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1.
Mol Ther ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32396851

RESUMO

Clear-cell renal cell carcinoma (ccRCC) is the most common histological type of RCC. To investigate the intratumoral heterogeneity of ccRCC, we analyzed single-cell RNA-sequencing data and identified 15 major cell types, along with 39 subgroups of cells derived from tumor or non-malignant tissues, and confirmed their presence by immunofluorescence staining in tissue chips. In this study, we verified that T cell exhaustion was the key factor responsible for the immunosuppressive property of ccRCC tissues, which was significantly related to poor prognosis. We also found that abnormal metabolic patterns occurred not only in cancer cells, but also in tumor-infiltrating stromal cells. Based on the fraction of each cell cluster detected by CIBERSORTx, 533 patients from The Cancer Genome Atlas (TCGA) KIRC dataset were divided into three groups. One group, which showed a lesser proportion of activated CD8+ cells and greater proportion of exhausted CD8+ cells, was associated with a poor prognosis. Hence, the blockade of immunosuppressive checkpoints, not only PD-1, but also LAG3, TIM-3, and other inhibitory checkpoints, could serve as a potential target for ccRCC immunotherapy. Our work will further the understanding of the heterogeneity among ccRCC tissues and provide novel strategies for treating ccRCC.

2.
Am J Gastroenterol ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32282342

RESUMO

OBJECTIVES: In colorectal cancer screening, implementing risk-adapted screening might be more effective than traditional screening strategies. We aimed to compare the effectiveness of a risk-adapted screening strategy with colonoscopy and fecal immunochemical test (FIT) in colorectal cancer screening. METHODS: A randomized controlled trial was conducted in 6 centers in China since May 2018. Nineteen thousand five hundred forty-six eligible participants aged 50-74 years were recruited and randomly allocated into 1 of the 3 screening groups in a 1:2:2 ratio: (i) one-time colonoscopy (n = 3,916), (ii) annual FIT (n = 7,854), and (iii) annual risk-adapted screening (n = 7,776). Based on the risk-stratification score, high-risk subjects were referred for colonoscopy and low-risk ones were referred for FIT. All subjects with positive FIT were referred for diagnostic colonoscopy. The detection rate of advanced neoplasm was the primary outcome. The study is registered with the China Clinical Trial Registry (www.chictr.org.cn Identifier: ChiCTR1800015506). RESULTS: For baseline screening, the participation rates of the colonoscopy, FIT, and risk-adapted screening groups were 42.5% (1,665/3,916), 94.0% (7,386/7,854), and 85.2% (6,628/7,776), respectively. For the intention-to-screen analysis, the detection rates of advanced neoplasm were 2.40% (94/3,916), 1.13% (89/7,854), and 1.66% (129/7,776), with odds ratios (95% confidence intervals) of 2.16 (1.61-2.90; P < 0.001) for colonoscopy vs FIT, 1.45 (1.10-1.90; P < 0.001) for colonoscopy vs risk-adapted screening, and 1.49 (1.13-1.97; P < 0.001) for risk-adapted screening vs FIT, respectively. The numbers of subjects who required a colonoscopic examination to detect 1 advanced neoplasm were 18 in the colonoscopy group, 10 in the FIT group, and 11 in the risk-adapted screening group. DISCUSSION: For baseline screening, the risk-adapted screening approach showed a high participation rate, and its diagnostic yield was superior to that of FIT at a similarly low load of colonoscopy.

3.
Sci Adv ; 6(14): eaaz7825, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32270046

RESUMO

Currently, there are no methods available offering solutions to select and identify antibodies binding to a specific conformational epitope of an antigen. Here, we developed a method to allow epitope-directed antibody selection from a phage display library by photocrosslinking bound antibodies to a site that specifically incorporates a noncanonical amino acid, p-benzoyl-l-phenylalanine (pBpa), on the target antigen epitope. By one or two rounds of panning against antibody phage display libraries, those hits that covalently bind to the proximity site of pBpa on specific epitopes of target antigens after ultraviolet irradiation are enriched and selected. This method was applied to specific epitopes on human interleukin-1ß and complement 5a. In both cases, more than one-third of hits identified bind to the target epitopes, demonstrating the feasibility and versatility of this method.

