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1.
BMJ Health Care Inform ; 28(1)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34642176

RESUMO

BACKGROUND: Despite wide usage across all areas of medicine, it is uncertain how useful standard reference ranges of laboratory values are for critically ill patients. OBJECTIVES: The aim of this study is to assess the distributions of standard laboratory measurements in more than 330 selected intensive care units (ICUs) across the USA, Amsterdam, Beijing and Tarragona; compare differences and similarities across different geographical locations and evaluate how they may be associated with differences in length of stay (LOS) and mortality in the ICU. METHODS: A multi-centre, retrospective, cross-sectional study of data from five databases for adult patients first admitted to an ICU between 2001 and 2019 was conducted. The included databases contained patient-level data regarding demographics, interventions, clinical outcomes and laboratory results. Kernel density estimation functions were applied to the distributions of laboratory tests, and the overlapping coefficient and Cohen standardised mean difference were used to quantify differences in these distributions. RESULTS: The 259 382 patients studied across five databases in four countries showed a high degree of heterogeneity with regard to demographics, case mix, interventions and outcomes. A high level of divergence in the studied laboratory results (creatinine, haemoglobin, lactate, sodium) from the locally used reference ranges was observed, even when stratified by outcome. CONCLUSION: Standardised reference ranges have limited relevance to ICU patients across a range of geographies. The development of context-specific reference ranges, especially as it relates to clinical outcomes like LOS and mortality, may be more useful to clinicians.

2.
J Pharmacol Exp Ther ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465632

RESUMO

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration (RCTR1) is an endogenous lipid mediator derived from DHA, exerting pro-resolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in Lipopolysaccharide-induced ARDS/ALI rat model. Rats were injected with RCTR1 (5 µg/kg) via caudal veins 8h after LPS (14 mg/kg) treatment, then AFC was estimated after 1h of ventilation. Primary type II alveolar epithelial cells (AEC II) were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 h. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase, and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased Nedd4-2 level via up-regulating P-Akt expression. Besides, inhibitors of ALX, cAMP, and PI3K (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase, and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. Significance Statement 1.RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. 2. RCTR1 up-regulates the expression of ENaC and Na, K-ATPase in vivo and in vitro to accelerate the AFC. 3. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent.

3.
J Genet Genomics ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34391677

RESUMO

Plants have a close relationship with their root microbiota, which comprises a complex microbial network. Histone methylation is an important epigenetic modification influencing multiple plant traits; however, little is known about the role of plant histone methylation in the assembly and network structure of the root microbiota. In this study, we established that the rice (Oryza sativa) histone methylation regulates the structure and composition of the root microbiota, especially the hub species in the microbial network. DJ-jmj703 (defective in histone H3K4 demethylation) and ZH11-sdg714 (defective in H3K9 methylation) showed significant different root microbiota compared with the corresponding wild types at the phylum and family levels, with a consistent increase in the abundance of Betaproteobacteria and a decrease in the Firmicutes. In the root microbial network, 35 of 44 hub species in the top 10 modules in the tested field were regulated by at least one histone methylation-related gene. These observations establish that the rice histone methylation plays a pivotal role in regulating the assembly of the root microbiota, providing insights into the links between plant epigenetic regulation and root microbiota.

4.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(4): 753-763, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34459176

