Biology and Life Sciences

Abstract: Hip resurfacing arthroplasty (HRA) preserves femoral bone and was widely adopted for young, active patients with hip osteoarthritis before the decline of large-diameter metal-on-metal (MoM) bearings, which was driven by adverse reactions to metal debris (ARMD) and raised cobalt and chromium levels. New bearing couples, notably ceramic-on-ceramic (CoC) and metal-on-polyethylene (MoP), together with lessons learned from registries, have renewed interest in the procedure. This narrative review summarizes the historical evolution of HRA, current indications and contraindications, the learning curve, and the documented biomechanical and functional advantages (bone preservation, sta-bility, return to sport, gait), and compares contemporary implants using registry and published data. Long-term registry data support selected MoM implants only in men with large femoral heads (Birmingham Hip Resurfacing: 88.5% survival at 20 years; ADEPT: 94.1% at 15 years). The CoC ReCerf (MatOrtho) shows 5-year survival of 98.0–99.6% irrespective of sex and head size, but follow-up is short (mean 4 years) and evidence is limited to level III–IV. Data on cementless CoC H1 (Zimmer) and metal-on-polyethylene designs remain preliminary. HRA should be restricted to experienced surgeons in high-volume centres, with rigorous patient selection. Long-term registry surveillance and prospective comparative studies, including comparisons with short-stem and dual-mobility total hip arthroplasty, are needed.

Abstract: Carotid body type II cells constitute a glial-like cellular compartment with emerging molecular roles in intercellular signaling and adaptive plasticity. This narrative review critically examines the molecular mechanisms underlying type II-cell function, with particular emphasis on purinergic and non-purinergic signaling pathways. It also addresses the expression of sensory ion channels and the molecular regulation of the adult carotid body neurogenic niche. Functional studies in rats demonstrate adenosine triphosphate-induced intracellular calcium mobilization and secondary nucleotide release, whereas studies in human tissues demonstrate the immunohistochemical expression of signaling proteins and ion channels in identified cell populations, without establishing their functional activity. Glial fibrillary acidic protein-positive progenitor cells contribute to hypoxia-induced carotid body growth, alongside the recruitment of lineage-committed neuroblasts and expansion within the type I-cell lineage. The relative contributions of these populations vary across experimental models. Aging and disease observations identify candidate molecular changes but rarely establish type II-cell-specific causality. The central challenge is to link molecular identity, functional signaling, and lineage potential within defined cell populations, particularly in human tissue.

Abstract: Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation and converts the aortic valve and proximal aorta into unusually vulnerable target tissues: a calcification-prone valve seated in front of an aneurysm-prone media governed by transforming growth factor-β (TGF-β) signalling and nitric oxide (NO) homeostasis. We ask where the therapeutic windows of three expanding drug classes — cannabis, tryptamines (psilocybin/psilocin, DMT, 5-MeO-DMT), and non-hallucinogenic neuroplastogen analogues — sit relative to that vulnerability. We integrate receptor pharmacology (CB1/CB2; 5-HT2A/5-HT2B; biased agonism), exposure patterns separating macrodose from microdose regimens, and the convergent effector pathways through which each class could plausibly interact with BAV disease, and we anchor the analysis to a reconstructed genetic resource: the complete archived openSNP phenotype-361 (“Bicuspid aortic valve”) cohort (22 members; 19 with recoverable genotypes across a 17-SNP panel), rebuilt from Internet Archive holdings after the platform closed in April 2025. We propose that the three classes threaten BAV through separable doors — cannabis hemodynamically and vasculopathically, tryptamines through 5-HT2B-mediated valvular fibrosis, and neuroplastogen analogues, by medicinal-chemistry design, through neither — and that cumulative 5-HT2B receptor occupancy above endogenous tone, not binding affinity, is the operative risk variable. Descriptively, most genotyped cohort members carry at least one TGFB1 −509 variant allele and five of eight covered members carry a NOS3 −786C allele, demonstrating that the substrate for pharmacogenomic interaction is common rather than rare. We close with an exposure × phenotype risk-stratification matrix and six falsifiable hypotheses for a registry-scale test. This is a hypothesis-generating mechanistic analysis, not clinical guidance.

