ABSTRACT
X-ray free-electron lasers can generate intense and coherent radiation at wavelengths down to the sub-ångström region1-5, and have become indispensable tools for applications in structural biology and chemistry, among other disciplines6. Several X-ray free-electron laser facilities are in operation2-5; however, their requirement for large, high-cost, state-of-the-art radio-frequency accelerators has led to great interest in the development of compact and economical accelerators. Laser wakefield accelerators can sustain accelerating gradients more than three orders of magnitude higher than those of radio-frequency accelerators7-10, and are regarded as an attractive option for driving compact X-ray free-electron lasers11. However, the realization of such devices remains a challenge owing to the relatively poor quality of electron beams that are based on a laser wakefield accelerator. Here we present an experimental demonstration of undulator radiation amplification in the exponential-gain regime by using electron beams based on a laser wakefield accelerator. The amplified undulator radiation, which is typically centred at 27 nanometres and has a maximum photon number of around 1010 per shot, yields a maximum radiation energy of about 150 nanojoules. In the third of three undulators in the device, the maximum gain of the radiation power is approximately 100-fold, confirming a successful operation in the exponential-gain regime. Our results constitute a proof-of-principle demonstration of free-electron lasing using a laser wakefield accelerator, and pave the way towards the development of compact X-ray free-electron lasers based on this technology with broad applications.
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The evolutionarily conserved C-terminal binding protein (CtBP) has been well characterized as a transcriptional co-repressor. Herein, we report a previously unreported function for CtBP, showing that lowering CtBP dosage genetically suppresses Polycomb group (PcG) loss-of-function phenotypes while enhancing that of trithorax group (trxG) in Drosophila, suggesting that the role of CtBP in gene activation is more pronounced in fly development than previously thought. In fly cells, we show that CtBP is required for the derepression of the most direct PcG target genes, which are highly enriched by homeobox transcription factors, including Hox genes. Using ChIP and co-IP assays, we demonstrate that CtBP is directly required for the molecular switch between H3K27me3 and H3K27ac in the derepressed Hox loci. In addition, CtBP physically interacts with many proteins, such as UTX, CBP, Fs(1)h and RNA Pol II, that have activation roles, potentially assisting in their recruitment to promoters and Polycomb response elements that control Hox gene expression. Therefore, we reveal a prominent activation function for CtBP that confers a major role for the epigenetic program of fly segmentation and development.
Subject(s)
Drosophila Proteins , Genes, Homeobox , Alcohol Oxidoreductases , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/metabolism , Polycomb-Group Proteins/genetics , Polycomb-Group Proteins/metabolism , Protein Binding , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptional Activation/geneticsABSTRACT
BACKGROUND: Whole genome variants offer sufficient information for genetic prediction of human disease risk, and prediction of animal and plant breeding values. Many sophisticated statistical methods have been developed for enhancing the predictive ability. However, each method has its own advantages and disadvantages, so far, no one method can beat others. RESULTS: We herein propose an Ensemble Learning method for Prediction of Genetic Values (ELPGV), which assembles predictions from several basic methods such as GBLUP, BayesA, BayesB and BayesCπ, to produce more accurate predictions. We validated ELPGV with a variety of well-known datasets and a serious of simulated datasets. All revealed that ELPGV was able to significantly enhance the predictive ability than any basic methods, for instance, the comparison p-value of ELPGV over basic methods were varied from 4.853E-118 to 9.640E-20 for WTCCC dataset. CONCLUSIONS: ELPGV is able to integrate the merit of each method together to produce significantly higher predictive ability than any basic methods and it is simple to implement, fast to run, without using genotype data. is promising for wide application in genetic predictions.
Subject(s)
Genome , Plant Breeding , Animals , Humans , Genotype , Genomics , Machine Learning , Models, Genetic , Phenotype , Polymorphism, Single Nucleotide , Bayes TheoremABSTRACT
BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.
