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. 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.

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.

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 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.

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.

Skin biomarkers predict the development of food allergy in early life.

BACKGROUND: Food allergy (FA) often occurs in early childhood with and without atopic dermatitis (AD). FA can be severe and even fatal. For primary prevention, it is important to find early biomarkers to predict the future onset of FA before any clinical manifestations. OBJECTIVE: Our aim was to find early predictors of future onset of FA in the stratum corneum (SC). METHODS: Skin tape strips were collected from the forearm of newborns (n = 129) at age 2 months, before any signs of clinical FA or AD. Children were clinically monitored until they reached age 2 years to confirm the presence or absence of FA and AD. Skin tape strips were subjected to lipidomic analyses by liquid chromatography-tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. RESULTS: Overall, 9 of 129 infants (7.0%) developed FA alone and 9 of 129 infants (7.0%) developed FA concomitantly with AD. In the stratum corneum of children with future FA and concomitant AD and FA, absolute amounts of unsaturated (N24:1)(C18-sphingosine)ceramide and (N26:1)(C18-sphingosine)ceramide and their relative percentages within the molecular group were increased compared with the amounts and percentages in healthy children, with P values ranging from less than .01 to less than .05 according to ANOVA. The children with future AD had normal levels of these molecules. IL-33 level was upregulated in those infants with future FA but not in those with future AD, whereas thymic stromal lymphopoietin was upregulated in those with future AD but not in those with future FA. Logistic regression analysis revealed strong FA predicting power for the combination of dysregulated lipids and cytokines, with an odds ratio reaching 101.4 (95% CI = 5.4-1910.6). CONCLUSION: Noninvasive skin tape strip analysis at age 2 months can identify infants at risk of FA in the future.

Integrative multi-omics characterization reveals sex differences in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with limited treatment modalities and poor prognosis. Recent studies have highlighted the importance of considering sex differences in cancer incidence, prognosis, molecular disparities, and treatment outcomes across various tumor types, including colorectal adenocarcinoma, lung adenocarcinoma, and GBM. METHODS: We performed comprehensive analyses of large-scale multi-omics data (genomic, transcriptomic, and proteomic data) from TCGA, GLASS, and CPTAC to investigate the genetic and molecular determinants that contribute to the unique clinical properties of male and female GBM patients. RESULTS: Our results revealed several key differences, including enrichments of MGMT promoter methylation, which correlated with increased overall and post-recurrence survival and improved response to chemotherapy in female patients. Moreover, female GBM exhibited a higher degree of genomic instability, including aneuploidy and tumor mutational burden. Integrative proteomic and phosphor-proteomic characterization uncovered sex-specific protein abundance and phosphorylation activities, including EGFR activation in males and SPP1 hyperphosphorylation in female patients. Lastly, the identified sex-specific biomarkers demonstrated prognostic significance, suggesting their potential as therapeutic targets. CONCLUSIONS: Collectively, our study provides unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes between male and female GBM patients and facilitates sex-specific treatment interventions. Highlights Female GBM patients were characterized by increased MGMT promoter methylation and favorable clinical outcomes compared to male patients. Female GBMs exhibited higher levels of genomic instability, including aneuploidy and TMB. Each sex-specific GBM is characterized by unique pathway dysregulations and molecular subtypes. EGFR activation is prevalent in male patients, while female patients are marked by SPP1 hyperphosphorylation.

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults with limited treatment modalities and dismal prognosis. A thorough understanding of sex differences could facilitate personalized therapeutic strategies in GBM. In this study, we conducted a comprehensive multi-omics analysis from TCGA, CPTAC, and GLASS studies, revealing distinct molecular and clinical disparities between male and female GBM patients. We discovered that female GBM patients exhibited enrichments of MGMT promoter methylation and high genomic instability, including aneuploidy and TMB. While male GBMs were characterized by activation of EGFR protein and phosphorylation activities, female GBM patients demonstrated hyperphosphorylation of SPP1. Notably, these proteins demonstrated prognostic significance, highlighting their potential as therapeutic targets. Our findings provide unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes in male and female GBM patients, offering valuable opportunities for sex-specific treatment interventions.

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.

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.

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.

Peptide-Decorated Microneedles for the Detection of Microplastics.

The escalating utilization of plastics in daily life has resulted in pervasive environmental pollution and consequent health hazards. The challenge of detecting and capturing microplastics, which are imperceptible to the naked eye, is exacerbated by their diminutive size, hydrophobic surface properties, and capacity to absorb organic compounds. This study focuses on the application of peptides, constituted of specific amino acid sequences, and microneedles for the rapid and selective identification of microplastics. Peptides, due to their smaller size and greater environmental stability compared with antibodies, emerge as a potent solution to overcome the limitations inherent in existing detection methodologies. To immobilize peptides onto microneedles, this study employed microneedles embedded with gold nanorods, augmenting them with sulfhydryl (SH) groups at the peptides' termini. The sensor developed through this methodology exhibited efficient peptide binding to the microneedle tips, thereby facilitating the capture of microplastics. Raman spectroscopy was employed for the detection of microplastics, with the results demonstrating successful attachment to the microneedles. This novel approach not only facilitates localized analysis but also presents a viable strategy for the detection of microplastics across diverse environmental settings.

