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The World Health Organization identifies a strong surveillance system for malaria and its mosquito vector as an essential pillar of the malaria elimination agenda. Anopheles salivary antibodies are emerging biomarkers of exposure to mosquito bites that potentially overcome sensitivity and logistical constraints of traditional entomological surveys. Using samples collected by a village health volunteer network in 104 villages in Southeast Myanmar during routine surveillance, the present study employs a Bayesian geostatistical modeling framework, incorporating climatic and environmental variables together with Anopheles salivary antigen serology, to generate spatially continuous predictive maps of Anopheles biting exposure. Our maps quantify fine-scale spatial and temporal heterogeneity in Anopheles salivary antibody seroprevalence (ranging from 9 to 99%) that serves as a proxy of exposure to Anopheles bites and advances current static maps of only Anopheles occurrence. We also developed an innovative framework to perform surveillance of malaria transmission. By incorporating antibodies against the vector and the transmissible form of malaria (sporozoite) in a joint Bayesian geostatistical model, we predict several foci of ongoing transmission. In our study, we demonstrate that antibodies specific for Anopheles salivary and sporozoite antigens are a logistically feasible metric with which to quantify and characterize heterogeneity in exposure to vector bites and malaria transmission. These approaches could readily be scaled up into existing village health volunteer surveillance networks to identify foci of residual malaria transmission, which could be targeted with supplementary interventions to accelerate progress toward elimination.
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Anopheles , Teorema de Bayes , Malária , Mosquitos Vetores , Animais , Anopheles/parasitologia , Mosquitos Vetores/parasitologia , Humanos , Malária/transmissão , Malária/epidemiologia , Malária/imunologia , Malária/parasitologia , Estudos Soroepidemiológicos , Mordeduras e Picadas de Insetos/epidemiologia , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/parasitologia , Esporozoítos/imunologiaRESUMO
Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.
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Antioxidantes , Astragalus propinquus , Drosophila melanogaster , Doenças Neurodegenerativas , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Astragalus propinquus/química , Drosophila melanogaster/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Extratos Vegetais/farmacologia , Animais Geneticamente Modificados , Medicamentos de Ervas Chinesas/farmacologia , Peróxido de Hidrogênio , Peptídeos beta-Amiloides/metabolismoRESUMO
BACKGROUND: Nitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes. RESULTS: Total N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar. CONCLUSIONS: N deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.
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Panax notoginseng , Plantas Medicinais , Nitrogênio/metabolismo , Plantas Medicinais/genética , Plantas Medicinais/metabolismo , Panax notoginseng/genética , Panax notoginseng/metabolismo , Simulação de Acoplamento Molecular , Melhoramento Vegetal , Aminoácidos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
The environmental deterioration caused by dye wastewater discharge has received considerable attention in recent decades. One of the most promising approaches to addressing the aforementioned environmental issue is the development of photocatalysts with high solar energy consumption efficiency for the treatment of dye-contaminated water. In this study, a novel low-cost π-π biomass-derived black carbon modified g-C3N4 coupled FeIn2S4 composite (i.e., FeInS/BC-CN) photocatalyst is successfully designed and fabricated that reveals significantly improved photocatalytic performance for the degradation of Eosin Yellow (EY) dye in aqueous solution. Under dark and subsequent visible light irradiation, the amount optimized composite reveals 99% removal performance for EY dye, almost three-fold compared to that of the pristine FeInS and BC-CN counterparts. Further, it is confirmed by means of the electron spin resonance spectrometry, quenching experiments, and density functional theory (DFT) calculations, that the hydroxyl radicals (â¢OH) and superoxide radicals (â¢O2 -) are the dominant oxidation species involved in the degradation process of EY dye. In addition, a systematic photocatalytic degradation route is proposed based on the resultant degradation intermediates detectedduring liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. This work provides an innovative idea for the development of advanced photocatalysts to mitigate water pollution.