Subject(s)
Carcinoma, Hepatocellular , Hepatic Stellate Cells , Interleukin-17 , Liver Neoplasms , Animals , Humans , Male , Rats , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Disease Models, Animal , Endopeptidases/metabolism , Endopeptidases/genetics , Gene Expression Regulation, Neoplastic , Hepatic Stellate Cells/metabolism , Interleukin-17/metabolism , Interleukin-17/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Membrane Proteins/metabolism , Membrane Proteins/genetics , Rats, Sprague-Dawley , Tumor MicroenvironmentABSTRACT
Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.
Subject(s)
Enterovirus Infections , Enterovirus , Child , Humans , Enterovirus/genetics , Enterovirus Infections/epidemiology , China/epidemiology , Antigens, Viral , HEK293 CellsABSTRACT
Polarization imaging techniques have been effective in improving the clarity of turbid underwater images affected by water scattering. These techniques offer valuable additional information compared to traditional methods. However, previous descattering methods have mostly been designed for targets with uniform distribution of polarimetric characteristics. Therefore, targets with complex polarization characteristics have non-uniform distribution of polarization characteristics when dealing with such problems, additional parameter estimation errors can limit the results of image recovery. This paper proposes what we believe is a novel approach to address this issue. The method involves obtaining a new set of images using the polarization images vector space transformation method. The angle of polarization (AOP) of the target reflected light is estimated using the additivity law of the Stokes vector. This information is then combined with the physical model of underwater imaging to recover the underwater images affected by scattering. Experimental results conducted under varying levels of water turbidity validate the effectiveness of the proposed method. Moreover, the proposed method significantly broadens the range of application scenarios.
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An electrodynamic model is presented in this Letter to describe thresholdless lasers, utilizing the application of photonic time crystals (PTCs). By integrating the distinctive physical properties of PTCs and employing a comprehensive model based on a four-level system, the feasibility of achieving thresholdless laser operation is demonstrated. The proposed electrodynamic model comprehensively captures the intricate interplay between the electromagnetic field and the PTC medium. The model takes into account the ultrafast periodic variations in the refractive index of the PTCs, which arise from their time crystal-like behavior. Additionally, the dynamic response of the four-level system is considered, factoring in the processes of population inversion and relaxation. This Letter seeks to elucidate the underlying mechanisms that facilitate thresholdless laser operation in PTC-based systems. Through our electrodynamic modeling approach, we demonstrate that the ultrafast variations in the refractive index of PTCs give rise to a self-sustaining laser action, obviating the need for a lasing threshold. Moreover, we investigate the impact of various parameters, including pump power and modulation period, on the laser's performance and output characteristics. The developed electrodynamic model provides a comprehensive framework for comprehending and designing thresholdless lasers based on photonic time crystals. This research contributes to the advancement of thresholdless laser technology and opens up possibilities for applications in optical communications, sensing, and quantum photonics.
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Copper iodide organic-inorganic hybrid materials have been favored by many researchers in the field of solid-state lighting (SSL) due to their structural diversity and optical adjustability. In this paper, three isomeric copper iodide cluster hybrid materials, Cu4I6(L)2(1), Cu5I4.5Cl2.5(L)2(2) and Cu5I7(L)2) (3) (L=1-(4-methylpyrimidin-2-yl)-1,4-diazabicyclo[2.2.2]octan-1-ium), were achieved by adjusting the reaction conditions. The crystal color transit from green, yellow to orange and the internal quantum yield (IQY) increase from 57% to 88%. All three complexes have good thermal stability, good solution processability, and high quantum yield. And origin and mechanism of luminescence of complexes were further studied. This study can provide ideas and theoretical basis for the regulation of cuprous iodide cluster luminescent materials.
