Publications by authors named "Yi Zhou"

1,994 Publications

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A review on the industrial solid waste application in pelletizing additives: Composition, mechanism and process characteristics.

J Hazard Mater 2021 Aug 30;423(Pt B):127056. Epub 2021 Aug 30.

School of Materials Science and Engineering, Taiyuan University of Science and Technology, Taiyuan, 030024, PR China.

Reducing the cost of pellet additives as a substitute for reducing bentonite binder is an important research direction of new pellet additives. There are some industrial solid wastes that have the similar physical and chemical properties to bentonite, and SiO content of them may be much lower than bentonite, but also contains a lot of FeO, AlO, MgO, BO and other components beneficial to the quality of pellets, which have been paid more attention by many pellet workers. In this review, the effect mechanism of FeO, NaO/KO, AlO, SiO, CaO, MgO and BO in the industrial solid wastes on the fired strength and reduction expansion of pellets were systematically summarized. At the same time, the influences of five representative large scale modified industrial solid waste additives including iron tailings, bauxite tailings, fly ash, red mud and boron sludge on the properties of green pellets and finished pellets were described in detail. It can be seen that the applications of industrial solid waste in pellet additives can partially or completely replace bentonite binder, especially fly ash, red mud and boron sludge, which can not only improve the quality of pellets, but also decrease the cost, save energy and reduce pollution, with significant economic benefits.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127056DOI Listing
August 2021

Financial incentives can improve secondary distribution of HIV self-tests.

Lancet Glob Health 2021 Oct;9(10):e1366

Dermatology Hospital of South Medical University, Guangzhou, China; University of North Carolina at Chapel Hill Project-China, Guangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/S2214-109X(21)00368-5DOI Listing
October 2021

Synthesizing Molecules with Linear Tricyclic 5/5/5 and 6/5/5 Skeletons via [5 + 2 + 1]/Ene Strategy.

Org Lett 2021 Sep 17. Epub 2021 Sep 17.

Department of Chemistry, Renmin University of China, Beijing 100872, China.

Report here is the development of a [5 + 2 + 1]/ene strategy for the synthesis of molecules with linear tricyclic 5/5/5 and 6/5/5 skeletons widely found in natural products. The first step of this strategy is applying a Rh-catalyzed [5 + 2 + 1] reaction of ene-vinylcyclopropanes and CO to synthesize 5/8 and 6/8 bicyclic compounds, which can then be transformed to the final target molecules by an InCl-catalyzed ene reaction.
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http://dx.doi.org/10.1021/acs.orglett.1c02766DOI Listing
September 2021

Effect of non-linearity on rheumatoid factor assay in Beckman system IMMAGE800.

Clin Chem Lab Med 2021 Sep 15. Epub 2021 Sep 15.

Department of Infectious Diseases, Changhai Hospital, SMMU, Shanghai, P. R. China.

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http://dx.doi.org/10.1515/cclm-2021-0481DOI Listing
September 2021

Clinical Features of Spontaneous Regression of Retinopathy of Prematurity in China: A 5-Year Retrospective Case Series.

Front Med (Lausanne) 2021 31;8:731421. Epub 2021 Aug 31.

Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

The aim of this study is to explore the clinical features of spontaneous regression of retinopathy of prematurity (ROP) in China, including fundus appearance, time course, and affecting factors. Data of pediatric patients in whom ROP spontaneously regressed without treatment were collected, including general demographics, medical history, zones and stages of ROP, and changes of fundus appearance. The fundus manifestations of spontaneous regression in ROP were systematically summarized. Meanwhile, the time course of spontaneous regression in ROP was further analyzed, including the onset time, completion time, and duration of regression, which were all compared across different ROP zones and stages. The associated factors were analyzed by survival analysis for their correlation with delayed regression for the first time. Two hundred thirty-seven eyes of 237 pediatric patients were included. The fundus manifestations of regression differed across stages. Lesions gradually subsided, and the retinal vessels gradually vascularized completely. However, despite ROP regression, some abnormalities remained. We observed avascular retina in the temporal periphery (19.0%), increased vascular branching (6.8%), retinal pigmentary changes (6.8%), and smaller angle between the upper and lower temporal retinal vessel trunks (3.0%). Acute ROP started to regress at a median 40 weeks of postmenstrual age (PMA) and completely regressed by median 49.0 weeks of PMA. The median duration for regression was 8.5 weeks. The zone II ROP and stage 3 ROP had a later time for onset and completion of regression, and longer duration. Anemia and retinal hemorrhage (RH) were identified as independent risk factors for delayed regression by survival analysis. During spontaneous regression, the fundus appearance is diverse, and the retinal vessels gradually vascularized completely. The time course of regression differs depending on the ROP zone and stage. Anemia and RH are independent risk factors for delayed regression. Further research of the natural course of the regression of ROP is needed to help design effective screening and follow-up plans.
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http://dx.doi.org/10.3389/fmed.2021.731421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439357PMC
August 2021

Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma.

BMC Cancer 2021 Sep 14;21(1):1020. Epub 2021 Sep 14.

Department of Interventional Radiology, The First Hospital of China Medical University, No.155 Nanjing Road, Heping District, Shenyang, 110000, Liaoning, China.

