Search Results (1,767)

Predicting the long-term degradation of bioresorbable poly(L-lactide) (PLLA)–hydroxyapatite (HA) composites remains a critical challenge in orthopedic implant design. An artificial implant must support bone tissue and maintain its mechanical and elastic properties for a certain period of time, corresponding to the rate of regeneration of damaged tissue; the time can reach several months. This study investigates the evolution of elastic properties and bulk microstructure in highly filled PLLA–HA composites (5–20 wt.% HA) during 76 weeks of in vitro hydrolytic degradation at 37 °C. Using high-frequency pulsed scanning acoustic microscopy (100 MHz), microstructural transformations and local elastic moduli were monitored non-destructively, complemented by mechanical testing and density measurements. Results indicate a concentration-dependent degradation mechanism: while initial stiffness increased with HA content, filler concentrations exceeding 10 wt.% accelerated degradation via early interfacial debonding and cavity formation around filler agglomerates. Conversely, the 5 wt.% HA composite exhibited superior stability, maintaining an elastic modulus of 6.7 GPa over 64 weeks with minimal microstructural damage. High-frequency ultrasound effectively quantified internal void formation and degradation kinetics in a non-invasive manner. These findings identify 5 wt.% HA as the optimal concentration for balancing mechanical reinforcement with controlled resorption rates. This work provides fundamental insights into the structure–property–degradation relationships in biocomposites and validates ultrasonic diagnostics as a vital tool for predicting the service life of resorbable implantable devices. Full article

Microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) define a molecular subtype of colorectal cancer (CRC) and predict benefit from immune checkpoint inhibition. Clinically, MSI/MMR assessment may yield discordant results across assays, anatomic sites, or time points. A challenging scenario occurs when tissue analysis identifies microsatellite-stable (MSS) or mismatch repair-proficient (pMMR) CRC, whereas circulating tumor DNA (ctDNA) analysis indicates MSI-H. This review evaluates evidence for MSI/MMR heterogeneity and subclonality in CRC. We reviewed literature on spatial, temporal and subclonal MSI/MMR heterogeneity across human cancers, focusing on CRC. Explanations for tissue–plasma and tissue–tissue discordance, including assay limitations, sampling bias, lesions misattribution, biological evolution, and treatment-related selection, were assessed. Although discordance more commonly reflects assay limitations, sampling bias, or profiling of different lesions, increasing evidence supports genuine biological heterogeneity. Distinct tumor regions may show retained MMR protein expression in one area and regional loss with MSI in another. Noncanonical MMR defects, epigenetic heterogeneity, post-treatment evolution, adaptive mutator-state, and immune selection may also generate dynamic or subclonal instability. Therapeutic relevance may depend not simply on MSI detection, but on whether the unstable clone is sufficiently dominant to generate broadly shared neoantigens across the disease burden. MSI/MMR discordance requires careful interpretation and should not automatically be considered as true biological heterogeneity. Nevertheless, genuine subclonality occurs in CRC and other cancers and may affect responsiveness to immune checkpoint inhibition. Integrated tissue, plasma, spatial and longitudinal analyses may improve treatment decisions and biomarker development. Full article

Polycaprolactone (PCL) is a widely used biodegradable polyester in tissue engineering, drug delivery, and temporary implant design. While its favorable processability, biocompatibility, and low melting temperature are highly advantageous, its slow and condition-dependent degradation remains a major limitation for precise temporal control in biomedical applications. Despite extensive literature on PCL, a critical knowledge gap remains in linking fundamental molecular chain scission directly to macroscopic structural evolution, mechanical failure, and predictable in vivo device performance. To address this, this review provides a comprehensive synthesis of PCL degradation mechanisms, with a particular emphasis on PCL-bioceramic composites designed for hard tissue engineering. We elucidate the progressive degradation pathway—distinguishing between initial hydrolytic chain scission, oligomer formation, the generation of low-molecular-weight degradation products, and their subsequent metabolic fate under physiological conditions. Furthermore, this review critically evaluates how fundamental variables—specifically molecular weight, crystallinity, bioceramic fillers, device geometry, and physiological environments—alter degradation kinetics. By connecting molecular weight reduction to subsequent mass loss, thermal behavior, and mechanical deterioration, we establish a framework for understanding how structural reorganization and crystallinity evolution govern material failure. This review bridges the gap between simplified in vitro models and complex in vivo realities, supporting the rational design of composite biomedical devices with tailored, predictable resorption profiles. Full article

