Publications by authors named "Long Bai"

129 Publications

Graphene-based nano-devices: high spin Seebeck and pure spin photogalvanic effects.

Phys Chem Chem Phys 2021 Dec 1;23(46):26476-26481. Epub 2021 Dec 1.

College of Electronic and Information Engineering, Changshu Institute of Technology, Changshu, 215500, P. R. China.

We investigate the magnetic, thermoelectric transport, and photogalvanic effect (PGE) properties of two nano-devices based on sawtooth edged graphene nanoribbons (SGNRs). It is found that a robust spin-semiconducting property exists in SGNRs. When SGNRs are arranged in a configuration, a large spin Seebeck coefficient is obtained, indicating a high Seebeck effect under a temperature difference. In addition, we also propose a new spatial inversion symmetry nano-device, which is constructed by two head to head semi-infinite SGNRs in a configuration. The results show that spin-up and spin-down currents are generated by the PGE with opposite flowing directions and the same magnitude. As a result, only a finite pure spin current arises without an accompanying charge current. More importantly, the pure spin current is robustly induced by photons and is independent of the photon energy, polarization angle and the model of polarization (linear or elliptical polarization), which is attributed to the symmetry of the spatial inversion and anti-symmetry of the spin density inversion. The results presented here provide a useful insight into the real application of both spin caloritronics and photoelectric carbon-based nano-devices.
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http://dx.doi.org/10.1039/d1cp04214aDOI Listing
December 2021

A robust approach to establish tolerance limits for the gamma passing rate-based patient-specific quality assurance using the heuristic control charts.

Med Phys 2021 Nov 14. Epub 2021 Nov 14.

Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

Purpose: Establishing the tolerance limits of patient-specific quality assurance (PSQA) processes based on the gamma passing rate (GPR) by using normal statistical process control (SPC) methods involves certain problems. The aim of this study was threefold: (a) to show that the heuristic SPC method can replace the quantile method for establishing tolerance limits in PSQA processes and is more robust, (b) to introduce an iterative procedure of "Identify-Eliminate-Recalculate" for establishing the tolerance limits in PSQA processes with unknown states based on retrospective GPRs, and (c) to recommend a workflow to define tolerance limits based on actual clinical retrospective GPRs.

Materials And Methods: A total of 1671 volumetric-modulated arc therapy (VMAT) pretreatment plans were measured on four linear accelerators (linacs) and analyzed by treatment sites using the GPRs under the 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. Normality testing was performed using the Anderson-Darling (AD) statistic and the optimal distributions of GPRs were determined using the Fitter Python package. The iterative "Identify-Eliminate-Recalculate" procedure was used to identify the PSQA outliers. The tolerance limits of the initial PSQAs, remaining PSQAs after elimination, and in-control PSQAs after correction were calculated using the conventional Shewhart method, two transformation methods, three heuristic methods, and two quantile methods. The tolerance limits of PSQA processes with different states for the respective methods, linacs, and treatment sites were comprehensively compared and analyzed.

Results: It was found that 75% of the initial PSQA processes and 63% of the in-control processes were non-normal (AD test, p < 0.05). The optimal distributions of GPRs for the initial and in-control PSQAs varied with different linacs and treatment sites. In the implementation of the "Identify-Eliminate-Recalculate" procedure, the quantile methods could not identify the out-of-control PSQAs effectively due to the influence of outliers. The tolerance limits of the in-control PSQAs, calculated using the quantile of optimal fitting distributions, represented the ground truth. The tolerance limits of the in-control PSQAs and remaining PSQAs after elimination calculated using the heuristic methods were considerably close to the ground truth (the maximum average absolute deviations were 0.50 and 1.03%, respectively). Some transformation failures occurred under both transformation methods. For the in-control PSQAs at 3%/2 mm gamma criteria, the maximum differences in the tolerance limits for four linacs and different treatment sites were 3.10 and 5.02%, respectively.

Conclusions: The GPR distributions of PSQA processes vary with different linacs and treatment sites but most are skewed. In applying SPC methodologies to PSQA processes, heuristic methods are robust. For in-control PSQA processes, the tolerance limits calculated by heuristic methods are in good agreement with the ground truth. For unknown PSQA processes, the tolerance limits calculated by the heuristic methods after the iterative "Identify-Eliminate-Recalculate" procedure are closest to the ground truth. Setting linac- and treatment site-specific tolerance limits for PSQA processes is necessary for clinical applications.
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http://dx.doi.org/10.1002/mp.15346DOI Listing
November 2021

Multiomics analysis of tumor mutational burden across cancer types.

Comput Struct Biotechnol J 2021 12;19:5637-5646. Epub 2021 Oct 12.

Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.

Whether tumor mutational burden (TMB) is related to improved survival outcomes or the promotion of immunotherapy in various malignant tumors remains controversial, and we lack a comprehensive understanding of TMB across cancers. Based on the data obtained from The Cancer Genome Atlas (TCGA), we conducted a multiomics analysis of TMB across 21 cancer types to identify characteristics related to TMB and determine the mechanism as it relates to prognosis, gene expression, gene mutation and signaling pathways. In our study, TMB was found to have a significant relationship with prognosis for 21 tumors, and the relationship was different in different tumors. TMB may also be related to different outcomes for patients with different tumor subtypes. TMB was confirmed to be correlated with clinical information, such as age and sex. Mutations in and in beast invasive carcinoma (BRCA), in colon adenocarcinoma (COAD), in esophageal carcinoma (ESCA), and in brain lower grade glioma (LGG), in stomach adenocarcinoma (STAD), and in uterine corpus endometrial carcinoma (UCEC) were demonstrated to be correlated with lower TMB. Moreover, we identified differentially expressed genes (DEGs) and differentially methylated regions (DMRs) according to different TMB levels in 21 cancers. We also investigated the correlation between enrichment of signaling pathways, immune cell infiltration and TMB. In conclusion, we identified multiomic characteristics related to the TMB in 21 tumors, providing support for a comprehensive understanding of the role of TMB in different tumors.
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http://dx.doi.org/10.1016/j.csbj.2021.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531462PMC
October 2021

Dimensionality reduction of ultrasonic array data for characterization of inclined defects based on supervised locality preserving projection.

Ultrasonics 2022 Feb 22;119:106625. Epub 2021 Oct 22.

