Publications by authors named "Sheng Zhang"

1,511 Publications

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Theaflavin Promotes Mitochondrial Abundance and Glucose Absorption in Myotubes by Activating the CaMKK2-AMPK Signal Axis via Calcium-Ion Influx.

J Agric Food Chem 2021 Jul 14. Epub 2021 Jul 14.

Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, Hunan, China.

Drinking tea has been proven to have a positive biological effect in regulating human glucose and lipid metabolism and preventing type 2 diabetes (T2D). Skeletal muscle (SkM) is responsible for 70% of the sugar metabolism in the human body, and its dysfunction is an important factor leading to the development of obesity, T2D, and muscle diseases. As one of the four known theaflavins (TFs) in black tea, the biological role of theaflavin (TF1) in regulating SkM metabolism has not been reported. In this study, mature myotubes induced by C2C12 cells in vitro were used as models. The results showed that TF1 (20 μM) promoted mitochondrial abundance and glucose absorption in myotubes by activating the CaMKK2-AMPK signaling axis via Ca influx. Moreover, it promoted the expression of slow muscle fiber marker genes (Myh7, Myl2, Tnnt1, and Tnnc1) and PGC-1α/SIRT1, as well as enhanced the oxidative phosphorylation capacity of myotubes. In conclusion, this study preliminarily clarified the potential role of TF1 in regulating SkM glucose absorption as well as promoting SkM mitochondrial biosynthesis and slow muscle fiber formation. It has potential research and application values for the prevention/alleviation of SkM-related T2D and Ca-related skeletal muscle diseases through diet.
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http://dx.doi.org/10.1021/acs.jafc.1c02892DOI Listing
July 2021

creation of [email protected] nanoflowers on ITO electrodes for sensitive photoelectrochemical detection of copper ions in blood.

J Mater Chem B 2021 Jul 13. Epub 2021 Jul 13.

College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, P. R. China and School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150090, P. R. China and School of Life Sciences, Huzhou University, Huzhou City, Zhejiang Province 313000, P. R. China.

A highly selective and sensitive photoelectrochemical (PEC) detection method has been developed for the analysis of copper (Cu2+) ions using nanoflower-like [email protected] heterojunctions, of which ZnO was first in situ grown onto the indium tin oxide electrodes by a hydrothermal method and then coated with CdS through the chemical bath deposition route. It was discovered that the [email protected] heterojunction so formed could serve as a photosensitive catalyst with improved charge separation for visible-light-driven PEC responses. Enhanced visible-light harvesting of nanocomposites could also be expected with CdS as the visible-light sensitizer. Furthermore, the introduction of Cu2+ ions could cause a rational decrease in the photocurrents of nanocomposites through the specific interaction between CdS and Cu2+ ions. A [email protected] heterojunction-based PEC sensor was thereby developed for the detection of Cu2+ ions in blood in the linear concentrations ranging from 0.50 to 80 nM, with a limit of detection of 0.18 nM. Such a heterojunction-based PEC detection platform constructed using two photocatalytic materials with matched band structures are promising for a wide range of applications for sensing Cu2+ ions in clinical diagnostics, food monitoring, and environmental analysis.
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http://dx.doi.org/10.1039/d1tb00989cDOI Listing
July 2021

Fabricating a wettable microwells array onto a nitrogen plasma-treated ITO substrate: high-throughput fluorimetric platform for selective sensing of ammonia in blood using polymer-stabilized NH-MIL-125.

J Mater Chem B 2021 Jul 14. Epub 2021 Jul 14.

College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, P. R. China and School of Life Sciences, Huzhou University, Huzhou, Zhejiang Province 313000, P. R. China.

A high-throughput and selective fluorimetric platform has been constructed for the analysis of ammonia in blood by using a polymer-stabilized metal-organic framework (MOF) of porous NH2-MIL-125, which was coated onto a wettable microwells array constructed on an indium tin oxide (ITO) substrate. It was found that the nitrogen plasma treatment for the ITO substrate could create a super-hydrophilic interface that combined with the hydrophobic pattern yielded a wettable microwells array, enabling the condensation-based enrichment of targets from the sample droplets. Moreover, the NH2-MIL-125 MOF encapsulated using polymers could be firmly coated onto the microwells to act as fluorescent probes for sensing NH3 with enhanced responses. In addition, the use of the polymer polyvinyl pyrrolidone could protect and stabilize the crystals of NH2-MIL-125 probe in aqueous media, revealing the improved hydrophilicity and significantly depressed signal background. The as-developed fluorimetric platform, containing a MOF-coated microwells array, can enable the detection of ammonia in blood, with concentrations ranging linearly from 0.10 to 300 μM. More importantly, this plasma treatment-based fabrication route may hold promise for designing different wettable microwells arrays for the high-throughput detection of multiple targets in the fields of biomedical analysis and environmental monitoring.
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http://dx.doi.org/10.1039/d1tb01304aDOI Listing
July 2021

Chiral Indolizidine Synthesis through the Ir-Catalyzed Asymmetric Hydrogenation of Cyclic Pyridinium Salts.

J Org Chem 2021 Jul 8. Epub 2021 Jul 8.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China.

