Search Results (4,107)

The development of anode-free sodium metal batteries (AFSMBs) offers a promising pathway to achieve ultrahigh energy density and cost efficiency inherent to conventional sodium ion/metal batteries. However, irreversible Na plating/stripping and dendritic growth remain critical barriers. Herein, we demonstrate that separator engineering is a pivotal strategy for stabilizing AFSMBs. Through systematic evaluation of four separators—2500 separator (PP), 2325 separator (PP/PE/PP), glass fiber (GF), and an Al₂O₃-coated PE membrane, we reveal that the Al₂O₃-coated separator uniquely enables exceptional interfacial kinetics and morphological control. Na||Na symmetric cells with Al₂O₃ coated separator exhibit ultralow polarization (4.5 mV) and the highest exchange current density (1.77 × 10⁻² mA cm⁻²), while the anode-free AlC-NFPP full cells retain 91.6% capacity after 150 cycles at 2C. Specifically, the Al₂O₃ coating homogenizes Na⁺ flux, promotes dense and planar Na deposition, and facilitates near-complete stripping with minimal “dead Na”. This work establishes ceramic-functionalized separators as essential enablers of practical high-energy AFSMBs. Full article

Conventional immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, has revolutionized cancer therapy over the past decade. Yet, the efficacy of these therapies is limited by tumor resistance, antigen escape mechanisms, poor persistence, and T-cell exhaustion, particularly in the treatment of solid tumors. The emergence of unconventional immunotherapies offers novel opportunities by leveraging diverse immune cell subsets and synthetic biologics. This review explores various immunotherapy platforms, including gamma delta T cells, invariant natural killer T cells, mucosal-associated invariant T cells, engineered regulatory T cells, and universal CAR platforms. Additionally, it expands on biologics, including bispecific and multispecific antibodies, cytokine fusions, agonists, and oncolytic viruses, showcasing their potential for modular engineering and off-the-shelf applicability. Distinct features of unconventional platforms include independence from the major histocompatibility complex (MHC), tissue-homing capabilities, stress ligand sensing, and the ability to bridge adaptive and innate immunity. Their compatibility with engineering approaches highlights their potential as scalable, efficient, and cost-effective therapies. To overcome translational challenges such as functional heterogeneity, immune exhaustion, tumor microenvironment-mediated suppression, and limited persistence, novel strategies will be discussed, including metabolic and epigenetic reprogramming, immune cloaking, gene editing, and the utilization of artificial intelligence for patient stratification. Ultimately, unconventional immunotherapies extend the therapeutic horizon of cancer immunotherapy by breaking barriers in solid tumor treatment and increasing accessibility. Continued investments in research for mechanistic insights and scalable manufacturing are key to unlocking their full clinical potential. Full article

The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article

Background/Objectives: This study evaluated the real-world effectiveness of prophylactic Human Papillomavirus (HPV) vaccination in Korean women aged over 26 years, focusing on its impact on persistent HPV infection and disease progression. Methods: This multicenter prospective study analyzed data from the Korea HPV Cohort (2010–2021). After applying exclusion criteria, the final analytical cohort included 1,231 women aged ≥ 27 years with cytologic findings of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions and HPV infection. Propensity score matching was used to compare vaccinated (n = 340) and unvaccinated (n = 891) participants. After matching, 273 vaccinated and 273 unvaccinated individuals were included in the final analysis. The primary outcomes were persistent HPV infection and progression to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Logistic and Cox regression models were employed, with additional age-stratified analyses. Results: Among women aged 27–39 years, vaccination was significantly associated with a 54% reduction in the odds of persistent HPV infection (odds ratio = 0.46; 95% CI: 0.22–0.96; p = 0.040). In the full cohort, vaccinated participants had a 62% lower risk of progression to CIN2+ compared with unvaccinated participants (hazard ratio = 0.38; 95% CI: 0.18–0.81; p = 0.011). Body mass index had a notable impact on HPV persistence in HPV 16/18 genotype groups. Conclusions: HPV vaccination effectively reduced persistent infection and progression to CIN2+ in Korean women, particularly those vaccinated before age 40. These findings support the age-extended HPV vaccination policies in South Korea. Full article

Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of nine most abundant, naturally occurring urinary COL(I)-derived peptides on human endothelial cells at physiological concentrations, using cell migration assays, mass spectrometry-based proteomics, flow cytometry, and AlphaFold 3. While none of the peptides significantly altered endothelial migration by themselves at physiological concentrations, full-length COL(I) increased cell migration, which was inhibited by Peptide 1 (²²⁹NGDDGEAGKPGRPGERGPpGp²⁴⁹). This peptide uniquely contains the DGEA and GRPGER motifs, interacting with integrin α2β1. Flow cytometry confirmed the presence of integrin α2β1 on human endothelial cells, and AlphaFold 3 modeling predicted an interaction between Peptide 1 and integrin α2. Mass spectrometry-based proteomics investigating signaling pathways revealed that COL(I) triggered phosphorylation events linked to integrin α2β1 activation and cell migration, which were absent in COL(I) plus peptide 1-treated cells. These findings identify Peptide 1 as a biologically active COL(I)-derived peptide at a physiological concentration capable of modulating collagen-induced cell migration, and provide a foundation for further investigation into its mechanisms of action and role in urine excretion. Full article

To further enhance the economic performance of fuel cell vehicles (FCVs), this study develops a model-adaptive model predictive control (MPC) strategy. This strategy leverages the dynamic relationship between proton exchange membrane fuel cell (PEMFC) output characteristics and temperature to track its optimal operating temperature (OOT), addressing challenges of temperature control accuracy and high energy consumption in the PEMFC thermal management system (TMS). First, PEMFC and TMS models were developed and experimentally validated. Subsequently, the PEMFC power–temperature coupling curve was experimentally determined under multiple operating conditions to serve as the reference trajectory for TMS multi-objective optimization. For MPC controller design, the TMS model was linearized and discretized, yielding a predictive model adaptable to different load demands for stack temperature across the full operating range. A multi-constrained quadratic cost function was formulated, aiming to minimize the deviation of the PEMFC operating temperature from the OOT while accounting for TMS parasitic power consumption. Finally, simulations under Worldwide Harmonized Light Vehicles Test Cycle (WLTC) conditions evaluated the OOT tracking performance of both PID and MPC control strategies, as well as their impact on stack efficiency and TMS energy consumption at different ambient temperatures. The results indicate that, compared to PID control, MPC reduces temperature tracking error by 33%, decreases fan and pump speed fluctuations by over 24%, and lowers TMS energy consumption by 10%. These improvements enhance PEMFC operational stability and improve FCV energy efficiency. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management. Full article

This paper presents a data-driven energy management scheme for fuel cell and battery electric vehicles, formulated as a constrained optimal control problem. The proposed method employs a co-state network trained using real-time measurements to estimate the control law without requiring prior knowledge of the system model or a complete dataset across the full operating domain. In contrast to conventional reinforcement learning approaches, this method avoids the issue of high dimensionality and does not depend on extensive offline training. Robustness is demonstrated by treating uncertain and time-varying elements, including power consumption from air conditioning systems, variations in road slope, and passenger-related demands, as unknown disturbances. The desired state of charge is defined as a reference trajectory, and the control input is computed while ensuring compliance with all operational constraints. Validation results based on a combined driving profile confirm the effectiveness of the proposed controller in maintaining the battery charge, reducing fluctuations in fuel cell power output, and ensuring reliable performance under practical conditions. Comparative evaluations are conducted against two benchmark controllers: one designed to maintain a constant state of charge and another based on a soft actor–critic learning algorithm. Full article

