The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved ...vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
Halide perovskites, in the form of thin films and colloidal nanocrystals, have recently taken semiconductor optoelectronics research by storm, and have emerged as promising candidates for ...high‐performance solar cells, light‐emitting diodes (LEDs), lasers, photodetectors, and radiation detectors. The impressive optical and optoelectronic properties, along with the rapid increase in efficiencies of solar cells and LEDs, have greatly attracted researchers across many disciplines. However, most advances made so far in terms of preparation (colloidal nanocrystals and thin films), and the devices with highest efficiencies are based on Pb‐based halide perovskites, which have raised concerns over their commercialization due to the toxicity of Pb. This has triggered the search for lower‐toxicity Pb‐free halide perovskites and has led to significant progress in the last few years. In this roadmap review, researchers of different expertise have joined together to summarize the latest progress, outstanding challenges, and future directions of Pb‐free halide perovskite thin films and nanocrystals, regarding their synthesis, optical spectroscopy, and optoelectronic devices, to guide the researchers currently working in this area as well as those that will join the field in the future.
This roadmap review summarizes the latest progress, outstanding challenges, and future directions of Pb‐free halide perovskites regarding their synthesis, optical spectroscopy, and optoelectronic devices.
Lead-free double perovskite phosphors are promising alternatives to lead halide perovskites for wide uses in optoelectronic applications, but suffer from a low quantum efficiency. Here, we propose to ...enhance the quantum efficiency of orange-emitting Cs2Ag0.4Na0.6InCl6:Bi via a codoping strategy. The internal quantum efficiency of Cs2Ag0.4Na0.6InCl6:1% Bi phosphor was increased from 89.9% to the record 98.4 and 98.6% by codoping with 1% Ni and 1% Ce, respectively. High-level density functional theory calculations have revealed that the enhanced efficiency is ascribed to the formation of shallow trap states by codoping with Ce, while codoping with Mn can create delocalized deep traps that decrease the quantum efficiency. By applying the (Bi,Ce)-codoped sample together with a blue BaMgAl10O17:Eu2+ phosphor, a white light-emitting diode with an excellent color rendering index of 95.7 and a correlated color temperature of 4430 K has been demonstrated. The developed Cs2Ag0.4Na0.6InCl6:Bi,Ce phosphor shows a great potential as down-conversion luminescent material in solid-state lighting for general illumination.
Abstract Background The aging rate in Taiwan is the second highest in the world. As the population ages quickly, the prevalence of dementia increases rapidly. There are some studies that have ...explored the association between air pollution and cognitive decline, but the association between air pollution and dementia has not been directly evaluated. Methods This was a case-control study comprising 249 Alzheimer's disease (AD) patients, 125 vascular dementia (VaD) patients, and 497 controls from three teaching hospitals in northern Taiwan from 2007 to 2010. Data of particulate matter <10 μm in diameter (PM10 ) and ozone were obtained from the Taiwan Environmental Protection Administration for 12 and 14 years, respectively. Blood samples were collected to determine the apolipoprotein E ( APOE ) ɛ4 haplotype. Bayesian maximum entropy was used to estimate the individual exposure level of air pollutants, which was then tertiled for analysis. Conditional logistic regression models were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals between the association of PM10 and ozone exposure with AD and VaD risk. Results The highest tertile of PM10 (≥49.23 μg/m3 ) or ozone (≥21.56 ppb) exposure was associated with increased AD risk (highest vs. lowest tertile of PM10 : AOR = 4.17; highest vs. lowest tertile of ozone: AOR = 2.00). Similar finding was observed for VaD. The association with AD and VaD risk remained for the highest tertile PM10 exposure after stratification by APOE ɛ4 status and gender. Conclusions Long-term exposure to the highest tertile of PM10 or ozone was significantly associated with an increased risk of AD and VaD.
which is called the Cantor series expansion of x. In this paper, we study the shrinking target problems for the system induced by the Cantor series expansion. More precisely, put ...T_{Q}^{n}(x)=q_1\cdots q_nx-\lfloor q_1\cdots q_nx\rfloor ; the shrinking target problem in such a nonautonomous system can be formulated as considering the size of the set
Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of ...schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.
Visceral adiposity is associated with cardiovascular disease, an association that may be mediated in part by inflammation. We hypothesized that regional measures of visceral adiposity would associate ...with commonly obtained clinical measures of immune status. We consecutively studied 3,291 subjects (mean age, 49.8±9.8 years) who underwent an annual cardiovascular risk survey. Peri-cardial (PCF) and thoracic peri-aortic adipose tissue (TAT) volumes were determined by dedicated computed tomography (CT) software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Hepatic steatosis was assessed by abdominal ultrasonography. We explored cross-sectional associations between visceral fat measures and high-sensitivity C-reactive protein (hs-CRP), leukocyte counts, and the neutrophil-to-lymphocyte ration (NLR). Among 3,291 study participants, we observed positive linear associations between PCF and TAT, higher degree of hepatic steatosis and hs-CRP, various leukocyte counts, either total and its differential counts, and NLR (all trend p<0.001). Multi-variate linear and logistic regression models showed independent associations between PCF/TAT (ß-Coef: 0.14/0.16, both p<0.05) and total WBC counts, with only TAT further demonstrated significant relations with neutrophil counts and NLR (both p<0.05) and independently identified abnormally high WBC and NLR (Odds ratio: 1.18 & 1.21, both p<0.05). C-statistics showed significant incremental model prediction for abnormally high WBC and NLR (both ΔAUROC<0.05) when TAT was superimposed on traditional cardiovascular risks and biochemical information. Greater visceral adiposity burden and hepatic steatosis may be associated with higher circulating leukocyte counts and markers for atherosclerosis, with more pronounced influences for peri-aortic adiposity. Our data suggested the differential biological impacts for region-specific visceral adiposity.