The Ir-catalyzed asymmetric hydrogenation of cyclic pyridinium salts is presented as a new strategy for the convenient and efficient synthesis of chiral indolizidines. The asymmetric hydrogenation of cyclic pyridinium salts derived from 2-(2-acylphenyl)pyridines proceeded smoothly in the presence of [Ir(cod)Cl] and ()-DM-SegPhos to provide the desired chiral 7,8-benzoindolizidines in high to excellent yields with moderate enantioselectivity (up to 86:14 er) and excellent diastereoselectivity (>20:1 dr). The enantiomeric purity of was increased to 92:8 through recrystallization.
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http://dx.doi.org/10.1021/acs.joc.1c00958DOI Listing
July 2021

Multispectral photodetectors based on 2D material/CsBiIheterostructures with high detectivity.

Nanotechnology 2021 Jul 20;32(41). Epub 2021 Jul 20.

School of Physics and Key Laboratory of MEMS of the Ministry of Education, Southeast University, Nanjing 211189, People's Republic of China.

Group VA metal halide-based perovskites have emerged as intensively explored Pb-free perovskites, owing to their excellent environmental stability and low-toxicity. However, the relatively low carrier mobility and high photocarrier recombination rates restrict their applications in photodetectors. One promising approach to achieve higher performance is to integrate these Pb-free perovskites with 2D materials to form heterostructures. Here, we report on the high sensitivity photodetectors based on MoS/CsBiIand graphene/CsBiIheterostructures for multispectral regions. The heterostructures combine the high carrier mobility of 2D materials with superior light-harvesting properties of perovskites, as well as the effective built-in electric filed at the junction area, leading to efficient photocarrier separation and extraction. The specific detectivity of MoS/CsBiIdevice reaches 1.15 × 10Jones for the detection of ultraviolet (UV) light of 325 nm, which is four orders of magnitude higher than UV detectors built on GaN. As a result of the efficient dark current suppression, the specific detectivity of graphene/CsBiIphotodetector can be promoted to 5.24 × 10Jones, 1.33 × 10Jones, and 1.12 × 10Jones for the detection of 325 nm, 447 nm, and 532 nm light, respectively.
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http://dx.doi.org/10.1088/1361-6528/ac1130DOI Listing
July 2021

Evaluation and Clinical Implication of Zhenwu Decoction on Seven Cytochrome P450 Enzyme in Chronic Heart Failure Rats.

Curr Drug Metab 2021 Jul 1. Epub 2021 Jul 1.

School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, China.

Background: Recently, the combination of Traditional Chinese Medicine (TCM) formulae and other drugs have been used frequently in clinical practice, while the possibility of herb-drug interaction (HDI) risk remains a challenge. Since metabolic enzymes mediate the majority of drug interactions, evaluating the effects of formulae on metabolic enzymes is instructive for the rational formulation of drug delivery plans.

Objective: Herein, we are devoted to estimating the effects of Zhenwu detection (ZWD) on activities and mRNA expression of 7 cytochrome P450 (CYP450) isoenzymes in chronic heart failure (CHF) rats.

Methods: The CHF rats were replicated by coronary artery ligation and were randomly divided into sham operation group, model group, ZWD low- (2.188 g/kg), middle- (4.375 g/kg), and high- (8.750 g/kg) dose groups, n=6. After 8 weeks, rats were administrated with ZWD and normal saline (NS) for four weeks. The mixed solution of 7 probe drugs (1 mL/kg) was subsequently injected into 30 rats through the caudal vein after the last administration. Pharmacokinetic parameters and mRNA expression of 7 probe drugs were measured by using UPLC-MS/MS and RT-qPCR, respectively.

Results: Activities and mRNA expression of CYP1A2, CYP2B1, CYP2C6, CYP2C11, CYP3A1 were inhibited in CHF rats, and ZWD could reverse this effect except for CYP2B1.

Conclusion: Overall, these findings underscore that for CHF patients, the HDI should be taken into consideration when ZWD is used on its own or combined with drugs meditated by CYP1A2 (CYP1A2 in rats), CYP2C9 (CYP2C6 in rats), CYP2C19 (CYP2C11 in rats) and CYP3A4 (CYP3A1 in rats). Furthermore, since amodiaquine, dextromethorphan and bupropion apparent volume of distribution (Vd) were proved far greater than the total volume of body fluids, we speculate that the dose adjustment and potential organotoxicity of these substrates may need further consideration.
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http://dx.doi.org/10.2174/1389200222666210701171047DOI Listing
July 2021

Vangl2 limits chaperone-mediated autophagy to balance osteogenic differentiation in mesenchymal stem cells.

Dev Cell 2021 Jun 29. Epub 2021 Jun 29.

Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Lysosomes are the recycling center and nutrient signaling hub of the cell. Here, we show that lysosomes also control mesenchymal stem cell (MSC) differentiation by proteomic reprogramming. The chaperone-mediated autophagy (CMA) lysosome subgroup promotes osteogenesis, while suppressing adipogenesis, by selectively removing osteogenesis-deterring factors, especially master transcriptional factors, such as adipogenic TLE3, ZNF423, and chondrogenic SOX9. The activity of the CMA-committed lysosomes in MSCs are controlled by Van-Gogh-like 2 (Vangl2) at lysosomes. Vangl2 directly binds to lysosome-associated membrane protein 2A (LAMP-2A) and targets it for degradation. MSC-specific Vangl2 ablation in mice increases LAMP-2A expression and CMA-lysosome numbers, promoting bone formation while reducing marrow fat. The Vangl2:LAMP-2A ratio in MSCs correlates inversely with the capacity of the cells for osteoblastic differentiation in humans and mice. These findings demonstrate a critical role for lysosomes in MSC lineage acquisition and establish Vangl2-LAMP-2A signaling as a critical control mechanism.
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http://dx.doi.org/10.1016/j.devcel.2021.06.011DOI Listing
June 2021

An Extended Correlation Dimension of Complex Networks.