In this work, graphite anodes and lithium iron phosphate (LFP) cathodes are used to examine the effects of sodium hexafluorophosphate (NaPF₆) and potassium hexafluorophosphate (KPF₆) electrolyte additives on the formation of the solid electrolyte interphase and the performance of lithium-ion batteries in both half-cell and full-cell designs. The objective is to assess whether these additives may increase cycle performance, decrease irreversible capacity loss, and improve interfacial stability. Compared to the control electrolyte (1.22 M Lithium hexafluorophosphate (LiPF₆)), cells with NaPF₆ and KPF₆ additives produced less SEI products, which decreased irreversible capacity loss and enhanced initial coulombic efficiency. Following the formation of the solid electrolyte interphase, the specific capacity of the control cell was 607 mA·h/g, with 177 mA·h/g irreversible capacity loss. In contrast, irreversible capacity loss was reduced by 38.98% and 37.85% in cells containing KPF₆ and NaPF₆ additives, respectively. In full cell cycling, a considerable improvement in capacity retention was achieved by adding NaPF₆ and KPF₆. The electrolyte, including NaPF₆, maintained 67.39% greater capacity than the LiPF₆ baseline after 20 cycles, whereas the electrolyte with KPF₆ demonstrated a 30.43% improvement, indicating the positive impacts of these additions. X-ray photoelectron spectroscopy verified that sodium (Na⁺) and potassium (K⁺) ions were present in the SEI of samples containing NaPF₆ and KPF₆. While K⁺ did not intercalate in LFP, cyclic voltammetry confirmed that Na⁺ intercalated into LFP with negligible impact on the energy storage of full cells. These findings demonstrate that NaPF₆ and KPF₆ are suitable additions for enhancing lithium-ion battery performance in the popular artificial graphite/LFP system. Full article

Background: Lymphomatoid papulosis (LyP) is a primary cutaneous CD30-positive T-cell lymphoproliferative disorder presenting with self-healing erythematous papulonodular lesions that may ulcerate and scar. Treatment varies by lesion extent, location, and severity. Case Report: We describe a 57-year-old man with acral LyP successfully treated with chlormethine gel (CG). The patient experienced impaired second finger mobility for over 3 months due to an ulcerated nodular mass. After 3 months of CG treatment, complete remission, symptom resolution, and full joint recovery were achieved. Six months post-treatment, the patient remained in remission. Conclusions: This case underscores the effectiveness of CG in achieving sustained remission in acral LyP, suggesting its potential as a treatment option for this rare condition. Full article

Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. In this case, a large MLS silently expanded and completely encased the sciatic nerve without causing deficits, highlighting the importance of early imaging, multidisciplinary planning, and individualized surgical strategy in managing complex soft tissue sarcomas. Case Presentation: This case report describes a 67-year-old male with a 30 cm encapsulated myxoid liposarcoma of the posterior left thigh. The tumor had grown insidiously over one year and completely encased the sciatic nerve without causing pain, paresthesia, or motor impairment. Selective embolization was performed preoperatively to minimize blood loss. A posteromedial surgical approach allowed for en bloc resection with negative margins and preservation of sciatic nerve integrity. Histopathology confirmed a myxoid liposarcoma composed primarily of spindle-shaped tumor cells. The patient experienced no postoperative complications or neurologic deficits. At the two-year follow-up, he remains disease-free with full functional recovery. Conclusions: This case illustrates the potential for large, asymptomatic myxoid liposarcomas to encase critical neurovascular structures without infiltration. Preoperative embolization as part of a multidisciplinary plan was key to achieving safe resection and excellent functional outcomes. Full article

