A stable and true-blue emissive hexacoordinate Si(IV) N-heterocyclic carbene complex and its use in organic light-emitting diodes.

A neutral hexacoordinate Si(IV) complex containing two tridentate N-heterocyclic carbene ligands is synthesised and characterized by X-ray crystallography, optical spectroscopy, electrochemistry and computational methods. The stable compound exhibits remarkable deep-blue photoluminescence particularly in the solid state, which enables its use as an electroluminescent material in organic light-emitting diodes.

Protocol to assess bioenergetics and mitochondrial fuel usage in murine autoreactive immunocytes using the Seahorse Extracellular Flux Analyzer.

Efficient metabolism, or the means by which cells produce energy resources, is critical for proper effector function. Here, we present a protocol for examining the bioenergetics and mitochondrial fuel utilization of primary murine autoreactive immunocytes using cellular metabolism-modulating drugs. We describe steps for plate calibration, isolation of primary immunocytes, and Seahorse assay plate preparation. We then detail procedures for performing the XF Cell Mito Stress Test followed by bioenergetics calculations and statistics. For complete details on the use and execution of this protocol, please refer to Wilson et al.1.

Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice.

OBJECTIVE: Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear. METHODS: This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment. RESULTS: PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways. CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.

Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Multilayer dielectric reflector using low-index nanolattices.

Dielectric mirrors based on Bragg reflection and photonic crystals have broad application in controlling light reflection with low optical losses. One key parameter in the design of these optical multilayers is the refractive index contrast, which controls the reflector performance. This work reports the demonstration of a high-reflectivity multilayer photonic reflector that consists of alternating layers of TiO2 films and nanolattices with low refractive index. The use of nanolattices enables high-index contrast between the high- and low-index layers, allowing high reflectivity with fewer layers. The broadband reflectance of the nanolattice reflectors with one to three layers has been characterized with peak reflectance of 91.9% at 527 nm and agrees well with theoretical optical models. The high-index contrast induced by the nanolattice layer enables a normalize reflectance band of Δλ/λo of 43.6%, the broadest demonstrated to date. The proposed nanolattice reflectors can find applications in nanophotonics, radiative cooling, and thermal insulation.

Major adverse cardiovascular events in advanced-stage lung cancer: a multicenter cohort study.

Background: Lung cancers are common worldwide. First-line targeted therapy and chemotherapy are both standard treatments in the current guidelines. With the development of new anticancer therapy, the lifespan of patients with late-stage lung cancer has increased. Cardiovascular events can occur during cancer treatment. This observational study aimed to report the incidence of major adverse cardiovascular events (MACE) after cancer treatment using real-world data. Objectives: Patients diagnosed with advanced-stage lung cancer between January 2011 and December 2017 were enrolled. Data were collected from the Chang Gung Research Database (CGRD). Design: Retrospective cohort study. Methods: Baseline characteristics, clinical stages, pathologies, and outcomes were retrieved from the CGRD. Results: We identified 4406 patients with advanced lung cancer, of whom 2197 received first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy and 2209 received first-line platinum-based chemotherapy. Most patients in the first-line EGFR-TKI group were never-smokers (74.9%), whereas those in the first-line chemotherapy group were ever-smokers (66.0%). The incidence of MACE was not significantly different between the two groups (12.0% versus 11.9%, p = 0.910). However, the incidence of ischemic stroke was higher in the first-line EGFR-TKI group than in the first-line chemotherapy group (3.9% versus 1.9%, p < 0.001). Conclusion: MACEs are common in patients with advanced-stage lung cancer during treatment. The incidence of MACE was similar between the first-line EGFR-TKI therapy and first-line chemotherapy groups. Although more patients in the EGFR-TKI group were female and never-smokers, the risk of ischemic stroke was higher in patients who received first-line EGFR-TKI therapy than in those who received first-line chemotherapy.

Precise control of the optical refractive index in nanolattices.

