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1.
Anal Chem ; 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32551501

RESUMO

Exosome-associated liquid biopsies are hampered by challenges in the exosomal quantification and phenotyping. Here, we present a bioinspired exosome-activated DNA molecular machine (ExoADM) with multivalent cyclic amplification that enables highly sensitive detection and phenotyping of circulating exosomes. ExoADM harbors two (an exposed and a hided) DNA toehold domains that actuate sequential branch migration and multivalent recycling in response to exosomal surface markers. Importantly, this self-powered ExoADM achieves a high sensitivity (33 particles/µL) and is compatible with another DNA nanomachine targeting different exosomal surface markers for dual-color phenotyping. Using this strategy, we can simultaneously track the dynamic changes of ExoPD-L1 and ExoCD63 expression induced by signaling molecules. Further, we found that their expression levels on circulating exosomes could well differentiate cancer patients from the normal individuals. More importantly, ExoPD-L1 level could reflect the efficacy of different treatments and guide anti-PD-1 immunotherapy, suggesting the potential of ExoPD-L1 in clinical diagnosis and targeted therapy monitoring.

2.
Behav Brain Res ; 392: 112709, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32479850

RESUMO

PURPOSE: To explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE). METHODS: 15 patients and eight healthy controls (HC) were enrolled and scanned by resting-state functional MRI to investigate changes in the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). A two-sample t-test or paired sample t-test was used to compare activity between the HCs, preoperative patients (EP-pre), and postoperative patients (EP-post). We also performed correlation analyses to examine the seizure improvement ratio. RESULTS: The voxel-level analyses indicated that, compared with the HC, the EP-pre group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral/postcentral gyrus, amygdala, insula, cerebellum, and lingual gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral gyrus, insula, anterior/median cingulate gyri, and cerebellum. The regions of interest-level analyses indicated that, compared with HC, the EP-pre group exhibited decreased fALFF or ReHo in the caudate nucleus, supramarginal gyrus, precuneus and middle temporal gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited increased fALFF or ReHo in the olfactory cortex, gyrus rectus, and superior temporal gyrus. Increased ReHo in the right superior or middle temporal gyrus was positively correlated with the improvement ratio. CONCLUSIONS: Altered regional activity in DRE patients was reorganized after 3 months of stimulation. Increased ReHo in the right superior or middle temporal gyrus was implicated in VNS-induced improvement in seizure frequency.

3.
Biomed Pharmacother ; 128: 110324, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32544782

RESUMO

Accumulating studies implied that long noncoding RNAs (lncRNAs) act as essential factors in regulating diverse biological behaviors of cancers. Small nucleolar RNA host gene 11 (SNHG11) has been reported as for its oncogenic properties in several cancer types. However, it is unclear whether SNHG11 exerts functions in non-small cell lung cancer (NSCLC) remains unclear. The aim of this study was to inspect the role and regulatory mechanism of SNHG11 in NSCLC. The expression of SNHG11 in NSCLC cells was analyzed by qRT-PCR. Functional experiments were carried out to determine the effects of SNHG11 silence on the biological behaviors of NSCLC cells, including growth, migration and epithelial-mesenchymal transition. The inhibition of above functions was observed after SNHG11 was silenced. Subcellular fractionation and FISH assays were performed to detect the cellular distribution of SNHG11. Moreover, SNHG11 was found to be a sponge of miR-485-5p that could directly target to Basigin (BSG) mRNA. The interaction between SNHG11 and miR-485-5p as well as between miR-485-5p and BSG was proven by RNA pull down and luciferase reporter assays. Restoration assay confirmed the involvement of miR-485-5p and BSG in SNHG11-mediated NSCLC cellular functions. Conclusively, SNHG11 was overexpressed in NSCLC and functioned as a miR-485-5p sponge to up-regulate BSG.