4.
Foods ; 9(4)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32244338

RESUMO

Changes in nutrient content and bioactivity are important indicators to evaluate the quality of products. Berries are rich in antioxidant anthocyanins, which are prone to degradation during drying. The effects of different variables on the stability of anthocyanins in berry puree during microwave assisted foam-mat drying (MFD) was investigated by path analysis and degradation kinetics analysis. The experimental results showed that the degradation of anthocyanins mainly occurred in the last drying stage. The temperature and the moisture content have both direct and indirect effects on the anthocyanin stability. The direct path coefficient of the moisture content on anthocyanins was 0.985, and the direct path coefficient of temperature on anthocyanins was -0.933. The moisture content to temperature ratio (M/T) was first put forward to estimate the anthocyanin degradation. The results of the regression analysis confirmed that the anthocyanins were stable at M/T of 0.96-3.60. A finite element simulation model was established to predict the anthocyanin degradation rate and content. These research results could provide a theoretical reference for use in optimizing the MFD processing technologies.

5.
Res Vet Sci ; 131: 31-37, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32283442

RESUMO

Hepatitis-hydropericardium syndrome (HHS) caused by hypervirulent fowl adenovirus 4 (FAdV-4) have been causing great economic losses to Chinese poultry industry since 2015. Elucidation of the pathogenesis of FAdV-4 will lay solid foundation for developing attenuated FAdV-4 vaccine and vaccine vector. Our previous study has demonstrated that the increased virulence of hypervirulent FAdV-4 was associated with fiber-2 and hexon genes. However, the roles of fiber-1 and penton in virulence of FAdV-4 have never been elucidated. To further investigate the roles of the major structural proteins fiber-1 and penton in the virulence of hypervirulent FAdV-4, the fiber-1- and penton-replaced mutant viruses were constructed based on the FAdV-4 infectious clones of hypervirulent strain HNJZ using Redαß recombineering techniques. The pathogenicity of the rescued viruses was evaluated in 3-week-old SPF chickens. Chickens infected with the rescued recombinant viruses carrying the fiber-1 or penton base gene from a nonpathogenic strain ON1 developed similar clinical signs to the natural hypervirulent FAdV-4 infection, including HHS-indicative gross lesions and histopathological changes in sick/dead chickens. Our results suggested that the increased virulence of hypervirulent FAdV-4 was independent of fiber-1 and penton. The detailed pathogenesis of FAdV-4 and the roles of fiber-1 and penton in the viral replication and infection process need to be further explored.

6.
Cells ; 9(2)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050592

RESUMO

Beyond comparative genomics, we identified 85 sugar transporter genes in Cordyceps militaris, clustering into nine subfamilies as sequence- and phylogenetic-based functional classification, presuming the versatile capability of the fungal growths on a range of sugars. Further analysis of the global gene expression patterns of C. militaris showed 123 genes were significantly expressed across the sucrose, glucose, and xylose cultures. The sugar transporters specific for pentose were then identified by gene-set enrichment analysis. Of them, the putative pentose transporter, CCM_06358 gene, was highest expressed in the xylose culture, and its functional role in xylose transport was discovered by the analysis of conserved structural motifs. In addition, a battery of molecular modeling methods, including homology modeling, transport pathway analysis, residue interaction network combined with molecular mechanics Poisson-Boltzmann surface area simulation (MM-PBSA), was implemented for probing the structure and function of the selected pentose transporter (CCM_06358) as a representative of sugar transportome in C. militaris. Considering the network bottlenecks and structural organizations, we further identified key amino acids (Phe38 and Trp441) and their interactions with other residues, contributing the xylose transport function, as verified by binding free energy calculation. The strategy used herein generated remarkably valuable biological information, which is applicable for the study of sugar transportome and the structure engineering of targeted transporter proteins that might link to the production of bioactive compounds derived from xylose metabolism, such as cordycepin.