Accurate river discharge forecasting remains a critical challenge in hydrology, particularly in data-scarce mountainous regions where in situ observations are limited. This study investigated the potential of long short-term memory (LSTM) networks to improve discharge prediction by leveraging spatially distributed reanalysis data. Using the ERA5-Land dataset, we developed an LSTM model that integrates grid-based meteorological inputs and assesses their relative importance. We conducted experiments on two snow-dominated basins with contrasting physiographic characteristics, the Uba River basin in Kazakhstan and the Flathead River basin in the USA, to answer three research questions: (1) whether full-grid input outperforms reduced configurations and models trained on Caravan, (2) the impact of spatial resolution on accuracy and efficiency, and (3) the effect of partial spatial coverage on prediction reliability. Specifically, we compared the full-grid LSTM with a single-cell LSTM, a basin-average LSTM, a Caravan-trained LSTM, and coarser cell aggregations. The results demonstrate that the full-grid LSTM consistently yields the highest forecasting performance, achieving a median Nash–Sutcliffe efficiency of 0.905 for Uba and 0.93 for Middle Fork Flathead, while using coarser grids and random subsets reduces performance. Our findings highlight the critical importance of spatial input richness and provide a reproducible framework for grid selection in flood-prone basins lacking dense observation networks. Full article

Protein degradation plays a fundamental role in maintaining protein homeostasis and ensures proper cellular function by regulating protein quality and quantity. Heat shock protein 100 (Hsp100), found in bacteria, plants, and fungi, is a unique chaperone family responsible for rescuing misfolded proteins from aggregated states in an ATP-dependent manner. To date, they are primarily known to mediate heat stress adaptation and enhance cellular survival under extreme conditions in higher plants and algae. Resting cyst formation in dinoflagellates is widely recognized as a response to adverse conditions, which offers an adaptive advantage to endure harsh environmental extremes that are unsuitable for vegetative cell growth and survival. In this study, based on a full-length cDNA sequence, we characterized an Hsp100 gene (SaHsp100) from the cosmopolitan bloom-forming dinoflagellate Scrippsiella acuminata, aiming to examine its life stage-specific expression patterns and preliminarily explore its potential functions. The qPCR results revealed that Hsp100 transcript levels were significantly elevated in newly formed resting cysts compared to vegetative cells and continued to increase during storage under simulated marine sediment conditions (darkness, low temperature, and anoxia). Parallel reaction monitoring (PRM)-based quantification further confirmed that Hsp100 protein levels were significantly higher in resting cysts than in vegetative cells and increased after three months of storage. These findings collectively highlighted the fundamental role of Hsp100 in the alteration of the life cycle and dormancy maintenance of S. acuminata, likely by enhancing stress adaptation and promoting cell survival through participation in proteostasis maintenance, particularly under natural sediment-like conditions that trigger severe abiotic stress. Our work deepens the current understanding of Hsp family members in dinoflagellates, paving the way for future investigations into their ecological relevance within this ecologically significant group. Full article

Automated generative design is increasingly used across engineering disciplines to accelerate innovation and reduce costs. Generative design offers the prospect of simplifying manual design tasks by exploring the efficacy of solutions automatically. However, existing generative design frameworks rely heavily on expensive optimisation procedures and often produce customised solutions, lacking reusable generative rules that transfer across different problems. This work presents a bioinspired generative design algorithm utilising the concept of evolutionary development (EvoDevo). This evolves a set of developmental rules that can be applied to different engineering problems to rapidly develop designs without the need to run full optimisation procedures. In this approach, an initial design is decomposed into simple entities called cells, which independently control their local growth over a development cycle. In biology, the growth of cells is governed by a gene regulatory network (GRN), but there is no single widely accepted model for this in artificial systems. The GRN responds to the state of the cell induced by external stimuli in its environment, which, in this application, is the loading regime on a bridge truss structure (but can be generalised to any engineering structure). Two GRN models are investigated: graph neural network (GNN) and graph-based Cartesian genetic programming (CGP) models. Both GRN models are evolved using a novel genetic search algorithm for parameter search, which can be re-used for other design problems. It is revealed that the CGP-based method produces results similar to those obtained using the GNN-based methods while offering more interpretability. In this work, it is shown that this EvoDevo approach is able to produce near-optimal truss structures via growth mechanisms such as moving vertices or changing edge features. The technique can be set up to provide design automation for a range of engineering design tasks. Full article