Deformation-encoding Deep Learning Transformer for High-Frame-Rate Cardiac Cine MRI.

Purpose To develop a deep learning model for increasing cardiac cine frame rate while maintaining spatial resolution and scan time. Materials and Methods A transformer-based model was trained and tested on a retrospective sample of cine images from 5840 patients (mean age, 55 years ± 19 [SD]; 3527 male patients) referred for clinical cardiac MRI from 2003 to 2021 at nine centers; images were acquired using 1.5- and 3-T scanners from three vendors. Data from three centers were used for training and testing (4:1 ratio). The remaining data were used for external testing. Cines with downsampled frame rates were restored using linear, bicubic, and model-based interpolation. The root mean square error between interpolated and original cine images was modeled using ordinary least squares regression. In a prospective study of 49 participants referred for clinical cardiac MRI (mean age, 56 years ± 13; 25 male participants) and 12 healthy participants (mean age, 51 years ± 16; eight male participants), the model was applied to cines acquired at 25 frames per second (fps), thereby doubling the frame rate, and these interpolated cines were compared with actual 50-fps cines. The preference of two readers based on perceived temporal smoothness and image quality was evaluated using a noninferiority margin of 10%. Results The model generated artifact-free interpolated images. Ordinary least squares regression analysis accounting for vendor and field strength showed lower error (P < .001) with model-based interpolation compared with linear and bicubic interpolation in internal and external test sets. The highest proportion of reader choices was "no preference" (84 of 122) between actual and interpolated 50-fps cines. The 90% CI for the difference between reader proportions favoring collected (15 of 122) and interpolated (23 of 122) high-frame-rate cines was -0.01 to 0.14, indicating noninferiority. Conclusion A transformer-based deep learning model increased cardiac cine frame rates while preserving both spatial resolution and scan time, resulting in images with quality comparable to that of images obtained at actual high frame rates. Keywords: Functional MRI, Heart, Cardiac, Deep Learning, High Frame Rate Supplemental material is available for this article. © RSNA, 2024.

Efficacy of live and inactivated recombinant Newcastle disease virus vaccines expressing clade 2.3.4.4b H5 hemagglutinin against H5N1 highly pathogenic avian influenza in SPF chickens, Broilers, and domestic ducks.

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).

Tailored synthesis of pH-responsive biodegradable microcapsules incorporating gelatin, alginate, and hyaluronic acid for effective-controlled release.

In response to escalating environmental concerns and the urgent need for sustainable drug delivery systems, this study introduces biodegradable pH-responsive microcapsules synthesized from a blend of gelatin, alginate, and hyaluronic acid. Employing the coacervation process, capsules were created with a spherical shape, multicore structure, and small sizes ranging from 10 to 20 µm, which exhibit outstanding vitamin E encapsulation efficiency. With substantial incorporation of hyaluronic acid, a pH-responsive component, the resulting microcapsules displayed noteworthy swelling behavior, facilitating proficient core ingredient release at pH 5.5 and 7.4. Notably, these capsules can effectively deliver active substances to the dermal layer under specific skin conditions, revealing promising applications in topical medications and cosmetics. Furthermore, the readily biodegradable nature of the designed capsules was demonstrated through Biochemical Oxygen Demand (BOD) testing, with over 80 % of microcapsules being degraded by microorganisms after one week of incubation. This research contributes to the development of responsive microcapsules and aligns with broader environmental initiatives, offering a promising pathway to mitigate the impact of microplastics while advancing various applications.

Advanced fructo-oligosaccharides improve itching and aberrant epidermal lipid composition in children with atopic dermatitis.

Introduction: The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined. Methods: In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks. Results: The SCORAD and itching scores were reduced in patients treated with both FOS (all p < 0.01) and maltose (p < 0.05 and p < 0.01). Sleep disturbance was improved only in the FOS group (p < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all p < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, p < 0.01). Discussion: FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy.

Purpose: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy. Materials and Methods: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data. Results: Among 208 consecutively enrolled patients, we selected 84 (41 males; median age 59, range 35 to 90) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, 7 mutations in 5 patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival. Conclusion: While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer's clonal evolution. Additionally, baseline-ctDNA's VAF values were prognostic after treatment.

Effects of infant care posture and weight on static postural balance.