RESUMO

As a low-load physiological monitoring technology, wearable devices can provide new methods for monitoring, evaluating and managing chronic diseases, which is a direction for the future development of monitoring technology. However, as a new type of monitoring technology, its clinical application mode and value are still unclear and need to be further explored. In this study, a central monitoring system based on wearable devices was built in the general ward (non-ICU ward) of PLA General Hospital, the value points of clinical application of wearable physiological monitoring technology were analyzed, and the system was combined with the treatment process and applied to clinical monitoring. The system is able to effectively collect data such as electrocardiogram, respiration, blood oxygen, pulse rate, and body position/movement to achieve real-time monitoring, prediction and early warning, and condition assessment. And since its operation from March 2018, 1 268 people (657 patients) have undergone wearable continuous physiological monitoring until January 2020, with data from a total of 1 198 people (632 cases) screened for signals through signal quality algorithms and manual interpretation were available for analysis, accounting for 94.48 % (96.19%) of the total. Through continuous physiological data analysis and manual correction, sleep apnea event, nocturnal hypoxemia, tachycardia, and ventricular premature beats were detected in 232 (36.65%), 58 (9.16%), 30 (4.74%), and 42 (6.64%) of the total patients, while the number of these abnormal events recorded in the archives was 4 (0.63%), 0 (0.00%), 24 (3.80%), and 15 (2.37%) cases. The statistical analysis of sleep apnea event outcomes revealed that patients with chronic diseases were more likely to have sleep apnea events than healthy individuals, and the incidence was higher in men (62.93%) than in women (37.07%). The results indicate that wearable physiological monitoring technology can provide a new monitoring mode for inpatients, capturing more abnormal events and provide richer information for clinical diagnosis and treatment through continuous physiological parameter analysis, and can be effectively integrated into existing medical processes. We will continue to explore the applicability of this new monitoring mode in different clinical scenarios to further enrich the clinical application of wearable technology and provide richer tools and methods for the monitoring, evaluation and management of chronic diseases.


Assuntos
Síndromes da Apneia do Sono , Dispositivos Eletrônicos Vestíveis , Frequência Cardíaca , Humanos , Monitorização Fisiológica , Movimento
5.
JMIR Mhealth Uhealth ; 9(8): e25415, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34387554

RESUMO

BACKGROUND: With the development and promotion of wearable devices and their mobile health (mHealth) apps, physiological signals have become a research hotspot. However, noise is complex in signals obtained from daily lives, making it difficult to analyze the signals automatically and resulting in a high false alarm rate. At present, screening out the high-quality segments of the signals from huge-volume data with few labels remains a problem. Signal quality assessment (SQA) is essential and is able to advance the valuable information mining of signals. OBJECTIVE: The aims of this study were to design an SQA algorithm based on the unsupervised isolation forest model to classify the signal quality into 3 grades: good, acceptable, and unacceptable; validate the algorithm on labeled data sets; and apply the algorithm on real-world data to evaluate its efficacy. METHODS: Data used in this study were collected by a wearable device (SensEcho) from healthy individuals and patients. The observation windows for electrocardiogram (ECG) and respiratory signals were 10 and 30 seconds, respectively. In the experimental procedure, the unlabeled training set was used to train the models. The validation and test sets were labeled according to preset criteria and used to evaluate the classification performance quantitatively. The validation set consisted of 3460 and 2086 windows of ECG and respiratory signals, respectively, whereas the test set was made up of 4686 and 3341 windows of signals, respectively. The algorithm was also compared with self-organizing maps (SOMs) and 4 classic supervised models (logistic regression, random forest, support vector machine, and extreme gradient boosting). One case validation was illustrated to show the application effect. The algorithm was then applied to 1144 cases of ECG signals collected from patients and the detected arrhythmia false alarms were calculated. RESULTS: The quantitative results showed that the ECG SQA model achieved 94.97% and 95.58% accuracy on the validation and test sets, respectively, whereas the respiratory SQA model achieved 81.06% and 86.20% accuracy on the validation and test sets, respectively. The algorithm was superior to SOM and achieved moderate performance when compared with the supervised models. The example case showed that the algorithm was able to correctly classify the signal quality even when there were complex pathological changes in the signals. The algorithm application results indicated that some specific types of arrhythmia false alarms such as tachycardia, atrial premature beat, and ventricular premature beat could be significantly reduced with the help of the algorithm. CONCLUSIONS: This study verified the feasibility of applying the anomaly detection unsupervised model to SQA. The application scenarios include reducing the false alarm rate of the device and selecting signal segments that can be used for further research.