Abstract: Background: Activation of the trigeminovascular system, calcitonin gene-related peptide (CGRP) release, and central sensitization of the trigeminocervical complex are the mainstream framework for migraine and related syndromes. This framework explains the event cascade after attack initiation. It does not adequately explain why the attack threshold is systematically lowered in some individuals, such that routine head and neck movement or minor mechanical loading triggers symptoms.Objective: To propose the investing fascia–carotid sheath coupling hypothesis. In this hypothesis, the same upstream fascial mechanical abnormality produces downstream vascular events with different thresholds and phenotypes in the anterior and posterior circulations.Methods: This is a hypothesis paper, not an empirical study. Published evidence was synthesized into a testable causal chain. No new primary data are presented. The hypothesis is positioned as a peripheral mechanical upstream complement to, not a replacement for, the trigeminovascular system and central sensitization theories.Results: The proposed causal chain begins with investing fascial fibrosis and mechanical conduction through the deep cervical fascial network to the carotid sheath. Within the sheath, PIEZO mechanotransduction and CGRP signaling amplify the signal. The resulting effects are superimposed and mutually amplifying across five pathways: arterial, venous, lymphatic/glymphatic, sympathetic, and vagal. The five-pathway superposition is threshold-dependent rather than simultaneous, with the threshold defined by the sympathetic hemodynamic threshold. The term "conditional" is used once here in its standard sense, namely dependent on a stated condition; thereafter the term "threshold-dependent" is used throughout to denote the same property. Below that threshold, the superposition mainly involves the arterial, venous, lymphatic/glymphatic, and vagal pathways. The sympathetic pathway joins only after its threshold is crossed. The anterior circulation has greater autoregulatory reserve, with the compensation threshold as its characteristic node. In vivo evidence shows that dynamic cerebral autoregulation in the posterior circulation is more pressure-passive. Posterior circulation arterial walls also tend toward passive stiffening during head rotation, whereas anterior circulation arteries exhibit compensatory softening. Vertebral artery hypoplasia (VAH) provides independent systematic-review evidence for the association between posterior circulation low reserve and clinical vulnerability. However, VAH is used only as a structural reference for validation design, not as causal evidence. Two core gaps remain: Gap 1, the investing fascia-to-sheath wall transmission coefficient; and Gap 2, the reliability of mechanical measurement of the sheath wall itself. Because Gap 2 is logically prior to Gap 1 in measurement terms, a transitional measurement framework for the Gap 1–Gap 2 pair is specified so that Gap 1 study design can proceed before Gap 2 is formally closed. The framework has three components: cadaveric cervical-block indentation with deep ultrasound displacement mapping, Bayesian indirect estimation anchored on published effect sizes, and phantom–specimen two-tier calibration of device, depth, and stiffness biases. This framework yields a posterior interval and a feasibility bound for the transmission coefficient; it does not substitute for direct measurement of Gap 1 or for reliability validation of Gap 2.Conclusions: The hypothesis is at the stage of literature derivation, quantitative prediction, and tiered validation. It provides refutation criteria and a five-tier validation-method minimal testable hypothesis set comprising histology, mechanics, computation, cohort, and intervention, with tier-specific minimal test sets. These five validation-method tiers are distinct from the evidence tiers of Section 5. The anterior circulation is treated as a representative-artery construct rather than a homogeneous unit; a minimal internal stratification into cervical ICA, MCA, and ACA nodes is specified so that the anterior–posterior contrast is not confounded by unequal stratification resolution. The hypothesis should be judged not by whether it explains all functional syndromes, but by whether it can give a more precise and more falsifiable answer than the generalized statement that the neck is related to the cerebral circulation. This answer must specify the differentiated dose–response of the anterior and posterior circulations.

Abstract: The clinical association between internal jugular vein (IJV) outflow obstruction and symptoms such as headache, pulsatile tinnitus, and cognitive decline has been repeatedly observed; however, “venous compression” alone is insufficient to explain the marked clinical heterogeneity of the condition. Among 283 patients with nonthrombotic IJV stenosis, the prevalence of headache was 65.02%; however, within the framework of this hypothesis, risk depends more on whether collateral compensatory capacity (and concurrent valvular antireflux function) is adequate than on the anatomical severity of stenosis—severe vertebral vein dilation, as a marker of adequate collateral compensation, was independently inversely associated with headache risk (OR = 0.184, 95% CI 0.092–0.366). Clinical consequences depend more on whether collateral compensation and valvular function remain sufficient to maintain outflow after compression. This hypothesis attributes this difference to whether compensation is adequate when IJV outflow is obstructed and proposes its upstream factor: sclerotic fibrosis of the investing fascia. Core proposition: Fibrosis of the investing fascia, through loss of elastic buffering and transmission of abnormal mechanical stress via the deep cervical fascial network to the carotid sheath, reduces collateral compensatory capacity when IJV outflow is obstructed and may coexist with insufficient valvular antireflux function; this state of inadequate compensation—centered on collateral compensation with valvular function as a parallel dimension—rather than luminal stenosis itself, is the key mediator linking extrasheath fascial pathology to fluctuating elevation of intracranial venous pressure. This framework provides a unified upstream mechanical perspective for understanding diseases and clinical phenotypes that share a common component of venous outflow obstruction, including headache associated with IJV stenosis, pulsatile tinnitus and cerebral tinnitus, exertional headache, Ménière disease, transient monocular blindness, insomnia, autonomic dysfunction, anxiety/depression/brain fog, vertigo, facial pain, and Eagle jugular syndrome. The hypothesis predicts that investing fascial stiffness is independently associated with compensatory indicators during IJV outflow obstruction; collateral compensatory capacity modifies the association between investing fascial fibrosis and symptoms; and relief of extrasheath mechanical constraint produces paired improvements in venous flow parameters and symptoms.

