Biology and Life Sciences

Abstract: The evolution of biological coordination is often framed as a progression toward specialized nervous systems. Here, we propose the Evolutionary Information Layering Framework, arguing that complexity emerges not by replacing ancestral mechanisms, but through their retention, specialization, and integration. We posit that pre-neural regulatory layers—including extracellular matrix (ECM) remodeling, mechanical forces, and endogenous bioelectric states—provided foundational organization later co-opted by neural systems. This hypothesis generates testable predictions: under neural disruption, non-neural layers (e.g., bioelectric gradients) sustain tissue coordination. By bridging evolutionary developmental biology (evo-devo), systems biology, and bioelectricity, this framework redefines nervous systems as specialized amplification layers embedded in an ancient, multi-scale regulatory architecture.

Abstract: The formation of the cardiac and skeletal striated muscles is a highly coordinated process during embryogenesis, emanating in both cases as mesodermal derivatives. Over the last decades the transcriptional regulatory networks that govern cardiac and skeletal muscle morphogenesis have been extensively studied. However, non-coding RNAs (ncRNAs) have emerged as new players modulating different aspects of gene expression, adding thus a novel layer of complexity to those developmental programs, by acting at epigenetic, transcriptional and post-transcriptional levels. In this review, we provide a state-of-the-art view of the functional contribution of long non-coding RNAs during cardiac and skeletal muscle development, highlighting the distinct molecular mechanisms currently described in these morphogenic processes.

Abstract: Understanding human cardiac development, disease, and therapeutic response requires experimental models that reproduce defined aspects of myocardial organization and function. However, no single in vitro or ex vivo preparation captures the complete structural, electrophysiological, contractile, metabolic, vascular, stromal, and immune context of the human heart. This review critically compares five partly overlapping model families: cardiac spheroids and aggregate-based microtissues, developmentally self-organizing cardiac organoids and assembly-guided constructs, engineered heart tissues, heart-on-a-chip systems, and living myocardial slices. The comparison distinguishes how tissue organization is generated or preserved, which variables can be controlled, how function is measured, and which conclusions are supported by the resulting evidence. Across model families, interpretation is shaped by species and cell source, maturation state, cellular composition, conditioning, transport, measurement design, and donor variables. Representative studies illustrate applications in cardiac development, functional perturbation, fibrosis, immune -cardiac interactions, genotype attribution, and retained adult tissue physiology. Major limitations include domain-specific and incomplete maturation, restricted oxygen delivery, variable cellular persistence, technical reproducibility, limited access to human tissue, and insufficient consideration of donor sex and hormonal context. Rather than identifying a universally superior platform, this review proposes a claim-validation alignment in which model selection is guided by the biological question, the required tissue features, the relevant endpoint, and the level of inference supported by validation.

Abstract: Background/Objectives: Simple, reproducible in vitro liver models are increasingly important for early screening strategies aligned with the 3Rs principles. However, three-dimensional culture effects depend strongly on spatial organization, and greater structural complexity does not nec-essarily improve functional performance. This study compared five AML12 culture configura-tions to evaluate their effects on hepatocyte-associated characteristics. Methods: AML12 cells were cultured for 7 days under matched conditions using conventional tissue-culture plastic (2D-TC), two-dimensional collagen-supported culture (2D-Coll), three-dimensional culture on a collagen gel (3D-Coll), collagen sandwich culture (3D-SW), and collagen-supported spheroid cul-ture (3D-Sph). Cellular organization, cell abundance and size, metabolic and biochemical param-eters, and transcriptional markers were evaluated using four biological replicates for gene-expression analyses and six for biochemical measurements. Multivariate analyses were used to characterize transcriptional patterns. Results: Cell number remained comparable across con-figurations, whereas cell size, metabolic activity, biochemical endpoints, and transcriptional pro-files differed. The collagen sandwich produced the most consistent hepatocyte-associated profile, with increased Alb, Hnf4a, Ttr, and Trf expression and the highest urea production. Spheroids showed the highest cell-normalized resazurin activity and multicellular aggregation, while 2D collagen exhibited a stronger stress-associated profile. PERMANOVA confirmed an overall effect of culture configuration on transcriptional profiles (R² = 0.442, p < 0.001). Conclusions: AML12 responses depended on culture configuration rather than following a simple 2D-versus-3D pattern, highlighting the importance of spatial organization when selecting in vitro liver models.

