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1.
Magn Reson Imaging ; 75: 156-161, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33130057

RESUMO

PURPOSE: Spectrally selective fat saturation (FatSat) sequence is commonly used to suppress signal from adipose tissue. Conventional SINC-shaped pulses are sensitive to B0 off-resonance and B1+ offset. Uniform fat saturation with large spatial coverage is especially challenging for the body and breast MRI. The aim of this study is to develop spectrally selective FatSat pulses that offer more immunity to B0/B1+ field inhomogeneities than SINC pulses and evaluate them in bilateral breast imaging at 3 T. MATERIALS AND METHODS: Optimized composite pulses (OCP) were designed based on the optimal control theory with robustness to a targeted B0/ B1+ conditions. OCP pulses also allows flexible flip angles to meet different requirements. Comparisons with the vendor-provided SINC pulses were conducted by numerical simulation and in vivo scans using a 3D T1-weighted (T1w) gradient-echo (GRE) sequence with coverage of the whole-breast. RESULTS: Simulation revealed that OCP pulses yielded almost half of the transition band and much less sensitivity to B1+ inhomogeneity compared to SINC pulses with B0 off-resonance within ±200 Hz and B1+ scale error within ±0.3 (P < 0.001). Across five normal subjects, OCP FatSat pulses produced 25-41% lower residual fat signals (P < 0.05) with 27-36% less spatial variation (P < 0.05) than SINC. CONCLUSION: In contrast to conventional SINC-shaped pulses, the newly designed OCP FatSat pulses mitigated challenges of wide range of B0/ B1+ field inhomogeneities and achieved more uniform fat suppression in bilateral breast T1w imaging at 3 T.

2.
Methods Mol Biol ; 2214: 241-252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32944914

RESUMO

ChIP-seq is a powerful technique that allows the detection of chromatin localization for proteins and epigenetic modifications. However, conventional ChIP-seq usually requires millions of cells. This becomes a daunting task for applications in which only limited experimental materials are available. For example, during mammalian embryo development, the epigenomes undergo drastic reprogramming which endows a fertilized egg with the potential to develop into the whole body. Low-input ChIP-seq methods would be instrumental to help decipher molecular mechanisms underlying such epigenetic reprogramming. Here we describe an optimized ChIP-seq method-STAR (Small-scale TELP-Assisted Rapid) ChIP-seq-that allows the detection of histone modifications using only a few hundred cells. This method is proven to be robust in epigenomic profiling in both embryos and cultured cells.

3.
Ann Lab Med ; 41(1): 25-43, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829577

RESUMO

The rapid development of next-generation sequencing (NGS) technology, including advances in sequencing chemistry, sequencing technologies, bioinformatics, and data interpretation, has facilitated its wide clinical application in precision medicine. This review describes current sequencing technologies, including short- and long-read sequencing technologies, and highlights the clinical application of NGS in inherited diseases, oncology, and infectious diseases. We review NGS approaches and clinical diagnosis for constitutional disorders; summarize the application of U.S. Food and Drug Administration-approved NGS panels, cancer biomarkers, minimal residual disease, and liquid biopsy in clinical oncology; and consider epidemiological surveillance, identification of pathogens, and the importance of host microbiome in infectious diseases. Finally, we discuss the challenges and future perspectives of clinical NGS tests.