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African swine fever virus (ASFV) is a large DNA virus that causes African swine fever (ASF), an acute and hemorrhagic disease in pigs with lethality rates of up to 100%. To date, how ASFV efficiently suppress the innate immune response remains enigmatic. In this study, we identified ASFV cysteine protease pS273R as an antagonist of type I interferon (IFN). Overexpression of pS273R inhibited JAK-STAT signaling triggered by type I IFNs. Mechanistically, pS273R interacted with STAT2 and recruited the E3 ubiquitin ligase DCST1, resulting in K48-linked polyubiquitination at K55 of STAT2 and subsequent proteasome-dependent degradation of STAT2. Furthermore, such a function of pS273R in JAK-STAT signaling is not dependent on its protease activity. These findings suggest that ASFV pS273R is important to evade host innate immunity. IMPORTANCE ASF is an acute disease in domestic pigs caused by infection with ASFV. ASF has become a global threat with devastating economic and ecological consequences. To date, there are no commercially available, safe, and efficacious vaccines to prevent ASFV infection. ASFV has evolved a series of strategies to evade host immune responses, facilitating its replication and transmission. Therefore, understanding the immune evasion mechanism of ASFV is helpful for the development of prevention and control measures for ASF. Here, we identified ASFV cysteine protease pS273R as an antagonist of type I IFNs. ASFV pS273R interacted with STAT2 and mediated degradation of STAT2, a transcription factor downstream of type I IFNs that is responsible for induction of various IFN-stimulated genes. pS273R recruited the E3 ubiquitin ligase DCST1 to enhance K48-linked polyubiquitination of STAT2 at K55 in a manner independent of its protease activity. These findings suggest that pS273R is important for ASFV to escape host innate immunity, which sheds new light on the mechanisms of ASFV immune evasion.
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Vírus da Febre Suína Africana , Febre Suína Africana , Cisteína Proteases , Interferon Tipo I , Animais , Cisteína Proteases/genética , Cisteína Proteases/metabolismo , Imunidade Inata/genética , Interferon Tipo I/metabolismo , Sus scrofa , Suínos , Ubiquitina-Proteína Ligases/metabolismo , Fator de Transcrição STAT2/metabolismo , Transdução de SinaisRESUMO
ASFV is a large DNA virus that is highly pathogenic in domestic pigs. How this virus is sensed by the innate immune system as well as why it is so virulent remains enigmatic. In this study, we show that the ASFV genome contains AT-rich regions that are recognized by the DNA-directed RNA polymerase III (Pol-III), leading to viral RNA sensor RIG-I-mediated innate immune responses. We further show that ASFV protein I267L inhibits RNA Pol-III-RIG-I-mediated innate antiviral responses. I267L interacts with the E3 ubiquitin ligase Riplet, disrupts Riplet-RIG-I interaction and impairs Riplet-mediated K63-polyubiquitination and activation of RIG-I. I267L-deficient ASFV induces higher levels of interferon-ß, and displays compromised replication both in primary macrophages and pigs compared with wild-type ASFV. Furthermore, I267L-deficiency attenuates the virulence and pathogenesis of ASFV in pigs. These findings suggest that ASFV I267L is an important virulence factor by impairing innate immune responses mediated by the RNA Pol-III-RIG-I axis.
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Vírus da Febre Suína Africana/patogenicidade , Imunidade Inata/imunologia , Fatores de Virulência/imunologia , Virulência/imunologia , Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/imunologia , Animais , RNA Polimerase III/imunologia , Receptores de Superfície Celular/imunologia , SuínosRESUMO
BACKGROUND: Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis. RESULTS: A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients. CONCLUSIONS: Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.
