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1.
Comput Biol Med ; 125: 104015, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33035961

RESUMO

Despite great progress in nitric oxide (NO) controlled releasing strategies, the in vivo spatiotemporal NO distribution of arteries is still unclear, which makes it impossible to assess the status of arteries and render NO-based therapies in vivo largely fruitless. Here, we presented personalized computational modelling to calculate the NO distribution on the endothelial surface and in the arterial wall of human atherosclerotic carotid artery bifurcations using models constructed from MRI. The computational results indicated the distribution of NO in the atherosclerotic artery is highly uneven. The volume-weighted average NO concentration (CV) in regions with lipid plaques (9.76 ± 2.82 nM) was about 22 times higher than that in the plaque-free regions. Regions where also the calcified plaque components and the intraplaque hemorrhages are present would increase and abate the CV, respectively. The dynamic blood flow during the cycle would directly affect the distribution of NO on the endothelial surface. The luminal NO distribution is closely related to hemodynamic indicators, including wall shear stress (WSS), time averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residence time (RRT). In conclusion, atherosclerotic components determine the space-averaged NO concentration in arterial wall and blood flow controls the luminal NO concentration.

2.
Nucleic Acids Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045734

RESUMO

In this report, we investigated the molecular mechanism underlying a deafness-associated m.7516delA mutation affecting the 5' end processing sites of mitochondrial tRNAAsp and tRNASer(UCN). An in vitro processing experiment demonstrated that m.7516delA mutation caused the aberrant 5' end processing of tRNASer(UCN) and tRNAAsp precursors, catalyzed by RNase P. Using cytoplasmic hybrids (cybrids) derived from one hearing-impaired Chinese family bearing the m.7516delA mutation and control, we demonstrated the asymmetrical effects of m.7516delA mutation on the processing of tRNAs in the heavy (H)-strand and light (L)-strand polycistronic transcripts. Specially, the m.7516delA mutation caused the decreased levels of tRNASer(UCN) and downstream five tRNAs, including tRNATyr from the L-strand transcripts and tRNAAsp from the H-strand transcripts. Strikingly, mutant cybrids exhibited the lower level of COX2 mRNA and accumulation of longer and uncleaved precursors of COX2 from the H-strand transcripts. Aberrant RNA metabolisms yielded variable reductions in the mitochondrial proteins, especially marked reductions in the levels of ND4, ND5, CO1, CO2 and CO3. The impairment of mitochondrial translation caused the proteostasis stress and respiratory deficiency, diminished ATP production and membrane potential, increased production of reactive oxygen species and promoted apoptosis. Our findings provide new insights into the pathophysiology of deafness arising from mitochondrial tRNA processing defects.

3.
Obes Surg ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047288

RESUMO

Abnormal anatomic findings are a major concern before performing bariatric surgery, while pathological changes are considered less often. The present study aimed to investigate the incidences of gastric lesions warranting follow-up in patients undergoing bariatric surgery. Meta-analyses were conducted to calculate the pooled incidences of gastric lesions in patients undergoing bariatric surgery. Fifty-nine studies including 32,789 patients were included: 26 on endoscopic biopsy, 26 on pathological findings of the excised specimen, five on the intraoperative exploration results, and two on both preoperative endoscopy and postoperative specimen. Generally, atrophic gastritis (3.05% (95% CI (confidence interval) 1.53-6.09)), intestinal metaplasia (2.44% (95% CI 1.76-3.25)), and GIST (gastrointestinal stromal tumor) (0.45% (95% CI 0.31-0.60)) were not rarely found. Routine preoperative endoscopy was applied in 16 studies, and the pooled incidences of atrophic gastritis and intestinal metaplasia were 2.64% (95% CI 0.78-8.9) and 2.70% (95% CI 0.9-5.42), respectively. Hp. (Helicobacter pylori) screening and eradication were routinely performed in 10 studies, and that was related to a reduced incidence of atrophic gastritis (0.94% (95% CI 0.03-2.92)) vs. 4.31% (95% CI 2.01-9.23). GIST was more likely to be found by intraoperative exploration than by preoperative endoscopy (0.68% (95% CI 0.50-0.93) vs. 0.23% (95% CI 0.11-0.52)). Patients undergoing bariatric surgery demonstrated non-negligible incidences of gastric pathologies warranting follow-up. Preoperative endoscopy and careful intraoperative exploration should be routinely performed, and Hp. screening and eradication are suggested before endoscopy. In condition that such findings are detected, sleeve gastrectomy may be preferred over Roux-en-Y gastric bypass.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(9): 1056-1060, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33081890