6.
Acta Neurol Belg ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34339020
7.
Environ Sci Technol ; 55(15): 10300-10309, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34296598

RESUMO

Atmospheric black carbon (BC) concentrations are governed by both emissions and meteorological conditions. Distinguishing these effects enables quantification of the effectiveness of emission mitigation actions by excluding meteorological effects. Here, we develop reduced-form models in both direct (RFDMs) and inverse (RFIMs) modes to estimate ambient BC concentrations. The models were developed based on outputs from multiyear simulations under three conditional scenarios with realistic or fixed emissions and meteorological conditions. We established a set of probabilistic functions (PFs) to quantify the meteorological influences. A significant two-way linear relationship between multiyear annual emissions and mean ambient BC concentrations was revealed at the grid cell scale. The correlation between them was more significant at grid cells with high emission densities. The concentrations and emissions at a given grid cell are also significantly correlated with emissions and concentrations of the surrounding areas, respectively, although to a lesser extent. These dependences are anisotropic depending on the prevailing winds and source regions. The meteorologically induced variation at the monthly scale was significantly higher than that at the annual scale. Of the major meteorological parameters, wind vectors, temperature, and relative humidity were found to most significantly affect variation in ambient BC concentrations.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Meteorologia , Fuligem/análise , Vento
8.
Talanta ; 233: 122519, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215134

RESUMO

Inflammatory bowel disease has become a global burden given its high incidence and refractory to medical treatment. Improved diagnostic strategies to monitor disease activity more accurately are necessary to conduct and evaluate medical treatment. High level of neutrophil infiltration in colon is associated with poor prognosis and enhanced risk of developing colitis-associated cancer. Herein, to accurately monitor neutrophil levels in colitis condition, we designed and constructed a specific probe (CPM), consisting of a neutrophil formyl peptide receptor targeting group (cFLFLFK), a short PEG linker and a near-infrared fluorescent dye. CPM selectively identified neutrophils in vitro and preferentially recognized neutrophils in vivo with enhanced targeting ability and biodistribution property. After verified the ability to target activated neutrophils, CPM was used to detect neutrophils in experimental colitis by systemic and topical administration. Compared to systemic administration, topical administration of CPM allows lower dosage, higher target-to-background ratio and longer duration of effective monitoring. More importantly, we used CPM to assess neutrophil levels in the course of colitis development. The fluorescence intensity of CPM increased along with colitis progression. Additionally, CPM was used to detected neutrophil levels in colitis-associated cancer and enhanced neutrophil infiltration in the tumor sites was detected. In conclusion, the probe CPM is a promising tool for in vivo improved diagnosis of colitis severity by monitoring the extent of neutrophil infiltration.


Assuntos
Colite , Neutrófilos , Administração Tópica , Colite/induzido quimicamente , Colite/diagnóstico , Corantes Fluorescentes , Humanos , Distribuição Tecidual
9.
J Clin Lab Anal ; 35(8): e23883, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34184796

RESUMO

PURPOSE: The purpose of this study was to explore the predictive value of the ratio of the product of neutrophils and hemoglobin to lymphocytes (NHL) in patients with non-muscular invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively collected clinical and pathological data of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) at our hospital between 2013 and 2018. The ratio of neutrophils to lymphocytes (NLR), the Systemic Immune Inflammation Index (SII), and NHL were obtained based on routine blood settlement within a week before surgery. The receiver operating characteristic curve was used to determine the optimal cutoff value of each index, and different groups were grouped accordingly. Kaplan-Meier survival curve and Cox regression model were used to study the factors affecting the prognosis of NMIBC patients. RESULTS: There was significant difference in recurrence-free survival (RFS) rate between the high NLR group and the low NLR group, the high SII group and the low SII group, and the high NHL group and the low NHL group. Cox univariate regression analysis showed that tumor number, tumor size, tumor pathological grade, tumor pathological stage, NLR, SII, and NHL were related to postoperative RFS in patients with NMIBC. The tumor number, tumor pathological grade, SII, and NHL were independent predictors of RFS in multivariate analysis. CONCLUSIONS: The preoperative clinical inflammatory indexes NLR, SII, and NHL have certain predictive value for postoperative RFS in NMIBC patients.