7.
Am J Sports Med ; 48(3): 697-705, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32023083

RESUMO

BACKGROUND: After a rotator cuff (RC) is repaired, its signal intensity (SI) on magnetic resonance imaging (MRI) gradually changes to normal and could reflect the degree of RC healing. Nevertheless, it remains unclear how long it takes for SI to recover to normal and whether the SI progression correlates with clinical outcomes after RC repair (RCR). PURPOSE: To serially evaluate the SIs of the repaired RC tendon on MRI and the postoperative clinical outcomes and then analyze the correlation between them. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study prospectively included 25 patients who underwent arthroscopic RCR with the suture-bridge technique between June 2016 and July 2017. Twenty-three patients accepted full follow-ups at 1, 3, 6, 9, and 12 months. Before surgery and at each follow-up, visual analog scale (VAS) for pain and 4 functional scores were evaluated: Constant-Murley score, American Shoulder and Elbow Surgeons shoulder evaluation form, modified University of California at Los Angeles score, and Fudan University shoulder score. The patients underwent MRI examinations at every follow-up. The values of the signal/noise quotient at the distal (SNQd) and proximal (SNQp) areas were calculated to evaluate the SI of the repaired tendon. The correlations of clinical outcomes with SNQd and SNQp values were analyzed, and subgroup analyses were performed. RESULTS: Overall, the mean postoperative VAS score significantly decreased at postoperative 1 month (P < .001), and the functional scores were all significantly higher than the preoperative values at 6 months (all P < .001). SNQd and SNQp values were both significantly higher than normal at 1 and 3 months (all P < .001) and reduced to normal after 9 and 6 months, respectively. Correlation analyses showed that the SNQp value significantly correlated with VAS score (positive) and all functional scores (negative) at 1 and 3 months postoperatively. Further comparison indicated that the patients with VAS score >3 had higher SNQp values than patients with VAS score ≤3 at 1 and 3 months postoperatively (both P = .01). CONCLUSION: After RCR with the suture-bridge technique, it took longer for SI to become relatively normal than it did to have a significant clinical improvement. Early after surgery (1-3 months), worse clinical outcome correlated with higher SI on proximal cuff tendon.

8.
Microb Cell Fact ; 19(1): 18, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005241

RESUMO

BACKGROUND: Amphotericin B (AmB) is widely used against fungal infection and produced mainly by Streptomyces nodosus. Various intracellular metabolites of S. nodosus were identified during AmB fermentation, and the key compounds that related to the cell growth and biosynthesis of AmB were analyzed by principal component analysis (PCA) and partial least squares (PLS). RESULTS: Rational design that based on the results of metabolomics was employed to improve the AmB productivity of Streptomyces nodosus, including the overexpression of genes involved in oxygen-taking, precursor-acquiring and product-exporting. The AmB yield of modified strain S. nodosus VMR4A was 6.58 g/L, which was increased significantly in comparison with that of strain S. nodosus ZJB2016050 (5.16 g/L). This was the highest yield of AmB reported so far, and meanwhile, the amount of by-product amphotericin A (AmA) was decreased by 45%. Moreover, the fermentation time of strain S. nodosus VMR4A was shortened by 24 h compared with that of strain. The results indicated that strain S. nodosus VMR4A was an excellent candidate for the industrial production of AmB because of its high production yield, low by-product content and the fast cell growth. CONCLUSIONS: This study would lay the foundation for improving the AmB productivity through metabolomics analysis and overexpression of key enzymes.

