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PubMed2026

Comprehensive analysis suggests CRIF1 is a potential target in breast cancer associated with prognosis and immune infiltration.

BACKGROUND: CRIF1 is a multifunctional factor that regulates cell biological processes such as the cell cycle, cell proliferation, and energy metabolism, and it is a new molecule that contributes to the poor prognosis of many malignancies. However, its involvement in breast cancer development is not fully known. MATERIALS AND METHODS: To investigate the relationship between CRIF1 expression, prognosis, and clinical characteristics using The Cancer Genome Atlas (TCGA-BRCA). The relationship between CRIF1 expression and the immunological microenvironment was investigated using CIBERSORT, ESTIMATE. Breast tissue and CRIF1 expression were validated by IHC. A tiny interfering plasmid was designed to transiently transfect breast cancer cell lines, and proliferation-related functional tests were carried out. The effect of sh CRIF1 on tumor formation was confirmed using a subcutaneous tumor experiment in naked mice. RESULTS: We discovered that CRIF1 was highly elevated in breast cancer tissues and associated with a poor prognosis. CRIF1 stimulates breast cancer cell proliferation, migration, and invasion. Knockdown decreased PI3K/AKT/mTOR signaling, which boosted autophagy activity. Immune infiltration research revealed that patients with high CRIF1 expression had higher CD8+ T cell expression but reduced macrophage M2 expression. CONCLUSION: Upregulation of CRIF1 in breast cancer cells enhances malignant behavior, which may be mediated by PI3K/AKT/mTOR signaling and is linked to cellular autophagy.

Humans↗
PubMed2026

Single-cell RNA sequencing provides further insights into the immunostimulatory action of freeze-dried Lactiplantibacillus plantarum on Penaeus vannamei shrimp.

Immunostimulation through dietary interventions opened new avenues in developing disease control and prevention tools for shrimp aquaculture. We have previously shown that feeding with freeze-dried Lactiplantibacillus plantarum (LAB) increased disease resistance of Penaeus vannamei against both Vibrio parahaemolyticus and white spot syndrome virus (WSSV) based on bulk RNA sequencing of shrimp gills. This tissue participates in ion transport and serves as a first line of defense against environmental stressors and pathogenic infections. However, characterization of their cell composition and functions remains limited. Here, we implemented a single-cell RNA sequencing approach to further gather insights into how feeding with freeze-dried LAB modulates host immunity which may not be evident with bulk RNA sequencing approach. A total of five clusters with unique transcriptional signatures were identified, corresponding to pillar cells, septal cells, and sessile hemocytes. Pseudo-bulk analyses at global- and cluster-levels showed differential expression of genes related to host immunity and metabolism. We further revealed how overall transcriptomic changes are not exclusively caused by gene expression changes but may also be driven by cell population dynamics. This study highlighted how single-cell RNA sequencing approach may shed light on the mechanisms of action of immunostimulants which may be masked in bulk transcriptome analyses.

Animals↗
PubMed2026

Single-cell transcriptome revealed the aberrant keratinocytes activation in antigen presentation in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD), a common chronic inflammatory skin disease, has been extensively studied using single-cell genomics. However, keratinocytes, as key effector cells in AD, have underlying mechanisms remain incompletely understood and require further investigation. METHODS: We integrated single-cell transcriptomic data from skin tissues of healthy controls, chronic active AD patients, spontaneously healed AD (SHAD) patients, and an ovalbumin-induced AD mouse model. The study particularly emphasized the gene expression and cellular dynamics of keratinocytes across the different groups, as well as their interactions with immune cells. RESULTS: Compared to healthy controls, we observed significant changes in the keratinocyte transcriptome, cellular state, and keratinocyte-immune cell ligand-receptor interactions in AD skin, particularly the marked activation of genes involved in antigen processing and presentation. Interestingly, such gene activation was not observed in keratinocytes from the ovalbumin-induced AD mouse model, despite its phenotype closely resembling human AD. Furthermore, in SHAD, we identified a recovery of both the ligand-receptor interaction patterns and antigen processing and presentation genes, accompanied by a notable shift in the transcriptome. This involved a significant downregulation of genes related to cytoplasmic transcription and oxidative phosphorylation. Notably, this pattern was not observed in the self-healing mouse model following the removal of ovalbumin stimulation. CONCLUSION: Our results suggest that the persistent activation of antigen processing and presentation pathways in keratinocytes may be a key driver of chronic inflammation in AD. Therefore, redirecting anti-allergic therapeutic strategies from solely targeting immune cells to targeting of keratinocyte-mediated antigen presentation may offer a more effective approach. Furthermore, we raise concerns about the use of ovalbumin-induced mouse models to recapitulate human chronic AD, as the underlying mechanisms may differ significantly.

