERT) framework, which conceptualizes addiction as dysregulation across three interacting systems—Alarm, Seeking, and Balance—and six transdiagnostic symptom dimensions, with a proposed expansion into twenty clinically observable domains (TDPM-20). Results: Pharmacological interventions consistently target neurobiological systems related to stress, reward, impulsivity, and compulsivity. Across studies, the most clinically relevant outcomes remain abstinence, reduction in substance use, and treatment retention. While these outcomes are essential, expanding outcome frameworks to incorporate dimensional and mechanistically informed measures may enhance the identification of clinically meaningful subgroups. Across studies, multiple pharmacological classes show transdiagnostic potential, but their clinical application remains variably aligned with dimensional clinical profiles. Conclusions: A dimensionally oriented approach grounded in neurobiological principles may improve alignment between clinical processes and therapeutic strategies. The DREXI3/ACERT model provides a structured framework for individualized treatment planning and research integration. This approach should be understood as complementary to, rather than a replacement for, established evidence-based treatments for specific substance use disorders, particularly in contexts where therapeutic options remain limited or insufficient. Advancing transdiagnostic pharmacology will require broader dimensional stratification, expanded outcome frameworks capable of capturing patient heterogeneity, and integrative trial designs to strengthen precision psychiatry in addictive disorders. Full article

Natural product research has experienced substantial growth over the past two decades, driven by a renewed appreciation for the structural complexity and biological relevance of compounds derived from nature. Technological advances in separation science, spectroscopic characterization, and high-sensitivity bioassays have collectively restored natural products to a position of prominence in modern drug discovery efforts. Nature remains the most prolific source of bioactive molecular diversity, drawing from microorganisms, plants, and marine life to offer a vast reservoir of structurally novel scaffolds whose pharmacological potential remains largely unexplored. Effective extraction and isolation remain foundational to natural product research, as the quality and purity of isolated compounds directly govern the reliability of downstream biological evaluation. Recent years have witnessed remarkable innovation in this space, spanning green and designer solvent systems, pressurized and ultrasound-assisted extraction platforms, supercritical fluid techniques, and integrated purification workflows that dramatically reduce processing time while improving compound recovery and analytical throughput. Particularly noteworthy is the growing application of artificial intelligence and machine learning tools for solvent selection, extraction optimization, and metabolite dereplication, which in combination with advanced phase-separation strategies and informatic platforms have substantially expanded the scope of detectable and characterizable metabolites within complex biological matrices. This review summarizes recent progress in extraction and isolation methodologies supporting natural product research, with particular emphasis on combinatorial extraction strategies, next-generation solvent systems, and AI-driven applications that have collectively improved operational efficiency, selectivity, and analytical output over the past five years. Full article

Dysphagia and age-related oral processing limitations are rising with population aging and the growing burden of neurological diseases. Texture-modified diets remain the most common non-pharmacological intervention, yet conventional pureeing and thickening often yield meals with low visual appeal, variable textures, and diluted nutrient density, which contribute to reduced intake and malnutrition risk. Extrusion-based three-dimensional food printing, especially when combined with gel-derived edible inks, offers a digital route to standardize geometry, portioning, and texture while enabling individualized nutrition and sensory design. In the past three years, the field has progressed from simple single-ingredient pastes to engineered soft-matter systems including emulsion gels, high-internal-phase emulsion gels, Pickering-stabilized gels, bigels, and multi-material constructs enabled by dual and coaxial printing. These advances are underpinned by improved rheological windowing, microstructure engineering, and post-print gelation strategies such as ionic crosslinking, thermal setting, enzymatic bridging, and pH-triggered network formation. Meanwhile, dysphagia-oriented product development has matured from “shape recovery” demonstrations toward clinically relevant texture targets, leveraging the IDDSI tests to anchor swallowability. This review synthesizes the recent literature across materials science, food engineering, and clinical nutrition to connect gel microstructure to extrusion performance, post-processing stability, and oral processing outcomes that are relevant to older adults and dysphagia patients. We propose design principles for gel network selection, phase structuring, and process control that simultaneously satisfy print fidelity and swallowing safety targets. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden, yet effective therapeutic options remain limited. This study investigated the protective mechanisms of Astragalus membranous extract (AM) against high-fat diet (HFD)-induced MAFLD in mice using an integrated strategy combining network pharmacology, hepatic metabolomics, and 16S rRNA sequencing. UPLC–Q-Orbitrap–MS/MS identified 37 major constituents in AM, mainly phenolic acids and flavonoids. Iristectorin A, isorhamnetin, ononin, and rhamnocitrin were identified as key candidate compounds due to their relatively high abundance and confirmation as absorbed constituents in vivo. Network pharmacology and molecular docking indicated favorable interactions with hub targets (TNF, EGFR, and AKT1; binding energies < −5.0 kcal/mol) and highlighted the involvement of the AGE–RAGE signaling pathway and inflammation- and lipid metabolism-related processes. In vivo, AM significantly attenuated HFD-induced weight gain, decreased serum ALT and AST levels, and reduced hepatic lipid deposition. AM also alleviated oxidative stress by lowering malondialdehyde (MDA) and increasing superoxide dismutase (SOD) activity, while suppressing hepatic IL-1β and IL-6. Moreover, AM improved gut microbial homeostasis by restoring α-diversity and enriching beneficial genera, including Akkermansia and Bacteroides. Hepatic metabolomics further showed that AM partially normalized lipid metabolic disturbances, particularly glycerophospholipid and sphingolipid metabolism. Collectively, these results suggest that AM mitigates MASLD via a multi-component, multi-target mechanism, potentially through modulation of AGE–RAGE-associated inflammatory signaling and the gut–liver axis, supporting its development as a functional food-derived candidate for metabolic liver disorders. Full article

