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1.
Proc Natl Acad Sci U S A ; 121(4): e2312556121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38227655

RESUMO

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.


Assuntos
Febre Hemorrágica com Síndrome Renal , Ratos , Animais , Febre Hemorrágica com Síndrome Renal/epidemiologia , Febre Hemorrágica com Síndrome Renal/etiologia , Clima , Zoonoses , China/epidemiologia , Murinae , Incidência
2.
Nucleic Acids Res ; 51(7): 3150-3165, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-36869674

RESUMO

DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.


Assuntos
Cádmio , Instabilidade Genômica , Infertilidade Masculina , Espermatócitos , Animais , Humanos , Masculino , Camundongos , Cádmio/toxicidade , DNA/metabolismo , Reparo do DNA por Junção de Extremidades , Reparo do DNA , Instabilidade Genômica/efeitos dos fármacos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Íons/metabolismo , Fosforilação , Reparo de DNA por Recombinação , Espermatócitos/efeitos dos fármacos
3.
Proc Natl Acad Sci U S A ; 119(44): e2200944119, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36288285

RESUMO

Neuron-immune interaction through secreted factors contributes significantly to the complex microenvironment in the central nervous system that could alter cell functionalities and fates in both physiological and pathological conditions, which remains poorly characterized at the single-cell level. Herein, using a spatially patterned antibody barcode microchip, we realized the mapping of 12 different secretomes, covering cytokines, neurotrophic factors (NFs), and neuron-derived exosomes (NDEs) from high-throughput, paired single cells (≥ 600) simultaneously under normal conditions and an Alzheimer's disease (AD) model induced with amyloid beta protein 1-42 (Aß1-42). We applied the platform to analyze the secretion profiles from paired neuron-macrophage and neuron-microglia single cells with human cell lines. We found that pairwise neuron-macrophage interaction would trigger immune responses and attenuate neuron cells' secretion, while neuron-microglia interaction generally results in opposite outcomes in secretion. When neuron cells are induced with Aß1-42 protein into the AD model, both neuron-macrophage and neuron-microglia interactions lead to increased cytokines and NDEs and decreased NFs. Further analysis of AD patients' serum showed that NDEs were significantly higher in patients' samples than in the control group, validating our observation from the interaction assay. Furthermore, we resolved previously undifferentiated heterogeneity underlying the secretions from single-neuron cells. We found that the NDE and NF secretion was less dependent on the paracrine signaling between one another and that secretions from neuron cells would attenuate after differentiation with Aß1-42. This study demonstrates the mapping of the different secretomes from paired neuron-immune single cells, providing avenues for understanding how neurons and immune cells interact through the complex secretome network.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/metabolismo , Secretoma , Doença de Alzheimer/metabolismo , Neurônios/metabolismo , Microglia/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo , Fatores de Crescimento Neural/metabolismo
4.
Int J Cancer ; 154(7): 1285-1297, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180065

RESUMO

CD25, also known as the interleukin-2 receptor α chain (IL-2Rα), is highly expressed on regulatory T cells (Tregs), but relatively lower on effector T cells (Teffs). This makes it a potential target for Treg depletion, which can be used in tumor immunotherapy. However, marketed anti-CD25 antibodies (Basiliximab and Daclizumab) were originally developed as immunosuppressive drugs to prevent graft rejection, because these antibodies can block IL-2 binding to CD25 on Teffs, which in turn destroys the function of Teffs. Recent studies have shown that non-IL-2-blocking anti-CD25 antibodies have displayed exciting antitumor effects. Here, we screened out a non-IL-2-blocking anti-CD25 monoclonal antibody (mAb) 7B7 by hybridoma technology, and confirmed its antitumor activity via depleting Tregs in a CD25 humanized mouse model. Subsequently, we verified that the humanized 7B7, named as h7B7-15S, has comparable activities to 7B7, and that its Treg depletion is further increased when combined with anti-CTLA-4, leading to enhanced remodeling of the tumor immune microenvironment. Moreover, our findings reveal that the Fab form of h7B7-15S has the ability to deplete Tregs, independent of the Fc region. Taken together, our studies expand the application of anti-CD25 in tumor immunotherapy and provide insight into the underlying mechanism.