9.
J Ethnopharmacol ; 252: 112531, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31926314

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The classical and traditional Chinese medicine prescription, Liuwei Dihuang (LWDH), has been commonly used to treat the menopausal syndrome. It has been reported that LWDH could improve estrogen receptor α (ERα) expression to prevent atherosclerosis (AS), while the mechanism of LWDH on regulating ERα expression was still unknown. AIM OF THE STUDY: To reveal the mechanism of LWDH on regulating the ERα expression. MATERIALS AND METHODS: The protective effect of LWDH on Hcy-induced apoptosis of human umbilical vein endothelial cells (HUVECs) was examined. The expression of ERα and DNA methyltransferases 1 (DNMT1) were detected by Western blot and real-time polymerase chain reaction (RT-PCR). The methylation rate of the ERα gene was assayed by the bisulfite sequencing PCR (BSP). High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was applied to determine the level of S-Adenosyl methionine (SAM) and S-Adenosyl homocysteine (SAH). In vivo, the ApoE-/- mice were ovariectomized to establish postmenopausal atherosclerosis (AS) model. RESULTS: In vitro study showed that LWDH protects HUVECs from Hcy-induced apoptosis. Treatment with LWDH significantly increased the ERα expression and reduced the methylation rate of the ERα gene by inhibiting the DNMT1 expression. The level of main methyl donor SAM and the ration of SAM/SAH were reduced by LWDH. In vivo, LWDH prevented the formation of plaque and reduced the concentration of Hcy. In addition, LWDH upregulated the ERα expression, as well as inhibiting the expression of DNMT1 in atherosclerotic mice. CONCLUSIONS: LWDH exerted protective effects on postmenopausal AS mice, and HUVECs treated with Hcy. LWDH increased of ERα expression via inhibiting DNMT1-dependent ERα methylation.

10.
Vaccine ; 38(8): 1989-1997, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31948818

RESUMO

Newcastle disease (ND) is one of the most important and devastating avian diseases with considerable threat to the global poultry industry. Hepatitis-hydropericardium syndrome (HHS), caused by virulent fowl adenovirus serotype 4 (FAdV-4), is another highly infectious disease in chickens with severe economic impact. The effective way to combat ND and HHS is by vaccinating the poultry. In the present study, a recombinant NDV LaSota vaccine strain expressing full length fiber-2 gene of FAdV-4 (rLaSota-fiber2) was generated using reverse genetics. The FAdV-4 fiber-2 protein was expressed as a soluble form rather than NDV membrane-anchored form. The rLaSota-fiber2 was genetically stable, and it showed growth patterns in embryonated eggs comparable to that of parental rLaSota virus. Since our unpublished data demonstrated that delivery of live rLaSota-fiber2 in drinking water or ocular delivery of the vaccine didn't produce protection against hypervirulent FAdV-4 challenge, even though the vaccine provide full protection against NDV challenge, the efficacy of the rLaSota-fiber2 was evaluated by delivering the vaccine intramuscularly in this study. Single-dose intramuscular vaccination of 2-week-old SPF White Leghorn chicks with the live or inactivated rLaSota-fiber2 provided complete protection against virulent NDV challenge. However, single-dose intramuscular vaccination with the live rLaSota-fiber2 vaccine provided better protection against virulent FAdV-4 challenge and significantly reduced faecal viral shedding comparing to the inactivated vaccine. These results indicate that the NDV-vectored FAdV-4 vaccine is a promising bivalent vaccine candidate to control both HHS and ND.

