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1.
Artigo em Inglês | MEDLINE | ID: mdl-34985788

RESUMO

We present herein our experimental and DFT computational studies on the directing ability of chalcogenoether motifs in Pd-catalyzed atroposelective C-H functionalization. Thioether motif was found to be a superior directing group compared to the corresponding ether and selenoether in terms of reactivity and enantiocontrol. Remarkably, DFT calculation provided a predictive model for the optimization of reaction conditions and the interpretation of the origin of enantioselectivity. Both Pd-catalyzed enantioselective C-H olefination and allylation reactions were successfully developed using chiral phosphoric acids as efficient ligands, providing a broad range of axially chiral biaryls in good yields with excellent enantioselectivities. The highly enantio- and diastereoselective construction of polyaryls bearing multiple stereogenic axes, gram-scale reaction and various chemical transformations make this protocol more attractive and significant.

2.
Anal Methods ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006220

RESUMO

The authors report a self-oriented beacon liquid crystal (LC) biosensor for kanamycin (Kana) detection with gold nanoparticle (AuNPs) signal enhancement. In this study, an assay was proposed for Kana detection using the aptamer as a self-oriented beacon. Without an additional orientation agent, the Kana aptamer was used as a self-oriented beacon both as an orientation agent for the LCs and as a signal recognition probe for biological molecules. Gold nanoparticles are blended with desired concentrations of the target molecules, which can greatly improve the performance of the biosensor. In the presence of Kana, AuNPs-Kana-aptamer conjugates will form on the sensing interface of the biosensor, which can remarkably destroy the orientated arrangement of the LCs, resulting in changes in the corresponding polarized images of the LCs. The limit of Kana detection is as low as 0.1 pmol L-1. It is important to note that the self-oriented beacons are immobilized on the assembled film of the glass slides for the specific recognition of Kana, simultaneously allowing the homeotropic orientation of the LCs. This study also provides a mechanism for the self-orientation beacon and liquid crystal biosensing.

3.
Chin J Dent Res ; 24(4): 257-265, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029097

RESUMO

OBJECTIVE: To investigate the time efficiency of prefabricated prostheses located by an anchor pin stereolithographic attachment system for immediate loading implant reconstruction of completely edentulous jaws and compare it with the conventional protocol. METHODS: Edentulous patients were recruited and randomly assigned into two groups: the full digital workflow group (digital group) and the conventional workflow group (conventional group). In the digital group, a provisional prosthesis was fabricated before surgery using a fully digital workflow and delivered immediately after implant placement. The positioning of the provisional prosthesis was guided precisely by the anchor pin attachment system. In the conventional group, the provisional prosthesis was fabricated after implant placement using a conventional procedure. Clinical and laboratory time efficiency were recorded, and clinician and patient satisfaction were evaluated. RESULTS: Six patients were enrolled in this pilot study and 57 implants were placed following the guided surgery protocol. Of these, 54 were immediately loaded. The total clinical chair time in the digital workflow group was significantly less than that in the conventional workflow group (digital 60.0 ± 13.2 minutes; conventional 106.7 ± 24.7 minutes) (P = 0.045). The total post-surgery procedure took significantly less time in the digital group than the conventional group (digital 202.5 ± 22.5 minutes; conventional 403.7 ± 55.4 minutes) (P = 0.004). The patients' and clinicians' satisfaction with the provisional prostheses was similar in both groups. CONCLUSION: Time efficiency in immediate loading of implant-supported full-arch fixed restorations was improved with prefabricated prostheses located by the anchor-pin-attachment system. Less postoperative chair time was required in the digital group than in the conventional group.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35023315

RESUMO

Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human immunoglobulin G4 (IgG4 ) to form monovalent hybrid molecules. A mechanistic population model was developed to quantitatively characterize the dynamic Fab-arm exchange of tralokinumab, a human IgG4  monoclonal antibody currently being developed for the treatment of atopic dermatitis, with endogenous IgG4 in healthy volunteers. The estimated pharmacokinetic parameters for IgG4 were similar to those of immunoglobulin G1 or immunoglobulin G2 in humans. However, the mechanistically modeled clearance of half molecules is 21-fold higher, likely due to the loss of avidity for the neonatal Fc receptor. Half molecules of tralokinumab randomly associate with those of endogenous IgG4 to form monovalent hybrid molecules, which became the dominant form of tralokinumab within 1 day postdose in healthy volunteers. As the potency of monovalent tralokinumab is comparable with that of bivalent tralokinumab, the IgG4 Fab-arm exchange with endogenous IgG4 is not expected to affect the potency of neutralization of interleukin-13 in vivo.