10.
Environ Sci Technol ; 55(12): 7869-7879, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34096723

RESUMO

Accurate estimation of black carbon (BC) emissions is essential for assessing the health and climate impact of this pollutant. Past emission inventories were associated with high uncertainty due to data limitations, and recent information has provided a unique updating opportunity. Moreover, understanding the drivers that cause temporal emission changes is of research value. Here, we update the global BC emission estimates using new data on the activities and emission factors (EFs). The new inventory covers 73 detailed sources at 0.1° × 0.1° spatial resolution and monthly temporal resolution from 1960 to 2017. The estimated annual emissions were 32% higher than the average of several previous inventories, which was primarily due to field-measured EFs for residential stoves and differentiated EFs for motor vehicles. In addition, the updated emissions show an inverse U-shaped temporal trend, which was mainly driven by the interaction between the positive effects of population growth, per capita energy consumption, and vehicle fleet and the negative effects of residential energy switching, stove upgrading, phasing out of beehive coke ovens, and reduced EFs for vehicles and industrial processes. Urbanization caused a significant increase in urban emissions accompanied by a more significant decline in rural emissions.


Assuntos
Poluentes Atmosféricos , Utensílios Domésticos , Poluentes Atmosféricos/análise , Carbono , Monitoramento Ambiental , Veículos Automotores , Fuligem/análise , Emissões de Veículos/análise
11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(3): 583-593, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34180205

RESUMO

Wearable physiological parameter monitoring devices play an increasingly important role in daily health monitoring and disease diagnosis/treatment due to their continuous dynamic and low physiological/psychological load characteristics. After decades of development, wearable technologies have gradually matured, and research has expanded to clinical applications. This paper reviews the research progress of wearable physiological parameter monitoring technology and its clinical applications. Firstly, it introduces wearable physiological monitoring technology's research progress in terms of sensing technology and data processing and analysis. Then, it analyzes the monitoring physiological parameters and principles of current medical-grade wearable devices and proposes three specific directions of clinical application research: 1) real-time monitoring and predictive warning, 2) disease assessment and differential diagnosis, and 3) rehabilitation training and precision medicine. Finally, the challenges and response strategies of wearable physiological monitoring technology in the biomedical field are discussed, highlighting its clinical application value and clinical application mode to provide helpful reference information for the research of wearable technology-related fields.


Assuntos
Dispositivos Eletrônicos Vestíveis , Monitorização Fisiológica
12.
Front Immunol ; 12: 666361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168643

RESUMO

The accumulation of macrophages in degenerated discs is a common phenomenon. However, the roles and mechanisms of M2a macrophages in intervertebral disc degeneration (IDD) have not been illuminated. This study investigated the expression of the M2a macrophage marker (CD206) in human and rat intervertebral disc tissues by immunohistochemistry. To explore the roles of M2a macrophages in IDD, nucleus pulposus (NP) cells were co-cultured with M2a macrophages in vitro. To clarify whether the CHI3L1 protein mediates the effect of M2a macrophages on NP cells, siRNA was used to knock down CHI3L1 transcription. To elucidate the underlying mechanisms, NP cells were incubated with recombinant CHI3L1 proteins, then subjected to western blotting analysis of the IL-13Rα2 receptor and MAPK pathway. CD206-positive cells were detected in degenerated human and rat intervertebral disc tissues. Notably, M2a macrophages promoted the expression of catabolism genes (MMP-3 and MMP-9) and suppressed the expression of anabolism genes (aggrecan and collagen II) in NP cells. These effects were abrogated by CHI3L1 knockdown in M2a macrophages. Exposure to recombinant CHI3L1 promoted an extracellular matrix metabolic imbalance in NP cells via the IL-13Rα2 receptor, along with activation of the ERK and JNK MAPK signaling pathways. This study elucidated the roles of M2a macrophages in IDD and identified potential mechanisms for these effects.


