Publications by authors named "Lin Zhao"

1,153 Publications

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Morphological and molecular identification of two new species (Ascomycota, Pleosporaceae) in section Radicina from China.

MycoKeys 2021 9;78:187-198. Epub 2021 Apr 9.

Institute of Plant Protection, Guangxi Academy of Agricultural Sciences and Guangxi Key Laboratory of Biology for Crop Diseases and Insect Pests, Nanning, Guangxi, 530007, China Institute of Plant Protection, Guangxi Academy of Agricultural Sciences and Guangxi Key Laboratory of Biology for Crop Diseases and Insect Pests Nanning China.

The fungal genus was distributed widely and found in different habitats such as plant or indoor environment. During an investigation into this genus in China, two new species, and were respectively isolated from diseased leaves of and , which both belonged to Umbelliferae. Phylogenetically, they were determined as new species belonging in the section Radicina of based on the combined four gene fragments of ITS, , and . Morphologically, the two species were illustrated and compared with other relevant Alternaria species in section Radicina.
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http://dx.doi.org/10.3897/mycokeys.78.64853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052298PMC
April 2021

Specific MicroRNAs Found in Extracellular Matrix Vesicles Regulate Proliferation and Differentiation in Growth Plate Chondrocytes.

Calcif Tissue Int 2021 May 5. Epub 2021 May 5.

College of Engineering, Virginia Commonwealth University, 601 W. Main Street, Richmond, VA, 23284, USA.

Matrix vesicles (MVs) are extracellular organelles produced by growth plate cartilage cells in a zone-specific manner. MVs are similar in size to exosomes, but they are tethered to the extracellular matrix (ECM) via integrins. Originally associated with matrix calcification, studies now show that they contain matrix processing enzymes and microRNA that are specific to their zone of maturation. MVs produced by costochondral cartilage resting zone (RC) chondrocytes are enriched in microRNA 503 whereas those produced by growth zone (GC) chondrocytes are enriched in microRNA 122. MVs are packaged by chondrocytes under hormonal and factor regulation and release of their contents into the ECM is also under hormonal control, suggesting that their microRNA might have a regulatory role in growth plate proliferation and maturation. To test this, we selected a subset of these enriched microRNAs and transfected synthetic mimics back into RC and GC cells. Transfecting growth plate chondrocytes with select microRNA produced a broad range of phenotypic responses indicating that MV-based microRNAs are involved in the regulation of these cells. Specifically, microRNA 122 drives both RC and GC cells toward a proliferative phenotype, stabilizes the matrix and inhibits differentiation whereas microRNA 22 exerts control over regulatory factor production. This study demonstrates the strong regulatory capability possessed by unique MV enriched microRNAs on growth plate chondrocytes and their potential for use as therapeutic agents.
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http://dx.doi.org/10.1007/s00223-021-00855-yDOI Listing
May 2021

Monoclinic EuSn_{2}As_{2}: A Novel High-Pressure Network Structure.

Phys Rev Lett 2021 Apr;126(15):155701

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

The layered crystal of EuSn_{2}As_{2} has a Bi_{2}Te_{3}-type structure in rhombohedral (R3[over ¯]m) symmetry and has been confirmed to be an intrinsic magnetic topological insulator at ambient conditions. Combining ab initio calculations and in situ x-ray diffraction measurements, we identify a new monoclinic EuSn_{2}As_{2} structure in C2/m symmetry above ∼14  GPa. It has a three-dimensional network made up of honeycomblike Sn sheets and zigzag As chains, transformed from the layered EuSn_{2}As_{2} via a two-stage reconstruction mechanism with the connecting of Sn-Sn and As-As atoms successively between the buckled SnAs layers. Its dynamic structural stability has been verified by phonon mode analysis. Electrical resistance measurements reveal an insulator-metal-superconductor transition at low temperature around 5 and 15 GPa, respectively, according to the structural conversion, and the superconductivity with a T_{C} value of ∼4  K is observed up to 30.8 GPa. These results establish a high-pressure EuSn_{2}As_{2} phase with intriguing structural and electronic properties and expand our understandings about the layered magnetic topological insulators.
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http://dx.doi.org/10.1103/PhysRevLett.126.155701DOI Listing
April 2021

Efficacy of statins on renal function in patients with chronic kidney disease: a systematic review and meta-analysis.

Ren Fail 2021 Dec;43(1):718-728

Health Management Center, Tianjin Medical University General Hospital, Tianjin, P.R. China.

Background: Studies have shown that the use of statins could significantly improve lipid profiles; however, it remains controversial whether the use of statins could improve renal function in patients with chronic kidney disease (CKD). Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of statins on renal function in patients with CKD.

Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library databases for eligible RCTs from inception to October 2020. Pooled effect estimates were assigned as weighted mean differences (WMDs) with 95% confidence intervals (CIs) using the random-effects model.

Results: We selected 33 RCTs that recruited 37,391 patients with CKD patients. The summary results suggested that statin use significantly reduced urinary albumin (WMD: -2.04; 95%CI: -3.53 to -0.56;  = .007) and protein (WMD: -0.58; 95%CI: -0.95 to -0.21;  = .002) excretions and increased creatinine clearance (WMD: 0.86; 95%CI: 0.32-1.41;  = .002). However, there were no significant differences between statin and control groups in terms of changes in estimated glomerular filtration rate (WMD: 0.38; 95%CI: -0.04 to 0.79;  = .075), and serum creatinine levels (WMD: -0.07; 95%CI: -0.25, 0.12;  = .475).

Conclusions: We found that statin use in patients with CKD may slow CKD progression by lowering urinary albumin and protein excretions or increasing creatinine clearance. Further large-scale RCTs should be conducted to evaluate the long-term effects of statins on renal outcomes. CKD: chronic kidney disease; RCT: randomized controlled trials; WMD: weighted mean differences; CI: confidence intervals; ACEI: angiotensin-converting enzyme inhibitors; eGFR: estimated glomerular filtration rate.
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http://dx.doi.org/10.1080/0886022X.2021.1915799DOI Listing
December 2021

Rapid identification, isolation, and evaluation on anti-neuroinflammatory activity of limonoids derivatives from the root bark of Dictamnus dasycarpus.

