Treatment extent of femoropopliteal disease and clinical outcomes following endovascular therapy.

BACKGROUND: Endovascular therapy (EVT) has become the preferred treatment modality for femoropopliteal disease. However, there is limited evidence regarding its procedural and clinical outcomes according to the affected area. AIMS: The aim of this study is to investigate clinical outcomes and device effectiveness according to treatment extent in the superficial femoral artery (SFA), popliteal artery (PA), or both. METHODS: In this study, we analysed EVT for SFA (2,404 limbs), PA (155 limbs), SFA/PA (383 limbs) using the population in the K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) registry. The primary endpoint was target lesion revascularisation (TLR) at 2 years. RESULTS: The SFA/PA group exhibited a higher prevalence of anatomical complexity, characterised by long lesions, moderate to severe calcification, and total occlusion. The procedures were successful in 97.2% of SFA, 92.9% of PA, and 95.6% of SFA/PA EVTs. The 2-year TLR rates were 21.1%, 18.6%, and 32.7% in the SFA, PA, and SFA/PA groups, respectively. SFA/PA EVT was associated with a significantly increased risk for TLR compared to the SFA group (adjusted hazard ratio [HR] 1.48 [1.09-2.00]; p=0.008) and a trend towards an increased risk compared to the PA group (adjusted HR 1.80 [1.00-3.27]; p=0.052). After overlap weighting, the use of a drug-coated balloon (DCB) was shown to be beneficial, with the lowest TLR rate after SFA and SFA/PA EVT. CONCLUSIONS: In this large real-world registry, SFA/PA EVT was associated with an increased risk for TLR at 2 years compared to the SFA or PA EVT groups, with favourable outcomes when using a DCB or drug-eluting stent in the SFA/PA EVT group.

A facile strategy for synthesizing isosorbide-based polyurethane structural adhesives and core-shell rubber.

A structural adhesive series of biomass-based polyurethane (Biomass-PU) is synthesized using polypropylene glycol (PPG2000), isosorbide-based polyol (RPO300) as polyols, isophorone diisocyanate (IPDI) as an isocyanate and 4-tert-butylphenol (BP) as a capping agent. Three different equivalent ratios of PPG2000/RPO300, 9/1 (Biomass-PU1), 7/3 (Biomass-PU2), and 1/1 (Biomass-PU3), are evaluated to determine the effect of isosorbide-based polyol content on the properties and the optimizing formulation of biomass-PU structure adhesive. The 9/1 ratio of PPG2000/RPO300 substantially leads to the improvement of impact strength by up to 35 MPa, and the PPG2000/RPO300 = 9/1 ratio exhibits better thermal properties and impact strength than those of other ratios. To achieve more compatibility between biomass-PU structure adhesive and core-shell rubber (CSR) toughener, novel CSRs are successfully synthesized using acryl-PU as a shell and biomass-based PU as a core. The chemical structure of biomass-PU structure adhesives is analyzed through FT-IR Spectroscopy and NCO% titration. Thermal properties are evaluated using TGA and DSC analysis. Their molecular weights are measured by GPC. Also, the core-shell rubber (CSR) with a polyurethane shell is prepared to reinforce the impact strength of Biomass-PU structure adhesive.

Effectiveness of cyclosporine nanoemulsion eye drops in patients with mild-to-moderate dry eyes: objective and subjective evaluation.

BACKGROUND: To compare and evaluate objective and subjective clinical parameters between 0.05% cyclosporine nanoemulsion (CsN) and 0.15% hyaluronic acid (HA) administration in patients with mild-to-moderate dry eyes. METHODS: In this prospective, randomized, double-masked, single-center, and placebo-controlled parallel study, patients with mild-to-moderate dry eyes were randomly allocated to be treated with 0.05% CsN or 0.15% HA twice daily. Patients were followed-up at 4, 8, and 12 weeks. Objective and subjective parameters were evaluated during each visit. RESULTS: A total of 35 patients were enrolled in this study. Compared with baseline, tear film break-up time and fluorescein staining scores at 4, 8, and 12 weeks significantly improved in the CsN group. However, the Schirmer I test showed no statistically significant change until week 12. Using the Symptom Assessment in Dry Eye (SANDE) score, both groups gradually showed significant improvement compared with baseline values. However, the Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) showed no statistically significant change during the treatment period. CONCLUSIONS: Both 0.05% CsN and 0.15% HA administration twice a day effectively improved the objective signs and subjective symptoms of patients with mild-to-moderate dry eyes. However, patients treated with 0.05% CsN experienced greater and faster improvement.