Entropy (Basel) 2021 Jun 3;23(6). Epub 2021 Jun 3.

Military Exercise and Training Center, Academy of Army Armored Force, Beijing 100072, China.

Fractal and self-similarity are important characteristics of complex networks. The correlation dimension is one of the measures implemented to characterize the fractal nature of unweighted structures, but it has not been extended to weighted networks. In this paper, the correlation dimension is extended to the weighted networks. The proposed method uses edge-weights accumulation to obtain scale distances. It can be used not only for weighted networks but also for unweighted networks. We selected six weighted networks, including two synthetic fractal networks and four real-world networks, to validate it. The results show that the proposed method was effective for the fractal scaling analysis of weighted complex networks. Meanwhile, this method was used to analyze the fractal properties of the Newman-Watts (NW) unweighted small-world networks. Compared with other fractal dimensions, the correlation dimension is more suitable for the quantitative analysis of small-world effects.
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http://dx.doi.org/10.3390/e23060710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229313PMC
June 2021

Implications of Habitual Alcohol Intake With the Prognostic Significance of Mean Corpuscular Volume in Stage II-III Colorectal Cancer.

Front Oncol 2021 14;11:681406. Epub 2021 Jun 14.

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

Objective: To elucidate the prognostic significance of mean corpuscular volume (MCV), with implications of habitual alcohol intake in stage II-III colorectal cancer (CRC).

Background: MCV had the potential to become an ideal prognostic biomarker and be put into clinical application. Few studies, however, have explored whether habitual alcohol intake which greatly increased the value of MCV would affect the prognostic role of MCV.

Methods: Eligible patients were identified from the CRC database of Fudan University Shanghai Cancer Center (FUSCC) between January 2012 and December 2013. Survival analyses were constructed using the Kaplan-Meier method to evaluate the survival time distribution, and the log-rank test was used to determine the survival differences. Univariate and multivariate Cox proportional hazard models were built to calculate the hazard ratios of different prognostic factors.

Results: A total of 694 patients diagnosed with stage II-III CRC between January 2012 and December 2013 were identified from FUSCC. Low pretreatment MCV was independently associated with 72.0% increased risk of overall mortality compared with normal MCV (HR = 1.720, 95%CI =1.028-2.876, P =0.039, using normal MCV as the reference). In patients with habitual alcohol intake, however, pretreatment MCV positively correlated with the mortality (P = 0.02) and tumor recurrence (P = 0.002) after adjusting for other known prognostic factors.

Conclusions: In CRC patients without habitual alcohol intake, low (<80 fL) level of pretreatment MCV was a predictor of poor prognosis. In patients with habitual alcohol intake, however, pretreatment MCV showed the opposite prognostic role, which would elicit many fundamental studies to elucidate the mechanisms behind.
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http://dx.doi.org/10.3389/fonc.2021.681406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236820PMC
June 2021

[Comparison of the efficacy between open and arthroscopic Latarjet procedure in the treatment of anterior shoulder instability:a Meta-analysis].

Zhongguo Gu Shang 2021 Jun;34(6):573-83

The Forth Department of Joint, Wangjing Hospital of China Academy of Chinese Medical Science, Beijing 100102, China.

Objective: To compare the clinical efficacy between open and arthroscopic Latarjet procedure in the treatment of anterior shoulder instability by using Meta-analysis.

Methods: Search PubMed, Medline, Embase, Cochrane, China National Knowledge Infrastructure(CNKI), Wanfang database, China Biological Literature system(CBM) and VIP database. Review all retrospective or prospective cohort studies and randomized controlled trials on open and arthroscopic Latarjet procedure for anterior shoulder instability. Binary variables (postoperative recurrence rate, incidence of intraoperative and postoperative complications) and continuousvariables [shoulder external rotation range of motion, Walch-Duplay score, Rowe score, WOSI score, postoperative visual analogue scale (VAS), postoperative anxiety degree and operation time] were selected for analysis. NOS bias risk assessment criteria (recommended by Cochrane collaboration Network) were used to evaluate the literature quality of retrospective or prospective cohort studies, and modified Jadad scale was used to evaluate the quality of randomized controlled trials. Literature screening, literature quality evaluation and data extraction were carried out independently by two observers. RevMan 5.3 software was used for Meta analysis.

Results: (1)A total of 9 studies were included, including 8 retrospective cohort studies and 1 prospective cohort study. A total of 956 patients were included in this study, including open Latarjet procedure(=436) and arthroscopic Latarjet procedure(=520). (2)The postoperative WOSI score in the open group was better than that of arthroscopic group (=93.74, 95%:26.00 to 161.49, =0.007), and the α angle was smaller than arthroscopic group(=-6.44, 95%:-12.08 to 0.81, =0.02). (3)The recurrence rate of open Latarjet group was lower than that of arthroscopic Latarjet group, but there was no significant difference between the two groups (=0.84, 95%:0.23 to 3.05, =0.79). (4)There were no significant difference in shoulder external rotation, Walch-Duplay score, Rowe score, postoperative visual analogue score, postoperative anxiety degree and operation time between open and arthroscopic Latarjet group.