J Pharm Biomed Anal 2021 Apr 18;200:114079. Epub 2021 Apr 18.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China. Electronic address:

A total of 49 limonoids derivatives were rapidly identified by UNIFI software and three new limonoids derivatives, named dasycarinone (1, DAS), isodictamdiol C (2) and dasycarinone A (3), along with nineteen known compounds, were isolated from the root bark of Dictamnus dasycarpus, named as "Baixianpi" in Chinese. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, NMR, CD spectra and OR). All the compounds were tested for anti-inflammatory activities by suppressing the nitric oxide (NO) production in lipopolysaccharide (LPS) induced BV-2 cells. DAS exhibited a strong anti-inflammatory activity with IC value of 1.8 μM. Nuclear Factor kappa B (NF-κB) luciferase assay and enzyme-linked immune sorbent assay indicated that DAS can suppress the release of inflammatory cytokines such as Tumor Necrosis Factor α (TNF-α), interleukin 6 (IL-6) via inactivating NF-κB signaling pathways. Moreover, we found that anti-inflammatory activities of obacunone-class are better than those of limonin-class by analyzing structure-activity relationship. Our results suggested that obacunone derivatives play an important role on anti-inflammation of Baixianpi. As a representative among them, DAS showed a strong anti-inflammatory activity via suppressing NF-κB signaling pathways.
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http://dx.doi.org/10.1016/j.jpba.2021.114079DOI Listing
April 2021

Identification of Novel Mutations in : Expanding the Mutational Spectrum for Female Infertility.

Front Cell Dev Biol 2021 9;9:647130. Epub 2021 Apr 9.

Institute of Pediatrics, Children's Hospital of Fudan University and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.

Oocyte maturation and fertilization are fundamental processes for successful human reproduction, and abnormalities in these processes will cause infertility. Recently, we identified biallelic mutations in that are responsible for human oocyte maturation arrest, fertilization failure, and early embryonic development arrest. In this study, we screened for further mutations in a new cohort of patients with abnormalities in oocyte maturation, fertilization, and early embryonic development. Through whole-exome sequencing, we identified the four novel mutations c.887G > A (p. Arg296Gln), c.964C > T (p.Arg322), c.1155G > C (p.Trp385Cys), and c.330 + 1G > A (p. Glu111Ilefs36) and one previously reported mutation c.965G > A (p.Arg322Gln) in in four infertile individuals from three independent families. The patients had different phenotypes of oocyte maturation arrest and fertilization failure resulting from the different mutations. This study confirms our previous research and expands the spectrum of known mutations in , providing new evidence supporting the function of in the genetic etiology of female infertility characterized by oocyte maturation arrest and fertilization failure.
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http://dx.doi.org/10.3389/fcell.2021.647130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063106PMC
April 2021

Construction and immune efficacy of recombinant Lactobacillus casei expressing OmpAI of Aeromonas veronii C5-I as molecular adjuvant.

Microb Pathog 2021 Apr 20:104827. Epub 2021 Apr 20.

College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China. Electronic address:

Despite advancements in diagnosis and control, Aeromonas infections are considered the leading cause of economic aquaculture loss. In this study, to enhance DNA vaccine efficacy against Aeromonas infections, a fused DNA fragment (1504 bp) of the OmpAI gene from Aeromonas veronii (A. veronii) combined with the C5-I gene from the common carp was generated with splicing by overlapping PCR (SOE-PCR) and expressed in Lactobacillus casei strain CC16. Protein C5-I served as a molecular adjuvant for the antigen OmpAI. Two types of fusion antigens were developed (anchored and secretory). Generally, anchored-type antigens are more effective in inducing immune responses in fish than secretory antigens. Western blot analysis showed that the bands of both antigens were present at 58 kDa. After oral immunization, both DNA vaccines enhanced the serum levels of AKP, ACP, SOD and LZM in immunized carp; the genes IL-10, IL-1β, TNF-α, and IFN-γ in the heart, liver, spleen, head kidney, and intestinal tract were upregulated; and a stronger phagocytic response was triggered in immunized fish. In addition, common carp administered the fused antigens were more protected from Aeromonas challenge (60-73.3% protection). Recombinant Lactobacillus bacteria expressing the fused protein showed a greater propensity for colonization in the intestinal tract in immunized fish than in controls. Here, we provide a promising approach to improve DNA vaccine immunogenicity for protecting common carp from A. veronii infections.
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http://dx.doi.org/10.1016/j.micpath.2021.104827DOI Listing
April 2021

Anti-Oxidative and Immuno-Protective Effect of Camel Milk on Radiation-Induced Intestinal Injury in C57BL/6 J Mice.

Dose Response 2021 Jan-Mar;19(1):15593258211003798. Epub 2021 Mar 30.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.

Purpose: The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury.

Methods: The C57BL/6 J mice in 2 experiments were assigned into control group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors.

Results: Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1β and increased IL-10 level.

Conclusions: CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.
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http://dx.doi.org/10.1177/15593258211003798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020251PMC
March 2021

TNF-α promotes insulin resistance in obstructive sleep apnea-hypopnea syndrome.

Exp Ther Med 2021 Jun 29;21(6):568. Epub 2021 Mar 29.

