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BACKGROUND: Cerebral aneurysms are life-threatening cerebrovascular disorders. Currently, there are no effective treatments for preventing disease progression. Mendelian randomisation (MR) is widely used to repurify licensed drugs and identify new therapeutic targets. Therefore, this study aims to investigate effective drug targets for preventing the formation and rupture of cerebral aneurysms and analyse their potential mechanisms. METHODS: We performed a comprehensive study integrating two-sample MR analysis, colocalisation analysis and summary data-based Mendelian randomisation (SMR) to assess the causal effects of blood and brain druggable cis-expression quantitative trait loci (cis-eQTLs) on intracranial aneurysm (IA), unruptured intracranial aneurysm (UIA) and subarachnoid haemorrhage of IA rupture (SAH). Druggable genes were obtained from the study by Chris Finan et al, cis-eQTLs from the eQTLGen and PsychENCODE consortia. Results were validated using proteomic and transcriptomic data. Single-gene functional analyses probed potential mechanisms, culminating in the construction of a drug-gene regulation network. RESULTS: Through the MR analysis, we identified four potential drug targets in the blood, including prolylcarboxypeptidase (PRCP), proteasome 20S subunit alpha 4 (PSMA4), LTBP4 and GPR160 for SAH. Furthermore, two potential drug targets (PSMA4 and SLC22A4) were identified for IA and one potential drug target (KL) for UIA after accounting for multiple testing (P(inverse-variance weighted)<8.28e-6). Strong evidence of colocalisation and SMR analysis confirmed the relevance of PSMA4 and PRCP in outcomes. Elevated PRCP circulating proteins correlated with a lower SAH risk. PRCP gene expression was significantly downregulated in the disease cohort. CONCLUSIONS: This study supports that elevated PRCP gene expression in blood is causally associated with the decreased risk of IA rupture. Conversely, increased PSMA4 expression in the blood is causally related to an increased risk of IA rupture and formation.
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A novel, to the best of our knowledge, cross-spectral optical computing imaging experiment has been achieved through a single exposure of a charge-coupled device. The experimental setup integrates single-pixel imaging (SPI) with ghost imaging (GI) through a photoelectric conversion circuit and a synchronous modulation system. The experimental process involves modulation in one wavelength band (in SPI) and demodulation using the GI algorithm in another. Significantly, our approach utilizes optical computing demodulation, a departure from the conventional electronic demodulation in GI (SPI), which involves the convolution between the bucket optical signals and the modulated patterns on the digital micromirror device. A proof-of-concept cross-band imaging experiment from near-infrared to visible light has been carried out. The results highlight the system's ability to capture images at up to 20 frames per second using near-infrared illumination, which are then reconstructed in the visible light spectrum. This success not only validates the feasibility of our approach but also expands the potential applications in the SPI or GI fields, particularly in scenarios where two-dimensional detector arrays are either unavailable or prohibitively expensive in certain electromagnetic spectra such as x-ray and terahertz.
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Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53's relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.
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Fibrose , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Animais , Transição Epitelial-Mesenquimal , Apoptose , Terapia de Alvo MolecularRESUMO
Photoelectrocatalysis stands as an exceptionally efficient and sustainable method, significantly addressing both energy scarcity and environmental pollution challenges. Within this realm, quantum dots (QDs) have garnered immense attention for their outstanding catalytic properties. Their unique features-cost-effectiveness, high efficiency, remarkable stability, and exceptional photovoltaic characteristics-set them apart from other tunable semiconductor materials. Heterojunction structures based on quantum dots remarkably boost solar energy conversion efficiency. This review aims to provide a comprehensive overview of the impacts generated by heterojunctions formed using diverse quantum dots and delve into their catalytic applications. Moreover, it sheds light on recent advancements utilizing quantum dots in modifying optoelectronic semiconductor materials for diverse purposes, ranging from hydrogen (H2) generation to carbon and nitrogen reduction, as well as pollutant degradation. Additionally, the paper offers valuable insights into challenges faced by quantum dot applications and outlines promising future prospects.