4.
Eur Respir J ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430428

RESUMO

BACKGROUND: The duration of viral shedding is central to guide the decisions of isolation precautions and antiviral treatment. However, studies regarding the risk factors associated with prolonged SARS-CoV-2 shedding and the impact of Lopinavir/Ritonavir (LPV/r) treatment on viral shedding remain scarce. METHODS: Data were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had reverse transcription polymerase chain-reaction conversion at the No.3 People's Hospital of Hubei province between 31 January and 09 March 2020. We compared clinical characteristics and SARS-CoV-2 RNA shedding between patients initiated with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate the risk factors associated with prolonged viral shedding. RESULTS: Of 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment. The median duration of SARS-CoV-2 RNA detection from symptom onset was 23 days (IQR, 18-32 days). Older age (odd ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05, p=0.03) and the lack of LPV/r treatment (OR 2.42, 95% CI 1.10-5.36, p=0.029) were independent risk factors of prolonged SARS-CoV-2 RNA shedding. Patients who initiated LPV/r treatment within 10 days from symptom onset, but not initiated from day 11 onwards, had significantly shorter viral shedding duration compared with those without LPV/r treatment (median 19 days versus 28.5 days, Log-rank p<0.001). CONCLUSION: Older age and the lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with COVID-19. Earlier administration of LPV/r treatment could shorten viral shedding duration.

5.
Biomed Pharmacother ; 127: 110214, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32403047

RESUMO

Non-small cell lung cancer (NSCLC) is a type of malignant tumor which threatens human health and life. Recently, some researches on long non-coding RNAs (lncRNAs) in NSCLC has elucidated critical regulatory roles in cell proliferation, migration, and invasion, the relative clinical significance and mechanisms of action are still unclear. This study focuses on the important role of a novel lncRNA LINC00665 in the development of NSCLC. Long intergenic non-protein coding RNA 665 gene (LINC00665) was found through microarray analysis and was measured by real-time quantitative PCR (RT-qPCR). The interactions between LINC00665 and miR-138-5p as well as the interactions between miR-138-5p and E2F3 (E2F transcription factor 3) were explored by bioinformatics analysis and dual-luciferase assays. CCK-8, transwell and mouse xenograft assays were performed to investigate the effects of LINC00665 and miR-138-5p on NSCLC proliferation and invasion. As a result, LINC00665 expression was upregulated in NSCLC lung tissues and cells. Downregulated LINC00665 could arrest A549 and H1299 cell proliferation and invasion in vitro, and this finding was recapitulated in vivo. LINC00665 directly regulated the expression of miR-138-5p. Additionally, E2F3 was one of the targets of miR-138-5p; E2F3 without 3'UTR could reverse the inhibitory effects of downregulated LINC00665 on proliferation and invasion in A549 and H1299 cells. In conclusion, dysregulation of LINC00665 plays a vital role in NSCLC progression, indicating that its downregulation may confer decreased cell proliferation and invasion via the miR-138-5p/E2F3 signaling pathway.

6.
Ann Neurol ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396256

RESUMO

OBJECTIVE: Pharmaco-refractory focal motor epileptic seizures pose a significant challenge. Deep brain stimulation (DBS) is a recently recognized therapeutic option for the treatment of refractory epilepsy. To identify the specific target for focal motor seizures, we evaluate the modulatory effects of the subthalamic nucleus (STN) stimulation because of the critical role of STN in cortico-subcortical motor processing. METHODS: Seven patients with epilepsy with refractory seizures who underwent chronic stereoelectroencephalography (SEEG) monitoring were studied in presurgical evaluation. Seizure onset zone was hypothesized to be partially involved in the motor areas in 6 patients. For each patient, one electrode was temporally implanted into the STN that was ipsilateral to the seizure onset zone. The cortical-subcortical seizure propagation was systemically evaluated. The simultaneously electrophysiological responses over distributed cortical areas to STN stimulation at varied frequencies were quantitatively assessed. RESULTS: We observed the consistent downstream propagation of seizures from the motor cortex toward the ipsilateral STN and remarkable cortical responses on motor cortex to single-pulse STN stimulation. Furthermore, we showed frequency-dependent upstream modulatory effect of STN stimulation on motor cortex specifically. In contrast to the enhanced effects of low frequency stimulation, high-frequency stimulation of the STN can significantly reduce interictal spikes, high-frequency oscillations over motor cortex disclosing effective connections to the STN. INTERPRETATION: This result showed that the STN is not only engaged in as a propagation network of focal motor seizures but STN stimulation can profoundly modulate the epileptic activity of motor cortex in humans, suggesting a mechanism-based alternative for patients suffering from refractory focal motor seizures. ANN NEUROL 2020.