4.
PLoS One ; 15(11): e0242061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166367

RESUMO

Biomedical question answering (QA) represents a growing concern among industry and academia due to the crucial impact of biomedical information. When mapping and ranking candidate snippet answers within relevant literature, current QA systems typically refer to information retrieval (IR) techniques: specifically, query processing approaches and ranking models. However, these IR-based approaches are insufficient to consider both syntactic and semantic relatedness and thus cannot formulate accurate natural language answers. Recently, deep learning approaches have become well-known for learning optimal semantic feature representations in natural language processing tasks. In this paper, we present a deep ranking recursive autoencoders (rankingRAE) architecture for ranking question-candidate snippet answer pairs (Q-S) to obtain the most relevant candidate answers for biomedical questions extracted from the potentially relevant documents. In particular, we convert the task of ranking candidate answers to several simultaneous binary classification tasks for determining whether a question and a candidate answer are relevant. The compositional words and their random initialized vectors of concatenated Q-S pairs are fed into recursive autoencoders to learn the optimal semantic representations in an unsupervised way, and their semantic relatedness is classified through supervised learning. Unlike several existing methods to directly choose the top-K candidates with highest probabilities, we take the influence of different ranking results into consideration. Consequently, we define a listwise "ranking error" for loss function computation to penalize inappropriate answer ranking for each question and to eliminate their influence. The proposed architecture is evaluated with respect to the BioASQ 2013-2018 Six-year Biomedical Question Answering benchmarks. Compared with classical IR models, other deep representation models, as well as some state-of-the-art systems for these tasks, the experimental results demonstrate the robustness and effectiveness of rankingRAE.

5.
Sheng Wu Gong Cheng Xue Bao ; 36(10): 1992-2000, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33169565

RESUMO

Hepatocellular carcinoma (HCC) is one of the five most common malignant tumors. According to the latest statistics of the World Health Organization (WHO), the incident and mortality rates of HCC ranks the eighth and third in the world, respectively, which severely affect people's health. Exosomes are extracellular vesicles with a bilayer of phospholipids, which carry active substances such as proteins and nucleic acids derived from their mother cells. These exosomes greatly facilitate the exchange of substances and information between cells, and coordinate physiological and pathological processes in the body. In recent years, a large number of studies have shown that exosomal proteins play important roles in the tumorigenesis, development, diagnosis and treatment of HCC. Here we review the composition and functions of exosomes and the role of exosomal proteins in HCC.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , Proteômica , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/terapia , Exossomos/genética , Exossomos/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/terapia , MicroRNAs/genética
6.
BMC Surg ; 20(1): 271, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160352

RESUMO

BACKGROUND: Liver resection (LR) and enucleation (EN) are the main surgical treatment for giant hepatic hemangioma (HH), but how to choose the type of surgery is still controversial. This study aimed to explore the efficacy and the factors affecting the choice of open procedure for HH. METHODS: The data for patients with pathologically confirmed HH who underwent open surgery from April 2014 to August 2020 were analyzed retrospectively. Univariate and multivariate analyses with logistic regression were performed to disclose the factors associated with the choice of EN or LR. Propensity score matching (PSM) analysis was used to compare the efficacy of the two procedures. RESULTS: A total of 163 and 110 patients were enrolled in the EN and LR groups. Following 1:1 matching by PSM analysis, 66 patients were selected from each group. Centrally located lesions (OR: 0.131, 95% CI 0.070-0.244), tumors size > 12.1 cm (OR: 0.226, 95% CI 0.116-0.439) and multiple tumors (OR: 1.860, 95% CI 1.003-3.449) were independent factors affecting the choice of EN. There was no significant difference in the median operation time (156 vs. 195 min, P = 0.156), median blood loss (200 vs. 220 ml, P = 0.423), blood transfusion rate (33.3% vs. 33.3%, P = 1.000), mean postoperative feeding (3.1 vs. 3.3 d, P = 0.460), mean postoperative hospital stay (9.5 vs. 9.0 d, P = 0.206), or the major complication rates between the two groups. CONCLUSIONS: Peripherally located lesions, tumors size ≤ 12.1 cm and multiple tumors were more inclined to receive EN. There was no significant difference in the efficacy of EN or LR.

