Search Results (44,488)

Syngas fermentation in combination with chain elongation offers great promise for sustainable medium-chain fatty acid production. While immobilization has proven effective for stabilizing monocultures of C. kluyveri for chain elongation, its applicability to co-cultures involving C. carboxidivorans for simultaneous syngas fermentation remains unexplored. This study investigates the physiological compatibility of C. carboxidivorans with agar-based hydrogel immobilization and its co-cultivation potential with C. kluyveri in a synthetic dual-layer biofilm reactor. First, we conducted autotrophic batch fermentations using suspended and immobilized cells, proving metabolic activity similar for both. Applying different sulfur feeding rates, experiments showed best ethanol formation with C. carboxidivorans at increased sulfur feeding, enabling better conditions for chain elongation with C. kluyveri. In the synthetic dual-layer biofilm reactor, with the C. carboxidivorans biofilm in contact with the CO-containing gas phase above the C. kluyveri biofilm, the formation of 1-butyrate and 1-hexanoate was observed with product formation rates of 0.46 g L⁻¹ d⁻¹ 1-butyrate, and 0.91 g L⁻¹ d⁻¹ 1-hexanoate, respectively. The formation rate of 1-hexanoate in the dual-layer biofilm reactor was approximately 7.6 times higher than that reported with suspended cells in a stirred tank bioreactor. Spatial analysis revealed species-specific migration behavior and confirmed that C. carboxidivorans reduced local CO concentrations, improving the environment for C. kluyveri. Full article

Arabinogalactan proteins (AGPs) and extensins influence cell wall assembly and regulate plant cell mechanical properties through interactions with extracellular matrix polymers. These proteins may play a key role in the biochemical events underlying postharvest treatments aimed at controlling fruit texture and turgor loss associated with senescence-related disorders. We studied the temporal and spatial accumulation patterns of extensin and AGP isoforms constitutively expressed along with the profiling of nucleotide sugars UDP-galactose, UDP-arabinose, UDP-glucuronic acid, and UDP-rhamnose in Mara des Bois strawberries under different storage conditions. We also assessed the expression timing of AGP-encoding genes (FvAFP4, FvAGP5) and genes involved in key steps of post-translational glycosylation (FvP4H1, FvGAT20, FvGAT7). Whereas extensins are down-regulated, AGPs are transcriptionally regulated by cold and cold-high CO₂ and post-translationally modulated after transfer to 20 °C. Based on their subcellular localization, molecular properties, isoform-specific glycosylation, UDP-sugar availability, and timing-regulated expression, AGPs are likely involved in cell wall assembly and modulation of mechanical properties. Consequently, they may influence fruit texture and enhanced softening resistance, potentially counteracting senescence-associated disorders through CO₂-responsive signaling mechanisms. Conversely, the decrease in both UDP-galactose levels and AGPs gene expression in non-cold-stored senescent strawberries at 20 °C further supports their relevance in AGPs biosynthesis regulation and underscores their potential as markers for improving postharvest storage strategies. Full article

Background: Peptide-loaded antigen-presenting cell (APC)-based vaccines have been under investigation as a therapeutic approach for treating cancer. However, in general they have demonstrated limited efficacy in clinical trials. Dendritic cells (DCs) have been the primary choice for APC-based vaccines given their ability to cross-present antigens. B cells have been less studied as APCs for vaccines. Here we compare the phenotype and anti-tumor activity of activated T cells that result from peptide-specific priming using either B cells or DCs. Methods: B cells and DCs were isolated from C57Bl/6 mice, and either treated or not treated with lipopolysaccharide (LPS) for maturation, and then either loaded or not loaded with SIINFEKL peptide to prime CD8+ T cells from OT-1 mice. Activated T cells were then analyzed for their phenotype and anti-tumor efficacy. Results: We report that both immature B cells and immature DCs were similarly capable of activating antigen-specific CD8+ T cells. However, LPS-matured DCs generated a stronger CD8+ T cell activation profile in vitro compared to LPS-matured B cells. Immature B cells, mature DCs and immature DCs all generated a similar anti-tumor response upon adoptive transfer of primed CD8+ T cells to tumor-bearing mice. Conclusion: Collectively, our data suggests that B cells and DCs are each capable of priming CD8+ T cells and generating anti-tumor responses. Given that B cells are relatively easier to culture and expand compared to DCs, our study suggests that, following further validation, B cells could be further investigated as APCs for peptide-based human cancer vaccines. Full article

