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1.
Cell ; 186(26): 5859-5875.e24, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38052213

ABSTRACT

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-ß, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.


Subject(s)
Embryo, Mammalian , Embryonic Stem Cells , Animals , Coculture Techniques , Macaca fascicularis , Embryonic Stem Cells/metabolism , Cell Differentiation , Endoderm/metabolism , Cell Lineage
2.
Cell ; 185(23): 4376-4393.e18, 2022 11 10.
Article in English | MEDLINE | ID: mdl-36318920

ABSTRACT

The function of biomolecular condensates is often restricted by condensate dissolution. Whether condensates can be suppressed without condensate dissolution is unclear. Here, we show that upstream regulators of the Hippo signaling pathway form functionally antagonizing condensates, and their coalescence into a common phase provides a mode of counteracting the function of biomolecular condensates without condensate dissolution. Specifically, the negative regulator SLMAP forms Hippo-inactivating condensates to facilitate pathway inhibition by the STRIPAK complex. In response to cell-cell contact or osmotic stress, the positive regulators AMOT and KIBRA form Hippo-activating condensates to facilitate pathway activation. The functionally antagonizing SLMAP and AMOT/KIBRA condensates further coalesce into a common phase to inhibit STRIPAK function. These findings provide a paradigm for restricting the activity of biomolecular condensates without condensate dissolution, shed light on the molecular principles of multiphase organization, and offer a conceptual framework for understanding upstream regulation of the Hippo signaling pathway.


Subject(s)
Hippo Signaling Pathway , Protein Serine-Threonine Kinases , Signal Transduction
3.
Proc Natl Acad Sci U S A ; 120(25): e2221956120, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37307491

ABSTRACT

Investigating coherent acoustic vibrations in nanostructured materials provides fundamental insights into optomechanical responses and microscopic energy flow. Extensive measurements of vibrational dynamics have been performed for a wide variety of nanoparticles and nanoparticle assemblies. However, virtually all of them show that only the dilation modes are launched after laser excitations, and the acoustic bending and torsional motions, which are commonly observed in photoexcited chemical bonds, are absent. Unambiguous identification and refined characterization of these "missing" modes have been a long-standing issue. In this report, we investigated the acoustic vibrational dynamics of individual Au nanoprisms on free-standing graphene substrates using an ultrafast high-sensitivity dark-field imaging approach in four-dimensional transmission electron microscopy. Following optical excitations, we observed low-frequency multiple-mode oscillations and higher superposition amplitudes at nanoprism corners and edges on the subnanoparticle level. In combination with finite-element simulations, we determined that these vibrational modes correspond to out-of-plane bending and torsional motions, superimposed by an overall tilting effect of the nanoprisms. The launch and relaxation processes of these modes are highly pertinent to substrate effects and nanoparticle geometries. These findings contribute to the fundamental understanding about acoustic dynamics of individual nanostructures and their interaction with substrates.

4.
Nature ; 571(7764): E4, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31235950

ABSTRACT

Change history: In this Letter, the bottom blot in Fig. 2g (for 'IB: Myc') was missing. This has been corrected online.