Background: The optimal timing of adjuvant chemotherapy after cytoreductive surgery in epithelial ovarian cancer remains uncertain, and perioperative wound-healing responses may transiently create a pro-tumorigenic and drug-resistant microenvironment. This study aimed to characterize time-dependent wound-induced transcriptomic alterations and to identify pharmacologic agents capable of reversing these responses. Methods: An ID8 murine ovarian cancer model was used to compare no treatment, anesthesia alone, and anesthesia plus surgical wounding mimicking futile laparotomy. Tumors were collected at baseline, 1 day (T1), 1 week (T2), and 2 weeks (T3) after intervention. RNA sequencing was performed, and wound-specific differentially expressed genes (WsDEGs) were defined by excluding anesthesia- and progression-related signatures. Functional enrichment analyses were conducted, followed by transcriptome-based drug repurposing using the REMEDY platform to identify compounds predicted to reverse wound-induced gene expression profiles. Results: Surgical wounding significantly increased tumor burden at T1. Transcriptomic analyses revealed distinct, time-dependent wound-associated programs. At T1, WsDEGs were enriched in inflammatory signaling, coagulation, angiogenesis, and immune cell migration, with Vorinostat and Homoharringtonine identified as top candidates to counteract these signatures. At T2, pathways related to cell survival, adhesion, and morphogenesis predominated, with LY-2090314, Artesunate, and Birinapant emerging as potential modulators. At T3, cell-cycle regulation and lipid metabolic pathways were dominant, and Fulvestrant, Atorvastatin, Imatinib, and ABT-737 were predicted to inhibit these processes. Conclusions: Perioperative surgical wounding induces dynamic, stage-specific transcriptomic programs that may promote ovarian cancer progression and alter drug responsiveness. These findings support time-adapted perioperative pharmacologic strategies to optimize postoperative cancer therapy. Full article