Abstract: Primary cultures and organoids from lung cancer patients preserve tumor heterogeneity and enable patient-specific functional testing. Their generation has relied largely on surgical resection, which most patients never undergo because their disease is diagnosed too late. This review examines whether minimally invasive sources, namely cryobiopsy, endobronchial ultrasound-guided transbronchial needle aspiration, bronchoscopic biopsy, computed tomography (CT)-guided transthoracic needle biopsy, and malignant pleural effusion, can serve as alternatives. To compare outcomes across studies, we distinguish four endpoints: tissue adequacy, initial formation, long-term validated establishment, and molecular fidelity to the source tumor. Reported establishment rates from these sources range from 10% to over 80%, and some matched or exceeded surgical tissue within the same study. Yet these figures depend on how success is defined. In one cohort, organoids formed from 41% of specimens, but only 17% yielded verified tumor organoids. In another, cancer-associated fibroblasts dominated 46 of 51 cultures. Anatomical site, medium composition, and overgrowth by stromal or normal airway cells therefore explain outcomes better than acquisition route alone. Ex vivo drug responses have been linked to clinical outcomes, but prospective validation is lacking. Standardized multi-endpoint reporting and routine confirmation of molecular fidelity are needed before these models can guide therapy.

Abstract: Dendritic cells (DCs) play an important role in coordinating innate and adaptive immunity through antigen processing, presentation and activation of immune effectors. However, DC vaccine-induced immune activation has not consistently translated into clinical benefit. In this review, we discuss the potential of engineered allogeneic DC vaccines, with emphasis on CD34+ progenitor-derived DCs expressing CD93, CD40 ligand (CD40L) and CXCL13. These preparations were found to enhance lymphocyte activation and reduce pancreatic tumor burden in humanized mouse models. Vector optimization retained tumor-inhibitory activity, although small cohorts and substantial attrition limit interpretation of the advanced-disease findings. We also discuss the differential effects of osteoclasts and DCs on natural killer (NK)-cell function and CD4+ and CD8+ T-cell expansion, and the importance of separating donor-directed alloreactivity from tumor-antigen-specific responses. Clinical studies in pancreatic cancer support the induction of antigen-specific immunity, whereas randomized DC studies in prostate cancer, melanoma and mesothelioma demonstrate the continuing challenge of translating immune activation into improved outcomes. We propose that further development should focus on recipient-human leukocyte antigen (HLA)-compatible tumor recognition, the contribution of individual transgenes, reproducible product potency, post-thaw function and product-specific safety. Together, these findings support continued investigation of engineered allogeneic DC vaccination as a strategy to coordinate antitumor immune responses, while clinical benefit remains to be established in controlled studies.

Abstract: The adult mammalian heart does not regenerate. After myocardial infarction, cardiomyocytes are lost permanently because the surviving cells are terminally differentiated and post-mitotic. Regenerative vertebrates such as zebrafish and newts retain proliferative, centriole-bearing cardiomyocytes and repair the heart completely, whereas mammals lose this capacity within the first postnatal week. I propose that the centriole functions as a differentiation ratchet: a heritable structural input that couples proliferative potential to centriole integrity through the mitotic surveillance pathway (MSP). The strongest natural evidence comes from the heart. Shortly after birth, mammalian cardiomyocytes undergo programmed centrosome disassembly, with pericentriolar material relocating to the nuclear envelope. Pharmacological depletion of centrioles is sufficient to drive the post-mitotic transition in human cardiomyocytes, and failure of this step is pathogenic: a mutation in the centrosomal gene RTTN causes infantile dilated cardiomyopathy. Because the adult cardiomyocyte is one of the few naturally and permanently acentriolar somatic cells, it offers a ready-made testbed for asking whether the ratchet can be reversed. A single-nucleus transcriptomic analysis of the developing human heart (fetal, young and adult) presented here shows that this shutdown is actively installed during maturation rather than a passive decay: adult cardiomyocytes reduce their centriolar program—PLK4, CEP192, SASS6, STIL and NEK2 are all down-regulated—while the p53 effector p21 (CDKN1A) is elevated, the signature of a p53-maintained post-mitotic lock. The roadmap proceeds in three steps, all conducted in cell culture: (i) release the G0 lock and assess TRIM37 and PLK1 status; (ii) restore a licensed centriole from an autologous low-entropy adult stem cell, with PLK1 and Ect2 co-delivery; and (iii) enforce a strict safety gate that includes TRIM37, p53 pathway, and contractile function assessment. Eight pre-registered, falsifiable hypotheses are stated below, and the principal risks are analyzed.