State Key Laboratory of Digital Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address:

Ultrasonic arrays are increasingly used for inspection of the structural components in non-destructive testing (NDT) applications. The ultrasonic array data can be processed to form high-resolution images for detection and localization of defects. Alternatively, the scattering matrix can be extracted from the full matrix of array data and used for defect characterization if the defect size is small (i.e., comparable to an ultrasonic wavelength). This paper studies the dimensionality reduction problem of scattering matrix databases. In particular, we focus on accurate characterization of inclined defects for which previous approaches based on principal component analysis (PCA) yielded high characterization uncertainty. We propose a supervised approach based on locality preserving projection (LPP) and introduce noise constraints to the objective function of LPP. In simulation, the proposed approach is shown to produce a well-resolved defect manifold for 45°ellipses. Characterization results obtained using the simulated noisy measurements of four 60°ellipses confirm the performance improvement of LPP over PCA. In experiments, three 60°ellipses and two surface-breaking cracks have been characterized. On average, the root-mean-square (RMS) sizing error given by the LPP approach is 39.0% lower compared to PCA for the ellipses and 11.1% lower for the surface-breaking cracks.
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http://dx.doi.org/10.1016/j.ultras.2021.106625DOI Listing
February 2022

The prognostic value of preoperative serum lactate dehydrogenase levels in patients underwent curative-intent hepatectomy for colorectal liver metastases: A two-center cohort study.

Cancer Med 2021 Nov 12;10(22):8005-8019. Epub 2021 Oct 12.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.

Background: The prognostic value of lactate dehydrogenase (LDH) in colorectal cancer patients has remained inconsistent between nonmetastatic and metastatic settings. So far, very few studies have included LDH in the prognostic analysis of curative-intent surgery for colorectal liver metastases (CRLM).

Patients And Methods: Five hundred and eighty consecutive metastatic colorectal cancer patients who underwent curative-intent CRLM resection from Sun Yat-sen University Cancer Center (434 patients) and Sun Yat-sen University Sixth Affiliated Hospital (146 patients) in 2000-2019 were retrospectively collected. Overall survival (OS) was the primary end point. Cox regression model was performed to identify the prognostic values of preoperative serum LDH levels and other clinicopathology variables. A modification of the established Fong CRS scoring system comprising LDH was developed within this Chinese population.

Results: At the median follow-up time of 60.5 months, median OS was 59.5 months in the pooled cohort. In the multivariate analysis, preoperative LDH >upper limit of normal (250 U/L) was the strongest independent prognostic factor for OS (HR 1.73, 95% confidence interval [CI], 1.22-2.44; p < 0.001). Patients with elevated LDH levels showed impaired OS than patients with normal LDH levels (27.6 months vs. 68.8 months). Five-year survival rates were 53.7% and 22.5% in the LDH-normal group and LDH-high group, respectively. Similar results were also confirmed in each cohort. In the subgroup analysis, LDH could distinguish the survival regardless of most established prognostic factors (number and size of CRLM, surgical margin, extrahepatic metastases, CEA, and CA19-9 levels, etc.). Integrating LDH into the Fong score contributed to an improvement in the predictive value.

Conclusion: Our study implicates serum LDH as a reliable and independent laboratory biomarker to predict the clinical outcome of curative-intent surgery for CRLM. Composite of LDH and Fong score is a potential stratification tool for CRLM resection. Prospective, international studies are needed to validate these results across diverse populations.
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http://dx.doi.org/10.1002/cam4.4315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607270PMC
November 2021

The Exploration of Poor Ovarian Response-Related Risk Factors: A Potential Role of Growth Differentiation Factor 8 in Predicting Ovarian Response in IVF-ET Patient.

Front Endocrinol (Lausanne) 2021 24;12:708089. Epub 2021 Sep 24.

Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Controlled ovarian hyperstimulation (COH) is the most common therapeutic protocol to obtain a considerable number of oocytes in IVF-ET cycles. To date, the risk factors affecting COH outcomes remain elusive. Growth differentiation factor 8 (GDF-8), a member of transforming growth factor β (TGF-β) superfamily, has been long discerned as a crucial growth factor in folliculogenesis, and the aberrant expression of GDF-8 is closely correlated with the reproductive diseases. However, less is known about the level of GDF-8 in IVF-ET patients with different ovarian response. In the present study, the potential risk factors correlated with ovarian response were explored using logistic regression analysis methods. Meanwhile, the expression changes of GDF-8 and its responsible cellular receptors in various ovarian response patients were determined. Our results showed that several factors were intensely related to poor ovarian response (POR), including aging, obesity, endometriosis, surgery history, and IVF treatment, while irregular menstrual cycles and PCOS contribute to hyperovarian response (HOR). Furthermore, POR patients exhibited a decrease in numbers of MII oocytes and available embryos, thereby manifesting a lower clinical pregnancy rate. The levels of GDF-8, ALK5, and ACVR2B in POR patients were higher compared with those in control groups, whereas the expression level of ACVR2A decreased in poor ovarian response patients. In addition, clinical correlation analysis results showed that the concentration of GDF-8 was negatively correlated with LH and estradiol concentration and antral follicle count. Collectively, our observations provide a novel insight of ovarian response-associated risk factors, highlighting the potential role of GDF-8 levels in ovarian response during COH process.
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http://dx.doi.org/10.3389/fendo.2021.708089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499678PMC
September 2021

A micro/nano-biomimetic coating on titanium orchestrates osteo/angio-genesis and osteoimmunomodulation for advanced osseointegration.

Biomaterials 2021 11 4;278:121162. Epub 2021 Oct 4.

Laboratory of Biomaterial Surfaces & Interfaces, Institute of New Carbon Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, China. Electronic address:

Osseointegration is a sophisticated bone and implant healing process comprising of initial hematoma formation, immediate osteoimmunomodulation, angiogenesis, and osteogenesis. To fulfill rapid and satisfying osseointegration, this study developed a biomimetic implant coating that could confer the intraosseous implants a systematical regulation of the participatory processes. Herein, we shaped dissimilar nano-scale (NS) to form highly biomimetic structures of natural extracellular matrix (ECM) of the host bone and bone healing hematoma with micro/nano-scale (MNS) titania fiber-like network on the surface of titanium (Ti) implants. In vitro experiments revealed that the MNS not only facilitated osteogenic and angiogenic differentiation of bone marrow stromal cells (BMSCs) and endothelial cells, respectively, but also suppressed M1 macrophages (MΦs), whereas, stimulated pro-healing M2 phenotype. Notably, BMSCs on MNS surfaces enabled a significant immunomodulatory effect on MΦs resulting in the downregulation of inflammation-related cell signaling pathways. The favorable osteoimmune microenvironment manipulated by MNS further facilitated osteo-/angio-genesis via the crosstalk of multi-signaling pathways. In vivo evaluation mirrored the aforementioned results, and depicted that MNS induced ameliorative osseointegration when compared with the NS as well as the pristine Ti implant. The study demonstrated the modulatory effect of the multifaceted biomimetic structure on spatiotemporal regulation of the participatory processes during osseointegration.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121162DOI Listing
November 2021

Cardiac microvascular functions improved by MSC-derived exosomes attenuate cardiac fibrosis after ischemia-reperfusion via PDGFR-β modulation.