Abstract: Central clearance dysfunction in neurodegenerative diseases has long been regarded as an intracerebral event. However, the final outlet for cerebral metabolic waste—the deep cervical lymphatic system—shares the same mechanical space as the vascular and neural structures within the carotid sheath. This article proposes a hypothesis of conditional coupling between the investing layer of the deep cervical fascia (investing fascia) and the carotid sheath, centered on the lymph node within the carotid sheath (intrasheath lymph node). The central proposition is that chronic forward head posture, aging, and low-grade inflammation synergistically drive investing fascia fibrosis and reduce its elastic buffering capacity. Abnormal shear forces are then transmitted to the carotid sheath through composite pathways involving the deep cervical fascia, visceral fascia, or interstitial tissue pressure, thereby altering the conditional mechanical environment of lymphatic structures within the sheath. Six functional domains—arterial perfusion, venous return, deep cervical lymphatic drainage, lymphatic-glymphatic coupling, sympathetic tone, and the vagal anti-inflammatory pathway—are conditionally co-susceptible under shared mechanical boundaries, but they are not assumed to be equally affected, equally weighted, or involved in an identical sequence. The lymphatic and glymphatic systems constitute a serial clearance chain. Within the carotid sheath region, the intrasheath lymph node is the core structure and the conditional shared bottleneck at the cervical level. Functional stenosis, as defined here, refers to functional limitation of lymphatic structures within the sheath under a conditional mechanical environment; it does not presuppose homogeneous sheath-wall narrowing or constant direct fibrous continuity. Its downstream outcome should be described as altered clearance function (reduction or pathological redistribution) rather than a decline in a single clearance measure. Existing evidence is uneven across nodes of the chain. Meningeal lymphatic anatomy and functional necessity are independently validated; glymphatic driving and coupling frameworks are becoming clearer; human intrathecal tracer magnetic resonance imaging (MRI) shows drainage to deep cervical lymph nodes; external mechanical and intrinsic physiological regulation can alter cerebrospinal fluid (CSF) drainage; aging-related lymphatic decline is a systemic vulnerability axis; phosphorylated tau 181 (pTau181) enrichment in deep cervical lymph nodes supports the central-to-cervical transport direction; and fibrotic remodeling of deep cervical lymph nodes localizes the bottleneck to the lymph node level. The core empirical gap is whether, within the same individual, a decline in investing fascia elasticity precedes or accompanies changes in the mechanical state of lymph nodes within the carotid sheath and mediates altered clearance function, while remaining statistically independent of cervical bone-ligament structural parameters and global spinal alignment parameters.

Abstract: Inhalation represents a primary entry route for airborne pollutants, aerosols, pathogens, and therapeutic agents. Their pathological impacts depend on a complex interplay of physical transport, deposition patterns, cellular crosstalk, mechanical forces, and localized microenvironmental responses. However, traditional 2D cell cultures and animal models fall short in mimicking these human-specific microenvironments, particularly due to the lack of air-exposed barriers, dynamic fluid flow, physiological motion, and precise aerosol dosage control. Respiratory organ-on-a-chip technologies address these limits by integrating air–liquid interfaces, microfluidic perfusion, and tissue-specific mechanics. In this review, we examine the principles of inhaled exposure, disease mechanisms across the respiratory tract, and recent advances in chip design and exposure delivery. We highlight key applications in modeling respiratory infections, chronic inflammatory and fibrotic diseases, airway injury, and carcinogenesis. Finally, we discuss critical requirements for translational impact, emphasizing that advanced model complexity must be supported by accurate dosimetry, robust tissue validation, and defined contexts of use.

Abstract: Background and Objective: Maximal strength is a critical indicator of neuromuscular function essential for assessing physical performance and prescribing resistance training. Nevertheless, indirect estimation of one-repetition maximum (1RM) depends on both the predictive model and joint positioning during task execution. The aim of this study was to evaluate the influence of different glenohumeral joint positions on the estimated 1RM of the triceps brachii muscle in trained and untrained individuals, using the Matveev, Adams, and Epley equations. Methods: Utilizing a descriptive, cross-sectional, and quantitative design, this study examined 20 men separated into trained (n = 10) and untrained (n = 10) groups. Unilateral elbow extension was executed at three glenohumeral positions: 10 degrees flexion, 45 degrees extension, and 130 degrees flexion. The 1RM was estimated via the Matveev, Adams, and Epley equations, with data assessed using analysis of variance and a subsequent Tukey test (p <0.01). Results: Trained individuals exhibited higher estimated 1RM values in all evaluated positions. Glenohumeral joint position influenced estimated 1RM, with higher values at 10° of flexion and lower values at 130° of flexion. No significant differences were observed between the Matveev, Adams, and Epley equations. Conclusion: Training level and glenohumeral joint positioning influence the estimated 1RM of the triceps brachii, whereas the three equations show similar performance when applied using a standardized protocol.