Assuntos
Anticorpos Monoclonais , Neoplasias , Camundongos , Animais , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Imunossupressores , Linfócitos T Reguladores , Microambiente Tumoral
5.
Hum Mol Genet ; 31(15): 2595-2605, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35288736

RESUMO

Prior studies have shown that genetic factors play important roles in ovarian endometriosis. Herein, we first analyzed the whole-exome sequencing data from 158 patients with ovarian endometriosis and 385 local control women without endometriosis. Among which, a rare missense variant in the MMP7 (p.I79T, rs150338402) gene exhibited a significant frequency difference. This rare variant was screened in an additional 1176 patients and 600 control women via direct DNA sequencing. Meanwhile, a total of 38 available clinical characteristics were collected. Our results showed 45 out of 1334 (3.37%) patients, while 15 out of 985 control women (1.52%) (P = 0.0076) harbored this rare variant, respectively. This rare variant was associated with clinical features such as follicle-stimulating hormone (Padj = 0.0342), luteinizing hormone (Padj = 0.0038), progesterone (Padj = 1.4e-7), testosterone (Padj = 0.0923), total bilirubin (Padj = 0.0699), carcinoembryonic antigen (Padj = 0.0665) and squamous cell carcinoma antigen (Padj = 0.0817), respectively. Functional assays showed that this rare variant could promote cell migration, invasion, epithelial-mesenchymal transition (EMT) and increase the proteolytic protein activity of MMP7, implicating that the increased capacities of cell invasion, migration and EMT might be mediated by enhanced proteolytic activity of MMP7 mutant. These results showed that the MMP7 rare missense variant (p.I79T) played important roles in the pathogenesis of ovarian endometriosis. In conclusion, we identified, for the first time, a significantly enriched MMP7 rare variant in ovarian endometriosis; this rare variant was closely associated with certain clinical features in ovarian endometriosis; thus, it could be a promising early diagnostic biomarker for this disease.


Assuntos
Endometriose , Metaloproteinase 7 da Matriz/genética , Neoplasias Ovarianas , Endometriose/genética , Transição Epitelial-Mesenquimal , Feminino , Humanos , Metaloproteinase 7 da Matriz/metabolismo , Mutação de Sentido Incorreto/genética , Neoplasias Ovarianas/patologia , Sequenciamento do Exoma
6.
Anal Chem ; 96(1): 381-387, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38154078

RESUMO

Artificial olfactory systems have been widely used in medical fields such as in the analysis of volatile organic compounds (VOCs) in human exhaled breath. However, there is still an urgent demand for a portable, accurate breath VOC analysis system for the healthcare industry. In this work, we proposed a Janus colorimetric face mask (JCFM) for the comfortable evaluation of breath ammonia levels by combining the machine learning K-nearest neighbor (K-NN) algorithm. Such a Janus fabric is designed for the unidirectional penetration of exhaled moisture, which can reduce stickiness and ensure facial dryness and comfort. Four different pH indicators on the colorimetric array serve as recognition elements that cross-react with ammonia, capturing the optical fingerprint information on breath ammonia by mimicking the sophisticated olfactory structure of mammals. The Euclidean distance (ED) is used to quantitatively describe the ammonia concentration between 1 ppm and 10 ppm, indicating that there is a linear relationship between the ammonia concentration and the ED response (R2 = 0.988). The K-NN algorithm based on RGB response features aids in the analysis of the target ammonia level and achieves a prediction accuracy of 96%. This study integrates colorimetry, Janus design, and machine learning to present a wearable and portable sensing system for breath ammonia analysis.


Assuntos
Amônia , Compostos Orgânicos Voláteis , Humanos , Amônia/análise , Colorimetria , Máscaras , Testes Respiratórios , Compostos Orgânicos Voláteis/análise
7.
Cell Mol Neurobiol ; 44(1): 24, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372822

RESUMO

Neuroinflammation is an important pathogenesis of neurological diseases and causes a series of physiopathological changes, such as abnormal activation of glial cells, neuronal degeneration and death, and disruption of the blood‒brain barrier. Therefore, modulating inflammation may be an important therapeutic tool for treating neurological diseases. Mesenchymal stem cells (MSCs), as pluripotent stem cells, have great therapeutic potential for neurological diseases due to their regenerative ability, immunity, and ability to regulate inflammation. However, recent studies have shown that MSC-derived exosomes (MSC-Exos) play a major role in this process and play a key role in neuroprotection by regulating neuroglia. This review summarizes the recent progress made in regulating neuroinflammation by focusing on the mechanisms by which MSC-Exos are involved in the regulation of glial cells through signaling pathways such as the TLR, NF-κB, MAPK, STAT, and NLRP3 pathways to provide some references for subsequent research and therapy.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Humanos , Doenças Neuroinflamatórias , Inflamação , Barreira Hematoencefálica
8.
FASEB J ; 37(3): e22802, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36786696