Int J Cardiol 2021 Dec 14;344:13-24. Epub 2021 Sep 14.

Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, China.

Microvascular dysfunction caused by cardiac ischemia-reperfusion (I/R) leads to multiple severe cardiac adverse events, such as heart failure and ventricular modeling, which plays a critical role in outcomes. Though marrow mesenchymal stem cell (MSC) therapy has been proven effective for attenuating I/R injury, the limitations of clinical feasibility cannot be ignored. Since exosomes are recognized as the main vehicles for MSCs paracrine effects, we assumed that MSC-derived exosomes could prevent microvascular dysfunction and further protect cardiac function. By establishing a rat cardiac I/R model in vivo and a cardiac microvascular endothelial cells (CMECs) hypoxia-reperfusion (H/R) model in vitro, we demonstrated that MSC-derived exosomes enhanced microvascular regeneration under stress, inhibited fibrosis development, and eventually improved cardiac function through platelet-derived growth factor receptor-β (PDGFR-β) modulation. Furthermore, we found that MSC-derived exosomes possessed better therapeutic effects than MSCs themselves.
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http://dx.doi.org/10.1016/j.ijcard.2021.09.017DOI Listing
December 2021

Performance assessment of surface-guided radiation therapy and patient setup in head-and-neck and breast cancer patients based on statistical process control.

Phys Med 2021 Sep 21;89:243-249. Epub 2021 Aug 21.

Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Purpose: To assess the effectiveness of SGRT in clinical applications through statistical process control (SPC).

Methods: Taking the patients' positioning through optical surface imaging (OSI) as a process, the average level of process execution was defined as the process mean. Setup errors detected by cone-beam computed tomography (CBCT) and OSI were extracted for head-and-neck cancer (HNC) and breast cancer patients. These data were used to construct individual and exponentially weighted moving average (EWMA) control charts to analyze outlier fractions and small process shifts from the process mean. Using the control charts and process capability indices derived from this process, the patient positioning-related OSI performance and setup error were analyzed for each patient.

Results: Outlier fractions and small shifts from the process mean that are indicative of setup errors were found to be widely prevalent, with the outliers randomly distributed between fractions. A systematic error of up to 1.6 mm between the OSI and CBCT results was observed in all directions, indicating a significantly degraded OSI performance. Adjusting this systematic error for each patient using setup errors of the first five fractions could effectively mitigate these effects. Process capability analysis following adjustment for systematic error indicated that OSI performance was acceptable (process capability index C = 1.0) for HNC patients but unacceptable (C < 0.75) for breast cancer patients.

Conclusion: SPC is a powerful tool for detecting the outlier fractions and process changes. Our application of SPC to patient-specific evaluations validated the suitability of OSI in clinical applications involving patient positioning.
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http://dx.doi.org/10.1016/j.ejmp.2021.08.007DOI Listing
September 2021

The Role of Formyl Peptide Receptor 1 in Uterine Contraction During Parturition.

Front Pharmacol 2021 29;12:696697. Epub 2021 Jul 29.

Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Parturition involves the transformation of the quiescent myometrium into a highly excitable and contractile state, a process that is driven by changes in myometrial gene expression. This study aimed to identify myometrial transcriptomic signatures and potential novel hub genes in parturition, which have great significance for understanding the underlying mechanisms of successful parturition and treating labor-associated pathologies such as preterm birth. In our study, comparative transcriptome analysis was carried out on human myometrial tissues collected from women undergoing caesarean section at term in the presence (TL = 8) and absence of labor (TNL = 8). A total of 582 differentially expressed genes (DEGs) between TL and TNL tissues were identified. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) revealed that the DEGs were enriched in signal transduction, regulation of signaling receptor activity, inflammatory response, cytokine-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, among others. Thus, transcriptome analysis of the myometrium during term labor revealed that labor onset was associated with an inflammatory response. Moreover, protein-protein interactions network analysis identified FPR1, CXCL8, CXCL1, BDKRB2, BDKRB1, and CXCL2 as the hub genes associated with onset of labor. Formyl peptide receptor 1 (FPR1) was highly expressed in laboring myometrial tissues, with the activation of FPR1 experiments resulting in increased myometrial contraction. Our findings demonstrate the novel role of FPR1 as a modulator of myometrial contraction.
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http://dx.doi.org/10.3389/fphar.2021.696697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358927PMC
July 2021

FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis.

Oncogene 2021 Aug 3;40(33):5168-5181. Epub 2021 Jul 3.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.

Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (mA) demethylase, participates in tumor progression and metastasis in many malignancies, but its role in colorectal cancer (CRC) is still unclear. Here, we found that FTO protein levels, but not RNA levels, were downregulated in CRC tissues. Reduced FTO protein expression was correlated with a high recurrence rate and poor prognosis in resectable CRC patients. Moreover, we demonstrated that hypoxia restrained FTO protein expression, mainly due to an increase in ubiquitin-mediated protein degradation. The serine/threonine kinase receptor associated protein (STRAP) might served as the E3 ligase and K216 was the major ubiquitination site responsible for hypoxia-induced FTO degradation. FTO inhibited CRC metastasis both in vitro and in vivo. Mechanistically, FTO exerted a tumor suppressive role by inhibiting metastasis-associated protein 1 (MTA1) expression in an mA-dependent manner. Methylated MTA1 transcripts were recognized by an mA "reader", insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA. Together, our findings highlight the critical role of FTO in CRC metastasis and reveal a novel epigenetic mechanism by which the hypoxic tumor microenvironment promotes CRC metastasis.
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http://dx.doi.org/10.1038/s41388-021-01916-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376648PMC
August 2021

Sirtuin 3 Ameliorates Lung Senescence and Improves Type II Alveolar Epithelial Cell Function by Enhancing the FoxO3a-Dependent Antioxidant Defense Mechanism.

Stem Cells Dev 2021 Sep 16;30(17):843-855. Epub 2021 Jul 16.

Department of Cardiovascular Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.

Lung aging alters the intrinsic structure of the lung and pulmonary surfactant system and increases the mortality and morbidity due to respiratory diseases in elderly individuals. We hypothesized that lung aging results from an insufficiency of type II alveolar epithelial cells (AECIIs) in the lung tissue. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased SIRT3 expression has been linked to an extended life span in humans. Hence, we speculated that the overexpression of SIRT3 may help to ameliorate lung senescence and improve AECII function. AECIIs were isolated from young and old patients with pneumothorax caused by pulmonary bullae. The expression of SIRT3, manganese superoxide dismutase, and catalase, as well as cell function and senescence indicators of young and old AECIIs, was measured before and after SIRT3 overexpression. After SIRT3 overexpression, the aged state of old AECIIs improved, and antiapoptotic activity, proliferation, and secretion were dramatically enhanced. Surfactant protein C (SPC), which is secreted by AECIIs, reduces alveolar surface tension, repairs the alveolar structure, and regulates inflammation. SPC deficiency in patients is associated with increased inflammation and delayed repair. SIRT3 deacetylated forkhead box O3a, thereby protecting mitochondria from oxidative stress and improving cell function and the senescent state of old AECIIs. These findings provide a possible direction for aging-delaying therapies and interventions for diseases of the respiratory system.
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http://dx.doi.org/10.1089/scd.2021.0099DOI Listing
September 2021

Bioinformatics analysis of the key potential ceRNA biomarkers in human thymic epithelial tumors.