BACKGROUND: Studies investigating postural balance during various infant care postures have not been reported yet. OBJECTIVE: The aim of this study was to measure static postural balance when holding an infant dummy in-arms and carrying an infant dummy on back according to different infant dummy weights. METHODS: Sixteen healthy young subjects participated in a balance test. Infant dummies with weights of 4.6 kg (1-month) and 9.8 kg (12-month) were used in this study. All subjects were asked to naturally stand on a force platform in two infant care postures (holding an infant in-arms and carrying an infant on one's back). Center of pressure (COP) was measured from the force platform. Quantitative variables were derived from the COP. Two-way repeated measure analysis of variance (ANOVA) was performed to determine main effects of infant care postures, infant weight, and their interactions on COP variables. RESULTS: Back carrying a 12-month infant dummy had the greatest amplitude in all COP variables. Back carrying posture showed significantly greater mean distance and peak power, faster mean velocity, and wider COP area compared to holding posture (P< 0.05). There were significant weight effects of most COP variables mainly in AP direction (P< 0.01). CONCLUSIONS: Our results could contribute to the prevention of musculoskeletal diseases or prevention of fall due to various infant care activities by developing an assisting device to improve postural balance.

Ischemic stroke outcome after promoting CD4+CD25+ Treg cell migration through CCR4 overexpression in a tMCAO animal model.

The importance of neuroinflammation during the ischemic stroke has been extensively studied. The role of CD4+CD25+ regulatory T (Treg) cells during the recovery phase have shown infarct size reduction and functional improvement, possibly through the mitigation of inflammatory immune responses. We aimed to investigate the molecular factors involved in microglia-Treg cell communication that result in Treg trafficking. First, we observed the migration patterns of CD8+ (cytotoxic) T cells and Treg cells and then searched for chemokines released by activated microglia in an oxygen-glucose deprivation (OGD) model. The transwell migration assay showed increased migration into OGD media for both cell types, in agreement with the increase in chemokines involved in immune cell trafficking from the mouse chemokine profiling array. MSCV retrovirus was transduced to overexpress CCR4 in Treg cells. CCR4-overexpressed Treg cells were injected into the mouse transient middle cerebral artery occlusion (tMCAO) model to evaluate the therapeutic potential via the tetrazolium chloride (TTC) assay and behavioral tests. A general improvement in the prognosis of animals after tMCAO was observed. Our results suggest the increased mobility of CCR4-overexpressed Treg cells in response to microglia-derived chemokines in vitro and the therapeutic potential of Treg cells with increased mobility in cellular therapy.

A Janus carbaporphyrin pseudo-dimer.

Carbaporphyrin dimers, investigated for their distinctive electronic structures and exceptional properties, have predominantly consisted of systems containing identical subunits. This study addresses the associated knowledge gap by focusing on asymmetric carbaporphyrin dimers with Janus-like characteristics. The synthesis of a Janus-type carbaporphyrin pseudo-dimer 5 is presented. It displays antiaromatic characteristics on the fused side and nonaromatic behavior on the unfused side. A newly synthesized tetraphenylene (TPE) linked bis-dibenzihomoporphyrin 8 and a previously reported dibenzo[g,p]chrysene (DBC) linked bis-dicarbacorrole 9 were prepared as controls. Comprehensive analyses, including 1H NMR spectral studies, single crystal X-ray diffraction analyses, and DFT calculations, validate the mixed character of 5. A further feature of the Janus pseudo-dimer 5 is that it may be transformed into a heterometallic complex, with one side coordinating a Cu(III) center and the other stabilizing a BODIPY complex. This disparate regiochemical reactivity underscores the potential of carbaporphyrin dimers as versatile frameworks, with electronic features and site-specific coordination chemistry controlled through asymmetry. These findings position carbaporphyrin dimers as promising candidates for advances in electronic structure studies, coordination chemistry, materials science, and beyond.

Risk of cardiovascular disease with high-dose versus low-dose use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis.