The purpose of this narrative review is to critically appraise recent advances in sports injury rehabilitation—primarily focusing on biopsychosocial (BPS) approaches alongside emerging technological innovations—and identify current gaps and future directions. A literature search was conducted in PubMed, Scopus, and Web of Science for the years 2018–2024. Eligible records were English-language, human studies comprising systematic reviews, clinical trials, and translational investigations on wearable sensors, artificial intelligence (AI), virtual reality (VR), regenerative therapies (platelet-rich plasma [PRP], bone marrow aspirate concentrate [BMAC], stem cells, and prolotherapy), and BPS rehabilitation models; single-patient case reports, editorials, and non-scholarly sources were excluded. The synthesis yielded four themes: (1) BPS implementation remains underutilised owing to a lack of validated tools, variable provider readiness, and system-level barriers; (2) wearables and AI can enhance real-time monitoring and risk stratification but are limited by data heterogeneity, non-standardised pipelines, and sparse external validation; (3) VR/gamification improves engagement and task-specific practice, but evidence is dominated by pilot or laboratory studies with scarce longitudinal follow-up data; and (4) regenerative interventions show mechanistic promise, but conclusions are constrained by methodological variability and regulatory hurdles. Conclusions: BPS perspectives and emerging technologies have genuine potential to improve outcomes, but translation to practice hinges on (1) pragmatic or hybrid effectiveness–implementation trials, (2) standardisation of data and intervention protocols (including core outcome sets and effect-size reporting), and (3) integration of psychological and social assessment into routine pathways supported by provider training and interoperable digital capture. Full article

Background: Alterations in peripheral red blood cell (RBC) indices have been proposed as potential biomarkers for Parkinson’s disease (PD), but their diagnostic utility and relation to clinical features remain uncertain. Methods: We conducted a pilot case–control study involving 70 PD patients and 122 controls from two neurology centers in Mexico. Standardized hematology analyses provided RBC indices, and neuropsychiatric assessments included the Hamilton Depression Rating Scale (HAM-D) and Mini-Mental State Examination (MMSE). Associations between RBC indices and PD were tested using multivariable logistic regression adjusted for age, sex, and smoking. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Subgroup analyses stratified PD patients by age at onset, disease duration, and Hoehn and Yahr (HY) stage. Results: PD patients exhibited significantly higher mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) than controls. Elevated MCHC was independently associated with PD (OR = 1.68, 95% CI 1.35–2.09; p < 0.001). Sex-stratified models confirmed consistent associations in women (OR = 1.57) and men (OR = 1.79). ROC analysis demonstrated fair diagnostic accuracy for MCHC (AUC 0.72, 95% CI 0.65–0.80; cutoff 33.9 g/dL, sensitivity 62.9%, specificity 72.1%). Sex-specific thresholds improved sensitivity in women (90.6%) and specificity in men (74.6%). Within the PD group, MCHC did not differ by HY stage or disease duration, and showed no correlation with UPDRS, HAM-D, or MMSE scores. Early-onset cases (<50 years) showed numerically higher MCHC, though numbers were limited. Conclusions: This pilot study confirms that an elevated MCHC is independently associated with PD, a finding consistent across both sexes and independent of disease severity. MCHC demonstrates fair diagnostic performance, supporting its potential as a low-cost, accessible biomarker. Larger longitudinal studies integrating RBC indices with inflammatory and iron-regulatory markers are warranted to establish their role in the diagnosis and differential diagnosis of PD. Elevated MCHC was associated with PD, and an MCHC-based index (cutoff 33.9 g/dL; AUC 0.72, sensitivity 62.9%, specificity 72.1%) showed potential as a simple diagnostic marker. Full article