5.
Arthritis Res Ther ; 24(1): 17, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996506

RESUMO

BACKGROUND: Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. OBJECTIVE: To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). METHODS: In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. RESULTS: Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. CONCLUSION: PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. TRIAL REGISTRATION: ChiCTR2000036192.

6.
Sci Rep ; 12(1): 394, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013471

RESUMO

Delayed luminescence (DL) is gradually used in various detection of biological systems as a rapid detection technique, however, its biological mechanism was still not clear. In this study, a new model of DL detection system for liquid biological samples is established to investigate the DL emission of Saccharomyces cerevisiae cells cultured in different glucose concentrations. We analyzed the relationship between the DL emission and cell growth, cell vitality, mitochondrial morphology, mitochondrial DNA (mtDNA) copy number, adenosine triphosphate (ATP), oxygen consumption rate (OCR), as well as mitochondria membrane potential (MMP) in S. cerevisiae cells cultured with 0.01, 0.05, 0.15, 3, 10 and 20 g/L glucose respectively. It was found that the DL emission had strong correlation with mitochondrial morphology, OCR, and MMP. The results suggested that DL is an indicator of mitochondria status under different glucose supply conditions, and may be an effective method to detect mitochondrial metabolism related disorders.

7.
Nanoscale Res Lett ; 17(1): 14, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35032235

RESUMO

In this work, a vertical gallium nitride (GaN)-based trench MOSFET on 4-inch free-standing GaN substrate is presented with threshold voltage of 3.15 V, specific on-resistance of 1.93 mΩ·cm2, breakdown voltage of 1306 V, and figure of merit of 0.88 GW/cm2. High-quality and stable MOS interface is obtained through two-step process, including simple acid cleaning and a following (NH4)2S passivation. Based on the calibration with experiment, the simulation results of physical model are consistent well with the experiment data in transfer, output, and breakdown characteristic curves, which demonstrate the validity of the simulation data obtained by Silvaco technology computer aided design (Silvaco TCAD). The mechanisms of on-state and breakdown are thoroughly studied using Silvaco TCAD physical model. The device parameters, including n--GaN drift layer, p-GaN channel layer and gate dielectric layer, are systematically designed for optimization. This comprehensive analysis and optimization on the vertical GaN-based trench MOSFETs provide significant guide for vertical GaN-based high power applications.

8.
Artigo em Chinês | MEDLINE | ID: mdl-34979626

RESUMO

Chronic otitis media is a common condition in otology, which mainly manifests as repeated purulence, hearing loss, eardrum perforation and other discomforts. It often causes adverse impacts on the health and quality of life of patients. In the past, the assessment of symptoms and prognosis of chronic otitis media was limited to objective examinations such as audiometry or ear endoscopy, while patients' subjective feelings about the disease were ignored. This study reviewed the content, characteristics and current clinical application of quality of life scales for chronic otitis media, with the aim of providing a basis for the selection of quality of life scales for chronic otitis media.


Assuntos
Otite Média , Perfuração da Membrana Timpânica , Audiometria , Doença Crônica , Humanos , Qualidade de Vida
9.
Artigo em Inglês | MEDLINE | ID: mdl-34986110

RESUMO

Functional near-infrared spectroscopy (fNIRS) is a promising neuroimaging technology. The fNIRS classification problem has always been the focus of the brain-computer interface (BCI). Inspired by the success of Transformer based on self-attention mechanism in the fields of natural language processing and computer vision, we propose an fNIRS classification network based on Transformer, named fNIRS-T. We explore the spatial-level and channel-level representation of fNIRS signals to improve data utilization and network representation capacity. Besides, a preprocessing module, which consists of one-dimensional average pooling and layer normalization, is designed to replace filtering and baseline correction of data preprocessing. It makes fNIRS-T an end-to-end network, called fNIRS-PreT. Compared with traditional machine learning classifiers, convolutional neural network (CNN), and long short-term memory (LSTM), the proposed models obtain the best accuracy on three open-access datasets. Specifically, in the most extensive ternary classification task (30 subjects) that includes three types of overt movements, fNIRS-T, CNN, and LSTM obtain 75.49%, 72.89%, and 61.94% on test sets, respectively. Compared to traditional classifiers, fNIRS-T is at least 27.41% higher than statistical features and 6.79% higher than well-designed features. In the individual subject experiment of the ternary classification task, fNIRS-T achieves an average subject accuracy of 78.22% and surpasses CNN and LSTM by a large margin of +4.75% and +11.33%. fNIRS-PreT using raw data also achieves competitive performance to fNIRS-T. Therefore, the proposed models improve the performance of fNIRS-based BCI significantly.