OBJECTIVE: To investigate the risk of cardiovascular disease (CVD) associated with increasing dose of a non-steroidal anti-inflammatory drug (NSAID) in patients with ankylosing spondylitis (AS). METHODS: Using the Korean National Health Insurance database, patients newly diagnosed with AS without prior CVD between 2010 and 2018 were included in this nationwide cohort study. The primary outcome was CVD, a composite outcome of ischaemic heart disease, stroke or congestive heart failure. Exposure to NSAIDs was evaluated using a time-varying approach. The dose of NSAIDs was considered in each exposure period. Cox proportional hazard regression was used to investigate the risk of CVD associated with NSAID use. RESULTS: Of the 19 775 patients (mean age, 36 years; 75% were male), 19 706 received NSAID treatment. During follow-up period of 98 290 person-years, 1663 cases of CVD occurred including 1157 cases of ischaemic heart disease, 301 cases of stroke and 613 cases of congestive heart failure. Increasing dose of NSAIDs was associated with incident CVD after adjusting for confounders (adjusted HR (aHR) 1.10; 95% CI 1.08 to 1.13). Specifically, increasing dose of NSAIDs was associated with incident ischaemic heart disease (aHR 1.08; 95% CI 1.05 to 1.11), stroke (aHR 1.09; 95% CI 1.04 to 1.15) and congestive heart failure (aHR 1.12; 95% CI 1.08 to 1.16). The association between NSAID dose and higher CVD risk was consistent in different subgroups. CONCLUSION: In a real-world AS cohort, higher dose of NSAID treatment was associated with a higher risk of CVD, including ischaemic heart disease, stroke and congestive heart failure.

Designing Novel LiDAR-Detectable Plate-Type Materials: Synthesis, Chemistry, and Practical Application for Autonomous Working Environment.

Plate-type hollow black TiO2 (HL/BT) with a high NIR reflectance was fabricated for the first time as a LiDAR-detectable black material. A TiO2 layer was formed on commercial-grade glass by using the sol-gel method to obtain a plate-type structure. The glass template was then etched with hydrofluoric acid to form a hollow structure, and blackness was further achieved through NaBH4 reduction, which altered the oxidation state of TiO2 to black TixO2x-1 or Ti4+ to Ti3+ and Ti2+. The blackness of the HL/BT material was maintained by a novel approach that involved etching prior to reduction. The thickness of the TiO2 layer was controlled to maximize the NIR reflectance when applied as paint. The HL/BT material with a thickness of 140 nm (HL/BT140) showed a blackness (L*) of 13.3 and high NIR reflectance of 23.6% at a wavelength of 905 nm. This is attributed to the effective light reflection at the interface created by the TiO2 layer and the hollow structure. Plate-type HL/BT140 provides excellent spreadability, durability, and thermal stability in practical paint applications compared with sphere-type materials due to the higher contacting area to the applied surface, making it suitable for use as a LiDAR-detectable inorganic black pigment in autonomous environments.

Uncovering risk factors for adverse events and infections in rheumatoid arthritis and rheumatoid arthritis with interstitial lung disease under treatment with biologics or targeted synthetic DMARDs: insights from the KOBIO Registry.

OBJECTIVES: This study aimed to identify the risk factors associated with overall adverse events (AEs) and infections in patients with rheumatoid arthritis (RA) and comorbid interstitial lung disease (ILD), receiving biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), using data from the Korean College of Rheumatology Biologics registry. METHODS: We analysed data from a cohort of 2,266 adult patients with RA who received b/tsDMARDs, including 169 patients with comorbid ILD. We identified the risk factors for overall AEs and infections in both the all RA group and the subgroup of patients with RA-ILD and investigated the impact of infections on mortality in patients with RA-ILD. RESULTS: Among all patients with RA, 45.7% withdrew b/tsDMARDs, whereas among those with RA-ILD, a higher proportion of 57.4% withdrew their treatment regimen. The main reason for withdrawing b/tsDMARDs in the RA-ILD group was AEs, with infections accounting for the largest proportion of reported AEs. In multivariable analysis of the risk factors for overall AEs and infections in the RA-ILD group, older age was identified as a risk factor for overall AEs (odds ratio [OR], 3.01; p=0.014), and only a current smoking status was identified as a risk factor for infections (OR, 2.11; p=0.035). CONCLUSIONS: Patients with RA-ILD exhibited a higher rate of b/tsDMARDs withdrawal due to overall AEs and infections than those with RA without ILD. In the RA-ILD group, older age was identified as a risk factor for overall AEs, whereas a current smoking status was identified as a risk factor for infections.

Designing a highly near infrared-reflective black nanoparticles for autonomous driving based on the refractive index and principle.