Medicine (Baltimore) 2021 Jun;100(24):e26271

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang.

Background: Thymic epithelial tumors (TETs), originating from the thymic epithelial cells, are the most common primary neoplasms of the anterior mediastinum. Emerging evidence demonstrated that the competing endogenous RNAs (ceRNAs) exerted a crucial effect on tumor development. Hence, it is urgent to understand the regulatory mechanism of ceRNAs in TETs and its impact on tumor prognosis.

Methods: TETs datasets were harvested from the UCSC Xena as the training cohort, followed by differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) at different pathologic type (A, AB, B, and TC) identified via DESeq2 package. clusterProfiler package was utilized to carry out gene ontology and Kyoto encyclopedia of genes and genomes functional analysis on the DEmRNAs. Subsequently, the lncRNA-miRNA-mRNA regulatory network was constructed to screen the key DEmRNAs. After the key DEmRNAs were verified in the external cohort from Gene Expression Omnibus database, their associated-ceRNAs modules were used to perform the K-M and Cox regression analysis to build a prognostic significance for TETs. Lastly, the feasibility of the prognostic significance was validated by receiver operating characteristic (ROC) curves and the area under the curve.

Results: Finally, a total of 463 DEmRNAs, 87 DElncRNAs, and 20 DEmiRNAs were obtained from the intersection of differentially expressed genes in different pathological types of TETs. Functional enrichment analysis showed that the DEmRNAs were closely related to cell proliferation and tumor development. After lncRNA-miRNA-mRNA network construction and external cohort validation, a total of 4 DEmRNAs DOCK11, MCAM, MYO10, and WASF3 were identified and their associated-ceRNA modules were significantly associated with prognosis, which contained 3 lncRNAs (lncRNA LINC00665, lncRNA NR2F1-AS1, and lncRNA RP11-285A1.1), 4 mRNAs (DOCK11, MCAM, MYO10, and WASF3), and 4 miRNAs (hsa-mir-143, hsa-mir-141, hsa-mir-140, and hsa-mir-3199). Meanwhile, ROC curves verified the accuracy of prediction ability of the screened ceRNA modules for prognosis of TETs.

Conclusion: Our study revealed that ceRNAs modules might exert a crucial role in the progression of TETs. The mRNA associated-ceRNA modules could effectively predict the prognosis of TETs, which might be the potential prognostic and therapeutic markers for TETs patients.
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http://dx.doi.org/10.1097/MD.0000000000026271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213305PMC
June 2021

Ultrasonic Defect Characterization Using the Scattering Matrix: A Performance Comparison Study of Bayesian Inversion and Machine Learning Schemas.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 10 27;68(10):3143-3155. Epub 2021 Sep 27.

Accurate defect characterization is desirable in the ultrasonic nondestructive evaluation as it can provide quantitative information about the defect type and geometry. For defect characterization using ultrasonic arrays, high-resolution images can provide the size and type information if a defect is relatively large. However, the performance of image-based characterization becomes poor for small defects that are comparable to the wavelength. An alternative approach is to extract the far-field scattering coefficient matrix from the array data and use it for characterization. Defect characterization can be performed based on a scattering matrix database that consists of the scattering matrices of idealized defects with varying parameters. In this article, the problem of characterizing small surface-breaking notches is studied using two different approaches. The first approach is based on the introduction of a general coherent noise model, and it performs characterization within the Bayesian framework. The second approach relies on a supervised machine learning (ML) schema based on a scattering matrix database, which is used as the training set to fit the ML model exploited for the characterization task. It is shown that convolutional neural networks (CNNs) can achieve the best characterization accuracy among the considered ML approaches, and they give similar characterization uncertainty to that of the Bayesian approach if a notch is favorably oriented. The performance of both approaches varied for unfavorably oriented notches, and the ML approach tends to give results with higher variance and lower biases.
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http://dx.doi.org/10.1109/TUFFC.2021.3084798DOI Listing
October 2021

Recent Innovations in Emulsion Science and Technology for Food Applications.

J Agric Food Chem 2021 Aug 13;69(32):8944-8963. Epub 2021 May 13.

Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.

Emulsion technology has been used for decades in the food industry to create a diverse range of products, including homogenized milk, creams, dips, dressings, sauces, desserts, and toppings. Recently, however, there have been important advances in emulsion science that are leading to new approaches to improving food quality and functionality. This article provides an overview of a number of these advanced emulsion technologies, including Pickering emulsions, high internal phase emulsions (HIPEs), nanoemulsions, and multiple emulsions. Pickering emulsions are stabilized by particle-based emulsifiers, which may be synthetic or natural, rather than conventional molecular emulsifiers. HIPEs are emulsions where the concentration of the disperse phase exceeds the close packing limit (usually >74%), which leads to novel textural properties and high resistance to gravitational separation. Nanoemulsions contain very small droplets (typically < 200 nm), which leads to useful functional attributes, such as high optical clarity, resistance to gravitational separation and aggregation, rapid digestion, and high bioavailability. Multiple emulsions contain droplets that have smaller immiscible droplets inside them, which can be used for reduced-calorie, encapsulation, and delivery purposes. This new generation of advanced emulsions may lead to food and beverage products with improved quality, health, and sustainability.
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http://dx.doi.org/10.1021/acs.jafc.1c01877DOI Listing
August 2021

Effectiveness of P-wave ECG index and left atrial appendage volume in predicting atrial fibrillation recurrence after first radiofrequency catheter ablation.

BMC Cardiovasc Disord 2021 04 6;21(1):164. Epub 2021 Apr 6.

Department of Cardiology, Second Hospital of Hebei Medical University, No. 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.

Background: The primary aim was to observe the predictive value of P-wave ECG index and left atrial appendage volume (LLAV) for atrial fibrillation recurrence after first radiofrequency catheter ablation.

Methods: A total of 196 patients with paroxysmal atrial fibrillation were enrolled. The preoperative LLAV was measured by cardiac enhanced CT. The P-wave ECG index including minimum P-wave duration (P-min), maximum P-wave duration (P-max), mean P-wave duration (mPWD), P-wave dispersion (PWD), P-wave terminal force in lead V1 (PtfV1), PR interval prolongation, and interatrial block (IAB) were analyzed and recorded in 12-lead ECG of sinus rhythm.

