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1.
Artículo en Inglés | MEDLINE | ID: mdl-33853105

RESUMEN

ABSTRACT: Acetyl fentanyl (AF) is a Schedule I fentanyl analog that has been increasingly seen in heroin and fentanyl polydrug toxicity overdoses in Michigan (MI). Drug users are often unaware of the presence of AF in their drugs because it is often sold mixed into or disguised as heroin. High levels of AF in heroin drug products can cause increased incidence of overdose. This article describes data from a longitudinal opioid surveillance program and details 102 decedents in MI who were found to have evidence of heroin in their postmortem blood. A large portion of these decedents were also found to have evidence of fentanyl and AF. Our data further show significant overlap in incidence rates of AF and heroin-related overdose deaths in several MI counties, suggesting that AF is becoming enmeshed in heroin trafficking. Furthermore, we report unprecedented high incidence rates of AF and heroin-related overdose deaths in Calhoun county, and we propose that it is a high-intensity drug trafficking area. Highways US-131 and US-31 are likely used to transport these drugs. More study is needed into the drug trafficking trends in MI to ascertain drug sources and monitor the ever developing and dangerous polydrug heroin combinations.

2.
Molecules ; 26(7)2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33806149

RESUMEN

Bacillus subtilis SH21 was observed to produce an antifungal protein that inhibited the growth of F. solani. To purify this protein, ammonium sulfate precipitation, gel filtration chromatography, and ion-exchange chromatography were used. The purity of the purified product was 91.33% according to high-performance liquid chromatography results. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed that the molecular weight of the protein is 30.72 kDa. The results of the LC-MS/MS analysis and a subsequent sequence-database search indicated that this protein was a chitosanase, and thus, we named it chitosanase SH21. Scanning and transmission electron microscopy revealed that chitosanase SH21 appeared to inhibit the growth of F. solani by causing hyphal ablation, distortion, or abnormalities, and cell-wall depression. The minimum inhibitory concentration of chitosanase SH21 against F. solani was 68 µg/mL. Subsequently, the corresponding gene was cloned and sequenced, and sequence analysis indicated an open reading frame of 831 bp. The predicted secondary structure indicated that chitosanase SH21 has a typical a-helix from the glycoside hydrolase (GH) 46 family. The tertiary structure shared 40% similarity with that of Streptomyces sp. N174. This study provides a theoretical basis for a topical cream against fungal infections in agriculture and a selection marker on fungi.

3.
Sensors (Basel) ; 21(6)2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33803673

RESUMEN

Robot grasping is an important direction in intelligent robots. However, how to help robots grasp specific objects in multi-object scenes is still a challenging problem. In recent years, due to the powerful feature extraction capabilities of convolutional neural networks (CNN), various algorithms based on convolutional neural networks have been proposed to solve the problem of grasp detection. Different from anchor-based grasp detection algorithms, in this paper, we propose a keypoint-based scheme to solve this problem. We model an object or a grasp as a single point-the center point of its bounding box. The detector uses keypoint estimation to find the center point and regress to all other object attributes such as size, direction, etc. Experimental results demonstrate that the accuracy of this method is 74.3% in the multi-object grasp dataset VMRD, and the performance on the single-object scene Cornell dataset is competitive with the current state-of-the-art grasp detection algorithm. Robot experiments demonstrate that this method can help robots grasp the target in single-object and multi-object scenes with overall success rates of 94% and 87%, respectively.