Dermatitis, Atopic↗
PubMed2026

Generation of spCAS9 expressing human mesenchymal stem cell line to study gene function during osteoblast differentiation.

Human bone marrow-derived stromal cells (hMSCs) are a great resource for studying how genes influence cell fate and differentiation into various cell types like osteoblasts, adipocytes, and chondrocytes, among other cell types. However, genetic manipulation of primary hMSCs has been challenging due to their short lifespan and cellular senescence after limited passaging. Their low and unstable transfection efficiency also complicates gene delivery or inactivation, hindering long-term functional studies. The limited lifespan has been effectively solved by immortalizing hMSCs with telomerase reverse transcriptase (hMSCs-TERT). The use of these cells is ideal for functional studies of osteoblast and adipocyte differentiation through genetic manipulation, providing a stable and reliable model. Here, we have engineered a stable CAS9 expressing hMSC-TERT cell line (hMSC-TERTCAS9) via lentiviral transduction. The constitutive expression of spCas9 enables efficient and reproducible gene editing. We demonstrate the potential of these hMSC-TERTCAS9 cells for generating gene disruptions using plasmid delivery of guide RNAs as a fast and efficient strategy for targeted genome editing. The edited cells can be sorted and expanded as single cells to obtain homogenous clonal cell lines with mono- as well as bi-allelic gene deletions, a crucial step for producing reliable experimental results. We further validate this cell line as a powerful tool for studying gene function during hMSC proliferation and differentiation, providing 3 distinct examples of its utility. Through the generation of indels, single-cell sorting, and clonal selection, we have efficiently inactivated the vitamin D receptor and created both larger (256 nucleotides) gene disruptions in Forkhead box protein O1 and precise removals of a small genomic sequence (73 nucleotides) coding for microRNA MIR675. This novel hMSC-TERTCAS9 cell line represents a significant advancement, offering a stable, efficient, and versatile platform for advanced genetic studies, high-throughput screening, and the creation of reliable cellular disease models.

CRISPR-Cas9↗
PubMed2026

Integrin-Linked Kinases 1, 4, and 5 participate in cell wall-mediated innate immunity to leaf and root pathogens.

The cell wall integrity (CWI) pathway is triggered by plasma membrane-localized receptors in plant cells and serves to orchestrate responses to cell wall damage by initiating compensatory changes under stressful environments. The essential role of CWI maintenance as part of plants' interactions with pests or pathogens and during growth is well known. Nevertheless, CWI pathways remain to be fully characterized. Here, we show that altered Integrin-Linked Kinase 1 (ILK1) expression causes widespread defects in the transcriptional program activated by the bacterial elicitor flg22, primarily in genes associated with cell wall integrity and immunity. These transcriptional deficiencies are recapitulated in mutant lines with altered ILK4 or ILK5 expression. Analysis of molecular and cellular defenses in ilk mutants revealed reduced callose accumulation in leaves treated with bacterial (elf18) and plant (pep1) elicitors and increased pathogen susceptibility. Histochemical analysis of cell-wall-associated staining across diverse cells and organs of ilk mutants revealed modified lignin-associated patterns in the root xylem and altered calcofluor staining patterns in the seed coat. All ilk mutants exhibited altered root morphology due to mechano-touch and high-NaCl stress. Based on these results, we propose that ILKs contribute to pathways connecting elicitor-triggered immune signaling with cell-wall-associated stress responses and that ILK-related defense functions may extend to the cotton root-nematode interaction, while the mechanism remains to be elucidated.