Abstract: For decades, classical anatomical dogma has dictated that "without the kidney, the renal fascia cannot form." However, this premise was based on historical anatomical specimens lacking both the kidneys and adrenal glands, likely reflecting broad developmental field defects. In this study, congenital unilateral renal agenesis was examined as a natural "subtraction experiment" to test the mechanical model of retroperitoneal fascial lamination. In three adult cases identified from 5,509 unenhanced abdominal CT scans, despite the lifelong absence of the kidney, a distinct fascial plane corresponding to the parietal lamina (outer layer) of the renal fascia was consistently preserved. Uniform thinning (mean 1.52 mm on the agenesis side vs. 1.85 mm on the contralateral healthy side) was observed, supporting the selective absence of the organ-dependent "inner lamina" and the autonomous formation of the systemically derived "outer lamina." By integrating fetal embryology, materials science, and mechanobiology, we hypothesize that fascial lamination is driven by a strict three-step mechanobiological sequence. First, the primitive jelly-like mesenchyme undergoes a material phase transition into an isotropic poroelastic solid during the mid-trimester (15–20 weeks). Second, coupled with human-specific early trunk stiffening (evolutionary front-loading), this mature matrix unlocks the capacity to respond to multiaxial tension fields. Third, tension-induced Poisson compression may trigger massive fluid expulsion (syneresis), collapsing the isotropic matrix into anisotropic 2D fascial sheets. We outline a two-stage alignment model consisting of this passive Poisson compression followed by active mechanotransduction. Furthermore, we propose a conceptual causal loop wherein fascial sheets structurally primed by fetal tension fields are functionally co-opted (exapted) to disperse and transmit gravitational loads encountered during postnatal upright bipedalism. These findings suggest that retroperitoneal fascial morphogenesis is governed not merely by local organ-dependent mechanisms, but also by systemic biomechanical fields and material phase transitions.

Abstract: The aim of this paper is to demonstrate the feasibility of applying immunohistochemical interrogation of cleared embryos to reveal three-dimensional distribution of protein expression related to facial skeletal development while preserving anatomic context. Here we show the development of a collagen 3 facial bone precursor involved in the formation of the embryonic mandible. Within the tissue volume occupied by the collagen 3 mandible form, collagen 1 is expressed. The process is dependent on developmental stage. This event is demonstrated in the e15.5 mouse embryo. In the e11.5 mouse embryo, collagen 3 expression is demonstrated surrounding early vessels but there is no evidence of mandible formation at that stage. We show that this acquisition method allows analysis of collagen 1, collagen 3, and others in the same specimen while maintaining congruency of the data sets.

Abstract: This exploratory pilot used targeted bisulfite sequencing to profile 16 imprinting control regions (ICRs) across 8 imprinted genes in 12 individuals from 4 families, testing whether ICR methylation carries molecular signals of two behavioral dimensions of innate predisposition. Personality traits are moderately heritable, yet their molecular carriers remain largely unknown. Within a dual-layer framework of innate predisposition and acquired personality, the author identified through long-term observation a set of highly reproducible non-Mendelian intergenerational transmission patterns, suggesting that innate predisposition may be linked to methylation at imprinting control regions. Using molecular features selected under the independently observed ABCD framework, the author found that the signals resided not in the average level of ICR methylation but in its internal spatial structure. The rationality dimension corresponded to methylation at specific KvDMR1 subregions (KCNQ1 difference r = +0.760), and the dominance dimension to the asymmetric methylation distribution within the PEG3 ICR (3′-half skewness r = +0.785). The two axes were nearly completely orthogonal at the epigenetic level (r = −0.038), and nearest-centroid classification matched behavioral labeling in 91.7% (11/12, full-sample resubstitution; exploratory finding).