Drug-coated balloon versus drug-eluting stent for femoropopliteal total occlusions: intraluminal versus subintimal approaches.

Because there is a lack of comparative studies assessing drug-coated balloon (DCB) and drug-eluting stent (DES) outcomes with respect to intraluminal (IL) and subintimal (SI) approaches in femoropopliteal (FP) total occlusive lesions, we compared the outcomes between DCB (including bailout stenting) and DES treatments for this lesion. A total of 487 limbs (434 patients) were divided into the IL (n = 344, DCB: n = 268, DES: n = 76) and SI (n = 143, DCB: n = 83, DES: n = 60) approach groups. The primary outcome was a major adverse limb event (MALE), defined as above-ankle amputation or repeat revascularization of the index limb. Secondary outcomes included clinically driven target lesion revascularization (TLR), loss of clinical patency, and all-cause death. After adjustment, in each IL and SI approach, the 2-year rates of MALE (p = 0.180 and p = 0.236, respectively), TLR, loss of clinical patency, and all-cause death were similar between the DCB and DES groups. In the DCB and DES groups, both primary and secondary outcomes were similar between the IL and SI approaches. DCB and DES strategies for patients presenting with FP total occlusive lesions demonstrated similar outcomes regardless of the IL or SI approach.Clinical Trial Registration: NCT02748226.

Visible and near-infrared modulating tungsten suboxide nanorods electrochromic films in acidic aqueous electrolytes.

Proton-based aqueous electrolytes can be used to achieve high performance electrochromic nanocrystal thin films due to their small ion size. However, acidic aqueous electrolyte systems have not yet been explored in near-infrared (NIR) absorbing plasmonic tungsten oxide nanocrystal films. Here, we demonstrate tungsten suboxide nanorod films with excellent visible and NIR modulation performance in the H+-based aqueous electrolytes, thanks to their mesoporous structure, nanosized domains, and open tunnel structure. Colloidally synthesized WO2.83 nanorods with an average width of 6 nm and length of 48 nm were converted to WO2.90 nanorod film via annealing in air, while still preserving open tunnels. These films exhibit fast switching speed (tc = 0.9 s, tb = 2.1 s), excellent cycling stability over 2500 cycles, wide optical modulation up to ΔT = 53.8 % in the NIR region, and a high coloration efficiency (CE) of 167 cm2 C⁻1 at 1300 nm. Additionally, introducing a thin spacer (25 µm) reduced intrinsic NIR absorption from water, thereby enhancing the NIR modulation properties. These highly performing aqueous proton-electrolytes-based electrochromic devices open new possibilities for implementing visible and NIR electrochromism.

Impact of Health Informatics Analyst Education on Job Role, Career Transition, and Skill Development: Survey Study.