Results: According to the follow-up results, the patients were divided into two groups: the non-recurrence group and the recurrence group. P-min, PWD, P-max, PtfV1 ≥ 0.04 mV·s, PR interval prolongation, and the ratio of first and third-degree IAB in the recurrence group were higher than those in the non-recurrence group, with significant statistical differences (P < 0.05). Kaplan-Meier curve analysis was performed on time to atrial fibrillation recurrence after catheter ablation when PtfV1 ≥ 0.04 mv s by comparison between groups (Log Rank test: 2 = 4.739, P < 0.001). Kaplan-Meier curve analysis showed that the survival rate without recurrence of atrial fibrillation after catheter ablation was lower when the LLAV exceeded 8.0 mL (log-rank test P < 0.001).

Conclusion: PWD, P-max, PtfV1, PR interval prolongation, first and third-degree IAB, and LLAV can effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation. The combination might be a valid and alternative independent predictor of recurrence.
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http://dx.doi.org/10.1186/s12872-021-01930-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022391PMC
April 2021

Regulation of endothelial functionality through direct and immunomodulatory effects by Ni-Ti-O nanospindles on NiTi alloy.

Mater Sci Eng C Mater Biol Appl 2021 Apr 3;123:112007. Epub 2021 Mar 3.

Laboratory of Biomaterial Surfaces & Interfaces, Institute of New Carbon Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China. Electronic address:

Stent implantation has become one of the most widely used methods for the treatment of cardiovascular diseases. However, endothelial dysfunction and abnormal inflammatory response following implantation may lead to delayed re-endothelialization, resulting in vascular restenosis and stent thrombus. To address the concerns, we constructed nanospindles composed of TiO and TiNiO through hydrothermal treatment of amorphous Ni-Ti-O nanopores anodically grown on NiTi alloy. The results show the treatment can significantly improve hydrophilicity and reduce Ni ion release, essentially independent of hydrothermal duration. The nanospindle surfaces not only promote the expression of endothelial functionality but also activate macrophages to induce a favorable immune response, downregulate pro-inflammatory M1 markers and upregulate pro-healing M2 markers. Moreover, nitric oxide (NO) synthesis, VEGF secretion, and migration of endothelial cells are enhanced after cultured in macrophage conditioned medium. The nanospindles thus are promising as vascular stent coatings to promote re-endothelization.
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http://dx.doi.org/10.1016/j.msec.2021.112007DOI Listing
April 2021

Correlation between LncRNA Profiles in the Blood Clot Formed on Nano-Scaled Implant Surfaces and Osseointegration.

Nanomaterials (Basel) 2021 Mar 9;11(3). Epub 2021 Mar 9.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4059, Australia.

Implant surfaces with a nanoscaled pattern can dominate the blood coagulation process resulting in a defined clot structure and its degradation behavior, which in turn influence cellular response and the early phase of osseointegration. Long non-coding (Lnc) RNAs are known to regulate many biological processes in the skeletal system; however, the link between the LncRNA derived from the cells within the clot and osseointegration has not been investigated to date. Hence, the sequence analysis of LncRNAs expressed within the clot formed on titania nanotube arrays (TNAs) with distinct nano-scaled diameters (TNA 15 of 15 nm, TNA 60 of 60 nm, TNA 120 of 120 nm) on titanium surfaces was profiled for the first time. LncRNA LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 were identified as the pivotal players in the early formed clot on the nano-scaled surfaces. Further bioinformatic prediction results were used to generate co-expression networks of LncRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that distinct nano-scaled surfaces could regulate the biological functions of target mRNAs in the clot. LOC103346307, LOC108175175, and LOC108176660 upregulated mRNAs related to cell metabolism and Wnt, TGF-beta, and VEGF signaling pathways in TNA 15 compared with P-Ti, TNA 60, and TNA 120, respectively, whereas LOC103352121, LOC103348180, and LOC108176465 downregulated mRNAs related to bone resorption and inflammation through negatively regulating osteoclast differentiation, TNF, and NF-kappa signaling pathways. The results indicated that surface nano-scaled characteristics can significantly influence the clot-derived LncRNAs expression profile, which affects osseointegration through multiple signaling pathways of the targeted mRNAs, thus paving a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and de novo bone formation.
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http://dx.doi.org/10.3390/nano11030674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001142PMC
March 2021

Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin.

Front Cell Dev Biol 2021 16;9:645658. Epub 2021 Mar 16.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Galectin-14 is specifically expressed in placental trophoblasts, and its expression is reduced in trophoblasts retrieved from the cervix of women destined to develop early pregnancy loss. However, the roles of galectin-14 in regulating trophoblasts and in the pathogenesis of pregnancy complication have never been investigated. In the current research, we aimed to investigate the roles of galectin-14 in the regulation of trophoblasts. Tissues of the placenta and villi were collected. Primary trophoblasts and human trophoblast cell line HTR-8/SVneo were used. Western blotting and RT-PCR were used to quantify gene expression. The siRNA-mediated galectin-14 knockdown and lentivirus-mediated overexpression were performed to manipulate the gene expression in trophoblasts. Transwell migration and invasion assays were used to evaluate cell migration and invasion capacity. Gelatin zymography was used to determine the gelatinase activity. Galectin-14 was significantly decreased in the villi of early pregnancy loss and the placenta of preeclampsia. Knockdown of galectin-14 in primary trophoblasts inhibited cell migration and invasion, downregulated the expression of matrix metalloproteinase (MMP)-9 and N-cadherin, the activity of MMP-9, and decreased the phosphorylation of Akt. Meanwhile, the overexpression of galectin-14 in HTR-8/SVneo promoted cell migration and invasion, upregulated the expression of MMP-9 and N-cadherin, the activity of MMP-9, and increased the phosphorylation of Akt. Increased Akt phosphorylation promoted cell migration and invasion and upregulated the expression and activity of MMP-9, while decreased Akt phosphorylation inhibited cell migration and invasion and downregulated the expression and activity of MMP-9. Thus, galectin-14 promotes trophoblast migration and invasion by enhancing the expression of MMP-9 and N-cadherin through Akt phosphorylation. The dysregulation of galectin-14 is involved in the pathogenesis of early pregnancy loss and preeclampsia.
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http://dx.doi.org/10.3389/fcell.2021.645658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007908PMC
March 2021

Pickering Emulsions Interfacial Nanoparticle Complexation of Oppositely Charged Nanopolysaccharides.

ACS Appl Mater Interfaces 2021 Mar 3;13(10):12581-12593. Epub 2021 Mar 3.

Bioproducts Institute, Departments of Chemical & Biological Engineering, Chemistry, and Wood Science, The University of British Columbia, 2360 East Mall, Vancouver, British Columbia V6T 1Z3, Canada.

