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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118872, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32889341

RESUMO

The spores of Bacillus anthracis are highly deadly to human beings and animals, and are concurrently potential biological warfare agents. Hence, the rapid and sensitive monitoring Bacillus anthracis biomarker, dipicolinic acid (DPA), is very desirable. Herein, orange/green dual-emissive carbon dots (OG-CDs) were synthesized via the hydrothermal approach. The OG-CDs not only emitted dual fluorescence at 527 and 590 nm under the single 503 nm excitation, but also exhibited excellent water solubility, good photostability and great salt tolerance. The fluorescence of the OG-CDs at 527 nm can be completely quenched when chelated with Cu(II). However, because of the stronger chelation between DPA and Cu(II), the fluorescence restored rapidly on subsequent addition of DPA. As such, the CD-Cu(II) system can be used for determination of DPA based on the fluorescence "off-on" response. Under optimum conditions, the detection limit for DPA was 56 nM, with a linear range of 0.5-12.5 µM. The established CD-Cu(II) based spectrofluorometric method has been applied to the analysis of DPA in real water samples with recoveries of 93.6%-104.3%. More remarkably, the CD-Cu(II) probe also has been successfully applied for the imaging of DPA in Escherichia coli with excellent bio-compatibility.

2.
Methods Mol Biol ; 2198: 349-367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32822044

RESUMO

Here, we provide a detailed protocol for our previously published technique, APOBEC-Coupled Epigenetic Sequencing (ACE-Seq), which localizes 5-hydroxymethylcytosine at single nucleotide resolution using nanogram quantities of input genomic DNA. In addition to describing suggested troubleshooting workflows, these methods include four important updates which should facilitate widespread implementation of the technique: (1) additionally optimized reaction conditions; (2) redesigned quality controls which can be performed prior to resource-consumptive deep sequencing; (3) confirmation that the less active, uncleaved APOBEC3A (A3A) fusion protein, which is easier to purify, can be used to perform ACE-Seq ; and (4) an example bioinformatic pipeline with suggested filtering strategies. Finally, we have provided a supplementary video which gives a narrated overview of the entire method and focuses on how best to perform the snap cool and A3A deamination steps central to successful execution of the method.

3.
Int J Biol Macromol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038404

RESUMO

Hyaluronic acid (HA) is an anionic linear polysaccharide abundantly distributed in the extracellular matrix of mammalian connective, growing, and tumor tissues. Hyaluronidase is used as an important drug diffusion promoter and a tool enzyme to produce HA oligosaccharides. However, there is no thermostable hyaluronidase suitable for application to date. In this study, a thermophilic hyaluronate lyase, TcHly8C, from Thermasporomyces composti DSM22891 was expressed in Escherichia coli. The recombinant TcHly8C was most active at 70 °C, and it retained about 30% of initial activity after incubation at 60 °C for 28 days. The half-lives of TcHly8C at 60 °C and 70 °C were 16.1 d and 2.3 h, respectively. The optimum pH of TcHly8C is 5.93, and it was stable at pH 6.15-10.90. The presence of Mg2+ could enhance its enzymatic activity significantly. Km, kcat, and kcat/Km of TcHly8C towards HA were 3.69 mg∙ml-1, 17.82 s-1, and 4.82 ml∙mg-1∙s-1, respectively. TcHly8C degraded HA in an exolytic mode, and the end product was unsaturated HA disaccharide (ΔUA-GlcNAc). Overall, our results show that TcHly8C is the first reported PL8 exo-type hyaluronate lyase with high thermostability, which provides a potential enzyme used in medicine and production of HA oligosaccharides.

4.
J Control Release ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039481

RESUMO

Development of liposomal nanomedicine with robust stability, high drug loading and synergistic efficacy is a promising strategy for effective cancer therapy. Here, we present an iron-crosslinked rosmarinic liposome (Rososome) which can load high contents of drugs (including 25.8% rosmarinic acid and 9.04% doxorubicin), keep stable in a high concentration of anionic detergent and exhibit synergistic anti-cancer efficacy. The Rososomes were constructed by rosmarinic acid-lipid conjugates which not only work synergistically with doxorubicin by producing reactive oxygen species but also provide catechol moieties for the iron cross-linkages. The cross-linkages can lock the payloads tightly, endowing the crosslinked Rososome with better stability and pharmacokinetics than its non-crosslinked counterpart. On the syngeneic mouse model of breast cancer, the iron-crosslinked Rososomes exhibit better anticancer efficacy than free rosmarinic acid, doxorubicin, non-crosslinked Rososome and commercial liposomal formulation of doxorubicin (DOXIL). This study introduces a novel strategy for the development of liposomes with robust stability, high drug loading and synergistic anti-cancer efficacy.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1762-1768, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067987

