Publications by authors named "Xiaodong Wu"

387 Publications

Spatiotemporal variations and regional differences in air temperature in the permafrost regions in the Northern Hemisphere during 1980-2018.

Sci Total Environ 2021 Jun 8;791:148358. Epub 2021 Jun 8.

Cryosphere Research Station on Qinghai-Xizang Plateau, State Key Laboratory of Cryospheric Sciences, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China.

Surface air temperature is an important factor for the permafrost thermal state in the Northern Hemisphere. It is therefore necessary to understand the variations and regional differences in air temperature to determine the interactions between permafrost degradation and climate change. In this study, we used observational data from the National Centers for Environmental Information, the China Meteorological Administration, and the World Data Centre for Meteorology to quantitatively analyze the variations and regional differences in air temperature from 1980 to 2018. The results demonstrated that the annual mean air temperatures were low in continuous permafrost regions and high in sporadic and isolated permafrost regions, with a significant warming rate of 0.371 ± 0.086 °C/decade. Air temperatures warmed the slowest during the winter and fastest during the spring, and no "warming hiatus" was observed in the permafrost regions of the Northern Hemisphere. The spatial patterns of freezing degree-days (FDDs) and thawing degree-days (TDDs) had different spatial characteristics. The decreasing rate of FDDs was -6.97 °C·days/year, while the increasing rate of TDDs was 6.4 °C·days/year. The air temperatures and warming trends had largely regional differences with respect to high latitude, transitional, and high altitude permafrost regions. Air temperature and its warming trend was the highest in high altitude regions. In addition, air temperature warming trends gradually decreased from the continuous permafrost zone to the island permafrost zone. The FDDs had a significant decreasing trend from the continuous permafrost zone to the island permafrost zone, whereas TDDs exhibited the opposite trend. The results indicate that the air temperature warming rate in the permafrost regions was approximately 2.0 times that of the global warming rate, and 1.3 times the global land warming rate from 1980 to 2018. These findings offer a perspective on the differences in permafrost and its thermal state across different regions under climate change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.148358DOI Listing
June 2021

Usefulness of F-FDG PET/CT in treatment-naive patients with thymic squamous cell carcinoma.

Ann Nucl Med 2021 Jun 8. Epub 2021 Jun 8.

Department of Nuclear Medicine, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai, 200433, China.

Objective: Thymic squamous cell carcinoma (TSCC) is very rare. This study aims to investigate the clinical utility of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in treatment-naive patients with TSCC.

Methods: The tumor metabolic parameters of F-FDG PET/CT, including maximum standard uptake value (SUVmax), metabolic tumor volume of primary lesion (MTV-P) and combination of primary lesion and metastases (MTV-C), and total lesion glycolysis of primary lesion (TLG-P) and combination of primary lesion and metastases (TLG-C) were collected. Age, sex, smoking, serum tumor markers, tumor size, Masaoka-Koga stage, TNM stage, contrast-enhanced CT scan, and tumor immunity were also reviewed. Moreover, progression-free survival (PFS) and overall survival (OS) of these patients were analyzed.

Results: Forty-two treatment-naive patients with TSCC were enrolled in this study. All primary tumors were FDG-avid with the average SUVmax of 10.0 ± 4.5 (range, 1.5-20.4). Higher SUVmax, MTV-C, and TLG-C were observed in advanced Masaoka-Koga stage than early stage, and higher SUVmax was found in advanced TNM stage than early stage. Next, 36 out of 42 patients performed chest contrast-enhanced CT scan, which showed SUVmax associated with the enhancement degree of CT. Moreover, 27 out of 42 lesions were assessed tumor immunity, and the detective rates of PD-L1, PD-1, CD4, CD8, and Foxp3 were 59.3%, 37.0%, 59.3%, 100%, and 77.8%, respectively. Higher SUVmax was observed in lesions with lower CD4-positive tumor-infiltrating lymphocytes. Furthermore, 12- and 24-month PFS and OS rates were 62.0% vs 32.8% and 84.5% vs 68.9%, respectively. Multivariate Cox regression analysis showed that only MTV-C was an independent predictor of PFS.

