Search Results (565)

Alpha-synuclein (αsyn) misfolding and aggregation underlie several neurodegenerative disorders, including Parkinson’s disease. Early oligomeric intermediates are particularly toxic yet remain challenging to detect and characterize within cellular systems. Here, we employed the luminescent conjugated oligothiophene h-FTAA to investigate early aggregation events of human wildtype (huWT) and A53T-mutated αsyn (huA53T) both in vitro and in HEK293 cells stably expressing native human-αsyn. Comparative fibrillation assays revealed that h-FTAA detected αsyn aggregation with higher sensitivity and earlier onset than Thioflavin T, with the A53T variant displaying accelerated fibrillation. HEK293 cells stably expressing huWT- or huA53T-αsyn were exposed to respective pre-formed fibrils (PFFs), assessed via immunocytochemistry, h-FTAA staining, spectral emission profiling, and fluorescence lifetime imaging microscopy (FLIM). Notably, huA53T PFFs promoted earlier aggregation patterns and yielded narrower fluorescence lifetime distributions compared with huWT PFFs. Spectral imaging showed h-FTAA emission maxima (~550–580 nm) red-shifted and broadened in cells along with variable lifetimes (0.68–0.87 ns), indicating heterogeneous aggregate conformations influenced by cellular milieu. These findings demonstrate that h-FTAA is useful for distinguishing early αsyn conformers in living systems and, together with stable αsyn-expressing HEK293 cells, offers a platform for probing early αsyn morphotypes. Taken together, this opens for further discovery of biomarkers and drugs that can interfere with αsyn aggregation. Full article

Introduction: Lumbar radiculopathies involving the entrapment of nerve roots in the lumbar spine are common neuropathic conditions. These conditions affect 40% to 70% of individuals in their lifetime and lead to significant medical costs. Objective: This study aims to identify clinical, psychological, and biomarker-based prognostic factors that predict functional outcomes following surgery for lumbar radiculopathy. Materials and Methods: This prospective cohort study, conducted at Hospital Central de la Defensa Gómez Ulla, Madrid (Spain), adheres to the STROBE guidelines. The study includes patients aged 18–75 with lumbar radiculopathy, confirmed by clinical diagnosis, imaging, and electromyography (EMG) findings. Exclusion criteria include previous lumbar spine surgeries and systemic diseases. The primary outcome is the Oswestry Low Back Pain Disability Questionnaire. Sample size calculations, based on a conservative effect size (f² = 0.20), determined the need for 172 participants, accounting for a 15% dropout rate and 80% power. Procedure: Patients will undergo an initial assessment, including EMG tests, sociodemographic and psychological questionnaires, blood sample tests, and physical questionnaires. This process will be repeated six months post-intervention, except for the blood sample test, expectations questionnaire, and EMG, which will be performed only once. Statistical Analyses: Data will be analyzed using Python 3.12.3, employing a multivariate linear regression analysis. Assumptions of linearity, independence, homoscedasticity, normality, and no multicollinearity will be validated. Corrective measures will be applied if assumptions are violated. Ethics and Dissemination: The study follows the Declaration of Helsinki guidelines and has been approved by the Ethics Committee of Universidad Rey Juan Carlos (070220241052024). Potential risks will be minimized, and adverse events will be recorded and addressed. Findings will be published in high-impact journals and presented at conferences. Full article

Power metal-oxide-semiconductor field-effect transistors (MOSFETs) provide numerous advantages and are widely utilized in various power circuits. The junction temperature plays a critical role in determining the reliability, performance, and operational lifetime of power MOSFETs. Therefore, accurate monitoring of the junction temperature of power MOSFETs is essential to ensure the safe operation of power circuit systems. In bridge or motor drive circuits, MOSFETs often operate in a freewheeling state via the body diode, where the freewheeling current is typically variable. The proposed method for junction temperature measurement utilizes the body diode and is designed to accommodate varying forward currents. It also accounts for the temperature-dependent ideality factor to improve measurement accuracy. By integrating the forward voltage and forward current of the body diode, this approach reduces the required sampling frequency. To validate the method’s effectiveness, three representative types of power MOSFETs, a Si MOSFET (IRF520), a SiC MOSFET (C2M0080120D), and an aerospace-grade radiation-hardened MOSFET (RSCS25045T1RH), were used to measure junction temperatures before and after irradiation. Following ideality factor correction, the maximum absolute error compared to reference measurements from thermocouples and a thermal imager remained within 2 K across the temperature range of 300 K to 420 K. Experimental results confirm the feasibility of the proposed method. Full article