Background: Professionals with expertise in health informatics play a crucial role in the digital health sector. Despite efforts to train experts in this field, the specific impact of such training, especially for individuals from diverse academic backgrounds, remains undetermined. Objective: This study therefore aims to evaluate the effectiveness of an intensive health informatics training program on graduates with respect to their job roles, transitions, and competencies and to provide insights for curriculum design and future research. Methods: A survey was conducted among 206 students who completed the Advanced Health Informatics Analyst program between 2018 and 2022. The questionnaire comprised four categories: (1) general information about the respondent, (2) changes before and after program completion, (3) the impact of the program on professional practice, and (4) continuing education requirements. Results: The study received 161 (78.2%) responses from the 206 students. Graduates of the program had diverse academic backgrounds and consequently undertook various informatics tasks after their training. Most graduates (117/161, 72.7%) are now involved in tasks such as data preprocessing, visualizing results for better understanding, and report writing for data processing and analysis. Program participation significantly improved job performance (P=.03), especially for those with a master's degree or higher (odds ratio 2.74, 95% CI 1.08-6.95) and those from regions other than Seoul or Gyeonggi-do (odds ratio 10.95, 95% CI 1.08-6.95). A substantial number of respondents indicated that the training had a substantial influence on their career transitions, primarily by providing a better understanding of job roles and generating intrinsic interest in the field. Conclusions: The integrated practical education program was effective in addressing the diverse needs of trainees from various fields, enhancing their capabilities, and preparing them for the evolving industry demands. This study emphasizes the value of providing specialized training in health informatics for graduates regardless of their discipline.

Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease.

INTRODUCTION: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations. METHODS: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.8 years from the Dominantly Inherited Alzheimer's Network. Weekly exercise volume was measured via questionnaire and associations with brain volume (magnetic resonance imaging), cerebrospinal fluid biomarkers, and brain amyloid beta (Aß) measured by positron emission tomography were investigated. RESULTS: Greater volume of weekly exercise at baseline was associated with slower accumulation of brain Aß at preclinical disease stages ß = -0.16 [-0.23 to -0.08], and a slower decline in multiple brain regions including hippocampal volume ß = 0.06 [0.03 to 0.08]. DISCUSSION: Exercise is associated with more favorable profiles of AD-related biomarkers in individuals with ADAD mutations. Exercise may have therapeutic potential for delaying the onset of AD; however, randomized controlled trials are vital to determine a causal relationship before a clinical recommendation of exercise is implemented. HIGHLIGHTS: Greater self-reported weekly exercise predicts slower declines in brain volume in autosomal dominant Alzheimer's disease (ADAD). Greater self-reported weekly exercise predicts slower accumulation of brain amyloid beta in ADAD. Associations varied depending on closeness to estimated symptom onset.

Artificial intelligence-based analysis of behavior and brain images in cocaine-self-administered marmosets.

BACKGROUND: The sophisticated behavioral and cognitive repertoires of non-human primates (NHPs) make them suitable subjects for studies involving cocaine self-administration (SA) schedules. However, ethical considerations, adherence to the 3Rs principle (replacement, reduction and refinement), and other factors make it challenging to obtain NHPs individuals for research. Consequently, there is a need for methods that can comprehensively analyze small datasets using artificial intelligence (AI). NEW METHODS: We employed AI to identify cocaine dependence patterns from collected data. First, we collected behavioral data from cocaine SA marmosets (Callithrix jacchus) to develop a dependence prediction model. SHapley Additive exPlanations (SHAP) values were used to demonstrate the importance of various variables. Additionally, we collected positron emission tomographic (PET) images showing dopamine transporter (DAT) binding potential and developed an algorithm for PET image segmentation. RESULTS: The prediction model indicated that the Random Forest (RF) algorithm performed best, with an area under the curve (AUC) of 0.92. The top five variables influencing the model were identified using SHAP values. The PET image segmentation model achieved an accuracy of 0.97, a mean squared error of 0.02, an intersection over union (IoU) of 0.845, and a Dice coefficient of 0.913. COMPARISON WITH EXISTING METHODS AND CONCLUSION: Utilizing data from the marmoset SA experiment, we developed an ML-based dependence prediction model and analyzed variable importance rankings using SHAP. AI-based imaging segmentation methods offer a valuable tool for evaluating DAT availability in NHPs following chronic cocaine administration.

Trehalose catalytic shift is an intrinsic factor in Mycobacterium tuberculosis that enhances phenotypic heterogeneity and multidrug resistance.