Abstract: Vasomotion refers to spontaneous rhythmic oscillations in microvascular tone that are independent of cardiac and respiratory cycles and contribute to the regulation of tissue perfusion. These oscillations arise from intrinsic vascular mechanisms and are modulated by autonomic, cardiometabolic and neuroendocrine signals. Although traditionally considered a local vascular phenomenon, emerging evidence suggests that microvascular oscillations may exhibit temporal relationships across different vascular beds. Whether shared physiological inputs contribute to the coordination of vasomotion between cerebral and systemic microcirculation remains largely unexplored. This review covers the cellular basis of vasomotion and the potential contributors of autonomic nervous system, cardiometabolic signals and neuroendocrine mediators in cerebral-systemic microvascular interactions. We propose that these extrinsic influences constitute a superimposed regulatory layer that may modulate the amplitude, frequency, and phase of locally generated vasomotor oscillations, potentially contributing to coordination across distributed vascular networks while preserving vascular bed-specific regulation. We further discuss experimental approaches for investigating vasomotion across spatial and temporal scales, including intravital imaging, wavelet analysis, phase-coherence assessment, and simultaneous measurements of cerebral and peripheral hemodynamic signals. Methodological limitations, including the difficulty of assigning specific mechanisms to individual frequency bands and inability to establish causality from coherence alone, are also considered. This integrative framework identifies key questions for determining whether coordinated vasomotion contributes to functional coupling between cerebral and systemic microcirculation and helps maintain microvascular homeostasis.

Abstract: The vagus nerve travels through the carotid sheath in the neck. Its functional status has long been regarded as independent of the surrounding fascial environment. This article proposes the “Investing Fascia–Carotid Sheath–Vagus Nerve Mechanical Coupling Hypothesis.” Its central premise is that fibrotic thickening of the investing fascia—the superficial layer of the deep cervical fascia in the posterior triangle and between the sternocleidomastoid and trapezius muscles—or of the deep cervical fascial layers in the anterior triangle may transmit abnormal mechanical loads through the deep cervical fascial network to the carotid sheath. This transmission may alter the intra-sheath microenvironment and modulate vagal afferent and efferent activity. The result would be a mechanical coupling pathway linking tension in the superficial deep cervical fascia and deep cervical fascial network to the intra-sheath mechanical microenvironment and vagal tone. Recent anatomical, imaging, molecular, and clinical intervention studies suggest that the three layers of the deep cervical fascia—the investing fascia, the pretracheal fascia, and the prevertebral fascia—may form a structural coupling with the carotid sheath through a continuous or semi-continuous mechanical network. Together, these layers may constitute a fascial–sheath mechanical continuum capable of transmitting mechanical signals from the neck to the vagus nerve. PIEZO1 and PIEZO2 are core molecular components of vagal mechanotransduction. Their expression and function are regulated at multiple levels by MDFIC2, Nedd4-2, GPR146, ZBED6, and the neuroimmune microenvironment. Mechanosensitive potassium channels, TRPV2, TRPM4, and other channels participate cooperatively, suggesting that PIEZO channels are necessary but not necessarily the only molecular components. The cross-sectional area (CSA) of the cervical vagus nerve is reduced in neurodegenerative diseases such as Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). In contrast, CSA may be increased in metabolic diseases such as diabetic neuropathy. These findings suggest that the direction of CSA change may be disease-specific. This article systematically reviews the anatomical basis, mechanical transmission pathways, molecular conversion mechanisms, functional validation evidence, and clinical implications of this hypothesis and proposes testable directions for validation. Critically, the middle segment of this hypothetical chain—fascial mechanical changes, carotid sheath deformation, changes in the intra-sheath microenvironment, and changes in vagal mechanical exposure—currently lacks synchronized in vivo measurements in the same participant. This segment should be labeled as theoretical inference or pending direct validation, not as an established mechanism.

Abstract: Background: Fascia has been overlooked throughout most of the history of anatomy, but many recent studies have begun to showcase its role. The ventral thigh has been extensively studied in various fields, including anatomy, biomechanics, physiotherapy, histology, and orthopedics. Therefore, the fascia lata is a good model for synthesizing the recent knowledge accumulated from studying this organ. Methods: A review was constructed to describe the characteristics of the deep fascia, with articles highlighting the main roles of the fascia lata selected for this purpose. Results: Forces travel through the fascia lata according to knee and hip positioning, optimizing energy sparing. When the knee is extended, the forces are transmitted to the iliotibial band whereas, when the knee is flexed, the forces are transmitted to the patella. Additionally, the fascia lata is a propri-oceptive organ. Its lengthening during a stretch is felt as pain while the mechanical tension is felt as a feeling of tension. The fascia lata can be lengthened and maybe reinforced by stretching training. Moreover, it is likely that its stiffness can be responsible for a few of the main running pathologies. Conclusions: The fascia lata may provide an insight into the major roles of the fascial tissue. This literature review put in relief a few gaps in fascia histology and bridging these lacunes would be profitable to better understand the physiology underlying its proprioceptive role. Finally, a better understanding of fascia physiology may improve clinical reasoning in various medical specialties.