11.
Drug Des Devel Ther ; 13: 4115-4126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827318

RESUMO

Background: Hongjingtian injection (HJT) is administered in the treatment of vascular diseases, including diabetic angiopathies (DA). However, its underlying mechanisms have not been examined systematically. Methods: In this research, we explored potential mechanisms of HJT through network pharmacology. HG-stimulated A7r5 cells served as the cell model. Cell proliferation, migration and apoptosis were investigated. The effects on key targets and the AKT pathway were verified by Western blotting in experiments with the AKT inhibitor LY294002 or activator SC79. Results: Network analysis predicted that HJT targeted 10 candidate targets and 15 pathways including cell proliferation, migration and apoptosis in response to DA. Functional experiments showed that HJT markedly suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs, which validated the prediction. Mechanistically, HJT significantly downregulated the expression of pAKT, MMP9, and PCNA, upregulated the expression of p53 and cleaved caspase-3 and increased the Bax/Bcl-2 ratio compared with the HG group. SC79, an AKT activator, partially reversed the inhibitory effects of HJT on HG-induced VSMCs, confirming the involvement of the AKT pathway. Furthermore, the presence of the AKT inhibitor LY294002 had a similar inhibitory effect as HJT. Conclusion: These findings systematically evaluate the potential mechanisms of HJT for the treatment of DA. HJT suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs partly by inhibiting the AKT pathway. Additionally, this study may provide a quick and effective way to investigate the molecular mechanisms of traditional Chinese medicine.

12.
Cell Biochem Funct ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710120

RESUMO

Regeneration remains a major challenge in skeletal muscle repair after injury. Recently, transforming growth factor-ß (TGF-ß)/Smad pathway was found to play an important role in inhibiting myogenesis, a crucial stage in skeletal muscle regeneration. In our previous study, microRNA-122-5p (miR-122) was proved to have the function of downregulating TGF-ß/Smad pathway. Theoretically, miR-122 might also be involved in the process of skeletal muscle myogenesis through the regulation of TGF-ß/Smad pathway. In this study, we aimed to investigate the impact of miR-122 on skeletal muscle myogenesis and explore its underlying mechanism. Results showed that miR-122 and myogenic markers were downregulated in C2C12 cells after TGF-ß stimulation, and miR-122 overexpression could restore the myogenesis inhibited by TGF-ß. We then located TGFBR2 as the direct target of miR-122 and discovered the effect of miR-122 overexpression could be rescued by TGFBR2 overexpression. Further, the downstream molecules of TGFBR2 in the TGF-ß/Smad pathway were found to be suppressed by miR-122. In conclusion, miR-122 could suppress the TGF-ß/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. SIGNIFICANCE OF THE STUDY: Regeneration remains a major challenge in skeletal muscle repair after injury. In this study, it was found that miR-122 could suppress the TGF-ß/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. Our findings could inspire future experiments on the role of miRs in skeletal muscle diseases and future translational studies on potential novel gene therapy for skeletal muscle injury.

13.
Int J Biol Macromol ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31712154

RESUMO

Mesenchymal stem cell (MSC) delivery has been broadly investigated as a cell-based therapy strategy towards various diseases and tissue injury. In these applications, the cell-delivery vehicle plays a crucial role in determining the therapeutic performance of MSCs and their fate post-implantation. We report here the development of a microcarrier system combining platelet-derived growth factor-BB (PDGF-BB) and a PDGF-BB-binding polysaccharide - Eucommia ulmoides (EUP3) - for MSC cultivation. First, we investigated the optimal conditions to prepare the EUP3-PDGF-BB complex, by comparing its i) diameter, ii) morphology, and iii) bioactivity to promote MSC proliferation and fibroblast migration in vitro, under different PDGF-BB/EUP3 ratios. Then, we fabricated microspheres using gelatin and EUP3 as the matrix while stabilizing PDGF-BB at the optimal ratio for MSC adhesion and growth. Live staining and SEM observation indicated that the prepared microspheric carrier supported MSC growth and maintained cell stemness. We suggest that the EUP3/PDGF-gelatin microcarriers can potentially serve as a cell-delivery vehicle for tissue engineering.