7.
Clin Lab ; 66(11)2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33180440

RESUMO

BACKGROUND: We explored the dynamic expression of platelet-derived growth factor-D (PDGF-D) and phosphorylated platelet-derived growth factor receptor-ß (p-PDGFR-ß) after traumatic brain injury in rats to provide theoretical basis for selecting therapeutic target and intervention time after traumatic brain injury. METHODS: This study prepared the weight drop/impact acceleration-induced traumatic brain injury (TBI) model in rats, including sham group and TBI groups at different observation time points (6 hours, 12 hours, 24 hours, 3 days, and 7 days after TBI). The dynamic expression of PDGF-D and p-PDGFR-ß after TBI were detected by western blot and immunofluorescence staining. RESULTS: The expression level of PDGF-D and p-PDGFR-ß after TBI was detected by western blot. The PDGF-D level was increased (p < 0.05) 6 hours after TBI and remained at the high level until 3 days after TBI (p < 0.05). The p-PDGFR-ß level was increased (p < 0.05) 12 hours after TBI and remained at the high level until 3 days after TBI (p < 0.05). PDGF-D and p-PDGFR-ß in brain tissues were found by immunofluorescence in the perihematoma area 24 hours after TBI. CONCLUSIONS: This study revealed the expression phenomenon of PDGF-D and p-PDGFR-ß after TBI in rats, suggesting that PDGF-D participates in the process of secondary brain injury after TBI through specific binding with PDGFR-ß, which provides a theoretical basis for further research on selecting therapeutic targets and intervention times after TBI.

8.
Clin Breast Cancer ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33183970

RESUMO

BACKGROUND: The ExteNET trial demonstrated improved invasive disease-free survival (iDFS) with neratinib, an irreversible pan-HER tyrosine kinase inhibitor, versus placebo in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) early-stage breast cancer (eBC). PATIENTS AND METHODS: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2+ eBC after neoadjuvant/adjuvant trastuzumab-based therapy. Patients were stratified by HR status and randomly assigned 1-year oral neratinib 240 mg/day or placebo. The primary endpoint was iDFS. Descriptive analyses were performed in patients with HR+ eBC who initiated treatment ≤ 1 year (HR+/≤ 1-year) and > 1 year (HR+/> 1-year) post-trastuzumab. RESULTS: HR+/≤ 1-year and HR+/> 1-year populations comprised 1334 (neratinib, n = 670; placebo, n = 664) and 297 (neratinib, n = 146; placebo, n = 151) patients, respectively. Absolute iDFS benefits at 5 years were 5.1% in HR+/≤ 1-year (hazard ratio, 0.58; 95% confidence interval [CI], 0.41-0.82) and 1.3% in HR+/>1-year (hazard ratio, 0.74; 95% CI, 0.29-1.84). In HR+/≤ 1-year, neratinib was associated with a numerical improvement in overall survival (OS) at 8 years (absolute benefit, 2.1%; hazard ratio, 0.79; 95% CI, 0.55-1.13). Of 354 patients in the HR+/≤ 1-year group who received neoadjuvant therapy, 295 had residual disease, and results showed absolute benefits of 7.4% at 5-year iDFS (hazard ratio, 0.60; 95% CI, 0.33-1.07) and 9.1% at 8-year OS (hazard ratio, 0.47; 95% CI, 0.23-0.92). There were fewer central nervous system events with neratinib. Adverse events were similar to those previously reported. CONCLUSION: Neratinib significantly improved iDFS in the HER2+/HR+/≤ 1-year population, and a similar trend was observed in patients with residual disease following neoadjuvant treatment. Numerical improvements in central nervous system events and OS were consistent with iDFS benefits and suggest long-term benefit for neratinib in this population.