HYPOTHESIS: The development of highly NIR reflective black single-shell hollow nanoparticles (BSS-HNPs) can overcome the Light Detection and Ranging (LiDAR) sensor limitations of dark-tone materials. The crystalline phase of TiO2 and the refractive index can be controlled by calcination temperature. The formation of hollow structure and the refractive index is expected to simultaneously increase the light reflection and LiDAR detectability. EXPERIMENTS: The BSS-HNPs are synthesized using the sol-gel method, calcination, NaBH4 reduction, and etching to form a hollow structure with true blackness. The computational bandgap calculation is conducted to determine the bandgap energy (Eg) of the white and black TiO2 with different crystalline structures. The blackness of the as-synthesized materials is determined by the Commission on Illumination (CIE) L*a*b* color system. FINDINGS: The hydrophilic nature of BSS-HNPs enables the formulation of hydrophilic paints, allowing the mono-layer coating. With the synergistic effects of hollow structure and the refractive index, BSS-HNPs manifested superb NIR reflectance at LiDAR detection wavelengths. The high detectability, blackness, and hollow structure of BSS-HNPs can expand the variety of LiDAR-detectable dark-tone materials.

Fear of Sexual Victimization in Metaverse: A Comparison of Adolescent and Adult Female Users.

Metaverse platforms have gained worldwide popularity in recent years. This increase in popularity has also heightened safety concerns, as virtual sexual assault against children and the youth is on the rise. The issue of sexual abuse in the metaverse is becoming increasingly controversial due to the gaps in the current regulatory framework that result from the uncertain consequences of such virtual crimes. Drawing on an online survey of female users of Zepeto (n = 343), a metaverse social network platform where users interact with others while creating personalized avatars and virtual spaces, this study aims to explore how female users interpret the risk of sexual harassment in Zepeto, examining the triggers of emotional distress and behavioral change that result from such risk assessments by users. It investigates how these interpretations and responses vary depending on their sense of presence and engagement in the virtual environment and identification with their avatars and how all these processes differ between adolescent and adult female users. Overall, this study provides insights into the complex dynamics of virtual victimization. The findings could inform the development of regulatory frameworks that protect users from virtual sexual assault and create a safer environment for all users, especially the youngest generations.

Metalla-Carbaporphyrinoids Consisting of an Acyclic N-Confused Tetrapyrrole Analogue Served as Stable Near-Infrared-II Dyes.

We present herein the synthesis of novel pseudo-metalla-carbaporphyrinoid species (1M: M=Pd and Pt) achieved through the inner coordination of palladium(II) and platinum(II) with an acyclic N-confused tetrapyrrin analogue. Despite their tetrapyrrole frameworks being small, akin to well-known porphyrins, these species exhibit an unusually narrow HOMO-LUMO gap, resulting in an unprecedentedly low-energy absorption in the second near-infrared (NIR-II) region. Density functional theory (DFT) calculations revealed unique dπ-pπ-conjugated electronic structures involving the metal dπ-ligand pπ hybridized molecular orbitals of 1M. Magnetic circular dichroism (MCD) spectroscopy confirmed distinct electronic structures. Remarkably, the complexes feature an open-metal coordination site in the peripheral NN dipyrrin site, forming hetero-metal complexes (1Pd-BF2 and 1Pt-BF2) through boron difluoride complexation. The resulting hetero metalla-carbaporphyrinoid species displayed further redshifted NIR-II absorption, highly efficient photothermal conversion efficiencies (η; 62-65 %), and exceptional photostability. Despite the challenges associated with the theoretical and experimental assessment of dπ-pπ-conjugated metalla-aromaticity in relatively larger (more than 18π electrons) polycyclic ring systems, these organometallic planar tetrapyrrole systems could serve as potential molecular platforms for aromaticity-relevant NIR-II dyes.

Postpartum Maternal Anxiety Affects the Development of Food Allergy Through Dietary and Gut Microbial Diversity During Early Infancy.

PURPOSE: We aimed to investigate the mediating factors between maternal anxiety and the development of food allergy (FA) in children until 2 years from birth. METHODS: In this longitudinal cohort of 122 mother-child dyads from pregnancy to 24 months of age, we regularly surveyed maternal psychological states, infant feeding data, and allergic symptoms and collected stool samples at 6 months of age for microbiome analysis. Considering the temporal order of data collection, we investigated serial mediating effects and indirect effects among maternal anxiety, dietary diversity (DD), gut microbial diversity, and FA using structural equation modeling. RESULTS: Among the 122 infants, 15 (12.3%) were diagnosed with FA. Increased maternal anxiety between 3 and 6 months after delivery was associated with a lower DD score. Infants with low DD at 4 months showed low gut microbial richness, which was associated with FA development. When the infants were grouped into 4 subtypes, using consensus clustering of 13 gut bacteria significantly associated with maternal anxiety and DD, Prevotella, Eubacterium, Clostridiales and Lachnospiraceae were more abundant in the group with lower FA occurrence. CONCLUSIONS: Postpartum maternal anxiety, mediated by reduced DD and gut microbial diversity, may be a risk factor for the development of FA in infants during the first 2 years of life.