RESUMO

OBJECTIVE: To assess the impact of not inflated lung tissue (NILT) volume on the prognosis of patients with moderate-to-severe acute respiratory distress syndrome (ARDS). METHODS: The clinical data of 131 patients with moderate-to-severe ARDS admitted to the intensive care unit (ICU) of Tianjin Third Central Hospital from March 2016 to June 2019 were collected. The basic data of patients, including gender, age, body mass index (BMI), causes of ARDS, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score and oxygenation index (PaO2/FiO2), were collected. The CT imaging data of patients on the 1st and 7th day in the ICU were collected. According to the CT value, they were divided into hyperventilated areas (-1 000 to -900 HU), normal ventilation areas (-899 to -500 HU), poorly ventilated areas (-499 to -100 HU), and atelectasis area (-99 to 100 HU). The total lung volume and the percentage of NILT to the total lung volume (NILT%) were calculate. At the same time, duration of mechanical ventilation, length of ICU stay, total length of hospital stay were collected. According to the 28-day follow-up, they were divided into survival group and death group. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in ARDS patients. The receiver operating characteristic (ROC) curve was drawn, the area under ROC curve (AUC) and 95% confidence interval (95%CI) were calculated to determine the accuracy of NILT% in predicting the 28-day prognosis of ARDS patients, and the NILT% threshold was used for subgroup analysis of patients. RESULTS: Among the 131 patients with moderate-to-severe ARDS, patients were excluded for more than 48 hours after ARDS diagnosis, repeated admission to ICU due to ARDS, the ICU duration less than 7 days, death within 72 hours of admission, chronic interstitial lung disease or congestive heart failure, no chest CT examination within 7 days of admission to ICU, and no specimen collection within 2 hours of admission to ICU. Finally, a total of 53 patients were enrolled in the analysis. Of the 53 patients, 31 patients survived and 22 patients died. The 28-day mortality was 41.5%. Compared with the survival group, patients in the death group were older (years old: 65.32±11.29 vs. 55.77±14.23), and had a higher SOFA score (11.68±3.82 vs. 8.39±2.23) with significant differences (both P < 0.05), while there were no significant differences in gender, BMI, ARDS cause, APACHE II score and PaO2/FiO2 between the two groups. There was no significant difference in CT value, total lung volume and NILT% between the two groups at 1st day after admission to ICU; NILT% on day 7 after admission to ICU in the death group was significantly higher than that in the survival group [(28.95±8.40)% vs. (20.35±5.91)%, P < 0.01], but there was no significant difference in CT value and total lung volume between the two groups. Multivariate Logistic regression analysis showed that the 28-day prognosis of ARDS was related to age, SOFA score and NILT% independently [age: odds ratio (OR) = 0.892, 95%CI was 0.808-0.984, P = 0.023; SOFA score: OR = 0.574, 95%CI was 0.387-0.852, P = 0.006; NILT%: OR = 0.841, 95%CI was 0.730-0.968, P = 0.016]. ROC curve analysis showed that 7-day NILT% could predict the 28-day prognosis of patients with moderate-to-severe ARDS, and AUC was 0.810 (95%CI was 0.678-0.952, P < 0.01). The NILT% threshold was 15.50%, sensitivity was 95.5%, specificity was 80.6%, positive predictive value was 85.7%, and negative predictive value was 74.6%. According to the 7-day NILT% threshold, a subgroup analysis of patients was performed, and 7-day NILT% > 15.50% was defined as a high-risk clinical prognosis, and ≤ 15.50% was a low-risk. Compared with low-risk patients (n = 7), the duration of mechanical ventilation, the length of ICU stay and total length of hospital stay in high-risk patients (n = 46) were significantly prolonged [duration of mechanical ventilation (days): 9.37±6.14 vs. 4.43±1.72, length of ICU stay (days): 12.11±5.85 vs. 7.57±1.13, total length of hospital stay (days): 18.39±5.87 vs. 11.29±2.22, all P < 0.05]. CONCLUSIONS: The 7-day NILT% > 15.50% of patients with moderate-to-severe ARDS after ICU admission is related to poor prognosis.