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BACKGROUND: Chronic kidney disease (CKD) is associated with increased, and early cardiovascular disease risk. Changes in hemodynamics within the left ventricle (LV) respond to cardiac remodeling. The LV hemodynamics in nondialysis CKD patients are not clearly understood. PURPOSE: To use four-dimensional blood flow MRI (4D flow MRI) to explore changes in LV kinetic energy (KE) and the relationship between LV KE and LV remodeling in CKD patients. STUDY TYPE: Retrospective. POPULATION: 98 predialysis CKD patients (Stage 3: n = 21, stage 4: n = 21, and stage 5: n = 56) and 16 age- and sex-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP) cine sequence, 4D flow MRI with a fast field echo sequence, T1 mapping with a modified Look-Locker SSFP sequence, and T2 mapping with a gradient recalled and spin echo sequence. ASSESSMENT: Demographic characteristics (age, sex, height, weight, blood pressure, heart rate, aortic regurgitation, and mitral regurgitation) and laboratory data (eGFR, Creatinine, hemoglobin, ferritin, transferrin saturation, potassium, and carbon dioxide bonding capacity) were extracted from patient records. Myocardial T1, T2, LV ejection fraction, end diastolic volume (EDV), end systolic volume, LV flow components (direct flow, delayed ejection, retained inflow, and residual volume) and KE parameters (peak systolic, systolic, diastolic, peak E-wave, peak A-wave, E/A ratio, and global) were assessed. The KE parameters were normalized to EDV (KEiEDV). Parameters were compared between disease stage in CKD patients, and between CKD patients and healthy controls. STATISTICAL TESTS: Differences in clinical and imaging parameters between groups were compared using one-way ANOVA, Kruskal Walls and Mann-Whitney U tests, chi-square test, and Fisher's exact test. Pearson or Spearman's correlation coefficients and multiple linear regression analysis were used to compare the correlation between LV KE and other clinical and functional parameters. A P-value of <0.05 was considered significant. RESULTS: Compared with healthy controls, peak systolic (24.76 ± 5.40 µJ/mL vs. 31.86 ± 13.18 µJ/mL), systolic (11.62 ± 2.29 µJ/mL vs. 15.27 ± 5.10 µJ/mL), diastolic (7.95 ± 1.92 µJ/mL vs. 13.33 ± 5.15 µJ/mL), peak A-wave (15.95 ± 4.86 µJ/mL vs. 31.98 ± 14.51 µJ/mL), and global KEiEDV (9.40 ± 1.64 µJ/mL vs. 14.02 ± 4.14 µJ/mL) were significantly increased and the KEiEDV E/A ratio (1.16 ± 0.67 vs. 0.69 ± 0.53) was significantly decreased in CKD patients. As the CKD stage progressed, both diastolic KEiEDV (10.45 ± 4.30 µJ/mL vs. 12.28 ± 4.85 µJ/mL vs. 14.80 ± 5.06 µJ/mL) and peak E-wave KEiEDV (15.30 ± 7.06 µJ/mL vs. 14.69 ± 8.20 µJ/mL vs. 19.33 ± 8.29 µJ/mL) increased significantly. In multiple regression analysis, global KEiEDV (ß* = 0.505; ß* = 0.328), and proportion of direct flow (ß* = -0.376; ß* = -0.410) demonstrated an independent association with T1 and T2 times. DATA CONCLUSION: 4D flow MRI-derived LV KE parameters show altered LV adaptations in CKD patients and correlate independently with T1 and T2 mapping that may represent myocardial fibrosis and edema. TECHNICAL EFFICACY: Stage 3.
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AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.
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RATIONALE: Ethylene oxide (EO) sterilization is commonly employed for the sterilization of medical devices and has a very high market share. However, EO and its metabolite ethylene chlorohydrin (ECH) are toxic to humans. In compliance with the classification and residue limits of medical devices defined by ISO 10993-7, our study established two extraction methods for the testing of EO and ECH. METHODS: The first method involves simulated-use extraction using water as the extraction solvent. While the second, exhaustive extraction, directly extracts sample through headspace sampling analysis. Gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode was utilized, requiring only 16 min. Then, the developed method was applied to assess 10 commercially available medical devices sterilized by EO. RESULTS: In simulated-use extraction, calibration curves were evaluated in the range of 1-100 and 5-500 µg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 85.0% to 95.2% and from 94.8% to 102.4%. In exhaustive extraction, calibration curves spanned 0.5-50 and 2-200 µg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 101.6% to 102.1% for EO and from 98.1% to 102.2% for ECH. After analysis of the 10 commercially available medical devices, two cotton swabs were found to have ECH of 35.1 and 28.4 µg per device, and four medical devices were found to have EO with concentration below the limit of quantification. Meanwhile, we found that the EO internal standard (propylene oxide) recommended by ISO 10993-7 had interference problems with other similar substances and was not suitable as an internal standard for EO. CONCLUSIONS: This study offers a sensitive and straightforward analytical approach to EO and ECH residues in a variety of medical devices. In addition, the results show that the EO or ECH content of these types of medical devices in our study falls below the regulatory limits, therefore instilling confidence among consumers regarding their safe use.