5.
Nature ; 570(7762): 538-542, 2019 06.
Article in English | MEDLINE | ID: mdl-31189955

ABSTRACT

Ribosome-associated quality control (RQC) provides a rescue pathway for eukaryotic cells to process faulty proteins after translational stalling of cytoplasmic ribosomes1-6. After dissociation of ribosomes, the stalled tRNA-bound peptide remains associated with the 60S subunit and extended by Rqc2 by addition of C-terminal alanyl and threonyl residues (CAT tails)7-9, whereas Vms1 catalyses cleavage and release of the peptidyl-tRNA before or after addition of CAT tails10-12. In doing so, Vms1 counteracts CAT-tailing of nuclear-encoded mitochondrial proteins that otherwise drive aggregation and compromise mitochondrial and cellular homeostasis13. Here we present structural and functional insights into the interaction of Saccharomyces cerevisiae Vms1 with 60S subunits in pre- and post-peptidyl-tRNA cleavage states. Vms1 binds to 60S subunits with its Vms1-like release factor 1 (VLRF1), zinc finger and ankyrin domains. VLRF1 overlaps with the Rqc2 A-tRNA position and interacts with the ribosomal A-site, projecting its catalytic GSQ motif towards the CCA end of the tRNA, its Y285 residue dislodging the tRNA A73 for nucleolytic cleavage. Moreover, in the pre-state, we found the ABCF-type ATPase Arb1 in the ribosomal E-site, which stabilizes the delocalized A73 of the peptidyl-tRNA and stimulates Vms1-dependent tRNA cleavage. Our structural analysis provides mechanistic insights into the interplay of the RQC factors Vms1, Rqc2 and Arb1 and their role in the protection of mitochondria from the aggregation of toxic proteins.


Subject(s)
ATP-Binding Cassette Transporters/chemistry , ATP-Binding Cassette Transporters/metabolism , Adenosine Triphosphatases/chemistry , Adenosine Triphosphatases/metabolism , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Homeostasis , Mitochondrial Proteins/metabolism , Ribosomes/metabolism , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/metabolism , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/ultrastructure , Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/ultrastructure , Amino Acid Sequence , Carrier Proteins/ultrastructure , Cryoelectron Microscopy , Models, Molecular , Proteome/metabolism , RNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/metabolism , Ribosome Subunits, Large, Eukaryotic/chemistry , Ribosome Subunits, Large, Eukaryotic/genetics , Ribosome Subunits, Large, Eukaryotic/metabolism , Ribosomes/chemistry , Ribosomes/genetics , Saccharomyces cerevisiae Proteins/antagonists & inhibitors , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/ultrastructure
6.
Small ; 20(2): e2306020, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37661358

ABSTRACT

To date, all-inorganic lead halide perovskite quantum dots have emerged as promising materials for photonic, optoelectronic devices, and biological applications, especially in solar cells, raising numerous concerns about their biosafety. Most of the studies related to the toxicity of perovskite quantum dots (PeQDs) have focused on the potential risks of hybrid perovskites by using zebrafish or human cells. So far, the neurotoxic effects and fundamental mechanisms of PeQDs remain unknown. Herein, a comprehensive methodology is designed to investigate the neurotoxicity of PeQDs by using Caenorhabditis elegans as a model organism. The results show that the accumulation of PeQDs mainly focuses on the alimentary system and head region. Acute exposure to PeQDs results in a decrease in locomotor behaviors and pharyngeal pumping, whereas chronic exposure to PeQDs causes brood decline and shortens lifespan. In addition, some abnormal issues occur in the uterus during reproduction assays, such as vulva protrusion, impaired eggs left in the vulva, and egg hatching inside the mother. Excessive reactive oxygen species formation is also observed. The neurotoxicity of PeQDs is explained by gene expression. This study provides a complete insight into the neurotoxicity of PeQD and encourages the development of novel nontoxic PeQDs.


Subject(s)
Inorganic Chemicals , Nanoparticles , Oxides , Titanium , Humans , Female , Animals , Caenorhabditis elegans , Zebrafish , Calcium Compounds/toxicity , Nanoparticles/toxicity
7.
Acc Chem Res ; 56(21): 2933-2943, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37802125