7.
Cell Biol Int ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32281700

RESUMO

To better treat patients with non-small cell lung cancer (NSCLC), the investigations on novel molecules affecting NSCLC progression are of vital importance. Long noncoding RNAs (lncRNAs) are identified as pivotal regulators that can affect the cellular activities of carcinomas. Long intergenic non-protein coding RNA 667 (LINC00667) is a newly found lncRNA, and its expression pattern and potent mechanisms are still obscure in NSCLC. Our study was the first to illustrate that LINC00667 was upregulated in NSCLC and LINC00667 silence refrained the proliferation, migration, and angiogenesis of NSCLC cells in vitro. In addition, vascular endothelial growth factor A (VEGFA) was modulated by LINC00667 at posttranscriptional level. Furthermore, mechanism experiments depicted that LINC00667 recruited eukaryotic translation initiation factor 4A3 (EIF4A3) to stabilize VEGFA messenger RNA. Eventually, rescue assays implied that LINC00667 modulated NSCLC progression via EIF4A3-stabilized VEGFA. Jointly, these findings hinted that LINC00667 was a tumor promoter in NSCLC, providing guidance for the exploration on NSCLC treatment.

8.
Phys Rev Lett ; 124(11): 113202, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32242706

RESUMO

Feynman's path integral approach is to sum over all possible spatiotemporal paths to reproduce the quantum wave function and the corresponding time evolution, which has enormous potential to reveal quantum processes in the classical view. However, the complete characterization of the quantum wave function with infinite paths is a formidable challenge, which greatly limits the application potential, especially in the strong-field physics and attosecond science. Instead of brute-force tracking every path one by one, here we propose a deep-learning-performed strong-field Feynman's formulation with a preclassification scheme that can predict directly the final results only with data of initial conditions, so as to attack unsurmountable tasks by existing strong-field methods and explore new physics. Our results build a bridge between deep learning and strong-field physics through Feynman's path integral, which would boost applications of deep learning to study the ultrafast time-dependent dynamics in strong-field physics and attosecond science and shed new light on the quantum-classical correspondence.

9.
Epilepsy Res ; 163: 106322, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32278277

RESUMO

OBJECTIVE: Magnetoencephalography (MEG) is valuable for guiding resective surgery in patients with epilepsy. However, its value for minimally invasive treatment is still unknown. This study aims to evaluate the value of MEG for stereo-electroencephalogram (EEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in magnetic resonance imaging (MRI)-negative epilepsies. METHODS: An observational cohort study was performed and 19 MRI-negative patients who underwent SEEG-guided RF-TC in our epilepsy center were included. In addition, 16 MRI-positive patients were included as a reference group. Semiology, electrophysiology, and imaging information were collected. To evaluate the value of locating the MEG cluster, the proportion of the RF-TC contacts located in the MEG cluster out of all contacts used to perform RF-TC in each patient was calculated. All patients underwent the standard SEEG-guided RF-TC procedure and were followed up after the treatment. RESULTS: Nineteen MRI-negative patients were divided into two groups based on the existence of MEG clusters; 10 patients with MEG clusters were in group I and nine patients without any MEG cluster were in group II. No significant difference was observed in terms of age, sex, type of seizures, or number of SEEG electrodes implanted. The median of the proportion of contacts in the MEG cluster was 77.0 % (IQR 57.7-100.0 %). The follow-up results showed that the probability of being seizure-free at one year after RFTC in MRI-negative patients with an MEG cluster was 30.0 % (95 % CI 11.6-77.3 %), significantly (p = 0.014) higher than that in patients without an MEG cluster; there was no significant difference when compared with MRI-positive patients. CONCLUSION: This is the first study to evaluate the value of MEG in SEEG-guided RF-TC in MRI-negative epilepsies. MEG is a useful supplement for patients with MRI-negative epilepsy. MEG can be applied in minimally invasive treatment. MEG clusters can help identify better candidates and provide a valuable target for SEEG-guided RF-TC, which leads to better outcomes.

