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Biopsy, including tissue and liquid biopsy, offers comprehensive and real-time physiological and pathological information for disease detection, diagnosis, and monitoring. Fluorescent probes are frequently selected to obtain adequate information on pathological processes in a rapid and minimally invasive manner based on their advantages for biopsy. However, conventional fluorescent probes have been found to show aggregation-caused quenching (ACQ) properties, impeding greater progresses in this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) have promoted rapid advancements in molecular bionanomaterials owing to their unique properties, including high quantum yield (QY) and signal-to-noise ratio (SNR), etc. This review seeks to present the latest advances in AIEgen-based biofluorescent probes for biopsy in real or artificial samples, and also the key properties of these AIE probes. This review is divided into: (i) tissue biopsy based on smart AIEgens, (ii) blood sample biopsy based on smart AIEgens, (iii) urine sample biopsy based on smart AIEgens, (iv) saliva sample biopsy based on smart AIEgens, (v) biopsy of other liquid samples based on smart AIEgens, and (vi) perspectives and conclusion. This review could provide additional guidance to motivate interest and bolster more innovative ideas for further exploring the applications of various smart AIEgens in precision medicine.
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Corantes Fluorescentes , Medicina de Precisão , Humanos , Corantes Fluorescentes/química , Biópsia , Animais , Biópsia Líquida/métodosRESUMO
Wheat (Triticum aestivum L.) is a globally staple crop vulnerable to various fungal diseases, significantly impacting its yield. Plant cell surface receptors play a crucial role in recognizing pathogen-associated molecular patterns (PAMPs) and activating PAMP-triggered immunity, boosting resistance against a wide range of plant diseases. Although the role of plant chitin receptor CERK1 in immune recognition and defense has been established in Arabidopsis and rice, its function and potential agricultural applications in enhancing resistance to crop diseases remain largely unexplored. Here, we identify and characterize TaCERK1 in Triticeae crop wheat, uncovering its involvement in chitin recognition, immune regulation, and resistance to fungal diseases. By a comparative analysis of CERK1 homologs in Arabidopsis and monocot crops, we demonstrate that AtCERK1 in Arabidopsis elicits the most robust immune response. Moreover, we show that overexpressing TaCERK1 and AtCERK1 in wheat confers resistance to multiple fungal diseases, including Fusarium head blight, stripe rust, and powdery mildew. Notably, transgenic wheat lines with moderately expressed AtCERK1 display superior disease resistance and heightened immune responses without adversely affecting growth and yield, compared to TaCERK1 overexpression transgenics. Our findings highlight the significance of plant chitin receptors across diverse plant species and suggest potential strategies for bolstering crop resistance against broad-spectrum diseases in agricultural production through the utilization of plant immune receptors.
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The environment has constantly shaped plant genomes, but the genetic bases underlying how plants adapt to environmental influences remain largely unknown. We constructed a high-density genomic variation map of 263 geographically representative peach landraces and wild relatives. A combination of whole-genome selection scans and genome-wide environmental association studies (GWEAS) was performed to reveal the genomic bases of peach adaptation to diverse climates. A total of 2092 selective sweeps that underlie local adaptation to both mild and extreme climates were identified, including 339 sweeps conferring genomic pattern of adaptation to high altitudes. Using genome-wide environmental association studies (GWEAS), a total of 2755 genomic loci strongly associated with 51 specific environmental variables were detected. The molecular mechanism underlying adaptive evolution of high drought, strong UVB, cold hardiness, sugar content, flesh color, and bloom date were revealed. Finally, based on 30 yr of observation, a candidate gene associated with bloom date advance, representing peach responses to global warming, was identified. Collectively, our study provides insights into molecular bases of how environments have shaped peach genomes by natural selection and adds candidate genes for future studies on evolutionary genetics, adaptation to climate changes, and breeding.