Background: There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT).

Methods: Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival.

Results: No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p's ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3.

Conclusions: The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.
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http://dx.doi.org/10.1186/s12885-021-08680-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439081PMC
September 2021

A review of research progress on mechanisms and overcoming strategies of acquired osimertinib resistance.

Anticancer Drugs 2021 Sep 13. Epub 2021 Sep 13.

Department of Oncology, Dalian Third People's Hospital, Dalian, China.

Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) is the standard first-line treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Third-generation EGFR-TKIs, represented by osimertinib, have been approved to overcome the EGFR T790M mutation in patients who are resistant to first- or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. However, resistance to the third generation of EGFR-TKIs is still inevitable. Acquired drug resistance is the main reason for limiting the long-term effectiveness of targeted therapy in EGFR-mutated NSCLC patients. The mechanism of EGFR-TKI resistance of the third generation has become a focus of research in the field of targeted therapy. In this review, we summarize the research progress in resistance mechanisms of advanced NSCLC to osimertinib and the potential overcoming strategies and hope to provide a clinical basis and ideas for precision treatment of NSCLC.
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http://dx.doi.org/10.1097/CAD.0000000000001242DOI Listing
September 2021

MsTGANet: Automatic Drusen Segmentation from Retinal OCT Images.

IEEE Trans Med Imaging 2021 Sep 14;PP. Epub 2021 Sep 14.

Drusen is considered as the landmark for diagnosis of AMD and important risk factor for the development of AMD. Therefore, accurate segmentation of drusen in retinal OCT images is crucial for early diagnosis of AMD. However, drusen segmentation in retinal OCT images is still very challenging due to the large variations in size and shape of drusen, blurred boundaries, and speckle noise interference. Moreover, the lack of OCT dataset with pixel-level annotation is also a vital factor hindering the improvement of drusen segmentation accuracy. To solve these problems, a novel multi-scale transformer global attention network (MsTGANet) is proposed for drusen segmentation in retinal OCT images. In MsTGANet, which is based on U-Shape architecture, a novel multi-scale transformer non-local (MsTNL) module is designed and inserted into the top of encoder path, aiming at capturing multi-scale non-local features with long-range dependencies from different layers of encoder. Meanwhile, a novel multi-semantic global channel and spatial joint attention module (MsGCS) between encoder and decoder is proposed to guide the model to fuse different semantic features, thereby improving the model's ability to learn multi-semantic global contextual information. Furthermore, to alleviate the shortage of labeled data, we propose a novel semi-supervised version of MsTGANet (Semi-MsTGANet) based on pseudo-labeled data augmentation strategy, which can leverage a large amount of unlabeled data to further improve the segmentation performance. Finally, comprehensive experiments are conducted to evaluate the performance of the proposed MsTGANet and Semi-MsTGANet. The experimental results show that our proposed methods achieve better segmentation accuracy than other state-of-the-art CNN-based methods.
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http://dx.doi.org/10.1109/TMI.2021.3112716DOI Listing
September 2021

A three-dimensional bioprinting technique, based on a gelatin/alginate hydrogel, for the tissue engineering of hair follicle reconstruction.

Int J Biol Macromol 2021 Sep 9. Epub 2021 Sep 9.

Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address:

Hair loss remains a challenging clinical problem that influences the quality of life. Three-dimensional (3D) bioprinting has become a valuable tool for fabricating tissue constructs for transplantation and other biomedical applications. Although some simple organs, such as skin and cartilage, have been successfully simulated, it remains challenging to make hair follicles (HFs), which are highly complex organs. The tissue engineering of human HFs has been a long-standing challenge, and progress with this has lagged behind that with other lab-grown tissues. This is principally due to a lack of availability of a platform that can successfully recapitulate the microenvironmental cues required to maintain the requisite cellular interactions for hair neogenesis. In this study, we used a 3D bioprinting technique based on a gelatin/alginate hydrogel to construct a multilayer composite scaffold with cuticular and corium layers to simulate the microenvironment of dermal papilla cells (DPCs) in the human body. This new approach permits the controllable formation of self-aggregating spheroids of DPCs in a physiologically relevant extracellular matrix and the initiation of epidermal-mesenchymal interactions, which results in HF formation in vivo. In conclusion, our 3D-bioprinted multilayer composite scaffold prepared using a gelatin/alginate hydrogel provides a suitable 3D microenvironment for DPCs to induce HF formation. The ability to regenerate entire HFs should have a significant impact on the medical management of hair loss. This method may also have critical applications for skin tissue engineering, with its appendages, for other purposes.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.014DOI Listing
September 2021

Dissipation and residue of fosthiazate in tomato and cherry tomato and a risk assessment of dietary intake.

Environ Sci Pollut Res Int 2021 Sep 9. Epub 2021 Sep 9.

Department of Plant Protection, Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, China.