10.
J Clin Oncol ; 38(16): 1774-1784, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32275467

RESUMO

PURPOSE: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS: This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS: Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION: Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

11.
Clin Neurol Neurosurg ; 193: 105785, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32200220

RESUMO

OBJECTIVE: The aim of this study was to investigate the burst suppression (BS) pattern on intra-operative electrocorticography (ECoG) in patients with temporal lobe epilepsy (TLE) and the surgical outcome. PATIENTS AND METHODS: From January 2017 to June 2017, 45 patients with TLE underwent temporal lobe resection with intra-operative ECoG at the Beijing Institute of Functional Neurosurgery of Xuanwu Hospital of Capital Medical University, China. The scalp EEG, pre-operative and post-operative ECoG were analyzed. Surgical outcome was evaluated with Engel's classification every 3 months, 6 months and 1 year after surgery. RESULTS: Before temporal lobe resection the ECoG showed a variable amount of interictal spiks in all patients. A different pattern of burst suppression (BS) was recorded in 33.3% (n = 15; male:7, female:8; mean age, 26.9 years; range 3-45 years) in a small zone of temporal cortex. The BS is characterized of a suppression pattern with bursts of high-amplitude spike rhythm or low amplitude fast activity. After the temporal lobe resection, BS was disappeared in 26.7% (4/15), 73.3% (n = 11) showed the focal BS pattern in a cortex adjacent to the margin of resection, 20% (n = 3) had no epileptiform abnormality, and 40% (n = 6) had minor spikes. The mean postoperative follow-up was 14 ± 2.1 months, 73.3% (n = 11) were class I and 26.7% (n = 4) were class Ⅱ (Engel's classification). CONCLUSION: The focal BS was observed during temporal lobectomy and this unusual pattern does not affect the surgical outcome in patients with TLE.

13.
Int J Cancer ; 147(2): 490-504, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32020593

RESUMO

Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple-negative breast cancer (TNBC). Epithelial-mesenchymal transition (EMT) is thought to contribute to chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal-like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA-MB-231 cells gradually increases in a time-dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin-resistant MDA-MB-231 cells are significantly higher than wild-type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC.

14.
Neuromolecular Med ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32086739

RESUMO

Glioblastoma is the most common primary tumor of the central nervous system that develops chemotherapy resistance. Previous studies showed that Allicin could inhibit multiple cancer cells including glioblastoma, but the function of Allicin in glioblastoma is still unclear. Our work aimed to investigate the underlying molecular mechanism. The results showed that miR-486-3p levels were greatly increased in glioblastoma during Allicin treatment. Overexpression of miR-486-3p increased chemosensitivity to temozolomide (TMZ) in vitro and in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct target of miR-486-3p, and miR-486-3p overexpression prevented the protein translation of MGMT. Moreover, overexpression of MGMT restored miR-486-3p-induced chemosensitivity to TMZ. Taken together, our studies revealed that Allicin could upregulate miR-486-3p and enhance TMZ sensitivity in glioblastoma. The results suggested that in the future, Allicin can be used as an adjuvant therapy with TMZ to improve the prognosis of patients, and miR-486-3p may be a potential target for glioblastoma treatment to improve the curative effects.

15.
Neuroreport ; 31(4): 311-318, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32058427

RESUMO

Some epileptic spasms are classified into focal-onset seizures. However, the cortical network underlying this kind of spasm seizure is not yet clear. Four patients with epileptic spasms who underwent intracranial electrode implantation and focal resection surgery were studied. All the patients had good outcomes, and three of them with intellectual disability showed improved intelligence after surgery. The power spectra characteristics of electrocorticography and the dynamic functional network changes of epileptic spasms were investigated. Electrocorticography power in the resected zone peaked 0.5 seconds before the clinical seizure onset and was especially prominent in the γ and ripple bands. The functional network analysis showed particular dynamic patterns of high-frequency activity among the resected zone, sensorimotor cortex, and the other region. In the gamma band, during the interictal segment, the information flow from the resected zone and the other region to the sensorimotor cortex was prominent. During the preictal segment, the information flow from the resected zone and sensorimotor cortex to the other region became stronger. In the ripple band, during the interictal segment, the information flow from the resected zone to the sensorimotor cortex and the other region was high. During the preictal segment, the information flow between the resected zone and sensorimotor cortex became stronger. Our results suggest that the sensorimotor cortex is a requisite for spasm seizure initiation, and the ripple activity loop between the resected zone and sensorimotor cortex may give rise to the seizure onset with the help of the gamma activity loop between the sensorimotor cortex and the other region for activation spreading.

