Modulation of cardiac resident macrophages immunometabolism upon high-fat-diet feeding in mice.

Background: A high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice. Methods: C57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes. Results: Hyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes. Conclusion: Dysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms.

Multiparametric MRI-based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

A smart hypochlorous acid fluorescent probe enabling Ibuprofen-release for osteoarthritis theranostics.

Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro. Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.

Frontiers and hotspots in comorbid epilepsy and depression: a bibliometric analysis from 2003 to 2023.

Background: Epilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations. Methods: We conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY & BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including "recognitive impairment" and "mental health," indicating potential future research hotspots and trends. Conclusion: This study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.

Donor-acceptor bulk-heterojunction sensitizer for efficient solid-state infrared-to-visible photon up-conversion.

Solid-state infrared-to-visible photon up-conversion is important for spectral-tailoring applications. However, existing up-conversion systems not only suffer from low efficiencies and a need for high excitation intensity, but also exhibit a limited selection of materials and complex fabrication processes. Herein, we propose a sensitizer with a bulk-heterojunction structure, comprising both an energy donor and an energy acceptor, for triplet-triplet annihilation up-conversion devices. The up-conversion occurs through charge separation at the donor-acceptor interface, followed by the formation of charge transfer state between the energy donor and annihilator following the spin statistics. The bulk-heterojunction sensitizer ensures efficient charge generation and low charge recombination. Hence, we achieve a highly efficient solid-state up-conversion device with 2.20% efficiency and low excitation intensity (10 mW cm-2) through a one-step solution method. We also demonstrate bright up-conversion devices on highly-flexible large-area substrates. This study introduces a simple and scalable platform strategy for fabricating efficient up-conversion devices.

Effect of Mn2+ Doping on the Photoluminescence of Hybrid One-Dimensional Lead Halide Post-Perovskites.

Although organic-inorganic hybrid one-dimensional (1D) lead halide postperovskites (LHPPs) have been reported to show white luminescence and tunable photoluminescence quantum yield (PLQY), their structure-property relationships are not fully understood. Here, we used Mn2+ to test the doping effect on the luminescence of two 1D-LHPPs compounds, namely, {TETA[Pb2Br6]}n 1 and {TETA[Pb2Cl6]}n 2, where TETA = triethylenetetrammonium. We found the pristine compounds show yellowish (551 nm) and bluish (447 nm) emission for 1 and 2, respectively, nanosecond excitation lifetimes (4.17 ns for 1 and 2.29 ns for 2) and low PLQYs (4.65 and 3.57% for 1 and 2, respectively). By fine-doping the Mn2+ ions to ca. 8% the PLQYs for 1 and 2 are maximized to 24 and 25% for 1 and 2, respectively. Upon the increasing Mn2+ dopant, the emission wavelengths can also vary gradually from 551 to 615 nm and from 447 to 660 nm for 1 and 2, respectively, covering almost the whole visible-light range, and the excitation lifetimes are enhanced to microseconds (0.77 µs for 1 and 0.39 µs for 2), owing to the more spin-forbidden d-d transition (4T1-6A1) component from the Mn2+ ions present in the photoluminescence spectra. Moreover, these Mn2+-doped 1D-LHPPs demonstrate high structural and optical stability in humid and high-temperature environments. Hence, such doped materials can be fabricated into a UV-pumped white light-emitting diode, rendering the potential application for solid-state lighting and display systems.

Probabilistic Presurgical Language Functional MRI Atlas of Brain Tumor Patients.

BACKGROUND AND PURPOSE: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy-subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and silent word generation language paradigms using a large sample of patients with brain tumors. MATERIALS AND METHODS: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. 317 patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI dataset of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap map in Montreal Neurological Institute standard space. Wilcoxon signed-rank test was used to determine significant difference in the maximum Dice coefficient for our atlas compared to a meta-analysis-based template with respect to expert-delineated primary language area activations. RESULTS: Probabilities of activating left anterior primary language area and left posterior primary language area in temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in left anterior primary language area (0.351 and 0.326, respectively, P < .05) and left posterior primary language area in temporal lobe (0.274 and 0.244, respectively, P < .005). CONCLUSIONS: Brain tumor patient-and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients than the meta-analysis-based template. ABBREVIATIONS: SENT = sentence completion, LETT = letter fluency, CAT = category fluency, PLA = primary language area, aPLA = anterior PLA, pPLAT = posterior PLA in the temporal lobe, pPLAP = posterior PLA in the parietal lobe, SMA = supplementary motor area, DLPFC = dorsolateral prefrontal cortex, BTLA = basal temporal language area.

Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development.

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.

Parametric Control via the Algebraic Expression of Lotus-Type Pore Shapes in Metals.