Introduction: The elbow is a rare site for bone tumors, and for this reason, the literature provides little data on the epidemiology of metastatic lesions involving the distal humerus, proximal ulna, and radius. Before performing surgery of the metastatic bone, it is first necessary to consider both patients’ and metastatic lesions’ features in order to better choose the best possible treatment. This systematic review aims to collect data on elbow metastases, delineate primary tumors leading to such metastases, guide surgical treatment decisions, and evaluate reconstructive techniques and associated complications. Material and Methods: A systematic literature review was conducted in April 2024, searching the PubMed, MEDLINE, and Cochrane Library databases using specific search terms related to elbow metastases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was followed. Eligible studies reported at least one patient with metastatic bone disease involving the elbow region and specified the undertaken treatment. For studies reporting multiple skeletal sites, only elbow-specific data were extracted. We excluded recurrences of primary elbow tumors. The methodological quality of included studies was assessed with the modified Coleman Methodology Score (mCMS). Results: In total, 28 articles (103 patients) were included. The studies were predominantly case reports (68%), with a mean mCMS of 31. Gender was reported for only 41 patients: 71% were male and 29% female. The mean age at diagnosis of elbow metastatic lesion was 55 years old. Renal cell carcinoma was the most common primary tumor (28%), followed by breast (9%) and lung cancer (6%). The distal humerus was the most frequently affected site (85%). A surgical approach was adopted in 90% of cases, whereas 10% of patients were managed conservatively. Forty-five patients underwent wide tumor resection followed by reconstructive surgery while forty-eight patients received a surgical treatment for either pathological fractures or impending fractures. Conclusions: When treating elbow metastasis, a thorough evaluation of the patient is crucial, considering the patient’s functional status, pain management needs, and overall prognosis; all these features influence the treatment of choice. The selected treatment should aim to provide optimal functional outcomes and minimize complications. For patients with pathological or impending fractures, single or double plate fixation is typically the preferred approach. For patients with severe, symptomatic lesions unresponsive to conservative therapy, resection followed by the implantation of a modular prosthesis usually offers the best clinical and functional outcomes. Full article

Cardiogenesis and heart cell composition and function constitute fundamental areas of cardiovascular medicine research, and exploring their underlying mechanisms is closely tied to the goals of precision medicine. This review comprehensively examines the composition and functions of the heart from embryonic organogenesis to maturity, and highlights the main breakthroughs of treatment strategies associated with these processes. By elaborating on the spatiotemporally specific signaling pathways and transcriptional networks that drive heart organogenesis and progenitor cell fate determination during the pivotal stages of cardiac development, and by systematically presenting the molecular biomarkers and functional characteristics of the principal cell types in mature heart, the latest advancements in related applications are summarized, with a particular emphasis on breakthroughs in gene/cell therapy, organoid development, and tissue engineering and regenerative medicine. This paper provides a theoretical foundation for precision interventions and regenerative medicine in cardiovascular disease using an axis that integrates cardiogenesis, cellular architecture, and therapeutic translation. Full article