RESUMO

OBJECTIVE: To investigate the effect of dasatinib on the expansion of NK cells in vitro, as well as the subsets, receptor expression and cytotoxic function of NK cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult volunteers and cultured with SCGM added IL-2 and IL-15 for expansion of NK cells. In this culture system, dasatinib of different concentrations were added. Cell counting and phenotyping by flow cytometry were used to evaluate the amplification efficiency of NK cells. FCM was used to detect the expression of receptors on the surface of NK cells and the distribution of subsets. Subsequently, degranulation assay and CFSE/7AAD based cytotoxicity assay were used to detect the effects of dasatinib on NK cytotoxicity against leukemia cell line K562 cells. RESULTS: The expansion efficiency of NK cells in vitro could be increased by dasatinib at the concentration range of 5-50 nmol/L, and the expansion efficiency of NK cells reached the peak at 20 nmol/L of dasatinib. The NK cytotoxicity against K562 cells in dasatinib cultured group at the concentration of 20 nmol/L was significantly higher than that in control group. For the cells cultured by disatinib in vitro, the MFI of CD226, NKP46 and NKG2D was up-regulated; the ratio of NKG2A+CD57- subset was down-regulated, while the ratio of NKG2A-CD57+ subset was up-regulated.The degranulation response of NKG2A-CD57+ NK cells to K562 cells was stronger than that of NKG2A+CD57- NK cells. CONCLUSION: The results shows that appropriate dose of dasatinib(20 nmol/L) can increases the amplification efficiency of NK cells, simultaneously up-regulates the expression of NK activating receptors and increases the NKG2A-CD57+ subset, which lead to the enhancement of NK cytotoxicty against leukemia cell lines.


Assuntos
Antineoplásicos , Leucócitos Mononucleares , Adulto , Antineoplásicos/farmacologia , Dasatinibe/farmacologia , Humanos , Células K562 , Células Matadoras Naturais
6.
Artigo em Inglês | MEDLINE | ID: mdl-33079782

RESUMO

BACKGROUND: The involvement of gastrointestinal tract is rare in sarcoidosis. Endoscopic and histologic evaluation likely provides diagnostic clue in sarcoidosis patients. The aims were to assess the frequency of abnormal endoscopy and histology in patients with sarcoidosis undergoing endoscopic evaluation and to characterize the endoscopic and histologic features in sarcoidosis of the gastrointestinal tract. METHODS: This was a retrospective study that included 230 patients with a confirmed diagnosis of sarcoidosis in a tertiary care center. The endoscopic and pathology reports were assessed, and serum angiotensin converting enzyme analysis was performed. RESULTS: Of 230 patients, 63 upper endoscopies and 142 colonoscopies were performed. The most common indication for upper endoscopy was abdominal pain (36.8%) while colonoscopy was most frequently performed for colorectal cancer screening (58.2%). There were 25 upper gastrointestinal biopsies performed (biopsy rate 39.7%) with a diagnostic yield of 92.0% abnormal biopsies, of which the main findings were esophageal tissue eosinophilia, gastritis and duodenal villous blunting. There were 99 lower gastrointestinal biopsies (biopsy rate 64.1%) with a diagnostic yield of 68.7% abnormal biopsies for adenocarcinoma, adenoma, inflammation, low-grade dysplasia, or polyp. Only one gastric biopsy revealed evidence of non-necrotizing granulomas. Of note, patients undergoing esophagogastroduodenoscopy or colonoscopy were more likely to have underlying gastrointestinal comorbidities (62.5%, P < 0.001). CONCLUSION: Patients with sarcoidosis undergoing endoscopic evaluation have high histologic abnormalities with a low probability of characteristic histologic (i.e. granulomas, Schaumann and asteroid bodies) findings.