4.
Biology (Basel) ; 10(4)2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33808347

RESUMEN

Intense and frequent drought events strongly affect plant survival. Non-structural carbohydrates (NSCs) are important "buffers" to maintain plant functions under drought conditions. We conducted a drought manipulation experiment using three-year-old Pinus tabulaeformis Carr. seedlings. The seedlings were first treated under different drought intensities (i.e., no irrigation, severe, and moderate) for 50 days, and then they were re-watered for 25 days to explore the dynamics of NSCs in the leaves, twigs, stems, and roots. The results showed that the no irrigation and severe drought treatments significantly reduced photosynthetic rate by 93.9% and 32.6% for 30 days, respectively, leading to the depletion of the starch storage for hydraulic repair, osmotic adjustment, and plant metabolism. The seedlings under moderate drought condition also exhibited starch storage consumption in leaves and twigs. After re-watering, the reduced photosynthetic rate recovered to the control level within five days in the severe drought group but showed no sign of recovery in the no irrigation group. The seedlings under the severe and moderate drought conditions tended to invest newly fixed C to starch storage and hydraulic repair instead of growth due to the "drought legacy effect". Our findings suggest the depletion and recovery of starch storage are important strategies for P. tabulaeformis seedlings, and they may play key roles in plant resistance and resilience under environmental stress.

5.
Aging (Albany NY) ; 132021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33819192

RESUMEN

Reticulophagy regulator 1 (RETEG1, also known as FAM134B) plays a crucial role in endoplasmic reticulum autophagy. We aimed to explore the effect of FAM134B-mediated endoplasmic reticulum autophagy in sepsis myocardial injury in mice. Sepsis myocardial injury mice were established via cecal ligation and puncture procedures. The expression of FAM134B and LC3-II/I was determined using immunohistochemistry. Myocardial tissue morphological changes and apoptosis were examined using hematoxylin and eosin (H&E) staining and TUNEL analysis. The effects of FAM134B knockdown or overexpression on mice with sepsis myocardial injury were also studied. The levels of TNF-α, IL-6, IL-8, and IL-10 were evaluated using enzyme-linked immunosorbent assay (ELISA). Autophagy- and apoptosis-related protein expression was detected using western blotting. The effect of FAM134B on Lipopolysaccharide (LPS) -induced cardiomyocytes was also studied. The expression of FAM134B and LC3-II/I increased in sepsis mice and lipopolysaccharide (LPS)-treated cardiomyocytes. 3-Methyladenine (3-MA) significantly inhibited FAM134B and LC3-II/I expression and promoted myocardial injury, inflammation response, and cardiomyocyte apoptosis. The overexpression of FAM134B could minimize myocardial injury, inflammation, and apoptosis, whereas FAM134B knockdown showed opposite effects. FAM134B-mediated endoplasmic reticulum autophagy had a protective effect on sepsis myocardial injury in mice by reducing inflammation and tissue apoptosis, which may provide new insights for sepsis myocardial injury therapies.

6.
Rev Sci Instrum ; 92(2): 025010, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33648130

RESUMEN

We propose an improved point cloud global descriptor for recognition and grasping of similar workpieces. In the industry, different types of workpieces need to be recognized precisely in some intelligent systems. Deep learning requires a lot of preparation work, and it is difficult to adapt to the variety of workpieces. Furthermore, traditional descriptors based on point pairs cannot meet the requirements of identification. To solve this problem, the Outline Viewpoint Feature Histogram (Outline-VFH) descriptor remains part of the recognition ability of the Viewpoint Feature Histogram (VFH) descriptor and contains an extra outline description, which is established based on the oriented bounding box theory. To validate the effectiveness of the proposed descriptor, experiments were conducted on public dataset and some physical workpieces. The results show that the Outline-VFH is much better than VFH and some other descriptors on recognition and has great potential in vision-based robot grasping applications.