Assuntos
Proteína 1 Semelhante à Quitinase-3/imunologia , Matriz Extracelular/metabolismo , Subunidade alfa2 de Receptor de Interleucina-13/metabolismo , Degeneração do Disco Intervertebral/imunologia , Sistema de Sinalização das MAP Quinases , Macrófagos/imunologia , Animais , Proteína 1 Semelhante à Quitinase-3/genética , Proteína 1 Semelhante à Quitinase-3/metabolismo , Matriz Extracelular/patologia , Feminino , Humanos , Degeneração do Disco Intervertebral/patologia , Lectinas Tipo C/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , Masculino , Lectinas de Ligação a Manose/metabolismo , Pessoa de Meia-Idade , Núcleo Pulposo/imunologia , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Ratos , Receptores de Superfície Celular/metabolismo
13.
Small ; : e2101524, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34139101

RESUMO

Thermochemical energy storage (TCES) materials have emerged as a promising alternative to meet the high-temperature energy storage requirements of concentrated solar power plants. However, most of the energy storage materials are facing challenges in redox kinetics and cyclic stability. Iron-doped manganese oxide attracts raising attention due to its non-toxicity, low cost, and high energy capacity over 800 °C. However, there are few investigations on the reversibility enhancement of the redox reaction from the microstructural-evolution-mechanism point of view. Herein, bixbyite-type (Mn0.8 Fe0.2 )2 O3 is synthesized and extruded into honeycomb units, which can maintain an 85% initial capacity after 100 redox cycles. It is also found that a self-assembled core-shell MnFe2 O4 @Mn2.7 Fe0.3 O4 structure forms during the reduction step, and then transforms into a homogeneous solid solution of (Mn0.8 Fe0.2 )2 O3 in the following oxidation step. During the reduction step, shells are formed spontaneously from the Mn2.7 Fe0.3 O4 with the MnFe2 O4 as cores due to the lower surface energy, which facilitates the oxygen adsorption and dissociation during subsequent oxidation step. Through the density functional theory calculation, it is revealed that the lower formation energy of oxygen vacancies in the shell contributes to the improvement of oxygen diffusion rate. This study can provide a guideline to design prospective materials for high-temperature TCES.

14.
Environ Sci Technol ; 55(11): 7316-7326, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33977718

RESUMO

Coal abatement actions for pollution reduction often target total coal consumption. The health impacts of coal uses, however, vary extensively among sectors. Here, we modeled the sectorial contributions of coal uses to emissions, outdoor and indoor PM2.5 (particulate matter with an aerodynamic diameter of less than 2.5 mm) concentrations, exposures, and health outcomes in China from 1970 to 2014. We show that in 2014, residential coal accounted for 2.9% of total energy use but 34% of premature deaths associated with PM2.5 exposure, showing that effects were magnified substantially along the causal path. The number of premature deaths attributed to unit coal consumption in the residential sector was 40 times higher than that in the power and industrial sectors. Emissions of primary PM2.5 were more important than secondary aerosol precursors in terms of health consequences, and indoor exposure accounted for 97% and 91% of total premature deaths attributable to PM2.5 from coal combustion in 1974 and 2014, respectively. Our assessment raises a critical challenge in the switching of residential coal uses to effectively mitigate PM2.5 exposure in the Chinese population.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Carvão Mineral/análise , Material Particulado/análise
15.
J Mater Chem B ; 9(22): 4577-4586, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34047746