7.
Nanoscale ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057537

RESUMO

Flexible capacitive pressure sensors have many important applications but usually exhibit a highly non-linear response as the sensitivity drops dramatically towards high pressure. Herein, we propose a novel strategy to achieve high linearity over a broad sensing range by using percolative composites as the dielectric layer. The linear response is attributed to the fast increase in dielectric constant that can compensate for the sensitivity drop caused by the decreased compressibility during compression. An analytical model is established to predict the linearity by coupling the percolation theory and Mooney-Rivlin equation. Based on the model, a capacitive pressure sensor using a spiky nickel/polydimethyl siloxane composite as the dielectric layer is fabricated as a demonstration and exhibits excellent linearity (R2 = 0.999) up to 1.7 MPa. In addition, owing to the nature of the polymer composite, its dispersion can be conformally coated on surfaces with complex shapes or be molded into films with surface microstructures to achieve a unique combination of high sensitivity and linear response over a wide pressure sensing range.

8.
Mol Cell ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33065002

RESUMO

Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-driven proton pumps comprised of a cytoplasmic V1 complex for ATP hydrolysis and a membrane-embedded Vo complex for proton transfer. They play important roles in acidification of intracellular vesicles, organelles, and the extracellular milieu in eukaryotes. Here, we report cryoelectron microscopy structures of human V-ATPase in three rotational states at up to 2.9-Å resolution. Aided by mass spectrometry, we build all known protein subunits with associated N-linked glycans and identify glycolipids and phospholipids in the Vo complex. We define ATP6AP1 as a structural hub for Vo complex assembly because it connects to multiple Vo subunits and phospholipids in the c-ring. The glycolipids and the glycosylated Vo subunits form a luminal glycan coat critical for V-ATPase folding, localization, and stability. This study identifies mechanisms of V-ATPase assembly and biogenesis that rely on the integrated roles of ATP6AP1, glycans, and lipids.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33063547

RESUMO

BACKGROUND: Computed tomography (CT) has become an important technique for assessing skeletal muscle mass. Low skeletal muscle mass (LSMM) is considered an unfavorable factor for postoperative complications in patients with gastric cancer (GC). METHODS: Patients who underwent laparoscopic gastrectomy for GC were included. Skeletal muscle mass at the third lumbar vertebra (L3) level was measured by preoperatively using CT. The patients were divided into an LSMM group and a non-LSMM group and the intergroup differences were analyzed. Furthermore, we divided the LSMM group into mild and severe LSMM subgroups. The study also analyzed the influence of obesity-related LSMM on postoperative complications. RESULTS: A total of 409 patients were enrolled; of them, 265 had LSMM and 41 had severe LSMM. LSMM was associated with age, body mass index, and Nutritional Risk Screening 2002 score. In the multivariate analysis, LSMM was not related to postoperative complications. Further analysis revealed that severe LSMM was a risk factor for postoperative complications. The study also found that the risk of postoperative complications was significantly increased in patients with obesity-related LSMM. CONCLUSIONS: LSMM was not significantly correlated with postoperative complications. Severe LSMM and obesity-related LSMM are unfavorable factors for postoperative complications with GC after gastrectomy.

10.
Sleep Breath ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011910

RESUMO

PURPOSE: To determine the predictive factors of initial and long-term adherence to positive airway pressure (PAP) therapy and factors leading to an unfavorable shift of PAP compliance. METHODS: This follow-up study was comprised of newly diagnosed patients with obstructive sleep apnea (OSA) amenable to PAP therapy from January 2017 to April 2019. Information on basic demographics, comorbidities, and sleep-related symptoms were collected. PAP adherence data were collected at the end of the first week and the third month. RESULTS: Of 166 patients enrolled, data from 142 (86%) were in the final analysis. Overall PAP usage was worse at 3 months declining from the first week. After adjusting for age and gender, multinomial logistic regression analysis showed that a small number of sleep-related symptoms (OR, 0.69; 95% CI, 0.52-0.91) and low arousal threshold (ArTH) (OR, 4.44; 95% CI, 1.52-12.98) were associated with higher odds of noncompliance. Low ArTH (OR, 2.87; 95% CI, 1.09-7.57) and lower body mass index (BMI) (OR, 0.88; 95% CI, 0.78-0.99) increased the risk of compliance-to-noncompliance shift. Sixty-two patients with polysomnography were analyzed separately. After adjustment for age and gender, poor sleep efficiency (OR, 0.80; 95% CI, 0.68-0.94) was associated with higher odds of consistent noncompliance. Low ArTH (OR, 15.36; 95% CI, 1.44-164.24) increased the risk of compliance-to-noncompliance shift in this subgroup. CONCLUSIONS: Lower BMI and low ArTH were associated with an unfavorable shift of PAP compliance over time in patients with OSA, which was different from the predictors of consistent PAP noncompliance of patients with OSA.