RESUMO

Recurrent spontaneous abortion (RSA) is characterized by two or more consecutive pregnancy losses in the first trimester of pregnancy, experienced by 5% of women during their reproductive age. As a complex pathological process, the etiology of RSA remains poorly understood. Recent studies have established that gene expression changes dramatically in human endometrial stromal cells (ESCs) during decidualization. N6-methyladenosine (m6 A) modification is the most prevalent epigenetic modification of mRNA in eukaryotic cells and it is closely related to the occurrence and development of many pathophysiological phenomena. In this study, we first confirmed that high levels of m6 A mRNA methylation in decidual tissues are associated with RSA. Then, we used m6 A-modified RNA immunoprecipitation sequence (m6 A-seq) and RNA sequence (RNA-seq) to identify the differentially expressed m6 A methylation in decidual tissues from RSA patients and identified the key genes involved in abnormal decidualization by bioinformatics analysis. Using m6 A-seq, we identified a total of 2169 genes with differentially expressed m6 A methylation, of which 735 m6 A hypermethylated genes and 1434 m6 A hypomethylated genes were identified. Further joint analysis of m6 A-seq and RNA-seq revealed that 133 genes were m6 A modified with mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in environmental information processing pathways, including the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathway. In summary, this study uncovered the transcriptome-wide m6 A modification pattern in decidual tissue of RSA, which provides a theoretical basis for further research into m6 A modification and new therapeutic strategies for RSA.


Assuntos
Aborto Habitual , Fosfatidilinositol 3-Quinases , Gravidez , Humanos , Feminino , Metilação , Transcriptoma , Adenosina/genética
9.
Langmuir ; 40(20): 10580-10588, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38728752

RESUMO

Porous composites, such as polyimide and polyetheretherketone (PEEK) polymer composites, became more attractive as a result of excellent specific strength, lightweightness, and smart lubrication. However, revealing the influence of a porous filler on the friction behaviors of polymer composites remains a challenge. The current work examines the effects of the pore structure and wettability on the mechanical and tribological performances of polymer composites reinforced with fillers. Three kinds of particles (non-porous, porous, and oleophobic porous) act as fillers within PEEK, respectively. It was identified that adding porous zeolite particles into PEEK slightly decreased the mechanical property. The zeolite particles significantly increased the oil adsorption of the composite, leading to a significant increase in the friction coefficient at 10 wt % content. However, the friction coefficient of the PEEK composite filled with 20 wt % modified zeolite was relatively low as a result of the weak adsorption. The interface analyses indicated that the thickness of the oil film was controlled via porous structures, changing the lubrication regime of the tribopair. The reason is the appropriate adsorption of oil and the release of zeolite from the composites during the friction process. These results can offer technical guidance to control the friction behaviors of composites under oil-lubricating conditions by a porous particle and pore modification.

10.
Eur Radiol ; 34(7): 4417-4426, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38127074

RESUMO

OBJECTIVES: To predict the functional outcome of patients with intracerebral hemorrhage (ICH) using deep learning models based on computed tomography (CT) images. METHODS: A retrospective, bi-center study of ICH patients was conducted. Firstly, a custom 3D convolutional model was built for predicting the functional outcome of ICH patients based on CT scans from randomly selected ICH patients in H training dataset collected from H hospital. Secondly, clinical data and radiological features were collected at admission and the Extreme Gradient Boosting (XGBoost) algorithm was used to establish a second model, named the XGBoost model. Finally, the Convolution model and XGBoost model were fused to build the third "Fusion model." Favorable outcome was defined as modified Rankin Scale score of 0-3 at discharge. The prognostic predictive accuracy of the three models was evaluated using an H test dataset and an external Y dataset, and compared with the performance of ICH score and ICH grading scale (ICH-GS). RESULTS: A total of 604 patients with ICH were included in this study, of which 450 patients were in the H training dataset, 50 patients in the H test dataset, and 104 patients in the Y dataset. In the Y dataset, the areas under the curve (AUCs) of the Convolution model, XGBoost model, and Fusion model were 0.829, 0.871, and 0.905, respectively. The Fusion model prognostic performance exceeded that of ICH score and ICH-GS (p = 0.043 and p = 0.045, respectively). CONCLUSIONS: Deep learning models have good accuracy for predicting functional outcome of patients with spontaneous intracerebral hemorrhage. CLINICAL RELEVANCE STATEMENT: The proposed deep learning Fusion model may assist clinicians in predicting functional outcome and developing treatment strategies, thereby improving the survival and quality of life of patients with spontaneous intracerebral hemorrhage. KEY POINTS: • Integrating clinical presentations, CT images, and radiological features to establish deep learning model for functional outcome prediction of patients with intracerebral hemorrhage. • Deep learning applied to CT images provides great help in prognosing functional outcome of intracerebral hemorrhage patients. • The developed deep learning model performs better than clinical prognostic scores in predicting functional outcome of patients with intracerebral hemorrhage.