Conclusion: The arthroscopic Latarjet stabilisation shows satisfactory and comparable results to open procedure, and the postoperative recurrence and complication rates are low in both group. Both open and arthroscopic Latarjet procedure are reliable surgical procedures in the treatment of anteriorly shoulder instability. Arthroscopic procedure has longer learning curve than open procedure, the doctors may either choose arthroscopic or open Latarjet procedure based on personal skills and preference, as well as the patient's condition. However, all the literatures included in this study are cohort studies with low level of evidence. The research lack randomized controlled trials, and small sample size is small. In the future, randomized controlled studies with large sample size and high level of evidence are still needed to determine the efficacy difference between the two.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.06.019DOI Listing
June 2021

Flow-induced surface crystallization of granular particles in cylindrical confinement.

Sci Rep 2021 Jun 24;11(1):13227. Epub 2021 Jun 24.

University of Chinese Academy of Sciences, Beijing, 100049, China.

An interesting phenomenon that a layer of crystallized shell formed at the container wall during an orifice flow in a cylinder is observed experimentally and is investigated in DEM simulation. Different from shear or vibration driven granular crystallization, our simulation shows during the flow the shell layer is formed spontaneously from stagnant zone at the base and grows at a constant rate to the top with no external drive. Roughness of the shell surface is defined as a standard deviation of the surface height and its development is found to disobey existed growth models. The growth rate of the shell is found linearly proportional to the flow rate. This shell is static and served as a rough wall in an orifice flow with frictionless sidewall, which changes the flow profiles and its stress properties, and in turn guarantees a constant flow rate.
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http://dx.doi.org/10.1038/s41598-021-92136-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225843PMC
June 2021

Thiophene-Based Double Helices: Radical Cations with SOMO-HOMO Energy Level Inversion.

Photochem Photobiol 2021 Jun 21. Epub 2021 Jun 21.

Department of Chemistry, University of Nebraska, Lincoln, NE, USA.

We report relatively persistent, open-shell thiophene-based double helices, radical cations 1 -TMS and 2 -TMS . Closed-shell neutral double helices, 1-TMS and 2-TMS , have nearly identical first oxidation potentials, E  ≈ +1.33 V, corresponding to reversible oxidation to their radical cations. The radical cations are generated, using tungsten hexachloride in dichloromethane (DCM) as an oxidant, E  ≈ +1.56 V. EPR spectra consist of a relatively sharp singlet peak with an unusually low g-value of 2.001-2.002, thus suggesting exclusive delocalization of spin density over π-conjugated system consisting of carbon atoms only. DFT computations confirm these findings, as only negligible fraction of spin density is found on sulfur and silicon atoms and the spin density is delocalized over a single tetrathiophene moiety. For radical cation, 1 -TMS , energy level of the singly occupied molecular orbital (SOMO) lies below the four highest occupied molecular orbitals (HOMOs), thus indicating the SOMO-HOMO inversion (SHI) and therefore, violating the Aufbau principle. 1 -TMS has a half-life of the order of only 5 min at room temperature. EPR peak intensity of 2 -TMS , which does not show SHI, is practically unchanged over at least 2 h.
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http://dx.doi.org/10.1111/php.13475DOI Listing
June 2021

CRISPLD2 attenuates pro-inflammatory cytokines production in HMGB1-stimulated monocytes and septic mice.

Am J Transl Res 2021 15;13(5):4080-4091. Epub 2021 May 15.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.

HMGB1 has been identified as a pro-inflammatory mediator which leads to sepsis lethality. Previous studies suggested that CRISPLD2 had anti-inflammatory property and might severe as a therapeutic agent in sepsis. In the present study, we first conducted bioinformatic analysis to explore the expression profile of HMGB1 in septic survivors and non-survivors. We found that the serum HMGB1 level of septic non-survivors was significantly higher than that of septic survivors, and there was a positive correlation between CRISPLD2 and HMGB1 in mRNA expression in most of the cancer and normal tissue types, revealing a co-expression or dependency relationship between the two genes. In vitro, using cultured THP-1 cells, we confirmed that HMGB1 can induce the expression of CRISPLD2 in a time dependent manner through TLR4-dependent pathway. Given that CRISPLD2 and HMGB1 shared a wide range of time scales in gene expression and the anti-inflammatory property of CRISPLD2, we further verified that HMGB1 induced cytokines production might be partially reversed by CRISPLD2. In vivo, intravenously treatment of CRISPLD2 failed to rescue septic mice, although the serum levels of inflammatory cytokines were decreased. In conclusion, our study demonstrated that HMGB1 can act as stimuli to up-regulate the expression of CRISPLD2 in THP-1 cells, and in turn, increased CRISPLD2 can curtail HMGB1 induced pro-inflammatory cytokines production. Unfortunately, the anti-inflammatory effects of CRISPLD2 did not translate into survival benefit in mice with sepsis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205833PMC
May 2021

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.

Nat Commun 2021 06 18;12(1):3734. Epub 2021 Jun 18.

Translational Research Institute, Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University, Henan, China.

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.
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http://dx.doi.org/10.1038/s41467-021-24099-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213729PMC
June 2021

Long noncoding RNA AFAP1-AS1 promotes tumor progression and invasion by regulating the miR-2110/Sp1 axis in triple-negative breast cancer.

Cell Death Dis 2021 Jun 18;12(7):627. Epub 2021 Jun 18.

Department of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College &Chinese Academy of Medical Sciences (CAMS), Beijing, China.