11.
J Anat ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011984

RESUMO

The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage, and plays an important role in the diffusion of nutrients into the intervertebral discs. Its damage may seriously affect the disc degeneration, and result in low back pain (LBP). However, the structural features of damaged CEPs have not been well characterized, and this hinders our understanding of the etiology of disc degeneration and pain. To present the structural features of micro-damaged CEPs in patients with disc degeneration and LBP that might even be regarded as an initial factor for disc degeneration, we performed a histological study of micro-damaged CEPs harvested from human lumbar intervertebral discs and analyzed its clinical implications. Human lumbar CEPs were excised from 35 patients (mean age 60.91 years) who had disc degeneration and LBP. Control tissue was obtained from 15 patients (mean age 54.67 years) with lumbar vertebral burst fractures. LBP and disability were assessed clinically, and all patients underwent anterior vertebral body fusion surgery. CEPs together with some adjacent nucleus pulposus (NP) were sectioned at 4 µm, and stained using H&E, Safranin O/Fast Green, and Alcian Blue. Immunostaining and PCR were used to identify various markers of degeneration, innervation, and inflammation. Histology demonstrated physical micro-damage in 14/35 CEPs from the disc degeneration group. Six major types of damage could be distinguished: fissure, traumatic nodes, vascular mimicry, incorporation of NP tissue within the CEP, incorporation of bone within the CEP, and incorporation of NP and bone within the CEP. Pain and disability scores (ODI: p = 0.0190; JOA: p = 0.0205; JOABPEQ: p = 0.0034) were significantly higher in those with micro-damaged CEPs (N = 14) than in those with non-damaged CEPs (N = 21). CEP damage was significantly associated with elevated MMP3 (p = 0.043), MMP13 (p = 0.0191), ADAMTS5 (p = 0.0253), TNF-α (p = 0.0011), and Substance P (p = 0.0028), and with reduced Sox9 (p = 0.0212), aggrecan (p = 0.0127), and type II collagen (p = 0.0139). In conclusion, we presented a new classification of human lumbar micro-damaged CEPs. Furthermore, we verify disc degeneration, innervation, and discogenic pain in micro-damaged CEPs.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33015724

RESUMO

Tanning industry has been identified as a significant source of heavy metals; however, heavy metals contamination in farmland soil due to small-scale tanning activities remains unstudied. Here, samples from topsoil, profile soil, water and sediments in the vicinity of a small-scale tanning area in Nanning, Guangxi Zhuang Autonomous Region, southern China, were collected to explore the contamination characteristics and source apportionment of Cd, Cr, Hg, As, Cu, Pb, Ni and Zn. The results show that the farmland soil was mainly contaminated by Cr and its content was 33.40-3830.00 mg kg-1. The highest level of Cr, Cd and Hg was above their thresholds, while the average contents of Cd, Cr, Pb and Hg exceeded the corresponding background levels. Moreover, enrichment of Cr in soil profiles and stream sediments were also observed, whose concentrations varied from 11.50 to 2590.00 mg kg-1 and 738.00 to 11,200.00 mg kg-1, respectively. Concentrations of Cr in top soils and soil profiles from farmland surrounding the stream were significantly higher than those from other areas, and the soils surrounding the stream were moderately to heavily polluted. The multivariate statistical analysis indicated that the heavy metals originated from traffic (Cu, Ni, Zn, Hg, and Pb), agriculture (Cr and Cd) and nature (As). Source apportionment with PMF model results showed that the relative contribution rates of heavy metals by traffic, tanning, agriculture, other industrial activities and natural sources were 16.00%, 18.88%, 20.88%, 22.04% and 22.20%, respectively. These findings indicate that small-scale tanning activities could also lead to heavy metal accumulation in the surrounding environment, which requires decision-makers to pay more attention and to develop effective remediation procedures.