Drug-resistance (DR) in many bacterial pathogens often arises from the repetitive formation of drug-tolerant bacilli, known as persisters. However, it is unclear whether Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), undergoes a similar phenotypic transition. Recent metabolomics studies have identified that a change in trehalose metabolism is necessary for Mtb to develop persisters and plays a crucial role in metabolic networks of DR-TB strains. The present study used Mtb mutants lacking the trehalose catalytic shift and showed that the mutants exhibited a significantly lower frequency of the emergence of DR mutants compared to wildtype, due to reduced persister formation. The trehalose catalytic shift enables Mtb persisters to survive under bactericidal antibiotics by increasing metabolic heterogeneity and drug tolerance, ultimately leading to development of DR. Intriguingly, rifampicin (RIF)-resistant bacilli exhibit cross-resistance to a second antibiotic, due to a high trehalose catalytic shift activity. This phenomenon explains how the development of multidrug resistance (MDR) is facilitated by the acquisition of RIF resistance. In this context, the heightened risk of MDR-TB in the lineage 4 HN878 W-Beijing strain can be attributed to its greater trehalose catalytic shift. Genetic and pharmacological inactivation of the trehalose catalytic shift significantly reduced persister formation, subsequently decreasing the incidence of MDR-TB in HN878 W-Beijing strain. Collectively, the trehalose catalytic shift serves as an intrinsic factor of Mtb responsible for persister formation, cross-resistance to multiple antibiotics, and the emergence of MDR-TB. This study aids in the discovery of new TB therapeutics by targeting the trehalose catalytic shift of Mtb.

Chimeric adenovirus-based herpes zoster vaccine with the tPA signal peptide elicits a robust T-cell immune response.

Herpes zoster (HZ), or shingles, is caused by reactivation of the varicella-zoster virus (VZV), which remains latent in the sensory ganglia until immunity wanes with age. The representative HZ vaccine, Shingrix is efficacious but causes side effects due to vaccine adjuvants. Therefore, the development of highly efficacious vaccines with minimal side effects is required. We developed chimeric adenovirus vector (ChimAd)-based HZ vaccine candidates encoding the VZV glycoprotein E (gE). These candidates include ChimAd-tPAgE, in which the signal peptide is replaced with tissue plasminogen activator (tPA), and ChimAd-WTgE, which retains the original signal peptide. C57BL/6 mice were immunized with VZV-vaccine candidates, and cellular and humoral immune responses were evaluated using interferon-γ ELISPOT and ELISA. The ChimAd-based HZ vaccines induced high levels of gE-specific antibodies and cell-mediated immunity. ChimAd-tPAgE (optimal dose: 1 × 107 IFU) elicited a more robust gE-specific T-cell response than Shingrix and Zostavax, showing potential as HZ prophylactic vaccines.

A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19.

In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.

Lactobacillus plantarum NCHBL-004 modulates high-fat diet-induced weight gain and enhances GLP-1 production for blood glucose regulation.

OBJECTIVES: This study investigated the therapeutic potential of Lactobacillus plantarum NCHBL-004 (NCHBL-004) in the treatment of obesity and associated metabolic disorders. METHODS: Mice were fed either a normal diet (ND) or a high-fat diet (HFD) with oral administration of NCHBL-004. After euthanasia, blood, liver and adipose tissue were collected. Furthermore, the microbiome and short-chain fatty acids (SCFAs) were analyzed from feces. RESULTS: Oral administration of live NCHBL-004 to mice fed a HFD resulted in notable reductions in weight gain, improvements in glucose metabolism, and maintenance of balanced lipid levels. A comparative analysis with other Lactobacillus strains highlighted the superior efficacy of NCHBL-004. Moreover, heat-killed NCHBL-004 demonstrated beneficial effects similar to those of live NCHBL-004. Additionally, administration of live NCHBL-004 induced glucagon-like peptide 1 (GLP-1) production and increased the levels of short-chain fatty acids (SCFAs), including acetate and propionate, in feces, positively influencing liver lipid metabolism and mitigating inflammation. Consistent with this, analysis of the gut microbiome following NCHBL-004 administration showed increases in SCFA-producing microbes with increased proportions of Lactobacillus spp. and a significant increase in the proportion of microbes capable of promoting GLP-1 secretion. CONCLUSIONS: These findings underscore the potential of both live and inactivated NCHBL-004 as potential therapeutic approaches to managing obesity and metabolic disorders, suggesting avenues for further investigation and clinical applications.