Fibromyalgia (FM) is a chronic pain syndrome characterized by central sensitization and impaired pain modulation, involving dysfunctional descending inhibitory pathways and altered nociceptive processing. These processes contribute to persistent musculoskeletal pain, difficulties with sleep, feelings of depression, and ongoing fatigue. Serotonin and norepinephrine are key mediators of pain control, and evidence indicates that dual reuptake inhibition provides superior analgesia compared to single-pathway approaches. Accordingly, serotonin–norepinephrine reuptake inhibitors (SNRIs), including milnacipran and duloxetine, approved for FM treatment, show favorable efficacy and tolerability compared with tricyclic antidepressants. This integrative literature review aimed to evaluate the impact of SNRIs on musculoskeletal pain, fatigue, depression, and quality of life in patients with FM by analyzing randomized clinical trials (RCTs), identified via PubMed/MEDLINE searches (2015–2025) in English/Portuguese using descriptors: “Fibromyalgia”, “Serotonin and Norepinephrine Reuptake Inhibitors”, “Duloxetine” and “Milnacipran”. From 195 records screened, 18 studies met inclusion criteria (9.2% inclusion rate); duloxetine evaluated in 16 studies (88.9%), milnacipran in 2 (11.1%); SNRIs demonstrated superior efficacy vs. placebo: pain reduction 30–40%, fatigue improvement 25%, quality of life enhancement 20%. SNRIs were overall more effective than placebo but did not achieve high levels of analgesia, underscoring the need for further research on long-term efficacy and comparisons with combination pharmacological and non-pharmacological therapies. SNRIs significantly alleviate musculoskeletal pain (30–50% of patients), fatigue, depression symptoms, and improve quality of life in FM versus placebo. Duloxetine showed superior efficacy for pain/depression; milnacipran excelled in sleep quality. Long-term studies and combination therapies warrant further investigation. Full article

Melatonin, a well-known antioxidant, has been widely used in sperm cryopreservation of various animals, but its regulatory mechanism in fish remains unclear. This first study on teleosts suggests a potential molecular mechanism by which melatonin may improve post-thaw sperm quality of Epinephelus fuscoguttatus via targeting mitochondrial function. Compared with the melatonin group, the MT1 receptor-inhibited group showed slightly higher sperm motility (77.09 ± 3.41% vs. 76.50 ± 1.10%), significantly inhibited mitochondrial permeability transition pore (mPTP) opening (12.64 ± 1.05% vs. 18.29 ± 1.38%), and maintained higher mitochondrial membrane potential (MMP; 85.86 ± 0.18% vs. 81.81 ± 0.69%), with both groups performing better than the control. In contrast, the MT2-inhibited and MT1/2 dual-inhibited groups exhibited reduced sperm quality compared with the MT group, suggesting that MT2 may serve as the core receptor for melatonin to regulate mitochondrial homeostasis in teleosts. Mechanistically, melatonin-activated MT2 potentially inhibits mPTP opening via the PI3K/Akt/GSK-3β pathway, and this protective effect was abrogated by the PI3K and GSK-3β inhibitors. This receptor-mediated process synergized with melatonin’s direct antioxidant effect, as ROS levels in all melatonin-treated groups were significantly lower than the control. This study is the first to find pharmacological evidence for the melatonin–MT2/PI3K/GSK-3β axis in maintaining teleost sperm mitochondrial function; it also reveals potential mechanistic differences between teleosts and mammals and fills a critical knowledge gap regarding this signaling cascade in teleost reproductive biology. Full article

Background/Objectives: Schizophrenia is a severe psychiatric disorder frequently characterised by sleep and circadian disturbances, which are closely linked to cognitive dysfunction, symptom exacerbation, and poor functional outcomes. A growing body of evidence implicates the orexin (hypocretin) system—an essential regulator of arousal, sleep–wake stability, metabolic processes, and motivated behaviour—in the pathophysiology and treatment response of psychotic disorders. We aimed to investigate the relationships between the orexinergic system and psychoses. Methods: On 3 March 2026, we searched the PubMed, Scopus, PsycInfo/Articles and Cinahl databases for studies dealing with the orexin system and psychotic disorders and treatment response. Results: We found 20 eligible studies reporting variable and inconsistent alterations in orexin signalling in patients with schizophrenia. Studies were mostly cross-sectional and heterogeneous in design. Antipsychotic medications interfere with orexin-dependent pathways, potentially contributing to both therapeutic effects and adverse outcomes such as sleep disruption and metabolic dysregulation. Conclusions: While evidence from preclinical studies could point to an influence of dopaminergic activity through orexinergic mechanisms, with possible attenuation of antipsychotic-induced motor side effects and improvement of attentional deficits associated with NMDA receptor hypofunction, the utility of dual orexin receptor antagonists (DORAs) in psychoses is unclear. Despite the high prevalence of insomnia in schizophrenia, its pharmacological management remains suboptimal, with current treatments often limited by reduced efficacy or tolerability concerns. DORAs, which are currently approved medications for the treatment of insomnia, represent a novel and mechanistically distinct therapeutic option that may improve sleep while modulating arousal- and cognition-related circuits relevant to psychosis. Full article