13.
Toxicol Appl Pharmacol ; 408: 115263, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022283

RESUMO

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat because there are no targeted therapies. Currently, chemotherapy is the only clinical option for TNBC despite development of resistance. New therapeutic agents with unique mechanisms of action are urgently needed; therefore, this study investigated the potential anti-TNBC effects of budlein A methylacrylate (BAM), a natural sesquiterpene lactone isolated from plants of the Helianthus genus. We discovered that BAM selectively suppressed and induced apoptosis TNBC cell growth versus other breast cancer or normal mammary epithelial cells. Mechanistically, BAM co-inhibited inhibitor of nuclear factor κBα (IκBα) kinase subunit ß (IKKß) and exportin-1 (XPO-1; chromosome region maintenance 1, CRM1), which are two dysregulated onco-related proteins in TNBC cells, by covalently modifying key functional cysteine residues (Cys179 of IKKß, Cys528 of XPO-1). Dual inhibition led to the stabilization and nuclear retention of IκBα, impairment of NF-κB transcriptional activity, and consequent induction of TNBC cell apoptosis. In conclusion, this study provides evidence that co-inhibition of IKKß and XPO-1 by BAM was effective against TNBC, demonstrating it as a representative new generation inhibitor with potential for TNBC treatment.

14.
Redox Biol ; 37: 101761, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33080440

RESUMO

Macrophage recruitment and pro-inflammatory differentiation are hallmarks of various diseases, including infection and sepsis. Although studies suggest that mitochondria may regulate macrophage immune responses, it remains unclear whether mitochondrial mass affects macrophage pro-inflammatory differentiation. Here, we found that lipopolysaccharide (LPS)-activated macrophages possess higher mitochondrial mass than resting cells. Therefore, this study aimed to explore the functional role and molecular mechanisms of increased mitochondrial mass in pro-inflammatory differentiated macrophages. Results show that an increase in the mitochondrial mass of macrophages positively correlates with inflammatory cytokine generation in response to LPS. RNA-seq analysis revealed that LPS promotes signal transducers and activators of transcription 2 (Stat2) and dynamin-related protein 1 (Drp1) expression, which are enriched in positive mitochondrial fission regulation. Meanwhile, knockdown or pharmacological inhibition of Drp1 blunts LPS-induced mitochondrial mass increase and pro-inflammatory differentiation. Moreover, Stat2 boosts Drp1 phosphorylation at serine 616, required for Drp1-mediated mitochondrial fission. LPS also causes Stat2-and Drp1-dependent biogenesis, which contributes to the generation of additional mitochondria. However, these mitochondria are profoundly remodeled, displaying fragmented morphology, loose cristae, reduced Δψm, and metabolic programming. Furthermore, these remodeled mitochondria shift their function from ATP synthesis to reactive oxygen species (ROS) production, which drives NFκB-dependent inflammatory cytokine transcription. Interestingly, an increase in mitochondrial mass with constitutively active phosphomimetic mutant of Drp1 (Drp1S616E) boosted pro-inflammatory response in macrophages without LPS stimulation. In vivo, we also demonstrated that Mdivi-1 administration inhibits LPS-induced macrophage pro-inflammatory differentiation. Importantly, we observed Stat2 phosphorylation and Drp1-dependent mitochondrial mass increase in macrophages isolated from LPS-challenged mice. In conclusion, we comprehensively demonstrate that a Stat2-Drp1 dependent mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages. Therefore, targeting the Stat2-Drp1 axis may provide novel therapeutic approaches for treating infection and inflammatory diseases.