7.
Anal Chim Acta ; 1152: 338299, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33648636

RESUMEN

Single atom nanomaterials possess catalytic activity like natural enzymes are termed as SAzymes which have gained great attention during last two years because of the maximal utilization of atoms and the benefit of understanding structure-property relationship. However, most of SAzymes are fabricated based on hydrophobic carbon, which disperse poorly in water and exhibit inferior affinity towards substrates, which may limit their biomedical applications. Here, we report a peroxidase-like SAzyme through the post-modification route based on hydrophilic defective metal-organic frameworks. Hydrochloric acid (HCl) is employed as ligand modulator to fabricate defective NH2-UiO-66 nanoparticles (HCl-NH2-UiO-66 NPs). Compared with the NPs fabricated through acetic acid modulation method (Ac-NH2-UiO-66 NPs), HCl-NH2-UiO-66 NPs have more missing linkers. Hence, more Fe(Ⅲ) ions can be successfully doped onto Zr6 clusters in HCl-NH2-UiO-66 NPs in a single atom state via formation of Fe-O-Zr bridge. The HCl-NH2-UiO-66 NPs doped with Fe(Ⅲ) ions (Fe-HCl-NH2-UiO-66 NPs) possess higher peroxidase-like activity than Fe-Ac-NH2-UiO-66 NPs due to the higher loading amount of Fe. Besides, both Fe-HCl-NH2-UiO-66 NPs and Fe-Ac-NH2-UiO-66 NPs exhibit lower Michaelis-Menten constants (Km) for hydrogen peroxide (H2O2) than most reported nanomaterials, indicating their higher affinity to H2O2. Due to their excellent catalytic activity to low concentration of substrates, Fe-HCl-NH2-UiO-66 NPs can detect H2O2 with a limit of detection (LOD) of 1.0 µM. Thus, our system can be used to detect the low cellular H2O2 concentration. With high peroxidase-like activity induced by plenty of single atom Fe(Ⅲ) sites, Fe-HCl-NH2-UiO-66 NPs can also find wide applications in other fields including nanomedicine, pollution degradation and catalysis.

8.
Mol Ther ; 2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33744470

RESUMEN

Abnormal cholesterol/lipid homeostasis is linked to neurodegenerative conditions such as age-related macular degeneration (AMD), which is a leading cause of blindness in the elderly. The most prevalent form, termed "dry" AMD, is characterized by pathological cholesterol accumulation beneath the retinal pigment epithelial (RPE) cell layer and inflammation-linked degeneration in the retina. We show here that the cholesterol-regulating microRNA miR-33 was elevated in the RPE of aging mice. Expression of the miR-33 target ATP-binding cassette transporter (ABCA1), a cholesterol efflux pump genetically linked to AMD, declined reciprocally in the RPE with age. In accord, miR-33 modulated ABCA1 expression and cholesterol efflux in human RPE cells. Subcutaneous delivery of miR-33 antisense oligonucleotides (ASO) to aging mice and non-human primates fed a Western-type high fat/cholesterol diet resulted in increased ABCA1 expression, decreased cholesterol accumulation, and reduced immune cell infiltration in the RPE cell layer, accompanied by decreased pathological changes to RPE morphology. These findings suggest that miR-33 targeting may decrease cholesterol deposition and ameliorate AMD initiation and progression.

9.
Infect Dis Poverty ; 10(1): 32, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33736710

RESUMEN

BACKGROUND: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). METHODS: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

10.
Front Immunol ; 12: 630358, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33746967

RESUMEN

N 6-methyladenosine (m6A) modification, the addition of a methylation decoration at the position of N6 of adenosine, is one of the most prevalent modifications among the over 100 known chemical modifications of RNA. Numerous studies have recently characterized that RNA m6A modification functions as a critical post-transcriptional regulator of gene expression through modulating various aspects of RNA metabolism. In this review, we will illustrate the current perspectives on the biological process of m6A methylation. Then we will further summarize the vital modulatory effects of m6A modification on immunity, viral infection, and autoinflammatory disorders. Recent studies suggest that m6A decoration plays an important role in immunity, viral infection, and autoimmune diseases, thereby providing promising biomarkers and therapeutic targets for viral infection and autoimmune disorders.