Traditional Chinese medicine (TCM) is considered a valuable asset in China's medical tradition. YPF is a classic prescription that has been derived from the "Jiu Yuan Fang" formula and consists of ...three herbs: Huangqi (Astragalus membranaceus Bunge), Baizhu (Atractylodes rubra Dekker), and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk). This prescription is widely acclaimed for its exceptional pharmacological properties, including potent antioxidant effects, hormone regulation, and immune modulation effects.
Previous research provides evidence suggesting that YPF may have therapeutic effects on pulmonary fibrosis. Further exploration is essential to confirm its effectiveness and elucidate the fundamental processes.
First, the active components and target genes of YPF were extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Next, the GSE53845 dataset, which contains information on pulmonary fibrosis, was downloaded from the GEO database. Network informatics methods was then be utilized to identify target genes associated with pulmonary fibrosis. A YPF-based network of protein-protein interactions was constructed to pinpoint possible target genes for pulmonary fibrosis treatment. Additionally, an in vitro model of pulmonary fibrosis induced by bleomycin (BLM) was established to further investigate and validate the possible mechanisms underlying the effectiveness of YPF.
In this study, a total of 24 active ingredients of YPF, along with 178 target genes associated with the treatment, were identified. Additionally, 615 target genes related to pulmonary fibrosis were identified. Functional enrichment analysis revealed that 18 candidate genes (CGs) exhibited significant responses to tumor necrosis factor, NF-kB survival signaling, and positive regulation of apoptosis processes. Among these CGs, CAV1, VCAM1, and TP63 were identified as key target genes. Furthermore, cell experiments confirmed that the expression of CAV1 protein and RNA expression was increased in pulmonary fibrosis, but significantly decreased after treatment with YPF. Additionally, the expression of pSmad2, α-SMA, TGF-β1, and TNF-α was also decreased following YPF treatment.
Network pharmacology analysis revealed that YPF exhibits significant potential as a therapeutic intervention for pulmonary fibrosis by targeting various compounds and pathways. This study emphasizes that the efficacy of YPF in treating pulmonary fibrosis may be attributed to its ability to up-regulate CAV1 expression and inhibiting pulmonary fibrosis via modulation of the TGF-β1/Smad2 signaling pathway. These findings underscore the promising role of YPF and its ability to potentially alleviate pulmonary fibrosis.
Display omitted
•YPF has significant potential as a therapeutic intervention for pulmonary fibrosis.•CAV1 may contribute to the therapeutic effects of YPF in treating pulmonary fibrosis.•YPF can inhibit pulmonary fibrosis by modulating the TGF-β1/Smad2 signaling pathway.
Thoracic aortic calcification (TAC) is tightly linked to pathological atherosclerosis and associated with certain cardiovascular diseases. While diabetes mellitus (DM) is known as a coronary heart ...disease equivalent, we examined the presence of TAC across the dysglycemic spectrum of diabetes mellitus (DM). We consecutively studied 3003 asymptomatic ethnic Asians underwent annual cardiovacular health survey, and further categorized them into: 1) 1760 normo-glycemic, 2) 968 pre-diabetic, and 3) 274 overt DM based on dysglycemic indices and medical histories. Several TAC parameters were assessed using non-contrast multi-detector computed tomography (MDCT), and related to dysglycemic indices or diabetes mellitus status. A remarkably graded increases of adjusted total TAC calcium burden, volume and density were seen across Non-diabetes, Pre-diabetes, and diabetes mellitus categories and positively correlated with all dysglycemic profiles (all p<0.001). Multi-variate logistic and linear regression models demonstrated independent associations between greater TAC density and all dysglycemic indices (Coef: 2.5, 1.4, 6.8 for fasting, postprandial sugar and HbA1c) and diabetes mellitus status (all p<0.05). Furthermore, Receiver-operating characteristic curves (ROC) showed fasting sugar and postprandial sugar set at 103mg/dL and 111mg/dL, separately, with HbA1c set at 5.8% all predict the presence of aortic calcification. Dysglycemic status, even without overt diabetes mellitus, were tighly linked to subclinical, pathological thoracic aortic calcification.
To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a
missense mutation in members with atypical aniridia.
Eleven ...family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation.
Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of
was identified in all affected family members but not in the unaffected members or in healthy control subjects.
A rare missense mutation in the
gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by
missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.
PDF