5.
Neural Plast ; 2020: 8851525, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029120

RESUMO

The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell (HC) mechanotransduction and hearing. Cell junctions are indispensable for the establishment of compositionally distinct fluid compartments in the inner ear. Ototoxic drug cisplatin can damage SV and cause sensorineural hearing loss; however, the underlying mechanisms behind such injury are unclear. In this study, after the intraperitoneal injection of cisplatin (3 mg/kg/day for 7 days) in mice, we determined the auditory function by EP recording and auditory brainstem response (ABR) analysis, observed the ultrastructure of SV by transmission electron microscopy (TEM), and examined the expression and distribution of cell junction proteins by western blot, PCR, and immunofluorescence staining. We discovered that the EP was significantly reduced while ABR thresholds were significantly elevated in cisplatin-treated mice; cisplatin induced ultrastructural changes in marginal cells (MCs), endothelial cells (ECs), pericytes, etc. We found that cisplatin insulted auditory function not only by reducing the expression of zonula occludens protein-1 (ZO-1) in MCs of the SV but also by decreasing the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in MCs and basal cells (BCs). More importantly, cisplatin induced activations of perivascular-resident macrophage-like melanocytes (PVM/Ms) and interleukin-1beta (IL-1ß) as well as increased expressions of profibrotic proteins such as laminin and collagen IV in SV. Thus, our results firstly showed that cisplatin induced fibrosis, inflammation, and the complex expression change of cell junctions in SV.

6.
Chemosphere ; 264(Pt 1): 128532, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33038753

RESUMO

Bioelectrochemical system (BES) based biosensors for organic sensing has long been investigated. However, there is no uniform criterion to evaluate directly the performance of the BES based biosensors due to their different scale. Here, for the first time, we show that the normalized maximum detection range (NMDR) and normalized sensing time (NST) can potentially be used as the two criteria in BES based biosensors for organic sensing. Thereafter, the recently emerged, relatively larger scale BES (i.e. constructed wetland-microbial fuel cell, CW-MFC) was specifically examined in this study. The biocathode formation and the influence of anodic material on sensor performance were systematically evaluated. The system with metal-based anode was found to produce a more stable and quicker response (low NST) than that with carbon-based anode. Significantly, the continuous loading mode was found to greatly reduce the NMDR compared to the batch mode, and the hydraulic residence time (HRT) is the critical factor determining the NMDR. Furthermore, it was found that the electrical signals generated from the CW-MFC system were insignificantly influenced by some specific chemical disturbances, such as Cu2+ and herbicide. Therefore, normalized toxicity (NT) is suggested to be considered in BES based biosensor. However, for chemicals with higher reduction potentials (NO3- in this work), the system presented a high response, enabling its potential for monitoring NO3- in effluents or groundwater. This study can hopefully contribute to further development of the sustainable BES based biosensors in CW.

7.
Chem Biol Drug Des ; 96(3): 973-983, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33058459

RESUMO

Deep learning-based methods have been extensively developed to improve scoring performance in structure-based drug discovery. Extending multitask deep networks in addressing pharmaceutical problems shows remarkable improvements over single task network. Recently, grid featurization has been introduced to convert protein-ligand complex co-ordinates into fingerprints with the advantage of incorporating inter- and intra-molecular information. The combination of grid featurization with multitask deep networks would hold great potential to boost the scoring performance. We examined the performance of three novel multitask deep networks (standard multitask, bypass, and progressive network) in reproducing the binding affinities of protein-ligand complexes in comparison with AutoDock Vina docking and MM/GBSA method. Among five evaluated methods, progressive network combined with grid featurization provided the best Pearson correlation coefficient (0.74) and least mean absolute average error (0.98) for the overall scoring performance. Moreover, all networks increased screening ability for the re-docking pose and progressive network even achieved AUC of 0.87 over 0.52 of AutoDock Vina. Our results demonstrated that progressive network combined with grid featurization would be one powerful rescoring approach to strengthen screening results after obtaining protein-ligand complex in the conventional docking software.