Abstract: Rehabilitation interventions do not act independently of the physical conditions in which movement occurs. Orthoses, positioning systems, and movement-assistance devices modify the mechanical conditions under which movement is performed. The Pavlik harness provides a classical clinical example. Developed for the treatment of developmental dysplasia of the hip (DDH), it maintains the hip in a therapeutic position while allowing a degree of movement within mechanically imposed constraints [1–3]. The Pavlik method was developed within pediatric orthopedics rather than rehabilitation engineering. Its clinical logic can nevertheless be reconsidered from an engineering perspective: movement may be guided by modifying its mechanical environment rather than simply eliminating movement. Modern rehabilitation technologies provide ways to make selected movement conditions explicit, adjustable, and reproducible. Continuous passive motion (CPM) is one such example, because joint movement can be generated according to predefined mechanical parameters [4]. This Perspective does not propose CPM as an extension or replacement of the Pavlik method. The relationship is conceptual rather than therapeutic. Pavlik illustrates mechanical guidance with preserved movement; CPM illustrates how a movement condition can be translated into a programmable mechanical input. The central proposition is therefore narrower: the physical conditions surrounding movement can themselves become variables for rehabilitation engineering research.

Abstract: Sex chromosomes originate from a homologous pair of chromosomes becoming restricted to one sex (referred to as Y in males in the X/Y system; W in females in the ZW system) via inhibition of crossing over followed by gene loss. In contrast, most other forms of chromosomal dosage change caused by meiotic or mitotic errors, or experimental aneuploidy, are strongly deleterious or lethal. The viability of individuals with the heteromorphic sex chromosomes in various species comes from the acquisition of some type of dosage compensation that counteracts any issues with “genomic imbalance”. Here we review lessons learned about gene expression modulation from experimentally produced aneuploidy and from evolutionary genomics. These lessons from genome balance principles are applied to how different examples of sex chromosome dosage compensation (Drosophila, mosquito, mammals, nematodes) have evolved to counteract any detrimental global effects on gene expression. New perspectives and questions are raised to revise ideas about sex chromosomal evolution and to direct re-analyses of previous hypotheses.

Abstract: Background: Unhealthy dietary patterns and nutrition literacy level are some of the major modifiable risk factors for non-communicable disease in Saudi Arabia. Theoretically, nutrition knowledge, self-efficacy for healthy eating and perceived social support are believed to play a role in healthy lifestyle adoption, but there is a limited local evidence of these constructs from university samples in the Jazan region. Design: A descriptive study.Objective: To describe the nutrition knowledge, self-efficacy and perceived social support of female students and staff of Jazan University and to investigate their relationships with self-reported Body Mass Index (BMI). Methods: A cross-sectional design was used. The researcher gathered the data using a self-administered online questionnaire, filled out in Arabic and English, which included the following items: sociodemographic items, eight multiple-choice items on nutrition knowledge, a seven-item self-efficacy scale and a six-item perceived social support scale (both on 5-point Likert scales) and self-reported height and weight. Internal consistency was measured for the Likert scales with Cronbach’s alpha and for the knowledge items with KR-20. Spearman correlation coefficient, Kruskal-Wallis test and multiple linear regression were used to look at associations. A p-value of < 0.05 was defined as statistically significant. Twenty-four people filled out the survey (75.0% students, 20.8% faculty, 4.2% administrative/technical staff; 62.5% age 18-22 years). The mean score for nutrition knowledge was 6.58/8 (SD = 1.59; 82.3% correct) with the lowest mean item correctness rate of 41.7% on the recommended daily fruit/vegetable servings item. Mean self-efficacy was 3.39 (SD = 0.65, range 1-5) and mean perceived social support was 3.36 (SD = 0.57). The reliability of the self-efficacy scale was acceptable (Cronbach’s alpha = 0.70), as was that of the knowledge scale (KR-20 = 0.64), but not for the social support scale (alpha = 0.54). After two underweight/height and overweight/height pairs were excluded, the average self-reported BMI of the remaining 22 cases was 23.9 kg/m2 (SD = 5.2) and 29.2% of the subjects were classified as underweight and 20.8% were considered obese. There was a significant (Spearman’s rho = -0.47, p = 0.026) and negative correlation between BMI and perceived social support in a multiple regression model controlling for nutrition knowledge (B = -6.89, p = 0.009). The role and age group were not significantly related to knowledge or self-efficacy or to social support (p > 0.05 for all). Conclusion: This preliminary sample showed that nutrition knowledge was relatively high, but varied by topic. Self-reported BMI was most closely related to perceived social support, and not to nutrition knowledge. Although these preliminary findings from a small convenience sample should be interpreted with caution and future studies with a larger, more adequately powered sample are needed to confirm these results, the results do suggest that social-support oriented components would be a potentially useful addition to campus nutrition education programming.