In this study, the safety and risk of fosthiazate as a nematicide against root-knot nematode in tomato and cherry tomato were evaluated. The dissipation and residue of fosthiazate for 28 days in tomatoes and cherry tomatoes were determined and studied by HPLC after simple, rapid pre-treatment. The mean recovery was 83.79~94.18%, and the relative standard deviations were 3.97~7.40%. Results showed that the half-lives of fosthiazate in tomatoes (4.81~5.37 days) were significantly lower than that in cherry tomatoes (5.25~5.73 days). At the pre-harvest interval (PHI) of 21 days, the residues of tomatoes and cherry tomatoes were 0.032~0.046 mg/kg, which were lower than the maximum residue level (MRL) established in China. The potential risks of fosthiazate exposure through the dietary intake of tomatoes and cherry tomatoes to different populations were also studied. According to the results of dietary risk assessment, the residual levels of fosthiazate were within the acceptable range of long-term dietary risk in different populations in China within the sampling interval of 21 days after the application of fosthiazate. Our results show that fosthiazate at 2250 g.a.i./ha in the field control of root-knot nematode has high safety and low risk, and can provide a reference for the safe and reasonable use of fosthiazate as a nematicide in the field.
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http://dx.doi.org/10.1007/s11356-021-16305-zDOI Listing
September 2021

Effect of Surface Integrity on Hot Fatigue Life of TiAlNb Intermetallic Alloy.

Materials (Basel) 2021 Aug 26;14(17). Epub 2021 Aug 26.

Materials Evaluation Center for Aeronautical and Aeroengine Applications, AECC Beijing Institute of Aeronautical Materials, Beijing 100095, China.

The effect of surface integrity on the hot fatigue performance of TiAlNb alloy was investigated. A turning process was used to prepare the standard specimens for hot fatigue tests. The surface integrity characterization and axial fatigue tests were performed. The results show that the influence of surface roughness on the hot fatigue performance of the TiAlNb alloy is a secondary factor. The compressive residual stress and enhanced microhardness in the surface layer has a significant effect on the hot fatigue life and they are dominant in the hot fatigue behavior of the TiAlNb alloy. Through the investigation on the characteristics of the fatigue fractures, the fatigue propagation process was significantly suppressed because of the strong residual compressive stress and microhardness distribution on the surface layer of the TiAlNb specimen.
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http://dx.doi.org/10.3390/ma14174841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432654PMC
August 2021

CISD3 inhibition drives cystine-deprivation induced ferroptosis.

Cell Death Dis 2021 Sep 8;12(9):839. Epub 2021 Sep 8.

Department of Central Laboratory, Affiliated Hangzhou first people's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China.

Ferroptosis, a new form of programmed cell death, not only promotes the pathological process of various human diseases, but also regulates cancer progression. Current perspectives on the underlying mechanisms remain largely unknown. Herein, we report a member of the NEET protein family, CISD3, exerts a regulatory role in cancer progression and ferroptosis both in vivo and in vitro. Pan-cancer analysis from TCGA reveals that expression of CISD3 is generally elevated in various human cancers which are consequently associated with a higher hazard ratio and poorer overall survival. Moreover, knockdown of CISD3 significantly accelerates lipid peroxidation and accentuates free iron accumulation triggered by Xc inhibition or cystine-deprivation, thus causing ferroptotic cell death. Conversely, ectopic expression of the shRNA-resistant form of CISD3 (CISD3res) efficiently ameliorates the ferroptotic cell death. Mechanistically, CISD3 depletion presents a metabolic reprogramming toward glutaminolysis, which is required for the fuel of mitochondrial oxidative phosphorylation. Both the inhibitors of glutaminolysis and the ETC process were capable of blocking the lipid peroxidation and ferroptotic cell death in the shCISD3 cells. Besides, genetic and pharmacological activation of mitophagy can rescue the CISD3 knockdown-induced ferroptosis by eliminating the damaged mitochondria. Noteworthily, GPX4 acts downstream of CISD3 mediated ferroptosis, which fails to reverse the homeostasis of mitochondria. Collectively, the present work provides novel insights into the regulatory role of CISD3 in ferroptotic cell death and presents a potential target for advanced antitumor activity through ferroptosis.
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http://dx.doi.org/10.1038/s41419-021-04128-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426496PMC
September 2021

Effect of Environmental Stress on the Nutrient Stoichiometry of the Clonal Plant in Inland Riparian Wetlands of Northwest China.

Front Plant Sci 2021 19;12:705319. Epub 2021 Aug 19.

College of Geography and Environment Science, Northwest Normal University, Lanzhou, China.

Clonal plants play an important role in determining ecosystem properties such as community stability, species diversity and nutrient cycling. However, relatively little information is available about the stoichiometric characteristics of clonal plants and their drivers in inland riparian wetlands under strong environmental stress. In this manuscript, we studied the clonal plant in an inland riparian wetland of Northwest China and compared its nutrient distribution and stoichiometry trade-offs as well as its responses to soil environmental factors in three different environments, namely, a wetland, a salt marsh, and a desert. We found that (1) could adapt to heterogeneous environments by changing its nutrient allocation strategies, as evidenced by the significant decrease in N and P concentrations, and significant increase in whole-plant C:P and N:P ratios from the wetland to the desert habitats. (2) adapted to stressful environments by changing its nutrient allocation patterns among different modules, showing a greater tendency to invest N and P in underground modules (rhizomes and roots) and an increase in the utilization efficiency of N and P in the leaves, and stems as environmental stress increased. (3) The C-N, C-P, and N:P-C in the whole plant and in each module showed significant anisotropic growth relationships in the three habitats ( < 0.05). (4) Soil water, pH and salt were the main factors limiting nutrient stoichiometry. The results of this study clarified the ecological adaptation mechanism of the clonal plant to heterogeneous environments and provided targeted protection strategies for inland riparian wetlands in Northwest China.
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http://dx.doi.org/10.3389/fpls.2021.705319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416684PMC
August 2021

Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis.