Acute appendicitis remains one of the most common surgical emergencies, with a lifetime incidence of approximately 7–8% in the USA and Europe. Despite the widespread adoption of the laparoscopic approach and advances made in perioperative care, post-operative infections—particularly intra-abdominal abscesses—continue to pose a substantial clinical challenge, with an overall probability that ranges from 5 to 15%. Nowadays, it is essential not only to improve patient outcomes by reducing these complications but also to promote responsible antibiotic use. This review provides an in-depth examination of post-appendectomy infections in adults, synthesizing research from the past decade. It explores the various risks involved, including those related to the patient, the disease itself, and the surgical techniques employed. There is particular emphasis on the impact of surgical approach, closure methods, timing of surgery, and intraoperative decisions such as drain placement, peritoneal lavage, and routine bacterial cultures. Part of the discussion is about emerging data regarding the use of antiseptic solutions and specimen retrieval techniques. Additionally, the review examines current approaches to managing postoperative intra-abdominal abscesses. It assesses when antibiotics are necessary, evaluates image-guided percutaneous drainage, and considers laparoscopic re-intervention as a possible solution. While recent studies offer valuable insights, the heterogeneity of available evidence highlights the pressing need for high-quality, standardized research. Ultimately, a deeper understanding of infection pathways and preventative strategies is vital—not only for reducing morbidity and hospital readmissions, but also for safeguarding the long-term efficacy of antibiotics and delivering safer, more effective surgical care. Full article

Protein–protein interactions (PPIs) play a crucial role in various biological processes, including signal transduction, transcriptional regulation, and metabolic pathways. Over the years, many methods have been developed to study PPIs, such as yeast two-hybrid (Y2H), co-immunoprecipitation (Co-IP), pull-down assays, and surface plasmon resonance (SPR). However, each of these techniques has its own limitations, including false positives, a lack of specific binding partners, and restricted interaction zones. Fluorescence resonance energy transfer (FRET) has emerged as a powerful technique for investigating PPIs, offering several advantages over traditional methods. Recent advancements in fluorescence microscopy have further enhanced its application in PPI studies. In this review, we summarize recent developments in FRET-based approaches and their applications in PPIs research over the past five years, including conventional FRET, time-resolved FRET (TR-FRET), fluorescence lifetime imaging microscopy-FRET (FLIM-FRET), single-molecule FRET (smFRET), fluorescence cross-correlation spectroscopy FRET (FCCS-FRET), and provide guidance on selecting the most appropriate method for PPIs studies. Full article

Although laser cavitation was discovered half a century ago, novel geometries and regimes to excite this effect have been vigorously explored during the past few decades. This research is driven by a variety of applications of laser cavitation in demanding branches of science and technology, such as microfabrication, synthesis of nanoparticles, manipulation of cells, surgery, and lithotripsy. In this work, we combine experimental studies using high-repetition-rate imaging and numerical simulations to uncover a novel regime of the laser cavitation observed upon excitation of a liquid by a train of laser pulses with the pulse energy of 140 mJ and duration of 1.2 μs delivered through a quartz optical fiber. Once the lifetime of the initial cavitation bubble (excited by the first laser pulse) is larger than the period between pulses, which is 34.3 μs, the secondary pulses in the train pass the gas in a bubble and evaporate additional liquid. This results in the formation of a cascaded cavitation bubble of larger volume and elongated shape of $4.6$ mm length compared to $3.8$ mm in case of excitation by a single laser pulse. In addition, the results of acoustic measurements confirm the presence of shock waves in the applied liquid. Finally, potential applications of the uncovered laser cavitation regime are discussed. Full article