Validity and Reliability of the Korean Versions of the Food Allergy Quality of Life Questionnaire-Child Form and Teenager Form.

We aimed to assess the validity and reliability of the Korean versions of the Food Allergy Quality of Life Questionnaire-Child Form (K-FAQLQ-CF) and the Food Allergy Quality of Life Questionnaire-Teenager Form (K-FAQLQ-TF). Patients aged 8-17 years with food allergy (FA) were enrolled and completed the Korean versions of the questionnaires, including the K-FAQLQ-CF, the Food Allergy Independent Measure-Child Form (K-FAIM-CF), and the Pediatric Quality of Life Inventory™ (K-PedsQL™ 4.0) for children and the K-FAQLQ-TF, the Food Allergy Independent Measure-Teenager Form (K-FAIM-TF), and the K-PedsQL™ 4.0 for adolescents. We enrolled 56 children and 23 adolescents in this study. The K-FAQLQ-CF showed a good internal consistency (Cronbach's α coefficient = 0.969) and an excellent test-retest reliability (intraclass correlation coefficient = 0.914, P = 0.011). There was a moderate correlation between the K-FAQLQ-CF and K-FAIM-CF scores (ß = 0.736, P < 0.001), indicating construct validity. The K-FAQLQ-CF score was weakly associated with the K-PedsQL™ 4.0 score (ß = -0.289, P = 0.031), verifying convergent and discriminant validities. The K-FAQLQ-TF also showed a good internal consistency (Cronbach's α coefficient = 0.966) and test-retest reliability (intraclass correlation coefficient = 0.974, P = 0.005). Construct validity was also established by a moderate correlation with the K-FAIM-TF (ß = 0.699, P < 0.001). Our results suggest that the K-FAQLQ-CF and K-FAQLQ-TF are valid and reliable tools to evaluate the quality of life of children and adolescents with FA in Korea.

Anticancer and Antibacterial Properties of Curcumin-Loaded Mannosylated Solid Lipid Nanoparticles for the Treatment of Lung Diseases.

Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcription-quantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.

Acute to long-term characteristics of impedance recordings during neurostimulation in humans.

Objective.This study aims to characterize the time course of impedance, a crucial electrophysiological property of brain tissue, in the human thalamus (THL), amygdala-hippocampus, and posterior hippocampus over an extended period.Approach.Impedance was periodically sampled every 5-15 min over several months in five subjects with drug-resistant epilepsy using an investigational neuromodulation device. Initially, we employed descriptive piecewise and continuous mathematical models to characterize the impedance response for approximately three weeks post-electrode implantation. We then explored the temporal dynamics of impedance during periods when electrical stimulation was temporarily halted, observing a monotonic increase (rebound) in impedance before it stabilized at a higher value. Lastly, we assessed the stability of amplitude and phase over the 24 h impedance cycle throughout the multi-month recording.Main results.Immediately post-implantation, the impedance decreased, reaching a minimum value in all brain regions within approximately two days, and then increased monotonically over about 14 d to a stable value. The models accounted for the variance in short-term impedance changes. Notably, the minimum impedance of the THL in the most epileptogenic hemisphere was significantly lower than in other regions. During the gaps in electrical stimulation, the impedance rebound decreased over time and stabilized around 200 days post-implant, likely indicative of the foreign body response and fibrous tissue encapsulation around the electrodes. The amplitude and phase of the 24 h impedance oscillation remained stable throughout the multi-month recording, with circadian variation in impedance dominating the long-term measures.Significance.Our findings illustrate the complex temporal dynamics of impedance in implanted electrodes and the impact of electrical stimulation. We discuss these dynamics in the context of the known biological foreign body response of the brain to implanted electrodes. The data suggest that the temporal dynamics of impedance are dependent on the anatomical location and tissue epileptogenicity. These insights may offer additional guidance for the delivery of therapeutic stimulation at various time points post-implantation for neuromodulation therapy.