Sonchus oleraceus L., a member of the Asteraceae family native to Eurasia, is a herbaceous plant whose young stems and leaves are consumed globally as a medicinal and edible wild vegetable; it is rich in flavonoids and exhibits various pharmacological activities, including anti-inflammatory and anti-tumor effects. This study optimized the extraction process of flavonoids from Xinjiang S. oleraceus using response surface methodology and evaluated the anti-inflammatory activity of luteoloside in vitro. Based on single-factor experiments and Box–Behnken design, the effects of ethanol concentration, extraction time, solid-to-liquid ratio, and extraction temperature on flavonoid yield were investigated. The optimal extraction conditions were determined as ethanol concentration 62%, extraction time 30 min, solid-to-liquid ratio 1:91 g/mL, and extraction temperature 64 °C, with a flavonoid yield of 21.64 mg/g. After purification via polyamide column chromatography, the luteoloside content was determined by HPLC to be 44.06 μg/g. Cytotoxicity assays revealed that a luteoloside concentration of 100 μmol/L reduced the viability of Oryctolagus cuniculus colon epithelial cells to approximately 80%. ELISA results demonstrated that luteoloside significantly inhibited the release of pro-inflammatory factors, including TNF-α, while promoting the expression of the anti-inflammatory factor IL-10. These findings indicate that luteoloside effectively alleviates LPS-induced cellular inflammation. Full article

Ischemic cardiomyopathy is defined as coronary artery disease accompanied by left ventricular dysfunction with an ejection fraction equal to or less than 40%. The substrate of ischemic cardiomyopathy is heterogeneous, characterized by the coexistence of normal, stunned, hibernating, and scarred myocardium within the same myocardial region. Altogether, these components may represent different phases of a single pathological process. It is well-established that the assessment of isolated myocardial viability and ischemia alone has failed to reliably guide the indication for coronary artery bypass grafting (CABG). CABG in patients with low ejection fraction carries a significant risk of perioperative mortality and morbidity, largely related to the development of postcardiotomy shock. Preoperative optimization with pharmacologic or mechanical circulatory support (MCS) is often essential; the decision requires integrating multiple complex factors, including clinical presentation, response to optimization therapy, myocardial viability, the presence of hibernating or scarred myocardium, left ventricular end-systolic volume index, coronary angiography findings, hemodynamic assessment, and the Pulmonary Arterial Pressure Index score. A preoperative evaluation that incorporates anatomical, morphological, functional, and hemodynamic domains enables more precise selection and timing of MCS. Preemptive left ventricular unloading mitigates the physiological impact of cardiopulmonary bypass, preserves end-organ perfusion, and reduces the need for high-dose vasopressors. However, the risk–benefit ratio remains uncertain and may be associated with serious complications. Careful judgment regarding the indications for MCS has the potential to enhance the safety of CABG in high-risk patients, but robust, long-term, prospective studies are needed to determine its true impact on clinical outcomes. In this review, we will examine the indications and criteria for the use of MCS in patients with advanced ischemic cardiomyopathy, as well as the various devices available for preoperative or intraoperative support, including technical considerations, advantages and disadvantages, and associated complications. Full article