Abstract: Background: Dorsocervical fat pad, commonly referred to as neck hump, is a common soft-tissue lesion at the cervicothoracic junction. Its systemic pathophysiological significance has long been underestimated. Hypothesis: This article proposes the investing fascia–carotid sheath mechanical coupling hypothesis. The hypothesis posits that the deep indurated tissue of the dorsocervical fat pad is not merely fat but rather a fascial–ligamentous–adipose complex. This complex is centered on fibrotic thickening of the superficial layer of the deep cervical fascia (investing fascia) and includes the ligamentum nuchae, supraspinous ligament, trapezius aponeurosis, and surrounding fibrofatty tissue. Once the investing fascia loses its viscoelastic buffering capacity, abnormal shear forces generated by routine micromovements of the head and neck can be transmitted through the deep cervical fascial network to the carotid sheath. Evidence: The carotid sheath is an anatomic hub in which multiple structures coexist within a single sheath. The structures within and adjacent to the sheath can be categorized into six functional domains: arterial perfusion, venous return, lymphatic immune clearance, glymphatic cerebrospinal fluid–interstitial fluid clearance, sympathetic output, and the vagal anti-inflammatory pathway. These six functional domains are not mutually exclusive; rather, they are spatially shared, functionally coupled anatomic–physiologic units. Among these, the arterial baroreflex, sympathetic output, and the vagal anti-inflammatory pathway are neurally related pathways that participate in central integration via the nucleus tractus solitarius (NTS) and related nuclei. Venous return, lymphatic immune clearance, and glymphatic cerebrospinal fluid–interstitial fluid clearance contribute more to amplification through pressure coupling, humoral immunity, and clearance functions. Humoral immunity and pressure-coupling pathways participate in amplifying the pathologic process through mechanisms such as Ang II/AT1R-YAP, GPR146-PIEZO1, and impaired lymphatic clearance. In this hypothesis, these steps constitute a hypothetical positive feedback loop: investing fascia fibrosis → carotid sheath compression → coordinated dysfunction of the six functional domains → elevated blood pressure → pathologic vascular remodeling → increased plaque instability. Elevated blood pressure may, in turn, aggravate investing fascia fibrosis. Increased neck circumference has been clearly associated epidemiologically with cardiovascular events and the progression of carotid atherosclerosis. The latter is one of the important upstream risk factors for cerebral infarction. However, direct population-based evidence linking the dorsocervical fat pad to increased neck circumference remains lacking. Most existing studies have used neck circumference or posterior cervical fat accumulation as surrogate markers; no population-based study has used the dorsocervical fat pad as an inclusion criterion. Implications: Within this framework, eliminating the dorsocervical fat pad—that is, relieving the sustained mechanical constraint of the investing fascia on the carotid sheath—has a pathophysiological rationale worthy of systematic investigation for the prevention of cardiovascular and cerebrovascular diseases, especially cerebral thrombosis. Nonetheless, this remains a hypothetical inference. Conclusion: This article systematically elaborates the anatomic basis, mechanical transmission mechanisms, pathophysiology of the six functional domains, derivation of the causal chain, relationship between promoting vascular patency and preventing thrombosis and dorsocervical fat pad, testable predictions, and interventional implications of this hypothesis. It also clarifies its evidentiary boundaries.