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Adaptação Fisiológica/genética , Mudança Climática , Genoma de Planta/genética , Genômica , Prunus persica/genéticaRESUMO
Approximately 50% of Alzheimer's disease (AD) patients will develop psychotic symptoms and these patients will experience severe rapid cognitive decline compared with those without psychosis (AD-P). Currently, no medication has been approved by the Food and Drug Administration for AD with psychosis (AD+P) specifically, although atypical antipsychotics are widely used in clinical practice. These drugs have demonstrated modest efficacy in managing psychosis in individuals with AD, with an increased frequency of adverse events, including excess mortality. We compared the differences between the genetic variations/genes associated with AD+P and schizophrenia from existing Genome-Wide Association Study and differentially expressed genes (DEGs). We also constructed disease-specific protein-protein interaction networks for AD+P and schizophrenia. Network efficiency was then calculated to characterize the topological structures of these two networks. The efficiency of antipsychotics in these two networks was calculated. A weight adjustment based on binding affinity to drug targets was later applied to refine our results, and 2013 and 2123 genes were identified as related to AD+P and schizophrenia, respectively, with only 115 genes shared. Antipsychotics showed a significantly lower efficiency in the AD+P network than in the schizophrenia network (P < 0.001) indicating that antipsychotics may have less impact in AD+P than in schizophrenia. AD+P may be caused by mechanisms distinct from those in schizophrenia which result in a decreased efficacy of antipsychotics in AD+P. In addition, the network analysis methods provided quantitative explanations of the lower efficacy of antipsychotics in AD+P.
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Doença de Alzheimer , Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/etiologiaRESUMO
Bud dormancy is crucial for winter survival and is characterized by the inability of the bud meristem to respond to growth-promotive signals before the chilling requirement (CR) is met. However, our understanding of the genetic mechanism regulating CR and bud dormancy remains limited. This study identified PpDAM6 (DORMANCY-ASSOCIATED MADS-box) as a key gene for CR using a genome-wide association study analysis based on structural variations in 345 peach (Prunus persica (L.) Batsch) accessions. The function of PpDAM6 in CR regulation was demonstrated by transiently silencing the gene in peach buds and stably overexpressing the gene in transgenic apple (Malus × domestica) plants. The results showed an evolutionarily conserved function of PpDAM6 in regulating bud dormancy release, followed by vegetative growth and flowering, in peach and apple. The 30-bp deletion in the PpDAM6 promoter was substantially associated with reducing PpDAM6 expression in low-CR accessions. A PCR marker based on the 30-bp indel was developed to distinguish peach plants with non-low and low CR. Modification of the H3K27me3 marker at the PpDAM6 locus showed no apparent change across the dormancy process in low- and non-low- CR cultivars. Additionally, H3K27me3 modification occurred earlier in low-CR cultivars on a genome-wide scale. PpDAM6 could mediate cell-cell communication by inducing the expression of the downstream genes PpNCED1 (9-cis-epoxycarotenoid dioxygenase 1), encoding a key enzyme for ABA biosynthesis, and CALS (CALLOSE SYNTHASE), encoding callose synthase. We shed light on a gene regulatory network formed by PpDAM6-containing complexes that mediate CR underlying dormancy and bud break in peach. A better understanding of the genetic basis for natural variations of CR can help breeders develop cultivars with different CR for growing in different geographical regions.
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Malus , Prunus persica , Prunus , Prunus persica/genética , Prunus persica/metabolismo , Prunus/genética , Prunus/metabolismo , Histonas/metabolismo , Estudo de Associação Genômica Ampla , Malus/genética , Regulação da Expressão Gênica de Plantas , Dormência de Plantas/genéticaRESUMO
We present and experimentally demonstrate a method for determining the spectral characterization of a single-photon state. This technique is based on the Hong-Ou-Mandel interference between a well-defined weak coherent state and a measured single-photon state. We estimate the spectrum of the single-photon state by fitting the measured interference dip with proposed model and least square method. Our method is particularly useful for characterising spectral property the single-photon state. It opens a way for robust and efficient on-line monitoring the single-photon emitters.
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OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.