Department of Nursing, Jiangsu Union Technical Institute Nantong Health Branch, Nantong, Jiangsu 226010, P.R. China.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is the most serious among children with sleep disordered breathing. The present study aimed to investigate whether TNF-α could decrease the glucose transporter type 4 insulin-responsive (GLUT-4) expression to promote insulin resistance through the TNF-α/IKKβ/IKβ/NF-κB signaling pathway in OSAHS. In total, 30 obese children with OSAHS and 30 non-OSAHS obese children were enrolled into the present study. TNF-α expression in adenoid tissues was detected by western blot analysis and immunohistochemistry. The expression of inflammatory factors (IL-1β, IL-6 and IFN-γ) and TNF-α/IKKβ/IKβ/NF-κB signaling pathway-associated proteins was also detected by western blot analysis. The expression of insulin resistance-associated factors, insulin receptor substrate 1 (IRS1) and GLUT4, was determined by western blot analysis and immunohistochemistry. TNF-α expression was increased in adenoid tissues of children with OSAHS, which was also confirmed by immunohistochemistry. The expression levels of IL-1β, IL-6 and IFN-γ were all upregulated in adenoid tissues of children with OSAHS. The expression of IRS1 and GLUT4 was decreased in adenoid tissues of obese children with OSAHS and the result of immunohistochemistry was consistent with the result of western blot analysis. The protein level of TNF-α, and ratio of phosphorylated (p-)/total (t)-IKKβ, p/t-IKβ and p/t-NF-κB was increased in adenoid tissues of children with OSAHS. TNF-α could suppress the GLUT4 expression to promote insulin resistance by TNF-α/IKKβ/IKβ/NF-κB signaling pathway in OSAHS.
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http://dx.doi.org/10.3892/etm.2021.10000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027756PMC
June 2021

Is Induced by Short Days in Soybean and May Accelerate Flowering When Overexpressed in via Inhibiting .

Front Plant Sci 2021 26;12:629069. Epub 2021 Feb 26.

Key Laboratory of Soybean Biology of Ministry of Education, China (Key Laboratory of Biology and Genetics and Breeding for Soybean in Northeast China), Northeast Agricultural University, Harbin, China.

Photoperiod is one of the main climatic factors that determine flowering time and yield. Some members of the INDETERMINATE DOMAIN (IDD) transcription factor family have been reported to be involved in regulation of flowering time in Arabidopsis, maize, and rice. In this study, the domain analysis showed that GmIDD had a typical ID domain and was a member of the soybean IDD transcription factor family. Quantitative real-time PCR analysis showed that was induced by short day conditions in leaves and regulated by circadian clock. Under long day conditions, transgenic Arabidopsis overexpressing flowered earlier than wild-type, and mutants flowered later, while the overexpression of rescued the late-flowering phenotype of mutants. Chromatin immunoprecipitation sequencing assays of binding sites in Arabidopsis further identified potential direct targets, including a transcription factor, (). might inhibit the transcriptional activity of flower repressor by binding to the motif of promoter. Furthermore, the results also showed that overexpression increased the transcription levels of flowering time-related genes (), (), () and () in Arabidopsis. Taken together, appeared to inhibit the transcriptional activity of and induced the expression of gene to promote Arabidopsis flowering.
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http://dx.doi.org/10.3389/fpls.2021.629069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029582PMC
February 2021

Stanozolol for the treatment of anemic lower-risk myelodysplastic syndromes without del(5q) after failure of epoetin alfa: findings from a retrospective study.

Ann Hematol 2021 Apr 10. Epub 2021 Apr 10.

Department of Hematology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 200120, China.

Options for anemic lower-risk myelodysplastic syndromes (MDS) without del(5q) after failure of erythropoiesis-stimulating agents (ESAs) are very limited. The effectiveness of second-line treatments is uncertain. We retrospectively reviewed the clinical effectiveness and overall survival (OS) of lower-risk MDS without del(5q) patients exclusively treated with stanozolol (STZ) after failure of epoetin alfa. The response was defined according to the 2006 International Working Group (IWG) criteria. Fifty-six patients were included. The median follow-up time was 55 months (range: 5-156 months). Twenty-seven patients (48.2%) achieved hematologic improvement-erythroid response (HI-E). Higher response rates were observed in patients with lower IPSS-R scores (≤3.5, P = 0.008) and hypocellular bone marrow (P = 0.002). In univariate Cox analysis, HI-E was the strongest factor associated with better OS (P = 0.0003). In multivariate Cox, HI-E, age ≤ 50, and transfusion independence (TI) at the onset of STZ were factors associated with better OS. The estimated 5-year OS was 88.6% (68.7-96.2%) and 33.8% (14.9-54.0%) in responders and non-responders (P < 0.01), respectively. The most common side effects included masculinization and liver damage, but they were manageable with supportive measures and dose adjustments. STZ may be considered an alternative treatment in lower-risk MDS after failure of epoetin alfa.
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http://dx.doi.org/10.1007/s00277-021-04508-wDOI Listing
April 2021

Effect of "drip-and-ship" and "drip-and-drive" on endovascular treatment of acute ischemic stroke with large vessel occlusion: a single-center retrospective study.

Acta Radiol 2021 Apr 7:2841851211006897. Epub 2021 Apr 7.

Department of Interventional Radiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.

Background: Patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) were usually transferred from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (drip-and-ship [DS]), while driving the doctor from a CSC to a PSC to perform a procedure is an alternative strategy (drip-and-drive [DD]).

Purpose: To compare the efficacy and prognosis of the two strategies.

Material And Methods: From February 2017 to June 2019, 62 patients with LVO received endovascular treatment via the DS and DD models and were retrospectively analyzed from the stroke alliance based on our CSC. Primary endpoint was door-to-reperfusion (DTR) time. Secondary endpoints included puncture-to-recanalization (PTR) time, modified Thrombolysis in Cerebral Infarction (mTICI) rates at the end of the procedure, and modified Rankin Scale (mRS) at 90 days.