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with limited diagnosis. Mesenchymal epithelial transition factor (c-Met) has become a hot target for cancer diagnosis and therapy, which is overexpressed in HCC. In this study, we labeled a novel c-Met targeting peptide YQ-M3 with a near-infrared fluorescent dye MPA and a radionuclide technetium-99m for HCC detection. YQ-M3-MPA showed high affinity for c-Met positive HepG2 tumor in vitro and higher tumor uptake and higher T/N ratio than GE137-MPA (a positive tracer for c-Met) in HepG2 tumor-bearing mice in vivo by fluorescence imaging. In addition, 99mTc-HYNIC-YQ-M3 also showed significant tumor uptake in vivo through SPECT imaging. These results indicated that c-Met positive tumors were successfully detected via fluorescence and SPECT imaging using YQ-M3-MPA and 99mTc-HYNIC-YQ-M3, respectively, and further suggested that YQ-M3-MPA and 99mTc-HYNIC-YQ-M3 have some possibly potential clinical applications for HCC diagnosis.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Peptídeos/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Células Hep G2 , Humanos
16.
Nat Commun ; 12(1): 2790, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986286

RESUMO

SARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.


Assuntos
COVID-19/diagnóstico , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Replicação Viral/genética , Animais , COVID-19/imunologia , COVID-19/virologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetinae , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Mesocricetus , Camundongos Endogâmicos BALB C , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Vero , Virulência/genética , Virulência/imunologia
17.
Eur J Med Chem ; 219: 113440, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33892274

RESUMO

Breast cancer is the most dangerous, among all malignant tumors that threaten women's lives and health. Surgical resection can effectively prolong the survival time of patients with early breast cancer. Insulin-like growth factor type 1 receptor (IGF1R) is a member of the large family of receptor tyrosine kinases, and it's significantly overexpressed in breast cancer cells, which make them ideal biomarkers for the diagnosis and surgery navigation of breast cancer. Herein, we developed a series of IGF1R-targeted probes (YQ-L) for fluorescent imaging in breast cancer based on the strategy of drug repositioning. YQ-L exhibited specific IGF1R binding both in vitro and in vivo, especially probe 5d exhibited higher tumor uptake with a high tumor/normal ratio in the MCF-7 tumor bearing mouse. The maximum T/N ratio of probe 5d was 4.9, which was about 3 times that of indocyanine green (ICG). Meanwhile, probe 5d displayed more favorable in vivo pharmacokinetic properties than that of ICG with less hepatic and intestinal uptake. Convenient preparation, excellent IGF1R specificity in breast cancer, rapid clearance from normal organs and good biosafety profiles of probe 5d warrant further investigations for clinical translation in detection and surgery navigation of breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Corantes Fluorescentes/química , Receptor IGF Tipo 1/metabolismo , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/metabolismo , Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Imagem Óptica , Ligação Proteica , Receptor IGF Tipo 1/química , Receptor IGF Tipo 1/genética , Distribuição Tecidual , Transplante Heterólogo
18.
J Hazard Mater ; 411: 125143, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-33858103

RESUMO

The most common environmental pollutants such as cadmium (Cd), glyphosate and tetracycline have led to profoundly adverse impacts on plant productivity. However, how tropical crops such as cassava sense these pollutants via roots and how rhizosphere microbiome interacts with the host and pollutants remain largely unknown. In this study, we found these stresses significantly inhibited plant growth and triggered cell damage in a dosage-dependent manner, and the toxic effect on redox homeostasis was correlated with antioxidant metabolism. Using metagenomics technique, we found the rhizosphere microbiomes dynamically altered as the dose of these stresses increased. We also identified stressor-associated metagenome-assembled genomes and microbial metabolic pathways as well as mobile genetic elements in the rhizosphere microbiomes. Next, a co-occurrence network of both physiological and microbiome features was constructed to explore how these pollutants derived oxidative damage through the microbiome succession. Notably, phyllosphere transplantation of Agrobacterium tumefaciens or Pseudomonas stutzeri can significantly alleviate the negative effects of stresses on cassava growth and redox homeostasis. Collectively, this study demonstrated the dynamics of rhizosphere bacterial microbiome of cassava under three common environmental stresses, and A. tumefaciens and P. stutzeri could be developed as potential beneficial bacteria to alleviate Cd, glyphosate and tetracycline-triggered damage to cassava.