Abstract: The deep cervical fascial system consists of three layers: the investing layer of the deep cervical fascia (investing fascia), the pretracheal fascia (middle layer), and the prevertebral fascia (deep layer). This hypothesis proposes that chronic forward head posture or sustained cervical stress may lead to fibrotic remodeling of the investing fascia, resulting in abnormally elevated passive tension. This abnormal tension may be transmitted indirectly to the carotid sheath region through the interwoven collagen fiber network among the layers of the deep cervical fascia, or through intermediate interfaces such as the visceral fascia, thereby contributing to fibrotic thickening of the sheath wall and surrounding tissues. Thickening of the posterior wall of the carotid sheath may exert sustained mechanical compression on the cervical sympathetic trunk immediately posterior to it, thereby causing sympathetic dysfunction and autonomic imbalance. It should be noted that the fascial composition of the carotid sheath remains controversial. The investing fascia and the sheath wall may not be directly fused; instead, they may be indirectly connected through intermediate interfaces such as the visceral fascia. Zhao et al. confirmed in a rabbit model that the carotid sheath has a three-layered fascial architecture: the inner fascial layer on the arterial side appears earliest and is the thickest, and the outer fascial layer shows potential fusion between adjacent structures, suggesting a possible spatial gradient in sheath wall thickening. However, that study was performed at a developmental stage and in an animal model, and it cannot directly prove that pathological fibrotic thickening causes compression of the sympathetic trunk. Lyons and Mills found during human cadaveric dissection that the cervical sympathetic trunk was located inside the carotid sheath in some individuals. Park et al. further integrated the anatomical features of the middle cervical ganglion through meta-analysis, and Salazar-Orellana et al. reported a clinical case in which venous dilation within the sheath compressed the sympathetic trunk and caused sympathetic overactivity. He et al. confirmed in a rat model that atlantoaxial misalignment can cause hypertension, and blood pressure decreased after removal of the implant. Cassaglia et al. confirmed in anesthetized lambs that mechanical elevation of blood pressure can directly increase sympathetic activity in the superior cervical ganglion, suggesting that the causal chain from upper cervical mechanical misalignment or an altered mechanical environment to sympathetic activation and elevated blood pressure is verifiable in animal models. Lee et al. reported a case in which scar formation after rhabdomyolysis of the longus colli and scalene muscles compressed and tethered the cervical sympathetic trunk, causing Horner syndrome, providing direct human clinical evidence for the pathway from cervical soft tissue pathological change to mechanical compression of the sympathetic trunk and sympathetic dysfunction. Okamoto et al. and Farage et al. respectively reported cases of marked fibrosis around the carotid artery and inflammatory pseudotumor of the carotid sheath, providing histological and imaging evidence that fibrosis can occur in the carotid sheath region. Langevin et al. used ultrasound to confirm that fascial thickness and echogenicity increased by approximately 25% in patients with chronic low back pain, providing a methodological precedent for ultrasound quantification of pathological fascial thickening. If this mechano-neural coupling pathway holds true, it may contribute to the peripheral drive of distal pathological conditions such as cervicogenic hypertension, cerebral hypoperfusion, and ocular disorders. However, its core components have not yet been directly validated in animal or human models. This hypothesis is based on evidence from anatomy, histology, biomechanics, molecular biology, pathophysiology, and clinical research. It constructs an evidence integration framework spanning anatomical structure, histological basis, mechanical properties, molecular transduction, pathological experiments, physiological effects, human epidemiology, alternative mechanism controls, and interventional validation, and it proposes testable predictions and a validation framework. At the same time, this hypothesis incorporates negative control evidence and alternative mechanism evidence to define the boundary conditions of the effects of cervical sympathetic trunk intervention. Currently, no animal model or human study has directly simulated sympathetic trunk compression caused by fibrotic thickening of the carotid sheath wall. This is the main evidence gap of this hypothesis, rather than a gap in the literature.

Abstract: The adult configuration of the aortic arch complex (AoAC) results from transformation of its embryonic precursor. Concepts of the embryology of variants and malformations of the AoAC traditionally focus on transformation processes that are driven by regression and persistence of embryonic vascular segments. However, such concepts cannot explain every variant or malformation since they neglect other morphogenetic processes involved in the transformation of the embryonic AoAC, such as blood vessel “migration”, and septation of the aortic sac (AoS) and distal outflow tract (OFT) of the embryonic heart. This article focuses on the hitherto neglected role of septation of the AoS and embryonic OFT in normal and abnormal patterning of the AoAC. It is shown (1) how phylogenetic “deviations” from the mammalian “standard” of AoS septation lead to the AoAC branching patterns found in non-mammalian vertebrates; and (2) how ontogenetic deviations from the human “standard” can lead to AoAC anomalies, such as “bovine arch”; subclavian artery as first branch of the aortic arch; anomalous origin of supra-aortic branches from the proximal ascending aorta; anomalous origin of one pulmonary artery from the proximal ascending aorta; anomalous origin of one common carotid artery from the proximal pulmonary trunk; and tritruncal hearts.