16.
Anal Chem ; 92(5): 4006-4015, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32040907

RESUMO

Cancerous microvesicles (MVs), which are heterogeneous membrane-bound nanovesicles shed from the surfaces of cancer cells into the extracellular environment, have been widely recognized as promising "biofingerprints" for various cancers. High-performance identification of cancerous MVs plays a vital role in the early diagnosis of cancer, yet it is still technically challenging. Herein, we report a gold nanoparticle (AuNP)-decorated, dual-aptamer modified reduced graphene oxide (RGO) field-effect transistor (AAP-GFET) nanosensor for the label-free, specific, and sensitive quantification of HepG2 cell-derived MVs (HepG2-MVs). After GFET chips were fabricated, AuNPs were then decorated on the RGO surface. For specific capture and detection of HepG2-MVs, both sulfhydrylated HepG2 cell specific TLS11a aptamer (AptTLS11a) and epithelial cell adhesion molecule aptamer (AptEpCAM) were immobilized on the AuNP surface through an Au-S bond. This developed nanosensor delivered a broad linear dynamic range from 6 × 105 to 6 × 109 particles/mL and achieved a high sensitivity of 84 particles/µL for HepG2-MVs detection. Moreover, this AAP-GFET platform was able to distinguish HepG2-MVs from other liver cancer-related serum proteins (such as AFP and CEA) and MVs derived from human normal cells and other cancer cells of lung, pancreas, and prostate, suggesting its excellent method specificity. Compared with those modified with a single type of aptamer alone (AptTLS11a or AptEpCAM), such an AAP-GFET nanosensor showed greatly enhanced signals, suggesting that the dual-aptamer-based bio-nano interface was uniquely designed and could realize more sensitive quantification of HepG2-MVs. Using this platform to detect HepG2-MVs in clinical blood samples, we found that there were significant differences between healthy controls and hepatocellular carcinoma (HCC) patients, indicating its great potential in early HCC diagnosis.

17.
Sci Rep ; 10(1): 1568, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005939

RESUMO

Central nervous system infection (CNSI) is a significant type of infection that plagues the fields of neurology and neurosurgical science. Prompt and accurate diagnosis of CNSI is a major challenge in clinical and laboratory assessments; however, developing new methods may help improve diagnostic protocols. This study evaluated the second-generation micro/nanofluidic chip platform (MNCP-II), which overcomes the difficulties of diagnosing bacterial and fungal infections in the CNS. The MNCP-II is simple to operate, and can identify 44 genus or species targets and 35 genetic resistance determinants in 50 minutes. To evaluate the diagnostic accuracy of the second-generation micro/nanofluidic chip platform for CNSI in a multicenter study. The limit of detection (LOD) using the second-generation micro/nanofluidic chip platform was first determined using six different microbial standards. A total of 180 bacterium/fungi-containing cerebrospinal fluid (CSF) cultures and 26 CSF samples collected from CNSI patients with negative microbial cultures were evaluated using the MNCP-II platform for the identification of microorganism and determinants of genetic resistance. The results were compared to those obtained with conventional identification and antimicrobial susceptibility testing methods. The LOD of the various microbes tested with the MNCP-II was found to be in the range of 250-500 copies of DNA. For the 180 CSF microbe-positive cultures, the concordance rate between the platform and the conventional identification method was 90.00%; eight species attained 100% consistency. In the detection of 9 kinds of antibiotic resistance genes, including carbapenemases, ESBLs, aminoglycoside, vancomycin-related genes, and mecA, concordance rates with the conventional antimicrobial susceptibility testing methods exceeded 80.00%. For carbapenemases and ESBLs-related genes, both the sensitivity and positive predictive values of the platform tests were high (>90.0%) and could fully meet the requirements of clinical diagnosis. MNCP-II is a very effective molecular detection platform that can assist in the diagnosis of CNSI and can significantly improve diagnostic efficiency.

