Pathogenic variants in VPS13A cause chorea-acanthocytosis, classically presenting as chorea, dystonia, and orolingual dyskinesias. Parkinsonism is an underreported presenting symptom, particularly in the absence of these classical features, and may lead to misdiagnosis. We report the case of a 52-year-old man evaluated for heart transplantation, during which the neurology service was consulted for recently diagnosed Parkinson's disease to inform transplant candidacy. His history revealed progressive gait difficulty, falls, slurred speech, nonresponse to levodopa, and absence of resting tremor or other involuntary movements. Initial examination revealed moderate hypophonic dysarthria, reduction in facial expression, asymmetric rigidity and bradykinesia, and severe postural instability. Magnetic resonance imaging of the brain revealed basal ganglia atrophy, especially in the bilateral caudate nuclei. Bloodwork revealed a normal creatine kinase level, elevated ferritin, copper, and ceruloplasmin levels, and acanthocytosis. Genetic testing revealed heterozygous pathogenic variants in VPS13A, c.7420-2A>C, and c3961-2A>G, consistent with autosomal recessive chorea-acanthocytosis. Chorea-acanthocytosis, as discovered in this patient via genetic testing, may present without typical symptoms and lead to misdiagnosis as idiopathic Parkinson's disease. Presence of atypical parkinsonian features, acanthocytes on peripheral blood smear, and basal ganglia abnormalities on structural imaging should raise the index of suspicion for this rare disorder.

Skin fibroblasts exhibit remarkable heterogeneity across their multilayered cutaneous architecture, yet their roles during wound repair remain elusive, mainly due to the lack of layer-specific genetic tools. Here, we employed a dual-recombinase strategy to develop genetic lineage-tracing tools for all five layers of skin fibroblasts: papillary, reticular, hypodermal, panniculus carnosus (PC), and fascia fibroblasts. Our study revealed an intricate spatiotemporal pattern of fibroblast contributions across different wound severities. Temporally, deep wounds elicited a sequential contribution of these fibroblasts in three stages, while superficial wounds involved two. The early-contributing fibroblasts predominantly occupied the wound bed during the closure stage, while subsequently recruited populations mainly entered during tissue remodeling and scar formation. Spatially, as remodeling progressed, fibroblasts reorganized into a hierarchical arrangement closely mirroring their pre-injury spatial distribution. Our study elucidates the coordinated spatiotemporal interplay of fibroblasts during wound repair and may spur novel therapeutic modalities and interventions for cutaneous healing.

Spur-type apple growth, characterized by shortened internodes and compact tree architecture, is an important trait for high-density apple production; however, its underlying molecular basis remains insufficiently understood. Previous work identified the MYB-CC transcription factor MdγMYB2 as a candidate regulator of shoot elongation in spur-type apple. Here, we investigated the phylogenetic relationships, molecular characteristics, and biological functions of MdγMYB2 to elucidate its role in shoot elongation and internode development. During shoot development, MdγMYB2 expression was significantly higher in the standard-type cultivar 'Shansha' ('SS') than in the spur-type cultivar 'Hanfu' ('HF'). MdγMYB2 was localized to the nucleus and exhibited transcriptional activation activity. Phenotypic analysis of transgenic apple plants showed that MdγMYB2 overexpression significantly increased plant height, internode length, leaf area, and longitudinal stem cell length, whereas RNA interference resulted in the opposite phenotypes. Transcriptome profiling revealed that altered MdγMYB2 expression was accompanied by coordinated changes in genes associated with hormone responses, cell wall polysaccharide biosynthesis, pectin and xyloglucan remodeling, secondary cell wall formation, and lignin biosynthesis. Notably, genes involved in cell wall remodeling and lignin deposition exhibited opposite expression patterns between MdγMYB2 overexpression lines (MdγMYB2-OE) and RNA interference lines (MdγMYB2-RNAi) plants, consistent with their contrasting cellular and internode phenotypes. Collectively, these findings establish MdγMYB2 as a positive regulator of apple shoot and internode elongation. MdγMYB2 appears to affect vegetative growth by inducing coordinated transcriptional changes in genes associated with hormone responses and cell wall metabolism. This study identifies MdγMYB2 as a regulator of shoot and internode elongation in apple, providing new insights into the molecular basis of compact growth habits and a valuable genetic resource for the breeding of spur-type apple cultivars.