8.
BMC Med Imaging ; 20(1): 115, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059621

RESUMO

BACKGROUND: This study aimed to compare the sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and ultrasonography (US) in patients with secondary hyperparathyroidism (SHPT), and to explore the factors that affect the sensitivity of 99mTc-MIBI SPECT/CT. METHODS: In this retrospective study, forty-six patients with SHPT who underwent 99mTc-MIBI planar scintigraphy, 99mTc-MIBI SPECT/CT and US were enrolled. They underwent surgery within 1 month. We compared the sensitivity of the different imaging methods based on the lesions according to the pathological results. The parathyroid lesions on 99mTc-MIBI SPECT/CT images were divided into missed diagnosis group (MDG) and non-missed diagnosis group (NMDG). We compared the lesion to background ratio (LBR), maximum diameter, volume, the mean CT Hounsfield unit values (CTmean) and location of lesions between MDG and NMDG. RESULTS: The sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and US were 70.30% versus 48.48% versus 61.82%, respectively. The sensitivity of 99mTc-MIBI SPECT/CT combined US was 79.39%, which was higher than 99mTc-MIBI SPECT/CT with significant difference (P = 0.000). On 99mTc-MIBI SPECT/CT images, the LBR, maximum diameter and volume of lesions in MDG was smaller than those in NMDG with significant difference (P < 0.001). The average LBR, maximum diameter and volume of lesions in MDG and NMDG were 3.42 ± 1.28, 9.32 ± 2.69 mm, 208.51 ± 163.22 mm3 versus 6.75 ± 5.08, 15.03 ± 4.94 mm and 863.85 ± 1216.0 mm3, respectively. CONCLUSIONS: 99mTc-MIBI SPECT/CT exhibited the highest sensitivity among the three methods. When 99mTc-MIBI SPECT/CT combined with US, the sensitivity can be further improved. Lesions with lower MIBI uptake and smaller lesions on 99mTc-MIBI SPECT/CT images were easily missed.

9.
Int J Surg ; 83: 206-215, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022414

RESUMO

BACKGROUND: Studies have provided controversial and limited knowledge regarding the impact of sarcopenia on surgical outcomes in esophageal cancers due to retrospective study designs and single muscle-mass assessment. This prospective cohort study aimed to resolve these issues. METHODS: Bioelectrical impedance analysis, handgrip strength measurement, and the 4-m walking test were conducted before surgery. Sarcopenia was diagnosed as low appendicular skeletal muscle mass index (<7.0 kg/m2 in men and <5.7 kg/m2 in women) plus low handgrip strength (<26 kg in men and <18 kg in women) and/or low gait speed (<0.8 m/s). Presarcopenia was diagnosed as either: (1) solely low muscle mass index; or (2) solely low handgrip strength and/or gait speed. Endpoints included perioperative biochemical indicators, postoperative complications, and the recovery of postoperative quality of life (QOL). RESULTS: In total, 212 patients were enrolled, including 55 (25.9%) and 60 (28.3%) patients diagnosed with sarcopenia and presarcopenia, respectively. The presarcopenic and normal patients showed a similar risk of postoperative complications and were combined. Despite similar baseline levels, sarcopenic patients (vs. non-sarcopenic) showed decreased prealbumin on postoperative day (POD) 1, decreased albumin on PODs 1, 3, and 5, and delayed recovery of lymphocyte counts (all P < 0.05). The levels of C-reactive protein in sarcopenic patients was lower than in non-sarcopenic patients on POD 1 (P = 0.010) but higher on POD 5 (P = 0.001). Multivariate analyses demonstrated the independent predictive value of sarcopenia for overall complications (P < 0.001), major complications (Clavien-Dindo grade ≥ III, P = 0.001), and delayed hospital discharge (>12 days, P < 0.001). Sarcopenia was demonstrated as a risk factor for deteriorated global QOL (P = 0.001), physical (P = 0.001) and role functions (P = 0.006), and severe fatigue (P = 0.004) at four weeks after surgery. CONCLUSIONS: Sarcopenia was associated with poor metabolic stress and immune responses surrounding esophagectomy and was a potential target for reducing complications and promoting recovery of QOL.

10.
Nat Commun ; 11(1): 4964, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009394

RESUMO

Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.


Assuntos
Plaquetas/metabolismo , Diferenciação Celular , Micropartículas Derivadas de Células/metabolismo , Megacariócitos/citologia , MicroRNAs/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Endocitose , Perfilação da Expressão Gênica , Humanos , Fígado/lesões , Fígado/patologia , Masculino , Megacariócitos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , Poliploidia , Proteína rhoB de Ligação ao GTP/metabolismo
11.
Mol Med Rep ; 22(5): 4442-4451, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000224