Background and Objectives: Combining osimertinib (OSI) with pemetrexed (PEM) can enhance antitumor efficacy; however, the benefit is schedule-dependent. Our previous pharmacodynamic (PD) study showed that concurrent PEM + OSI is limited by OSI-induced G1 arrest, attenuating early PEM cytotoxicity. In contrast, sequential PEM→OSI allows PEM to fully induce S-phase arrest and DNA damage but elicits a pro-survival EGFR rebound; subsequent OSI suppresses this rebound and promotes apoptosis of damaged cells, yielding strong synergy. Here, we investigated whether pharmacokinetic (PK) drug–drug interactions (DDIs) contribute to this synergy and predicted the relative advantage of PEM→OSI versus PEM + OSI under clinically relevant conditions using a PK/PD approach. Method and Results: Potential PK-DDIs were assessed at cellular uptake, plasma exposure, and intratumoral distribution levels. No meaningful PK-DDIs were observed, supporting a primary PD-driven synergy. We integrated mouse PK with in vitro/in vivo PD data to build a mechanistic Quantitative System Pharmacology (QSP)–PK–PD model linking drug disposition to folate biology, Epidermal Growth Factor Receptor (EGFR) signaling, and tumor growth inhibition. The model recapitulated schedule dependence and explained PEM→OSI superiority: PEM initiates damage and EGFR compensatory rebound, after which OSI suppresses EGFR signaling and enhances apoptosis. In contrast, concurrent PEM + OSI induced G1 arrest, reduced the pool of damaged apoptosis-susceptible cells, and weakened the synergy. Global sensitivity analysis identified intrinsic OSI sensitivity and the pro-apoptotic protein Bim as key determinants; reduced OSI sensitivity or Bim activity diminished the advantage of the sequential strategy. The simulations indicated that OSI can start 48 h after PEM exposure (no extended drug holiday is needed) and that the PEM→OSI benefit remains robust across heterogeneity, including BIM-deletion polymorphisms and inter-individual variability in tumor drug sensitivity. Conclusions: This mechanism-based QSP–PK–PD framework connects whole-body PK to core PD processes, explains schedule-dependent synergy, and supports optimization of sequencing intervals and identification of likely responders. Full article

Background and Objectives: Psychological resilience is increasingly recognized as a determinant of how patients respond to surgical stress, yet its role in perioperative medicine remains poorly defined. This narrative review aims to synthesize current evidence on resilience in surgical populations from a psychobiological perspective, spanning conceptual models, measurement approaches, clinical correlates, biological mechanisms, and intervention strategies. Materials and Methods: This narrative review was conducted to examine psychological resilience in adult surgical populations from an integrated psychobiological and perioperative perspective. A structured literature search was performed in December 2026 using PubMed, Scopus, and PsycInfo, combining resilience-related constructs with surgical, perioperative, biological, and clinical outcome keywords. Eligible publications included observational, longitudinal, interventional, translational, and conceptually relevant studies addressing resilience in adult surgical settings. Evidence was synthesized qualitatively across predefined domains, including conceptualization and measurement of resilience, associations with perioperative outcomes, neuroendocrine and inflammatory mechanisms, and resilience-modulating interventions within perioperative and Enhanced Recovery After Surgery (ERAS) frameworks. Results: Contemporary models conceptualize resilience as a dynamic, context-dependent process supported by interacting psychological, biological, and social factors. In surgical cohorts, higher resilience is consistently associated with better patient-reported outcomes, including quality of life, pain control, and emotional adjustment, and in some studies with survival and functional recovery. Preoperative depression, anxiety, maladaptive coping, and low social support converge as components of a broader “resilience profile” linked to poorer postoperative trajectories. Biologically, resilient phenotypes are characterized by more regulated hypothalamic–pituitary–adrenal and autonomic responses and reduced inflammatory activation. Psychological therapies, prehabilitation programs, and selected pharmacological strategies show convergent, though heterogeneous, signals of benefit and can be interpreted as indirect resilience-enhancing interventions. Conclusions: Resilience appears to be a clinically meaningful, potentially modifiable construct that links psychosocial functioning, biological vulnerability, and postoperative outcomes. Incorporating resilience assessment into preoperative risk stratification and systematically embedding resilience-building strategies within perioperative and ERAS pathways may support more personalized, psychologically informed surgical care. Prospective, multidomain studies are needed to validate measurement tools, clarify mechanisms, and test resilience-targeted interventions in surgical populations. Full article

Heart failure (HF) is a systemic syndrome in which cardiac dysfunction is closely linked to multiorgan involvement, including the gastrointestinal tract. Increasing evidence highlights the relevance of the gut–heart axis in HF pathophysiology, whereby intestinal hypoperfusion, congestion, and barrier dysfunction promote gut microbiota dysbiosis, systemic inflammation, and adverse cardiovascular outcomes. In parallel, the advent of novel HF therapies, particularly sodium–glucose cotransporter 2 inhibitors (SGLT2i) and the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan, has markedly improved clinical outcomes across HF phenotypes. Beyond their established cardiovascular benefits, these therapies may exert pleiotropic effects that extend to the intestinal environment and the gut microbiota. Through integrated actions on hemodynamics, neurohormonal activation, metabolic pathways, and inflammatory processes, recent data suggest that novel HF drugs may indirectly influence the gut-microbial composition and function. Conversely, the gut microbiota may modulate drug efficacy and result in interindividual variability in therapeutic responses, suggesting a bidirectional interaction between pharmacological treatment and the gut ecosystem. This narrative review summarizes current evidence of gut microbiota alterations in HF and critically examines emerging data on interactions between the gut microbiota and novel HF therapies, focusing on SGLT2 inhibitors and sacubitril/valsartan. Understanding this crosstalk may support the development of microbiota-informed, personalized therapeutic strategies in heart failure. Full article