Immune dysregulation is being increasingly recognized as a leading sign of a wide spectrum of inborn errors of immunity (IEIs). Therefore, patients with IEIs are frequently managed in non-immunological settings, including hematology and oncology units, during the diagnostic process or follow-up. The most relevant hematological signs associated with IEIs comprise autoimmune cytopenia (AIC), lymphoproliferative diseases (LPD), malignancies, hemophagocytic lymphohystiocitosis (HLH), bone marrow failure (BMF), myelodysplastic syndromes (MDS), and peripheral or tissue eosinophilia. The prognosis of patients with IEIs can significantly improve when a molecular diagnosis is established, as it can allow the use of targeted treatments, guide appropriate follow-up strategies and, in some cases, support the rationale for hematopoietic stem cell transplantation or gene therapy. Therefore, there is an urgent need to recognize the warning signs suggestive for an underlying IEI among patients presenting with common hematological features and to ensure an appropriate diagnostic approach. As a general rule, clinicians should always provide a clinical alert in the presence of two or more IEI-associated hematological signs, as well as a positive familial history for IEI or hematologic immune dysregulation, a personal history of severe infections, and other signs of immune dysregulation. Concerning AIC, an increased likelihood of IEI is characteristic of patients with treatment refractoriness, autoimmune hemolytic anemia, or multilineage cytopenia. In the case of LPD, the main elements of suspicion are represented by the chronic or recurrent disease course, the persistence of Epstein–Barr Virus (EBV) infection, and the development of lymphoproliferation in atypical localizations. Among patients with malignancy, clinicians should investigate for IEI those with rare neoplasia, virus-associated tumors, and an association with syndromic features, while patients with HLH should always receive an immunological assessment when a clear rheumatologic trigger, underlying malignancy, or well-recognized cause is not evident. The case of MDS and BMF is complex, as new monogenic entities are continuously being described. However, it is pivotal to consider the presence of monocytopenia, warts, vasculitis, and neurological disease, as well as specific cytogenetic abnormalities, such as chromosome 7 monosomy, as warning sings for IEIs. Finally, the main red flags for IEIs in patients with eosinophilia are skeletal/facial abnormalities, recurrent abscesses, refractory eczema, organomegaly, or thrombocytopenia. Full article

Background: Macrophages are key components of the tumor microenvironment and play a critical role in melanoma progression. However, the dynamics of different macrophage subsets, particularly CD68⁺ and CD163⁺ populations, in relation to tumor thickness and stage remain insufficiently characterized. Objective: This study aimed to quantitatively assess intratumoral and peritumoral CD68⁺ and CD163⁺ macrophages in cutaneous melanoma and to investigate their associations with Breslow thickness, pT stage, and AJCC stage. Methods: We conducted a retrospective cohort study of 126 patients with cutaneous melanoma (AJCC stages IA–IIID). Tumor samples were examined histologically and immunohistochemically for CD68⁺ and CD163⁺ macrophages, and quantitative analysis was performed in intratumoral and peritumoral regions. Results: This study included 126 patients with cutaneous melanoma, ranging in stage from IA to IIID. Histopathological analysis revealed that melanoma tissues were primarily composed of irregular clusters of atypical melanocytic cells infiltrating the dermis and subcutaneous fat. Immunohistochemical staining identified CD68⁺ and CD163⁺ macrophages both within the tumor and in the surrounding stroma. Macrophage infiltration significantly increased with tumor thickness (Breslow) and progression to more advanced stages. Specifically, at Breslow thickness <1.0 mm, the mean number of CD68⁺ macrophages in the intratumoral zone was 29.7 ± 4.3 cells, increasing to 70.3 ± 6.4 cells in tumors >4.0 mm. CD163⁺ macrophages showed similar trends, with a rise from 15.6 ± 2.8 cells at <1.0 mm to 39.8 ± 4.6 cells at >4.0 mm in the intratumoral zone. Additionally, macrophage density was higher in tumors with ulceration, and both CD68⁺ and CD163⁺ macrophage numbers increased progressively with tumor stage, particularly in advanced stages. The number of CD68⁺ macrophages at stage IA in the intratumoral zone was 21.6 ± 3.1 cells and increased to 56.4 ± 6.8 cells at stage IIID, while CD163⁺ macrophages rose from 13.8 ± 3.2 cells at stage IA to 36.4 ± 4.6 cells at stage IIID. This suggests that macrophage infiltration, particularly CD163⁺ cells, correlates with melanoma progression. Conclusions: Our findings highlight distinct spatial and phenotypic patterns of macrophage infiltration in melanoma progression. The prominent increase in CD68⁺ and CD163⁺macrophages suggests their important role in tumor-associated immunomodulation. Further studies are warranted to elucidate macrophage polarization states and their prognostic and therapeutic implications in melanoma. Full article