Recent developments in photonic devices, light field display, and wearable electronics have resulted from a competitive development toward new technologies to improve the user experience in the field of optics. These advances can be attributed to the rise of nanophotonics and meta-surfaces, which can be designed to manipulate light more efficiently. In these elements the performance scales are favorable to the index contrast, making the use of low-index material important. In this research, we examine the precise control of refractive indices of a low-index nanolattice material. This approach employs three-dimensional (3D) lithography and atomic layer deposition (ALD), allowing for precise control of the nanolattice geometry and its refractive index. The refractive indices of the fabricated nanolattices are characterized using spectroscopic ellipsometry and agree well with models based on effective medium theory. By controlling the unit-cell geometry by the exposure conditions and the shell thickness by the ALD process, the effective index of the nanolattice film can be precisely controlled to as low as 5 × 10-4. The proposed index control technique opens a gamut of opportunities and enables better performance in nanophotonic elements used in displays and other integrated devices.

Modeling the co-assembly of binary nanoparticles.

In this work, we present a binary assembly model that can predict the co-assembly structure and spatial frequency spectra of monodispersed nanoparticles with two different particle sizes. The approach relies on an iterative algorithm based on geometric constraints, which can simulate the assembly patterns of particles with two distinct diameters, size distributions, and at various mixture ratios on a planar surface. The two-dimensional spatial-frequency spectra of the modeled assembles can be analyzed using fast Fourier transform analysis to examine their frequency content. The simulated co-assembly structures and spectra are compared with assembled nanoparticles fabricated using transfer coating method are in qualitative agreement with the experimental results. The co-assembly model can also be used to predict the peak spatial frequency and the full-width at half-maximum bandwidth, which can lead to the design of the structure spectra by selection of different monodispersed particles. This work can find applications in fabrication of non-periodic nanostructures for functional surfaces, light extraction structures, and broadband nanophotonics.

Glucose oxidation-dependent survival of activated B cells provides a putative novel therapeutic target for lupus treatment.

Aberrant metabolic demand is observed in immune/inflammatory disorders, yet the role in pathogenesis remains unclear. Here, we discover that in lupus, activated B cells, including germinal center B (GCB) cells, have remarkably high glycolytic requirement for survival over T cell populations, as demonstrated by increased metabolic activity in lupus-activated B cells compared to immunization-induced cells. The augmented reliance on glucose oxidation makes GCB cells vulnerable to mitochondrial ROS-induced oxidative stress and apoptosis. Short-term glycolysis inhibition selectively reduces pathogenic activated B in lupus-prone mice, extending their lifespan, without affecting T follicular helper cells. Particularly, BCMA-expressing GCB cells rely heavily on glucose oxidation. Depleting BCMA-expressing activated B cells with APRIL-based CAR-T cells significantly prolongs the lifespan of mice with severe autoimmune disease. These results reveal that glycolysis-dependent activated B and GCB cells, especially those expressing BCMA, are potentially key lupus mediators, and could be targeted to improve disease outcomes.

High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma.

Background: The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA. Methods: Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed. Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function. Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.

Intratumoral thermo-chemotherapeutic alginate hydrogel containing doxorubicin loaded PLGA nanoparticle and heating agent.

Chemotherapy has been widely used to treat cancer; however, the non-specific systemic toxicity of chemotherapeutic agents has always been an issue. Local injection treatment is a strategy used to reduce the undesired adverse effects of chemotherapeutic drugs. In addition, chemotherapeutic agents combined with thermotherapy are effective in further enhancing therapeutic potency. In the present study, we prepared an injectable hydrogel, namely, doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticle (DPN) and magnetite nanoparticle (MNP) embedded in alginate hydrogel (DPN/MNP-HG), where DPN and MNP were the chemotherapeutic and heating agents, respectively, for intratumoral thermo-chemotherapy. Injectable DPN/MNP-HG, which possesses solid-like elastic properties, was conveniently prepared via ionic cross-linking at room-temperature. When exposed to an alternating magnetic field (AMF), DPN/MNP-HG exhibited controllable heat generation with a reversible temperature-rise profile. Regarding the kinetics of DOX release, both with and without AMF, DPN/MNP-HG exhibited a slow initial burst and sustained release profile. In cytotoxicity studies and subcutaneous mouse cancer models, successful thermo-chemotherapy with DPN/MNP-HG resulted in significantly lower cell viability and increased tumor-growth suppression; mice also exhibited good tolerance to injected DPN/MNP-HG both with(+) and without AMF application. In conclusion, the proposed thermo-chemotherapeutic DPN/MNP-HG for local intratumoral injection is a promising formulation for cancer treatment.

Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice.