Lotus-type porous metals, characterized by low densities, large surface areas, and directional properties, are contemporarily utilized as lightweight, catalytic, and energy-damping materials; heat sinks; etc. In this study, the effects of dimensionless working parameters on the morphology of lotus-type pores in metals during unidirectional solidification were extensively investigated via general algebraic expressions. The independent dimensionless parameters include metallurgical, transport, and geometrical parameters such as Sieverts' law constant, a partition coefficient, the solidification rate, a mass transfer coefficient, the imposed mole fraction of a solute gas, the total pressure at the top free surface, hydrostatic pressure, a solute transport parameter, inter-pore spacing, and initial contact angle. This model accounts for transient gas pressure in the pore, affected by the solute transfer, gas, capillary, and hydrostatic pressures, and Sieverts' laws at the bubble cap and top free surface. Solute transport across the cap accounts for solute convection at the cap and the amount of solute rejected by the solidification front into the pore. The shape of lotus-type pores can be described using a proposed fifth-degree polynomial approximation, which captures the major portions between the initial contact angle and the maximum radius at a contact angle of 90 degrees, obtained by conserving the total solute content in the system. The proposed polynomial approximation, along with its working parameters, offers profound insights into the formation and shape of lotus-type pores in metals. It systematically provides deep insights into mechanisms that may not be easily revealed with experimental studies. The prediction of a lotus-type pore shape is thus algebraically achieved in good agreement with the available experimental data and previous analytical results.

Unveiling fenpropathrin resistance levels in field populations of Tetranychus cinnabarinus (Boisduval): Insights, risks, and RNAi strategy.

Indoor cases of Tetranychus cinnabarinus displaying resistance have been documented, but the resistance level in field populations remains unexplored in China. This study delves into the resistance dynamics of T. cinnabarinus to fenpropathrin in various field populations across China, a pressing concern in contemporary agricultural pest control. The conventional bioassay and amplicon sequencing reveal a notable absence of significant fenpropathrin resistance in field populations, contrasting with known resistance in indoor cases. Current study highlights the limitations of traditional bioassays in detecting early-stage resistance and underscores the nuanced capabilities and constraints of amplicon sequencing in resistance gene frequency analysis. By employing an integrated approach, we combined dose-response bioassays, amplicon sequencing, and statistical modeling to assess resistance levels and investigate underlying genetic factors. The model with empirical data indicates that a 5% mutation frequency represents the threshold before resistance emerges. However, the detection of the kdr mutation in certain populations ranging from 0 to 1.2%, signals an early looming threat of future resistance emergence. Additionally, we further assessed a specific dsRNA targeting VGSC genes at two concentrations (10 ng/µL and 100 ng/µL), both inducing substantial mortality by silencing target genes effectively. The exploration of RNA interference (RNAi) as a novel, more environmentally friendly pest control measure opens new avenues, despite the ongoing challenge of resistance evolution. Overall, this study underscores the necessity for evolving pest management strategies, integrating advanced biotechnological approaches with traditional methods, to effectively counter pesticide resistance and ensure sustainable agricultural productivity.

Adolescent administration of ketamine impairs excitatory synapse formation onto parvalbumin-positive GABAergic interneurons in mouse prefrontal cortex.

Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.

Dissecting PM sensor capabilities: A combined experimental and theoretical study on particle sizing and physicochemical properties.

Recent advancements in particulate matter (PM) optical measurement technology have enhanced the characterization of particle size distributions (PSDs) across various temporal and spatial scales, offering a more detailed analysis than traditional PM mass concentration monitoring. This study employs field experiments, laboratory tests, and model simulations to evaluate the influence of physicochemical characteristics of particulate matter (PM) on the performance of a compact, multi-channel PM sizing sensor. The sensor is integrated within a mini air station (MAS) designed to detect particles across 52 channels. The field experiments highlighted the sensor's ability to track hygroscopicity parameter κ-values across particle sizes, noting an increasing trend with particle size. The sensor's capability in identifying the size and mass concentration of different PM types, including ammonium nitrate, sodium chloride, smoke, incense, and silica dust particles, was assessed through laboratory tests. Laboratory comparisons with the Aerodynamic Particle Sizer (APS) showed high consistency (R2 > 0.96) for various PM sources, supported by Kolmogorov-Smirnov tests confirming the sensor's capability to match APSsize distributions. Model simulations further elucidated the influence of particle refractive index and size distributions on sensor performance, leading to optimized calibrant selection and application-specific recommendations. These comprehensive evaluations underscore the critical interplay between the chemical composition and physical properties of PM, significantly advancing the application and reliability of optical PM sensors in environmental monitoring.