The rapid shift toward electric vehicles (EVs) has underscored the critical importance of battery pack crashworthiness, creating a demand for lightweight, energy-absorbing protective systems. This review systematically explores bio-inspired cellular structures as promising solutions for improving the impact resistance of EV battery packs. Inspired by natural geometries, these designs exhibit superior energy absorption, controlled deformation behavior, and high structural efficiency compared to conventional configurations. A comprehensive analysis of experimental, numerical, and theoretical studies published up to mid-2025 was conducted, with emphasis on design strategies, optimization techniques, and performance under diverse loading conditions. Findings show that auxetic, honeycomb, and hierarchical multi-cell architectures can markedly enhance specific energy absorption and deformation control, with improvements often exceeding 100% over traditional structures. Finite element analyses highlight their ability to achieve controlled deformation and efficient energy dissipation, while optimization strategies, including machine learning, genetic algorithms, and multi-objective approaches, enable effective trade-offs between energy absorption, weight reduction, and manufacturability. Persistent challenges remain in structural optimization, overreliance on numerical simulations with limited experimental validation, and narrow focus on a few bio-inspired geometries and thermo-electro-mechanical coupling, for which engineering solutions are proposed. The review concludes with future research directions focused on geometric optimization, multi-physics modeling, and industrial integration strategies. Collectively, this work provides a comprehensive framework for advancing next-generation crashworthy battery pack designs that integrate safety, performance, and sustainability in electric mobility. Full article

Background/Objectives: Hepatitis B virus (HBV) infection poses a major global health challenge, with current therapies like nucleos(t)ide analogs and pegylated interferon alpha offering limited functional cure rates due to persistent HBsAg-driven immune tolerance. This study aimed to develop a targeted immunoadsorption system using a high-affinity humanized anti-HBsAg monoclonal antibody for efficient HBsAg and viral particle clearance, providing a novel approach to overcome therapeutic bottlenecks in chronic hepatitis B (CHB). Methods: A murine anti-HBsAg monoclonal antibody was humanized via complementarity-determining region grafting, resulting in HmAb-12 (equilibrium dissociation constant, K_D = 0.36 nM). A stable Chinese Hamster Ovary K1 (CHO-K1) cell line was established for high-yield expression (fed-batch yield: 8.31 g/L). The antibody was covalently coupled to agarose microspheres (coupling efficiency > 95%) to prepare the immunoadsorbent. Efficacy was evaluated through in vitro dynamic circulation assays with artificial sera and preclinical trials using an integrated blood purification system in two CHB participants. Clearance rates for HBsAg and HBV DNA were quantified, with safety assessed via blood component monitoring. Results: In vitro, a single treatment cycle achieved HBsAg clearance rates of 70.14% (high antigen load, >10⁵ IU/mL) and 92.10% (low antigen load, ~3000 IU/mL). Preclinically, one treatment session resulted in acute HBsAg reductions of 78.30% and 74.31% in participants with high and moderate antigen loads, respectively, alongside HBV DNA decreases of 65.66% and 73.55%. Minimal fluctuations in total protein and albumin levels (<15%) confirmed favorable safety profiles, with no serious adverse events observed. Conclusions: Preliminary findings from this study indicate that the HBsAg-specific immunoadsorption system can achieve efficient HBV antigen clearance with an initial favorable safety profile in a small cohort. These results support its further investigation as a potential therapeutic strategy for functional cure in CHB. Future work will focus on validating these findings in larger studies and exploring the system’s combinatory potential with existing blood purification platforms. Full article