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Pontos Quânticos , Pontos Quânticos/química , Catálise , Semicondutores , Hidrogênio/química , Energia Solar , Nitrogênio/química , Carbono/químicaRESUMO
Gastric cancer (GC) presents a formidable global health challenge, and conventional therapies face efficacy limitations. Ubiquitin-specific protease 7 (USP7) plays pivotal roles in GC development, immune response, and chemo-resistance, making it a promising target. Various USP7 inhibitors have shown selectivity and efficacy in preclinical studies. However, the mechanistic role of USP7 has not been fully elucidated, and currently, no USP7 inhibitors have been approved for clinical use. In this study, DHPO is identified as a potent USP7 inhibitor for GC treatment through in silico screening. DHPO demonstrates significant anti-tumor activity in vitro, inhibiting cell viability and clonogenic ability, and preventing tumor migration and invasion. In vivo studies using orthotopic gastric tumor mouse models validate DHPO's efficacy in suppressing tumor growth and metastasis without significant toxicity. Mechanistically, DHPO inhibition triggers ferroptosis, evidenced by mitochondrial alterations, lipid Reactive Oxygen Species (ROS), Malondialdehyde (MDA) accumulation, and iron overload. Further investigations unveil USP7's regulation of Stearoyl-CoA Desaturase (SCD) through deubiquitination, linking USP7 inhibition to SCD degradation and ferroptosis induction. Overall, this study identifies USP7 as a key player in ferroptosis of GC, elucidates DHPO's inhibitory mechanisms, and highlights its potential for GC treatment by inducing ferroptosis through SCD regulation.
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Ferroptose , Estearoil-CoA Dessaturase , Neoplasias Gástricas , Peptidase 7 Específica de Ubiquitina , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Peptidase 7 Específica de Ubiquitina/metabolismo , Peptidase 7 Específica de Ubiquitina/genéticaRESUMO
Optical encryption based on single-pixel imaging (SPI) has made great advances with the introduction of deep learning. However, the use of deep neural networks usually requires a long training time, and the networks need to be retrained once the target scene changes. With this in mind, we propose an SPI encryption scheme based on an attention-inserted physics-driven neural network. Here, an attention module is used to encrypt the single-pixel measurement value sequences of two images, together with a sequence of cryptographic keys, into a one-dimensional ciphertext signal to complete image encryption. Then, the encrypted signal is fed into a physics-driven neural network for high-fidelity decoding (i.e., decryption). This scheme eliminates the need for pre-training the network and gives more freedom to spatial modulation. Both simulation and experimental results have demonstrated the feasibility and eavesdropping resistance of this scheme. Thus, it will lead SPI-based optical encryption closer to intelligent deep encryption.
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BACKGROUND: Patients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood. OBJECTIVE: The aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci. METHODS: We used the summary statistics from genome-wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed. RESULTS: MiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function-related biological processes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune-related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society.
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Estudo de Associação Genômica Ampla , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Predisposição Genética para Doença/genética , Fenótipo , Encéfalo/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único/genética , Loci GênicosRESUMO
BACKGROUND: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine. METHODS: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes. RESULTS: We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine. CONCLUSIONS: Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine.
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Transtornos de Enxaqueca , Proteoma , Humanos , Proteoma/genética , Estudo de Associação Genômica Ampla , Proteômica , Transcriptoma , Transtornos de Enxaqueca/genéticaRESUMO
Background: Cerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases. The purpose of this study was to investigate whether serum NGAL levels could predict disease severity in patients with CSVD. Methods: The patients with CSVD who visited the Department of Neurology at the First Affiliated Hospital of Zhengzhou University between January 2018 and June 2022 were prospectively included. The total CSVD burden score was calculated using whole-brain magnetic resonance imaging (MRI), and the patients were divided into a mild group (total CSVD burden score < 2 points) and a severe group (total CSVD burden score ≥ 2 points). Age, sex, height, smoking and alcohol consumption history, medical history, and serological results of patients were collected to perform the univariate analysis. Multivariate logistic regression was used to analyze the risk factors that affect CSVD severity. The multiple linear regression method was used to analyze which individual CSVD markers (periventricular white matter hyperintensities, deep white matter hyperintensities, lacune, and cerebral microbleed) play a role in the association between total CSVD burden score and NGAL. Results: A total of 427 patients with CSVD (140 in the mild group and 287 in the severe group) were included in the study. A multivariate logistic regression analysis showed that the following factors were significantly associated with CSVD severity: male sex [odds ratio(OR), 1.912; 95% confidence interval (CI), 1.150-3.179], age (OR, 1.046; 95% CI, 1.022-1.070), history of cerebrovascular disease (OR, 3.050; 95% CI, 1.764-5.274), serum NGAL level (OR, 1.005; 95% CI, 1.002-1.008), and diabetes (OR, 2.593; 95% CI, 1.424-4.722). A multivariate linear regression shows that periventricular white matter hyperintensities and cerebral microbleed are associated with serum NGAL concentrations (P < 0.05). Conclusion: Serum NGAL level is closely related to CSVD severity and is a risk factor for the burden of CSVD brain damage. Serum NGAL has high specificity in reflecting the severity of CSVD.