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Procedimentos Endovasculares , AVC Isquêmico , Humanos , Masculino , Feminino , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Idoso , Procedimentos Endovasculares/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Futilidade Médica , Trombectomia/métodos , Estudos Prospectivos , PrognósticoRESUMO
BACKGROUND: Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities. METHODS: In our study, we created a natural language processing (NLP) workflow to analyze electronic medical record (EMR) data and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, all-mpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh Medical Center. Subsequently, we showcased the significance of our approach by extracting and visualizing RDoC information in two use cases: (i) across multiple patient populations and (ii) throughout various disease trajectories. RESULTS: The sentence transformer model demonstrated high F1 macro scores across all RDoC domains, achieving the highest performance with a cosine similarity threshold value of 0.3. This ensured an F1 score of at least 80% across all RDoC domains. The study revealed consistent reductions in all six RDoC domains among PTSD patients after psychotherapy. We found that 60.6% of PTSD women have at least one abnormal instance of the six RDoC domains as compared to PTSD men (51.3%), with 45.1% of PTSD women with higher levels of sensorimotor disturbances compared to men (41.3%). We also found that 57.3% of PTSD patients have at least one abnormal instance of the six RDoC domains based on our records. Also, veterans had the higher abnormalities of negative and positive valence systems (60% and 51.9% of veterans respectively) compared to non-veterans (59.1% and 49.2% respectively). The domains following first diagnoses of PTSD were associated with heightened cue reactivity to trauma, suicide, alcohol, and substance consumption. CONCLUSIONS: The findings provide initial insights into RDoC functioning in different populations and disease trajectories. Natural language processing proves valuable for capturing real-time, context dependent RDoC instances from extensive clinical notes.
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Registros Eletrônicos de Saúde , Processamento de Linguagem Natural , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
Wild species of domesticated crops provide valuable genetic resources for resistance breeding. Prunus davidiana, a wild relative of peach with high heterozygosity and diverse stress tolerance, exhibits high resistance against aphids. However, the highly heterozygous genome of P. davidiana makes determining the underlying factors influencing resistance traits challenging. Here, we present the 501.7 Mb haplotype-resolved genome assembly of P. davidiana. Genomic comparisons of the two haplotypes revealed 18,152 structural variations, 2,699 Pda_hap1-specific and 2,702 Pda_hap2-specific genes, and 1,118 allele-specific expressed genes. Genome composition indicated 4.1% of the P. davidiana genome was non-peach origin, out of which 94.5% was derived from almond. Based on the haplotype genome, the aphid resistance quantitative trait locus (QTL) was mapped at the end of Pda03. From the aphid resistance QTL, PdaWRKY4 was identified as the major dominant gene, with a 9-bp deletion in its promoter of the resistant phenotype. Specifically, PdaWRKY4 regulates aphid resistance by promoting PdaCYP716A1-mediated anti-aphid metabolite betulin biosynthesis. Moreover, we employed a genome design to develop a breeding workflow for rapidly and precisely producing aphid-resistant peaches. In conclusion, this study identifies a novel aphid resistance gene and provides insights into genome design for the development of resistant fruit cultivars.
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To investigate the effects of Luhong Yixin Granules on myocardial fibrosis in rats with heart failure and its possible mechanism, a total of 60 male Wistar rats were randomly divided into the control group, model group, and low-, medium-and high-dose Luhong Yixin Granules groups, with 12 rats in each group. Except for those in the control group, rats in the other groups were induced by intraperitoneal injection of doxorubicin(DOX) into a rat model. After the Luhong Yixin Granules were dissolved in the same amount of normal saline, they were given by gavage at low, medium and high doses(2.8, 5.6, 11.2 g·kg~(-1)·d~(-1)), and the control group and the model group were given the same amount of normal saline by gavage for 40 days. After the end of dosing, echocardiography was used to measure left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS). Rat body weight(BW) and heart weight(HW) were calculated as HW/BW. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin-6(IL-6), interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), transforming growth factor-ß1(TGF-ß1), growth stimulation expressed gene 2 protein(ST2), N-terminal pro-B-type natriuretic peptide(NT-proBNP), galectin-3(Gal-3) and creatine kinase isoenzyme(CK-MB) in serum. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of myocardial tissue. Western blot and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, Smad7, α-smooth muscle actin(α-SMA), and collagen â (COL-â ), respectively. RESULTS:: showed that compared with those in the control group, LVEF, LVFS, and HW/BW in the model group were decreased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3, and CK-MB were increased(P<0.05). HE staining showed inflammatory changes in myocardial tissue; Masson staining showed decreases in the cross-sectional area and ventricular cavity area of the heart, and myocardial fibrosis of varying degrees(P<0.05). The protein and mRNA expression of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-â were increased(P<0.05), and the protein and mRNA expression of Smad7 protein was decreased(P<0.01). Compared with those in the model group, LVEF, LVFS and HW/BW of the low-, medium-and high-dose Luhong Yixin Granules groups were increased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3 and CK-MB were decreased(P<0.05). HE staining showed gradually reduced inflammatory changes of myocardial tissue, and Masson staining showed increased cross-sectional area and ventricular cavity area of the heart and decreased area of myocardial fibrosis(P<0.05). The protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-â were decreased(P<0.05), while the protein and mRNA expression levels of Smad7 were increased(P<0.05). Luhong Yixin Granules may be of great value in the treatment of heart failure by regulating the TGF-ß1/Smads signaling pathway, inhibiting the expression of inflammation-related proteins, reducing the deposition of extracellular matrix, and alleviating myocardial fibrosis.