Conclusion: F-FDG PET/CT is useful in evaluating tumor staging, assessing CT enhancement degree, and detecting tumor immunity of TSCC before treatment. F-FDG PET/CT could also be a promising tool to provide prognostic information for treatment-naive patients with TSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12149-021-01640-5DOI Listing
June 2021

Shear stress and ROS-responsive biomimetic micelles for atherosclerosis via ROS consumption.

Mater Sci Eng C Mater Biol Appl 2021 Jul 4;126:112164. Epub 2021 May 4.

Key Laboratory of Special Engineering Plastics Ministry of Education, College of Chemistry, Jilin University, Changchun 130012, China. Electronic address:

Reactive oxygen species (ROS) are well-known important initiating factors required for atherosclerosis formation, which leads to endothelial dysfunction and plaque formation. Most of the existing antithrombotic therapies use ROS-responsive drug delivery systems, which have a certain therapeutic effect but cannot eliminate excess ROS. Therefore, the atherosclerosis cannot be treated from the source. Moreover, nanoparticles are easily cleared by the immune system during blood circulation, which is not conducive to long-term circulation. In this study, we developed an intelligent response system that could simultaneously respond to ROS and the shear stress microenvironment of atherosclerotic plaques. This system was formed by red blood cells (RBCs) and simvastatin-loaded micelles (SV MC). The micelles consisted of poly(glycidyl methacrylate)-polypropylene sulfide (PGED-PPS). The hydrophobic PPS could react with excess ROS to become hydrophilic, which forced the micelle rupture, resulting in drug release. Most importantly, PPS could also significantly deplete the ROS level, realizing the synergistic treatment of atherosclerosis with drugs and materials. The positively charged SV MC and negatively charged RBCs were self-assembled through electrostatic adsorption to obtain SV [email protected] The SV [email protected] could respond to the high shear stress at the atherosclerotic plaque, and the shear stress induced SV MC desorption from the RBC surface. Using biomimetic methods to evade the SV [email protected] elimination by the immune system and to reduce the ROS plays a vital role in improving atherosclerosis treatment. The results of in vitro and in vivo experiments showed that SV [email protected] could effectively treat atherosclerosis. Moreover, not only does the SV [email protected] system avoid the risk of bleeding, but it also has excellent in vivo safety. The study results indicate that the SV [email protected] system is a promising therapeutic nanomedicine for treating ROS-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112164DOI Listing
July 2021

LncRNA CPhar Induces Cardiac Physiological Hypertrophy and Promotes Functional Recovery After Myocardial Ischemia-Reperfusion Injury.

Circulation 2021 May 21. Epub 2021 May 21.

Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai 200444, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.

Exercise training's benefits in cardiovascular system have been well accepted, however, the underlying mechanism remains to be explored. Here, we report the initial functional characterization of an exercise-induced cardiac physiological hypertrophy associated novel lncRNA. Using lncRNA microarray profiling, we identified lncRNAs in contributing the modulation of exercise-induced cardiac growth that we termed Cardiac Physiological hypertrophy associated regulator (CPhar). Mice with Adeno-associated virus serotype 9 (AAV9) driving CPhar overexpression and knockdown were used in experiments. Swim training was used to induce physiological cardiac hypertrophy in mice and ischemia reperfusion injury (IR/I) surgery was conducted to investigate the protective effects of CPhar in mice. To investigate the mechanisms of CPhar's function, we performed various analysis including RTqPCR, western blot, histology, cardiac function (by echocardiography), functional rescue experiments, mass spectrometry, RNA transcription, RNA pull down, RNA immunoprecipitation, chromatin immunoprecipitation assay, luciferase reporter assay, and coimmunoprecipitation assays. We screened the lncRNAs in contributing the modulation of exercise-induced cardiac growth via lncRNA microarray profiling and found that CPhar was increased with exercise and was necessary for exercise-induced physiological cardiac growth. Gain- and loss- of function of CPhar regulated the expression of proliferation markers, hypertrophy, and apoptosis in cultured neonatal mouse cardiomyocytes (NMCMs). Overexpression of CPhar prevented myocardial ischemia reperfusion injury and cardiac dysfunction . We identified DDX17 as a binding partner of CPhar in regulating CPhar downstream factor ATF7 by sequestering C/EBPβ. Our study of this lncRNA CPhar provides new insights into the regulation of exercise-induced cardiac physiological growth, demonstrating the cardioprotective role of CPhar in the heart, as well as expanding our mechanistic understanding of lncRNA function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050446DOI Listing
May 2021