We consider the variables relevant to adsorption of renewable nanoparticles and stabilization of multiphase systems, including the particle's hydrophilicity, electrostatic charge, axial aspect, and entanglement. Exploiting the complexation of two oppositely charged nanopolysaccharides, cellulose nanofibrils (CNFs) and nanochitin (NCh), we prepared CNF/NCh aqueous suspensions and identified the conditions for charge balance (turbidity and electrophoretic mobility titration). By adjusting the composition of CNF/NCh complexes, below and above net neutrality conditions, we produced sunflower oil-in-water Pickering emulsions with adjustable droplet diameters and stability against creaming and oiling-off. The adsorption of CNF/NCh complexes at the oil/water interface occurred with simultaneous partitioning (accumulation) of the CNF on the surface of the droplets in net negative or positive systems (below and above stochiometric charge balance relative to NCh). We further show that the morphology of the droplets and size distribution were preserved during storage for at least 6 months under ambient conditions. This long-term stability was held with a remarkable tolerance to changes in pH (, 3-11) and ionic strength (, 100-500 mM). The mechanism explaining these observations relates to the adsorption of the CNF in the complexes, counteracting the charge losses resulting from the deprotonation of NCh or charge screening. Overall, CNF/NCh complexes and the respective interfacial nanoparticle exchange greatly extend the conditions, favoring highly stable, green Pickering emulsions that offer potential in applications relevant to foodstuff, pharmaceutical, and cosmetic formulations.
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http://dx.doi.org/10.1021/acsami.0c22560DOI Listing
March 2021

Real-time liver tracking algorithm based on LSTM and SVR networks for use in surface-guided radiation therapy.

Radiat Oncol 2021 Jan 14;16(1):13. Epub 2021 Jan 14.

Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Background: Surface-guided radiation therapy can be used to continuously monitor a patient's surface motions during radiotherapy by a non-irradiating, noninvasive optical surface imaging technique. In this study, machine learning methods were applied to predict external respiratory motion signals and predict internal liver motion in this therapeutic context.

Methods: Seven groups of interrelated external/internal respiratory liver motion samples lasting from 5 to 6 min collected simultaneously were used as a dataset, D. Long short-term memory (LSTM) and support vector regression (SVR) networks were then used to establish external respiratory signal prediction models (LSTMpred/SVRpred) and external/internal respiratory motion correlation models (LSTMcorr/SVRcorr). These external prediction and external/internal correlation models were then combined into an integrated model. Finally, the LSTMcorr model was used to perform five groups of model updating experiments to confirm the necessity of continuously updating the external/internal correlation model. The root-mean-square error (RMSE), mean absolute error (MAE), and maximum absolute error (MAX_AE) were used to evaluate the performance of each model.

Results: The models established using the LSTM neural network performed better than those established using the SVR network in the tasks of predicting external respiratory signals for latency-compensation (RMSE < 0.5 mm at a latency of 450 ms) and predicting internal liver motion using external signals (RMSE < 0.6 mm). The prediction errors of the integrated model (RMSE ≤ 1.0 mm) were slightly higher than those of the external prediction and external/internal correlation models. The RMSE/MAE of the fifth model update was approximately ten times smaller than that of the first model update.

Conclusions: The LSTM networks outperform SVR networks at predicting external respiratory signals and internal liver motion because of LSTM's strong ability to deal with time-dependencies. The LSTM-based integrated model performs well at predicting liver motion from external respiratory signals with system latencies of up to 450 ms. It is necessary to update the external/internal correlation model continuously.
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http://dx.doi.org/10.1186/s13014-020-01729-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807524PMC
January 2021

Aberrant elevation of GDF8 impairs granulosa cell glucose metabolism via upregulating SERPINE1 expression in patients with PCOS.

Mol Ther Nucleic Acids 2021 Mar 11;23:294-309. Epub 2020 Nov 11.

Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310002, China.

Clinical investigations have demonstrated that polycystic ovary syndrome (PCOS) is often accompanied by insulin resistance (IR) in more than 70% of women with PCOS. However, the etiology of PCOS with IR remains to be characterized. Growth differentiation factor 8 (GDF8) is an intraovarian factor that plays a vital role in the regulation of follicle development and ovulation. Previous studies have reported that GDF8 is a pathogenic factor in glucose metabolism disorder in IR patients. To date, the role of GDF8 on glucose metabolism of granulosa cell in PCOS patients remains to be determined. In the current study, we demonstrated that the expression and accumulation of GDF8 in human granulosa-lutein (hGL) cells and follicular fluid from PCOS patients were higher compared with those of non-PCOS women. GDF8 treatment caused glucose metabolism defects in hGL cells. Transcriptome sequencing results showed that SERPINE1 mediated GDF8-induced impairment of hGL glucose metabolism defects. Using pharmacological and small interfering RNA (siRNA)-mediated knockdown approaches, we demonstrated that GDF8 upregulated the expression of SERPINE1 via the ALK5-mediated SMAD2/3-SMAD4 signaling pathway. Interestingly, the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway was also activated with GDF8 treatment but did not participate in the effect of GDF8 on SERPINE1 expression. Our results also showed that TP53 was required for the GDF8-stimulated increase in SERPINE1 expression. Importantly, our study demonstrated that SB-431542 treatment significantly improved DHEA-induced PCOS-like ovaries. These findings support a potential role for GDF8 in metabolic disorders in PCOS.
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http://dx.doi.org/10.1016/j.omtn.2020.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779537PMC
March 2021

Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study.

Invest New Drugs 2021 06 7;39(3):836-845. Epub 2021 Jan 7.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.

Background Gemcitabine plus cisplatin is regarded as the standard first-line therapy for patients with advanced biliary tract cancer (BTC); however, no standard chemotherapy has yet been recommended after treatment failure. Modified FOLFIRINOX (mFOLFIRINOX) appears to be a better-tolerated regimen, which leads to improved survival in metastatic pancreatic cancer that has histological and molecular similarities with BTC. We assessed the efficacy and safety of mFOLFIRINOX as salvage therapy in advanced BTC patients who were refractory to previous chemotherapy. Methods A total of 15 consecutive patients with documented unresectable locally advanced or metastatic BCT who received the mFOLFIRINOX regimen were included in the study. Patients were intravenously administrated with oxaliplatin (65 mg/m), leucovorin (400 mg/m), irinotecan (150 mg/m), and continuous infusion of fluorouracil (2400 mg/m) over 46 h. The objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were recorded. Results At least three cycles of mFOLFIRINOX regimen were delivered to 15 patients with a median number of 6.0 cycles (IQR 5.5-11.0). The median duration of treatment was 3.8 months (IQR 2.9-8.5). Four patients (26.7%) achieved an ORR, and 12 patients (80.0%) had a DCR. The median PFS and OS were 6.7 months (95%CI 2.3-11.1) and 13.2 months (95%CI 7.3-19.1), respectively. Five patients (33.3%) had treatment-related grade 3/4 AEs. The most common grade 3/4 AE was neutropenia (n = 3, 20.0%), while there was no occurrence of febrile neutropenia. Conclusion Treatment with mFOLFIRINOX has promising efficacy and favorable tolerance as salvage therapy in patients with refractory advanced BCT.
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http://dx.doi.org/10.1007/s10637-020-01045-7DOI Listing
June 2021

Associative structures formed from cellulose nanofibrils and nanochitins are pH-responsive and exhibit tunable rheology.