The free fibula flap (FFF) is a reference reconstructive option, particularly for extensive mandibular defects. This narrative review examines the evolution of implant–prosthetic rehabilitation from conventional free-hand reconstruction to prosthetically driven digital workflows. A structured, non-systematic search of PubMed/MEDLINE, Scopus, and Web of Science included English-language publications from 1989 to May 2026. Early approaches were limited by anatomical discrepancies, unfavorable implant positioning, excessive prosthetic space, and difficult peri-implant maintenance. Surgical refinements, including double-barrel reconstruction and soft-tissue procedures, improved rehabilitative conditions in selected cases. Virtual surgical planning, CAD/CAM guides, patient-specific fixation, and guided implant placement subsequently enabled closer coordination of reconstruction, implant positioning, and prosthetic design, supporting immediate protocols such as Jaw-in-a-Day. However, the available evidence remains heterogeneous and predominantly retrospective. Although digital workflows may improve accuracy and operative efficiency, their superiority in terms of long-term biological, prosthetic, functional, and patient-reported outcomes has not been conclusively demonstrated. Emerging technologies, including augmented reality, robotics, artificial intelligence, and digital twins, remain largely preliminary. Full article

Background: Prosthetic joint infections (PJI) are complex complications of arthroplasty. Detailed sequential polymicrobial infection during long clinical courses, with multiple interventions and sustained antibiotic pressure, has been described sparingly. Methods: We present a case of a 78-year-old woman with various comorbidities, including type 2 diabetes mellitus and grade I obesity (body mass index of 31.6), who developed an early PJI after total knee arthroplasty, followed by amputation. Results: Despite serial surgical procedures and antimicrobial therapies, the patient had progressive structural failure in a complex polymicrobial PJI. Therefore, above-knee amputation was required due to reconstructive failure. During the 23-month clinical course, infections caused by six distinct bacteria, some of which were resistant and associated with intramedullary osteomyelitis, were reported at different stages. Conclusions: This case illustrates the evolution and challenging complications of a rare yet dynamic process that developed under selective surgical and antimicrobial pressure. Early recognition of host, tissue, and microbial factors is crucial to achieving optimal PJI outcomes. Full article

Background and Clinical Significance: Interstitial lung disease (ILD) is an uncommon but potentially serious complication of imatinib. Its histopathological characterization has so far relied on surgical biopsy or transbronchial forceps sampling, and no case characterized by transbronchial lung cryobiopsy (TBLC) has been reported. The single previous description of a non-specific interstitial pneumonia (NSIP) pattern with imatinib came from a surgical specimen and was cellular in type, with complete radiological resolution after withdrawal. Case Presentation: A 69-year-old never-smoker began imatinib 400 mg daily for Philadelphia chromosome-positive chronic myeloid leukemia; chest computed tomography performed immediately beforehand was normal. Approximately three months later, she developed dyspnea, dry cough and a cutaneous rash, progressing to acute respiratory failure with forced vital capacity 49% and diffusing capacity 30% of predicted. Avian exposure had ceased one month before symptom onset, and she had never received amiodarone. Although serum precipitins were unavailable, hypersensitivity pneumonitis was considered less likely given the temporal relationship but could not be definitively excluded. TBLC yielded specimens showing fibrotic thickening of the alveolar septa by hyaline collagen deposition with a focal lymphomonocytic infiltrate, corresponding to a fibrotic NSIP pattern. After drug withdrawal and administration of corticosteroids, forced vital capacity rose to 82% of predicted. Multidisciplinary discussion concluded that this was drug-induced ILD, graded probable on the Naranjo scale. Imatinib was subsequently replaced by bosutinib for insufficient molecular response, without pulmonary recurrence. Conclusions: Imatinib-associated ILD may present with an organizing-pneumonia-like radiological pattern followed by a fibrosing pattern, with cryobiopsy performed later demonstrating fibrotic NSIP. Because no tissue was obtained during the acute phase, this sequence remains a hypothesis rather than a demonstrated evolution. Cryobiopsy can be performed safely when surgical biopsy is not appropriate. Full article