9.
J Hazard Mater ; : 124283, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33187796

RESUMO

Cardamine violifolia was found here to accumulate selenium (Se) to over 9000 mg kg-1 dry weight. To investigate the mechanism of Se accumulation and tolerance in C. violifolia, metabolome, transcriptome, and proteome technologies were applied to C. violifolia seedlings treated with selenate. Several sulfate transporter (Sultr) genes (Sultr1;1, Sultr1;2, and Sultr2;1) and sulfur assimilatory enzyme genes showed high expression levels in response to selenate. Many calcium protein and cysteine-rich kinase genes of C. violifolia were downregulated, whereas selenium-binding protein 1 (SBP1) and protein sulfur deficiency-induced 2 (SDI2) of C. violifolia were upregulated by selenate. The expression of genes involved in the ribosome and posttranslational modifications and chaperones in C. violifolia were also detected in response to selenate. Based on the results of this study and previous findings, we suggest that the downregulated expression of calcium proteins and cysteine-rich kinases, and the upregulated expression of SBP1 and SDI2, were important contributors to the Se tolerance of C. violifolia. The downregulation of cysteine-rich kinases and calcium proteins would enhance Se tolerance of C. violifolia is a novel proposition that has not been reported on other Se hyperaccumulators. This study provides us novel insights to understand Se accumulation and tolerance in plants.

10.
BMC Cancer ; 20(1): 1089, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176740

RESUMO

BACKGROUND: This study is designed to investigate the clinical value of systemic chemotherapy combined with bronchoscopic interventional cryotherapy in the treatment of lung cancer. METHODS: A total of 412 lung cancer patients admitted to Cangzhou People's Hospital from March 2018 to March 2020 were collected and divided into test group and control group based on their treatment schedules. The test group received systemic chemotherapy combined with bronchoscopic interventional cryotherapy, while the control group received systemic chemotherapy alone. Tumor objective response rate (ORR), disease control rate (DCR), serum tumor marker levels, serum matrix metalloproteinase (MMP) content, T cell subset level, survival time and adverse reactions of the two groups were observed. RESULTS: The ORR and DCR of the test group were better than those of the control group, while those of the non-small cell lung cancer (NSCLC) patients in the test group were better than patients with small-cell lung cancer (SCLC) (P <  0.05). There was no significant difference in serum tumor marker levels, MMP content and T cell subset level between the two groups before treatment. After treatment, the serum tumor marker levels along with serum MMP-2, MMP-9 and CD8+ levels in the test group decreased more remarkably, while CD4+ and CD4+/CD8+ levels increased more significantly than those in the control group (P <  0.05). The serum MMP-2 and MMP-9 of NSCLC patients in the test group decreased more remarkably than those of SCLC patients, while there was no significant difference in CD8+, CD4+ and CD4+/CD8+. The progression-free survival and overall survival of the test group were obviously longer than those of the control group. The same trend was observed in NSCLC patients compared with SCLC patients in the test group (P <  0.05). CONCLUSIONS: Systemic chemotherapy combined with bronchoscopic interventional cryotherapy for lung cancer has good clinical efficacy and safety, and can be widely used in clinical practice.

11.
Sci Rep ; 10(1): 19185, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154380

RESUMO

Olanzapine is a second-generation antipsychotic (AP) drug commonly prescribed for the treatment of schizophrenia. Recently, olanzapine has been found to cause brain tissue volume loss in rodent and primate studies; however, the underlying mechanism remains unknown. Abnormal autophagy and oxidative stress have been implicated to have a role in AP-induced neurodegeneration, while N-acetylcysteine (NAC) is a potent antioxidant, shown to be beneficial in the treatment of schizophrenia. Here, we investigate the role of olanzapine and NAC on cell viability, oxidative stress, mitochondrial mass and mitophagy in hypothalamic cells. Firstly, cell viability was assessed in mHypoA-59 and mHypoA NPY/GFP cells using an MTS assay and flow cytometric analyses. Olanzapine treated mHypoA-59 cells were then assessed for mitophagy markers and oxidative stress; including quantification of lysosomes, autophagosomes, LC3B-II, p62, superoxide anion (O2-) and mitochondrial mass. NAC (10 mM) was used to reverse the effects of olanzapine (100 µM) on O2-, mitochondrial mass and LC3B-II. We found that olanzapine significantly impacted cell viability in mHypoA-59 hypothalamic cells in a dose and time-dependent manner. Olanzapine inhibited mitophagy, instigated oxidative stress and prompted mitochondrial abnormalities. NAC was able to mitigate olanzapine-induced effects. These findings suggest that high doses of olanzapine may cause neurotoxicity of hypothalamic neurons via increased production of reactive oxygen species (ROS), mitochondrial damage and mitophagy inhibition. This could in part explain data suggesting that APs may reduce brain volume.