Structures and catalytic performances of Me/SAPO-34 (Me = Mn, Ni, Co) catalysts for low-tem perature SCR of NO by ammonia.

J Environ Sci (China) 2021 Jun 18;104:137-149. Epub 2020 Dec 18.

Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China. Electronic address:

Me/SAPO-34 (Me = Mn, Ni, Co) series of catalysts were prepared by a wetness impregnation method and investigated for the selective catalytic reduction of nitrogen oxides with ammonia (NH-SCR). Among them, Mn/SAPO-34 catalyst was found as the most promising candidate based on its superior low-temperature activity. The catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy images (TEM), nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), temperature programmed reduction and desorption (TPR and TPD), and diffuse reflectance infrared Fourier transformed spectroscopy (DRIFTS) of NH/NO adsorption. Mn/SAPO-34 is obviously different from Ni/SAPO-34 and Co/SAPO-34 in the active species state and distribution. Surface MnO species which play an essential role in NO oxidation and NO adsorption, act as better active sites than nickel and cobalt mostly in the form of the aluminates and silicates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jes.2020.11.018DOI Listing
June 2021

The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies.

Front Cell Dev Biol 2021 22;9:650772. Epub 2021 Apr 22.

R&D Dept, Shanghai Proton and Heavy Ion Center (SPHIC), Shanghai, China.

Resistance to therapy is the major hurdle in the current cancer management. Cancer cells often rewire their cellular process to alternate mechanisms to resist the deleterious effect mounted by different therapeutic approaches. The major signaling pathways involved in the developmental process, such as Notch, Hedgehog, and Wnt, play a vital role in development, tumorigenesis, and also in the resistance to the various anticancer therapies. Understanding how cancer utilizes these developmental pathways in acquiring the resistance to the multi-therapeutic approach cancer can give rise to a new insight of the anti-therapy resistance mechanisms, which can be explored for the development of a novel therapeutic approach. We present a brief overview of Notch, Hedgehog, and Wnt signaling pathways in cancer and its role in providing resistance to various cancer treatment modalities such as chemotherapy, radiotherapy, molecular targeted therapy, and immunotherapy. Understanding the importance of these molecular networks will provide a rational basis for novel and safer combined anticancer therapeutic approaches for the improvement of cancer treatment by overcoming drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.650772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100510PMC
April 2021

Sheathless microflow cytometer utilizing two bulk standing acoustic waves.

Cytometry A 2021 May 6. Epub 2021 May 6.

School of Biomedical Engineering(Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Suzhou, Jiangsu, China.

In recent years, microflow cytometry has become a popular research field because of its potential to provide low-cost and disposable chips for complex cell analyses. Herein, we demonstrate a sheathless microflow cytometer which integrates a bulk standing acoustic wave based microchip capable of three dimensional cell focusing. Flow cytometry was successfully demonstrated using this system with a coefficient of variation (CV) of 2.16% with standard calibration beads. The sensitivities calibrated by rainbow beads are 518 MEFL in fluorescein Isothiocyanate (FITC) channel and 264 MEPE in P-phycoerythrin (PE) channels, respectively. The linearities are more than 99% in both channels. The capability of the proposed microflow cytometer is further demonstrated by immunologically labeled leukocytes differentiation in blood. This acoustic-based microflow cytometer did not require any sheath flows or complex structures and can be mass produced. Because of the simple fluid channel, the chip can be easily made pipeless, disposable for applications requiring no cross contamination. Moreover, with the gentle and bio-compatible acoustic waves used, this technique is expected to maintain the viability of cells and other bioparticles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cyto.a.24362DOI Listing
May 2021

Activity strategy and pattern of the Siberian jerboa () in the Alxa desert region, China.