RESUMO

Normal placentation and successful maintenance of pregnancy depend on the successful migration and invasion of trophoblasts into maternal tissues. Previous studies reported that microRNAs (miRs) are expressed in trophoblasts, and can regulate their migration and invasion. The present study aimed to investigate miR­181b­5p function in HTR­8/SVneo trophoblasts and explore its underlying mechanism in the pathogenesis of multiple abnormal trophoblast invasion­related events. Reverse­transcription quantitative PCR and western blotting were used to test the expression of miR­181b­5p and sphingosine­1­phosphate receptor 1 (S1PR1) in samples of multiple abnormal trophoblast invasion­related events. Transwell invasion and wound healing assays were performed to determine cell invasion and migration abilities. A luciferase reporter assay was conducted to identify the downstream target of miR­181b­5p. Overexpression of miR­181b­5p suppressed HTR­8/SVneo cell migration and invasion, whereas inhibition of miR­181b­5p induced an opposite effect. The S1PR1 gene was further identified as a novel direct target of miR­181b­5p. Specifically, miR­181b­5p bound directly to the 3'­untranslated region of S1PR1 and suppressed its expression. Moreover, overexpression of S1PR1 reversed the inhibitory effect of miR­181b­5p. Taken together, ectopic expression of miR­181b­5p impaired the migration and invasion of trophoblasts by directly targeting S1PR1, thereby providing new insights into the pathogenesis of multiple abnormal trophoblast invasion­related events.

12.
Chem Commun (Camb) ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034589

RESUMO

Next-generation high-performance lithium-ion batteries (LIBs) with high energy and power density, long cycle life and uncompromising safety standards require new electrode materials beyond conventional intercalation compounds. However, these materials face a tradeoff between the high capacity and stable cycling because more Li stored in the materials also brings instability to the electrode. Stress-resilient electrode materials are the solution to balance this issue, where the decoupling of strong chemomechanical effects on battery cycling is a prerequisite. This review covers the (de)lithiation behaviors of the alloy and conversion-type anodes and their stress mitigation strategies. We highlight the reaction and degradation mechanisms down to the atomic scale revealed by in situ methods. We also discuss the implications of these mechanistic studies and comment on the effectiveness of the electrode structural and chemical designs that could potentially enable the commercialization of the next generation LIBs based on high-capacity anodes.

13.
Ann Thorac Surg ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031778

RESUMO

BACKGROUND: The improved drainage strategy was the transperitoneal placement of a single mediastinal drainage tube after esophagectomy. This study aimed to explore its effect on the incidence of postoperative complications, pain scores, and hospital stay. METHODS: Data from 108 patients underwent minimally invasive esophagectomy (MIE) was retrospectively analysed. Patients were divided into two groups: those in Group A were treated with transthoracic placement of mediastinal drain, Group B with transperitoneal placement. The incidence of postoperative complications, pain scores, and postoperative hospital stay were compared. RESULTS: The maximum pain scores in Group B were significantly lower than those in Group A from the first to the fourth postoperative days: (3.9±0.7) vs. (2.3±0.7), (3.5±0.8) vs. (2.1±0.7), (3.3±0.8) vs. (1.7±0.8) and (3.1±0.7) vs. (1.7±0.8) (all p < 0.001). Compared to Group A, there were fewer postoperative analgesic drug users in Group B (44.6% vs. 17.9%, p = 0.005), fewer cases of pleural effusion (10.7% vs. 0%, p = 0.045), and fewer cases of closed thoracic drainage due to pleural effusion or pneumothorax (14.3% vs. 0%, p = 0.014). There were no significant differences in the incidence of anastomotic leakage, mediastinitis, major pulmonary complications, major abdominal complications, surgical site infection, and total postoperative complications, without statistical differences in postoperative hospital stay and 30-d mortality (all p > 0.05). CONCLUSIONS: The transperitoneal placement of a single mediastinal drain can reduce postoperative pain and the incidence of pleural effusion, without increasing the incidence of other major postoperative complications and postoperative hospital stay.