Results: Forty-one patients received the DS strategy and 21 patients received the DD strategy. The DTR time was significantly longer in the DS group compared to the DD group (315.5 ± 83.8 min vs. 248.6 ± 80.0 min;  < 0.05), and PTR time was shorter (77.2 ± 35.9 min vs. 113.7 ± 69.7 min;  = 0.033) compared with the DD group. Successful recanalization (mTICI 2b/3) was achieved in 89% (36/41) of patients in the DS group and 86% (18/21) in the DD group ( = 1.000). Favorable functional outcomes (mRS 0-2) were observed in 49% (20/41) of patients in the DS group and 71% (15/21) in the DD group at 90 days ( = 0.089).

Conclusion: Compared with the DS strategy, the DD strategy showed more effective and a trend of better clinical outcomes for AIS patients with LVO.
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http://dx.doi.org/10.1177/02841851211006897DOI Listing
April 2021

Toxicity and combined effects of antibiotics and nano ZnO on a phosphorus-removing Shewanella strain in wastewater treatment.

J Hazard Mater 2021 Feb 25;416:125532. Epub 2021 Feb 25.

School of Environmental Science and Engineering, Tianjin University, Tianjin 300072, China. Electronic address:

Antibiotics and nanoparticles, which are emerging contaminants, can occur simultaneously in biological wastewater treatment systems, potentially resulting in complex interactive effects. This study investigated the effects of individual and complex zinc oxide nanoparticles (nZnO) and antibiotics (quinolone and sulfonamide), on the Shewanella strain used to remove phosphorus (PO), metabolic processes, as well as its complexing and toxicity mechanisms. The inhibition of PO removal increased from 30.7% to 100.0% with increased nZnO concentrations (half maximal effective concentration (EC50) = 1.1 mg Zn/L) by affecting poly-p and glycogen metabolites. The combined exposure to nZnO and ciprofloxacin/norfloxacin (CIP/NOR) had a significant antagonistic effect on the removal of PO and on the metabolism of poly-p and glycogen in phosphate-accumulating organisms (PAOs), whereas the complexing of sulfonamide and nZnO had no significant additional effect. Thus, the complexing of nanoparticles and antibiotics exhibited different toxicity effects from the antibiotic structure-based complex reactions. These results can be used to improve wastewater treatment processes and reduce risks associated with wastewater discharge.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125532DOI Listing
February 2021

Multifunctional metalens generation using bilayer all-dielectric metasurfaces.

Opt Express 2021 Mar;29(6):9332-9345

Optical metasurfaces exhibit unprecedented ability in light field control due to their ability to locally change the phase, amplitude, and polarization of transmitted or reflected light. We propose a multifunctional metalens with dual working modes based on bilayer geometric phase elements consisting of low-loss phase change materials (SbSe) and amorphous silicon (a-Si). In transmission mode, by changing the crystalline state of the SbSe scatterer, a bifocal metalens with an arbitrary intensity ratio at the telecommunication C-band is realized, and the total focusing efficiency of the bifocal metalens is as high as 78%. Also, at the resonance wavelength of the amorphous SbSe scatterer, the scatterer can be regarded as a half-wave plate in reflection mode. The multifunctional metalens can reversely converge incident light into a focal point with a focusing efficiency of up to 30%. The high focusing efficiency, dynamic reconfigurability, and dual working modes of the multifunctional metalens contribute to polarization state detection, optical imaging, and optical data storage. In addition, the bilayer geometric phase elements can be easily extended to multilayer, which significantly improves the capability of manipulating the incident light field.
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http://dx.doi.org/10.1364/OE.420003DOI Listing
March 2021

Vitamin D3 induces mesenchymal-to-endothelial transition and promotes a proangiogenic niche through IGF-1 signaling.

iScience 2021 Apr 4;24(4):102272. Epub 2021 Mar 4.

Department of Internal Medicine, University of Nevada, Las Vegas School of Medicine, 1701 W. Charleston Boulevard, Suite 230, Las Vegas, NV 89102, USA.

Although vitamin D3 (VitD3) prevents angiogenesis in cancer, VitD3 deficiency is associated with greater incidence of cardiovascular events in patients. We examined the influence of VitD3 on the angiogenic potential of mesenchymal stem cells (MSCs). VitD3 treatment increased the expression of proangiogenic molecules in MSCs, which exhibited an endothelial cell-like phenotype and promoted vascularization and . VitD3 activated the IGF-1 promoter and boosted IGF-1 receptor (IGF-1R) signaling, which was essential for the mesenchymal-to-endothelial transition (MEndoT) of MSCs. VitD3-treated MSCs created a proangiogenic microenvironment for co-cultured arterial endothelial cells, as well as aortic rings. The induction of MEndoT and angiogenesis promotion by VitD3-stimulated MSCs was attenuated by IGF-1R inhibitor picropodophyllin. We conclude that VitD3 promotes MEndoT in MSCs, and VitD3-treated MSCs augment vascularization by producing a proangiogenic niche through continued IGF-1 secretion. These results suggest a potential therapeutic role of VitD3 toward enhancing MSC-induced angiogenesis.
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http://dx.doi.org/10.1016/j.isci.2021.102272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005757PMC
April 2021

Influence of CrC and VC Content on WC Grain Size, WC Shape and Mechanical Properties of WC-6.0 wt. % Co Cemented Carbides.

Materials (Basel) 2021 Mar 22;14(6). Epub 2021 Mar 22.

State Key Laboratory for Powder Metallurgy, Central South University, Changsha 410083, China.