A review of environmental epigenetics in aquatic invertebrates.

Aquatic ecosystems face significant challenges due to increasing human-induced environmental stressors. Recent studies emphasize the role of epigenetic mechanisms in the stress responses and adaptations of organisms to those stressors. Epigenetics influences gene expression, enabling phenotypic plasticity and transgenerational effects. Therefore, understanding the epigenetic responses of aquatic invertebrates to environmental stressors is imperative for aquatic ecosystem research. In this study, we organize the mechanisms of epigenetics in aquatic invertebrates and explore their roles in the responses of aquatic invertebrates to environmental stressors. Furthermore, we discuss the inheritance of epigenetic changes and their influence across generations in aquatic invertebrates. A comprehensive understanding of epigenetic responses is crucial for long-term ecosystem management and conservation strategies in the face of irreversible climate change in aquatic environments. In this review, we synthesize existing knowledge about environmental epigenetics in aquatic invertebrates to provide insights and suggest directions for future research.

3D engineering of diseased blood vessels for integrative in vitro-in silico mechanobiology study.

Vascular diseases are complex conditions orchestrated by multiple factors, including cellular components, biochemical stimuli, and mechanical forces. Despite the advancement of numerous therapeutic approaches, the global mortality associated with the diseases continues to escalate owing to a lack of understanding of the underlying pathologies. Tissue engineering and computational strategies have been recently developed to investigate diseased blood vessels from multifactorial perspective, enabling more accurate prediction of disease progression and opening new avenues for preclinical advances. This review focuses on in vitro and in silico blood vessel models to elucidate the pathomechanisms of vascular diseases. Following a discussion of biofabrication and computational modeling strategies, the recent research that utilizes the models of various blood vessel diseases, such as atherosclerosis, aneurysms, varicose veins, and thrombosis, are introduced. Finally, current breakthroughs, existing challenges, and outlooks in the field are described.

A Novel Ferrocene-Linked Thionine as a Dual Redox Mediator for the Electrochemical Detection of Dopamine and Hydrogen Peroxide.

We introduce a novel dual redox mediator synthesized by covalently linking ferrocene dicarboxylic acid (FcDA) and thionine (TH) onto a pre-treated glassy carbon electrode. This unique structure significantly enhances the electro-oxidation of dopamine (DA) and the reduction of hydrogen peroxide (H2O2), offering a sensitive detection method for both analytes. The electrode exhibits exceptional sensitivity, selectivity, and stability, demonstrating potential for practical applications in biosensing. It facilitates rapid electron transfer between the analyte and the electrode surface, detecting H2O2 concentrations ranging from 1.5 to 60 µM with a limit of detection (LoD) of 0.49 µM and DA concentrations from 0.3 to 230 µM with an LoD of 0.07 µM. The electrode's performance was validated through real-sample analyses, yielding satisfactory results.

The Effect of Organic Vegetable Mixed Juice on Blood Circulation and Intestine Flora: Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Epidemiological evidence suggests that fruit and vegetable intake significantly positively affects cardiovascular health. Since vegetable juice is more accessible than raw vegetables, it attracts attention as a health functional food for circulatory diseases. Therefore, this study measured blood lipids, antioxidants, blood circulation indicators, and changes in the microbiome to confirm the effect of organic vegetable mixed juice (OVJ) on improving blood circulation. This 4-week, randomized, double-blinded, placebo-controlled study involved adult men and women with borderline total cholesterol (TC) and low-density lipoprotein (LDL) levels. As a result, blood lipid profile indicators, such as TC, triglycerides, LDL cholesterol, and apolipoprotein B, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. Additionally, the antioxidant biomarker superoxide dismutase increased (p < 0.05). In contrast, systolic and diastolic blood viscosities, as blood circulation-related biomarkers, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. After the intervention, a fecal microbiome analysis confirmed differences due to changes in the intestinal microbiome composition between the OVJ and placebo groups. In conclusion, our research results confirmed that consuming OVJ improves blood circulation by affecting the blood lipid profile, antioxidant enzymes, and microbiome changes.