The stomach epithelium is a highly dynamic tissue that undergoes continuous self-renewal and responds robustly to injury through tightly regulated repair processes. Organoids have emerged as powerful tools for modelling gastrointestinal biology. This review focuses on the capacity of gastric organoids to model epithelial homeostasis, injury and repair in the stomach. We examine how organoid systems recapitulate key features of in vivo gastric architecture and stem cell dynamics, enabling detailed interrogation of lineage specification, proliferative hierarchies and regional identity. Gastric organoids have proven particularly useful for studying how environmental factors, such as Helicobacter pylori infection or inflammatory cytokines, disrupt epithelial equilibrium and drive metaplastic transformation. Furthermore, we discuss the emerging use of injury-mimicking conditions, co-cultures and bioengineered platforms to model regeneration and inflammatory responses in vitro. While organoids offer unparalleled accessibility and experimental manipulation, they remain limited by the absence of critical niche components such as immune, stromal and neural elements. Nevertheless, advances in multi-cellular and spatially resolved organoid models are closing this gap, making them increasingly relevant for disease modelling and regenerative medicine. Overall, gastric organoids represent a transformative approach to dissecting the cellular and molecular underpinnings of stomach homeostasis and repair. Full article

MYCN amplification without concurrent RB1 mutations characterizes a rare yet highly aggressive subtype of retinoblastoma; however, its precise developmental origins and therapeutic vulnerabilities remain incompletely understood. Here, we modeled this subtype by lentiviral-mediated MYCN overexpression in human pluripotent stem cell-derived retinal organoids, revealing a discrete developmental window (days 70–120) during which retinal progenitors showed heightened susceptibility to transformation. Tumors arising in this period exhibited robust proliferation, expressed SOX2, and lacked CRX, consistent with origin from primitive retinal progenitors. MYCN-overexpressing organoids generated stable cell lines that reproducibly gave rise to MYCN-driven tumors when xenografted into immunodeficient mice. Transcriptomic profiling demonstrated that MYCN-overexpressing organoids closely recapitulated molecular features of patient-derived MYCN-amplified retinoblastomas, particularly through activation of MYC/E2F and mTORC1 signaling pathways. Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype. Full article

Neutrophils are the most abundant immune cells in humans and the first responders to be recruited at the site of injury. They exhibit high microbicidal activity and a combination of cytotoxic mechanisms that may lead to bystander tissue damage. However, this classical and simplistic view of the neutrophil biology has recently dramatically changed. Emerging evidence indicates an active role for neutrophils in resolution of inflammation and tissue repair. This review specifically explores the mechanisms through which neutrophils perform their anti-inflammatory and tissue-repairing roles, which are also modulated by circadian rhythms—an aspect that influences immune activity and may have implications for treatment timing. A particular focus is placed on the role of platelet-derived products in modulating local neutrophil immune responses. The remarkable phenotypic plasticity of neutrophils and their crucial role in resolving inflammation and restoring homeostasis underscore their promise as a therapeutic approach. However, their activity must be finely regulated to prevent potential tissue damage. Full article

Hydrogen sulfide (H₂S) exerts regulatory functions in kidney diseases. However, its protective role against kidney stone formation remains unclear. Here, we demonstrate that hyperoxaluria or oxalate exposure impairs H₂S formation, leading to tubular injury and calcium oxalate (CaOx) crystal deposition in both in vivo and in vitro models. In male rats fed 5% hydroxy-L-proline (HP), time-dependent increases in urinary supersaturation, tubular damage, and renal CaOx deposition were observed compared to controls. These changes were associated with the decreased expression of H₂S-producing enzymes and elevated urinary secretion of osteopontin (OPN) and Tamm–Horsfall protein (THP). Notably, the protein level and activity of specificity protein 1 (Sp1), a transcription factor regulating these enzymes, were markedly decreased in HP-treated kidneys. Chronic supplementation with the H₂S donor GYY4137 (GYY) significantly attenuated HP-induced tubular injury and CaOx deposition by reducing OPN and THP secretion. Consistent with in vivo results, H₂S donors mitigated oxalate-induced tubular cell damage and CaOx formation in MDCK cells. Mechanistically, oxalate activated cyclic AMP/protein kinase A (PKA) signaling, which promoted OPN and THP secretion; these effects were eradicated by the PKA inhibitor H89 or GYY. These findings indicate that hyperoxaluria impairs Sp1 transcriptional activity, resulting in H₂S deficiency and compromised anticrystallization defense in oxalate-induced tubulopathy. Full article