In this paper, the influences of CrC/VC content on WC grain size, WC grain shape and mechanical properties of WC-6 wt. % Co cemented carbides were investigated. The results showed that the grain size first rapidly decreased and then slightly decreased with the increasing CrC/VC content, and VC led to finer grain size and narrower size distribution. HRTEM/EDS analysis of the WC/Co interface indicates that the segregation concentration of V is much larger than that of Cr, which may be a strong response to the higher inhibition efficiency of VC. The addition of CrC induced triangular prism shape WC grains while VC generated stepped triangular prism grains. Despite the grain growth inhibitor (GGI) mechanisms of CrC/VC have been extensively studied in the literature, the doping amount, especially the doping limit, has not been systematically investigated. In this work, the saturated solubilities of Cr and V in cobalt binder phase along with carbon content hare been predicted based on thermodynamic calculations. Based on the theoretical calculations, the doping amount of CrC/VC is designed to be gradually increasing until more or less over their maximum solubilities in the binder phase, thereby investigating the subsequent microstructure and mechanical properties. When the doping of CrC/VC exceeds the maximum solubility in Co phase, Co-rich Cr-carbides and Co-deficient V-carbides would form respectively, which were detrimental to the transverse rupture strength (TRS) and impact toughness. The hardness increased with the increasing CrC/VC content, while the fracture toughness decreased with the increasing CrC/VC content. The TRS initially enhanced and then declined, but the stepped triangular prism shape grains and low fraction of WC/Co interface in WC-6Co-VC cemented carbide led to a more pronounced decline in the TRS. The sample with 0.6 wt. % CrC addition had good comprehensive mechanical properties, its hardness, fracture toughness and TRS were 1880 kg/mm, 9.32 MPa·m and 3450 MPa, respectively.
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http://dx.doi.org/10.3390/ma14061551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004746PMC
March 2021

Discovery of a Potent and Selective FLT3 Inhibitor ()--(5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-4-methyl-1-pyrrol-3-yl)-3-(pyrrolidin-1-yl)propanamide with Improved Drug-like Properties and Superior Efficacy in FLT3-ITD-Positive Acute Myeloid Leukemia.

J Med Chem 2021 Apr 2;64(8):4870-4890. Epub 2021 Apr 2.

Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, P.R. China.

Overcoming the FLT3-ITD mutant has been a promising drug design strategy for treating acute myeloid leukemia (AML). Herein, we discovered a novel FLT3 inhibitor , which displayed potent inhibitory activity against the FLT3-ITD mutant (IC = 0.8 nM) and achieved good selectivity over c-KIT kinase (over 500-fold). Compound selectively inhibited the proliferation of FLT3-ITD-positive AML cell lines MV4-11 (IC = 23.5 nM) and MOLM-13 (IC = 35.5 nM) and exhibited potent inhibitory effects against associated acquired resistance mutations. In cellular mechanism studies, compound strongly inhibited FLT3-mediated signaling pathways and induced apoptosis by arresting the cell cycle in the sub-G1 phase. In in vivo studies, compound demonstrated a good bioavailability (73.6%) and significantly suppressed tumor growth in MV4-11 (10 mg/kg, TGI 93.4%) and MOLM-13 (20 mg/kg, TGI 98.0%) xenograft models without exhibiting obvious toxicity. These results suggested that compound may be a promising drug candidate for treating FLT3-ITD-positive AML.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02247DOI Listing
April 2021

mA RNA Methylation Regulators Impact Prognosis and Tumor Microenvironment in Renal Papillary Cell Carcinoma.

Front Oncol 2021 16;11:598017. Epub 2021 Mar 16.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

Accumulating evidence has proven that N6-methyladenosine (mA) RNA methylation plays an essential role in tumorigenesis. However, the significance of mA RNA methylation modulators in the malignant progression of papillary renal cell carcinoma (PRCC) and their impact on prognosis has not been fully analyzed. The present research set out to explore the roles of 17 mA RNA methylation regulators in tumor microenvironment (TME) of PRCC and identify the prognostic values of mA RNA methylation regulators in patients afflicted by PRCC. We investigated the different expression patterns of the mA RNA methylation regulators between PRCC tumor samples and normal tissues, and systematically explored the association of the expression patterns of these genes with TME cell-infiltrating characteristics. Additionally, we used LASSO regression to construct a risk signature based upon the mA RNA methylation modulators. Two-gene prognostic risk model including IGF2BP3 and HNRNPC was constructed and could predict overall survival (OS) of PRCC patients from the Cancer Genome Atlas (TCGA) dataset. The prognostic signature-based risk score was identified as an independent prognostic indicator in Cox regression analysis. Moreover, we predicted the three most significant small molecule drugs that potentially inhibit PRCC. Taken together, our study revealed that mA RNA methylation regulators might play a significant role in the initiation and progression of PRCC. The results might provide novel insight into exploration of mA RNA modification in PRCC and provide essential guidance for therapeutic strategies.
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http://dx.doi.org/10.3389/fonc.2021.598017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008109PMC
March 2021

Interaction between β-lactam antibiotic and phosphorus-accumulating organisms.

Environ Sci Pollut Res Int 2021 Apr 1. Epub 2021 Apr 1.

College of Environmental Science and Engineering, Tianjin University, Tianjin, 300350, China.

β-Lactam antibiotics have been widely used in clinic due to strong antibacterial activity with mild adverse side effects and have been detected in the environment. In the enhanced biological phosphorus removal (EBPR) process, phosphorus-accumulating organisms (PAOs) play a major role. In this study, amoxicillin, aztreonam, and cefoperazone are the selected antibiotics that applied in investigating the interaction mechanism of β-lactam antibiotics and PAO. The effects of β-lactam antibiotics on PAOs were analyzed comprehensively from the aspects of antibiotic impacts on phosphorus removal rate, intracellular polymer, their toxicity to PAOs, and PAO impacts on the fate of β-lactam antibiotics. It was found that the phosphorus removal rate of PAO increased by 19.21% and 15.75%, respectively at 10 mg/L amoxicillin and aztreonam, while cefoperazone had certain inhibition effect on phosphorus removal efficiency. Quantitative analysis shows that in the aerobic stage, three kinds of β-lactam antibiotics could promote the synthesis of polyphosphates (poly-P). The degradation rates of three antibiotics were as follows: amoxicillin > aztreonam > cefoperazone. The fate characteristics of antibiotics provide a theoretical basis for environmental risk assessment. The toxic effects of three antibiotics were as follows: cefoperazone > aztreonam > amoxicillin according to the bacteriostatic test. It provided a scientific theoretical basis for systematically evaluating the biological toxicity of antibiotic pollutants.
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http://dx.doi.org/10.1007/s11356-021-13631-0DOI Listing
April 2021

Circulating exosomal mRNA profiling identifies novel signatures for the detection of prostate cancer.