Redox Biol 2021 Aug 31;46:102122. Epub 2021 Aug 31.

Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China. Electronic address:

Hepatocellular carcinoma (HCC) is one of the paramount causes of cancer-related death worldwide. Despite recent advances have been made in clinical treatments of HCC, the general prognosis of patients remains poor. Therefore, it is imperative to develop a less toxic and more effective therapeutic strategy. Currently, series of cellular, molecular, and pharmacological experimental approaches were utilized to address the unrecognized characteristics of disulfiram (DSF), pursuing the goal of repurposing DSF for cancer therapy. We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells. Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death. Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu. Mechanically, we found that DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2. Notably, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis. Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu. Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase. In summary, these results provide experimental evidence that inhibition of the compensatory NRF2 elevation strengthens HCC cells more vulnerable to DSF/Cu induced ferroptosis, which facilitates the synergistic cytotoxicity of DSF/Cu and sorafenib.
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http://dx.doi.org/10.1016/j.redox.2021.102122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416961PMC
August 2021

Single-cell transcriptome and cell-specific network analysis reveal the reparative effect of neurotrophin-4 in preantral follicles grown in vitro.

Reprod Biol Endocrinol 2021 Sep 4;19(1):133. Epub 2021 Sep 4.

Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China.

Background: In-vitro-grow (IVG) of preantral follicles is essential for female fertility preservation, while practical approach for improvement is far from being explored. Studies have indicated that neurotrophin-4 (NT-4) is preferentially expressed in human preantral follicles and may be crucial to preantral follicle growth.

Methods: We observed the location and expression of Tropomyosin-related kinase B (TRKB) in human and mouse ovaries with immunofluorescence and Western blot, and the relation between oocyte maturation and NT-4 level in follicular fluid (FF). Mice model was applied to investigate the effect of NT-4 on preantral follicle IVG. Single-cell RNA sequencing of oocyte combined with cell-specific network analysis was conducted to uncover the underlying mechanism of effect.

Results: We reported the dynamic location of TRKB in human and mouse ovaries, and a positive relationship between human oocyte maturation and NT-4 level in FF. Improving effect of NT-4 was observed on mice preantral follicle IVG, including follicle development and oocyte maturation. Transcriptome analysis showed that the reparative effect of NT-4 on oocyte maturation might be mediated by regulation of PI3K-Akt signaling and subsequent organization of F-actin. Suppression of advanced stimulated complement system in granulosa cells might contribute to the improvement. Cell-specific network analysis revealed NT-4 may recover the inflammation damage induced by abnormal lipid metabolism in IVG.

Conclusions: Our data suggest that NT-4 is involved in ovarian physiology and may improve the efficiency of preantral follicle IVG for fertility preservation.
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http://dx.doi.org/10.1186/s12958-021-00818-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417972PMC
September 2021

Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial.

JAMA Oncol 2021 Sep 2. Epub 2021 Sep 2.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

Importance: Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).

Objective: To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.

Design, Setting, And Participants: This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018. Eligible patients were 18 years of age or older and had advanced, recurrent, or metastatic ALK-positive NSCLC.

Interventions: Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily.

Main Outcomes And Measures: The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary end points included systemic and intracranial response, time to central nervous system progression, and overall survival. Efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population consisting of patients with central laboratory-confirmed ALK-positive NSCLC.

Results: A total of 290 patients (149 men [51.4%]; median age, 54 years [range, 25-90 years]) were randomized. In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 [range, 0.03-44.0 months] vs 12.7 months [range, 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P < .001), with a median follow-up of 23.8 months (range, 0-44 months) for the ensartinib group and 20.2 months (range, 0-38 months) for the crizotinib group. In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (95% CI, 8.9-16.6 months; hazard ratio, 0.45; 95% CI, 0.30-0.66; log-rank P < .001). The intracranial response rate confirmed by a blinded independent review committee was 63.6% (7 of 11) with ensartinib vs 21.1% (4 of 19) with crizotinib for patients with target brain metastases at baseline. Progression-free survival for patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib as a result of a lower central nervous system progression rate (at 12 months: 4.2% with ensartinib vs 23.9% with crizotinib; cause-specific hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001). Frequencies of treatment-related serious adverse events (ensartinib: 11 [7.7%] vs crizotinib: 9 [6.1%]), dose reductions (ensartinib: 34 of 143 [23.8%] vs crizotinib: 29 of 146 [19.9%]), or drug discontinuations (ensartinib: 13 of 143 [9.1%] vs crizotinib: 10 of 146 [6.8%]) were similar, without any new safety signals.

Conclusions And Relevance: In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC.

Trial Registration: ClinicalTrials.gov Identifier: NCT02767804.
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http://dx.doi.org/10.1001/jamaoncol.2021.3523DOI Listing
September 2021

Molecular Recognition of the Self-Assembly Mechanism of Glycosyl Amino Acetate-Based Hydrogels.