ABSTRACT

The cyclic GMP-AMP synthase-stimulator interferon gene (cGAS-STING) pathway is an emerging therapeutic target for the prophylaxis and therapy of a variety of diseases, ranging from cancer, infectious diseases, to autoimmune disorders. As a cytosolic double stranded DNA (dsDNA) sensor, cGAS can bind with relatively long dsDNA, resulting in conformational change and activation of cGAS. Activated cGAS catalyzes the conversion of adenosine triphosphate (ATP) and guanosine triphosphate (GTP) into cGAMP, a cyclic dinucleotide (CDN). CDNs, including 2'3'-cGAMP, stimulate adapter protein STING on the endoplasmic membrane, triggering interferon regulatory factor 3 (IRF3) phosphorylation and nuclear factor kappa B (NF-κB) activation. This results in antitumor and antiviral type I interferon (IFN-I) responses. Moreover, cGAS-STING overactivation and the resulting IFN-I responses have been associated with a number of inflammatory and autoimmune diseases. This makes cGAS-STING appealing immunomodulatory targets for the prophylaxis and therapy of various related diseases. However, drug development of CDNs and CDN derivatives is challenged by their limited biostability, difficult formulation, poor pharmacokinetics, and inefficient tissue accumulation and cytosolic delivery. Though recent synthetic small molecular CDN- or non-CDN-based STING agonists have been reported with promising preclinical therapeutic efficacy, their therapeutic efficacy and safety remain to be fully evaluated preclinically and clinically. Therefore, it is highly desirable and clinically significant to advance drug development for cGAS-STING activation by innovative approaches, such as drug delivery systems and drug development for pharmacological immunomodulation of cGAS. In this Account, we summarize our recent research in the engineering and delivery of immunostimulatory or immunoregulatory modulators for cGAS and STING for the immunotherapy of cancer and autoimmune diseases. To improve the delivery efficiency of CDNs, we developed ionizable and pH-responsive polymeric nanocarriers to load STING agonists, aiming to improve the cellular uptake and facilitate the endosomal escape to induce efficient STING activation. We also codelivered STING agonists with complementary immunostimulatants in nanoparticle-in-hydrogel composites to synergetically elicit potent innate and adaptive antitumor responses that eradicate local and distant large tumors. Further, taking advantage of the simplicity of manufacturing and the established nucleic acid delivery system, we developed oligonucleotide-based cGAS agonists as immunostimulant immunotherapeutics as well as adjuvants for peptide antigens for cancer immunotherapy. To suppress the overly strong proinflammatory responses associated with cGAS-STING overactivation in some of the autoimmune disorders, we devised nanomedicine-in-hydrogel (NiH) that codelivers a cGAS inhibitor and cell-free DNA (cfDNA)-scavenging cationic nanoparticles (cNPs) for systemic immunosuppression in rheumatoid arthritis (RA) therapy. Lastly, we discussed current drug development by targeting cGAS-STING for cancer, infectious diseases, and autoimmune diseases, as well as the potential opportunities for utilizing cGAS-STING pathway for versatile applications in disease treatment.


Subject(s)
Autoimmune Diseases , Communicable Diseases , Interferon Type I , Neoplasms , Humans , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism , Interferon Type I/metabolism , DNA/metabolism , Neoplasms/therapy , Immunotherapy , Immunologic Factors , Adjuvants, Immunologic , Hydrogels
8.
Respir Res ; 25(1): 250, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902783

ABSTRACT

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.


Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Respiratory Tract Infections , Humans , Retrospective Studies , Male , Female , Middle Aged , High-Throughput Nucleotide Sequencing/methods , Metagenomics/methods , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Risk Factors , Aged , Adult , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , Hospitalization , Predictive Value of Tests
9.
Exp Eye Res ; 242: 109881, 2024 May.
Article in English | MEDLINE | ID: mdl-38554800

ABSTRACT

The retinal ganglion cells (RGCs) serve as the critical pathway for transmitting visual information from the retina to the brain, yet they can be dramatically impacted by diseases such as glaucoma. When investigating disease processes affecting RGCs in mouse models, accurately quantifying affected cells becomes essential. However, the use of pan RGC markers like RBPMS or THY1 presents challenges in accurate total cell counting. While Brn3a serves as a reliable RGC nuclear marker for automated counting, it fails to encompass all RGC subtypes in mice. To address this limitation and enable precise automated counting, our research endeavors to develop a method for labeling nuclei in all RGC subtypes. Investigating RGC subtypes labeled with the nuclear marker POU6F2 revealed that numerous RGCs unlabeled by Brn3a were, in fact, labeled with POU6F2. We hypothesize that using antibodies against both Brn3a and POU6F2 would label virtually all RGC nuclei in the mouse retina. Our experiments confirmed that staining retinas with both markers resulted in the labeling of all RGCs. Additionally, when using the cell body marker RBPMS known to label all mouse RGCs, all RBPMS-labeled cells also exhibited Brn3a or POU6F2 labeling. This combination of Brn3a and POU6F2 antibodies provides a pan-RGC nuclear stain, facilitating accurate automated counting by labeling cell nuclei in the retina.