Mol Cancer 2021 03 30;20(1):58. Epub 2021 Mar 30.

Department of Urology, Shanghai Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.

The landscape and characteristics of circulating exosomal messenger RNAs (emRNAs) are poorly understood, which hampered the accurate detection of circulating emRNAs. Through comparing RNA sequencing data of circulating exosomes with the corresponding data in tissues, we illustrated the different characteristics of emRNAs compared to tissue mRNAs. We then developed an improved strategy for emRNA detection based on the features of circulating emRNAs. Using the optimized detection strategy, we further validated prostate cancer (PCa) associated emRNAs discovered by emRNA-seq in a large cohort of patients and identified emRNA signatures for PCa screening and diagnosis using logistic regression analysis. The receiver operating characteristic curve (ROC) analysis showed that the circulating emRNA-based screening signature yielded an area under the ROC curve (AUC) of 0.948 in distinguishing PCa patients from healthy controls. The circulating emRNA-based diagnostic signature also showed a great performance in predicting prostate biopsy results (AUC: 0.851). In conclusion, our study developed an optimized emRNA detection strategy and identified novel emRNA signatures for the detection of PCa.
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http://dx.doi.org/10.1186/s12943-021-01349-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008633PMC
March 2021

Chemokine Receptor CCR2b Enhanced Anti-tumor Function of Chimeric Antigen Receptor T Cells Targeting Mesothelin in a Non-small-cell Lung Carcinoma Model.

Front Immunol 2021 11;12:628906. Epub 2021 Mar 11.

State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.

Chimeric antigen receptor (CAR) T cell therapy faces a number of challenges for the treatment of non-small-cell lung carcinoma (NSCLC), and efficient migration of circulating CAR T cells plays an important role in anti-tumor activity. In this study, a CAR specific for tumor antigen mesothelin (Msln-CAR) was co-expressed with cell chemokine receptors CCR2b or CCR4. Findings showed that CCR2b and CCR4 enhanced the migration of Msln-CAR T cell by transwell assay. When incubated with mesothelin-positive tumor cells, Msln-CCR2b-CAR and Msln-CCR4-CAR T cell specifically exerted potent cytotoxicity and produced high levels of proinflammatory cytokines, including IL-2, IFN-γ, and TNF-α. Furthermore, NSCLC cell line-derived xenograft (CDX) model was constructed by implanting subcutaneously modified A549 into NSG mice. Compared to conventional Msln-CAR T cells, living imaging indicated that Msln-CCR2b-CAR T cells displayed superior anti-tumor function due to enhanced migration and infiltration into tumor tissue shown by immunohistochemistry (IHC) analysis. In addition, histopathological examinations of mice organs showed that no obvious organic damages were observed. This is the first time that CAR T cell therapy combined with chemokine receptor is applied to NSCLC treatment.
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http://dx.doi.org/10.3389/fimmu.2021.628906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992009PMC
March 2021

Alkaloids bearing rare skeletons from Forsythia suspensa with anti-inflammatory and anti-viral activities in vitro.

Phytochemistry 2021 Jun 25;186:112739. Epub 2021 Mar 25.

College of Life Sciences, Yantai University, Yantai, 264005, People's Republic of China. Electronic address:

Five alkaloids, including two previously undescribed alkaloids, named forsyshiyanines A and B, attributable to the rare skeletons 4b,5,6,7,8,8a,9,10-octahydrobenzo[f]quinoline and (6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)methyl, respectively, along with three known ones (3-5), were isolated from the ripe fruits of Forsythia suspensa. The chemical structures including absolute configurations of two undescribed compounds were established using integrated spectroscopic techniques, electronic circular dichroism calculations, and single-crystal x-ray diffraction analysis. In vitro, five alkaloids showed anti-inflammatory activities, with the inhibition rates of the release of β-glucuronidase from polymorphonuclear leukocytes of rats being in the range 47.9%-56.0% at a concentration of 10 μM. Moreover, five compounds exhibited anti-viral activities against influenza A virus and respiratory syncytial virus, with IC values in the range of 7.3-32.5 μM and EC values in the range 3.7-14.1 μM.
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http://dx.doi.org/10.1016/j.phytochem.2021.112739DOI Listing
June 2021

Effect of vacuum impregnated fish gelatin and grape seed extract on moisture state, microbiota composition, and quality of chilled seabass fillets.

Food Chem 2021 Aug 15;354:129581. Epub 2021 Mar 15.

Department of Food Science & Technology, National University of Singapore, Singapore 117542, Singapore; National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China. Electronic address:

The effect of fish gelatin (FG) and grape seed extract (GSE) on microbiota composition and moisture state of fish was unexplored. Herein, this study aimed to evaluate the single and combined (FGG) effects on seabass during storage (4 °C) with assistant of vacuum impregnation and to elucidate the underlying preservative mechanism. As suggested by low-field NMR and magnetic resonance imaging, FGG-treated seabass presented higher water holding capacity by controlling transformation from immobilised to free water. Moreover, the total viable count and spoilage bacteria were reduced by > 1 log CFU/g as compared to the control. Changes in microbial flora analysed using high throughput sequencing further indicated that GSE contributed to the notably suppressed growth of Pseudomonas. Also, the accumulation of biogenic amines especially putrescine was decreased (over 0.5-fold) under the combination treatment as compared to the control (P < 0.05). The results suggest that FGG is promising for seabass preservation.
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http://dx.doi.org/10.1016/j.foodchem.2021.129581DOI Listing
August 2021

Mutational spectrum and precision oncology for biliary tract carcinoma.

Theranostics 2021 4;11(10):4585-4598. Epub 2021 Mar 4.

Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Wangfujing, Beijing 100730, China.

The genomic spectrum of biliary tract carcinoma (BTC) has been characterized and is associated with distinct anatomic and etiologic subtypes, yet limited studies have linked genomic alterations with personalized therapies in BTC patients. This study analyzed 803 patients with BTC:164 with gallbladder cancer, 475 with intrahepatic cholangiocarcinoma (ICC) and 164 with extrahepatic cholangiocarcinoma. We determined genomic alterations, mutational signatures related to etiology and histopathology and prognostic biomarkers. Personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. The median tumor mutation burden (TMB) was 1.23 Mut/Mb, with 4.1% of patients having hypermutated BTCs. Unlike the results obtained from the Western population, the most frequently altered cancer-related genes in our cohort included (53%), (26%), (18%), (14%) and (14%). Germline mutations occurred mostly in DNA damage repair genes. Notably, 35.8% of the ICCs harbored aristolochic acid related signatures and an elevated TMB. and mutations and amplified 7q31.2 were demonstrated to negatively affect patient prognosis. Moreover, 19 genes were proposed to be PATs in BTCs, with 25.4% of patients harboring these PATs. Forty-six patients received PAT-matched targeted therapies, achieving a 26.1% objective response rate; the median progression-free survival (PFS) was 5.0 months, with 56.8% of patients obtaining PFS benefits. Extensive genomic diversity and heterogeneity were observed among BTC patients, with contributions according to potential etiology exposures, anatomical subtypes and clinicopathological characteristics. We also demonstrated that patients with refractory BTCs who have PATs can derive considerable benefit from receiving a matched therapy, initiating further prospective clinical trials guided by molecular profiling among this aggressive cancer.
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http://dx.doi.org/10.7150/thno.56539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978308PMC
March 2021

The Surge of Hypervirulent ST398 MRSA Lineage With Higher Biofilm-Forming Ability Is a Critical Threat to Clinics.

Front Microbiol 2021 4;12:636788. Epub 2021 Mar 4.

Department of Laboratory Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

The global increase of community-associated (CA) infections with methicillin-resistant (MRSA) is a major healthcare problem. Although sequence type (ST) 398 MRSA was first described as a livestock-associated (LA) lineage, human-adapted MRSA (HO-MRSA) ST398 without livestock contact has subsequently been reported from China in our previous study and other later research. The proportion of ST398 HO-MRSA has also remarkably increased in recent years in China. Based on 3878 isolates that were collected in a general hospital between 2008 and 2018, we identified 56 ST398 HO-MRSA isolates. The four early appearing isolates of them have been sequenced by whole-genome sequencing (WGS) in our previous study. Here, by usage of WGS on the later-appearing 52 isolates and analyzing the phylogenetic dynamics of the linage, we found that 50 isolates clustered together with the former 4 isolates, making it a main clade out of MSSA clones and other MRSA clones, although ST398 HO-MRSA evolved with multiple origins. Drug resistance and virulence gene analysis based on the WGS data demonstrated that ST398 HO-MRSA main clade exhibited a similar pattern in both parts. Furthermore, they all carried a conserved variant of prophage 3 to guarantee virulence and a short SCC type V element of class D to maintain considerable lower methicillin resistance. Further phenotypical research verified that the epidemic HO-MRSA ST398 displayed enhanced biofilm formation ability when keeping high virulence. The dual advantages of virulence and biofilm formation in the HO-MRSA ST398 subtype promote their fitness in the community and even in the healthcare environment, which poses a serious threat in clinical infections. Therefore, further surveillance is required to prevent and control the problematic public health impact of HO-MRSA ST398 in the future.
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http://dx.doi.org/10.3389/fmicb.2021.636788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969815PMC
March 2021

The role of PKM2 nuclear translocation in the constant activation of the NF-κB signaling pathway in cancer-associated fibroblasts.

Cell Death Dis 2021 Mar 17;12(4):291. Epub 2021 Mar 17.

Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No. BZO381), 100005, Beijing, China.

Cancer-associated fibroblasts (CAFs) play critical roles in cancer progression by regulating tumor cell proliferation, angiogenesis, and metastasis. Recent studies demonstrated that CAFs induce inhibitory immune cell infiltration and chemotherapy resistance in gastric cancer by activating the NF-κB signaling pathway to secrete IL6, IL8, and other inflammatory factors. Inhibition of the NF-κB signaling pathway in CAFs might be a potential therapeutic strategy in gastric cancer. However, how the NF-κB pathway is activated in CAFs remains unclear. We showed that mesenchymal stem cells (MSCs) differentiated into CAFs, induced by the exosomes derived from gastric cancer cells. During the process of differentiation from MSCs into CAFs, we showed that nuclear PKM2 expression was continuously upregulated and associated with NF-κB P65 acetylation, contributing to P65 nuclear retention in CAFs and constant transcription of IL-6, IL-8, and other inflammatory factors, thus promoting gastric cancer cell proliferation. We showed that NF-κB P65 acetylation was induced by P300. We showed that nuclear PKM2 was derived from exosomes of gastric cancer cell lines and the positive feedback loop induced by PKM2-P65 combination. It is also proved that P300 inhibitors can inhibit tumor proliferation in an AGS subcutaneous xenograft tumor model. Our study showed that gastric cancer cells influence the continuous activation of the NF-κB signaling pathway in CAFs by secreting gastric cancer exosomes containing PKM2, thus inducing abnormal metabolism and inflammation activation. This study provides a new therapeutic target for CAF normalization or deactivation strategies.
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http://dx.doi.org/10.1038/s41419-021-03579-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969736PMC
March 2021

Interpretation of the absorbed constituents and pharmacological effect of Spica Schizonepetae extract on non-small cell lung cancer.

PLoS One 2021 17;16(3):e0248700. Epub 2021 Mar 17.

College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.