Long noncoding ribonucleic acids (LncRNAs) have been found to be involved in the proliferation, apoptosis, invasion, migration, and other pathological processes of triple-negative breast cancer (TNBC). Expression of the lncRNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) has been found to be significantly higher in TNBC than in other subtypes or in normal tissue samples, but the specific mechanism by which AFAP1-AS1 affects the occurrence and development of TNBC is yet to be revealed. In this study, we used Cell Counting Kit-8 (CCK-8), colony formation, wound healing migration, Transwell invasion, and nude mouse xenograft assays to confirm the role of AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. In addition, we performed bioinformatics analyses, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and dual-luciferase reporter assays (dual-LRA) to confirm interaction among AFAP1-AS1, micro-RNA 2110 (miR-2110), and Sp1 transcription factor (Sp1). We found that silencing AFAP1-AS1 and Sp1 or upregulating miR-2110 suppressed the proliferation, migration, and invasion of MDA-MB-231 and MDA-MB-468 cells in vitro as well as tumor growth in vivo. Mechanistically, the dual-LRA highlighted that miR-2110 was an inhibitory target of AFAP1-AS1, and that AFAP1-AS1 functioned as a miR-2110 sponge to increase Sp1 expression. AFAP1-AS1 silencing led to a reduction in Sp1 mRNA and protein levels, which could be reversed by joint transfection with miR-2110 inhibitor. Our findings demonstrated that AFAP1-AS1 could modulate the progression of breast cancer cells and affect tumorigenesis in mice by acting as a miR-2110 sponge, resulting in regulation of Sp1 expression. Therefore, AFAP1-AS1 could play a pivotal role in the treatment of TNBC.
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http://dx.doi.org/10.1038/s41419-021-03917-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213778PMC
June 2021

Nitrogen influenced competition between the genders of  Salix rehderiana.

Tree Physiol 2021 Jun 17. Epub 2021 Jun 17.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.

Male and female willow plants show spatial segregation of genders along the environmental gradients. Skewed gender ratio of willows is not only related to altitude, but also to nutrient status and sexual competition, which can affect their growth and defense by altering secondary metabolite production. The relationship between metabolites and nutrients in the two genders of Salix rehderiana was explored in the Gongga Mountain. We found gender ratio was altered with a change in soil nitrogen (N) status; in the high N habitats, secondary metabolites accumulated in males. Furthermore, pot experiment was conducted to test the effect of nitrogen supply on gender competition in S. rehderiana. Sufficient N supply stimulated females to produce amino acids and carbon-containing secondary metabolites for maintaining their carbon-nitrogen balance, but extra nitrogen for males was used for growth to occupy more space. N supply induced foliar nutrient imbalances and growth of opportunistic species, allowing them to outcompete neighbors. Better carbon allocation and storage in male than female willows would benefit intersexual competitiveness of males if environment N increases. Competition between the genders has a significant correlation with skewed gender ratio, spatial separation and resource utilization. Female willows would suffer fiercer competition for space by males with the increased soil N, which would result in the gender ratio alteration. Therefore, gender ratio of willows is likely to convert to gender balance from female-biased with long-term N deposition in the future.
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http://dx.doi.org/10.1093/treephys/tpab083DOI Listing
June 2021

Characteristics of circular RNAs expression of peripheral blood mononuclear cells in humans with Coronary Artery Disease.

Physiol Genomics 2021 06 14. Epub 2021 Jun 14.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Objective: Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD).

Methods: We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of 5 CAD patients and 5 controls. Bioinformatics analyses was adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the miRNA targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA.

Results: In total, 13160 downregulated and 12905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle and cellular metabolic process. Parental genes of the 10 dysregulated-circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges.

Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into diagnosis and prognosis of coronary artery disease.
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http://dx.doi.org/10.1152/physiolgenomics.00020.2021DOI Listing
June 2021

A five-gene signature is a prognostic biomarker in pan-cancer and related with immunologically associated extracellular matrix.

Cancer Med 2021 Jul 14;10(13):4629-4643. Epub 2021 Jun 14.

Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.

The tumor microenvironment (TME) is related to extracellular matrix (ECM) dynamics and has a broad fundamental and mechanistic role in tumorigenesis and cancer progression. We hypothesized that ECM regulators might play an essential role in pan-cancer attribution by causing a generic effect through its regulation of the dynamics of ECM alteration. By analyzing data from TCGA using GSEA and univariate Cox regression analysis, we found that ECM regulator genes were significantly enriched and contributed to mortality in various cancer types. Notably, UMAP analysis revealed that ECM regulator genes dominated the differences between tumor and adjacent normal tissues based on 59 or 31 pan-survival-related ECM gene sets. Subsequently, a five-gene signature consisting of the predominant ECM regulators ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3 was identified. We found that this five-gene signature was pro-mortality in 18 types of cancer in TCGA, and validated eleven other cancer types in TCGA and seven types in the TARGET and CoMMpass databases using overall survival analysis. KEGG pathway enrichment and Pearson correlation analysis indicated that these five component genes that were correlated with specific ECM proteins involved in tumorigenesis from the ECM receptor interaction gene set. Additionally, the fitted results of a linear model were applied to strengthen the discovery, demonstrating that the five genes were correlated with immune infiltration score and especially associated with typically immunologically "cold" tumors. We thus conclude that the ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3 signature showed a close association with a pan-cancer effect on prognosis and is related to ECM proteins in the TME which corresponding with immunologically "cold" cancer types.
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http://dx.doi.org/10.1002/cam4.3986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267129PMC
July 2021

Evidences for the mechanism of Shenmai injection antagonizing doxorubicin-induced cardiotoxicity.