12.
J Proteome Res ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172275

RESUMO

The Chromosome-Centric Human Proteome Project (C-HPP) was launched in 2012 to perfect the annotation of human protein existence by identifying stronger evidence of the expression of missing proteins (MPs) at the protein level. After an 8 year effort all over the world, the number of MPs in the neXtProt database significantly decreased from 5511 (2012-02-24) to 1899 (2020-01-17). It is now more difficult to provide confident evidence of the remaining MPs because of their specific characteristics, including low abundance, low molecular weight, unexpected modifications, transmembrane structure, tissue-expression specificity, and so on. A higher resolution mass spectrometry (MS) interpretation engine might provide an opportunity to identify these buried MPs in complex samples by the combination with multi-tissue large-scale proteomics. In this study, open-pFind was used to dig MPs from 20 pairs of healthy human tissues by Wang et al. ( Mol. Syst. Biol. 2019, 15 (2), e8503) combined with our large-scale testis data set digested by three enzymes (Glu-C, Lys-C, and trypsin) with specificity for different amino acid residues ( J. Proteme Res. 2019, 18 (12), 4189-4196). A total of 1 535 536 peptides with 17 283 477 peptide-spectrum matches (PSMs) were mapped to 14 279 protein entries at a false discovery rate of <1% at the PSM, peptide, and protein levels. A total of 103 MP candidates were identified, among which 86 candidates had more unique peptide numbers compared with our single testis tissue. After rigorous screening, manual checks, peptide synthesis, and matching with documented peptides from PeptideAtlas, we validated four MPs, P0C7T8 (duodenum and small intestine), Q8WWZ4 (stomach and rectum), Q8IV35 (fallopian tube), and O14921 (tonsil), at the protein level. All MS raw files have been deposited to the ProteomeXchange with identifier PXD021391.

13.
Plant Signal Behav ; : 1844508, 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222651

RESUMO

The ornamental plant Camellia japonica is widely distributed worldwide and is susceptible to various environmental stresses. The WRKY transcription factor (TF) is an important node of plant tolerance. However, WRKY TFs from C. japonica have not been reported yet. In this study, 48 CjWRKYs, namely, CjWRKY1 to CjWRKY48, were identified. Protein structure analysis revealed that CjWRKY proteins contain a highly conserved motif (WRKYGQK) and two variant motifs (WRKYGKK and WRKYGRK). Phylogenetic analysis indicated that the 48 CjWRKYs can be divided into three groups, which are further classified into six subgroups, namely, I-C, II-a, II-b, II-c, II-e, and III, which contain 10, 6, 8, 13, 7, and 4 members, respectively. The expression patterns of 15 CjWRKYs under salicylic acid (SA) treatment were investigated by real-time quantitative PCR (qRT-PCR). Results showed that the 15 CjWRKYs could be induced by SA treatment. This study is the first to screen CjWRKYs and identify the expression profile of CjWRKYs under SA treatment and provides a theoretical basis for analyzing the function of CjWRKY genes to SA stress tolerance in C. japonica.