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Medicamentos de Ervas Chinesas , Fibrose , Insuficiência Cardíaca , Miocárdio , Ratos Wistar , Transdução de Sinais , Proteínas Smad , Fator de Crescimento Transformador beta1 , Animais , Masculino , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Miocárdio/patologia , Miocárdio/metabolismo , Proteínas Smad/metabolismo , Proteínas Smad/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , HumanosRESUMO
Alkaline water electrolysis holds promise for large-scale hydrogen production, yet it encounters challenges like high voltage and limited stability at higher current densities, primarily due to inefficient electron transport kinetics. Herein, a novel cobalt-based metallic heterostructure (Co3Mo3N/Co4N/Co) is designed for excellent water electrolysis. In operando Raman experiments reveal that the formation of the Co3Mo3N/Co4N heterointerface boosts the free water adsorption and dissociation, increasing the available protons for subsequent hydrogen production. Furthermore, the altered electronic structure of the Co3Mo3N/Co4N heterointerface optimizes ΔGH of the nitrogen atoms at the interface. This synergistic effect between interfacial nitrogen atoms and metal phase cobalt creates highly efficient active sites for the hydrogen evolution reaction (HER), thereby enhancing the overall HER performance. Additionally, the heterostructure exhibits a rapid OH- adsorption rate, coupled with great adsorption strength, leading to improved oxygen evolution reaction (OER) performance. Crucially, the metallic heterojunction accelerates electron transport, expediting the afore-mentioned reaction steps and enhancing water splitting efficiency. The Co3Mo3N/Co4N/Co electrocatalyst in the water electrolyzer delivers excellent performance, with a low 1.58â V cell voltage at 10â mA cm-2, and maintains 100 % retention over 100â hours at 200â mA cm-2, surpassing the Pt/C||RuO2 electrolyzer.
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Active enrichment can detect nucleic acid at ultra-low concentrations without relatively time-consuming polymerase chain reaction (PCR), which is an important development direction for future rapid nucleic acid detection. Here, we reported an integrated active enrichment platform for direct hand-held detection of nucleic acid of COVID-19 in nanoliter samples without PCR. The platform consists of a capillary-assisted liquid-carrying system for sampling, integrated circuit system for ultrasound output, and cell-phone-based surface-enhanced Raman scattering (SERS) system. Considering the acoustic responsiveness and SERS-enhanced performance, gold nanorods were selected for biomedical applications. Functionalized gold nanorods can effectively capture and enrich biomarkers under ultrasonic aggregation. Such approaches can actively assemble gold nanorods in 1-2 s and achieved highly sensitive (6.15 × 10-13 M) SERS detection of COVID-19 biomarkers in nanoliter (10-7 L) samples within 5 min. We further demonstrated the high stability, repeatability, and selectivity of the platform, and validated its potential for the detection of throat swab samples. This simple, portable, and ultra-trace integrated active enrichment detection platform is a promising diagnostic tool for the direct and rapid detection of COVID-19.