J Colloid Interface Sci 2021 Apr 17;588:232-241. Epub 2020 Dec 17.

Department of Chemical & Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA. Electronic address:

Hypothesis: Nanocellulose and nanochitin are both biobased materials with complementary structures and properties. Both exhibit pH-dependent surface charges which are opposite in sign. Hence, it should be possible to manipulate them to form complexed structures via ionic bond formation at prescribed pH conditions.

Experiment: Nanocellulose and nanochitin were mixed after exposure to acidic or neutral conditions to influence their ionization state. The heat of interaction during the introduction of nanochitin to nanocellulose was monitored via isothermal titration calorimetry. The strength and gel properties of the resulting structures were characterized via rheological measurement.

Findings: The resultant gel properties in the designed hybrid systems were found to depend directly on the charge state of the starting materials, which was dictated by pH adjustment. Different interparticle interactions including ionic attraction, hydrophobic associations, and physical entanglement were identified in the systems and the influence of each was elucidated for different conditions of pH, concentration, and ratio of nanochitin to nanocellulose. Hydrophobic associations between neutralized nanochitin particles were found to contribute strongly to increased elastic modulus values. Ionic complex formation was found to provide enhanced stability under broader pH conditions, while physical entanglement of cellulose nanofibers was a substantial thickening mechanism in all systems.
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http://dx.doi.org/10.1016/j.jcis.2020.12.041DOI Listing
April 2021

Targeting Early Healing Phase with Titania Nanotube Arrays on Tunable Diameters to Accelerate Bone Regeneration and Osseointegration.

Small 2021 01 30;17(4):e2006287. Epub 2020 Dec 30.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, 4059, Australia.

Blood coagulation and inflammation are the earliest biological responses to implant surfaces. Implant nano-surfaces can significantly impact the osseointegration through the influence on the early phase of bone regeneration. However, the interplay between blood clot property and inflammatory reaction on nanosurfaces is rarely understood. Herein, titania nanotube arrays (TNAs) with different diameters are fabricated on titanium. In vitro evaluation with the whole blood indicates that TNA with a diameter of 15 nm (TNA 15) enables noteworthy platelet activation resulting in distinct clot features compared with that of pure Ti and TNA with a diameter of 120 nm (TNA 120). Further co-culture with macrophages on the clot or in the clot-conditioned medium shows that the clot on TNA 15 downregulates the inflammation and manipulates a favorable osteoimmunomodulatory environment for osteogenesis. In vivo studies further demonstrate that TNA 15 could downregulate the inflammation-related genes while upregulating growth metabolism-related genes in an early healing hematoma. Additionally, TNA 15 promotes de novo bone formation with improved extending of osteocyte dendrites, demonstrating the desired osseointegration. These findings indicate that surface nano-dimensions can significantly influence clot formation and appropriate clot features can manipulate a favorable osteoimmunomodulatory environment for bone regeneration and osseointegration.
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http://dx.doi.org/10.1002/smll.202006287DOI Listing
January 2021

Recent Advances in Food Emulsions and Engineering Foodstuffs Using Plant-Based Nanocelluloses.

Annu Rev Food Sci Technol 2021 03 9;12:383-406. Epub 2020 Dec 9.

Bioproducts Institute, Departments of Chemical and Biological Engineering, Chemistry, and Wood Science, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.

In this article, the application of nanocelluloses, especially cellulose nanofibrils and cellulose nanocrystals, as functional ingredients in foods is reviewed. These ingredients offer a sustainable and economic source of natural plant-based nanoparticles. Nanocelluloses are particularly suitable for altering the physicochemical, sensory, and nutritional properties of foods because of their ability to create novel structures. For instance, they can adsorb to air-water or oil-water interfaces and stabilize foams or emulsions, self-assemble in aqueous solutions to form gel networks, and act as fillers or fat replacers. The functionality of nanocelluloses can be extended by chemical functionalization of their surfaces or by using them in combination with other natural food ingredients, such as biosurfactants or biopolymers. As a result, it is possible to create stimuli-responsive, tailorable, and/or active functional biomaterials suitable for a range of foodapplications. In this article, we describe the chemistry, structure, and physicochemical properties of cellulose as well as their relevance for the application of nanocelluloses as functional ingredients in foods. Special emphasis is given to their use as particle stabilizers in Pickering emulsions, but we also discuss their potential application for creating innovative biomaterials with novel functional attributes, such as edible films and packaging. Finally, some of the challenges associated with using nanocelluloses in foods are critically evaluated, including their potential safety and consumer acceptance.
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http://dx.doi.org/10.1146/annurev-food-061920-123242DOI Listing
March 2021

A systematic review of etiology, epidemiology, clinical manifestations, image findings, and medication of 2019 Corona Virus Disease-19 in Wuhan, China.

Medicine (Baltimore) 2020 Oct;99(42):e22688

Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Unknown origin pneumonia has been furiously spreading since the late of December 2019, subsequently spread to approximately all provinces and areas in China and many countries, which was announced as a Public Health Emergency of International Concern by World Health Organization (WHO). The studies on 2019 Corona Virus Disease-19 (COVID-19) conducted from various fields around the world. Herein, the objective of the present study is to summarize the etiology, epidemiology, clinical manifestations, image findings, traceability analysis, and drug development of COVID-19.

Methods: The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Data. Other relevant literature will be manually searched as a compliment. We have reviewed etiology, epidemiology, clinical manifestations, image findings, and medication from case reports and retrospective clinical studies relating to COVID-19 published since the outbreak.

Results: The coronavirus is closely related to bat coronavirus and pangolin coronavirus. Besides, the infection pathway is confirmed to be the respiratory and digestive systems. The virus indicates person-to-person transmission and some patients present asymptomatic. The elderly have a higher mortality rate. Rapid and sensitive nucleic acid testing is usually used as a basis for diagnosis. Currently, there is no specific vaccine and antiviral drug. Intervention actions such as travel bans and quarantine adopted have effectively reduced the spread of the epidemic.