The genus Renanthera is valued for its fiery-red floral coloration and distinctive spider-like floral architecture; however, the molecular mechanisms underlying floral organ specialization and perianth color differentiation remain poorly understood. In this study, using integrated morphological, transcriptomic, and metabolomic analyses of R. coccinea, we found that the cell types of the dorsal and lateral perianth organs were broadly similar but clearly distinct from those of the lip and the column. Developmentally, the organ-specific expression patterns of AGAMOUS-LIKE6-1/2 (AGL6-1/2), APETALA3-1/2 (AP3-1/2), and AGAMOUS (AG) were consistent with the conserved orchid floral organ identity model. Furthermore, lip-enriched expression of brassinosteroid-responsive RING H2 (BRH1) and flavin-containing monooxygenase YUCCA10 (YUC10) suggests that brassinosteroid- and auxin-associated pathways may contribute to lip specialization, especially spur development. Regarding pigmentation, high expression of flavonoid 3'-hydroxylase (F3'H) was associated with a cyanidin-dominated anthocyanin profile. The color divergence among the dorsal sepal, petals, and lateral sepals was associated with differential expression of UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT), which was co-expressed with plant U-box protein 9 (PUB9) and carbon catabolite repressor 4 (CCR4), associated with distinct patterns of pigment modifications. These findings provide a molecular framework for understanding floral organ development and color patterning in R. coccinea and candidate genes for future validation and molecular breeding in Renanthera.

The assessment of dysmorphic red blood cells (RBCs) is of significant clinical interest in the evaluation of haematuria, particularly as a key tool for suggesting a possible glomerular origin. However, its actual utility depends on cautious, context-based interpretation supported by well-defined technical requirements. The lack of universal standardization, interobserver variability, and the influence of preanalytical factors continue to contribute to the heterogeneous implementation of this test in clinical practice. This document provides recommendations aimed at optimizing its use in the clinical laboratory. It reviews the underlying pathophysiological basis, principal indications, and the preanalytical and analytical conditions required to ensure reliable evaluation, as well as its integration with other findings from urinalysis and renal biochemistry. In this regard, erythrocyte dysmorphism should not be considered an isolated test, but rather a complementary parameter whose diagnostic performance improves when interpreted alongside proteinuria or albuminuria, renal function, the presence of pathological casts, and the patient's clinical context. Furthermore, the importance of a selective approach is emphasized, prioritizing clinical scenarios with higher diagnostic yield, such as persistent microhaematuria, haematuria associated with proteinuria, or suspected glomerular disease. Finally, guidance criteria are proposed for reporting and for integration into multidisciplinary clinical algorithms. Overall, these recommendations aim to promote a more rational, harmonized, and clinically meaningful use of dysmorphic RBC counts within advanced urinalysis.

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from infectious diseases globally. The complexity of host-Mtb interactions poses a fundamental challenge to developing effective prevention and control measures. Recent advances in multi-omics, spatiotemporal biology, and single-cell technologies have yielded transformative insights into Mtb infection dynamics and its intricate crosstalk with the host immune system. In this review, we will first introduce the current knowledge of Mtb-host immunological interplay and discuss it from three interconnected perspectives, including the balance between protective immunity and immunopathology, the coordination between local and systemic immunity, and the contribution of Mtb-induced immune dysregulation to TB comorbidities. We then further highlight translational opportunities via targeting the host-Mtb interface, including predictive biomarkers for Mtb infection and disease progression, next-generation vaccines for immune restoration and TB prevention, and precision strategies to overcome drug resistance and improve treatment outcomes. By integrating the latest discoveries and discussing key unresolved questions, we seek to provide an updated overview of TB pathogenesis with an aim to spur the development of transformative tools for TB control.