Abstract: Background: Efficient transport of mesenchymal stem cell (MSC) products represents a major practical barrier to the clinical implementation of regenerative medicine. Clinically approved intravenous preservation fluids are not optimised for MSC preservation, and many standard hypothermic preservation solutions are not approved for direct injection, necessitating an additional washing step prior to administration. Additionally, maintaining the immunophenotypic identity of MSCs—as defined by the International Society for Cell and Gene Therapy (ISCT) minimal criteria—during transport is essential to confirm that clinically significant cellular characteristics are preserved. Methods: Human adipose-derived MSCs were suspended in normal saline, 5% dextran L (a Japanese-approved injectable formulation), and Lactated Ringer's solution. Samples were stored at refrigerated (4°C), room temperature (25°C), and body temperature (37°C) conditions. Viability was determined by trypan blue exclusion using an automated cell counter at hourly intervals from 0 to 4 hours. Immunophenotypic characterisation by flow cytometry (FCM) was performed on MSCs stored in the optimal (4°C dextran L) and worst (37°C normal saline) conditions at both 0 hours (pre-storage baseline) and 4 hours to assess preservation of ISCT surface marker criteria. Cellular membrane integrity at both timepoints was additionally confirmed by 7-aminoactinomycin D (7-AAD) exclusion staining. Results: Viability was not markedly affected across solutions and temperatures up to 2 hours; however, viability declined from 3 hours onwards. Storage at 37°C had a pronounced detrimental effect. FCM analysis confirmed full ISCT compliance in 4°C dextran L at 4 hours: CD73⁺ (99.96%), CD105⁺ (99.98%), CD90⁺ (99.47%), CD34⁻ (0.08%), CD45⁻ (0.003%), and HLA-DR⁻ (0.61%). In contrast, MSCs stored in 37°C normal saline for 4 hours exhibited two ISCT violations: CD105+ expression fell to 92.51% (below the ≥95% threshold) and CD34− expression rose to 12.49% (above the ≤2% threshold). 7-AAD staining confirmed near-complete membrane integrity at baseline in both conditions (0.000% and 0.061% 7-AAD⁺, respectively). In 4°C dextran L, 7-AAD positivity remained at 0.000% at 4 hours. In 37°C normal saline, 7-AAD positivity was unchanged at 0.061% at 4 hours despite a 49-percentage-point trypan blue viability decline, indicating that cellular deterioration under warm-storage conditions occurs predominantly through sub-lytic membrane compromise not captured by 7-AAD exclusion alone. Conclusions: Cell death begins within 2–3 hours following suspension in clinically approved solutions, indicating that transport conditions critically affect viability. MSCs stored in 4°C dextran L maintain full ISCT-compliant immunophenotypic profile at 4 hours with 100% 7-AAD-confirmed membrane integrity, suggesting that dextran L preserves both phenotypic identity and structural integrity beyond the limits detectable by trypan blue alone. Critically, MSCs stored in 37°C normal saline for 4 hours demonstrated two ISCT violations—CD34 upregulation (12.49%) and reduced CD105+ expression (92.51%)—alongside a marked trypan blue viability decline (Δ ≈ −49 pp) without a corresponding 7-AAD increase. This discordance indicates that warm-storage cellular deterioration proceeds predominantly via sub-lytic stress mechanisms, underscoring the complementary value of trypan blue and 7-AAD for MSC product quality control. Furthermore, cells replated after 4-hour storage in 4°C dextran L demonstrated normal plastic adherence at 24 hours post-replating, confirming preservation of this fundamental MSC functional property. Dextran L offers the practical advantage of obviating a post-storage wash step and may represent a pragmatic transport medium for clinical MSC workflows.