ACS Omega 2021 Aug 13;6(33):21801-21808. Epub 2021 Aug 13.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China.

The self-assembly of supramolecular hydrogels has attracted the attention of many researchers, and it also has a broad application prospect in biomedical fields. However, there are few studies on the intrinsic mechanism of molecular self-assembly of hydrogels. In this paper, the self-assembly process of glycolipid-based hydrogels is studied by combining quantum chemistry calculation and molecular dynamics simulation. Using quantum chemistry calculation, the stable stacking mode of gelator dimers was explored. Then, by varying the water content in the gelation system, three different morphologies of hydrogels after self-assembly were observed on the nanoscale. When the water content is low, the molecular chains were entangled with each other to form a three-dimensional network structure. When the water content is moderate, the system had obvious stratification, forming the typical structure of "gel-water-gel". The gelators can only form small micelle-like agglomerations when the water content is too high. According to the analysis of the interaction between gelators and that between gelators and water molecules, combined with the study of the radial distribution function and hydrogen bonding, it is determined that the hydrogen bonds formed between gel molecules are the main driving force of the gelation process. Our work is of guiding significance for further exploration of the formation mechanism of a hydrogel and developing its application in other fields.
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http://dx.doi.org/10.1021/acsomega.1c03510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388079PMC
August 2021

Cerium oxide nanoparticles loaded nanofibrous membranes promote bone regeneration for periodontal tissue engineering.

Bioact Mater 2022 Jan 5;7:242-253. Epub 2021 Jun 5.

Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.

Bone regeneration is a crucial part in the treatment of periodontal tissue regeneration, in which new attempts come out along with the development of nanomaterials. Herein, the effect of cerium oxide nanoparticles (CeO NPs) on the cell behavior and function of human periodontal ligament stem cells (hPDLSCs) was investigated. Results of CCK-8 and cell cycle tests demonstrated that CeO NPs not only had good biocompatibility, but also promoted cell proliferation. Furthermore, the levels of alkaline phosphatase activity, mineralized nodule formation and expressions of osteogenic genes and proteins demonstrated CeO NPs could promote osteogenesis differentiation of hPDLSCs. Then we chose electrospinning to fabricate fibrous membranes containing CeO NPs. We showed that the composite membranes improved mechanical properties as well as realized release of CeO NPs. We then applied the composite membranes to study in rat cranial defect models. Micro-CT and histopathological evaluations revealed that nanofibrous membranes with CeO NPs further accelerated new bone formation. Those exciting results demonstrated that CeO NPs and porous membrane contributed to osteogenic ability, and CeO NPs contained electrospun membrane may be a promising candidate material for periodontal bone regeneration.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379477PMC
January 2022

Clinicopathologic Findings in Patients With Initial Diagnosis of Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) in Colorectal Mucosa.

Am J Clin Pathol 2021 Aug 31. Epub 2021 Aug 31.

Department of Laboratory Medicine and Pathology, School of Medicine, Seattle, WA, USA.

Objectives: To evaluate clinicopathologic features, management, and behavior of colorectal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT).

Methods: Clinical data, laboratory studies, and radiographic records were reviewed (2005-2018), and fluorescence in situ hybridization studies were performed.

Results: Eleven patients were identified, six of whom were discovered as an incidental finding on endoscopy. Morphologic and immunophenotypic features were similar to MALT lymphomas at other sites except that lymphoepithelial lesions were uncommon. Three of nine patients were positive for BIRC3/MALT1 fusions, two of whom had identical B-cell clones identified in subsequent gastric biopsy specimens. Eight of 10 patients had no clinically evaluable disease after observation (±antibiotics; n = 4) or radiation/chemotherapy (n = 4).

Conclusions: Patients with incidental and localized colonic MALT lymphoma demonstrated an excellent prognosis with conservative management, although longer follow-up and data based on consistent staging and surveillance methods (including gastric evaluation) are necessary for informed management.
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http://dx.doi.org/10.1093/ajcp/aqab089DOI Listing
August 2021

Gene fusions in tumourigenesis with particular reference to ovarian cancer.

J Med Genet 2021 Aug 30. Epub 2021 Aug 30.

Metabolism, Digestion and Reproduction, Imperial College London, London, UK

Gene fusion, a genomic event that generates a novel gene from two independent genes, has long been known to be implicated in tumourigenesis and cancer progression. It has thus served as a diagnostic and prognostic biomarker in cancer, as well as an ideal therapeutic target in cancer therapy. Gene fusion can arise from chromosomal rearrangement and alternative splicing of transcripts, resulting in deregulation of proto-oncogenes or creation of an oncogenic novel gene. Largely facilitated by next generation sequencing technologies, a plethora of novel gene fusions have been identified in a variety of cancers, which leaves us the challenge of functionally characterising these candidate gene fusions. In this review, we summarise the molecular mechanisms, the oncogenic consequences and the therapeutic implications of verified gene fusions. We also discuss recent studies on gene fusions in both common and rare subtypes of ovarian tumours and how these findings can be translated to cancer therapies to benefit patients carrying these gene fusions.
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http://dx.doi.org/10.1136/jmedgenet-2021-108010DOI Listing
August 2021

Neutrophil Extracellular Traps Exacerbate Secondary Injury Promoting Neuroinflammation and Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

Front Immunol 2021 11;12:698249. Epub 2021 Aug 11.

Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

As the first inflammatory cell recruited to the site of spinal cord injury (SCI), neutrophils were reported to be detrimental to SCI. However, the precise mechanisms as to how neutrophils exacerbate SCI remain largely obscure. In the present study, we demonstrated that infiltrated neutrophils produce neutrophil extracellular traps (NETs), which subsequently promote neuroinflammation and blood-spinal cord barrier disruption to aggravate spinal cord edema and neuronal apoptosis following SCI in rats. Both inhibition of NETs formation by peptidylarginine deiminase 4 (PAD4) inhibitor and disruption of NETs by DNase 1 alleviate secondary damage, thus restraining scar formation and promoting functional recovery after SCI. Furthermore, we found that NETs exacerbate SCI partly elevating transient receptor potential vanilloid type 4 (TRPV4) level in the injured spinal cord. Therefore, our results indicate that NETs might be a promising therapeutic target for SCI.
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http://dx.doi.org/10.3389/fimmu.2021.698249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385494PMC
August 2021

Preparation of binder-less activated char briquettes from pyrolysis of sewage sludge for liquid-phase adsorption of methylene blue.

J Environ Manage 2021 Aug 24;299:113601. Epub 2021 Aug 24.

School of Environmental Science and Engineering, Donghua University, 2999 North Renmin Road, Songjiang Dist., Shanghai, 201620, PR China.

Binder-less activated char briquettes from sewage sludge were prepared and used for the liquid-phase adsorption of methylene blue. The properties of sludge char briquettes prepared under the different initial sludge moisture content, compression pressure, and heating rate were systematically investigated through the tests of thermogravimetric analysis (TGA), scanning electron microscopy (SEM), surface and mechanical properties, burn-off rates, methylene blue adsorption kinetics and isotherms. All of the prepared briquettes presented hierarchical structures and microporous/mesoporous characteristics, and the increase of initial sludge moisture content from 10 to 30 wt% resulted in a great increase of surface area (S), total pore volume (V), apparent density, and a slight decrease of mechanical performance. The decrease of compression pressure markedly enhanced the equilibrium adsorption capacity (q), owing to the decreased diffusion resistance and blockage of diffusion pathways inside briquettes. In consideration of the mechanical performance and adsorption capacity, the optimum preparation condition was obtained at the initial moisture content of 30 wt%, compression pressure of 25 MPa, and heating rate of 10 °C/min, in which the axial compressive strength (ACS) and q of the prepared briquettes were as high as 22.2 ± 3.1 kg/m and 316.9 mg/g. The results also showed that the equilibrium adsorption data fit well into the pseudo-first order model system, and the adsorption isotherms followed the Langmuir isotherm model, suggesting that the adsorption process was attributed to physical adsorption, and was inclined to happen on the adsorption sites with the same energy level. Finally, the thermal regeneration tests demonstrated that the binder-less briquette had a good regeneration performance and was worthy of reusing for industrial applications.
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http://dx.doi.org/10.1016/j.jenvman.2021.113601DOI Listing
August 2021

Synthesis and evaluation of iridium(III) complexes on antineoplastic activity against human gastric carcinoma SGC-7901 cells.

J Biol Inorg Chem 2021 Sep 26;26(6):705-714. Epub 2021 Aug 26.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.

The study was intended to determine the antineoplastic effects of two new iridium(III) complexes [Ir(ppy)(PTTP)](PF) (1) (ppy = 2-phenylpyridine) and [Ir(piq)(PTTP)](PF) (2) (piq = 1-phenylisoquinoline, PTTP = 2-phenoxy-1,4,8,9-tetraazatriphenylene). In MTT assay, the ligand PTTP displayed ineffective inhibition on cell growth in SGC-7901, BEL-7402, HepG2 as well as NIH3T3 cell lines, while complexes 1 and 2 showed high cytotoxic activity on SGC-7901 cells with an IC value of 0.5 ± 0.1 µM and 4.4 ± 0.6 µM, respectively. Cellular uptake, cell cloning experiments, wound healing assay and cell cycle arrest indicated that the two complexes can inhibit the cell proliferation in SGC-7901 and induce cell cycle arrest at G0/G1 phase. Additionally, reactive oxygen species (ROS) and mitochondrial membrane potential suggested that the two complexes induced cell apoptosis through disrupting mitochondrial functions. Further, western blot analysis illustrated that the two complexes caused apoptosis via regulating expression levels of Bcl-2 family proteins. Moreover, complex 1 could suppress tumor growth in vivo with an inhibitory rate of 49.41%. Altogether, these results demonstrated that complexes 1 and 2 exert a potent anticancer effect against SGC-7901 cells via mitochondrial apoptotic pathway and have a potential to be developed as antineoplastic drug candidates for human gastric cancer.
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http://dx.doi.org/10.1007/s00775-021-01895-3DOI Listing
September 2021

DNA binding and evaluation of anticancer activity in vitro and in vivo of iridium(III) polypyridyl complexes.