10.
Anal Methods ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981794

RESUMO

The identification of ancient wool is of great significance in archaeology; however, conventional methods are unwieldy or even ineffective when testing contaminated or severely degraded ancient samples. Therefore, it is highly desirable to develop an ultrasensitive detection method for ancient wool. In this study, an ultrasensitive electrochemical immunosensor is proposed and developed to detect ancient wool, where graphene oxide (GO), aldehyde-functionalized ionic liquid (AFIL) composites and gold nanoparticles (AuNPs) are synthesized as efficient signal amplifiers. With their large surface area and excellent electron transfer efficiency, the combination of GO-AFIL and AuNPs endows the immunosensor with excellent electrochemical properties. The fabricated immunosensor measures over a wide linear range of 0.01-100 ng mL-1 with a low detection limit of 0.9 ± 0.2 pg mL-1. Moreover, the immunosensor demonstrates excellent performance for detecting ancient wool. The identification of wool fabrics unearthed from Xinjiang, Tibet and Kazakhstan supports the historicity of prosperous sheepherding and wool trade in Central Asia during the Bronze Age.

11.
Ann Surg Oncol ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994899

RESUMO

BACKGROUND: For patients with locoregional esophageal squamous cell carcinoma (ESCC), survival outcomes among neoadjuvant chemoradiotherapy followed by operation (nCRT-OP), definitive chemoradiotherapy (dCRT), and esophagectomy alone remain controversial. PATIENTS AND METHODS: Information from the 2008-2016 Taiwan Cancer Registry was used. A total of 7637 cT1b-4, N0/+, M0 ESCC patients receiving nCRT-OP (n = 1955), dCRT (n = 4122), or esophagectomy alone (n = 1560) were included. Propensity score matching was performed to balance clinical variables among the three groups. Stage-specific overall survival was compared before and after propensity score matching. Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Propensity score matching resulted in 1407 cases for comparison. The 5-year overall survival rates for matched patients treated via dCRT, nCRT-OP, and esophagectomy alone were 19.77%, 31.23%, and 30.52%, respectively (p < 0.001). On multivariable analysis, treatment modality was still an independent prognostic factor both before and after propensity score matching. nCRT-OP and esophagectomy alone were associated with significantly better overall survival than dCRT for locoregional ESCC patients. CONCLUSIONS: This propensity-matched study revealed that nCRT-OP and esophagectomy provided better survival than dCRT in cT1b-4, N0/+, M0 ESCC patients.

12.
Talanta ; 236: 122886, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635266

RESUMO

Rheumatoid arthritis (RA), an autoimmune and chronic inflammatory disorder, is an incurable disease. We developed a peptide-based electrochemical sensor using electrochemical impedance spectroscopy that can be used to detect autoantibodies for RA diagnostics. We first validated that the developed peptide showed high sensitivity and could compliment the current gold standard method of an anti-cyclic citrullinated peptide antibody (anti-CCP) ELISA. The developed peptide can be modified on the nanogold surface of the working electrode of sensing chips through the method of a self-assembling monolayer. The sensing process was first optimized using a positive control cohort and a healthy control cohort. Subsequently, 10 clinically confirmed samples from RA patients and five healthy control samples were used to find the threshold value of the impedance between RA and healthy subjects. Furthermore, 10 clinically confirmed samples but with low values of anti-CCP autoantibodies were used to evaluate the sensitivity of the present method compared to the conventional method. The proposed method showed better sensitivity than the current conventional anti-CCP ELISA method.


Assuntos
Artrite Reumatoide , Artrite Reumatoide/diagnóstico , Espectroscopia Dielétrica , Impedância Elétrica , Ensaio de Imunoadsorção Enzimática , Humanos , Peptídeos
13.
Cancer Nurs ; 45(1): E59-E67, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32541209

RESUMO

BACKGROUND: Patients with lung cancer suffer from significant psychological distress. The underlying theoretical model that may explain what predicts or mediates the degree of psychological distress has not been elucidated. OBJECTIVES: To describe the incidence of psychological distress in patients with lung cancer and to test a predictive theoretical model of psychological distress based on symptom burden, type D personality, social support, and intrusive thoughts. METHODS: Three hundred eighty-nine patients with stages I to IV lung cancer were recruited. Participants completed a battery of scales, including measures of psychological distress, symptom burden, type D personality, perceived social support, intrusive thoughts, and demographic and clinical characteristics. The predictive theoretical model was tested using structural equation modeling. RESULTS: Experiencing clinically significant psychological distress was reported by 63.75% of participants. Consistent with the social cognitive processing model, symptom burden, type D personality, social support, and intrusive thoughts all significantly and directly predicted the level of psychological distress in patients with lung cancer. Moreover, intrusive thoughts mediated the effects of type D personality and symptom burden on psychological distress; social support and symptom burden mediated the effects of type D personality on psychological distress. CONCLUSIONS: The majority of the participants experienced psychological distress at a clinically significant level. Intrusive thoughts and social support mediated the effects of type D personality and symptom burden on psychological distress. IMPLICATIONS FOR PRACTICE: Patients with type D personality and symptom burden should be identified. Interventions for targeting social support and intrusive thoughts might ultimately reduce their psychological distress.