Assuntos
Hemorragia Cerebral , Aprendizado Profundo , Alta do Paciente , Tomografia Computadorizada por Raios X , Humanos , Hemorragia Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Valor Preditivo dos Testes
11.
Diabetes Obes Metab ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698647

RESUMO

AIM: To evaluate gastric emptying (GE) and the glycaemic response to a 75-g oral glucose load in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12-15 months after insulin pump therapy. MATERIALS AND METHODS: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75-g glucose drink containing 150 mg 13C-acetate, to determine the gastric half-emptying time, and underwent assessment of plasma glucose and serum insulin, C-peptide and glucagon-like peptide-1 (GLP-1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re-assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12-15 months, GE was re-measured in 14 of the T2D participants. RESULTS: At baseline, participants with T2D exhibited substantially augmented fasting and post-glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP-1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP-1 secretion was attenuated, fasting and post-glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12-15 months of follow-up. CONCLUSIONS: In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short-term insulin pump therapy. The effect on GE is maintained for at least 12 months.

12.
Diabetes Obes Metab ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698649

RESUMO

AIM: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). METHODS: In cohort 1, 70 newly diagnosed, treatment-naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75-g glucose drink containing 150 mg 13C-acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi-solid mashed potato meal, labelled with 100 µl 13C-octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). RESULTS: Gastric emptying was slower in female than male subjects in both cohorts (both p < .01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p < .05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p < .001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p < .05). CONCLUSIONS: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume-adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D.

13.
Environ Sci Technol ; 58(14): 6226-6235, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38557021

RESUMO

The updated climate models provide projections at a fine scale, allowing us to estimate health risks due to future warming after accounting for spatial heterogeneity. Here, we utilized an ensemble of high-resolution (25 km) climate simulations and nationwide mortality data from 306 Chinese cities to estimate death anomalies attributable to future warming. Historical estimation (1986-2014) reveals that about 15.5% [95% empirical confidence interval (eCI):13.1%, 17.6%] of deaths are attributable to nonoptimal temperature, of which heat and cold corresponded to attributable fractions of 4.1% (eCI:2.4%, 5.5%) and 11.4% (eCI:10.7%, 12.1%), respectively. Under three climate scenarios (SSP126, SSP245, and SSP585), the national average temperature was projected to increase by 1.45, 2.57, and 4.98 °C by the 2090s, respectively. The corresponding mortality fractions attributable to heat would be 6.5% (eCI:5.2%, 7.7%), 7.9% (eCI:6.3%, 9.4%), and 11.4% (eCI:9.2%, 13.3%). More than half of the attributable deaths due to future warming would occur in north China and cardiovascular mortality would increase more drastically than respiratory mortality. Our study shows that the increased heat-attributable mortality burden would outweigh the decreased cold-attributable burden even under a moderate climate change scenario across China. The results are helpful for national or local policymakers to better address the challenges of future warming.


Assuntos
Temperatura Baixa , Temperatura Alta , Temperatura , Cidades , China/epidemiologia , Mudança Climática , Mortalidade
14.
Appl Opt ; 63(6): 1538-1545, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38437366

RESUMO

Frequency-modulated continuous-wave (FMCW) laser ranging technology is an important development direction of light detection and ranging (LiDAR) for the future. It has the advantages of high ranging accuracy, high resolution, wide range, and no ranging blind zone. A distributed feedback laser can be used as a high-quality light source in FMCW laser ranging systems because of its wide frequency modulation range, simple frequency modulation mode, and small package. Aiming at the nonlinear problem of the laser in the frequency modulation process, we present a novel, to our knowledge, predistortion algorithm based on interpolation linear fitting to enhance the linearity of the FMCW laser for LiDAR systems. The sweeping frequency curve of the laser is obtained using the Hilbert transform, and then the sweeping frequency curve is segmented and linearly fitted to calculate the interpolated driving current signals corresponding to linear frequency changes. Using this method, we achieved a nonlinearity error lower than 1e-7 for the swept-frequency signal and demonstrated that the ranging error is less than ±5c m at a distance of 100 m in the FMCW system. In addition, we also demonstrated a 3D static object point cloud with high imaging quality. Compared with the iterative predistortion algorithm based on the function fitting, this method avoids fitting errors at the inflection points of the triangular swept-frequency signal and the complexity of multiple iterative calculations. It enables rapid generation of pre-distorted swept-frequency signals, making it particularly suitable for real-time applications of automotive LiDAR systems.