14.
Acta Pharmacol Sin ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685975

RESUMO

Proximal renal tubular damage is a critical process underlying diabetic kidney disease (DKD). Our previous study shows that prostaglandin E1 (PGE1) reduces the apoptosis of renal tubular cells in DKD rats. But its underlying mechanisms remain unclear. In this study we investigated the protective effects of PGE1 in DKD rats and high glucose (HG, 30 mM)-treated HK-2 proximal tubular cells. Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established, the DKD rats were administered PGE1 (10 µg· kg-1· d-1, iv.) for 10 consecutive days. We showed that PGE1 administration did not change blood glucose levels, but alleviated diabetic kidney injury in the DKD rats, evidenced by markedly reduced proteinuria and renal tubular apoptosis. In the in vitro experiments, PGE1 (0.1-100 µM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 µM) significantly suppressed the c-Jun N-terminal kinase (JNK) and the mitochondrial apoptosis-related protein expressions such as Bim, Bax, caspase-3 and cleaved caspase-3; similar changes were also observed in the kidney of PGE1-treated DKD rats. By using two pharmacological tools-JNK activator anisomycin (AM) and JNK inhibitor SP600125, we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells; JNK was an upstream regulator of Bim. In conclusion, our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling pathway.

15.
Nat Cell Biol ; 21(10): 1261-1272, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31570835

RESUMO

The repression of transposons by the Piwi-interacting RNA (piRNA) pathway is essential to protect animal germ cells. In Drosophila, Panoramix enforces transcriptional silencing by binding to the target-engaged Piwi-piRNA complex, although the precise mechanisms by which this occurs remain elusive. Here, we show that Panoramix functions together with a germline-specific paralogue of a nuclear export factor, dNxf2, and its cofactor dNxt1 (p15), to suppress transposon expression. The transposon RNA-binding protein dNxf2 is required for animal fertility and Panoramix-mediated silencing. Transient tethering of dNxf2 to nascent transcripts leads to their nuclear retention. The NTF2 domain of dNxf2 competes dNxf1 (TAP) off nucleoporins, a process required for proper RNA export. Thus, dNxf2 functions in a Panoramix-dNxf2-dependent TAP/p15 silencing (Pandas) complex that counteracts the canonical RNA exporting machinery and restricts transposons to the nuclear peripheries. Our findings may have broader implications for understanding how RNA metabolism modulates heterochromatin formation.


Assuntos
Proteínas Argonauta/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Inativação Gênica , Heterocromatina/metabolismo , Proteínas Nucleares/genética , Proteínas de Transporte Nucleocitoplasmático/genética , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Proteínas Argonauta/química , Proteínas Argonauta/metabolismo , Montagem e Desmontagem da Cromatina , Elementos de DNA Transponíveis , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Heterocromatina/ultraestrutura , Modelos Moleculares , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Proteínas de Transporte Nucleocitoplasmático/química , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Oócitos/metabolismo , Oócitos/ultraestrutura , Ovário/citologia , Ovário/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
16.
Opt Express ; 27(16): 23029-23048, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510586

RESUMO

Compressive spectral imaging systems have promising applications in the field of object classification. However, for soil classification problem, conventional methods addressing this specific task often fail to produce satisfying results due to the tradeoff between the invariance and discrepancy of each soil. In this paper, we explore a liquid crystal tunable filters (LCTF)-based system and propose a three-dimensional convolutional neural network (3D-CNN) for soil classification. We first obtain a set of soil compressive measurements via a low spatial resolution detector, and soil hyperspectral images are reconstructed with improved resolution in spatial as well as spectral domains by a compressive sensing (CS) method. Furthermore, different from previous spectral-based object classification methods restricted to extract features from each type independently, on account of the potential of spectral property on individual solid, our method proposes to apply the principal component analysis(PCA) to achieve a dimensionality reduction in the spectral domain. Then, we explore a differential perception model for flexible feature extraction, and finally introduce a 3D-CNN framework to solve the multi-soil classification problem. Experimental results demonstrate that our algorithm not only is able to accelerate the ability of feature discriminability but also performs against conventional soil classification methods.