14.
Nucl Med Commun ; 43(1): 114-121, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34406147

RESUMO

OBJECTIVES: We explored the relationship between lymph node metastasis (LNM) and total lesion glycolysis (TLG) of primary lesions determined by 18fluoro-2-deoxyglucose PET/computed tomography (18F-FDG PET/CT) in patients with gastric adenocarcinoma, and evaluated the independent effect of this association. METHODS: This retrospective study included 106 gastric adenocarcinoma patients who were examined by preoperative 18F-FDG PET/CT imaging between April 2016 and April 2020. We measured TLG of primary gastric lesions and evaluated its association with LNM. Multivariate logistic regression and a two-piece-wise linear regression were performed to evaluate the relationship between TLG of primary lesions and LNM. RESULTS: Of the 106 patients, 75 cases (71%) had LNM and 31 cases (29%) did not have LNM. Univariate analyses revealed that a per-SD increase in TLG was independently associated with LNM [odds ratio (OR) = 2.37; 95% confidence interval (CI), 1.42-3.98; P = 0.0010]. After full adjustment of confounding factors, multivariate analyses exhibited that TLG of primary lesions was still significantly associated with LNM (OR per-SD: 2.20; 95% CI, 1.16-4.19; P = 0.0164). Generalized additive model indicated a nonlinear relationship and saturation effect between TLG of primary lesions and LNM. When TLG of primary lesions was <23.2, TLG was significantly correlated with LNM (OR = 1.26; 95% CI, 1.07-1.48; P = 0.0053), whereas when TLG of primary lesions was ≥ 23.2, the probability of LNM was greater than 60%, gradually reached saturation effect, as high as 80% or more. CONCLUSIONS: In this preliminary study, there were saturation and segmentation effects between TLG of primary lesions determined by preoperative 18F-FDG PET/CT and LNM. When TLG of primary lesions was ≥ 23.2, the probability of LNM was greater than 60%, gradually reached saturation effect, as high as 80% or more. TLG of primary lesions is helpful in the preoperative diagnosis of LNM in patients with gastric adenocarcinoma.

15.
Pharm Biol ; 60(1): 75-86, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34962429

RESUMO

CONTEXT: The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. OBJECTIVE: Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. MATERIALS AND METHODS: CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. RESULTS: For SMMC7721 (IC50 = 22.5 µM) and PLC8024 (IC50 = 18.4 µM), TET (10, 20 µM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 µM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). DISCUSSION AND CONCLUSIONS: TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.

16.
Oral Oncol ; 124: 105657, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34915261

RESUMO

BACKGROUND: The need for an effective tool to predict prognosis of head and neck squamous cell carcinoma (HNSCC) patients is critical and unmet. Microbiota has recently been found involved in tumor progression and response to immunotherapy. However, the association of microbiota with the prognosis of HNSCC patients remains obscure. This study aims to investigate the association between tumor microbiota and outcomes of HNSCC patients. METHODS: A retrospective study including 129 primary tumors of HNSCC was conducted. Using 16S rRNA sequencing, the profile and the composition of tumor microbiota were measured and their associations with overall survival (OS) and disease free survival (DFS) were examined. RESULTS: We observed a reduced richness and enriched abundances of genera Schlegelella and Methyloversatilis in tumor microbiota of HNSCC patients with poor prognosis. However, a richer tumor microbiota with greater abundances of genera Bacillus, and Lactobacillus and Sphingomonas was characterized in the patients with favorable prognosis.The ratio of these differentially abundant taxa, microbial dysbiosis index (MDI), was significantly associated with OS (hazard ratio [HR], 4.67, 95% confidence interval [CI], 2.51 to 8.69,P < 0.001) and DFS (HR, 2.89; 95% CI, 1.74 to 4.80, P < 0.001) independently of age, tumor size, lymph node metastasis, differentiation and p16 status. The risk score of multivariate Cox regression exhibited an excellent performance for estimating three-year OS (AUC of 0.826). We also found a richer tumor microbiota was correlated with moderate peritumoral inflammatory infiltration. CONCLUSION: These results indicate that tumor microbiota associates with outcomes of HNSCC patients.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34853598