Subject(s)
Ethylene Oxide , Gas Chromatography-Mass Spectrometry , Tandem Mass Spectrometry , Ethylene Oxide/analysis , Ethylene Oxide/chemistry , Tandem Mass Spectrometry/methods , Gas Chromatography-Mass Spectrometry/methods , Equipment and Supplies , Limit of Detection , Ethylenes/analysis , Ethylenes/chemistry , Reproducibility of Results , Equipment Contamination , Sterilization/methodsABSTRACT
Mg0.472Zn0.528O/Mg0.447Zn0.553O double layer structure UV detectors are made on single structure MgO substrate by PLD method, and the effect of different thickness top MgZnO layer on the UV response characteristics of the detector are studied. Compared with the single layer MgZnO detector that made by Mg0.3Zn0.7O target, the Mg0.472Zn0.528O/Mg0.447Zn0.553O double layer detector with 30 nm top layer, shows much higher deep UV response (21.3 A W-1at 265 nm), much smaller dark current(66.9 pA) and much higher signal-to-noise ratio (2.8 × 105) at 25 V bias voltage. And the device also shows relative high response (23.1 A W-1) at 235 nm deep UV light at 25 V bias voltage, which is mainly attributed by the bottom MgZnO layer with higher Mg composition. When the top layer is 66.7 nm thick, the response of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector reached 228.8 A W-1at 255 nm under 25 V bias voltage, the signal-to-noise ratio of which is 10573 under 20 V bias voltage, and the near UV response of the device is also big because of more h-MgZnO in top MgZnO layer. When the top layer reached 90.2 nm, there are much more h-MgZnO in the top MgZnO layer, the peak response of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector is just 6.65 A W-1at 320 nm under 25 V bias voltage, the signal-to-noise ratio of which is 1248. The high Mg composition bottom MgZnO decrease the dark current of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector, both the 2DEG effect of the double layer structure and the amplify effect of the mix-phase MgZnO top layer, increased theIuvand deep UV response of the Mg0.472Zn0.528O/Mg0.447Zn0.553O detector. Therefore, the double layer Mg0.472Zn0.528O/Mg0.447Zn0.553O detector is more sensitive at faint deep UV light compared with previous reported MgZnO detectors, and the MgxZn1-xO/MgyZn1-yO detector shows similarIuvand signal-noise-ratio at faint deep UV light as high-temperature fabricated AlxGa1-xN/AlyGa1-yN detectors.
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OBJECTIVES: The present study aims to explore the application value of the air bronchogram (AB) sign and other computed tomography (CT) signs in the early diagnosis of lung adenocarcinoma (LUAD). METHOD: The pathological information and CT images of 130 patients diagnosed with N0 and M0 solitary pulmonary nodules (diameter ≤3 cm) and treated with surgical resection in our hospital between June 2021 and June 2022 were analyzed. RESULTS: The patients were divided into the benign pulmonary nodule (BPN) group (14 cases), the AIS group (30 cases), the MIA group (10 cases), and the IAC group (76 cases). Among the 116 patients with AIS and LUAD, 96 showed an AB sign. Among the 14 patients with BPN, only 4 patients showed an AB sign. The average CT value and maximum diameter were significantly higher in the IAC group than in the AIS and MIA groups. In the BPN group, 5 patients had an average CT value of >80 HU. Among all LUAD-based groups, there was only 1 patient with a CT value of >60 HU. CONCLUSIONS: The identification of the AB sign based on CT imaging facilitates the differentiation between benign and malignant nodules. The CT value and maximum diameter of pulmonary adenocarcinoma nodules increase with the increase of the malignancy degree. The nodule type, CT value, and maximum diameter are useful for predicting the pathological type and prognosis. If the average CT value of pulmonary nodules is >80 HU, LUAD may be excluded.