Objective: This study aimed to evaluate the long-term degradation behavior, biostimulatory effects, and biocompatibility of a novel poly-L-lactic acid-block-polyethylene glycol/hyaluronic acid (PLLA–b–PEG/HA) composite filler for soft tissue augmentation. Methods: PLLA–b–PEG/HA microsphere properties were characterized via scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance hydrogen spectroscopy (¹H NMR), thermogravimetry (TG) and differential scanning calorimetry (DSC). A 104-week in vivo rabbit model was established to systematically observe filler degradation and tissue responses. Ultrasound monitoring, histological staining, ELISA and RT-PCR were performed to assess volumetric changes, inflammatory reactions and collagen synthesis-related signaling. Results: Physicochemical property tests demonstrated that PLLA–b–PEG retains the fundamental physicochemical properties of pristine PLLA while exhibiting enhanced hydrophilicity. B-ultrasound demonstrated a presented uniform in vivo distribution without displacement or diffusion over time, confirming steady and predictable degradation. SEM verified progressive morphological degradation and porous evolution of the microspheres. The filler induced a mild, balanced inflammatory microenvironment with early expression of both pro-inflammatory (IL-12, TNF-α) and anti-inflammatory (IL-4) cytokines, which resolved gradually over time. Sustained TGF-β upregulation persisted throughout the 104-week observation period, driving continuous neocollagenesis and prominent neoelastogenesis, thereby achieving favorable and long-term tissue remodeling with excellent biocompatibility. Conclusions: The PLLA–b–PEG/HA composite filler exhibits controllable degradation properties and homeostatic regulatory effects, along with outstanding long-term biosafety and tissue integration capacity. As an ideal biostimulatory filler for soft tissue augmentation, it can effectively facilitate the regeneration of high-quality functional extracellular matrix rich in collagen fibers and elastic fibers, and holds promising clinical prospects for natural and long-lasting soft tissue filling applications. Full article

Background: Traumatic auricular amputation represents a rare but complex reconstructive challenge, and numerous surgical techniques have been developed over the past century to optimize functional and aesthetic outcomes. This historical review examines current auricular reattachment and replantation strategies by comparing established surgical techniques for traumatic auricular amputation. Methods: A historical literature search was conducted in PubMed to identify relevant case reports on auricular reconstruction following amputation, dating from 1898 to the present. Eligible studies were reviewed according to the surgical technique used: composite graft reattachment, local flap, pocket techniques, rib cartilage reconstruction, microsurgical replantation, and tissue engineering. Key milestones were documented chronologically and visualized in a timeline. Results: A total of six major reconstructive approaches were identified in the literature, highlighting the historical evolution of auricular replantation methods from 1898 to 2018. Compiled data were visualized to underscore the procedural development and categorize surgical innovations over time. Conclusions: This review presents a synthesized treatment algorithm that integrates historical context and modern adaptations of auricular replantation techniques. The integrated approach provides a structured framework for managing auricular amputations and promotes standardized practices to optimize functional and aesthetic outcomes in auricular reconstructive surgery. Full article

Viral infections continue to pose a major global health challenge because of rapid viral evolution, immune escape, and the emergence of novel pathogens. This review examines the biological characteristics, antiviral mechanisms, production strategies, and therapeutic potential of camelid VHH as next-generation antiviral agents. The review synthesizes current evidence on the structural and functional properties of VHH, their methods of generation and engineering, and their applications against a broad range of respiratory and non-respiratory viruses. Camelid VHH nanobodies exhibit high specificity and affinity, exceptional physicochemical stability, efficient tissue penetration, and the unique ability to recognize conserved and cryptic epitopes that are often inaccessible to conventional antibodies. Engineering approaches, including multivalent, bispecific, Fc-fused, and half-life-extended constructs, further enhance their antiviral potency and pharmacokinetic properties. Evidence from preclinical studies demonstrates potent antiviral activity against multiple viral pathogens through mechanisms that include blocking viral attachment and fusion, inhibiting intracellular replication, targeting conserved viral proteins, and reducing the likelihood of viral escape. The review also highlights emerging advances in recombinant production platforms, artificial intelligence-assisted nanobody design, targeted delivery technologies, and One Health applications. Collectively, the available evidence indicates that camelid VHH represent a highly versatile and adaptable platform for antiviral therapeutics and diagnostics, with considerable potential to support pandemic preparedness and the development of broad-spectrum interventions against current and emerging viral diseases. Full article