18.
Transl Stroke Res ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997156

RESUMO

Ischemic stroke is associated with various physiological and pathological processes including neuronal apoptosis. Growth-arrest-specific transcript 5 (GAS5), a long non-coding RNA (lncRNA), has been recently reported to affect ischemic stroke-induced neuron apoptosis, while its mechanisms remain largely undefined. Through in silico analysis, GAS5 was predicted to interact with the promoter of MAP4K4. The aim of the present study was therefore to investigate the possible role of GAS5 in the progression of ischemic stroke via regulation of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) methylation. The expression of MAP4K4 was found to be lowly expressed in the clinical samples collected from 55 patients. MAP4K4 was suggested to be methylated in an in vitro model of oxygen-glucose deprivation (OGD)-treated mouse primary cortical neurons, while its overexpression could inhibit OGD-induced neuronal apoptosis. A series of dual-luciferase reporter, RIP, RNA pull-down, ChIP MSP, and BSP assays confirmed that GAS5 significantly induced MAP4K4 methylation and downregulated MAP4K4 expression through the recruitment of DNA methyltransferase 3B (DNMT3B). An in vivo ischemic stroke model was developed using middle cerebral artery occlusion (MCAO). Upregulation of GAS5 promoted OGD-induced neuronal apoptosis in the in vitro model and increased cerebral infarction size and neurological score in the in vivo model by reducing MAP4K4 expression. Collectively, the present study highlights that silencing GAS5 may inhibit neuronal apoptosis and improve neurological function in ischemic stroke by suppressing DNMT3B-mediated MAP4K4 methylation, which contributes to better understanding of the pathologies of ischemic stroke and development of novel therapeutic options for this disease.

19.
Biomed Pharmacother ; 122: 109692, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918268

RESUMO

Asthma is a chronic lung inflammatory disease with high incidence. MicroRNA-192-5p (miR-192-5p) was down-regulated in asthmatics. However, the role of miR-192-5p in asthma is still unclear. In current study, in vitro, the overexpression of miR-192-5p, matrix metalloproteinase (MMP)-16 and autophagy related 7 (ATG7) was conducted in airway smooth muscle cells (ASMCs). We found that miR-192-5p suppressed cell proliferation, and decreased MMP-16 and ATG7 expression. MMP-16 and ATG7 promoted cell proliferation, and further alleviated the down-regulation of miR-192-5p on proliferation of ASMCs. in vivo, miR-192-5p was down-regulated in asthma mice, and involved in improvement of asthma mice. MiR-192-5p was demonstrated to alleviate inflammation in asthma mice, including decreasing the level of ovalbumin (OVA)-specific IgE, interleukin (IL)-4, IL-5, IL-13, iNOS and COX-2. Moreover, the attenuation of airway remodeling induced by miR-192-5p in asthma mice were expressed by the reduction of fibroblast growth factor-23 (FGF-23) level, decrease in concentrations of MMP-2 and MMP-9 as well as down-regulation of collagen I deposition. Further, miR-192-5p also caused the suppression of autophagy in asthma mice, exhibiting a decrease in LC3II/I, beclin-1 and ATG7, and an increase in p62. Importantly, MMP-16 and ATG7 were confirmed to be targets of miR-192-5p. Therefore, our results indicate that miRNA-192-5p may attenuate airway remodeling and autophagy in asthma via targeting MMP-16 and ATG7.

20.
Sci Data ; 7(1): 5, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896793

RESUMO

Aroma is an important parameter for table grapes and wines; terpenes are typical compounds in Muscat-type grape cultivars and can be easily perceived by humans because of their low olfactory threshold. Volatile terpenes contribute directly to the aroma character, while glycoside-bound terpenes are potential aromatic compounds and can be changed to their volatile forms via hydrolysis. With gas chromatography-mass spectrometry and a solid-phase microextraction method, an automatic data analysis platform was constructed; terpene compounds were identified and quantified from three table grape cultivars at three stages during berry development, and the raw data were deposited in MetaboLights. Terpene metabolite accumulation profiles are presented in this article for integrative analysis with the transcriptome data and phenotypic data to elucidate the important candidate genes and mechanism for terpene biosynthesis. Our method has applications in the identification and quantification of terpene compounds with very low or trace concentrations.

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