15.
BMC Med Genomics ; 13(Suppl 10): 154, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33087120

RESUMO

BACKGROUND: DNA methylation is a key epigenetic regulator contributing to cancer development. To understand the role of DNA methylation in tumorigenesis, it is important to investigate and compare differential methylation (DM) patterns between normal and case samples across different cancer types. However, current pan-cancer analyses call DM separately for each cancer, which suffers from lower statistical power and fails to provide a comprehensive view for patterns across cancers. METHODS: In this work, we propose a rigorous statistical model, PanDM, to jointly characterize DM patterns across diverse cancer types. PanDM uses the hidden correlations in the combined dataset to improve statistical power through joint modeling. PanDM takes summary statistics from separate analyses as input and performs methylation site clustering, differential methylation detection, and pan-cancer pattern discovery. We demonstrate the favorable performance of PanDM using simulation data. We apply our model to 12 cancer methylome data collected from The Cancer Genome Atlas (TCGA) project. We further conduct ontology- and pathway-enrichment analyses to gain new biological insights into the pan-cancer DM patterns learned by PanDM. RESULTS: PanDM outperforms two types of separate analyses in the power of DM calling in the simulation study. Application of PanDM to TCGA data reveals 37 pan-cancer DM patterns in the 12 cancer methylomes, including both common and cancer-type-specific patterns. These 37 patterns are in turn used to group cancer types. Functional ontology and biological pathways enriched in the non-common patterns not only underpin the cancer-type-specific etiology and pathogenesis but also unveil the common environmental risk factors shared by multiple cancer types. Moreover, we also identify PanDM-specific DM CpG sites that the common strategy fails to detect. CONCLUSIONS: PanDM is a powerful tool that provides a systematic way to investigate aberrant methylation patterns across multiple cancer types. Results from real data analyses suggest a novel angle for us to understand the common and specific DM patterns in different cancers. Moreover, as PanDM works on the summary statistics for each cancer type, the same framework can in principle be applied to pan-cancer analyses of other functional genomic profiles. We implement PanDM as an R package, which is freely available at http://www.sta.cuhk.edu.hk/YWei/PanDM.html .

16.
Molecules ; 25(20)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066647

RESUMO

Naringenin is found mainly in citrus fruits, and is thought to be beneficial in the prevention and control of lung diseases. This study aims to investigate the mechanisms of naringenin against the damage in the lung caused by cigarette smoke. A system bioinformatic approach was proposed to predict the mechanisms of naringenin for protecting lung health. Then, we validated this prediction in BEAS-2B cells treated with cigarette smoke extract (CSE). System bioinformatic analysis indicated that naringenin exhibits protective effects on lung through the inhibition of inflammation and suppression of oxidative stress based on a multi-pathways network, mainly including oxidative stress pathway, Nrf2 pathway, Lung fibrosis pathway, IL-3 signaling pathway, and Aryl hydrocarbon receptor pathway. The in vitro results showed that naringenin significantly attenuated CSE-induced up-regulation of IL-8 and TNF-α. CSE stimulation increased the mRNA expressions of Nrf2, HO-1, and NQO1; the levels of total protein and nuclear protein of Nrf2; and the activity of SOD on days 2 and 4; but decreased these indexes on day 6. Naringenin can balance the antioxidant system by regulating Nrf2 and its downstream genes, preliminarily validating that Nrf2 pathway is involved in the protection offered by naringenin against cigarette smoke-induced damage to the lung. It suggests that dietary naringenin shows possible potential use in the management of lung health.

17.
Med Image Anal ; 67: 101830, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33096519

RESUMO

The detection and pathogenic factors analysis of Parkinson's disease (PD) has a practical significance for its diagnosis and treatment. However, the traditional research paradigms are commonly based on single neural imaging data, which is easy to ignore the complementarity between multimodal imaging genetics data. The existing researches also pay little attention to the comprehensive framework of patient detection and pathogenic factors analysis for PD. Based on functional magnetic resonance imaging (fMRI) data and single nucleotide polymorphism (SNP) data, a novel brain disease multimodal data analysis model is proposed in this paper. Firstly, according to the complementarity between the two types of data, the classical correlation analysis method is used to construct the fusion feature of subjects. Secondly, based on the artificial neural network, the fusion feature analysis tool named clustering evolutionary random neural network ensemble (CERNNE) is designed. This method integrates multiple neural networks constructed randomly, and uses clustering evolution strategy to optimize the ensemble learner by adaptive selective integration, selecting the discriminative features for PD analysis and ensuring the generalization performance of the ensemble model. By combining with data fusion scheme, the CERNNE is applied to forming a multi-task analysis framework, recognizing PD patients and predicting PD-associated brain regions and genes. In the multimodal data experiment, the proposed framework shows better classification performance and pathogenic factors predicting ability, which provides a new perspective for the diagnosis of PD.