Cell Wall↗
PubMed2026

Single-cell transcriptomics reveals heterogeneous stress responses and Mg2+-mediated survival mechanisms in Lactobacillus delbrueckii subsp. bulgaricus during freeze-drying and storage.

Maintaining the viability of lactic acid bacteria during dehydration and subsequent storage remains a significant challenge. Here, we employed single-cell RNA sequencing to reveal the heterogeneous stress responses of Lactobacillus delbrueckii subsp. bulgaricus, identifying seven distinct transcriptional clusters across the liquid culture, freeze-drying, and storage phases. The dominant clusters in the freeze-drying and storage were not completely consistent, showing significant functional differentiation. Genomic stability may be important for survival during freeze-drying and storage, while intracellular energy homeostasis appears important for viability during storage. The magnesium transporter mgtB was highly expressed in clusters tolerant to freeze-drying and storage, suggesting a critical role for Mg2+ homeostasis. Further experimental validation confirmed that Mg2+ treatment significantly bolstered stress resistance, increasing immediate post-freeze-drying survival by over 2-fold (up to 92.90%) and post-storage survival by over 5-fold (up to 5.98%). Proteomic data indicated that Mg2+ supplementation correlated with the maintenance of several biological functions potentially relevant to bacterial survival during freeze-drying and storage, including DNA repair, translation, and central carbon metabolism. These findings provide a map of microbial stress resistance through population heterogeneity and offer a potential strategy that may be adapted for enhancing the stability of other industrial lactic acid bacteria products.

Freeze Drying↗
PubMed2026

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50 μM, and intracellular concentrations and cell viability were monitored over 48 h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry↗
PubMed2026

Identification of CD55 as a downstream factor of EP4 receptor signaling in colorectal cancer cells.

Prostaglandin E2 (PGE2) signaling through the E-type prostanoid 4 (EP4) receptor has been implicated in the pathophysiology of colorectal cancer (CRC). We herein identified decay-accelerating factor, also known as CD55, as a novel CRC-associated downstream factor of the EP4 receptor. The integration of transcriptomic profiling of PGE2-stimulated HCA-7 human colon cancer cells with analyses of cancer genomic databases predicted CD55 as a potential EP4 receptor-regulated target. Inhibitor-based experiments showed the induction of CD55 after a PGE2 stimulation required the EP4 receptor and Gi protein in HCA-7 cells, whereas protein kinase A signaling was dispensable. In combination with a toxicogenomic database analysis, p38 mitogen-activated protein kinase (MAPK) was identified as the predominant effector connecting the EP4 receptor to CD55 upregulation. A single-cell RNA-seq re-analysis of human CRC tissues revealed CD55 upregulation and p38 MAPK-related gene set enrichment in epithelial cells expressing the EP4 receptor, suggesting that this induction mechanism may operate in a subset of epithelial cells in clinical specimens. Collectively, these results delineate a PGE2/EP4 receptor/Gi protein/p38 MAPK signaling axis that induces CD55 expression in HCA-7 cells and epithelial tumor cells, provide new mechanistic clues for understanding the regulation of complement regulatory molecule CD55 expression by prostaglandin signaling.

Humans↗
PubMed2026

Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.