Initial updosing phase of oral immunotherapy improves quality of life and psychological burden in parents of children with food allergy.

Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.

Creating augmented reality-based experiences for aviation weather training: Challenges, opportunities, and design implications for 3D authoring.

This paper examines opportunities and challenges of integrating augmented reality (AR) into education and investigates requirements to enable instructors to author AR educational experiences. Although AR technology is recognised for its potential in educational enhancement, it poses challenges for instructors creating AR-based experiences due to their limited digital skills and the complexity of 3D authoring tools. Semi-structured interviews with 17 aviation instructors identified current pedagogical approaches, gaps, and potential applications of AR in aviation weather education. Additionally, results highlighted the benefits of AR and obstacles to its integration into education, followed by outlining design priorities and user needs for educational AR authoring. For AR authoring toolkit development, this study recommended incorporating interactive AR lesson modules, early development of user requirements, and prebuilt AR modules. Findings will guide the development of a 3D authoring toolkit for non-technologist instructors, enabling wider AR use in aviation weather education and other educational fields.

Research interviews with aviation instructors were conducted to derive design implications of AR authoring toolkits for non-technologist instructors. Key findings highlighted gaps in aviation weather education, potential AR applications, and barriers to AR in education. Design recommendations emphasised incorporating interactive AR lesson modules, initial user requirements, and prebuilt AR modules.

Simple Functionalization of a Donor Monomer to Enhance Charge Transfer in Porous Polymer Networks for Photocatalytic Hydrogen Evolution.

Porous polymer networks (PPNs) are promising candidates as photocatalysts for hydrogen production. Constructing a donor-acceptor structure is known to be an effective approach for improving photocatalytic activity. However, the process of how a functional group of a monomer can ensure photoexcited charges transfer and improve the hydrogen evolution rate (HER) has not yet been studied on the molecular level. Herein, we design and synthesize two kinds of triazatruxene (TAT)-based PPNs: TATR-PPN with a hexyl (R) group and TAT-PPN without the hexyl group, to understand the relationship between the presence of the functional group and charge transfer. The hexyl group on the TAT unit was found to ensure the transfer of photoexcited electrons from a donor unit to an acceptor unit and endowed the TATR-PPN with stable hydrogen production.

Cardiovascular toxicities associated with bispecific T-cell engager therapy.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administration's Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.

Beauvericin, produced by Fusarium oxysporum inhibits bisphenol A-induced proliferation of human breast cancer cell line by regulating ERα/p38 pathway.

Beauvericin (BEA) is a cyclic depsipeptide secondary metabolite of Fusarium species. It causes chemical hazards in food products and exists in an environment containing soil and various food types. On the other hand, the purified BEA has various biological activities and is regarded as a potential candidate for pharmaceutical research. This study was performed to assess the anti-proliferation activity of BEA against human breast cancer cells by regulating the estrogen receptor-alpha (ERα)/p38 pathway. TA and BA assays verified that BEA is a completed ER antagonist. Additionally, BEA suppressed cell proliferation in the anti-proliferation assay involving ER-positive human breast cancer cells co-treated with BPA and BEA. In respect to an anti-proliferation activity, the BPA-induced phosphorylation of p38 protein was inhibited in the presence of BEA. These results suggested that BEA exerts inhibitory potentials on endocrine disrupting effect and possibly acts as a natural therapeutic material for human estrogen hormonal health.

Patient preference, efficacy, and compliance with zoledronic acid for glucocorticoid-induced osteoporosis in patients with autoimmune diseases.

PURPOSE: We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases. METHODS: We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1 year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1 year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment. Treatment efficacy was analysed by comparing bone mineral density changes and fractures with those in a control group of patients who continued oral BP use. RESULTS: Age, sex, treatment duration, and medication history did not differ significantly between the two groups. Among the participants, 86.7% preferred and were more satisfied with intravenous zoledronic acid than with oral BPs, primarily because of the convenience of its administration interval. Only two patients (4%) reported infusion-related adverse events with zoledronic acid. Furthermore, no significant differences were observed in the annualized percentage change in the bone mineral density of the lumbar spine, femur neck, and hip between patients receiving zoledronic acid and those receiving oral BPs. The occurrence of new fractures was consistent across both groups, with two cases in each, showing no significant differences. CONCLUSION: Patients showed a preference for and greater satisfaction with zoledronic acid, and its efficacy in treating osteoporosis was comparable to that of oral BPs. Therefore, zoledronic acid is a suitable treatment option for GIOP in patients with autoimmune diseases.

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 (AMG-HPC), and posterior hippocampus (post-HPC) over an extended period. Approach: Impedance was periodically sampled every 5-15 minutes over several months in five subjects with drug-resistant epilepsy using an experimental 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-hour 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 days 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-hour 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.