17.
Mol Med Rep ; 20(3): 2675-2684, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31524261

RESUMO

The present study investigated the effects of the ultrasound (US), a noninvasive technique, on ischemia­reperfusion injury (IRI) following cardiopulmonary resuscitation (CPR). The animals used in the present study were randomized into five groups (n=8 per group) as follows: i) The CPR group, where the rats underwent 6 min of untreated ventricular fibrillation (VF) followed by CPR and defibrillation; ii) the US group, in which the treatment was identical to the CPR group with the exception that rats were exposed to US treatment 24 h prior to CPR; iii) the MLA group, in which the treatment was identical to the US group with the exception that the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist MLA (4 mg/kg) was administered 30 min prior to US and VF respectively; iv) the GTS group, in which the treatment was identical to the CPR group with the exception that the α7nAChR agonist GTS­21 (4 mg/kg) was injected 30 min prior to VF; and v) the SHAM group, in which the rats were exposed to surgical preparation without CPR and US application. At 1 day prior to CPR, the US treatment was administered to the left kidney by US pulses (contrast general mode with 9 MHz) with a bursting mechanical index of 0.72 for 2 min. Following treatment of the left kidney, the right kidney was exposed to identical US treatment for an additional 2 min. The results demonstrated that US preconditioning decreased the number of defibrillations required and shortened the duration of CPR. US also suppressed tumor necrosis factor­α and interleukin­6 levels following resuscitation (P<0.05), and a significantly longer overall survival time was observed in the US­treated animals (P<0.01). In addition, US attenuated neuronal injury and promoted the expression of α7nAChR in hippocampal neurons (P<0.05). However, the protective effects of US were abolished by MLA and imitated by GTS­21. The results of the present study demonstrated that prior exposure to US may improve animal outcomes following CPR, and the protective effects of US may be dependent on the cholinergic anti­inflammatory pathway (CAP) via α7nAChR.


Assuntos
Reanimação Cardiopulmonar , Neuroimunomodulação , Ultrassonografia , Animais , Biomarcadores , Reanimação Cardiopulmonar/métodos , Citocinas/metabolismo , Parada Cardíaca/diagnóstico por imagem , Parada Cardíaca/etiologia , Parada Cardíaca/mortalidade , Parada Cardíaca/terapia , Masculino , Avaliação de Resultados da Assistência ao Paciente , Células Piramidais/metabolismo , Células Piramidais/efeitos da radiação , Ratos , Taxa de Sobrevida , Ultrassonografia/métodos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
18.
Cancer Biol Med ; 16(2): 350-360, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31516755

RESUMO

Objective: To examine the efficacy and safety of a sequential combination of chemotherapy and autologous cytokine-induced killer (CIK) cell treatment in triple-negative breast cancer (TNBC) patients. Methods: A total of 294 post-surgery TNBC patients participated in the research from January 1, 2009 to January 1, 2015. After adjuvant chemotherapy, autologous CIK cells were introduced in 147 cases (CIK group), while adjuvant chemotherapy alone was used to treat the remaining 147 cases (control group). The major endpoints of the investigation were the disease-free survival (DFS) and overall survival (OS). Additionally, the side effects of the treatment were evaluated. Results: In the CIK group, the DFS and OS intervals of the patients were significantly longer than those of the control group (DFS: P = 0.047; OS: P = 0.007). The multivariate analysis demonstrated that the TNM (tumor-node-metastasis) stage and adjuvant CIK treatment were independent prognostic factors for both DFS [hazard ratio (HR) = 0.520, 95% confidence interval (CI):0.271-0.998, P = 0.049; HR = 1.449, 95% CI:1.118-1.877, P = 0.005, respectively] and OS (HR=0.414, 95% CI:0.190-0.903, P = 0.027; HR = 1.581, 95% CI:1.204-2.077, P = 0.001, respectively) in patients with TNBC. Additionally, longer DFS and OS intervals were associated with increased number of CIK treatment cycles (DFS: P = 0.020; OS: P = 0.040). The majority of the patients who benefitted from CIK cell therapy were relatively early-stage TNBC patients. Conclusion: Chemotherapy in combination with adjuvant CIK could be used to lower the relapse and metastasis rate, thus effectively extending the survival time of TNBC patients, especially those at early stages.