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Transtorno Bipolar , Humanos , Mania , Mapeamento Encefálico/métodos , Vias Neurais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , EncéfaloRESUMO
BACKGROUND: Diagnostic performance of placenta accreta spectrum (PAS) by prenatal MRI is unsatisfactory. Deep learning radiomics (DLR) has the potential to quantify the MRI features of PAS. PURPOSE: To explore whether DLR from MRI can be used to identify pregnancies with PAS. STUDY TYPE: Retrospective. POPULATION: 324 pregnant women (mean age, 33.3 years) suspected PAS (170 training and 72 validation from institution 1, 82 external validation from institution 2) with clinicopathologically proved PAS (206 PAS, 118 non-PAS). FIELD STRENGTH/SEQUENCE: 3-T, turbo spin-echo T2-weighted images. ASSESSMENT: The DLR features were extracted using the MedicalNet. An MRI-based DLR model incorporating DLR signature, clinical model (different clinical characteristics between PAS and non-PAS groups), and MRI morphologic model (radiologists' binary assessment for the PAS diagnosis) was developed. These models were constructed in the training dataset and then validated in the validation datasets. STATISTICAL TESTS: The Student t-test or Mann-Whitney U, χ2 or Fisher exact test, Kappa, dice similarity coefficient, intraclass correlation coefficients, least absolute shrinkage and selection operator logistic regression, multivariate logistic regression, receiver operating characteristic (ROC) curve, DeLong test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI), calibration curve with Hosmer-Lemeshow test, decision curve analysis (DCA). P < 0.05 indicated a significant difference. RESULTS: The MRI-based DLR model had a higher area under the curve than the clinical model in three datasets (0.880 vs. 0.741, 0.861 vs. 0.772, 0.852 vs. 0.675, respectively) or MRI morphologic model in training and independent validation datasets (0.880 vs. 0.760, 0.861, vs. 0.781, respectively). The NRI and IDI were 0.123 and 0.104, respectively. The Hosmer-Lemeshow test had nonsignificant statistics (P = 0.296 to 0.590). The DCA offered a net benefit at any threshold probability. DATA CONCLUSION: An MRI-based DLR model may show better performance in diagnosing PAS than a clinical or MRI morphologic model. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.
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Aprendizado Profundo , Placenta Acreta , Doenças Placentárias , Gravidez , Feminino , Humanos , Adulto , Placenta Acreta/diagnóstico por imagem , Radiômica , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Diagnóstico Pré-NatalRESUMO
BACKGROUND: Malaria risk maps are crucial for controlling and eliminating malaria by identifying areas of varying transmission risk. In the Greater Mekong Subregion, these maps guide interventions and resource allocation. This article focuses on analysing changes in malaria transmission and developing fine-scale risk maps using five years of routine surveillance data in Laos (2017-2021). The study employed data from 1160 geolocated health facilities in Laos, along with high-resolution environmental data. METHODS: A Bayesian geostatistical framework incorporating population data and treatment-seeking propensity was developed. The models incorporated static and dynamic factors and accounted for spatial heterogeneity. RESULTS: Results showed a significant decline in malaria cases in Laos over the five-year period and a shift in transmission patterns. While the north became malaria-free, the south experienced ongoing transmission with sporadic outbreaks. CONCLUSION: The risk maps provided insights into changing transmission patterns and supported risk stratification. These risk maps are valuable tools for malaria control in Laos, aiding resource allocation, identifying intervention gaps, and raising public awareness. The study enhances understanding of malaria transmission dynamics and facilitates evidence-based decision-making for targeted interventions in high-risk areas.
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Malária , Laos/epidemiologia , Incidência , Humanos , Malária/epidemiologia , Malária/transmissão , Medição de Risco , Teorema de BayesRESUMO
OBJECTIVES: To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC). METHODS: This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, αCTRW, ßCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability. RESULTS: The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877. CONCLUSIONS: The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs. CLINICAL RELEVANCE STATEMENT: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue. KEY POINTS: ⢠Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM values compared with HER2-overexpressing breast cancer. ⢠The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. ⢠The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability.
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Neoplasias da Mama , Receptor ErbB-2 , Feminino , Humanos , Neoplasias da Mama/patologia , Estudos Prospectivos , Receptores de Progesterona , Imagem de Difusão por Ressonância Magnética , Receptores de Estrogênio/metabolismoRESUMO
The development of efficient and sustainable methods for reducing carbon dioxide (CO2) and converting it into valuable hydrocarbons has gained significant attention. In this study, researchers focused on Ti4+-doped metal-organic framework (MOF-74) photocatalysts. The incorporation of Ti4+ ions into the MOF-74 structure was achieved through a one-pot hydrothermal method. By replacing Zn2+ ions with Ti4+ ions in a substitutional manner, researchers have aimed to enhance the photocatalytic activity of the CO2 reduction. The obtained Ti4+-doped MOF-74 photocatalysts exhibited a significantly improved performance in the reduction of CO2 into carbon monoxide (CO). The doping of Ti4+ ions induced energy bands below the conduction band minimum (CBM) of MOF-74, extending the visible response range and enabling the photocatalysts to utilize a broader spectrum of light for catalytic reactions. This extension of the visible response range enables photocatalysts to utilize a broader spectrum of light for catalytic reactions. The incorporation of Ti4+ ions not only extends the visible response range but also suppresses charge carrier recombination. This work provides valuable insights into the design principles of MOF-based photocatalysts and paves the way for their practical implementation in addressing the energy crisis and reducing greenhouse gas emissions.