11.
Pediatr Neonatol ; 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33753004

RESUMEN

BACKGROUND: Diabetes during pregnancy is associated with an increased risk of foetal and neonatal complications and long-term complications in the offspring. Brain-derived neurotrophic factor (BDNF), a neurotrophin that has a crucial role in neurogenesis modulation and neural pathway maturation during neurodevelopment, may have a role in protecting neurons against injury and diseases by modulating glucose metabolism. The aim of this study was to investigate the possible relationship between the serum BDNF levels of infants of mothers with gestational diabetes (IMGD) and neurodevelopmental outcomes of the children after birth. METHODS: A total of 24 candidates, including 8 IMGD and 16 healthy infants, were recruited for the study. Medical records were reviewed. Serum BDNF levels of the study participants were collected at birth and at 6 and 12 months of age. Developmental outcomes of each candidate were assessed using the Bayley Scales of Infant Development III (BSID III) at 6 and 12 months of corrected age. RESULTS: Compared to non-IMGD, IMGD had greater mean body weight (p = 0.04) and height (p < 0.01) at age 12 months. The language composite score was significantly lower in IMGD at 12 months of age (p = 0.038). The BDNF content was significantly higher in the non-IMGD than in the IMGD group at 12 months of age (p = 0.013). CONCLUSION: In this study, we demonstrated that infants of mothers with gestational diabetes do worse in language development and have lower BDNF levels at 12 months of age. There may be a close correlation between language outcomes and serum BDNF levels at 12 months of age. A follow-up study on future developmental status is warranted.

12.
Antiviral Res ; 189: 105061, 2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33705864

RESUMEN

Coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may result in severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that HBV replication is suppressed by replicating HCV and often rebounds after treatment with drugs against HCV. Thus, a highly efficient cell culture system permissive for HBV/HCV would facilitate investigation on the interaction and pathogenesis after coinfection. Here we reported a robust HBV/HCV coinfection cell culture model by overexpressing human sodium-taurocholate cotransporting polypeptide (NTCP), CD81 and Mir122 into HepG2 cells and investigated interactions between HBV and HCV. In this system, HepG2-NTCP/CD81/Mir122 cells not only supported robust infection and replication of HBV and HCV, but also allowed HBV/HCV coinfection in the single cell level. Our result showed cells with replicating HBV still supported HCV infection. However, HBV replication was suppressed by HCV through the inhibition of HBV core promoter and S promoter II activity, and this inhibition was attenuated by the interferon alpha (IFNα) treatment, suggesting HCV influence on HBV at transcriptional level. Coinfection of HBV/HCV in this system did not block IFN stimulated genes expression. Inhibition of HCV by direct-acting antiviral drugs restored HBV replication and expression of viral genes. Conclusions: HepG2-NTCP/CD81/Mir122 fully supports HBV/HCV coinfection, replication and interaction. This novel cell model offers a platform to advance our understanding of the molecular details of the interaction, pathogenesis and outcomes of HBV/HCV coinfection.

13.
Artículo en Inglés | MEDLINE | ID: mdl-33779910

RESUMEN

Understanding the impact on the thermal effect by urbanization is of great significance for urban thermal regulation and is essential for determining the relationship between the urban heat island (UHI) effect and the complexities of urban function and landscape structure. For this purpose, we conducted case research in the metropolitan region of Beijing, China, and nearly 5000 urban blocks assigned different urban function zones (UFZs) were identified as the basic spatial analysis units. The seasonal land surface temperature (LST) retrieved from remote sensing data was used to represent the UHI characteristics of the study area, and the surface biophysical parameters, building forms, and filtered landscape pattern metrics were selected as the urban landscape factors. Then, the effects of urban function and landscape structure on the UHI effect were examined based on the optimal results of the ordinary least squares and geographically weighted regression models. The results indicated that (1) Significant spatiotemporal heterogeneity of the LST was found in the study area, and there was an obvious temperature gradient with "working-living-resting" UFZs. (2) All types of urban landscape factors showed a significant contribution to the seasonal LST, in the order of surface biophysical factors > building forms > landscape factors; however, their contributions varied in different seasons. (3) The major contributing factors showed a certain difference due to the variation of urban function and landscape complexity. This study expands the understanding on the complex relationship among urban landscape, function, and thermal environment, which could benefit urban landscape planning for UHI alleviation.