19.
Int J Chron Obstruct Pulmon Dis ; 14: 1517-1526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371937

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is a disease of continuous progress and environmental factors may affect the progress. COPD patients' activity tolerance and quality of life are associated with air quality. COPD exacerbation from the perspective of geographical air quality has not been reported. Objectives: To explore environmental effect of two different geographical places on COPD exacerbation and the effect of cigarette smoke extract and carbon particles on bronchial epithelial cell viability. Methods: Total 139 COPD patients, who lived in Beijing during summer and temporarily migrated to Sanya city in winter, have been enrolled. Respiratory symptoms and lung function data were collected when they were living in Beijing or Sanya, respectively. Effect of cigarette smoke extract plus ultrafine carbon particles on airway epithelial cells were studied. Measurements and main results: Air pollution as measured by air quality index (AQI) in Beijing summer (113.1±14.2) was significantly worse than that in Sanya winter (49.4±8.9, p<0.001). The COPD Assessment Test (CAT) score was significantly higher in Beijing (26.4±7.1) than that in Sanya (20.0±8.0, p=0.019). Modified Medical Research Council dyspnea scale was also significantly higher in Beijing (2.9±0.9) than that in Sanya (1.9±0.8, p<0.001). FEV1 was significantly improved when the patients were in Sanya (48.88±24.78%) compared to that in Beijing (41.79±20.06%, p<0.01). Compared with Beijing and Sanya, the relative risk (RR) of hospitalization and acute exacerbation were 1.64 and 3.36, respectively. In vitro study demonstrated that apoptosis of BEAS2B cells in response to cigarette smoke extract plus ultrafine carbon particles (25.50±2.10%) was significantly higher than that of control culture (2.30±1.05%, p<0.01). Conclusion: These findings suggested that ambient air pollution cause COPD exacerbation, and that air pollutants particle matters induce apoptosis of airway epithelial cells.


Assuntos
Poluição do Ar/efeitos adversos , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Saúde da População Urbana , Idoso , Idoso de 80 Anos ou mais , Apoptose/efeitos dos fármacos , Pequim , Brônquios/efeitos dos fármacos , Brônquios/patologia , Linhagem Celular , Progressão da Doença , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/patologia , Medição de Risco , Fatores de Risco , Estações do Ano , Fumaça/efeitos adversos , Fatores de Tempo
20.
Proc Natl Acad Sci U S A ; 116(32): 15889-15894, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31332018

RESUMO

To direct checkpoint inhibition to the tumor microenvironment, while avoiding systemic immune activation, we have synthesized a bispecific antibody [norleucine4, d-Phe7]-melanocyte stimulating hormone (NDP-MSH)-antiprogrammed cell death-ligand 1 antibody (αPD-L1) by conjugating a melanocyte stimulating hormone (α-MSH) analog to the antiprogrammed cell death-ligand 1 to (αPD-L1) antibody avelumab. This bispecific antibody can bind to both the melanocortin-1 receptor (MC1R) and to PD-L1 expressed on melanoma cells and shows enhanced specific antitumor efficacy in a syngeneic B16-SIY melanoma mouse model compared with the parental antibody at a 5 mg/kg dose. Moreover, the bispecific antibody showed increased infiltrated T cells in the tumor microenvironment. These results suggest that a tumor-targeted PD-L1-blocking bispecific antibody could have a therapeutic advantage in vivo, especially when used in combination with other checkpoint inhibitors.

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