A 29-year-old woman with a novel homozygous VPS13A frameshift variant presented with drug-resistant temporal-lobe epilepsy and severe sensory neuronopathy, but no acanthocytes on repeated blood smears-expanding the phenotypic spectrum of chorea-acanthocytosis beyond its defining haematological feature.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease worldwide, characterized by progressive cyst growth and inflammation, yet effective targeted therapies remain limited. Here we show that TMEM16A and MCP-1, key mediators of cyst-lining epithelial expansion and inflammatory macrophage recruitment respectively, are consistently upregulated in cyst-lining collecting duct (CD) epithelia across murine, porcine, and human ADPKD models. In human ADPKD patient cells, although individual silencing of TMEM16A or MCP-1 transcripts reduced cyst growth, combined silencing produced superior therapeutic efficacy, establishing the rationale for evaluating dual-target delivery. To achieve dual gene silencing in the kidneys, we delivered Tmem16a and Mcp-1 siRNA using peptide amphiphile micelles (PAMs), an ultrasmall nanoparticle platform that enables efficient renal targeting. To redirect siRNA-loaded PAMs to CD epithelia, we functionalized their surface with a CD-targeting peptide (CDM), which enabled preferential accumulation in cyst-lining CD epithelia. In an inducible Pkd1-deficient mouse model, co-delivery of CDMs loaded with Tmem16a and Mcp-1 siRNA reduced kidney enlargement, cystic burden, tubular injury, and macrophage infiltration, with efficacy exceeding non-targeted siRNA delivery at equivalent doses. CDM demonstrated enhanced uptake in primary human ADPKD patient-derived CD cells and dual gene silencing reduced target gene expression and cyst expansion, establishing translational relevance. These findings establish CD peptide-functionalized micelles as a route to cell-type-selective RNAi in the kidney, delivering siRNA to cyst-lining CD cells. Furthermore, because both targets, TMEM16A and MCP-1, are transcribed within CD cells, our siRNA-loaded CD-targeting micelles silence two drivers of cyst expansion, and their simultaneous suppression represents an effective therapeutic strategy for ADPKD.

While native mass spectrometry (native-MS) has been widely explored in academic laboratories, its practical role within biopharmaceutical research remains less clearly defined. In this perspective, we present an industry-driven view of how native-MS is currently applied, where it offers unique advantages over established analytical technologies, and where alternative methods remain more practical for routine characterization. Within biopharma workflows, characterization strategies traditionally rely on orthogonal techniques such as size-exclusion chromatography (SEC), ion-exchange chromatography (IEX), electrophoresis, light scattering, calorimetry, and denaturing liquid chromatography (LC) MS. Native-MS complements these methods by enabling direct assessment of intact molecular assemblies, including monoclonal antibodies (mAbs), multispecific antibodies, antibody-drug conjugates (ADCs), glycoproteins, and protein complexes. Applications include evaluation of higher-order assembly, ligand or cofactor binding, stoichiometry of target complexes, and heterogeneity that may be obscured under denaturing conditions. However, challenges related to throughput, sensitivity, automation, and accessibility have limited widespread adoption in industrial laboratories. Emerging developments, including chromatographic hyphenation, online buffer exchange (OBE), improved automation, and charge-detection MS (CDMS), are beginning to address these constraints. We argue that the future impact of native-MS in biopharma will depend on integrating these technological advances with platformed analytical workflows and software capable of supporting high-throughput characterization across therapeutic pipelines. We hope that the ideas raised in this article spur debate on when, how, and if native-MS would or should see increased adoption.

BackgroundWhole-body (WB) magnetic resonance imaging (MRI) is increasingly being used in children and often includes the paranasal sinuses.PurposeTo examine the prevalence of paranasal sinus opacifications by age and over time, as seen on WB-MRI.Material and MethodsProspective, population-based, bi-center study including healthy volunteers aged 6-18 years, undergoing WB-MRI (1.5 T) for research purposes only during 2018-2020, of whom 88 had a follow-up after a mean of 88 days. Paranasal sinuses and mastoid complexes were assessed separately for symmetry, presence of a nasal septal spur, bullous or inverted conchae, mucosal thickness, and presence/thickness of fluid levels. Opacification was graded on a scale of 0-3, as none/<2 mm, <33%, 33%-65%, and 66%-100% and according to the Lund-Mackay scoring system.ResultsA total of 171 volunteers (85 boys; mean age=11.9 ± 3.3 years) were included. On a 0-3 scale, 120/171 (70.2%) participants had opacification grade ≥1 in at least one paranasal sinus (67.8%) or mastoid air cell (6.4%). Corresponding findings for each sinus pair separately were 51.4% of the maxillary, 39.2% of the ethmoid, 23.4% of the sphenoid, and 4.7% of the frontal sinuses. Mean Lund-Mackay score for the initial scans was 2.85, with 47/171 (27.5%) scoring ≥4; 40.9% had a score of 0 or 1. In the majority, the grade of opacification remained stable over time.ConclusionThe prevalence of paranasal sinus opacifications in healthy 6-18-year-olds is high, with nearly one-third having a Lund-Mackay score ≥4, which, in a clinical setting, supports a diagnosis of rhinosinusitis.