Abstract: Post-translational modifications are rarely studied as an integrated system. Most studies have focused on acetylation or ubiquitination in isolation, despite both frequently targeting the same lysine residues on the same proteins. This study investigated whether the interplay between these modifications, rather than their individual effects, constitutes a meaningful regulatory layer in cervical cancer cells. Quantitative stoichiometric proteomics was applied to HPV-positive and HPV-negative cell models, with a non-cancerous keratinocyte serving as control. The results demonstrate that acetylation and ubiquitination form coordinated, context-dependent patterns rather than acting independently. In HPV-positive cells acetylation predominated and was enriched in transcriptional regulators. Conversely, the HPV-negative C33a line exhibited a substantially larger ubiquitinome, indicative of increased proteostatic surveillance. Site-specific stoichiometry analysis revealed that the relative occupancy of each modification at shared lysine residues determines regulatory outcomes, rather than their mere presence. This competition is proposed to constitute a "lysine fate code" that integrates transcriptional regulation, metabolic adaptation, and immune signaling into a unified proteostatic logic. Beyond their implications for cervical cancer biology, these findings suggest that the acetylation-ubiquitination balance may represent a key regulatory principle. Targeting enzymes that modulate this balance could provide novel therapeutic strategies that surpass single-pathway inhibition.

Abstract: Living organisms are materially dynamic systems. Proteins are continuously synthesized and degraded, membranes are remodeled, metabolites are exchanged, organelles are renewed, cells can be replaced, and tissues can undergo substantial structural change. In spite of all these, a living organism may remain the same biological individual throughout these transformations. This gives rise to a question: If persistence of matter is not required for persistence of the organism, what exactly is preserved through biological changes ? Autopoietic theory, organizational approaches to biology, and works on diachronic identity have all emphasized processes of self-maintenance, organizational closure and continuity through change. This paper does not claim to discover the general idea that biological identity is organizational rather than merely material. Rather, it identifies the following gap: biological discussions often move between material continuity, and numerical identity without separating these distinct notions clearly The paper argues that this distinction deserves explicit treatment in mainstream biological reasoning. “Material turnover” is a measurable empirical phenomenon, whereas “Organismal persistence” is a continuity judgment made across time. These two are not equivalent variables. An ideal framework should therefore distinguish the changing physical substrate from the persistence of the organization that coordinates this substrate, also recognizing the role of historical continuity. The central proposal of this paper is that studies of biological persistence should state explicitly whether they are tracking material, structural, functional, organizational or historical continuity. I end the paper with a research agenda for testing whether measures of organizational continuity provide a better description of organismal persistence than measures based on material similarity alone.

Abstract: Background: The "avascular plane," which surgeons navigate during total mesorectal excision (TME) and robot-assisted radical prostatectomy (RARP), has conventionally been explained as a static boundary, such as an "embryological plane" where different developmental compartments adjoin, or a "fusion fascia" where tissues contact during embryogenesis. However, these classical models harbor fundamental contradictions; they cannot causally explain clinical facts such as why blood vessels cannot invade despite the mesenchyme sharing the same mesodermal origin, why only nerves remain, the continuity between the lateral ligament and the neurovascular bundle (NVB), and the pronounced bilateral asymmetry of the prehypogastric nerve fascia. Methods: By analyzing the temporal gap between fetal fascial lamination (13–20 gestational weeks) and nerve wiring establishment, we constructed a biomechanical model integrating the extracellular matrix (ECM) poroelastic transition, anomalous Poisson effect (orthogonal compression), and organ-induced shear stress. The model's validity was evaluated against intraoperative observations regarding fascial lamination, bilateral asymmetry, and neurovascular condensation during TME and RARP. Results: Due to the phase transition of the ECM and the stiffening of the truncal skeleton between 13 and 20 gestational weeks, multiaxial tension accumulates in the mesenchymal tissue of the retroperitoneum and pelvis, which likely drives simultaneous lamination via anomalous Poisson compression. Shear stress associated with the cyclic volumetric changes of organs concentrates at the lamination boundaries and may physically destabilize the anchoring of capillaries, thereby likely perpetuating an avascular state. Conversely, nerves establish their wiring prior to lamination and remain safely in the gliding plane, mechanically consistent with their ability to withstand shear stress due to the robust perineurium. The three-layered fascia of the presacral space is formed as a mechanically logical structure through tension shadowing and passive lamination. Furthermore, it is reasonable to interpret the lateral ligament essentially as a shear refuge acting as the proximal root of the NVB. The pronounced bilateral asymmetry of the prehypogastric nerve fascia is explained by differences in the mechanical boundary conditions established by retroperitonealization of the ascending and descending colonic mesenteries. These asymmetric fixation interfaces likely influence the accumulation of developmental tension and subsequent Poisson compression, favoring more distinct fascial lamination on the left side. Conclusion: The avascular plane is not a static embryological boundary but may be better understood as a "biomechanical fault line" carved continuously by the tension field, Poisson compression, and shear stress generated during fetal life, which are hypothesized to physically inhibit the anchoring of angiogenesis. The act of a surgeon selecting a safe cleavage plane and preserving nerves is closely aligned with intraoperatively tracing these mechanical structures formed during fetal development. This study provides a novel anatomical paradigm that enhances the safety of pelvic surgery.