Myogenesis involves sequential stages of muscle satellite cell activation, myoblast proliferation, differentiation, and fusion into multinucleated myotubes. Teleost muscle exhibits indeterminate growth and is highly sensitive to environmental temperature, yet the underlying mechanisms by which temperature regulate proliferation and differentiation remain poorly understood. In this study, we established a primary skeletal muscle cell culture from the yellow drum (Nibea albiflora), an economically important marine fish, and integrated morphological observations with comparative transcriptomics analysis to characterize cellular and molecular responses at 28 °C and 20 °C during both proliferation and differentiation stages. Phenotypic analysis revealed that 28 °C significantly enhanced both myoblast proliferation and myogenic differentiation ability compared with 20 °C. Transcriptomic profiling revealed that at 28 °C, differentiation upregulated extracellular matrix(ECM) organization, calcium signaling, and sarcomere assembly, while proliferation enhanced focal adhesion, growth factor signaling, and lipid metabolism. At 20 °C, differentiation was characterized by glutathione metabolism, and ferroptosis, while proliferation involved cytokine-cytokine receptor interaction and negative regulation of signal transduction. Core myogenic regulatory factors (MRFs), particularly myogenin, were strongly upregulated at 28 °C during the differentiation stage, serving as an internal control. Based on these findings, we propose a testable model that elevated temperature coordinates Ca2+-dependent MRF activation with ECM-integrin signaling to drive sarcomere assembly and muscle growth. Key differentially expressed genes (DEGs) regulating myogenesis in N. albiflora were also identified. This study provides a mechanistic framework for temperature adaptation in teleost skeletal muscle and identifies candidate genes for functional validation and marker-assisted selection, as well as a rationale for temperature management strategies to improve aquaculture yield of N. albiflora.

Animals↗
PubMed2026

A genome-wide coverage-based pipeline for the identification of host-derived candidate DNA biomarkers from cell-free blood.

We have created a new data-analysis pipeline for the discovery of host-specific candidate DNA biomarkers derived from sequencing data of cell-free blood. Unlike approaches that rely on specific molecular or genetic signatures, our method leverages the coverage distribution of cell-free DNA sequences mapped to a reference genome, applying statistical analyses to identify informative short genomic regions for biomarker discovery. The pipeline is applicable to diverse diseases and can be used to analyze cell-free DNA sequences from plasma or serum to identify candidate biomarkers that are characteristic of disease states in mammals. Core functionalities were developed in Java and integrated with open-source software tools for the preprocessing of raw sequencing data, complemented by Python scripts for the machine-learning analysis and statistical validation. The pipeline is designed for HPC use and users can access the pipeline through a Galaxy workflow, which offers a user-friendly web interface for input selection prior to execution and analysis progress monitoring. Performance tests, carried out using duplicate sets of COVID-19 samples and controls, showed linear scalability of execution time with an increasing dataset size, as well as a substantial reduction in execution time through parallelized computation, whereby each HPC node is used to process the data of one chromosome. Further statistical tests confirmed the quality of the pipeline's results by showing that the set of identified candidate biomarkers remained stable across varying dataset sizes.

Biomarkers↗
PubMed2026

Association of hydroxyurea use and sickle cell retinopathy: A systematic review and meta-analysis.

Hydroxyurea (HU) is prescribed to reduce systemic complications of sickle cell disease; however, its association with sickle cell retinopathy (SCR) remains unclear. This meta-analysis (PROSPERO: CRD420251079006) evaluates the pooled association between HU use and SCR. In the primary analysis, HU use was not associated with a statistically significant reduction in SCR (OR = 0.90, 95% CI [0.41, 1.97], p = 0.79; I² = 77%). In a prespecified leave-one-out analysis, exclusion of the outlier study did not produce a statistically significant association, although the estimate shifted toward a stronger protective effect with reduced heterogeneity (OR = 0.70, 95% CI [0.39, 1.27], p = 0.25; I² = 67%). In a subgroup analysis excluding high-risk-of-bias studies, HU use was also not associated with a statistically significant reduction in SCR (OR = 0.84, 95% CI [0.39, 1.82], p = 0.66; I² = 77%). In post hoc analyses, HU use was not associated with a statistically significant reduction in SCR in non-adult populations (OR = 1.14, 95% CI [0.43, 3.05], p = 0.79; I² = 81%) or genotype-restricted analyses (OR = 1.22, 95% CI [0.81, 1.84], p = 0.35; I² = 0%). In post hoc analyses restricting studies to retinopathy phenotype, however, HU was associated with statistically significant lower odds of non-proliferative SCR (OR = 0.73, 95% CI [0.54, 0.98], p = 0.04; I² = 0%) and proliferative SCR (OR = 0.24, 95% CI [0.09, 0.60], p = 0.002; I² = 12%). Very low-certainty evidence suggests mixed associations between HU and SCR. Prospective studies are needed to clarify its role in SCR prevention.