18.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097545

RESUMO

Epidermal electrophysiology is widely carried out for disease diagnosis, performance monitoring, human-machine interaction, etc. Compared with thick, stiff, and irritating gel electrodes, emerging tattoo-like epidermal electrodes offer much better wearability and versatility. However, state-of-the-art tattoo-like electrodes are limited in size (e.g., centimeters) to perform electrophysiology at scale due to challenges including large-area fabrication, skin lamination, and electrical interference from long interconnects. Therefore, we report large-area, soft, breathable, substrate- and encapsulation-free electrodes designed into transformable filamentary serpentines that can be rapidly fabricated by cut-and-paste method. We propose a Cartan curve-inspired transfer process to minimize strain in the electrodes when laminated on nondevelopable skin surfaces. Unwanted signals picked up by the unencapsulated interconnects can be eliminated through a previously unexplored electrical compensation strategy. These tattoo-like electrodes can comfortably cover the whole chest, forearm, or neck for applications such as multichannel electrocardiography, sign language recognition, prosthetic control or mapping of neck activities.

19.
Cell Death Dis ; 11(10): 908, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097685

RESUMO

The long noncoding RNA (lncRNA) LUCAT1 was recently reported to be upregulated and to play an essential role in multiple cancer types, especially colorectal cancer (CRC), but the molecular mechanisms of LUCAT1 in CRC are mostly unreported. Here, a systematic analysis of LUACT1 expression is performed with data from TCGA database and clinic CRC samples. LUCAT1 is identified as a putative oncogene, which is significantly upregulated in CRC and is associated with poor prognosis. Loss of LUCAT1 restricts CRC proliferative capacities in vitro and in vivo. Mechanically, NCL is identified as the protein binding partner of LUCAT1 by using chromatin isolation by RNA purification coupled with mass spectrometry (ChIRP-MS) and RNA immunoprecipitation assays. We also show that NCL directly binds to LUCAT1 via its putative G-quadruplex-forming regions from nucleotides 717 to 746. The interaction between LUCAT1 and NCL interferes NCL-mediated inhibition of MYC and promote the expression of MYC. Cells lacking LUCAT1 show a decreased MYC expression, and NCL knockdown rescue LUCAT1 depletion-induced inhibition of CRC cell proliferation and MYC expression. Our results suggest that LUCAT1 plays a critical role in CRC cell proliferation by inhibiting the function of NCL via its G-quadruplex structure and may serve as a new prognostic biomarker and effective therapeutic target for CRC.

20.
Anal Chim Acta ; 1129: 40-48, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32891389

RESUMO

A novel label-free fluorescent biosensing strategy was described for the sensitive detection of mucin 1 (MUC1). It consisted of an M-shaped aptamer probe for exonuclease I (Exo I)-assisted target recycling (EATR) amplification, and two AgNCs-hairpin probes for graphene oxide (GO)-assisted hybridization chain reaction (HCR) amplification. Based on the specificity of aptamer-target recognition, the addition of MUC1 caused a conformational change in the M-shaped aptamer probe, which was split into a MUC1-P3 complex and a P1-P2 duplex. Exo I then catalyzed the cleavage of aptamer sequence P3 from the MUC1-P3 complex and released the target MUC1. The released target MUC1 was free to bind with a new M-shaped probe to perform EATR amplification. Furthermore, the P1-P2 duplex with three single-stranded arms can act as a primer to initiate HCR between hairpin probes AgNCs-H1 and AgNCs-H2. In the process of HCR, two AgNCs-hairpins were autonomously cross-opened, generating long linear double-stranded nanowires containing large numbers of AgNCs. These nanowires cannot be quenched by GO due to the weak affinity between the long double-stranded DNA and GO, thereby retaining a strong fluorescent signal indicative of the concentration of MUC1. With these designs, in addition to an extremely low detection limit of 0.36 fg mL-1, the method exhibited an acceptable linear response to detect MUC1 from 1 fg mL-1 to 1 ng mL-1. Additionally, this method could be exerted with a high degree of success to detect MUC1 in diluted human serum with satisfactory results.

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