15.
J Enzyme Inhib Med Chem ; 39(1): 2296355, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38234133

RESUMO

Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.


Assuntos
Artrite Reumatoide , Diterpenos , Orthosiphon , Humanos , Orthosiphon/química , Orthosiphon/metabolismo , Abietanos , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa , Diterpenos/farmacologia , Diterpenos/química , NF-kappa B/metabolismo
16.
Plant Dis ; 108(3): 550-557, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37807086

RESUMO

Almond band canker and prune Cytospora canker have become more severe in the last decade, especially in young orchards, in California. To test our hypothesis that young trees from nurseries could carry the canker-causing pathogens at latency phase to new orchards through transplanting, a multiyear survey on latent infection of canker-causing pathogens of budwood and young trees of almond and prune nurseries in California was conducted. A total of more than 1,730 samples including shoots of rootstocks and scions and grafting union cuttings were collected from 11 nurseries. A real-time quantitative PCR assay was applied to quantify the latent infection levels by six canker-causing pathogen taxa: Botryosphaeria dothidea and species of Cytospora, Diplodia, Lasiodiplodia, Neofusicoccum, and Phomopsis. For almond, the average incidences of latent infection caused by Lasiodiplodia spp. (43.6%) and Neofusicoccum spp. (24.2%) were significantly greater than those by the other four pathogen taxa. The molecular severity (MS) of latent infection caused by Neofusicoccum spp. (3.6) was significantly greater than those caused by other pathogen taxa, except for Lasiodiplodia spp. (2.6). For prune, the average incidence of latent infection caused by Cytospora spp. (13.5%) was significantly higher than those caused by B. dothidea (1.5%) and Diplodia spp. (1.3%) but not significantly higher than those caused by Lasiodiplodia spp. (6.9%), Neofusicoccum spp. (6.3%), and Phomopsis spp. (7.7%), respectively. Moreover, the average MS values caused by Cytospora spp. (3.8) and Neofusicoccum spp. (3.2) were the highest followed by those caused by B. dothidea (1.4), Lasiodiplodia spp. (2.2), and Phomopsis spp. (2.3). Different almond varieties showed various levels of susceptibilities to different canker-causing pathogens. This study concluded that Lasiodiplodia and Neofusicoccum are the predominant pathogen species in almond, and Cytospora is the most important canker-causing pathogen species in prune in nurseries. These findings confirmed the observations of predominancy of canker-causing pathogens in almond and prune orchards in California.


Assuntos
Berçários para Lactentes , Prunus dulcis , Humanos , Prunus dulcis/genética , Árvores , Doenças das Plantas , California
17.
Nano Lett ; 23(5): 1865-1871, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36790333

RESUMO

The urgent demand for atomically thin, superlubricating, and super wear-resistant materials in micro/nanoelectromechanical systems has stimulated the research of friction-reducing and antiwear materials. However, the fabrication of subnanometer-thick films with superlubricating and super wear-resistant properties under ambient conditions remains a huge challenge. Herein, high-quality monolayer (ML) NbSe2 (∼0.8 nm) with ultralow friction and super wear resistance in an atmospheric environment was successfully grown by chemical vapor deposition (CVD) for the first time. Moreover, compared with few-layered (FL) NbSe2, ML NbSe2 has a lower friction coefficient and better wear resistance. On the basis of density function theory (DFT) calculations, the adhesion and the degree of charge transfer between ML NbSe2 and the substrate is larger than that of the topmost layer to the underlying layers of NbSe2 with two or more layers, which can be used to explain that the ML NbSe2 favors ultralow friction and super wear resistance.