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Aqueous aluminum-ion batteries have many advantages such as their safety, environmental friendliness, low cost, high reserves and the high theoretical specific capacity of aluminum. So aqueous aluminum-ion batteries are potential substitute for lithium-ion batteries. In this paper, the current research status and development trends of cathode and anode materials and electrolytes for aqueous aluminum-ion batteries are described. Aiming at the problem of passivation, corrosion and hydrogen evolution reaction of aluminum anode and dissolution and irreversible change of cathode after cycling in aqueous aluminum-ion batteries. Solutions of different research routes such as ASEI (artificial solid electrolyte interphase), alloying, amorphization, elemental doping, electrolyte regulation, etc and different transformation mechanisms of anode and cathode materials during cycling have been summarized. Moreover, it looks forward to the possible research directions of aqueous aluminum-ion batteries in the future. We hope that this review can provide some insights and support for the design of more suitable electrode materials and electrolytes for aqueous aluminum-ion batteries.
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BACKGROUND: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children. METHOD: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed. RESULTS: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes. CONCLUSIONS: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens.
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Abscesso Hepático Piogênico , Humanos , Abscesso Hepático Piogênico/microbiologia , Abscesso Hepático Piogênico/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Criança , Lactente , Pequim/epidemiologia , Adolescente , Klebsiella pneumoniae/isolamento & purificação , Antibacterianos/uso terapêutico , Fatores de Risco , Staphylococcus aureus/isolamento & purificaçãoRESUMO
The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.
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Alcaloides , Antineoplásicos Fitogênicos , Apoptose , Proliferação de Células , Delphinium , Diterpenos , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Ovarianas , Feminino , Humanos , Delphinium/química , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Relação Estrutura-Atividade , Animais , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Simulação de Acoplamento MolecularRESUMO
Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 µM) or a COX-2 inhibitor Celecoxib (1, 3, 9 µM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.
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Neoplasias do Colo , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Antígeno B7-H1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ácido Rosmarínico , Celecoxib/farmacologia , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC1-co-DMA1) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC1-co-DMA1) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC1-co-DMA1) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.
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Antioxidantes , Lubrificantes , Animais , Coelhos , Antioxidantes/farmacologia , Materiais Biocompatíveis , Anti-Inflamatórios , Soluções Oftálmicas , Catecóis , InflamaçãoRESUMO
PURPOSE: To evaluate and compare the effect of decentration and tilt on the optical quality of monofocal and trifocal intraocular lenses (IOL). METHODS: Optical quality of a monofocal IOL (AcrySof IQ SN60WF; Alcon Laboratories, Inc., USA) and a trifocal IOL (AcrySof IQ PanOptix; Alcon Laboratories, Inc., USA) was assessed using an in vitro optical bench (OptiSpheric IOL R&D; Trioptics GmbH, Germany). At apertures of 3.0 mm and 4.5 mm, modulation transfer function (MTF) at spatial frequency of 50 lp/mm, MTF curve and the United States Air Force (USAF) resolution test chart of the two IOLs were measured and compared at their focus with different degrees of decentration and tilt. Optical quality at infinity, 60 cm and 40 cm and the through-focus MTF curves were compared when the two IOLs were centered at apertures of 3.0 mm and 4.5 mm. Spectral transmittance of the two IOLs was measured by the UV-visible spectrophotometer (UV 3300 PC; MAPADA, China). RESULTS: The SN60WF and the PanOptix filtered blue light from 400 to 500 nm. Both IOLs at the far focus and the PanOptix at the intermediate focus showed a decrease in optical quality with increasing decentration and tilt. The PanOptix demonstrated enhanced optical quality compared