Background/Objectives: The medical mushroom Ophiocordyceps sinensis (Caterpillar Fungus), known for its ability to enhance “vitality,” is one of the most popular medicines in Asian traditional medical systems. According to the Chinese Pharmacopeia, O. sinensis is standardized for its adenosine content, the precursor of ATP, which mediates numerous physiological and pathological processes in many diseases. The related fungus of order Hypocreales, Cordyceps militaris, and its major bioactive constituents, 3′-deoxyadenosine (cordycepin), also exhibit pleiotropic biological activities. This review aims to provide a rationale for the adaptogenic and resilience-supporting effects of these medicinal fungi and to align food and drug regulation in Western countries. Methods: In this narrative review, we integrated results from chemical, pharmacokinetic, network pharmacology, preclinical, and clinical studies of O. sinensis, C. militaris, and cordycepin using network pharmacology and bioinformatics tools. Results: Across studies, recurrent mechanistic hubs included PI3K–Akt, AMPK–mTOR, MAPK, NF-κB, apoptosis, and adaptive stress-response signaling pathways, linking immune regulation and metabolic homeostasis. Experimental studies confirmed modulation of cytokine production, kinase signaling, and mitochondrial regulators. Clinical meta-analyses demonstrate consistent adjunctive benefits in renal and pulmonary disorders, although heterogeneity in preparation and methodological limitations remains significant. The review reveals controversy regarding the bioavailability of cordycepin in vivo and its concentration in vitro studies, raising the hypothesis that cordycepin may act as a driver, triggering the organism’s adaptive stress response in stress-induced and aging-related diseases. Pharmacokinetic data indicate that systemic cordycepin concentrations after oral administration remain in the nanomolar range, suggesting that some predicted molecular interactions may occur indirectly or through systems-level mechanisms. The review, for the first time, suggests establishing a regulatory category for resilience-supporting physiological modulators to align food and drug regulation in the EU with contemporary systems biology, thereby complementing the work of EFSA, EMA, FDA, and Asian authorities. Conclusions:O. sinensis, C. militaris, and 3-deoxyadenosine share a common adaptogenic mechanism for maintaining homeostasis of cellular and integrated biological system functions. The systems-level network analysis and reductionistic molecular ligand preceptor pharmacology provide complementary approaches for understanding the multi-target bioactivity of these fungi. This review clarifies conceptual and regulatory barriers to recognizing resilience-supporting interventions and informs future regulatory innovation. Full article

Electromyographic (EMG) signals encode complex spatiotemporal dynamics reflecting neuromuscular coordination and pharmacological modulation. This study introduces a unified Hankel–topological framework for reconstructing and analyzing long-duration EMG recordings acquired from pigs under pharmacological influence, and for quantifying their bioelectrical organization. The method couples low-rank Hankel representations—capturing temporal redundancy and smoothness—with topological continuity constraints that stabilize activity packets defined by 5 s silence intervals. Six pigs were recorded across four experimental sessions (24 h each; four channels), and envelope reconstruction was performed using an ADMM-based solver. Quantitative analysis revealed consistent post-drug reductions in the packet rate ($-24.9\%$), the mean duration ($-2.3$ s), the amplitude ($-0.16$ a.u.), the effective Hankel rank ($-3.0$), and topological diversity ($\Delta {\beta }_0=-1.2$; all $p<0.01$). Deeper channels exhibited stronger suppression (interaction $p<0.02$), suggesting depth-dependent neuromuscular effects. The proposed framework unifies dynamical, statistical, and topological perspectives on EMG structure and yields interpretable biomarkers of neuromuscular inhibition and recovery. More broadly, it provides a generalizable signal processing methodology for analyzing structured, noisy physiological time series beyond EMG. Full article