Abstract: This hypothesis proposes, from a holistic perspective, that the human body can be viewed as a tension–sensation–immune integration network grounded in fascial continuity. Systematic reviews have confirmed moderate-strength evidence for intermuscular force transmission along myofascial chains, although evidence for some chains remains insufficient [1]. The central nervous system provides global regulation through procedural motor memory and conditioned reflexes, whereas the peripheral fascia forms mechanical memory and fascial reflexes—defined here as the modulation and amplification of neural reflexes by fascia as a peripheral mechanical–chemical transduction network—through the PIEZO1 and PIEZO2 mechanosensitive channels, axon reflexes, and intrinsic cellular circuits, thereby modulating neural reflex thresholds. The term “reflex coupling” as used here refers specifically to the circuit relationship between central encoding and peripheral fascial modulation, not to two parallel reflex systems.Recent studies have identified CD34+ membranous cells in the subcutaneous fascia that highly express PIEZO and other mechanosensitive genes [2]. Fibroblasts in fascial tissue from a mouse model of arthritis functionally express PIEZO1 and YAP1, and selective ablation of these cells attenuates the therapeutic effects of mechanical stimulation [3]. PIEZO1 and PIEZO2 protein expression has been confirmed in the sensory nerve structures of the human carotid sinus wall [4]. External pressure can be effectively transmitted to carotid sinus tissue with a conduction efficiency of 82%–89% [5]. In human carotid atherosclerotic plaques, Piezo1 expression in myofibroblasts is significantly elevated in symptomatic patients [6], and YAP expression in human carotid plaque tissue correlates with pathological status [7]. Cervical fascial stiffness has been reliably quantified by shear wave elastography (SWE) [8]. The pressure required to reach the deep cervical fascia is approximately 6 N/cm², and the cervical pressure pain threshold is significantly lower than that in the thoracolumbar region [9]. The shear modulus of target fascia is significantly reduced in the stretched position after fascial hydrorelease (FHR) [10]; FHR clinical efficacy has been supported by randomized controlled trials (RCTs) [11,12], and 12-month follow-up has confirmed long-term efficacy [13]. However, the 2026 Chinese expert consensus notes that this technique still lacks the highest level of evidence, and its analgesic mechanism remains incompletely established [14].At the molecular level, YAP has been directly confirmed in human deep fascia [15]. Multiple pathways—including Ang II–AT1R–YAP [16], PIEZO1–YAP [17], PIEZO1–ET-1–HIF-1α–TGF-β [18], and hydrostatic pressure–PIEZO1–YAP1–GLS1 (in rat bladder fibroblasts) [19]—are implicated in fibroblast activation. The functional necessity of the PIEZO1–YAP/TAZ axis for in vivo fibrosis has been verified by conditional gene knockout [20], and Wen et al. systematically reviewed the mechanisms and therapeutic prospects of this axis [21]. A recent study confirmed in human keloid fibroblasts that Piezo1 transfers mechanical signals to YAP via calcium flux to drive matrix production [22]; however, this evidence comes from keloid skin fibroblasts, not fascial tissue. Another study provided direct evidence in human dermal fibroblasts that mechanical stretch induces chromatin accessibility changes and H3K9me3 downregulation [23]; however, this evidence also comes from skin fibroblasts, not fascial fibroblasts. Traditional anatomical descriptions of the “investing fascia as a continuous fibrous layer surrounding the neck” have been challenged. The investing fascia does not exist in the anterior cervical triangle [24], nor between the sternocleidomastoid and trapezius muscles [25]; however, it does exist on the surface of the trapezius, and Diwan et al. confirmed its dense bilaminar structure [26]. A recent developmental histological study further confirmed a three-layered fascial architecture at the carotid sheath level [27]; this evidence comes from a rabbit model and cannot be directly equated with the human fascia surrounding the carotid sheath. This hypothesis therefore adopts the functional term “fascial integration layer surrounding the carotid sheath,” whose anatomical boundaries remain controversial.The core proposition is that central encoding is the primary component, peripheral fascia is the mechanical memory substrate and reflex modulator, and the fascial integration layer surrounding the carotid sheath may be a candidate strategic hub coupling the systemic fascial network with vital organs. This hypothesis has clear falsifiability. Its minimal falsifiable unit is the co-expression of PIEZO1/2 and YAP in resident cells of the human fascia surrounding the carotid sheath. The first-priority validation step is P1, namely directly confirming PIEZO1, PIEZO2, and YAP expression in these cells. If P1 is not confirmed, the direct molecular basis for the fascial resident cell component of this mechanism would be lacking, although PIEZO1/2 expression from other cellular sources might still partially support the pathway. The hypothesis further predicts that if P1 is not confirmed, FHR effects will not correlate with fascial PIEZO1/2 expression and that YAP-dependent fibrotic markers will be absent in fascial resident cells.

Abstract: Stroke direction in table tennis may require technique-specific adaptations of trunk–pelvis motion, but the timing and magnitude of these adjustments remain unclear. This study compared cross-court (CC) and long-line (LL) kinematics during forehand counter-topspin (F_FH), forehand topspin (TP_FH), and backhand topspin (TP_BH). Ten high-level players performed both target directions while whole-body kinematics were recorded using a 16-sensor inertial measurement unit system. A total of 580 valid strokes were analysed. Continuous torso–pelvis flexion–extension, lateral bending, and axial rotation trajectories were compared using one-dimensional statistical parametric mapping (SPM), while discrete variables were analysed using linear mixed-effects models with false discovery rate correction. CC and LL trajectories were largely similar across techniques; only a late follow-through axial-rotation difference was identified for TP_BH (SPM cluster, p = 0.030). Discrete analyses revealed technique-specific differences in selected contact angles, ranges of motion, trunk–pelvis separation measures, and angular velocities, with predominantly negligible-to-small effect sizes and no variable differentiating all three techniques. Stroke direction therefore appears to be accommodated mainly through brief, technique-specific kinematic adjustments rather than a global alteration of torso–pelvis movement patterns, highlighting the complementary information provided by continuous and discrete biomechanical analyses.