RESUMO

Osteoarthritis (OA) is a degressive and complex disease which is a growing public health problem on a global scale. On basis of an in-house database consisting of clinical records of 13,083 OA patients, the Traditional Chinese Medicine (TCM) was divided into 4 categories of medicines on the basis of the curative properties of herbs. Due to the lack of depth and internal relationship in the calculation results of TCM compatibility law data mining methods such as statistics and frequency analysis, we use a variety of multidimensional complex network methods that can efficaciously find the compatibility law of TCM, including similarity measure, graphical visualization of network diagram, random walking, and propensity score methods. We summarize common couplet medicines utilized for the treatment of osteoarthritis. The similarity measure method was used to investigate the commonly used drugs for the treatment of osteoarthritis. The method of association rule analysis is used to recognize the compatibility between the components. On basis of the propensity score methods, the evaluation displayed that, compared with single drug, the drug group increased ESR, CRP, C3, C4, IgG, and IgA more efficiently. Concluding, a random walk model was constructed to assess drug efficacy. After applying a random walk model, while revealing the compatibility among different components of TCM, their therapeutic efficacy against OA is analyzed. We obtained four groups of drug combination clusters by similarity measure and 11 pairs of highly connected drugs by association rules, which are cardinal drug combinations in the prescription for the treatment of OA. We also found that different traditional drug pairs were associated with different laboratory indexes, and drug combinations could better optimize laboratory indexes. This study presented that the TCM constituents complement one another. Besides, the therapeutic effects resulting from a variety of combinations of these constituents are quite different.

18.
Cancer Cell Int ; 21(1): 656, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876142

RESUMO

BACKGROUND: Accumulating evidence has demonstrated the close relation of SOX1 with tumorigenesis and tumor progression. Upregulation of SOX1 was recently shown to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) is not well characterized. METHODS: Expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined using public GEO database. Western blot and immunohistochemistry were used to confirm the expression levels. Cell proliferation assay (CCK-8) and colony formation assay were performed to assess proliferation of CCA cells. A mouse model of subcutaneous transplantable tumors was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were determined using Targetscan and dual-luciferase reporter assay. RESULTS: SOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and suppressed tumor growth in vivo. miR-155-5p directly targeted the 3'-untranslated region (3'UTR) of SOX1 and inhibited expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation, and thus CCA proliferation. However, restoration of SOX1 expression in miR-155-5p overexpressing cell lines decreased the phosphorylation level of RAF, MEK and ERK, as well as the proliferation of CCA cells. CONCLUSION: MiR-155-5p decreased the expression of SOX1 by binding to its 3'UTR, which activated the RAF/MEK/ERK signaling pathway and promoted CCA progression.

19.
Anal Chem ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851604

RESUMO

Surface coatings are extensively used in capillary electrophoresis to increase separation efficiency and resolution. The stability of these coatings across a wide pH range is desirable to achieve repeatable migration times; therefore, a comprehensive understanding of coating degradation timescales is needed. We present a novel platform for automated zeta potential analysis based upon current monitoring that delivers improved time resolution over the existing methods. Using our platform, we measure the zeta potential continuously during aminosilane coating reactions and infer changes in the surface composition. We found that the change in the zeta potential after coating depended on the monomer type and solvent, while its stability was influenced by the coating solvent and exposure pH. Our versatile platform provides an elegant approach for evaluating the molecular composition, reactivity, and stability of surfaces in real time.

20.
Front Genet ; 12: 754795, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868227

RESUMO

Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis. Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, and MMP-12. Accordingly, we retrieved summary statistics of three site-specific BMD, namely, forearm, femoral neck, and lumbar spine. We conducted an inverse variance weighted MR as the primary method to compute overall effects from multiple instruments, while additional MR approaches and sensitivity analyses were implemented. Bonferroni-adjusted significance threshold was set at p < 0.05/18 = 0.003. Results: Totally, there was no evidence for causal effects of genetically-predicted levels of MMPs on BMD measurement at three common sites. MR results indicated that there were no causal associations of circulating MMPs with forearm BMD (all p ≥ 0.023) by the inverse variance weighted method. Similarly, there were no causal effects of MMPs on femoral neck BMD (all p ≥ 0.120) and MR results did not support causal relationships between MMPs and lumbar spine BMD (all p ≥ 0.017). Multiple sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy or evident heterogeneity. Conclusion: We found no evidence for the causal relationship between MMPs and BMD in the European population.

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