TNFR2 signaling in oligodendrocyte precursor cells suppresses their immune-inflammatory function and detrimental microglia activation in CNS demyelinating disease.

Multiple Sclerosis (MS) is a chronic degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and progressive neurodegeneration. These processes, combined with the failure of reparative remyelination initiated by oligodendrocyte precursor cells (OPCs), lead to irreversible neurological impairment. The cytokine tumor necrosis factor (TNF) has been implicated in CNS repair via activation of its cognate receptor TNFR2 in glia. Here, we demonstrate the important role of TNFR2 in regulating OPC function in vivo during demyelinating disease, and that TNFR2 expressed in OPCs modulates OPC-microglia interactions. In PdgfrαCreERT:Tnfrsf1bfl/fl:Eyfp mice with selective TNFR2 ablation in OPCs, we observed an earlier onset and disease peak in experimental autoimmune encephalomyelitis (EAE). This was associated with accelerated immune cell infiltration and increased microglia activation in the spinal cord. Similarly, PdgfrαCreERT:Tnfrsf1bfl/fl:Eyfp mice showed rapid and increased microglia reactivity compared to control mice in the corpus callosum after cuprizone-induced demyelination, followed by chronic reduction in the number of mature myelinating oligodendrocytes (OLs). With EAE and cuprizone models combined, we uncovered that TNFR2 does not have a cell autonomous role in OPC differentiation, but may be important for survival of newly formed mature OLs. Finally, using an in vitro approach, we demonstrated that factors released by Tnfrsf1b ablated OPCs drove microglia to develop an exacerbated "foamy" phenotype when incubated with myelin-rich spinal cord homogenate, aberrantly increasing lysosomal lipid accumulation. Together, our data indicate that TNFR2 signaling in OPCs is protective by dampening their immune-inflammatory activation and by suppressing neurotoxic microglia reactivity. This suggests that boosting TNFR2 activation or its downstream cascades could be an effective strategy to restore OPC reparative capacity in neuroimmune and demyelinating disease.

Tau accumulation is cleared by the induced expression of VCP via autophagy.

Tauopathy, including frontotemporal lobar dementia and Alzheimer's disease, describes a class of neurodegenerative diseases characterized by the aberrant accumulation of Tau protein due to defects in proteostasis. Upon generating and characterizing a stable transgenic zebrafish that expresses the human TAUP301L mutant in a neuron-specific manner, we found that accumulating Tau protein was efficiently cleared via an enhanced autophagy activity despite constant Tau mRNA expression; apparent tauopathy-like phenotypes were revealed only when the autophagy was genetically or chemically inhibited. We performed RNA-seq analysis, genetic knockdown, and rescue experiments with clinically relevant point mutations of valosin-containing protein (VCP), and showed that induced expression of VCP, an essential cytosolic chaperone for the protein quality system, was a key factor for Tau degradation via its facilitation of the autophagy flux. This novel function of VCP in Tau clearance was further confirmed in a tauopathy mouse model where VCP overexpression significantly decreased the level of phosphorylated and oligomeric/aggregate Tau and rescued Tau-induced cognitive behavioral phenotypes, which were reversed when the autophagy was blocked. Importantly, VCP expression in the brains of human Alzheimer's disease patients was severely downregulated, consistent with its proposed role in Tau clearance. Taken together, these results suggest that enhancing the expression and activity of VCP in a spatiotemporal manner to facilitate the autophagy pathway is a potential therapeutic approach for treating tauopathy.

Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system xc- in liver cancer: A non-ferroptotic approach.

Erastin, a ferroptosis-inducing system xc- inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system xc-.