As a traditional Chinese medicine (TCM) with a usage history of over 2,000 years in China, Spica Schizonepetae possesses definite clinical activity in the treatment of non-small cell lung cancer (NSCLC). However, its active ingredients and mechanism of action remain unclear at present. The further exploration of its active components and underlying mechanism will provide a basis for the development of candidate anti-tumor drugs. Our previous study explored the chemical constituents of Spica Schizonepetae extract (SSE). On this basis, molecular networking technology was applied in analyzing the QTOF-MS/MS data of rat plasma after intragastric administration of SSE using the GNPS database platform. A total of 26 components were found, including 9 proterotype components and 17 metabolites, which revealed the potential active ingredients of SSE. Later, the Lewis lung cancer mouse model was established, and the inhibition rate and histopathological sections were used as the indicators to investigate the anti-tumor effect of SSE, whereas the body weight, survival rate, thymus index and spleen index served as the indicators to explore the pharmacological effects of SSE on improving mouse immunity. The results showed that SSE had comparable anti-tumor efficacy to cisplatin, which enhanced the immunity, improved the quality of life, and extended the survival time of lung cancer mice. Furthermore, human A549 lung tumor cells were selected to explore the mechanism of SSE in treating NSCLC based on cell metabonomics. After data mining by the MPP software, 23 differential endogenous metabolites were identified between SSE and tumor groups. Moreover, results of pathway enrichment analysis using the MetaboAnalyst 4.0 software indicated that these metabolites were mainly enriched in four metabolic pathways (p < 0.1). By adopting the network pharmacology method, the metabolic pathways discovered by cell metabolomics were verified against the ChEMBL, STITCH, UniProt and TCGA databases, and differences in the underlying mechanism between cells and humans were found. It was proved that SSE affected the metabolism of purine, arachidonic acid and histidine to exert the anti-tumor efficacy. Furthermore, the multi-target, multi-pathway, and immunoenhancement mechanism of SSE in anti-tumor treatment was revealed, which provided a scientific basis for new drug development and the rational application of Spica Schizonepetae in clinic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968677PMC
March 2021

A thermochromic tissue-mimicking phantom model for verification of ablation plans in thermal ablation.

Ann Transl Med 2021 Feb;9(4):354

Department of Ultrasound, Tianjin Third Central Hospital, Tianjin, China.

Background: Our study aims to develop a novel tissue-mimicking thermochromic with tumor model for visualization of thermal ablation and verification of ablation plans.

Methods: Polyacrylamide gel was mixed with thermochromic ink to produce a phantom model. A phantom model embedded in a tumor model was constructed and used to evaluate the ablation procedure. The phantom models were randomly divided into complete ablation group and incomplete ablation group. The ablation planning of the tumor was on the 3D US and performed on a phantom model. We guide the ablation procedures according to the ablation planning. The results measured in a gross specimen of the phantom model were compared with the expected results in ablation planning.

Results: The color of the model changes from cream white to magenta after heating. The mono-site ablation area is a spheroid after thermal ablation with a size of 3.0×1.8 cm at 60 W, 5 minutes, 3.5×2.5 cm at 60 W, 10 minutes, and 4.0×3.5 cm at 60 W, 15 minutes, respectively. According to the ablation planning, a total of 4 ablation points were needed to retrieve the complete ablation of a 3.0 cm tumor. The complete ablation and incomplete ablation were proved by a gross specimen of the phantom model as we expected.

Conclusions: A novel thermochromic tissue-mimicking phantom model with a spherical tumor model has been designed and developed. The ablation area can be visualized on this phantom model by the permanent color change. This phantom model can assess the ablation planning system's accuracy and train operators for ultrasound-guided thermal ablation.
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http://dx.doi.org/10.21037/atm-21-523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944255PMC
February 2021

A novel mono-modality fusion imaging method based on three-dimensional contrast-enhanced ultrasound for the evaluation of ablation margins after microwave ablation of hepatocellular carcinoma.

J Gastrointest Oncol 2021 Feb;12(1):184-195

Department of Ultrasound, Tianjin Third Central Hospital, Tianjin, China.

Background: To investigate the feasibility and accuracy of using preoperative and postoperative three-dimensional contrast-enhanced ultrasound (3D CEUS) fusion imaging in the evaluation of safety margins after thermal ablation of hepatocellular carcinoma (HCC).

Methods: A total of the 24 patients with HCC who underwent microwave ablation (MWA) between June 2020 and December 2020 were enrolled in this study. All patients received preoperative and postoperative 3D CEUS. The preoperative and postoperative 3D CEUS images were then fused. The success rate and evaluation time were recorded. The ablation margin and whether or not the safety margin was reached were calculated and recorded. If the ablation safety margin was not reached, the residual ablation volume needed to cover the safety margin was calculated automatically. The agreement between contrast-enhanced computed tomography(CECT) and 3D CEUS fusion imaging in the evaluation of ablation margins was explored using the kappa coefficient.

Results: The 3D CEUS fusion success rate was 95.8% (23/24), with a mean fusion time of (4.1±1.8) minutes. Twenty-three tumors were completely ablated, and the safety margin was achieved for 9 tumors. The ablation margin of 14 tumors was <5 mm. The mean uncovered safety margin volume was (2.27±2.11) mL, and the mean proportion of the uncovered safety margin to the whole safety margin was 16.8%. According to the results of preoperative and postoperative CECT fusion imaging, the ablation margin of 13 tumors was <5 mm, and the ablation margin of 10 tumors was >5 mm. The 2 methods showed excellent consistency, with a Kappa value of 0.911 (P=0.000012).

Conclusions: This study has presented a novel mono-modality fusion imaging method based on CEUS. We demonstrated that 3D CEUS fusion has a short fusion time and a high success rate, as well as good consistency with enhanced CT fusion. Therefore, 3D CEUS fusion is a feasible and accurate tool for evaluating the immediate efficacy of thermal ablation of HCC.
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http://dx.doi.org/10.21037/jgo-21-46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944154PMC
February 2021