Assuntos
Manihot , Microbiota , Bactérias/genética , Metagenoma , Metagenômica , Microbiota/genética , Raízes de Plantas , Rizosfera , Microbiologia do Solo
19.
JMIR Med Inform ; 9(4): e18803, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33856350

RESUMO

BACKGROUND: Without timely diagnosis and treatment, tachycardia, also called tachyarrhythmia, can cause serious complications such as heart failure, cardiac arrest, and even death. The predictive performance of conventional clinical diagnostic procedures needs improvement in order to assist physicians in detecting risk early on. OBJECTIVE: We aimed to develop a deep tachycardia onset prediction (TOP-Net) model based on deep learning (ie, bidirectional long short-term memory) for early tachycardia diagnosis with easily accessible data. METHODS: TOP-Net leverages 2 easily accessible data sources: vital signs, including heart rate, respiratory rate, and blood oxygen saturation (SpO2) acquired continuously by wearable embedded systems, and electronic health records, containing age, gender, admission type, first care unit, and cardiovascular disease history. The model was trained with a large data set from an intensive care unit and then transferred to a real-world scenario in the general ward. In this study, 3 experiments incorporated merging patients' personal information, temporal memory, and different feature combinations. Six metrics (area under the receiver operating characteristic curve [AUROC], sensitivity, specificity, accuracy, F1 score, and precision) were used to evaluate predictive performance. RESULTS: TOP-Net outperformed the baseline models on the large critical care data set (AUROC 0.796, 95% CI 0.768-0.824; sensitivity 0.753, 95% CI 0.663-0.793; specificity 0.720, 95% CI 0.645-0.758; accuracy 0.721; F1 score 0.718; precision 0.686) when predicting tachycardia onset 6 hours in advance. When predicting tachycardia onset 2 hours in advance with data acquired from our hospital using the transferred TOP-Net, the 6 metrics were 0.965, 0.955, 0.881, 0.937, 0.793, and 0.680, respectively. The best performance was achieved using comprehensive vital signs (heart rate, respiratory rate, and SpO2) statistical information. CONCLUSIONS: TOP-Net is an early tachycardia prediction model that uses 8 types of data from wearable sensors and electronic health records. When validated in clinical scenarios, the model achieved a prediction performance that outperformed baseline models 0 to 6 hours before tachycardia onset in the intensive care unit and 2 hours before tachycardia onset in the general ward. Because of the model's implementation and use of easily accessible data from wearable sensors, the model can assist physicians with early discovery of patients at risk in general wards and houses.

20.
Mol Pharm ; 18(5): 2082-2090, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33797932

RESUMO

The glypican-3 (GPC3) receptor is a membrane protein that is highly expressed in tumor tissues but rarely expressed in the normal liver and can be used as a target for early diagnosis of hepatocellular carcinoma (HCC). Herein, we developed a GPC3-targeted 99mTc-labeled probe for SPECT imaging in HCC. 99mTc-HPG was rapidly radiosynthesized within 20 min with an excellent radiochemical purity (>98%), possessing good stability. Results from in vitro cell binding assays indicated that the binding specificity of 99mTc-HPG to GPC3-positive HepG2 cells was acceptable. For SPECT/CT imaging, the HepG2 tumors were clearly visualized with the highest tumor/muscle ratio (11.55 ± 0.54) at 1 h post-injection, and the tumor uptake of 99mTc-HPG reduced from 2.99 ± 0.15 to 1.17 ± 0.09% ID/g in the blocking study. Convenient preparation, excellent GPC3 specificity in HCC, rapid clearance from normal organs, and good biosafety profiles of 99mTc-HPG warrant further investigations for clinical translation.

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