Abstract: Cells often behave differently after a brief stimulus has ended. This is called cellular memory, but persistence alone does not show it. The same phenotype can come from leftover agent or signal, selection of cells that were already different, a shift in the mix of cell states, genetic change, or a state held by the exposed cells. This Review compares how four fields use the word (trained immunity, stem-cell inflammatory memory, yeast transcriptional memory and cancer drug tolerance). It lists seven explanations and the test that separates each. It then proposes a framework for judging what a study can claim: four ordered gates and four claim labels (U, P, M, H). The labels are operational categories, not grades of truth or of study quality. A test not done counts as untested, not as negative. The framework is a proposal, not a validated standard. A planned audit, set out in the Supplement, would test it against failure conditions stated in advance.

Abstract: Prolonged spaceflight is associated with skeletal muscle atrophy, but the molecular mechanisms linking immune dysregulation, circadian disruption, and metabolic remodeling remain poorly understood. This study performed RNA-seq transcriptomic profiling of tibialis anterior muscle from mice flown on the International Space Station for 38 days, using data from NASA's Rodent Research-23 mission (OSD-576). Comparing flight mice with habitat ground controls, 311 genes were differentially expressed (FDR < 0.05, |log2FC| > 1.5). Flight mice showed an elevated expression of acute phase and stress response genes, including Lcn2 (log2FC = +3.65), Orm1 (+3.87), Pnmt (+3.07), and Cdkn1a (+2.39), and reduced expression of metabolic, circadian, and chemokine genes, including Nmrk2 (−3.90), Dbp (−1.96), Cxcl10 (−2.34), Ccl2 (−2.68), S100a8 (−2.61), and S100a9 (−2.97). Overrepresentation analysis identified shared gene membership (not directional concordance) with published gene sets for idiopathic pulmonary fibrosis, acute myocardial infarction, dilated cardiomyopathy, and colitis. Several overlapping genes moved in opposite directions relative to the disease reference sets. The findings are consistent with immunometabolic transcriptional remodeling of skeletal muscle, characterized by acute phase activation along with suppression of chemokine signaling, circadian control, and energy metabolism.

Abstract: Wearable devices, such as the Empatica E4, are increasingly used to assess stress-related electrodermal activity (EDA). The EmbracePlus has replaced the widely used Empatica E4. This study evaluated the validity of the EmbracePlus by comparing wrist-worn EDA measurements with the Shimmer3 GSR+ across signal-, parameter-, and event-level analyses. Healthy volunteers (n=53) completed breathing exercises, a Stroop stress task, and a virtual reality (VR) height stressor while wearing both devices simultaneously on the non-dominant wrist. Signal-level agreement was assessed using cross-correlation, parameter-level agreement using Bland–Altman analyses of mean skin conductance level (SCL), total phasic activity, skin conductance response (SCR) amplitude, and SCR count, and event-level agreement using within-device baseline-to-task comparisons and inter-device difference plots with a priori acceptability boundaries. Signal-level agreement was weak-to-moderate. Shimmer3 yielded systematically higher values across all metrics, indicating limited agreement in absolute EDA values. Shimmer3 detected significant increases across all metrics during both stress tasks. EmbracePlus detected the stronger VR stressor across all metrics, whereas during the milder Stroop task only total phasic activity and mean SCL increased. These findings indicate that EmbracePlus and Shimmer3 are not interchangeable for absolute EDA assessment and that EmbracePlus validity depends on stressor intensity and metric selection.

Abstract: Fingerprint dermatoglyphics is used in Ibero-America and Eastern Europe as a marker of physical ability for talent identification. A 2022 genome-wide study linked fingerprint loci to limb development and hand proportions, thereby supporting a morphological hypothesis. We quantified the association between quantitative fingerprint indices and objectively measured physical ability and assessed whether it persisted after adjustment for morphology. Following a registered protocol (PROSPERO CRD420261469333), we searched Web of Science and four Ibero-American databases and pooled Fisher z-transformed correlations in a correlated-and-hierarchical-effects model with cluster-robust variance estimation, with three-level and Bayesian models as companions. Twenty studies were eligible; nine contributed 122 effect estimates from 337 participants. The pooled correlation was r = 0.047 (95% confidence interval: −0.218 to 0.306); the three-level model gave r = 0.025 (−0.028 to 0.078), an anti-conservative interval. No study adjusted for anthropometry, maturation, or training; in four studies measuring all three, anthropometry correlated with performance (mean |r| = 0.45) more strongly than fingerprints (mean |r| = 0.17), and partial correlations did not increase the fingerprint–performance association. Certainty was very low. This study shows no practical association between morphological and physical capacities, which does not support using fingerprints to select young athletes.