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BACKGROUND: Previous studies revealed that obstructive sleep apnea (OSA) and smoking, alcohol consumption, and coffee intake are closely related. This study aimed to evaluate the causal effect between these factors and OSA. METHODS: The published genome-wide association study data (GWAS) provided genetic tools. We conducted a univariable two-sample Mendelian Randomization (MR) to estimate the causal effect between smoking initiation, never smoking, alcohol consumption, coffee intake, and coffee consumption with the risk of incidence OSA. Inverse variance weighting (IVW) was used as the main method for effect evaluation, and other MR methods were used for sensitivity analysis. After adjusting for body mass index (BMI), hypertension, and diabetes respectively by multivariable MR (MVMR), we further evaluate the causal effect of these factors on OSA. RESULTS: Under univariable MR analysis, we observed that smoking initiation was associated with an increased risk of incidence OSA (OR 1.326, 95% CI 1.001-1.757, p =0.049). Never smoking was associated with decreased risk of OSA (OR 0.872, 95% CI 0.807-0.942, p <0.001). Coffee intake and coffee consumption was associated with an increased incidence of OSA (OR 1.405, 95% CI 1.065-1.854, p =0.016) and (OR 1.330, 95% CI 1.013-1.746, p =0.040). Further multivariate MR showed that the causal relationship between never smoking and OSA existed but not coffee consumption, after adjusting for diabetes and hypertension. However, the all results did not support causality after adjusting for BMI. CONCLUSION: This two-sample MR study showed that genetically predicted smoking and higher coffee intake are causally associated with an increased risk of OSA.
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Hipertensão , Apneia Obstrutiva do Sono , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Fumar/efeitos adversos , Fumar/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The meninges, membranes surrounding the central nervous system (CNS) boundary, harbor a diverse array of immunocompetent immune cells, and therefore, serve as an immunologically active site. Meningeal immunity has emerged as a key factor in modulating proper brain function and social behavior, performing constant immune surveillance of the CNS, and participating in several neurological diseases. However, it remains to be determined how meningeal immunity contributes to CNS physiology and pathophysiology. With the advances in single-cell omics, new approaches, such as single-cell technologies, unveiled the details of cellular and molecular mechanisms underlying meningeal immunity in CNS homeostasis and dysfunction. These new findings contradict some previous dogmas and shed new light on new possible therapeutic targets. In this review, we focus on the complicated multi-components, powerful meningeal immunosurveillance capability, and its crucial involvement in physiological and neuropathological conditions, as recently revealed by single-cell technologies.
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Meninges , Doenças do Sistema Nervoso , Humanos , Sistema Nervoso CentralRESUMO
Photoelectrocatalysis (PEC) has long been regarded as an efficient and green method to eliminate various organic pollutants from wastewater. However, the lack of highly photoelectrocatalytic active and stable electrodes limits the development of the PEC technologies. Herein, a novel hierarchical photo-electrode with hollow Cu1.8S/NH2-La MOFs decorated black titanium dioxide nanotubes (Cu1.8S/NH2-La MOFs/Black TNTs) was fabricated by a two-step water-heating method. The prepared photoelectrode was used to degradation of 2, 4-dichlorophenol (2, 4-DCP). Analysis of photoelectrocatalytic degradation process of 2, 4-DCP was evaluated using UV-Vis absorption spectroscopy and the main degradation paths were analyzed by LC-MS. The results showed that 99.3% of the pollutant could be rapidly degraded within 180 min. Furthermore, the Cu1.8S/NH2-La MOFs/Black TNTs photoelectric pole exhibited excellent stability after 15 cycling experiments.
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Poluentes Ambientais , Nanotubos , Nanotubos/química , Poluentes Ambientais/química , Fenóis , Eletrodos , Titânio/química , CatáliseRESUMO
OBJECTIVE: GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease (CSVD), both diseases have white matter hyperintensity on T2-fluid-attenuated inversion recovery sequences of brain MRI, and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI. Therefore, we hypothesised that the GGC repeat expansions might also contribute to CSVD. To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD, we performed a genetic analysis of 814 patients with the disease. METHODS: We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD. Their Fazekas score was greater than or equal to 3 points. Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions, and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD. RESULTS: We identified nine (1.11%) patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats. The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%. CONCLUSION: Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD. This provides new thinking for studying the pathogenesis of CSVD.