14.
Chemosphere ; 275: 130032, 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33652278

RESUMEN

The effects of trace phosphate concentrations (0, 0.3 and 0.6 mg/L) in water source were investigated on microbial stability of the drinking water distribution systems (DWDSs). Obviously, the results verified that in the effluent of DWDSs simulated by annular reactors (ARs), the total microbial biomass and the absolute concentration of opportunistic pathogens such as Legionella pneumophila, Mycobacterium avium, and Hartmanella vermiformis increased significantly with phosphate concentration increasing. Based on X-ray powder diffractometer and zeta potentials measurement, trace phosphate did change physicochemical properties of corrosion products, hence promoting microbes escape from corrosion products to bulk water to a certain extent. Stimulated by chlorine disinfectant and phosphate, the extracellular polymeric substances (EPS) from the suspended biofilms of AR-0.6 gradually exhibited superior characteristics including higher content, flocculating efficiency, hydrophobicity and tightness degree, contributing to formation of large-scale suspended biofilms with strong chlorine-resistance ability. However, the disinfection by-products concentration in DWDSs barely changed due to the balance of EPS precursors contribution and biodegradation effect, covering up the microbiological water quality risk. Therefore, more attention should be paid to the trace phosphorus polluted water source though its concentration was much lower than wastewater. This is the first study successfully revealing the influence mechanism of trace phosphate on microbial stability in DWDSs, which may help to fully understand the biofilms transformation and microbial community succession in DWDSs.

15.
Pediatr Hematol Oncol ; : 1-13, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33667139

RESUMEN

Hepatoblastoma (HB) is the most common liver cancer in children, this study aims at analyzing the prognostic factors affecting the survival rates and summarizing the treatment experience. In this study, we reviewed patients with primary HB under the age of 14 years who underwent complete tumor resection from June 1997 to March 2019. The data of 72 patients were collected. Survival analysis was performed by Kaplan-Meier, multivariate Cox proportional hazards regression and linear mixed model for repeated measures (LMMRM). The 5-year and the 10-year event-free survival (EFS) of all patients were 78.2% and 73%, respectively. Both the 5-year and 10-year overall survival (OS) were 85.7%. Kaplan-Meier survival analysis showed that patients with tumor capsule infiltration (TCI) and patients with surgical margin less than 1 cm may also have a good prognosis. The Cox proportional hazards regression model analysis results were similar to the Kaplan-Meier analysis results. LMMRM analysis showed that there were significant differences in platelet, alpha-fetoprotein, C-reactive protein and hemoglobin values after surgery in the metastasis group (P < 0.05). This study suggests that patients with TCI or narrow surgical margin (<1 cm) may also have a good prognosis, and the risk stratification of HB can be used as the latest grading standard to evaluate the prognosis of patients.

16.
J Biol Chem ; : 100541, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33722606

RESUMEN

Vascular smooth muscle cells (VSMCs) contribute to the deposition of extracellular matrix proteins (ECMs), including Type IV collagen, in the vessel wall. ECMs coordinate communication among different cell types, but mechanisms underlying this communication remain unclear. Our previous studies have demonstrated that X-box binding protein 1 (XBP1) is activated and contributes to VSMC phenotypic transition in response to vascular injury. In this study, we investigated the participation of XBP1 in the communication between VSMCs and vascular progenitor cells (VPCs). Immunofluorescence and immunohistology staining revealed that Xbp1 gene was essential for COL4A1 expression during mouse embryonic development and vessel wall ECM deposition and stem cell antigen 1-positive (Sca1+)-VPC recruitment in response to vascular injury. Western blot analysis elucidated an Xbp1 gene dose-dependent effect on COL4A1 expression and that the spliced XBP1 protein (XBP1s) increased protease-mediated COL4A1 degradation as revealed by Zymography. RT-PCR analysis revealed that XBP1s in VSMCs not only upregulated COL4A1/2 transcription but also induced the occurrence of a novel transcript variant, COL4A1s, in which the front part of exon 4 is joined with the rear part of exon 42. Chromatin-immunoprecipitation, DNA/protein pulldown and in vitro transcription demonstrated that XBP1s binds to exon 4 and exon 42, directing the transcription from exon 4 to exon 42. This leads to transcription complex bypassing the internal sequences, producing a shortened soluble COL4A1s protein that increased Sca1+-VPC migration. Taken together, these results suggest that activated VSMCs may recruit Sca1+-VPCs via XBP1s-mediated COL4A1s secretion, leading to vascular injury repair or neointima formation.