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Head MRI images of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients during migraine attacks are rare.
Subject(s)
CADASIL , Magnetic Resonance Imaging , Migraine with Aura , Humans , CADASIL/diagnostic imaging , CADASIL/complications , Migraine with Aura/diagnostic imaging , Male , Brain/diagnostic imaging , Brain/pathology , Middle Aged , Female , AdultABSTRACT
Accumulating evidence indicates that chronic circadian rhythm disruption is associated with the development of neurodegenerative diseases induced by exposure to neurotoxic chemicals. Herein, we examined the relationship between cellular circadian rhythm disruption and cytotoxicity in neural cells. Moreover, we evaluated the potential application of an in vitro cellular circadian rhythm assay in determining circadian rhythm disruption as a sensitive and early marker of neurotoxicant-induced adverse effects. To explore these objectives, we established an in vitro cellular circadian rhythm assay using human glioblastoma (U87 MG) cells stably transfected with a circadian reporter vector (PER2-dLuc) and determined the lowest-observed-adverse-effect levels (LOAELs) of several common neurotoxicants. Additionally, we determined the LOAEL of each compound on multiple cytotoxicity endpoints (nuclear size [NC], mitochondrial membrane potential [MMP], calcium ions, or lipid peroxidation) using a multiparametric high-content screening (HCS) assay using transfected U87 MG cells treated with the same neurotoxicants for 24 and 72 h. Based on our findings, the LOAEL for cellular circadian rhythm disruption for most chemicals was slightly higher than that for most cytotoxicity indicators detected using HCS, and the LOAEL for MMP in the first 24 h was the closest to that for cellular circadian rhythm disruption. Dietary antioxidants (methylselenocysteine and N-acetyl-l-cysteine) prevented or restored neurotoxicant-induced cellular circadian rhythm disruption. Our results suggest that cellular circadian rhythm disruption is as sensitive as cytotoxicity indicators and occurs early as much as cytotoxic events during disease development. Moreover, the in vitro cellular circadian rhythm assay warrants further evaluation as an early screening tool for neurotoxicants.
Subject(s)
Circadian Rhythm , Neurons , HumansABSTRACT
In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.
Subject(s)
Colorectal Neoplasms , Immune Checkpoint Inhibitors , Immunotherapy , Microsatellite Instability , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , Colorectal Neoplasms/immunology , Immunotherapy/methods , Immune Checkpoint Inhibitors/therapeutic use , Drug Resistance, Neoplasm/genetics , MutationABSTRACT
In March 2022, local cases of COVID-19 infections of the Omicron variant were identified in Taiwan. In response to impending community transmission, the "Home-Hotel-Hospital" (3H) care model was implemented by the Far Eastern Memorial Hospital (FEMH). It established the first remote home care center in Taiwan and two quarantine centers in two hotels. The hospital focused on care for critical COVID-19 patients, community screening, and telehealth care. The home care call center evaluated and triaged up to 104,244 cases and provided remote home care for 96,894 cases within the first three months; in 2022, it provided home care to 107,095 patients. The two quarantine hotels admitted a total of 1834 individuals. A total of 3796 COVID-19 patients were admitted to the hospital-367 in intensive care. The telehealth outpatient clinic-including the online video clinic-served 25,775 cases; 21.5% (n = 5544) of them were prescribed oral anti-viral medications. In 2022, the FEMH prescribed oral anti-viral therapies to a total of 12,571 cases. The FEMH 3H care model not only enabled non-critical patients to recover at home, but also provided severely ill patients access to timely in-hospital care. In the future, this model will continue to play a significant role in COVID-19 management.