Subject(s)
Cell Nucleus , Mice, Inbred C57BL , Retinal Ganglion Cells , Transcription Factor Brn-3A , Animals , Retinal Ganglion Cells/cytology , Retinal Ganglion Cells/metabolism , Mice , Cell Count , Cell Nucleus/metabolism , Transcription Factor Brn-3A/metabolism , Staining and Labeling/methods , Biomarkers/metabolism
10.
Epilepsia ; 65(6): 1631-1643, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38511905

ABSTRACT

OBJECTIVE: We aim to improve focal cortical dysplasia (FCD) detection by combining high-resolution, three-dimensional (3D) magnetic resonance fingerprinting (MRF) with voxel-based morphometric magnetic resonance imaging (MRI) analysis. METHODS: We included 37 patients with pharmacoresistant focal epilepsy and FCD (10 IIa, 15 IIb, 10 mild Malformation of Cortical Development [mMCD], and 2 mMCD with oligodendroglial hyperplasia and epilepsy [MOGHE]). Fifty-nine healthy controls (HCs) were also included. 3D lesion labels were manually created. Whole-brain MRF scans were obtained with 1 mm3 isotropic resolution, from which quantitative T1 and T2 maps were reconstructed. Voxel-based MRI postprocessing, implemented with the morphometric analysis program (MAP18), was performed for FCD detection using clinical T1w images, outputting clusters with voxel-wise lesion probabilities. Average MRF T1 and T2 were calculated in each cluster from MAP18 output for gray matter (GM) and white matter (WM) separately. Normalized MRF T1 and T2 were calculated by z-scores using HCs. Clusters that overlapped with the lesion labels were considered true positives (TPs); clusters with no overlap were considered false positives (FPs). Two-sample t-tests were performed to compare MRF measures between TP/FP clusters. A neural network model was trained using MRF values and cluster volume to distinguish TP/FP clusters. Ten-fold cross-validation was used to evaluate model performance at the cluster level. Leave-one-patient-out cross-validation was used to evaluate performance at the patient level. RESULTS: MRF metrics were significantly higher in TP than FP clusters, including GM T1, normalized WM T1, and normalized WM T2. The neural network model with normalized MRF measures and cluster volume as input achieved mean area under the curve (AUC) of .83, sensitivity of 82.1%, and specificity of 71.7%. This model showed superior performance over direct thresholding of MAP18 FCD probability map at both the cluster and patient levels, eliminating ≥75% FP clusters in 30% of patients and ≥50% of FP clusters in 91% of patients. SIGNIFICANCE: This pilot study suggests the efficacy of MRF for reducing FPs in FCD detection, due to its quantitative values reflecting in vivo pathological changes. © 2024 International League Against Epilepsy.


Subject(s)
Magnetic Resonance Imaging , Malformations of Cortical Development , Humans , Magnetic Resonance Imaging/methods , Female , Male , Adult , Malformations of Cortical Development/diagnostic imaging , Malformations of Cortical Development/pathology , Adolescent , Young Adult , Epilepsies, Partial/diagnostic imaging , Epilepsies, Partial/pathology , Middle Aged , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/pathology , Imaging, Three-Dimensional/methods , Child , False Positive Reactions , Gray Matter/diagnostic imaging , Gray Matter/pathology , Image Processing, Computer-Assisted/methods , Focal Cortical Dysplasia
11.
Inorg Chem ; 63(7): 3327-3334, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38315152