17.
Ecotoxicol Environ Saf ; 212: 111980, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33545408

RESUMEN

This paper investigated the toxic effect and mechanism of ultrafine carbon black (UFCB) on splenocytes and enzymes in the digestive system. It was found that the toxicity of UFCB to splenocytes was dose-dependent. UFCB with a low concentration (<15 µg/mL) had no significant effect on splenocytes while UFCB with high concentration (>15 µg/mL) induced significant oxidative damage with increased content of reactive oxygen species (ROS) (134%) and malonaldehyde (MDA) (222.3%) along with the decreased activity of superoxide dismutase (SOD) (55.63%) and catalase (CAT) (87.73%). Analysis combined cellular and molecular levels indicated that UFCB induced splenocyte toxicity through oxidative stress. The interactions of UFCB with two important digestive enzymes, α-amylase and lipase, were also studied respectively. Results showed that the interaction of UFCB and the two enzymes altered the particle size and fluorescence intensity in both experimental systems. The formation of protein corona also resulted in the contraction of the polypeptide skeleton in both enzymes, which further inhibited their activity. Our work provided basic data on the toxicity of UFCB in the spleen and digestive system and fills the gap in the study of UFPs toxicity. CAPSULE: UFCB induced splenocyte toxicity and enzyme dysfunction through oxidative stress and protein corona formation respectively.


Asunto(s)
Hollín/toxicidad , Bazo/fisiología , Animales , Ratones , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Proteínas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Bazo/efectos de los fármacos , Bazo/metabolismo , Superóxido Dismutasa/metabolismo
18.
Cancer Cell Int ; 21(1): 137, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33637086

RESUMEN

BACKGROUND: Emerging evidence has shown that intra-tumor immune features are associated with response to immune checkpoint blockade (ICB) therapy. Accordingly, patient stratification is needed for identifying target patients and designing strategies to improve the efficacy of ICB therapy. We aimed to depict the specific immune features of patients with pancreatic cancer and explore the implication of immune diversity in prognostic prediction and individualized immunotherapy. METHODS: From transcriptional profiles of 383 tumor samples in TCGA, ICGC, and GEO database, robust immune subtypes which had different response immunotherapy, including ICB therapy, were identified by consensus clustering with five gene modules. DEGs analysis and tumor microarray were used to screen and demonstrate potential targets for improving ICB therapy. RESULTS: Three subtypes of pancreatic cancer, namely cluster 1-3 (C1-C3), characterized with distinct immune features and prognosis, were generated. Of that, subtype C1 was an immune-cold type in lack of immune regulators, subtype C2, with an immunosuppression-dominated phenotype characterized by robust TGFß signaling and stromal reaction, showed the worst prognosis, subtype C3 was an immune-hot type, with massive immune cell infiltration and in abundance of immune regulators. The disparity of immune features uncovered the discrepant applicability of anti-PD-1/PD-L1 therapy and potential sensitivity to other alternative immunotherapy for each subtype. Patients in C3 were more suitable for anti-PD-1/PD-L1 therapy, while patients in the other two clusters may need combined strategies targeted on other immune checkpoints or oncogenic pathways. A promising target for improving anti-PD-1/PD-L1 treatment, TGM2, was screened out and its role in the regulation of PD-L1 was investigated for the first time. CONCLUSION: Collectively, immune features of pancreatic cancer contribute to distinct immunosuppressive mechanisms that are responsible for individualized immunotherapy. Despite pancreatic cancer being considered as a poor immunogenic cancer type, the derived immune subtypes may have implications in tailored designing of immunotherapy for the patients. TGM2 has potential synergistic roles with ICB therapy.