GTD 111 has been employed in first-stage blades in different gas turbines. The study of microstructural evolution is essential for the lifetime assessment and development of turbine blades. The microstructural stability of a 130 MW gas turbine first-stage blade at 800 °C was studied. The microstructure’s evolution was analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermodynamic calculation. As thermal exposure time increases, the shape of γ′ precipitates changes from square to spherical. During thermal exposure, MC particles formed and coarsened along the grain boundaries, and primary MC carbide decomposed into the η phase and M₂₃C₆. The stability of MC carbide at the grain boundaries was lower than that within the grains. MC carbide precipitated at the grain boundaries tends to grow along the boundaries and eventually forms elongated carbide. High-resolution transmission electron microscopy (HRTEM) images indicate that the orientation of the γ′ precipitate changes during the coarsening process. The GTD 111 alloy can be deformed through dislocation shearing at 800 °C. The hardness value initially increases, then decreases with further exposure, which is related to the reduced precipitation strengthening by γ′ precipitates and the reduction in the hardness of the γ matrix. Full article

Zn-doped carbon dots (Zn@C-210 calcination temperature at 210 °C and Zn@C-260 calcination temperature at 260 °C) were synthesized via an in situ calcination method using zinc citrate complexes as precursors, aiming to investigate the mechanisms of their distinctive fluorescence properties. A range of analytical methods were employed to characterize these nanomaterials. The mechanism study revealed that the coordination structure of Zn-O, formed through zinc doping, can induce a metal–ligand charge-transfer effect, which significantly increases the probability of radiative transitions between the excited and ground states, thereby enhancing the fluorescence intensity. The Zn@C-210 in a solid state and Zn@C-260 in water exhibited approximately 71.50% and 21.1% quantum yields, respectively. Both Zn@C-210 and Zn@C-260 exhibited excitation-independent luminescence, featuring a long fluorescence lifetime of 6.5 μs for Zn@C-210 and 6.2 μs for Zn@C-260. Impressively, zinc-doped CDs displayed exceptional biosafety, showing no acute toxicity even at 1000 mg/kg doses. Zn@C-210 has excellent fluorescence in a solid state, showing promise in anti-photobleaching applications; meanwhile, the dual functionality of Zn@C-260 makes it useful as a folate sensor and cellular imaging probe. These findings not only advance the fundamental understanding of metal-doped carbon dot photophysics but also provide practical guidelines for developing targeted biomedical nanomaterials through rational surface engineering and doping strategies. Full article

The risk of developing symptomatic knee osteoarthritis (KOA) during a lifetime, i.e., pain, aching, or stiffness in a joint associated with radiographic KOA, was estimated in 2008 to be around 40% in men and 47% in women. The clinical and scientific communities lack an efficient diagnostic method to effectively monitor, evaluate, and predict the evolution of KOA before and during the therapeutic protocol. In this review, we summarize the main methods that are used or seem promising for the diagnosis of osteoarthritis, with a specific focus on non- or low-invasive methods. As standard diagnostic tools, arthroscopy, magnetic resonance imaging (MRI), and X-ray radiography provide spatial and direct visualization of the joint. However, discrepancies between findings and patient feelings often occur, indicating a lack of correlation between current imaging methods and clinical symptoms. Alternative strategies are in development, including the analysis of biochemical markers or acoustic emission recordings. These methods have undergone deep development and propose, with non- or minimally invasive procedures, to obtain data on tissue condition. However, they present some drawbacks, such as possible interference or the lack of direct visualization of the tissue. Other original methods show strong potential in the field of KOA monitoring, such as electrical bioimpedance or near-infrared spectrometry. These methods could permit us to obtain cheap, portable, and non-invasive data on joint tissue health, while they still need strong implementation to be validated. Also, the use of Artificial Intelligence (AI) in the diagnosis seems essential to effectively develop and validate predictive models for KOA evolution, provided that a large and robust database is available. This would offer a powerful tool for researchers and clinicians to improve therapeutic strategies while permitting an anticipated adaptation of the clinical protocols, moving toward reliable and personalized medicine. Full article