J Inorg Biochem 2021 Aug 16;224:111580. Epub 2021 Aug 16.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address:

In this report, we synthesized three new iridium(III) complexes: [Ir(piq)(apip)]PF (Ir1, piq = 1-phenylisoquinoline, apip = 2-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(piq)(maip)]PF (Ir2, maip = 3-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(piq)(paip)]PF (Ir3, paip = 4-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline). The DNA binding was investigated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the cytotoxic activity of Ir1, Ir2 and Ir3, the complexes show highly active against B16 cells with IC values of 0.3 ± 0.2 μM, 3.7 ± 0.2 μM and 4.6 ± 1.1 μM, respectively. Subsequently, cellular uptake suggested that the cytotoxicity of the complexes is attributed to their differences in cellular uptake levels. In addition, complexes Ir1, Ir2 and Ir3 induce cell cycle arrest at the G0/G1 phase and regulate the cell cycle mediators such as cyclin D1, CDK6 (cyclin-dependent kinase 6), CDK4 and p21, leading to the inhibition of B16 cells proliferation. The autophagy was investigated by monodansylcadaverine (MDC) staining. The complexes can promote the change from LC3-I to LC3-II, up-regulate levels of Beclin-1 and down-regulate expression of p62. The complexes induced apoptosis by regulating the expression levels of related indicators such as PARP (poly ADP-ribose polymerase), PI3K (phosphoinositide-3 kinase), AKT (protein kinase B), Caspase, Bcl-2 (B-cell lymphoma-2), Bad (Bcl2 associated death promoter), Bax (Bcl2-associated X) and Cyto C (cytochrome C). Additionally, Ir1 exerted significant antitumor activity in the suppression of malignant melanoma proliferation in vivo. As indicated in the above results, these complexes were highly effective for malignant melanoma treatment through the intrinsic pathway and provided much insight into anticancer drugs for tumor therapy.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111580DOI Listing
August 2021

Accessing depth-resolved high spatial frequency content from the optical coherence tomography signal.

Sci Rep 2021 Aug 24;11(1):17123. Epub 2021 Aug 24.

National University of Ireland, National Biophotonics and Imaging Platform, School of Physics, Tissue Optics and Microcirculation Imaging Group, Galway, H91 TK33, Ireland.

Optical coherence tomography (OCT) is a rapidly evolving technology with a broad range of applications, including biomedical imaging and diagnosis. Conventional intensity-based OCT provides depth-resolved imaging with a typical resolution and sensitivity to structural alterations of about 5-10 microns. It would be desirable for functional biological imaging to detect smaller features in tissues due to the nature of pathological processes. In this article, we perform the analysis of the spatial frequency content of the OCT signal based on scattering theory. We demonstrate that the OCT signal, even at limited spectral bandwidth, contains information about high spatial frequencies present in the object which relates to the small, sub-wavelength size structures. Experimental single frame imaging of phantoms with well-known sub-micron internal structures confirms the theory. Examples of visualization of the nanoscale structural changes within mesenchymal stem cells (MSC), which are invisible using conventional OCT, are also shown. Presented results provide a theoretical and experimental basis for the extraction of high spatial frequency information to substantially improve the sensitivity of OCT to structural alterations at clinically relevant depths.
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http://dx.doi.org/10.1038/s41598-021-96619-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385072PMC
August 2021

Anticancer effect evaluation in vitro and in vivo of iridium(III) polypyridyl complexes targeting DNA and mitochondria.

Bioorg Chem 2021 Aug 19;115:105290. Epub 2021 Aug 19.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address:

To investigate the antitumor effect of iridium complexes, three iridium (III) complexes [Ir(ppy)(dcdppz)]PF (ppy = 2-phenylpyridine, dcdppz = 11,12-dichlorodipyrido[3,2-a:2',3'-c]phenazine) (Ir1), [Ir(bzq)(dcdppz)]PF (bzq = benzo[h]quinoline) (Ir2) and [Ir(piq)(dcdppz)]PF (piq = 1-phenylisoquinoline) (Ir3) were synthesized and characterized. Geometry optimization, molecular dynamics simulation and docking studies have been performed to further explore the antitumor mechanism. The cytotoxicity of Ir1-3 toward cancer cells was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The localization of complexes Ir1-3 in the mitochondria, intracellular accumulation of reactive oxygen species (ROS) levels, the changes of mitochondrial membrane potential and morphological changes in apoptosis were investigated. Flow cytometry was applied to quantify fluorescence intensity and determine cell cycle distribution. Western blotting was used to detect the expression of apoptosis-related proteins. The anti-tumor effect of Ir1 in vivo was evaluated. The results showed that Ir1-3 had high cytotoxicity to most tumor cells, especially to SGC-7901 cells with a low IC value. Ir1-3 can increase the intracellular ROS levels, reduce the mitochondrial membrane potential. Additionally, the complexes induce an increase of apoptosis-related protein expression, enhance the percentage of apoptosis. The complexes inhibit the cell proliferation at G0/G1 phase. The results obtained from antitumor in vivo indicate that Ir1 can significantly inhibit the growth of tumors with an inhibitory rate of 54.08%. The docking studies show that complexes Ir1-3 interact with DNA through minor-groove intercalation, which increases the distance of DNA base pairs, leading to a change of DNA helix structure. These experimental and theoretical findings indicate that complexes Ir1-3 can induce apoptosis in SGC-7901 cells through the mitochondrial dysfunction and DNA damage pathways, and then exerting anti-tumor activity in vitro and vivo.
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http://dx.doi.org/10.1016/j.bioorg.2021.105290DOI Listing
August 2021

Correction to: Efficacy and safety among second‑generation and other basal insulins in adult patients with type 1 diabetes: a systematic review and network meta‑analysis.