Humans↗
PubMed2026

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi↗
PubMed2026

Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.

Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.

TLE↗
PubMed2026

Longitudinal Neurocognitive Changes for Patients With Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review With Structured Narrative Synthesis.

OBJECTIVES: Neurocognitive changes in hematological malignancies (HM) and as a sequela of hematopoietic stem cell transplantation (HSCT) remain under-recognized. These changes may substantially affect patients' quality of life. Therefore, this review systematically evaluated longitudinal neurocognitive changes in patients with HM undergoing HSCT. METHODS: Following PRISMA guidelines, PubMed, Scopus, and CINAHL were searched on October 30, 2025. Longitudinal studies assessing neurocognitive changes in patients with HM undergoing HSCT, with or without healthy controls, were included. Risk of bias was assessed using an adapted National Institutes of Health quality assessment tool for before-after studies. Effect sizes with 95% confidence intervals were calculated to quantify changes in neurocognitive performance. RESULTS: Nine of 2012 studies met the inclusion criteria, with overall moderate study quality. Improvements may occur post-HSCT; however, allogeneic HSCT and myeloablative conditioning were main risk factors identified for persistent cognitive decline. In line with white matter damage, executive function and attention/processing speed impairments likely represent core deficits, which may affect other cognitive impairments. Post-HSCT changes depend on task characteristics, cognitive load, and conditioning intensity. CONCLUSIONS: Future research should emphasize regular neurocognitive assessment to guide cognitive rehabilitation, implement pre-transplant cognitive rehabilitation strategies to mitigate post-HSCT cognitive decline, and enhance treatment outcomes.

Humans↗
PubMed2026

Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.

In periods of sustained hyper-nutrition, pancreatic β-cells undergo functional compensation through transcriptional upregulation of gene programs driving insulin secretion. This adaptation is essential for maintaining systemic glucose homeostasis and metabolic health. Using single nuclei multiomics, we have mapped the early transcriptional adaptive mechanisms in murine islets of Langerhans exposed to high-fat diet (HFD) for 1 and 3 wk. We show that β-cells exhibit the largest transcriptional response to HFD, characterized by early activation of pro-inflammatory eRegulons and down-regulation of β-cell identity genes, particularly in a distinct subset of β-cells. These observations extend to humans, where the prevalence of an β-cells with a high inflammatory signature is increased in diabetes. Collectively, these observations point to cellular crosstalk through pro-inflammatory signaling as a central and early driver of β-cell dysfunction that limits the compensatory capacity of β-cells, which is closely linked to the development of diabetes.

Animals↗
PubMed2026

Characteristics and functions of a cell adhesion molecule PvCadN in Penaeus vannamei during WSSV infection.

Cell adhesion not only maintains the integrity of the organism, but also plays an important role in the immune system, which is involved in modulation in the interaction between host and virus. In this study, a novel cell adhesion molecule from Penaeus vannamei, designated as PvCadN, was investigated. It had the typical molecular characteristics of cadherin family, with multiple extracellular cadherin repeat domains, a transmembrane region, and a conserved β-catenin-binding motif. Pvcadn is expressed ubiquitously across all detected tissues, with the highest transcriptional level in gills. RNA interference-mediated silencing of pvcadn significantly impaired the adhesion ability of shrimp hemocytes. Upon WSSV infection, pvcadn showed a tissue-specific expression pattern, with upregulation in gills and downregulation in hemocytes. Knockdown of pvcadn markedly suppressed the transcription of WSSV immediate-early gene ie1 and replication of the viral genome in vivo, suggesting that PvCadN acted as a potential virus-associated molecule. Furthermore, it was found that PvCadN was regulated by Lvβ-catenin, a core molecule in the Wnt signaling pathway that functions in innate immunity, at the transcriptional and protein levels. Silencing of lvβ-catenin significantly downregulated pvcadn transcription, and Lvβ-catenin bound directly to the Cadherin C domain of PvCadN. In summary, the study revealed that PvCadN was a key cell adhesion molecule involved in WSSV infection, which was regulated by Lvβ-catenin. Our findings will provide fundamental data for further investigation into cadherin-mediated immune regulation in shrimp, and offer new insights for the prevention and control of WSSV.