PeerJ 2021 10;9:e10996. Epub 2021 Mar 10.

College of Grassland, Resources and Environment, Inner Mongolia Agricultural University, Hohhot, China.

Rodents exhibit seasonal changes in their activity patterns as an essential survival strategy. We studied the activity patterns and strategies of the Siberian jerboa () in the Alxa desert region to better understand the habitats and behavioural ecology of xeric rodents. We conducted an experiment using three plots to monitor the duration, time, and frequency of the active period of the Siberian jerboa using infrared cameras in the Alxa field workstation, Inner Mongolia, China in 2017. The relationships between the activity time and frequency, biological factors (perceived predation risk, food resources, and species composition), and abiotic factors (temperature, air moisture, wind speed) were analysed using Redundancy Analysis (RDA). Our results showed that: (1) relative humidity mainly affected activities in the springtime; temperature, relative humidity and interspecific competition mainly affected activities in the summertime; relative humidity and perceived predation risk mainly influenced activities in the autumn. (2) The activity pattern of the Siberian jerboa altered depending on the season. The activity of the Siberian jerboa was found to be bimodal in spring and summer, and was trimodal in autumn. The activity time and frequency in autumn were significantly lower than the spring. (3) Animals possess the ability to integrate disparate sources of information about danger to optimize energy gain. The jerboa adapted different responses to predation risks and competition in different seasons according to the demand for food resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.10996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955674PMC
March 2021

Optimal design of a driver of interdigital transducers used to generate standing surface acoustic waves for cell sorting.

Rev Sci Instrum 2021 Mar;92(3):034705

University of Sciences and Technology of China, Hefei, Anhui 230026, China.

A compact driver based on current feedback amplifiers is designed to drive interdigital transducers (IDTs) that generate standing surface acoustic waves for cell sorting. Compared with commercial RF amplifiers, this driver can be used to drive a wider range of loads without impedance matching. Furthermore, the driver works in a switch mode triggered by target cells, which significantly reduces power consumption in the system. A Butterworth-Van Dyke equivalent circuit was fabricated to study the electrical characteristics of the IDTs, and the driver was designed and optimized by circuit simulations. A cell sorter was constructed and tested experimentally to demonstrate that the driver meets sorting requirements. The driver allows the cell sorter to extract rare cells while otherwise consuming low power.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0036856DOI Listing
March 2021

Unlocking the ultrafast potential of gold nanowires for mode-locking in the mid-infrared region.

Opt Lett 2021 Apr;46(7):1562-1565

In this Letter, we present the mode-locking operation of a 2.87 µm / codoped fluoride fiber laser, helped by the ultrafast nonlinear optical absorption behavior of gold nanowires (GNWs). The mode locker is fabricated by depositing the GNW solution onto a silver mirror. It has a modulation depth of 14.2%, a saturation intensity of 26.2/, and a non-saturation loss of 29.9% at 2.87 µm. With an increased pump power, the laser operates in -switched mode-locking, fundamental mode-locking, and harmonic mode-locking (HML) states. This represents the first, to our knowledge, mid-infrared mode-locked laser using gold nanomaterials. Additionally, the HML is also the first observation in a laser in this band using material saturable absorbers, implying the capability of GNWs for high repetition rate generation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.419060DOI Listing
April 2021

Association of body mass index with severity and mortality of COVID-19 pneumonia: a two-center, retrospective cohort study from Wuhan, China.