Familial Alzheimer’s disease (FAD) is caused by dominant missense mutations in amyloid precursor protein (APP) and presenilin-1 (PSEN1), the catalytic component of γ-secretase that generates amyloid β-peptides (Aβ) from the APP C-terminal fragment C99. While most FAD mutations increase the ratio of aggregation-prone Aβ42 relative to Aβ40, consistent with the amyloid hypothesis of Alzheimer pathogenesis, some mutations do not increase this ratio. The γ-secretase complex produces amyloid β-peptide (Aβ) through processive cleavage along two pathways: C99 → Aβ49 → Aβ46 → Aβ43 → Aβ40 and C99 → Aβ48 → Aβ45 → Aβ42 → Aβ38. Understanding how FAD mutations affect the multistep γ-secretase cleavage process is critical for elucidating disease pathogenesis. In a recent study, we discovered that FAD mutations lead to stalled γ-secretase/substrate complexes that trigger synaptic loss independently of Aβ production. Here, we further investigate this “stalled complex” hypothesis, focusing on five additional PSEN1 FAD mutations (M84V, C92S, Y115H, T116I, and M139V). A comprehensive biochemical analysis revealed that all five mutations led to substantially reduced initial proteolysis of C99 to Aβ49 or Aβ48 as well as deficiencies in one or more subsequent trimming steps. Results from fluorescence lifetime imaging microscopy support increased stabilization of enzyme–substrate complexes by all five FAD mutations. These findings provide further support for the stalled complex hypothesis, highlighting that FAD mutations impair γ-secretase function by promoting the accumulation of stalled enzyme–substrate complexes. Full article

(1) Background and Aims: Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) face a significantly increased risk of malignancies, including a 10-fold higher risk for colorectal cancer (CRC) and a lifetime risk for cholangiocarcinoma (CCA) exceeding 20%. The mechanisms underlying this elevated risk remain elusive. This review consolidates recent findings on cancer risk in PSC-IBD patients, focusing on molecular pathways, diagnostic innovations, and prevention strategies. (2) Methods: A comprehensive PubMed search was performed to identify studies published through to March 2025 on oncogenic processes, molecular mechanisms, and advancements in diagnostic and preventive strategies for CRC and CCA in PSC-IBD patients. (3) Results: Surveillance guidelines recommend an annual colonoscopy for CRC and imaging combined with CA 19-9 monitoring for CCA. Recent studies highlight the role of molecular alterations, including epigenetic modifications, in tumorigenesis. Advances in molecular diagnostics, imaging, and endoscopic technologies are improving the accuracy and timeliness of cancer detection. (4) Conclusions: PSC-IBD patients remain at high risk for CRC and CCA, emphasizing the need for vigilant surveillance and advanced prevention strategies. Advances in early detection and precision diagnostics offer new opportunities to reduce the cancer burden in this high-risk population. Full article

Transcatheter aortic valve replacement (TAVR) was first introduced as a minimally invasive treatment for patients with severe aortic stenosis (AS) who are at high or intermediate surgical risk. Recently, its application has expanded to include younger and lower-risk patients, establishing TAVR as a less invasive alternative to surgical aortic valve replacement (SAVR) across the entire surgical spectrum. The expanding utilization of TAVR has driven significant advancements that have greatly enhanced its safety and effectiveness, resulting in a substantial reduction in complications such as paravalvular leak, conduction abnormalities, and periprocedural strokes. Numerous trials have demonstrated the potential superiority of TAVR over conventional surgery in achieving favorable clinical outcomes. Furthermore, the increasing number of long-term trials has provided valuable insight into TAVR outcomes in previously under-studied populations, including patients with complex anatomies. However, significant challenges remain, particularly in ensuring the long-term durability of transcatheter valves, with younger patients likely to outlive their bioprosthetic valves. Consequently, the focus is shifting towards lifetime management strategies, including considerations for coronary re-access, the risk of coronary obstruction, and prosthesis–patient mismatch. This review explores key developments in the field, including TAVR for aortic regurgitation and bicuspid anatomy, the emerging role of TAVR in moderate and asymptomatic AS, and innovations in valve design and procedural planning. We also examine novel imaging tools, adjunctive technologies, and strategies to address coronary access and re-intervention. As long-term data accumulate, these evolving trends will shape the future of TAVR and its role in managing aortic valve disease across increasingly complex clinical scenarios. Full article