14.
J Hazard Mater ; 404(Pt A): 124140, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33070005

RESUMO

Amino-modified attapulgite (M-ATP) was prepared to remove Pb2+ and Cu2+ from the aqueous solution. Fourier transform infrared spectroscopy (FT-IR) spectrums and X-ray powder diffraction (XRD) patterns revealed that a new Si-O-Si bond formed after modification. The result indicates that the graft reaction of ATP occurred at Si-O (2 0 0) tetrahedron crystal face. No matter whether in a single or binary heavy metal ion system, the adsorption experiments displayed that the equilibrium adsorption capacity of M-ATP towards Pb2+ was much higher than Cu2+, which indicated M-ATP more readily adsorbs the Pb2+. The selective adsorption mechanism of Pb2+ and Cu2+ on modified attapulgite was studied by density functional theory (DFT). The Eads of Pb (- 2.01 eV) adsorbed on M-ATP is lower than Cu (- 1.79 eV) through the DFT calculation of adsorption energy (Eads), which indicate that the Pb2+ adsorbed on M-ATP is more stable than Cu2+. Both adsorption experiments and theoretical calculations revealed that due to the stability of Pb2+ adsorption on M-ATP, Pb2+ is more readily adsorbed by M-ATP, and it is difficult for Cu2+ to exchange Pb2+ from M-ATP.

15.
Vet Microbiol ; 251: 108893, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33096469

RESUMO

Porcine circovirus type 2 (PCV2) infection causes porcine circovirus associated diseases (PCVAD) worldwide. Identification of host factors that interact with viral proteins is a fundamental step to understand the pathogenesis of PCV2. Our previous study reported that ORF5, a newly identified PCV2 viral protein supports PCV2 replication and interacts with multiple host factors. Here, we showed that a host factor YWHAB is an ORF5-interacting protein and plays essential roles during PCV2 infection. By using protein-protein interaction assays, we confirmed that YWHAB directly interacts with PCV2-ORF5 protein. We further showed that YWHAB expression was potently induced upon ORF5 overexpression and PCV2 infection. Remarkably, we found that the YWHAB strongly inhibited PCV2 replication, suggesting its role in defending PCV2 infection. By using the ectopic overexpression and gene knockdown approaches, we revealed that YWHAB inhibits PCV2-induced endoplasmic reticulum stress (ERS), autophagy, reactive oxygen species (ROS) production and apoptosis, suggesting its vital role in alleviating PCV2-induced cellular damage. Together, this study demonstrated that an ORF5-interacting host factor YWHAB affects PCV2 infection and PCV2-induced cellular response, which expands the current understanding of YWHAB biological function and might serves as a new therapeutic target to manage PCV2 infection-associated diseases.

16.
Cell Commun Signal ; 18(1): 167, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097055

RESUMO

BACKGROUND: Metabolic reprogramming contributes significantly to tumor development and is tightly linked to drug resistance. The chemotherapeutic agent etoposide (VP-16) has been used clinically in the treatment of lung cancer but possess different sensitivity and efficacy towards SCLC and NSCLC. Here, we assessed the impact of etoposide on glycolytic metabolism in SCLC and NSCLC cell lines and investigated the role of metabolic rewiring in mediating etoposide resistance. METHODS: glycolytic differences of drug-treated cancer cells were determined by extracellular acidification rate (ECAR), glucose consumption, lactate production and western blot. DNA damage was evaluated by the comet assay and western blot. Chemoresistant cancer cells were analyzed by viability, apoptosis and western blot. Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction. RESULTS: Here we showed that exposure to chemotherapeutic drug etoposide induces an exacerbation of ROS production which activates HIF-1α-mediated the metabolic reprogramming toward increased glycolysis and lactate production in non-small cell lung cancer (NSCLC). We identified lactic acidosis as the key that confers multidrug resistance through upregulation of multidrug resistance-associated protein 1 (MRP1, encoded by ABCC1), a member of ATP-binding cassette (ABC) transporter family. Mechanistically, lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to induce formation of Snail/TAZ/AP-1 complex at the MRP1/ABCC1 promoter. Induction of MRP1 expression inhibits genotoxic and apoptotic effects of chemotherapeutic drugs by increasing drug efflux. Furthermore, titration of lactic acid with NaHCO3 was sufficient to overcome resistance. CONCLUSIONS: The chemotherapeutic drug etoposide induces the shift toward aerobic glycolysis in the NSCLC rather than SCLC cell lines. The increased lactic acid in extracellular environment plays important role in etoposide resistance through upregulation of MRP expression. These data provide first evidence for the increased lactate production, upon drug treatment, contributes to adaptive resistance in NSCLC and reveal potential vulnerabilities of lactate metabolism and/or pathway suitable for therapeutic targeting. Video Abstract The chemotherapeutic drug etoposide induces metabolic reprogramming towards glycolysis in the NSCLC cells. The secreted lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to activate the expression of MRP1/ABCC1 protein, thus contributing to chemoresistance in NSCLC.