Aging (Albany NY) 2021 03 24;13(6):7767-7780. Epub 2021 Mar 24.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

In this study, we aimed to investigate the relationship between body mass index (BMI) and multiple severe outcomes of the coronavirus disease 2019 (COVID-19) pneumonia. A total of 1091 patients hospitalized with COVID-19 pneumonia were included from Wuhan, China. Overall, 2.8% (n = 31) received invasive mechanical ventilation (IMV), 10.8% (n = 118) were admitted to the intensive care unit (ICU), 6.4% (n = 70) developed acute respiratory distress syndrome (ARDS), and 4.4% (n = 48) died. Multivariable-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of IMV therapy, ICU admission and ARDS associated with obesity were 2.86 (1.16-7.05), 2.62 (1.52-4.49) and 3.15 (1.69-5.88), respectively; underweight was significantly associated with death (HR 3.85, 95%CI 1.26-11.76). Restricted cubic spline analyses suggested U-shaped associations of BMI with ICU admission and death, but linear relationships of BMI with IMV therapy and ARDS. In conclusion, obesity had an increased risk of IMV therapy, ICU admission and ARDS, while underweight was associated with higher mortality in COVID-19 pneumonia. U-shaped associations of BMI with ICU admission and death, and linear relationships of BMI with IMV therapy and ARDS, were found. These findings indicate that extra caution should be taken when treating COVID-19 patients with underweight and obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034951PMC
March 2021

Study on soliton self-frequency shift in a Tm-doped fiber amplifier seeded by a Kelly-sideband-suppressed conventional soliton.

Opt Express 2021 Mar;29(5):6553-6562

We experimentally present mid-infrared Raman soliton self-frequency shift (SSFS) process in a Tm-doped fiber amplifier using sideband-suppressed conventional solitons as seed pulses. The strong Kelly sidebands of the soliton oscillator were efficiently suppressed (more than 21 dB) using a home-made all-fiber Lyot filter (AFLF). As a result, the Raman solitons with a continuously tunable wavelength of 1.95-2.34 µm were achieved, with a high soliton energy conversion of >93% over the range of 1.95-2.24 µm. The conversion efficiency and tunable range of Raman solitons were both significantly improved, comparing to the same amplifier seeded with sideband-unsuppressed pulses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.412345DOI Listing
March 2021

Risk assessment of potential thaw settlement hazard in the permafrost regions of Qinghai-Tibet Plateau.

Sci Total Environ 2021 Jul 20;776:145855. Epub 2021 Feb 20.

Cryosphere Research Station on the Qinghai-Tibet Plateau, State Key Laboratory of Cryospheric Science, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China.

Climate warming could exacerbate the occurrence of thaw settlement hazard in the permafrost regions of the Qinghai-Tibet Plateau (QTP), which would threaten the stability of engineering infrastructure in cold regions. The risk associated with permafrost settlement, valuable for the regional sustainable development, remains poorly assessed or understood on the QTP. In this study, three common Geo-hazard indices were used to assess the settlement risks in the permafrost regions of the QTP, including the settlement index, the risk zonation index, and the allowable bearing capacity index. However, large spatial differences existed in simulating the risk maps by using the abovementioned Geo-hazard indices. Hence, we developed a combined index (I) by integrating the three indices to reduce the uncertainty of the simulations. The results indicated that the ground ice is a critical factor for assessing the settlement risk in permafrost regions. We also applied the I to assess the settlement risk along the Qinghai-Tibet Railway (QTR). The proportion of low-risk area along the QTR would be the highest (45.38%) for the future periods 2061-2080 under Representative Concentration Pathway 4.5. The medium-risk area combined with the high-risk area would be accounted for more than 40%, which were located at the boundary of the present permafrost regions. Therefore, the corresponding adaptation measures should be taken to reduce the potential economic losses caused by the high-risk regions to the infrastructure. Overall, the results would present valuable references for engineering design, construction and maintenance, and provide insights for early warning and prevention of permafrost thaw settlement hazard on the QTP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.145855DOI Listing
July 2021

Combined High-Dose LATTICE Radiation Therapy and Immune Checkpoint Blockade for Advanced Bulky Tumors: The Concept and a Case Report.