Objective: We aimed to evaluate the feasibility, added value, and radiation dose of coronary computed tomography angiography (CCTA) and stress dynamic CT myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) in a real-world setting. Materials and Methods: This retrospective study included 65 patients (mean age: 51.2 ± 11.5 years; 21 female) with moderate CAD, selected from the Radiological Database of our hospital between May 2022 and December 2024. All patients underwent CCTA and stress dynamic CT-MPI using a third-generation dual-source CT scanner. The shuttle-mode acquisition technique was used for CT-MPI with 60 mL of contrast (iopamidol, 370 mg iodine/mL) administered at a flow rate of 6 mL/s. The mean myocardial blood flow (MBF) and other quantitative parameters were measured for both CAD and reference segments (RSs). A 17-segment-based analysis was employed (excluding the apex). The MBF ratio, defined as the mean MBF value of CAD segments divided by that of RS, was used with a cut-off value of 0.85 to distinguish hypoperfused from non-hypoperfused segments within CAD territories. Non-parametric statistical tests were applied. Results: A total of 1040 segments were evaluated. In 62 segments, the mean MBF of CAD territories was found to have decreased. The mean MBF and myocardial blood volume (MBV) in hypoperfused CAD segments were 65.1 ± 19.8 mL/100 mL/min and 14.5 ± 2.7 mL/100 mL, respectively, both significantly lower compared to non-hypoperfused CAD segments and RSs (p < 0.001). The mean effective dose of the protocol was 6.3 ± 1.4 mSv, corresponding to an estimated individual lifetime cancer risk of approximately 0.06% per test, based on BEIR VII Phase 2 modeling. This risk is cumulative, with repeat testing over a 10-year period potentially increasing lifetime cancer risk in proportion to total radiation exposure. The mean total examination time was 26 ± 4 min. Conclusion: The combined CCTA and dynamic CT-MPI protocol is feasible in real-world clinical practice and offers a comprehensive morphological and functional assessment of moderate CAD, with a manageable radiation dose and examination time. Full article

Rare earth elements (Ln: Sm, Eu, Tb, Dy) were complexed with caffeic acid (Caf), a natural phenolic compound, to synthesize novel luminescent complexes with enhanced biological activities. The complexes, formulated as Ln(Caf)₃·4H₂O, were characterized using infrared spectroscopy (IR), thermogravimetric analysis (TGA/DTA), mass spectrometry (MS), and fluorescence spectroscopy. Structural studies confirmed the coordination of caffeic acid via carboxylate and hydroxyl groups, forming stable hexacoordinate complexes. Luminescence analysis revealed intense emission bands in the visible spectrum (480–700 nm), attributed to f-f transitions of Ln³⁺ ions, with decay lifetimes ranging from 0.054 to 0.064 ms. Biological assays demonstrated significant antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, with inhibition zones up to 44 mm at 200 µg/mL. The complexes also exhibited potent anticancer activity against MCF7 breast cancer cells, with Sm(Caf)₃·4H₃O showing the lowest IC₅₀ value (15.5 µM). This study highlights the dual functionality of rare earth metal-caffeic acid complexes as promising candidates for biomedical imaging and therapeutic applications. Full article

Currently, the focus of intraoperative imaging in brain tumor surgery is beginning to shift to optical methods such as optical coherence tomography (OCT), Raman spectroscopy, confocal laser endomicroscopy (CLE), and fluorescence lifetime imaging (FLIM). Optical imaging technologies provide in vivo and real-time high-resolution images of tissues. “Optical biopsy” can be considered as an alternative to traditional approaches for intraoperative histopathologic consultation. Intraoperative optical imaging can help to achieve precise intraoperative identification of tumor infiltrations within the surrounding brain parenchyma. Therefore, it can be considered as a complement to existing approaches based on wide-field imaging modalities such as MRI, US, or 5-ALA fluorescence. A promising future direction for intraoperative guidance during brain tumor surgery or stereotactic biopsy lies in the integration of optical imaging with machine learning techniques, enabling automated differentiation between tumor tissue and healthy brain parenchyma. We present this review to increase knowledge and form critical opinions in the field of using optical imaging in brain tumor surgery. Full article