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COVID-19 , Nanopartículas Metálicas , Ácidos Nucleicos , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , COVID-19/diagnóstico , Análise Espectral Raman , OuroRESUMO
We experimentally investigate two-photon interference between a weak coherent state and a heralded single-photon state, producing from a spontaneous parametric down conversion. Both the unequal spectrum linewidth and average photon number ratio in a given time interval are considered in our model. We obtained excellent agreement between our experimental data and prediction from our model. Furthermore, the range of observing high visibility two-photon interference is significantly extended by isolating coincidence events from two-photon contributions in the weak coherent state. These results may throw some new light on quantum information technology when the two-photon interference with independent sources is required.
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Optical vortex orbital angular momentum modes, namely the twists number of the light does in one wavelength, play a critical role in quantum-information coding, super-resolution imaging, and high-precision optical measurement. Here, we present the identification of the orbital angular momentum modes based on spatial self-phase modulation in rubidium atomic vapor. The refractive index of atomic medium is spatially modulated by the focused vortex laser beam, and the resulted nonlinear phase shift of beam directly related to the orbital angular momentum modes. The output diffraction pattern carries clearly distinguishable tails, whose number and rotation direction correspond to the magnitude and sign of the input beam orbital angular momentum, respectively. Furthermore, the visualization degree of orbital angular momentums identification is adjusted on-demand in the terms of incident power and frequency detuning. These results show that the spatial self-phase modulation of atomic vapor can provide a feasible and effective way to rapidly readout the orbital angular momentum modes of vortex beam.
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The photonic graphene in atoms not only has the typical photonic band structures but also exhibits controllable optical properties that are difficult to achieve in the natural graphene. Here, the evolution process of discrete diffraction patterns of a photonic graphene, which is constructed through a three-beam interference, is demonstrated experimentally in a 5S1/2 - 5P3/2 - 5D5/2 85Rb atomic vapor. The input probe beam experiences a periodic refractive index modulation when traveling through the atomic vapor, and the evolution of output patterns with honeycomb, hybrid-hexagonal, and hexagonal geometric profiles is obtained by controlling the experimental parameters of two-photon detuning and the power of the coupling field. Moreover, the Talbot images of such three kinds of periodic structure patterns at different propagating planes are observed experimentally. This work provides an ideal platform to investigate manipulation the propagation of light in artificial photonic lattices with tunable periodically varying refractive index.
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Ultraviolet (UV) beam generation at 266â nm using the sum-frequency (SFG) method with CsB3O5 (CBO) crystals was first suggested in 1997 [Opt. Lett.22, 1840 (1997).10.1364/OL.22.001840]; however, there has been no further research in the past 25 years. Herein, by sum-frequency mixing in CBO crystals, we obtained a high conversion efficiency picosecond (ps) and a high-power nanosecond (ns) 266â nm UV beam output. First, a ps laser device with simultaneously radiated wavelengths of 1064 and 355â nm and repetition frequency of 10â Hz was used as the fundamental laser source, and the conversion efficiency from 1064 + 355â nm to 266â nm reached 20.35%. We then used a 1064â nm ns laser with a high output power and repetition frequency of 10 kHz as the pump source. We accurately modified the optimal phase matching direction of the CBO crystal, and the achieved output power at 266â nm reached 5.32 W.