Phytomedicine 2021 Jul 21;88:153597. Epub 2021 May 21.

Hangzhou Medical college, Hangzhou, China. Electronic address:

Background: Doxorubicin (DOX) is a widely used antitumor drug. However, its clinical application is limited for its serious cardiotoxicity. The mechanism of DOX-induced cardiotoxicity is attributed to the increasing of cell stress in cardiomyocytes, then following autophagic and apoptotic responses. Our previous studies have demonstrated the protective effect of Shenmai injection (SMI) on DOX-induced cardiotoxicity via regulation of inflammatory mediators for releasing cell stress.

Purpose: To further investigate whether SMI attenuates the DOX-induced cell stress in cardiomyocytes, we explored the mechanism underlying cell stress as related to Jun N-terminal kinase (JNK) activity and the regulation of autophagic flux to determine the mechanism by which SMI antagonizes DOX-induced cardiotoxicity.

Study Design: The DOX-induced cardiotoxicity model of autophagic cell death was established in vitro to disclose the protected effects of SMI on oxidative stress, autophagic flux and JNK signaling pathway. Then the autophagic mechanism of SMI antagonizing DOX cardiotoxicity was validated in vivo.

Results: SMI was able to reduce the DOX-induced cardiomyocyte apoptosis associated with inhibition of activation of the JNK pathway and the accumulation of reactive oxygen species (ROS). Besides, SMI antagonized DOX cardiotoxicity, regulated cardiomyocytes homeostasis by restoring DOX-induced cardiomyocytes autophagy. Under specific circumstances, SMI depressed autophagic process by reducing the Beclin 1-Bcl-2 complex dissociation which was activated by DOX via stimulating the JNK signaling pathway. At the same time, SMI regulated lysosomal pH to restore the autophagic flux which was blocked by DOX in cardiomyocytes.

Conclusion: SMI regulates cardiomyocytes apoptosis and autophagy by controlling JNK signaling pathway, blocking DOX-induced apoptotic pathway and autophagy formation. SMI was also found to play a key role in restoring autophagic flux for counteracting DOX-damaged cardiomyocyte homeostasis.
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http://dx.doi.org/10.1016/j.phymed.2021.153597DOI Listing
July 2021

Hypoxia inducible factor and diffuse white matter injury in the premature brain: perspectives from genetic studies in mice.

Neural Regen Res 2022 Jan;17(1):105-107

Department of Neurology, School of Medicine, the University of California, Davis; Institute for Pediatric Regenerative Medicine (IPRM), Shriners Hospitals for Children, Northern California, Sacramento, CA, USA.

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http://dx.doi.org/10.4103/1673-5374.314301DOI Listing
January 2022

Root Extract of (Sims) Kosterm. Modulates the Th17/Treg Balance to Attenuate DSS-Induced Colitis in Mice by IL-6/STAT3 Signaling Pathway.

Front Pharmacol 2021 13;12:615506. Epub 2021 May 13.

Center of Safety Evaluation, Hangzhou Medical College (Zhejiang Academy of Medical Sciences), Hangzhou, China.

Ulcerative colitis (UC) is a chronic, idiopathic and relapsing inflammatory disease of the gastrointestinal tract that has a prolonged disease duration. (Sims) Kosterm. is a traditional Chinese herb which has been used to treat gastrointestinal diseases for thousand years. However, there are few reports about the application of in the treatment of UC at present. Herein, we investigated the therapeutic effect of the root extract of (LREE) against UC and explored its underlying mechanisms based on IL-6 signaling pathway and the balance of T helper (Th) 17 and regulatory T (Treg) cells. Results showed that LREE could not only decrease the production and secretion of IL-6, but also could inhibit the signal transduction of IL-6/STAT3 signaling pathway. Moreover, LREE could significantly inhibit the differentiation of CD4 T cells to Th17 cells and decrease the proportion of Th17 cells in mesenteric lymph nodes (MLNs) of model mice . Besides, LREE could also alleviate the disease symptoms, reduce intestinal permeability and improve histopathological changes of colitis model mice. Together, LREE can significantly inhibit the production and secretion of IL-6, regulate IL-6/STAT3 signal transduction, and modulate the balance of Th17 and Treg cells and effectively attenuate UC.
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http://dx.doi.org/10.3389/fphar.2021.615506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170699PMC
May 2021

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells.

Front Cell Dev Biol 2021 18;9:656636. Epub 2021 May 18.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

We aimed to investigate differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in atherosclerosis and validate the expression of lncRNAs and co-expressed target genes in proliferation and migration models of human coronary artery smooth muscle cells (HCASMCs). Ten coronary artery specimens from a subject who died from a heart attack were employed. The pathological analysis was analyzed by hematoxylin and eosin (H&E) staining, and the lncRNAs and mRNAs were identified by RNA sequencing. Bioinformatic analyses were performed to predict possible mechanisms. The proliferation and migration of HCASMCs were induced with oxidized low-density lipoprotein (ox-LDL). Differentially expressed lncRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, 68 lncRNAs and 222 mRNAs were identified differentially expressed in atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the Fanconi anemia pathway may be involved in atherosclerosis. was found to be the co-localized target gene of LNC_000439, and 14 genes had high correlations with the expression of seven lncRNAs. In addition, nine lncRNA-miRNA-mRNA networks were constructed, and 53 co-expressed gene modules were detected with weighted gene co-expression network analysis (WGCNA). LNC_000684, LNC_001046, LNC_001333, LNC_001538, and LNC_002115 were downregulated, while LNC_002936 was upregulated in proliferation and migration models of HCASMCs. In total, six co-expressed mRNAs were upregulated in HCASMCs. This study suggests that the differentially expressed lncRNAs identified by RNA sequencing and validated in smooth muscle cells may be a target for regulating HCASMC proliferation and migration in atherosclerosis, which will provide a new diagnostic basis and therapeutic target for the treatment of cardiovascular diseases.
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http://dx.doi.org/10.3389/fcell.2021.656636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168468PMC
May 2021