Cutaneous wound healing is governed by dynamically interacting mechanical, redox, and bioelectrical signals that regulate cell migration, inflammation, angiogenesis, extracellular-matrix remodeling, and tissue regeneration. Hydrogels are increasingly engineered to modulate these cues; however, most systems are still described through independently measured properties such as stiffness, antioxidant activity, and conductivity, without demonstrating functional coupling among them. This review examines regenerative hydrogels from a cross-domain perspective, integrating the biological basis of mechanotransduction, redox signaling, endogenous bioelectricity, and their molecular convergence with the network-level mechanisms that control hydrogel behavior. Particular emphasis is placed on dynamic crosslinking, viscoelastic relaxation, hydration, redox-active chemistry, ionic and electronic transport, conductive and piezoelectric phases, and degradation-dependent evolution of material function. A conceptual hierarchy is proposed to distinguish property coexistence, structural integration, directional transduction, and adaptive feedback, together with experimental criteria and quantitative approaches for evaluating coupling. Current evidence indicates that mechanoelectrical coupling is the most mature, whereas mechanoredox and redox–electrical interactions remain less systematically quantified. Moving beyond descriptive multifunctionality toward controllable cross-domain transduction may enable hydrogels to function as adaptive soft interfaces capable of responding to the evolving physicochemical conditions of cutaneous regeneration. Full article

Liver disease represents a significant global health burden, and its effective management relies on early, accurate diagnosis. Established assessments for liver diseases, ranging from invasive biopsies to conventional noninvasive imaging (e.g., ultrasound, MRI, and CT), are often limited by inadequate specificity, potential safety risks, or unsuitability for dynamic tracking. Photoacoustic imaging (PAI), a hybrid modality that combines optical absorption contrast with deep ultrasonic detection, offers an attractive solution for noninvasive, high-sensitivity, and high-specificity imaging in deep organs such as the liver. This review summarizes recent advances in photoacoustic imaging for liver pathophysiology, beginning with the evolution of imaging systems and extending to the diverse molecules employed for preclinical studies and early clinical trials. Specifically, novel reconstruction algorithms improved the spatial resolution and acquisition speed by up to threefold, Monte Carlo-based fluence compensation increased the deep-tissue signal-to-background ratio by approximately 50%, and a 7-azaindole-modified probe exhibited one-magnitude-higher superoxide-triggered activation than conventional hemicyanine dyes. Furthermore, we discuss key challenges and future perspectives, highlighting the translational potential of PAI as an emerging liver imaging modality. Full article

The continued evolution of SARS-CoV-2 has reduced the protective effectiveness of first-generation vaccines and underscores the need for broadly reactive next-generation vaccine candidates. Here, we evaluated STFKB, an alum-adjuvanted bivalent recombinant protein vaccine composed of the monomeric Spike (STFK_prototype) and the engineered Spike (STFK_1628X). We assessed the immunogenicity, tolerability, and protective efficacy of STFKB in mice, rats, guinea pigs, rhesus macaques, and Syrian hamsters. STFKB induced robust STFK- and STFK_1628X-specific antibody responses and broadly reactive neutralizing antibodies against multiple SARS-CoV-2 variants in the tested animal models. In hamster challenge studies, STFKB vaccination protected animals from Omicron BA.1 and BA.5 challenge, as shown by reduced body-weight loss, lower viral RNA loads in respiratory tissues, and improved gross lung pathology. Across the tested preclinical models, STFKB was well tolerated, with no vaccine-related overt toxicity observed under the study conditions. These findings support the rationale and translational potential of the bivalent vaccine strategy proposed in this study. Full article

Porcine rotavirus A (PoRVA) is an important cause of diarrhea in neonatal piglets, resulting in significant economic losses in the swine industry. In this study, a PoRVA strain, designated QY, was isolated from diarrheic piglets and systematically characterized. The virus was propagated in MA104 cells and identified by immunofluorescence assay and transmission electron microscopy, showing typical cytopathic effects and spherical particles of approximately 70 nm. Whole-genome sequencing and phylogenetic analysis revealed that QY was a G4P[13] strain with a genotype constellation of G4–P[13]–I1–C1–M1–R1–A8–N1–T1–E1–H1. Several genome segments showed close phylogenetic relationships with human- or bat-associated RVA strains, a pattern consistent with a possible reassortment history of QY. Experimental infection showed that QY caused watery diarrhea, intestinal lesions, and viral shedding in neonatal piglets under the experimental conditions used in this study. High viral loads were detected in small intestinal tissues, accompanied by villous atrophy and epithelial degeneration. These findings provide new insights into the genetic diversity and evolution of PoRVA and further characterize the pathogenicity of the G4P[13] QY strain in neonatal piglets. Full article