19.
Medicine (Baltimore) ; 100(5): e23925, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33592845

RESUMEN

ABSTRACT: The World Health Organization (WHO) classified the spread of COVID-19 (Coronavirus Disease 2019) as a global pandemic in March. Scholars predict that the pandemic will continue into the coming winter and will become a seasonal epidemic in the following year. Therefore, the identification of effective control measures becomes extremely important. Although many reports have been published since the COVID-19 outbreak, no studies have identified the relative effectiveness of a combination of control measures implemented in Wuhan and other areas in China. To this end, a retrospective analysis by the collection and modeling of an unprecedented number of epidemiology records in China of the early stage of the outbreaks can be valuable.In this study, we developed a new dynamic model to describe the spread of COVID-19 and to quantify the effectiveness of control measures. The transmission rate, daily close contacts, and the average time from onset to isolation were identified as crucial factors in viral spreading. Moreover, the capacity of a local health-care system is identified as a threshold to control an outbreak in its early stage. We took these factors as controlling parameters in our model. The parameters are estimated based on epidemiological reports from national and local Center for Disease Control (CDCs).A retrospective simulation showed the effectiveness of combinations of 4 major control measures implemented in Wuhan: hospital isolation, social distancing, self-protection by wearing masks, and extensive medical testing. Further analysis indicated critical intervention conditions and times required to control an outbreak in the early stage. Our simulations showed that South Korea has kept the spread of COVID-19 at a low level through extensive medical testing. Furthermore, a predictive simulation for Italy indicated that Italy would contain the outbreak in late May under strict social distancing.In our general analysis, no single measure could contain a COVID-19 outbreak once a health-care system is overloaded. Extensive medical testing could keep viral spreading at a low level. Wearing masks functions as favorably as social distancing but with much lower socioeconomic costs.


Asunto(s)
Control de Enfermedades Transmisibles , Hospitalización/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud/métodos , /aislamiento & purificación , /economía , /prevención & control , China/epidemiología , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/organización & administración , Control de Enfermedades Transmisibles/normas , Trazado de Contacto/estadística & datos numéricos , Transmisión de Enfermedad Infecciosa/prevención & control , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Humanos , Modelos Teóricos , Mortalidad , Análisis de Sistemas , Tiempo de Tratamiento/estadística & datos numéricos
20.
Small ; : e2005357, 2021 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-33615728

RESUMEN

Despite numerous inherent merits of metal-organic frameworks (MOFs), structural fragility has imposed great restrictions on their wider involvement in many applications, such as in catalysis. Herein, a strategy for enhancing stability and enabling functionality in a labile Zr(IV)-MOF has been proposed by in situ porphyrin substitution. A size- and geometry-matched robust linear porphyrin ligand 4,4'-(porphyrin-5,15-diyl)dibenzolate (DCPP2- ) is selected to replace the 4,4'-(1,3,6,8-tetraoxobenzo[lmn][3,8]phenanthroline-2,7(1H,3H,6H,8H)-diyl)dibenzoate (NDIDB2- ) ligand in the synthesis of BUT-109(Zr), affording BUT-110 with varied porphyrin contents. Compared to BUT-109(Zr), the chemical stability of BUT-110 series is greatly improved. Metalloporphyrin incorporation endows BUT-110 MOFs with high catalytic activity in the photoreduction of CO2 , in the absence of photosensitizers. By tuning the metal species and porphyrin contents in BUT-110, the resulting BUT-110-50%-Co is demonstrated to be a good photocatalyst for selective CO2 -to-CO reduction, via balancing the chemical stability, photocatalytic efficiency, and synthetic cost. This work highlights the advantages of in situ ligand substitution for MOF modification, by which uniform distribution and high content of the incoming ligand are accessible in the resulting MOFs. More importantly, it provides a promising approach to convert unstable MOFs, which mainly constitute the vast MOF database but have always been neglected, into robust functional materials.

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