14.
Curr Mol Med ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33222668

RESUMO

Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

15.
BMC Infect Dis ; 20(1): 852, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198647

RESUMO

BACKGROUND AND PURPOSE: Pertussis is a serious infectious disease in young infants, and severe cases frequently cause death. Our study explored risk factors for death from severe pertussis. METHOD: A case-control study of infants with severe pertussis admitted to the paediatric intensive care unit (PICU) in the Children's Hospital of Chongqing Medical University, China, from January 1, 2013, to June 30, 2019, was conducted. Pertussis was confirmed by clinical features and laboratory examinations. Severe pertussis was defined as patients with pertussis resulting in PICU admission or death. To understand the risk factors for death, we compared fatal and nonfatal cases of severe pertussis in infants aged < 120 days by collecting clinical and laboratory data. RESULTS: The participants included 63 infants < 120 days of age with severe pertussis. Fifteen fatal cases were confirmed and compared with 44 nonfatal severe pertussis cases, Four patients with termination of treatment were excluded. In the univariate analysis, the risk factors associated with death included apnoea (P = 0.001), leukocytosis (white blood cell (WBC) count≥30 × 109/L (P = 0.001) or ≥ 50 × 109/L (P = 0)), highest lymphocyte count (P = 0), pulmonary hypertension (P = 0.001), and length of PICU stay (P = 0.003). The multivariate analysis revealed that apnoea (OR 23.722, 95%CI 2.796-201.26, P = 0.004), leukocytosis (OR 63.708, 95%CI 3.574-1135.674, P = 0.005) and pulmonary hypertension (OR 26.109, 95%CI 1.800-378.809, P = 0.017) were significantly associated with death. CONCLUSION: Leukocytosis and pulmonary hypertension exhibited the greatest associations with death in infants with severe pertussis admitted to the PICU. Vaccination is still the most effective protection method against pertussis.

16.
Cell Prolif ; : e12953, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211371

RESUMO

OBJECTIVES: Using strategy of drug repurposing, antiviral agents against influenza A virus (IAV) and newly emerging SARS-coronavirus 2 (SARS-CoV-2, also as 2019-nCoV) could be quickly screened out. MATERIALS AND METHODS: A previously reported engineered replication-competent PR8 strain carrying luciferase reporter gene (IAV-luc) and multiple pseudotyped IAV and SARS-CoV-2 virus was used. To specifically evaluate the pH change of vesicles containing IAV, we constructed an A549 cell line with endosomal and lysosomal expression of pHluorin2. RESULTS: Here, we identified azithromycin (AZ) as an effective inhibitor against multiple IAV and SARS-CoV-2 strains. We found that AZ treatment could potently inhibit IAV infection in vitro. Moreover, using pseudotyped virus model, AZ could also markedly block the entry of SARS-CoV-2 in HEK293T-ACE2 and Caco2 cells. Mechanistic studies further revealed that such effect was independent of interferon signalling. AZ treatment neither impaired the binding and internalization of IAV virions, nor the viral replication, but rather inhibited the fusion between viral and vacuolar membranes. Using a NPC1-pHluorin2 reporter cell line, we confirmed that AZ treatment could alkalize the vesicles containing IAV virions, thereby preventing pH-dependent membrane fusion. CONCLUSIONS: Overall, our findings demonstrate that AZ can exert broad-spectrum antiviral effects against IAV and SARS-CoV-2, and could be served as a potential clinical anti-SARS-CoV-2 drug in emergency as well as a promising lead compound for the development of next-generation anti-IAV drugs.

17.
Nano Lett ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231472

RESUMO

Chemical etching of metals generally brings about undesirable surface damage accompanied by deteriorated performance. However, new possibilities in view of structured interfaces and functional surfaces can be explored by wisely incorporating corrosion chemistry. Here, an ultrafast route to scalable Al foils with desired porous structures originating from Fe(III)-induced oxidation etching was presented. Coupling with efficient electron polarization involving microwave interaction, straightforward surface engineering is well established on various commercial Al foils within minutes, which can be successfully extended to bulk Al alloys. As a proof-of-concept demonstration, the well-defined porous Al foils featuring regulated surface energy, demonstrate great potential as current collectors in promoting cycling stability, for example, 85.2% reversible capacity sustained after 550 cycles (comparable to commercial Al/C foils), and energy density, that is, approximately 3 times of that by using pristine Al foils for LiFePO4-Li half cells.