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Doenças Neurodegenerativas , Humanos , Corpos de Inclusão Intranuclear/genética , Corpos de Inclusão Intranuclear/patologia , Mutação , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: A loss-of-function mutation in ATPase phospholipid transporting 11-B (putative) (ATP11B) gene causing cerebral small vessel disease (SVD) in vivo, and a single intronic nucleotide polymorphism in ATP11B: rs148771930 that was associated with white matter hyperintensities burden in European patients with SVD, was recently identified. Our results suggest that ATP11B may not play an essential role in SVD in the Chinese population. RESULTS: We performed target region sequencing including ATP11B gene in 182 patients with sporadic SVD, and identified five rare variants and two novel variants of ATP11B. A case-control study was then performed in 524 patients and matched 550 controls to investigate the relationship between ATP11B and sporadic SVD in the Chinese Han population. Although none of these variants were significantly associated with SVD in our samples, it is important to mention that we identified a novel variant, p. G238W, which was predicted to be pathogenic in silico. This variant was present in our cohort of patients with an extremely low frequency and was absent in the controls. CONCLUSION: Our results suggest that ATP11B may not play an essential role in SVD in the Chinese population.
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Adenosina Trifosfatases , Doenças de Pequenos Vasos Cerebrais , População do Leste Asiático , Humanos , Estudos de Casos e Controles , Doenças de Pequenos Vasos Cerebrais/genética , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Polimorfismo de Nucleotídeo Único , Adenosina Trifosfatases/genéticaRESUMO
Signal transducer and activator of transcription 3 (STAT3) is a key regulator of many human cancers and has been widely recognized as a promising target for cancer therapy. A variety of small-molecule inhibitors have been developed for targeting STAT3, and some of them are now undergoing clinical trials. S3I-201, a known STAT3 inhibitor, may block STAT3 function in cancer cells by binding to the STAT3 SH2 domain to disrupt STAT3 protein complex formation. Using S3I-201 as a starting point for drug development, we synthesized a series of new STAT3 inhibitors 9a-x in this study by introducing naphthoquinone unit, a privileged fragment in STAT3 inhibitors. Most of the compounds exhibited strong anti-proliferation activity of gastric cancer cells (MGC803, MKN28, MNK1, and AGS). The representative compound 9n (SIL-14) could effectively inhibit the colony formation and migration of gastric cancer cells MGC803, arrest the cell cycle and induce MGC803 cell apoptosis at low micromolar concentrations in vitro. In addition, SIL-14 can also inhibit the phosphorylation of STAT3 protein and significantly decrease the expression of total STAT3, suggesting that it may exert anticancer effects by blocking the STAT3 signaling pathway. These results support that SIL-14 may be a promising STAT3 inhibitor for the further development of potential anti-gastric cancer candidates.
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Naftoquinonas , Neoplasias Gástricas , Ácidos Aminossalicílicos/farmacologia , Ácidos Aminossalicílicos/uso terapêutico , Benzenossulfonatos , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismoRESUMO
Background Recent evidence suggests that presence of an intracranial arterial thrombus with a hyperdense artery sign (HAS) at noncontrast CT (NCCT) is associated with better response to intravenous alteplase. Patients with HAS may benefit more from combined intravenous alteplase and endovascular treatment (EVT). Purpose To investigate whether HAS at NCCT modifies the treatment effect of adding intravenous alteplase on clinical outcome in patients with acute large-vessel occlusion undergoing EVT. Materials and Methods This study is a secondary analysis of a prospective randomized trial (Direct Intra-arterial thrombectomy in order to Revascularize AIS patients with large-vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicenter randomized clinical Trial [DIRECT-MT]), which compared adding alteplase to EVT versus EVT alone in participants with acute large-vessel occlusion between February 2018 and July 2019. Participants with catheter angiograms and adequate NCCT for HAS evaluation were included. HAS was determined visually by two independent investigators at baseline NCCT. Treatment effect of intravenous alteplase administration according to presence of HAS on the primary clinical outcome (modified Rankin Scale [mRS] score at 90 days) and secondary and safety outcomes were assessed using adjusted multivariable regression models. Results Among 633 included participants (356 men [56%]; median age, 69 years), HAS was observed in 283 participants (45%): 142 of 313 participants (45%) in the EVT-only group and 141 of 320 participants (44%) in the group with added intravenous alteplase. Treatment-by-HAS interaction was observed for the primary outcome (P < .001), whereby a shift in favor of better outcomes with added intravenous alteplase occurred in participants with HAS (adjusted odds ratio [OR]: 1.82; 95% CI: 1.18, 2.79), while an adverse effect was seen in participants without HAS (adjusted OR: 0.62; 95% CI: 0.42, 0.91). This also held true for three secondary outcomes (excellent outcome [mRS score of 0-1 at 90 days], P = .005; good outcome [mRS score of 0-2 at 90 days], P = .008; final successful reperfusion, P = .04) in the adjusted models. Conclusion After acute ischemic stroke, presence of hyperdense artery sign (HAS) at baseline noncontrast CT indicated better outcomes when alteplase was added to endovascular treatment, but adding alteplase to endovascular treatment resulted in worse outcomes in participants without HAS. Clinical trial registration no. NCT03469206 © RSNA, 2022 Online supplemental material is available for this article.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Humanos , Masculino , Artérias , Isquemia Encefálica/etiologia , Procedimentos Endovasculares/métodos , Fibrinolíticos/uso terapêutico , Fibrinolíticos/efeitos adversos , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , FemininoRESUMO