Animals↗
PubMed2026

Mitochondrial dysfunction in muscle cells induced by snoring vibrations.

Snoring-related vibrations have been proposed as a pathogenic factor contributing to upper airway muscle dysfunction in patients with obstructive sleep apnea (OSA). To investigate whether exposure to snoring vibration is linked to muscle weakness, we used an in vitro vibration model to examine its effects on mitochondrial homeostasis in L6 muscle cells at 8, 12, 24, and 48 h. The findings were then compared with mitochondrial alterations in the upper airway muscles from snorers and patients with OSA. Proteomic analysis of L6 myoblasts revealed extensive remodeling of the mitochondrial proteome at 8 h, affecting pathways involved in oxidative phosphorylation, protein import, ribosome biogenesis, and RNA processing. Respiratory chain remodeling was subunit-specific, with increased abundance of selected components of Complexes I, IV, and V, including NDUFS4, COX5A, and ATP5PD. However, reductions in spliceosome-associated factors, such as SRSF2 and DDX46, along with alterations in mitochondrial ribosomal proteins, indicated impaired RNA processing and protein synthesis. Furthermore, both proteomic and transcriptomic analyses revealed activation of a mechanosensing-mechanotransduction axis, with early upregulation of integrin subunits and mechanosensitive ion channels, followed by transient activation of focal adhesion signaling. Despite transcriptional upregulation of selected Complex IV subunits Cox5a and Cox6a2, this response was accompanied by accumulation of unspliced pre-mRNA, indicating impaired RNA processing efficiency and a decoupling between transcript and protein levels. Real-time Seahorse assay revealed a collapse of mitochondrial respiration and glycolytic reserve at 8 h. Although mitochondrial oxygen consumption recovered after 48 h, the ability to dynamically upregulate glycolysis remained impaired. In patients, muscle capillarization was impaired, COX activity was reduced, and mitochondrial organization was disrupted. Moreover, transcription of Complex IV subunits COX5A and COX6A2 was, as in vibrated L6 cells, upregulated, suggesting a mismatch between transcript levels and protein expression. We conclude that snoring-induced vibrations are an unrecognized stressor that disrupts mitochondrial homeostasis in muscle by impairing RNA processing, protein synthesis, and mechanotransduction-driven mitochondrial remodeling, leading to transcript-protein uncoupling and likely muscle dysfunction.

Humans↗
PubMed2026

Vitamin B12 Deficiency in Sickle Cell Disease: Method-Driven Estimates and Systematic Diagnostic Misclassification.

OBJECTIVES: To determine whether the reported 0%-70% prevalence of vitamin B12 deficiency in sickle cell disease (SCD) reflects true population variation or diagnostic misclassification. METHODS: We conducted a PRISMA 2020-compliant systematic review of observational studies (January 1, 2000-May 13, 2026; PROSPERO CRD420251087800) assessing B12 status in SCD. PubMed, AJOL, and Google Scholar were searched with citation tracking and dual screening. Diagnostic validity was assessed across biomarker strategy, analytical platform, thresholds, and confounder control using a proposed context-integrated framework to classify methodological robustness and discordance. RESULTS: Fourteen studies were included (57% high-income; 43% LMIC). The evidence base was dominated by limited diagnostic approaches: 71% used immunoassays, over one-third relied on circulating B12 alone, and functional biomarkers were inconsistently applied without systematic confounder adjustment. Prevalence estimates were strongly influenced by diagnostic methods rather than underlying population biology, ranging from 0% to 70% in single-marker studies (mostly 0%-7.1%, with outliers ~50%-70%) and 6.9%-53% in multi-marker studies. Discordance was substantial and greater in LMIC settings than HIC. CONCLUSION: Current diagnostic approaches in SCD appear method-dependent, generating heterogeneous prevalence estimates with uncertain clinical validity. These findings challenge existing estimates and have implications for clinical practice, research design, and diagnostic equity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420251087800.

Humans↗