18.
Aging (Albany NY) ; 122020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231567

RESUMO

OBJECTIVE: Tumor necrosis factor superfamily protein 14 (TNFSF14) was recently identified as a risk factor in some fibrosis diseases. However, the role of TNFSF14 in renal fibrosis pathogenesis remains unknown. RESULTS: It was found that TNFSF14 levels were significantly increased both in UUO-induced renal fibrotic mice and in patients with fibrotic nephropathy, compared with those in controls. Accordingly, Tnfsf14 deficiency led to a marked reduction in renal fibrosis lesions and inflammatory cytokines expression in the UUO mice. Furthermore, the levels of Sphk1, a critical molecule that causes fibrotic nephropathy, were remarkably reduced in Tnfsf14 KO mice with UUO surgery. In vitro recombinant TNFSF14 administration markedly up-regulated the expression of Sphk1 of primary mouse renal tubular epithelial cells (mTECs). CONCLUSION: TNFSF14 is a novel pro-fibrotic factor of renal fibrosis, for which TNFSF14 up-regulates Sphk1 expression, which may be the underlying mechanism of TNFSF14-mediated renal fibrosis. METHODS: We investigated the effect of TNFSF14 on renal fibrosis and the relationship between TNFSF14 and pro-fibrotic factor sphingosine kinase 1 (Sphk1) by using the unilateral urethral obstruction (UUO)-induced mice renal fibrosis as a model and the specimen of patients with fibrosis nephropathy, by Masson trichrome staining, immunohistochemistry, qRT-PCR, and western blot analysis.

19.
Arch Osteoporos ; 15(1): 173, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141362

RESUMO

The present study demonstrated that the lower-extremity muscle performance in Chinese community-dwelling postmenopausal women with lower bone mineral density (BMD) was positively associated with hip BMD and negatively associated with estimated fracture risk. PURPOSE: Postmenopausal women are at high risk for osteoporotic fractures. It has been shown that decreased lower-extremity muscle performance is associated with osteoporotic fractures. However, the relationship between muscle performance and bone mineral density in postmenopausal women is inconsistent in the literature. The present study was to investigate the relationship between lower-extremity muscle performance and BMD or estimated fracture risk in community-dwelling postmenopausal women. METHODS: Two hundred forty-seven postmenopausal women aged 50-85 years were recruited in the study. The short physical performance battery (SPPB) tool including the chair stand test (CST), gait speed test (GST), and balance test (BT) was used to determine lower-extremity functioning and the CST, GST, BT, and SPPB total scores were recorded. The BMD of lumbar spine (LSBMD), femoral neck (FNBMD), and total hip (THBMD) were measured by dual-energy X-ray absorptiometry (DXA), and the vertebral fracture was confirmed by lateral spine X-rays radiographs. In addition, patients' 10-year estimated major osteoporotic fracture risk (MOFR) and hip fracture risk (HFR) were assessed by the Fracture Risk Assessment Tool (FRAX). Linear regression analysis was used to analyze the association between muscle performance and BMD. RESULTS: The CST, GST, and SPPB total scores were positively associated with LSBMD, THBMD, and FNBMD before adjustment for age, height, and weight. The SPPB total score was positively associated with FNBMD and THBMD, but not with LSBMD after adjustment for age, height, and weight. The BT score was positively associated with FNBMD and THBMD, but not with LSBMD before and after adjustment for age, height, and weight. Moreover, the CST, GST, BT, and SPPB scores were negatively associated with the FRAX score. CONCLUSION: The lower-extremity muscle performance in community-dwelling postmenopausal women is positively associated with FNBMD and THBMD and negatively associated with the FRAX score.

20.
Signal Transduct Target Ther ; 5(1): 250, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122640

RESUMO

Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types of cancer. NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex. The discovery of the NK's potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers. NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy. The effector role of these cells is reliant on the balance of inhibitory and activating signals. Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation. Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment; this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers. Accordingly, this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function, as well as their potential application in tumor immunotherapy.

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