Gastric cancer remains a significant health burden worldwide. In continuation of our previous study and development of effective small molecules against gastric cancer, a series of benzochalcone analogues involving heterocyclic molecules were synthesised and biologically evaluated in vitro and in vivo. Among them, the quinolin-6-yl substituted derivative KL-6 inhibited the growth of gastric cancer cells (HGC27, MKN28, AZ521, AGS, and MKN1) with a submicromolar to micromolar range of IC50, being the most potent one in this series. Additionally, KL-6 significantly inhibited the colony formation, migration and invasion, and effectively induced apoptosis of MKN1 cells in a concentration-dependent manner. The mechanistic study revealed that KL-6 could concentration-dependently suppress STAT3 phosphorylation, which may partly contribute to its anticancer activity. Furthermore, in vivo antitumour study on the MKN1 orthotopic tumour model showed that KL-6 effectively inhibited tumour growth (TGI of 78%) and metastasis without obvious toxicity. Collectively, compound KL-6 may support the further development of candidates for gastric cancer treatment.
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Chalconas , Fator de Transcrição STAT3 , Neoplasias Gástricas , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chalconas/farmacologia , Humanos , Terapia de Alvo Molecular , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológicoRESUMO
In existing cryptographic key distribution (CKD) protocols based on computational ghost imaging (CGI), the interaction among multiple legitimate users is generally neglected, and the channel noise has a serious impact on the performance. To overcome these shortcomings, we propose a multi-party interactive CKD protocol over a public network, which takes advantage of the cascade ablation of fragment patterns (FPs). The server splits a quick-response (QR) code image into multiple FPs and embeds different "watermark" labels into these FPs. By using a CGI setup, the server will acquire a series of bucket value sequences with respect to different FPs and send them to multiple legitimate users through a public network. The users reconstruct the FPs and determine whether there is an attack in the public channel according to the content of the recovered "watermark" labels, so as to complete the self-authentication. Finally, these users can extract their cryptographic keys by scanning the QR code (the cascade ablation result of FPs) returned by an intermediary. Both simulation and experimental results have verified the feasibility of this protocol. The impacts of different attacks and the noise robustness have also been investigated.
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Segurança Computacional , Insuficiência Renal Crônica , Computadores , Confidencialidade , Diagnóstico por Imagem , HumanosRESUMO
Single-pixel imaging (SPI) has attracted widespread attention because it generally uses a non-pixelated photodetector and a digital micromirror device (DMD) to acquire the object image. Since the modulated patterns seen from two reflection directions of the DMD are naturally complementary, one can apply complementary balanced measurements to greatly improve the measurement signal-to-noise ratio and reconstruction quality. However, the balance between two reflection arms significantly determines the quality of differential measurements. In this work, we propose and demonstrate a simple secondary complementary balancing mechanism to minimize the impact of the imbalance on the imaging system. In our SPI setup, we used a silicon free-space balanced amplified photodetector with 5 mm active diameter which could directly output the difference between two optical input signals in two reflection arms. Both simulation and experimental results have demonstrated that the use of secondary complementary balancing can result in a better cancellation of direct current components of measurements, and can acquire an image quality slightly better than that of single-arm single-pixel complementary measurement scheme (which is free from the trouble of optical imbalance) and over 20 times better than that of double-arm dual-pixel complementary measurement scheme under optical imbalance conditions.
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Soft robots have attracted increasing attention due to their excellent versatility and broad applications. In this article, we present a minimally designed soft crawling robot (SCR) capable of robust locomotion in unstructured pipes with various geometric/material properties and surface topology. In particular, the SCR can squeeze through narrow pipes smaller than its cross section and propel robustly in spiked pipes. The gait pattern and locomotion mechanism of this robot are experimentally investigated and analysed by the finite element analysis, revealing that the resultant forward frictional force is generated due to the asymmetric mechanical properties along the length direction of the robot. The proposed simple yet working SCR could inspire novel designs and applications of soft robots in unstructured narrow canals such as large intestines or industrial pipelines.