Naunyn Schmiedebergs Arch Pharmacol 2021 Aug 19. Epub 2021 Aug 19.

Graduate School of Pharmaceutical Sciences, Osaka University, 1‑6 Yamadaoka, Suita, Osaka, 565‑0871, Japan.

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http://dx.doi.org/10.1007/s00210-021-02143-wDOI Listing
August 2021

Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma.

Bioengineered 2021 Dec;12(1):5241-5252

The First Department of General Surgery, Shidong Hospital, Shanghai, P.R. China.

Colon adenocarcinoma (COAD) is one of the most common types of malignancy and accounts for >3 million deaths worldwide each year. The present study aimed to evaluate the role of notum palmitoleoyl-protein carboxylesterase (NOTUM) in and , and to identify the relationship between NOTUM and the apoptosis of COAD. Moreover, the present study aimed to investigate whether NOTUM regulated Fas cell surface death receptor (FAS)-mediated apoptosis was affected by the Wnt signaling pathway. Gene expression profiling interactive analysis (GEPIA) was used to predict the potential function of NOTUM. Western blotting and reverse transcription-quantitative PCR were conducted to detect the protein and mRNA expression levels of NOTUM in different tissues or cell lines. The occurrence and development of COAD was detected after NOTUM knockdown lentivirus administration. The apoptosis of COAD was also observed. SKL2001 was applied to examine whether the role of NOTUM was regulated by Wnt. GEPIA analysis demonstrated that NOTUM expression in COAD tumor tissue was higher compared with in normal tissues. Pair-wise gene correlation analysis identified a potential relationship between NOTUM and Wnt. NOTUM protein and mRNA expression levels in colon carcinoma tissues and RKO cells were increased. NOTUM knockdown lentivirus serves a role in inhibiting COAD development by reducing tumor proliferation, reducing tumor size, and increasing the level of apoptosis and . Moreover, NOTUM could increase apoptosis in COAD, which was regulated by FAS, and SKL2001 blocked the progress of apoptosis after NOTUM regulation by NOTUM knockdown lentivirus and . Collectively, the present results suggested that NOTUM may be able to regulate the apoptosis of COAD, and that Wnt may be the down-stream target signaling of NOTUM in apoptosis.
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http://dx.doi.org/10.1080/21655979.2021.1961657DOI Listing
December 2021

Dispersive and filter loss performance of calcium carbonate nanoparticles in water for drilling fluid applications.

Nanotechnology 2021 Sep 6;32(48). Epub 2021 Sep 6.

School of New Energy and Materials, Southwest Petroleum University, Xindu, Chengdu, People's Republic of China.

Adding nanoparticles in a drilling fluid can aid in the sealing of the nanopores in the borehole wall rock and the mud cake; in this way, the filtrate loss of the drilling fluid can be reduced and the borehole wall is stabilized. In this work, the spectrophotometric method was used to study the effect of dispersants on calcium carbonate nanoparticles. The best dispersion effect was achieved at cetyltrimethyl ammonium bromide (CTAB) concentration of 4 wt%, dispersing time of 45 min, pH value of 8 and stirring speed of 900 rpm. The structure analysis showed that the adsorption layer was formed on the surface of calcium carbonate nanoparticles after CTAB modification, and no new crystalline compounds appeared. Under these optimized dispersing conditions, aggregation was prevented as manifested by the dramatically decreased average particle size of calcium carbonate nanoparticles while the surface hydrophilicity and Zeta potential of calcium carbonate nanoparticles both increased. Furthermore, we showed that a drilling fluid incorporating such well dispersed calcium carbonate nanoparticles exhibit decreased filter loss and thus better performance in sealing compared to the calcium carbonate nanoparticles without dispersants.
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http://dx.doi.org/10.1088/1361-6528/ac1dd2DOI Listing
September 2021

Human umbilical cord-derived mesenchymal stem cells affect urea synthesis and the cell apoptosis of human induced hepatocytes by secreting IL-6 in a serum-free co-culture system.

Biotechnol J 2021 Aug 11:e2100096. Epub 2021 Aug 11.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, P. R. China.

Background: Bioartificial livers (BALs) are emerging as a potential supportive therapy for liver diseases. However, the maintenance of hepatocyte function and viability is a major challenge. Mesenchymal stem cells (MSCs) have attracted extensive attention for providing trophic support to hepatocytes, but only few studies have explored the interaction between human MSCs and human hepatocytes, and very little is known about the underlying molecular mechanisms whereby MSCs affect hepatocyte function, especially in serum-free medium (SFM).

Conclusion: The SFM co-culture strategy showed major advantages in maintaining hiHep function and viability, which is of great significance for the clinical application of hiHeps in BALs. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/biot.202100096DOI Listing
August 2021
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