Effects of different concentrations of metformin on osteoclast differentiation and apoptosis and its mechanism.

Pharmazie 2021 Jun;76(6):244-248

Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, People's Republic of China;, Email:

This study aimed to investigate the effect of metformin on osteoclast differentiation and apoptosis. Low concentration of metformin inhibited osteoclast differentiation and downregulated the expression of TRAP, RANK, Cathepsink, NFATC-1, MMP-9 and TRAF-6. High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.
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http://dx.doi.org/10.1691/ph.2021.1378DOI Listing
June 2021

Divergent early antibody responses define COVID-19 disease trajectories.

bioRxiv 2021 May 25. Epub 2021 May 25.

Serologic markers that predict severe COVID-19 disease trajectories could enable early medical interventions and reduce morbidity and mortality. We found that distinct features of IgG Fab and Fc domain structures were present within three days of a positive test that predicted two separate disease trajectories in a prospective cohort of patients with COVID-19. One trajectory was defined by early production of neutralizing antibodies and led to mild disease. A distinct trajectory, characterized by an initial period of mild symptoms followed by rapid progression to more severe outcomes, was predicted by the absence of early neutralizing antibody responses with concomitant production of afucosylated IgGs. Elevated frequencies of monocytes expressing the receptor for afucosylated IgGs, FcγRIIIa (CD16a), were an additional antecedent in patients with the more severe outcomes. In mechanistic studies, afucosylated immune complexes in the lung triggered an inflammatory infiltrate and cytokine production that was dependent on CD16a. Finally, in healthy subjects, mRNA SARS-CoV-2 vaccination elicited neutralizing antibodies that were enriched for Fc fucosylation and sialylation and distinct from both infection-induced trajectories. These data show the importance of combined Fab and Fc domain functions in the antiviral response, define an early antibody signature in people who progressed to more severe COVID-19 outcomes and have implications for novel therapeutic strategies targeting FcγRIIIa pathways.
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http://dx.doi.org/10.1101/2021.05.25.445649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168384PMC
May 2021

Orientational Alignment of Oxygen Vacancies: Electric-Field-Inducing Conductive Channels in TiO Film to Boost Photocatalytic Conversion of CO into CO.

Nano Lett 2021 Jun 1;21(12):5060-5067. Epub 2021 Jun 1.

National Laboratory of Solid State Microstructures and Jiangsu Provincial Key Laboratory for Nanotechnology, School of Physics, Nanjing University, Nanjing 210093, People's Republic of China.

Oxide semiconductors are widely used in the photocatalytic fields, and introducing oxygen vacancies is an effective strategy to improve their photocatalytic efficiency. However, oxygen vacancies in the bulk often act as the recombination centers of electron-hole pairs, which accelerates the recombination of electron-hole pairs. In this paper, we propose a strategy of electric field treatment and apply it to a TiO film with oxygen vacancies to promote the photocatalytic efficiency. After treatment by an electric field, the conductive channels consisting of oxygen vacancies are formed in the TiO film, which greatly decreases the resistance by almost 6 × 10 times. The yield of CO can reach up to 1.729 mmol g h, which is one of the best performances among the reported TiO-based catalysts. This work provides an effective and feasible way for enhancing photocatalytic activity through an electric field, and this method is promising for wide use in the field of catalysis.
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http://dx.doi.org/10.1021/acs.nanolett.1c00897DOI Listing
June 2021

Sex-biased genes and metabolites explain morphologically sexual dimorphism and reproductive costs in Salix paraplesia catkins.

Hortic Res 2021 Jun 1;8(1):125. Epub 2021 Jun 1.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.

Dioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions. As reproductive organs, unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism. To date, little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers. We investigated male and female flowers of Salix paraplesia in three flowering stages before pollination (the early, blooming and late stages) via transcriptional sequencing as well as metabolite content and phenotypic analysis. We found that a large number of sex-biased genes, rather than sex-limited genes, were responsible for sexual dimorphism in S. paraplesia flowers and that the variation in gene expression in male flowers intensified this situation throughout flower development. The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages. Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes. These sex-biased genes were involved mainly in signal transduction, photosynthesis, respiration, cell proliferation, phytochrome biosynthesis, and phenol metabolism; therefore, they resulted in more biomass accumulation and higher energy consumption in male catkins. Our results indicated that sex-biased gene expression in S. paraplesia flowers is associated with different reproductive investments in unisexual flowers; male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.
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http://dx.doi.org/10.1038/s41438-021-00566-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166972PMC
June 2021

Palladium-Catalyzed Three-Component Coupling Reaction via Benzylpalladium Intermediate.

Chem Rec 2021 May 24. Epub 2021 May 24.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116023, China.