OBJECTIVE: Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear. METHODS: This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment. RESULTS: PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways. CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.

Salivary Biomarkers to Differentiate between Streptococcus pneumoniae and Influenza A Virus-Related Pneumonia in Children.

Community-acquired pneumonia (CAP) is common among children and can be fatal in certain conditions. In children, CAP can be caused by viral or bacterial infections. Identification of pathogens can help select appropriate therapeutic strategies. Salivary analysis may be a potential diagnostic tool because it is noninvasive, patient-friendly, and easy to perform in children. A prospective study was conducted in children with pneumonia admitted to a hospital. Salivary samples from patients with definite Streptococcus pneumoniae and influenza A strains were used for gel-free (isobaric tag for relative and absolute quantitation (iTRAQ)) proteomics. No statistically significant difference was detected in salivary CRP levels between Streptococcus pneumoniae and influenza A pneumonia in children. Several potential salivary biomarkers were identified using gel-free iTRAQ proteomics to differentiate pneumonia from Streptococcus pneumoniae or influenza A virus infections in pediatric patients. ELISA validated that Streptococcus pneumoniae group has a higher abundance of salivary alpha 1-antichymotrypsin than those in the influenza A group. Whether these salivary biomarkers can be used to distinguish other bacteria from viral pneumonia requires further verification.

Synergistic Effects of Silicate-Platelet Supporting Ag and ZnO, Offering High Antibacterial Activity and Low Cytotoxicity.

Silver nanoparticles (AgNPs) are remarkably able to eliminate microorganisms, but induce cytotoxicity in mammalian cells, and zinc oxide nanoparticles (ZnONPs) are considered to have a wide bactericidal effect with weak cytotoxicity. In this study, both zinc oxide nanoparticles and silver nanoparticles were co-synthesized on a nano-silicate platelet (NSP) to prepare a hybrid of AgNP/ZnONP/NSP. Ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction (XRD), and transmission electron microscopy (TEM) were used to characterize the formation of nanoparticles on the NSP. Synthesized ZnONP/NSP (ZnONP on NSP) was confirmed by the absorption peaks on UV-Vis and XRD. AgNP synthesized on ZnONP/NSP was also characterized by UV-Vis, and ZnONP/NSP showed no interference with synthesis. The images of TEM demonstrated that NSP provides physical support for the growth of nanoparticles and could prevent the inherent aggregation of ZnONP. In antibacterial tests, AgNP/ZnONP/NSP exhibited more efficacy against Staphylococcus aureus (S. aureus) than ZnONP/NSP (ZnONP was synthesized on NSP) and AgNP/NSP (AgNP was synthesized on NSP). In cell culture tests, 1/10/99 (weight ratio) of AgNP/ZnONP/NSP exhibited low cytotoxicity for mammalian cells (>100 ppm). Therefore, AgNP/ZnONP/NSP, containing both AgNP and ZnONP, with both strong antibacterial qualities and low cytotoxicity, showed potentially advantageous medical utilizations due to its antibacterial properties.

The exacerbated hypokalemia in membranous glomerulonephritis due to proximal tubular injury: a neglect issue from a case report and literature review.

BACKGROUND: Membranous glomerulonephritis is the most common primary etiology for the nephrotic syndrome in adults. Beyond the clinical hallmark of nephrotic syndrome such as fluid overloading, dyslipidemia and hypoalbuminemia, the dysregulated homeostasis of potassium and its possible mechanism is seldomly discussed, and its association with the clinical course of membranous GN is lacking. CASE PRESENTATION: A 65 year-old female attended to our emergent department for progressive lower leg edema after taking 15-h of flight. Hypoalbuminemia and hyperlipidemia were both noted, and 24-h urinary total protein was up to 17,950 mg/day. Elevated creatin-phospho-kinase developed at the initial presentation with hypokalemia due to excressive renal excretion. Glycosuria without elevated glycated Hemoglobin occurred. The pathology of kidney biopsy revealed subepithelial immunocomplex deposits with spike formation in the electron microscopy and the positive anti-Phosphlipase A2 receptor antibodies(PLA-2R) with hallmark of membranous glomerulonephritis. In the light microscopy, the vacuolization of proximal tubules was noted, which contributed to the potassium wasting. After 1 year following up duration, the patient's proteinuria persisted after maintenance treatment with calcineurin inhibitor. CONCLUSION: Hypokalemia is a neglected issue in the membranous glomerulonephritis. Unlike the previous literature, our patient had the vacuolization of proximal tubule at the initial presentation with hypokalemia, which might contribute the potassium wasting. The proximal tubular damage with hypokalemia might be a predictive factor for membranous glomerulonephritis.