ABSTRACT

Recently, facilely designable metal-organic frameworks have gained attention in the construction of photothermal conversion materials. Nonetheless, most of the previously reported photothermal conversion metal-organic frameworks exhibit limited light absorption capabilities. In this work, a distinctive metal-organic framework with heterogeneous periodic alternate spatial arrangements of metal-oxygen clusters and perylene-based derivative molecules was prepared by in situ synthesis. The building blocks in this inimitable structure behave as both electron donors and electron acceptors, giving rise to the significant inherent charge transfer in this crystalline material, resulting in a narrow band gap with excellent panchromatic absorption, with the ground state being the charge transfer state. Moreover, it can retain excellent air-, photo-, and water-stability in the solid state. The excellent stability and broad light absorption characteristics enable the effective realization of near-infrared (NIR) photothermal conversion, including infrequent NIR-II photothermal conversion, in this perylene-based metal-organic framework.

12.
Eur Arch Psychiatry Clin Neurosci ; 274(1): 165-180, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37000246

ABSTRACT

Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed abnormalities in specific brain regions in obsessive-compulsive disorder (OCD), but results have been inconsistent. We conducted a whole-brain voxel-wise meta-analysis on resting-state functional imaging and VBM studies that investigated differences of functional activity and gray matter volume (GMV) between patients with OCD and healthy controls (HCs) using seed-based d mapping (SDM) software. A total of 41 independent studies (51 datasets) for resting-state functional imaging and 42 studies (46 datasets) for VBM were included by a systematic literature search. Overall, patients with OCD displayed increased spontaneous functional activity in the bilateral inferior frontal gyrus (IFG) (extending to the bilateral insula) and bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), as well as decreased spontaneous functional activity in the bilateral paracentral lobule, bilateral cerebellum, left caudate nucleus, left inferior parietal gyri, and right precuneus cortex. For the VBM meta-analysis, patients with OCD displayed increased GMV in the bilateral thalamus (extending to the bilateral cerebellum), right striatum, and decreased GMV in the bilateral mPFC/ACC and left IFG (extending to the left insula). The conjunction analyses found that the bilateral mPFC/ACC, left IFG (extending to the left insula) showed decreased GMV with increased intrinsic function in OCD patients compared to HCs. This meta-analysis demonstrated that OCD exhibits abnormalities in both function and structure in the bilateral mPFC/ACC, insula, and IFG. A few regions exhibited only functional or only structural abnormalities in OCD, such as the default mode network, striatum, sensorimotor areas, and cerebellum. It may provide useful insights for understanding the underlying pathophysiology of OCD and developing more targeted and efficacious treatment and intervention strategies.


Subject(s)
Brain , Obsessive-Compulsive Disorder , Humans , Brain/diagnostic imaging , Cerebral Cortex , Gray Matter , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/diagnostic imaging
13.
Cereb Cortex ; 33(7): 3562-3574, 2023 03 21.
Article in English | MEDLINE | ID: mdl-35945683

ABSTRACT

Quantitative magnetic resonance (MR) has been used to study cyto- and myelo-architecture of the human brain non-invasively. However, analyzing brain cortex using high-resolution quantitative MR acquisition can be challenging to perform using 3T clinical scanners. MR fingerprinting (MRF) is a highly efficient and clinically feasible quantitative MR technique that simultaneously provides T1 and T2 relaxation maps. Using 3D MRF from 40 healthy subjects (mean age = 25.6 ± 4.3 years) scanned on 3T magnetic resonance imaging, we generated whole-brain gyral-based normative MR relaxation atlases and investigated cortical-region-based T1 and T2 variations. Gender and age dependency of T1 and T2 variations were additionally analyzed. The coefficient of variation of T1 and T2 for each cortical-region was 3.5% and 7.3%, respectively, supporting low variability of MRF measurements across subjects. Significant differences in T1 and T2 were identified among 34 brain regions (P < 0.001), lower in the precentral, postcentral, paracentral lobule, transverse temporal, lateral occipital, and cingulate areas, which contain sensorimotor, auditory, visual, and limbic functions. Significant correlations were identified between age and T1 and T2 values. This study established whole-brain MRF T1 and T2 atlases of healthy subjects using a clinical 3T scanner, which can provide a quantitative and region-specific baseline for future brain studies and pathology detection.


Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Young Adult , Adult , Infant , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Phantoms, Imaging , Healthy Volunteers , Image Processing, Computer-Assisted/methods
14.
Environ Res ; 255: 119130, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38735375

ABSTRACT

OBJECTIVES: This study aims to assess the specific PM2.5-bound metallic elements that contribute to asthma emergency department visits by using a case-crossover study design. METHODS: This study analyzed data from 11,410 asthma emergency department visits as case group and 22,820 non-asthma onset dates occurring one week and two weeks preceding the case day as controls from 2017 to 2020. PM2.5 monitoring data and 35 PM.2.5-bound metallic elements from six different regions in Taiwan were collected. Conditional logistic regression models were used to assess the relationship between asthma and PM2.5-bound metallic elements. RESULTS: Our investigation revealed a statistically significant risk of asthma emergency department visits associated with PM2.5 exposure at lag 0, 1, 2, and 3 during autumn. Additionally, PM2.5-bound hafnium (Hf), thallium (Tl), rubidium (Rb), and aluminum (Al) exhibited a consistently significant positive correlation with asthma emergency department visits at lags 1, 2, and 3. In stratified analyses by area, age, and sex, PM2.5-bound Hf showed a significant and consistent correlation. CONCLUSIONS: This study provides evidence of PM2.5-bound metallic elements effects in asthma exacerbations, particularly for Hf. It emphasizes the importance of understanding the origins of these metallic elements and pursuing emission reductions to mitigate regional health risks.


Subject(s)
Air Pollutants , Asthma , Cross-Over Studies , Emergency Service, Hospital , Particulate Matter , Asthma/epidemiology , Asthma/chemically induced , Taiwan/epidemiology , Emergency Service, Hospital/statistics & numerical data , Particulate Matter/analysis , Humans , Male , Female , Middle Aged , Adult , Air Pollutants/analysis , Aged , Adolescent , Young Adult , Metals/analysis , Child , Environmental Exposure/adverse effects , Child, Preschool , Infant , Emergency Room Visits
15.
J Nanobiotechnology ; 22(1): 52, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38321555

ABSTRACT

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.


Subject(s)
Acellular Dermis , Cystitis , Urinary Tract Infections , Swine , Animals , Levofloxacin , Hydrogels
16.
J Formos Med Assoc ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519322

ABSTRACT

Biological disasters pose a growing challenge in the 21st century, significantly impacting global society. Taiwan has experienced such disasters, resulting in long-term consequences like loss of life, trauma, economic decline, and societal disruptions. Post-disaster, mental health issues such as fear, anxiety, depression, post-traumatic stress disorder (PTSD), and stress surge, accompanied by increased suicide rates. The Coronavirus disease 2019 (COVID-19) (also called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) pandemic, recognized as a biological disaster, triggered lockdowns and quarantines in Taiwan, causing lifestyle changes, economic recession, and so on. These shifts may elevate uncertainty about the future, intensifying mental stress and leading to a rise in various mental illnesses. This article reviews mental health studies conducted in Taiwan during the pandemic, emphasizing the need to integrate this research for future preparedness and interventions regarding the mental health impacts of biological disasters, including COVID-19. Further research is essential to explore long-term effects, interventions, and generalizability.

17.
Chem Soc Rev ; 52(20): 7071-7136, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37755573

ABSTRACT

Porous crystalline materials usually include metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs) and zeolites, which exhibit exceptional porosity and structural/composition designability, promoting the increasing attention in memory and neuromorphic computing systems in the last decade. From both the perspective of materials and devices, it is crucial to provide a comprehensive and timely summary of the applications of porous crystalline materials in memory and neuromorphic computing systems to guide future research endeavors. Moreover, the utilization of porous crystalline materials in electronics necessitates a shift from powder synthesis to high-quality film preparation to ensure high device performance. This review highlights the strategies for preparing porous crystalline materials films and discusses their advancements in memory and neuromorphic electronics. It also provides a detailed comparative analysis and presents the existing challenges and future research directions, which can attract the experts from various fields (e.g., materials scientists, chemists, and engineers) with the aim of promoting the applications of porous crystalline materials in memory and neuromorphic computing systems.