Conclusion: This systemic review will provide high-quality evidence to summarize etiology, epidemiology, clinical manifestations, image findings, traceability analysis, drug development in patients with COVID-19.
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http://dx.doi.org/10.1097/MD.0000000000022688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572017PMC
October 2020

Safety and Efficacy of Long-Term Zoledronic Acid in Advanced Breast Cancer with Bone Metastasis in South China.

J Oncol 2020 30;2020:5670601. Epub 2020 Sep 30.

Department of VIP Section, Sun Yat-sen University Cancer Center, State Key Laboratory Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.

Background: This retrospective study aimed to characterize the long-term (>24 months) safety profile of zoledronic acid (ZA). We aimed to investigate whether long-term ZA treatment had greater benefits than short-term treatment in patients from southern China with advanced breast cancer (ABC) with bone metastasis. . A total of 566 metastatic breast cancer cases were included and divided into two groups according to the duration of ZA treatment. The included patients had at least one lytic bone lesion and had no skeletal-related events (SREs) prior to ZA therapy. The primary endpoint was to analyze the safety and long-term adverse effects, which covered osteonecrosis of jaws (ONJ), renal impairment, and hearing impairment. The second objective was to determine the efficacy of long-term ZA treatment by the incidence of SREs.

Results: Fifteen patients were diagnosed with ONJ (2.7%): nine in the short-term group (3.1%) and six in the long-term group (2.2%,  = 0.606). Five cases (0.9%) had renal function impairment: two in the short-term group (0.7%) and four in the long-term group (1.1%,  = 0.676). One patient (0.2%) in the long-term group had hearing impairment after 23 months of ZA treatment (0.4%,  = 0.482). In total, 103 cases in the short-term group (35.2%) and 138 cases in long-term group (50.5%) developed SREs ( < 0.001). The mean annual SRE rate was 0.3 in the short-term group (range, 0-3.1) versus 0.2 in the long-term group (0-1.0,  = 0.269). Subgroup analysis suggested that cases with non-load-bearing bone involvement and those who received systematic anticancer therapy without chemotherapy might benefit from long-term ZA treatment. Cox regression analysis indicated poor performance status, and nonvisceral organ involvement predicted high risk for SRE.

Conclusions: The extension of ZA treatment did not increase the long-term adverse events and reduced the annual incidence of SREs beyond 24 months. Although longer treatment of ZA over 24 months appeared to be safe, further prospective investigation is required.
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http://dx.doi.org/10.1155/2020/5670601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545466PMC
September 2020

BMP2 increases the production of BDNF through the upregulation of proBDNF and furin expression in human granulosa-lutein cells.

FASEB J 2020 12 13;34(12):16129-16143. Epub 2020 Oct 13.

Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Locally produced in human granulosa cells of the developing follicle, bone morphogenetic protein 2 (BMP2) plays a crucial role in the regulation of ovarian folliculogenesis and luteal formation. Brain-derived neurotrophic factor (BDNF) is an intraovarian neurotrophic factor that has been shown to promote oocyte maturation and subsequent fertilization competency. At present, little is known regarding the intracellular regulation, assembly and secretion of endogenous BDNF in human granulosa cells. The aim of this study was to explore the effect of BMP2 on the expression and production of BDNF in human granulosa cells and the molecular mechanisms underlying this effect. An immortalized human granulosa cell line (SVOG) and primary human granulosa-lutein (hGL) cells were utilized as in vitro study models. Our results showed that BMP2 significantly increased the mRNA and secreted levels of BDNF. Additionally, BMP2 upregulated the expression of furin at the transcriptional and translational levels. Knockdown of endogenous furin partially attenuated the BMP2-induced increase in BDNF production, indicating that furin is involved in the maturation process of BDNF. Using pharmacological (kinase receptor inhibitors) and siRNA-mediated inhibition approaches, we demonstrated that BMP2-induced upregulation of BDNF and furin expression is most likely mediated by the activin receptor-like kinase (ALK)2/ALK3-SMAD4 signaling pathway. Notably, analysis using clinical samples revealed that there was a positive correlation between follicular fluid concentrations of BMP2 and those of BDNF. These results indicate that BMP2 increases the production of mature BDNF by upregulating the precursor BDNF and promoting the proteolytic processing of mature BDNF. Finally, we also investigated the effects of BMP2 on ovarian steroidogenesis and the results showed that BMP2 treatment significantly increased the accumulated level of estradiol (by upregulating the expression of FSH receptor and cytochrome P450 aromatase), whereas it decreased the accumulated level of progesterone (by downregulating the expression of LH receptors and steroidogenic acute regulatory protein) in primary hGL cells. Our findings provide a novel paracrine mechanism underlying the regulation of an intraovarian growth factor in human granulosa cells.
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http://dx.doi.org/10.1096/fj.202000940RDOI Listing
December 2020

Effectiveness of Atorvastatin in the Treatment of Asymptomatic Heart Failure After Myocardial Infarction: A Clinical Study.

Adv Ther 2020 11 23;37(11):4649-4659. Epub 2020 Sep 23.

The Sixth Department of Cardiovascular Medicine, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Introduction: Silent heart failure after myocardial infarction has not been effectively treated. Atorvastatin has certain efficacy in the treatment of heart failure. Our clinical study aimed to investigate the effectiveness of atorvastatin in patients with asymptomatic heart failure after myocardial infarction.

Methods: A total of 162 patients with asymptomatic heart failure after myocardial infarction in our hospital from August 2018 to August 2019 were randomly divided into the observation group (81 cases were treated with atorvastatin on the basis of routine therapy) and the control group (81 cases were treated with routine symptomatic treatment). The clinical curative effect, the level of related inflammatory cytokines, cardiac function index, and vascular endothelial function were compared between the two groups.

Results: Before intervention, there was no significant difference in tumor necrosis factor (TNFα), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), plasma N-terminal B-type natriuretic peptide (NT-ProBNP), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular posterior wall thickness (LVPWT), asymmetric dimethyarginine (ADMA), activity of nitric oxide synthase (NOS), nitric oxide (NO) and flow-mediated dilation (FMD) between the two groups. After intervention, TNFα, hs-CRP, IL-6, NT-ProBNP, LVEF, LVEDD, LVESD, LVPWT, ADMA, NOS, NO, and FMD were improved in both groups. The clinical curative effect, TNFα, hs-CRP, IL-6, NT-ProBNP, LVEF, LVEDD, LVESD, LVPWT, ADMA, NOS, NO, and FMD in the observation group showed significantly greater results than those in the control group (P < 0.05).

Conclusion: Atorvastatin exerted a great effect in treating asymptomatic heart failure after myocardial infarction, which can evidently reduce the level of related inflammatory cytokines, improve cardiac function, and regulate vascular endothelial function. Hence, atorvastatin is considered a valid and alternative approach in clinical practice.
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http://dx.doi.org/10.1007/s12325-020-01441-8DOI Listing
November 2020
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