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The continuous zoonotic circulation and reassortment potential of influenza A viruses (IAV) in nature represents an enormous public health threat to humans. Beside vaccination antivirals are needed to efficiently control spreading of the disease. The previous research has shown that NOX2 involved in IAV replication, but the detailed mechanism has not been reported. In the present study we investigated the roles of NOX2 in host inflammatory response and IAV replication using a novel inhibitor GSK2795039. The drug significantly reduced H1N1 virus induced NOX2 activity and ROS release in human lung epithelial cells. The results of time course experiments suggested that GSK2795039 inhibited an early post-entry step of viral infection. Concomitantly, there was a decreased expression of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-ß and interleukin (IL)-6) in NOX2 suppressed cells. In vivo, compared with control groups, suppression of NOX2 improved the survival rate of mice infected with H1N1 virus (42.9% in GSK2795039 treated mice versus >0% of control mice) and viral burden also decreased in the GSK2795039 treated group. Thus, our data demonstrated a critical role for NOX2 in the establishment of H1N1 infection and subsequent inflammatory reactions, which suggest that GSK2795039 may be a potential therapeutic drug for IAV infection.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Humanos , Camundongos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Oxirredutases , Infecções por Orthomyxoviridae/patologia , Influenza Humana/tratamento farmacológico , Interleucina-6 , Replicação ViralRESUMO
The Rydberg atomic receiver, sensing microwave electric field with high sensitivity and broad bandwidth, possesses the potential to be the staple for precise navigation and remote sensing. In this Letter, a Ku-band three-dimensional location system using an L-shaped array of Rydberg atomic receivers is theoretically proposed and experimentally demonstrated, and the proof of principle results show excellent consistency between the location-derived and the setting coordinates. The novel L-shaped array, together with the triangulation method, gives both phase difference and angle of arrival, achieving location of the horn for a signal microwave field in three-dimensional space. The concluded validity of this location system in the testing scene remains at approximately 90% with a theoretical maximum location tolerance of 5.7 mm. Furthermore, the estimation of two different spatiotemporal coordinates for the moving target confirms the velocity measurement capability of the system with errors less than 0.5 mm/s. The proposed location system using a Rydberg atomic receiver array is a verification for the most basic element and can be extended through repetition or nesting to a multi-input-multi-output system as well as multi-channel information processing.
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The introduction of vector beams (VBs), with space-variant polarization, into the polarization-resolved spectrum, provides a convenient and rapid pathway for revealing micro-structure. Here, we realize the spatial mapping of the polarization-resolved spectrum based on VB-assisted nondegenerate four-wave mixing (FWM) in a diamond atomic system of 85Rb. The 780 nm radial VB and 776 nm linearly polarized Gaussian beam serve as the probe and pump beams in the FWM process, respectively. The generated 420 nm coherent blue light (CBL) possesses a space-variant intensity profile due to the spatially polarized atomic medium. Accordingly, the polarization-resolved spectrum can be directly mapped from a single CBL profile and the polarization information of the input 776 nm beam can be accurately extracted. In particular, such nondegenerate FWM based on VB provides a proof of principle for rapid and visual polarization-related detection by converting to a frequency domain where efficient detectors are readily available.
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OBJECTIVE: Based on ultrasound (US) images, this study aimed to detect and quantify calcifications of thyroid nodules, which are regarded as one of the most important features in US diagnosis of thyroid cancer, and to further investigate the value of US calcifications in predicting the risk of lymph node metastasis (LNM) in papillary thyroid cancer (PTC). METHODS: Based on the DeepLabv3+ networks, 2992 thyroid nodules in US images were used to train a model to detect thyroid nodules, of which 998 were used to train a model to detect and quantify calcifications. A total of 225 and 146 thyroid nodules obtained from two centers, respectively, were used to test the performance of these models. A logistic regression method was used to construct the predictive models for LNM in PTCs. RESULTS: Calcifications detected by the network model and experienced radiologists had an agreement degree of above 90%. The novel quantitative parameters of US calcification defined in this study showed a significant difference between PTC patients with and without cervical LNM (p < 0.05). The calcification parameters were beneficial to predicting the LNM risk in PTC patients. The LNM prediction model using these calcification parameters combined with patient age and other US nodular features showed a higher specificity and accuracy than the calcification parameters alone. CONCLUSIONS: Our models not only detect the calcifications automatically, but also have value in predicting cervical LNM risk of PTC patients, thereby making it possible to investigate the relationship between calcifications and highly invasive PTC in detail. CLINICAL RELEVANCE STATEMENT: Due to the high association of US microcalcifications with thyroid cancers, our model will contribute to the differential diagnosis of thyroid nodules in daily practice. KEY POINTS: ⢠We developed an ML-based network model for automatically detecting and quantifying calcifications within thyroid nodules in US images. ⢠Three novel parameters for quantifying US calcifications were defined and verified. ⢠These US calcification parameters showed value in predicting the risk of cervical LNM in PTC patients.