Peutz–Jeghers syndrome (PJS) presents an apparent biological paradox: heterozygous germline pathogenic variants in STK11 predispose to predominantly benign hamartomatous growth while conferring a markedly elevated lifetime risk of cancer, whereas somatic STK11 inactivation in established tumors is frequently associated with aggressive progression and therapeutic resistance. STK11 encodes liver kinase B1 (LKB1), a serine/threonine kinase that integrates metabolic, oxidative, architectural, and immune stress responses. Rather than acting solely as a direct brake on proliferation, LKB1 couples cellular growth, survival, and tissue organization to environmental fitness. We therefore propose a context-dependent stress adaptation framework in which impairment of STK11/LKB1 signaling relaxes stress-imposed constraints on cellular fitness, while the ultimate biological outcome is determined by allelic status, tissue context, and cooperating genetic alterations. In PJS, a heterozygous germline STK11 pathogenic variant creates a constitutional cancer predisposed state in which one functional allele is initially retained, although subsequent loss or impairment of the remaining allele may occur during tumor evolution. In sporadic cancers, somatic STK11 inactivation is often biallelic and frequently cooperates with alterations in KRAS, KEAP1, TP53, NF1, or PI3K-pathway genes. These genetic contexts can promote metabolic reprogramming, redox adaptation, autophagy dependence, immune exclusion, cellular plasticity, and therapeutic resistance, with the strongest mechanistic and clinical evidence currently derived from lung adenocarcinoma (LUAD). Within this framework, enhanced persistence under metabolic, oxidative, immune, and therapy-induced stress does not exclude proliferative effects of STK11 loss but provides a permissive background upon which cooperating oncogenic programs can drive clonal expansion and malignant progression. Stress adaptation creates dependencies on interconnected buffering systems, including antioxidant defenses, autophagy, metabolic plasticity, and ferroptosis suppression. Therapeutic strategies that simultaneously disrupt multiple compensatory pathways may therefore exceed tumor adaptive capacity, convert stress tolerance into therapeutic vulnerability, and provide a rational framework for treating LKB1-deficient tumors and other stress-adapted cancers. Full article

Background: Pleural effusion is a common clinical presentation in both benign and malignant conditions. The advent of liquid biopsy allowed new possibilities for non-invasive molecular profiling using body fluids. Pleural fluid, by virtue of its proximity to thoracic malignancies and its rich tumour-derived content, represents a particularly compelling matrix for liquid biopsy analysis. This review synthesises current evidence regarding the diagnostic, predictive, and prognostic utility of pleural liquid biopsy in clinical medicine. Methods: A narrative review was conducted using PubMed, MEDLINE, and EMBASE databases. Search terms included combinations of “pleural effusion”, “liquid biopsy”, “circulating tumour DNA”, “circulating tumour cells”, “exosomes”, “next-generation sequencing”, and “biomarkers”. Priority was given to original research articles, systematic reviews, and meta-analyses published between 2013 and 2026. Results: Pleural fluid contains a diverse repertoire of tumour-derived analytes, including cell-free and circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), exosomes, and soluble proteins. These biomarkers enable molecular characterisation of underlying malignancies with sensitivity that often exceeds that of plasma-based liquid biopsy and complements histological tissue biopsy. Detection of actionable mutations, including EGFR, ALK, KRAS, and BRAF alterations, directly informs targeted therapy selection. Furthermore, serial sampling facilitates real-time monitoring of therapeutic resistance, disease progression, and clonal evolution. Conclusions: Pleural liquid biopsy offers a minimally invasive, reproducible, and clinically informative approach to molecular profiling in patients with pleural disease, particularly those with thoracic malignancies. Despite existing challenges in standardisation and analytical sensitivity, its integration into routine clinical pathways holds significant promise for advancing personalised oncological care. Multi-omics integration and artificial intelligence may further consolidate its role in therapeutic decision-making. Full article