Abstract: Pannexin 1 (Panx1) participates in ATP release, purinergic signaling, and neuroinflammation, but its cellular context in ischemic stroke remains incompletely defined. We integrated bibliometric analysis with single-cell and bulk transcriptomic analyses to characterize Panx1-associated biological and cellular states. Bibliometric trends showed increasing emphasis on ischemia, inflammation, mitochondrial stress, calcium signaling, and regulated cell death. In GSE174574, Panx1 transcript detection was sparse but more frequent after MCAO than in sham brain and was associated with disease-remodeled myeloid populations, including activated microglial and monocyte/macrophage states. Pseudotime analysis placed Panx1-detected cells along an MCAO-associated myeloid activation structure without a strictly monotonic increase in Panx1 detection. Independent validation in GSE58720 further supported enrichment of Panx1-associated myeloid/stress and inflammatory signatures after MCAO. Together, these findings identify an injury-associated inflammatory/myeloid context for Panx1 in ischemic stroke and provide a basis for future mechanistic investigation.

Abstract: The metabolic landscape of the post-implantation mouse embryo and its associated placenta remains incompletely characterised. Here, we performed untargeted LC–MS-based metabolomics on mouse embryos from E9.5 to E13.5 and on placentas from E10.5 to E12.5, and integrated these data with a published single-cell transcriptomic atlas of the same developmental window. We found that the embryonic metabolome undergoes progressive remodelling, with the most pronounced changes occurring around E11.5. By combining time-course analysis, WGCNA-based network prioritisation, and embryo–placenta comparison, we identified 56 core metabolites that increased coordinately in both tissues during this period. Single-cell analysis revealed that the definitive erythroid lineage was enriched for nicotinate and nicotinamide metabolism, with progressive upregulation of the NAD+ biosynthetic enzyme Nmnat2 during erythroid maturation. Correspondingly, niacinamide, NAD, and 1-methylnicotinamide increased in the embryo from E10.5 to E13.5. Regulon analysis showed that haematopoiesis-related transcriptional programmes, including Spi1 and Gfi1, correlated with development-associated metabolic modules. Together, our data provide a stage-resolved metabolomic resource and identify candidate metabolites that may support embryo growth in vitro.

Abstract: Telomeres, the ends of linear chromosomes, form a cap composed of specific telomeric DNA asso-ciated with specialized proteins that ensures efficient protection against chromosome degrada-tion and, consequently, overall genome instability. Three main complexes have been implicated in chromosome end protection, namely telomerase, shelterin, and the CST complex (CTC1/Cdc13-STN1-TEN1). In a recent study, we uncovered mutants of the S. cerevisiae CST in which damage was sensed both by the two major spindle checkpoints and the major DNA damage checkpoint. In the best-studied of these mutants, stn1-sz2, the stability and organization of the mitotic tubulin spindle was profoundly affected, as were the organization of the centrosomes and the kineto-chores. Here, we find that the stn1-sz2 mutant is hypersensitive to deletion mutants of two mem-bers of the kinetochores, Ctf19 and Mcm21, which correlated with mis-localization of their asso-ciated subunit in the COMA complex, Okp1, during anaphase. Defects in interactions between the kinetochores and the tubulin spindle are entirely sensed by the SAC (spindle assembly check-point). Here, we find that some of the stn1-sz2 damage is recognized by the Mad2 checkpoint pro-tein independently from the SAC. The data presented here contribute to a better understanding of the damage in stn1-sz2, the prototype of novel mutants of telomeric CST characterized by mitotic-spindle-damage in addition to the classical telomeric-DNA-damage.