18.
J Environ Manage ; 357: 120653, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38574704

ABSTRACT

In this research, we established an enhanced aerobic biological method utilizing a high-density bacterial flora for the treatment of low-biochemical plating parts washing wastewater. The elucidation of pollutant removal mechanisms was achieved through a comprehensive analysis of changes in sludge characteristics and bacterial community structure. The results demonstrated that throughout the operational period, the organic load remained stable within the range of 0.01-0.02 kgCOD/kgMLSS·d, the BOD5/COD ratio increased from 0.004 mg/L to 0.33 mg/L, and the average removal rates for key pollutants, including COD, NH4+-N, and TN, reached 98.13%, 99.86%, and 98.09%. MLSS concentration remained at 7627 mg/L, indicating a high-density flora. Notably, Proteobacteria, Bacteroidota, and Acidobacteriota, which have the ability to degrade large organic molecules, had been found in the system. This study affirms the efficacy of the intensive aerobic biological method for treating low-biochemical plating washing wastewater while ensuring system stability.


Subject(s)
Environmental Pollutants , Wastewater , Waste Disposal, Fluid/methods , Bioreactors/microbiology , Nitrogen/analysis , Sewage/chemistry , Bacteria/metabolism , Environmental Pollutants/analysis
19.
Cleft Palate Craniofac J ; : 10556656241233220, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347701

ABSTRACT

OBJECTIVE: To determine whether facial growth at five years is different for children with a left versus right sided cleft lip and palate. DESIGN: Retrospective cohort study. SETTING: Seven UK regional cleft centres. PATIENTS: Patients born between 2000-2014 with a complete unilateral cleft lip and palate (UCLP). MAIN OUTCOMES MEASURE: 5-Year-Old's Index scores. RESULTS: 378 children were included. 256 (68%) had a left sided UCLP and 122 (32%) had a right sided UCLP. 5-Year-Old's index scores ranged from 1 (good) to 5 (poor). There was a higher proportion of patients getting good scores (1 and 2) in left UCLP (43%) compared to right UCLP (37%) but there was weak evidence for a difference (Adjusted summary odds ratio 1.27, 95% CI 0.87 to 1.87; P = .22). CONCLUSIONS: Whilst maxillary growth may be different for left versus right sided UCLP, definitive analysis requires older growth indices and arch forms.

20.
J Xray Sci Technol ; 32(1): 69-85, 2024.
Article in English | MEDLINE | ID: mdl-38189729

ABSTRACT

BACKGROUND: Slow kVp switching technique is an important approach to realize dual-energy CT (DECT) imaging, but its performance has not been thoroughly investigated yet. OBJECTIVE: This study aims at comparing and evaluating the DECT imaging performance of different slow kVp switching protocols, and thus helps determining the optimal system settings. METHODS: To investigate the impact of energy separation, two different beam filtration schemes are compared: the stationary beam filtration and dynamic beam filtration. Moreover, uniform tube voltage modulation and weighted tube voltage modulation are compared along with various modulation frequencies. A model-based direct decomposition algorithm is employed to generate the water and iodine material bases. Both numerical and physical experiments are conducted to verify the slow kVp switching DECT imaging performance. RESULTS: Numerical and experimental results demonstrate that the material decomposition is less sensitive to beam filtration, voltage modulation type and modulation frequency. As a result, robust material-specific quantitative decomposition can be achieved in slow kVp switching DECT imaging. CONCLUSIONS: Quantitative DECT imaging can be implemented with slow kVp switching under a variety of system settings.


Subject(s)
Iodine , Tomography, X-Ray Computed , Phantoms, Imaging , Tomography, X-Ray Computed/methods , Algorithms
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