Transition-metal catalyzed multi-component reactions have captured the attention of researchers in organic synthesis and drug synthesis due to their advantages of simple operation, easy availability of raw materials and without separation of intermediates. Among the multi-component reactions, the three-component processes have been developed into effective organic procedures. This personal account reviews our and other group's studies on the development of three-component coupling reaction for the rapid construction of two new chemical bonds simultaneously via benzylpalladium intermediates. Catalyst-switched three-component reactions of benzyl halides, activated olefins, and allyltributylstannane were successfully conducted to produce the corresponding benzylallylation products. Activation and conversion of carbon monoxide and carbon dioxide via π-benzylpalladium intermediates provide access to a wide range of unsaturated ketones and esters with excellent functional group tolerance. Meanwhile, other methods to produce benzylpalladium intermediates, including Heck insertion of alkenes into arylpalladium complexes, the oxidative addition of benzyl carbonate to palladium complexes and palladium-carbene migratory insertion, were also highlighted.
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http://dx.doi.org/10.1002/tcr.202100112DOI Listing
May 2021

Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis.

Free Radic Biol Med 2021 08 8;171:55-68. Epub 2021 May 8.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China. Electronic address:

Ferroptosis and pyroptosis have not been fully studied in atherosclerosis. We aimed to investigate the expression of ferroptosis-related and pyroptosis-related proteins in human coronary arteries and analyse correlation with severity of atherosclerosis and clarify the interactions between proteins and possible mechanisms of atherosclerosis. 40 human coronary artery specimens were employed. The atherosclerotic lesions were characterized by Haematoxylin and Eosin (H&E) staining. The expression of prostaglandin-endoperoxide synthase 2 (PTGS2), anti-acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), caspase-1, and NOD-like receptor protein 3 (NLRP3) were analysed by immunohistochemical assay. Correlations between expression of proteins and severity of atherosclerosis were assessed using Spearman correlation analysis. Bioinformatic and coexpression analyses were performed to study the possible pathways and interactions. In the present study, PTGS2, ACSL4, caspase-1, and NLRP3, were upregulated, while GPX4 was downregulated in the advanced stages of atherosclerosis. The severity of atherosclerosis was positively associated with the expression of PTGS2, ACSL4, caspase-1, and NLRP3 and negatively associated with the expression of GPX4. Biological processes of lipid metabolism and inflammation and C-type lectin receptor signaling pathway were enriched. The five proteins interacted with each other directly or indirectly and PTGS2 might be the hub gene of atherosclerosis. Ferroptosis and pyroptosis may regulate the occurrence and development of atherosclerosis. These findings may shed light on new ideas and potential targets for the prevention and treatment of coronary artery atherosclerosis and the proteins may be used as biomarkers for the severity of atherosclerosis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.05.009DOI Listing
August 2021

Lung Stereotactic Body Radiotherapy (SBRT) Using Spot-Scanning Proton Arc (SPArc) Therapy: A Feasibility Study.

Front Oncol 2021 22;11:664455. Epub 2021 Apr 22.

Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States.

Purpose: We developed a 4D interplay effect model to quantitatively evaluate breathing-induced interplay effects and assess the feasibility of utilizing spot-scanning proton arc (SPArc) therapy for hypo-fractionated lung stereotactic body radiotherapy (SBRT). The model was then validated by retrospective application to clinical cases.

Materials And Methods: A digital lung 4DCT phantoms was used to mimic targets in diameter of 3cm with breathing motion amplitudes: 5, 10, 15, and 20 mm, respectively. Two planning groups based on robust optimization were generated: (1) Two-field Intensity Modulated Proton Therapy (IMPT) plans and (2) SPArc plans a partial arc. 5,000 cGy relative biological effectiveness (RBE) was prescribed to the internal target volume (ITV) in five fractions. To quantitatively assess the breathing induced interplay effect, the 4D dynamic dose was calculated by synchronizing the breathing pattern with the simulated proton machine delivery sequence, including IMPT, Volumetric repainting (IMPT), iso-layered repainting (IMPT) and SPArc. Ten lung patients' 4DCT previously treated with VMAT SBRT, were used to validate the digital lung tumor model. Normal tissue complicated probability (NTCP) of chestwall toxicity was calculated.

Result: Target dose were degraded as the tumor motion amplitude increased. The 4D interplay effect phantom model indicated that motion mitigation effectiveness using SPArc was about five times of IMPT or IMPT using maximum MU/spot as 0.5 MU at 20 mm motion amplitude. The retrospective study showed that SPArc has an advantage in normal tissue sparing. The probability of chestwall's toxicity were significantly improved from 40.2 ± 29.0% (VMAT) (p = 0.01) and 16.3 ± 12.0% (IMPT) (p = 0.01) to 10.1 ± 5.4% (SPArc). SPArc could play a significant role in the interplay effect mitigation with breathing-induced motion more than 20 mm, where the target D99 of 4D dynamic dose for patient #10 was improved from 4,514 ± 138 cGy [RBE] (IMPT) vs. 4,755 ± 129 cGy [RBE] (SPArc) (p = 0.01).

Conclusion: SPArc effectively mitigated the interplay effect for proton lung SBRT compared to IMPT with repainting and was associated with normal tissue sparing. This technology may make delivery of proton SBRT more technically feasible and less complex with fewer concerns over underdosing the target compared to other proton therapy techniques.
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http://dx.doi.org/10.3389/fonc.2021.664455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100671PMC
April 2021
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