17.
Diagnostics (Basel) ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008011

RESUMO

This study aims to explore computed tomography (CT) and magnetic resonance imaging (MRI) features of patients diagnosed with primary cardiac angiosarcoma. The study involved the analysis of 12 patients diagnosed with primary cardiac angiosarcoma who underwent non-contrast (8/12) or contrast-enhanced CT (10/12) or MRI (4/12). Imaging appearances, including the tumor location and adjacent infiltration, were analyzed. All 12 lesions were located in the right atrium with a broad base. Adjacent invasion including the tricuspid valve and right ventricle (2/12), inferior or superior vena cava (2/12), pericardium (10/12), and right coronary artery (7/12) was common. On unenhanced CT scans, tumors in two patients were homogeneous in density, whereas the others were inhomogeneous. Ten patients showed heterogeneous enhancement. The enhancement pattern showed no direct correlation with the differentiation degree of the tumor. Four lesions manifested as heterogeneous intensity, with hyperintense hemorrhage foci on both T1- and T2-weighted MRI. Three showed rim enhancement and one showed patchy enhancement. Primary cardiac angiosarcoma often involves the right side of the heart with infiltration of peripheral structures. CT features include typical inhomogeneous density on unenhanced scans and heterogeneous centripetal enhancement on enhanced scans. A cauliflower-like appearance on both T1- and T2-weighted MRI is common. The characteristic enhancement pattern of MRI remains to be determined.

18.
ACS Nano ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025784

RESUMO

Sluggish kinetics and limited reversible capacity present two major challenges for layered titanates to achieve satisfactory sodium-ion storage performance at subzero-temperatures (subzero-T). To facilitate sodiation dynamics and improve reversible capacity, we proposed an additive-free anode with Sn(II) located between layers. Sn-5s in interlayer-confining Sn(II), which has a larger negative charge, will hybridize with O-2p to trigger charge redistribution, thereby enhancing electronic conductivity. H-titanates with an open framework are designed to stabilize Sn(II) and restrain subsequent volume expansion, which could potentially surpass the capacity limitation of titanate-based materials via a joint alloying-intercalation reaction with high reversibility. Moreover, the generation of conductive Na14Sn4 and the expansion of interlayer spacing resulting from the interlayered alloying reaction are beneficial for charge transfer. These effects synergistically endow the modified sample with a considerably lower activation energy and a 3-fold increase in diffusion. Consequently, the designed anode delivers excellent subzero-T adaptability when compared to the unmodified sample, maintaining capacity retention of 91% after 1200 cycles at -20 °C and 90% after 850 cycles at -30 °C.

19.
Brief Bioinform ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33003206

RESUMO

Single-cell RNA-sequencing (scRNA-seq) data widely exist in bioinformatics. It is crucial to devise a distance metric for scRNA-seq data. Almost all existing clustering methods based on spectral clustering algorithms work in three separate steps: similarity graph construction; continuous labels learning; discretization of the learned labels by k-means clustering. However, this common practice has potential flaws that may lead to severe information loss and degradation of performance. Furthermore, the performance of a kernel method is largely determined by the selected kernel; a self-weighted multiple kernel learning model can help choose the most suitable kernel for scRNA-seq data. To this end, we propose to automatically learn similarity information from data. We present a new clustering method in the form of a multiple kernel combination that can directly discover groupings in scRNA-seq data. The main proposition is that automatically learned similarity information from scRNA-seq data is used to transform the candidate solution into a new solution that better approximates the discrete one. The proposed model can be efficiently solved by the standard support vector machine (SVM) solvers. Experiments on benchmark scRNA-Seq data validate the superior performance of the proposed model. Spectral clustering with multiple kernels is implemented in Matlab, licensed under Massachusetts Institute of Technology (MIT) and freely available from the Github website, https://github.com/Cuteu/SMSC/.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33006185

RESUMO

Inspired by the exquisite helices in Nature, fabrication of helical materials with controlled handedness has attracted considerable attention. Herein, we report on precis synthesis of single left- and right-handed helical polyisocyanides through living polymerization of achiral monomers using chiral palladium catalysts under helix-sense-selective manner. Mechanism study revealed that the yielded helices with opposite handedness showed different activity of the living chain end. The helix with unfavoured handedness was self-terminated, while the other one with favoured handedness showed high activity and can undergoes chain propagation to form a high molecular weight polymer with maintained single-handed helicity.

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