18.
J Environ Manage ; 362: 121250, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833921

RESUMO

To investigate the impact and mechanism of Cd-tolerant bacteria in soil on promoting Cd accumulation in Ageratum conyzoides L., we verified the impact of inoculating two strains, B-1 (Burkholderia contaminans HA09) and B-7 (Arthrobacter humicola), on Cd accumulation in A. conyzoides through a pot experiment. Additionally, we investigated the dissolution of CdCO3 and nutrient elements, as well as the release of indoleacetic acid (IAA) by the two strains. The results showed that both strains can significantly improve the dissolution of CdCO3. Strains B-1 and B-7 had obvious effect of dissolving phosphorus, which was 5.63 and 2.76 times higher than that of the control group, respectively. Strain B-7 had significant effect of dissolution potassium, which was 1.79 times higher than that of the control group. Strains B-1 and B-7 had significant nitrogen fixation effect, which was 29.53 and 44.39 times higher than that of the control group, respectively. In addition, inoculating with strain B-1 and B-7 significantly increased the Cd extraction efficiency of A. conyzoides (by 114% and 45% respectively) through enhancing Cd accumulation and the biomass of A. conyzoides. Furthermore, the inoculation of strain B-1 and B-7 led to a significant increase in the activities of CAT and SOD, as well as the content of chlorophyll a and total chlorophyll in the leaves of A. conyzoides. To sum up, strain B-1 and B-7 can promote the phytoremediation efficiency of A. conyzoides on Cd by promoting the biomass and Cd accumulation of A. conyzoides.


Assuntos
Ageratum , Arthrobacter , Biodegradação Ambiental , Cádmio , Poluentes do Solo , Cádmio/metabolismo , Arthrobacter/metabolismo , Poluentes do Solo/metabolismo , Ageratum/metabolismo , Burkholderia/metabolismo , Ácidos Indolacéticos/metabolismo
19.
Heart Lung Circ ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38876846

RESUMO

BACKGROUND: Occurrence of chronic thromboembolic disease (CTED) after 3 or 6 months of standard and effective anticoagulation is not uncommon in patients with acute pulmonary embolism (PE). To date, there has been no scoring model for the prediction of CTED occurrence. METHODS: A Prediction Rule for CTED (PRC) was established in the establishment cohort (n=1,124) and then validated in the validation cohort (n=211). Both original and simplified versions of the PRC score were provided by using different scoring and cut-offs. RESULTS: The PRC score included 10 items: active cancer (3.641; 2.338-4.944; p<0.001), autoimmune diseases (2.218; 1.545-2.891; p=0.001), body mass index >30 kg/m2 (2.186; 1.573-2.799; p=0.001), chronic immobility (2.135; 1.741-2.529; p=0.001), D-dimer >2,000 ng/mL (1.618; 1.274-1.962; p=0.005), PE with deep vein thrombosis (3.199; 2.356-4.042; p<0.001), previous venous thromboembolism (VTE) history (5.268; 3.472-7.064; p<0.001), thromboembolism besides VTE (4.954; 3.150-6.758; p<0.001), thrombophilia (3.438; 2.573-4.303; p<0.001), and unprovoked VTE (2.227; 1.471-2.983; p=0.001). In the establishment cohort, the sensitivity, specificity, Youden index (YI), and C-index were 85.5%, 79.7%, 0.652, and 0.821 (0.732-0.909) when using the original PRC score, whereas they were 87.9%, 74.6%, 0.625, and 0.807 (0.718-0.897) when using the simplified one, respectively (Kappa coefficient 0.819, p-value of McNemar's test 0.786). In the validation cohort, the sensitivity, specificity, YI, and C-index were 86.3%, 76.3%, 0.626, and 0.815 (0.707-0.923) when using the original PRC score, whereas they were 85.0%, 78.6%, 0.636, and 0.818 (0.725-0.911) when using the simplified one, respectively (Kappa coefficient 0.912, p-value of McNemar's test 0.937); both were better than that of the DASH score (72.5%, 69.5%, 0.420, and 0.621 [0.532-0.710]). CONCLUSIONS: A prediction score for CTED occurrence, termed PRC, predicted the likelihood of CTED occurrence after 3 or 6 months of standard anticoagulation in hospitalised patients with a diagnosis of acute PE.

20.
J Am Chem Soc ; 145(13): 7101-7106, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36961355

RESUMO

Interest in main group chemistry related to the Haber-Bosch process has drawn less attention than that of transition metal species. Herein, we show that the steric demands in (tBuO2CN)2 block initial interaction of B(C6F5)3 with nitrogen and prompt loss of methylpropene and CO2 to diazene (N2H2) borane adduct 1 and the analogous hydrazine (N2H4) adduct 2. These species react with basic phosphines to give anions of 3 and 5 containing N2H and N2H3 fragments, respectively. While these species are not derived directly from N2, they represent metal-free species containing N2Hn (n = 1-4) fragments, which model plausible intermediates in the reduction of N2.

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