to the previous gradient at the near focus at a decentration range of 0.3-0.7 mm with a 3.0 mm aperture, and 0.5 mm with a 4.5 mm aperture, whereas other conditions exhibited diminished optical quality with increasing decentration and tilt at the focus of both IOLs. When the two IOLs were centered, the SN60WF had better optical quality at infinity, while the PanOptix had better optical quality at 60 cm and 40 cm defocus. The optical quality of the SN60WF exceeded that of the PanOptix at far focus, with a 3 mm aperture decentration up to 0.7 mm and a 4.5 mm aperture decentration up to 0.3 mm; this observation held true for all tilts, irrespective of aperture size. As both decentration and tilt increased, the optical quality of the SN60WF deteriorated more rapidly than that of the PanOptix at the far focal point. CONCLUSIONS: The SN60WF showed a decrease in optical quality with increasing decentration and tilt. Optical quality of the PanOptix at the near focus increased in some decentration conditions and decreased in some conditions, while it showed a decrease at the other focuses with increasing decentration. While tilt only had a negative effect on optical quality. When both IOLs were centered, the PanOptix provided a wider range of vision, while the SN60WF provided better far distance vision. At the far focus, the SN60WF has better resistance to tilt than the PanOptix, but the optical quality degrades more quickly when decentered and tilted.
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Currently, the visual detection of a target's shock flow field through background schlieren technology is a novel detection system. However, there are very few studies on the long-distance background schlieren imaging mechanism and its application in system design in the field of target detection. This paper proposes a design optimization method for space-based BOS detection system metrics. By establishing sensitivity evaluation models and image signal-to-noise ratio evaluation models for BOS detection systems, the influence of the different flight parameters and key parameters of BOS systems (detection spectral bands and spatial resolution) on target detection efficiency is explored. Furthermore, an optimization method based on the image signal-to-noise ratio of the BOS system and the overall metrics for specific scenarios are provided. The simulation results demonstrate that under satellite background images and speckle background images, the system metrics can detect and identify the schlieren of high-speed targets, with better applicability to disordered and complex real background images. This research contributes to advancing the development of high-speed target detection technology based on BOS.
RESUMO
Korean mistletoe (Viscum album L. var. coloratum) is renowned for its medicinal properties, including anti-cancer and immunoadjuvant effects. This study aimed to elucidate the mechanisms by which Korean mistletoe lectin (V. album L. var. coloratum agglutinin; VCA) modulates breast cancer cell apoptosis and macrophage polarization. The specific objectives were to (1) investigate the direct effects of VCA on MCF-7 breast cancer cells and THP-1-derived M1/M2 macrophages; (2) analyze the impact of VCA on the paracrine interactions between these cell types; and (3) compare the efficacy of VCA in 2D vs. 3D co-culture models to bridge the gap between in vitro and in vivo studies. We employed both 2D and 3D models, co-culturing human M1/M2 macrophages with human MCF-7 breast cancer cells in a Transwell system. Our research demonstrated that M1 and M2 macrophages significantly influenced the immune and apoptotic responses of breast cancer cells when exposed to VCA. M1 macrophages exhibited cytotoxic characteristics and enhanced VCA-induced apoptosis in both 2D and 3D co-culture models. Conversely, M2 macrophages initially displayed a protective effect by reducing apoptosis in breast cancer cells, but this protective effect was reversed upon exposure to VCA. Furthermore, our findings illustrate VCA's ability to modulate M1 and M2 polarization in breast cancer cells. Finally, the use of magnetic 3D cell cultures suggests their potential to yield results comparable to conventional 2D cultures, bridging the gap between in vitro and in vivo studies.
Assuntos
Apoptose , Neoplasias da Mama , Técnicas de Cocultura , Macrófagos , Humanos , Apoptose/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Células MCF-7 , Feminino , Viscum album/química , Lectinas de Plantas/farmacologia , Células THP-1RESUMO
Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.