Subject(s)
COVID-19 , Home Care Services , Humans , COVID-19/epidemiology , SARS-CoV-2 , Taiwan/epidemiology , Hospitals , Antiviral AgentsABSTRACT
Exosomal microRNAs (miRNAs) are novel, non-invasive biomarkers for facilitating communication and diagnosing cancer. However, only a few studies have investigated their function and role in the clinical diagnosis of breast cancer. To address this gap, we established a stable cell line, MDA-MB-231-CD63-RFP, and recruited 112 female participants for serum collection. We screened 88 exosomal miRNAs identified through microarray analysis of 231-CD63 and literature screening using real-time PCR; only exosomal miR-92b-5p was significantly increased in patients with breast cancer. It had a significant correlation with stage and discriminated patients from the control with an AUC of 0.787. Exosomal miR-92b-5p impacted the migration, adhesion, and spreading ability of normal human mammary epithelial recipient cells through the downregulation of the actin dynamics regulator MTSS1L. In clinical breast cancer tissue, the expression of MTSS1L was significantly inversely correlated with tissue miR-92b-5p, and high expression of MTSS1L was associated with better 10-year overall survival rates in patients undergoing hormone therapy. In summary, our studies demonstrated that exosomal miR-92b-5p might function as a non-invasive body fluid biomarker for breast cancer detection and provide a novel therapeutic strategy in the axis of miR-92b-5p to MTSS1L for controlling metastasis and improving patient survival.
Subject(s)
Biomarkers , Breast Neoplasms , Exosomes , MicroRNAs , Female , Humans , Biomarkers/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Transformation, Neoplastic/metabolism , Exosomes/genetics , Exosomes/metabolism , MicroRNAs/metabolism , Neoplasm Proteins/antagonists & inhibitorsABSTRACT
Subsidy policies are instrumental in driving the development of new energy. However, the effective allocation of new energy subsidies over time is challenging given fiscal constraints. This study addresses this challenge by considering the learning effect associated with the new energy industry. A two-stage dynamic programming model is proposed to capture the investment decision-making process of companies under new energy subsidy policies and government subsidy setups. Theoretical findings suggest that company investment decisions in new energy are influenced by a guiding principle: The subsidy rate should be negatively correlated with the variation rate of production scale increment (VRPSI). We calibrate this investment decision principle using wind power data from 14 countries. According to this principle, excessive subsidy rates may result in a low VRPSI, thereby diminishing future investment profitability in the new energy industry and leading to subsidy inefficiency. Upon investigating the efficiency of annual subsidy allocation, we find that the subsidy rates were potentially set too high in 2014, 2016, and 2017. Furthermore, the government should exercise caution regarding an inefficient subsidy pattern whereby companies invest in new energy only when the subsidy rate exceeds a certain threshold, neglecting traditional power sources. It is crucial to note that although this study uses wind power industry data for calibration and simulation, the theoretical model can be broadly applied to other new energy industries and emerging industries with increasing marginal net profit.
Subject(s)
Industry , Wind , Public Policy , Models, Theoretical , InvestmentsABSTRACT
Despite the widespread investigations on the M-N-C type single atom catalysts (SACs) for oxygen evolution reaction (OER), an internal conflict between its intrinsic thermodynamically structural instability and apparent catalytic steadiness has long been ignored. Clearly unfolding this contradiction is necessary and meaningful for understanding the real structure-property relation of SACs. Herein, by using the well-designed pH-dependent metal leaching experiments and X-ray absorption spectroscopy, an unconventional structure reconstruction of M-N-C catalyst during OER process was observed. Combining with density functional theory calculations, the initial Ni-N coordination is easily broken in the presence of adsorbed OH*, leading to favorable formation of Ni-O coordination. The formed Ni-O works stably as the real active center for OER catalysis in alkaline media but unstably in acid, which clearly explains the existing conflict. Unveiling the internal contradiction between structural instability and catalytic steadiness provides valuable insights for rational design of single atom OER catalysts.