HIV associated cell death: Peptide-induced apoptosis restricts viral transmission.

The human immunodeficiency virus (HIV) is still a global pandemic and despite the successful use of anti-retroviral therapy, a well-established cure remains to be identified. Viral modulation of cell death has a significant role in HIV pathogenesis. Here we sought to understand the major mechanisms of HIV-induced death of lymphocytes and the effects on viral transmission. Flow cytometry analysis of lymphocytes from five latent HIV-infected patients, and HIV IIIB-infected MT2 cells demonstrated both necrosis and apoptosis to be the major mechanisms of cell death in CD4+ and CD4-/CD8- lymphocytes. Significantly, pro-apoptotic tumor necrosis factor (TNF) peptide (P13) was found to inhibit HIV-related cell death and reduced viral transmission. Whereas pro-necrotic TNF peptide (P16) had little effect on HIV-related cell death and viral transmission. Understanding mechanisms by which cell death can be manipulated may provide additional drug targets to reduce the loss of CD4+ cells and the formation of a viral reservoir in HIV infection.

White Light-Emitting Electrochemical Cells Employing Phosphor-Sensitized Thermally Activated Delayed Fluorescence to Approach All-Phosphorescent Device Efficiencies.

Solid-state light-emitting electrochemical cells (LECs) show promising advantages of simple device architecture, low operation voltage, and insensitivity to the electrode work functions such that they have high potential in low-cost display and lighting applications. In this work, novel white LECs based on phosphor-sensitized thermally activated delayed fluorescence (TADF) are proposed. The emissive layer of these white LECs is composed of a blue-green phosphorescent host doped with a deep-red TADF guest. Efficient singlet-to-triplet intersystem crossing (ISC) on the phosphorescent host and the subsequent Förster energy transfer from the host triplet excitons to guest singlet excitons can make use of both singlet and triplet excitons on the host. With the good spectral overlap between the host emission and the guest absorption, 0.075 wt.% guest doping is sufficient to cause substantial energy transfer efficiency (ca. 40 %). In addition, such a low guest concentration also reduces the self-quenching effect and a high photoluminescence quantum yield of up to 84 % ensures high device efficiency. The phosphor-sensitized TADF white LECs indeed show a high external quantum efficiency of 9.6 %, which is comparable with all-phosphorescent white LECs. By employing diffusive substrates to extract the light trapped in the substrate, the device efficiency can be further improved by ca. 50 %. In the meantime, the intrinsic EL spectrum and device lifetime of the white LECs recover since the microcavity effect is destroyed. This work successfully demonstrates that the phosphor-sensitized TADF white LECs are potential candidates for efficient white light-emitting devices.

A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10-7-7.31 × 10-6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10-7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10-6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

Random-modulated pulse lidar using a gain-switched semiconductor laser with a delayed self-homodyne interferometer.

We propose the generation of random-modulated pulses using a gain-switched semiconductor laser with a delayed self-homodyne interferometer (DSHI) for lidar applications. By emitting non-repetitive random-modulated pulses, ambiguity in ranging and interference in detection can be mitigated. When gain-switched, the wavelength of the laser fluctuates abruptly at the beginning of the pulse and then drops until it stabilizes toward its continuous-wave (CW) state. By beating the two pulses with instantaneous frequency detuning from the DSHI, pulses consisting of random and down-chirped modulations can be generated without any complex code generation and modulation. In this study, we investigate the waveforms and spectra of the random-modulated pulses generated under various homodyne delay lengths, switching currents, and pulsewidths. We characterize their signal-to-noise ratio (SNR), precision, and cross-correlation between consecutive pulses to evaluate their performance in lidar applications. For a good SNR of over 12 dB, the generated pulses have an optimal precision of approximately 1 mm in ranging, which is substantially better than the chaos-modulated pulses generated based on laser feedback dynamics. By establishing a random-modulated pulse lidar based on the proposed gain-switched homodyne scheme, we successfully demonstrate 3D imaging and profiling with good precision.