Front Oncol 2020 12;10:548132. Epub 2021 Feb 12.

Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China.

Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. Since only a small fraction of the tumor volume receive high dose in a SFRT treatment, even with the anticipated bystander effects, total tumor eradications are rare. Backed by the evidence of immune activation of high dose radiation, it is logical to postulate that the combination of High-Dose LATTICE radiation therapy (HDLRT) with immune checkpoint blockade would be effective and could subsequently lead to improved local tumor control without added toxicities, through augmenting the effects of radiation in-situ vaccine and T-cell priming. We herein present a case of non-small cell lung cancer (NSCLC) with multiple metastases. The patient received various types of palliative radiation treatments with combined chemotherapies and immunotherapies to multiple lesions. One of the metastatic lesions measuring 63.2 cc was treated with HDLRT combined with anti-PD1 immunotherapy. The metastatic mass regressed 77.84% over one month after the treatment, and had a complete local response (CR) five months after the treatment. No treatment-related side effects were observed during the follow-up exams. None of the other lesions receiving palliative treatments achieved CR. The dramatic differential outcome of this case lends support to the aforementioned postulate and prompts for further systemic clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.548132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907519PMC
February 2021

18F-FDG PET/CT and circulating tumor cells in treatment-naive patients with non-small-cell lung cancer.

Eur J Nucl Med Mol Imaging 2021 Feb 25. Epub 2021 Feb 25.

Department of Nuclear Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai, 200433, China.

Purpose: This study retrospectively investigated the clinical utility of 2-deoxy-18F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) in the diagnosis and prognosis of treatment-naive patients with non-small-cell lung cancer (NSCLC).

Methods: The blood samples of treatment-naive patients with NSCLC were collected for CTCs detection, and the tumor metabolic parameters of F-FDG PET/CT, including maximum standard uptake value (SUVmax), metabolic tumor volume of primary lesion (MTV-P) and combination of primary lesion and metastases (MTV-C), and total lesion glycolysis of primary lesion (TLG-P) and combination of primary lesion and metastases (TLG-C), were analyzed. Age, sex, smoking, serum tumor markers, tumor size, location, TNM stage, and genetic mutations were also reviewed. Moreover, progression-free survival (PFS) and overall survival (OS) of these patients were analyzed.

Results: A total of 309 patients with NSCLC (200 men, 109 women; mean age: 61 ± 9 years) were enrolled in this study, including 217 patients with adenocarcinoma and 92 with squamous cell carcinoma. Of the 309 cases, 11 were misdiagnosed with benign diseases by F-FDG PET/CT. CTCs positivity was detected in 234 cases. The sensitivity of F-FDG PET/CT and CTCs in NSCLC were 96.4% and 75.7%, respectively. SUVmax, MTV-P, TLG-P, MTV-C, TLG-C, tumor size, and serum CYFRA211 levels were significantly higher in CTCs positive group than negative group; and advanced TNM stage, squamous cell carcinoma, and EGFR wild type presented higher CTCs positivity. Multivariate logistic regression analysis revealed that SUVmax was significantly associated with CTCs positivity. Multivariate cox regression analysis showed that TLG-P, TLG-C, and CTCs were independent predictors of PFS in patients with NSCLC, and TLG-C and CTCs were independent predictors of OS.

Conclusions: F-FDG PET/CT was superior to CTCs in the diagnosis of treatment-naive patients with NSCLC. The levels of CTCs in the peripheral blood were associated with tumor glucose metabolism in NSCLC. Metabolic parameters of F-FDG PET/CT and CTCs could separately predict the outcomes of treatment-naive patients with NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-021-05260-zDOI Listing
February 2021

Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1.

Front Chem 2020 2;8:625437. Epub 2021 Feb 2.

Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.

Rac1 is a small signaling protein, which belongs to the Rho subfamily of Ras superfamily. It is activated by binding GTP and inactivated by exchanging GDP for GTP. The ability of nucleotide exchange depends on guanine nucleotide exchange factors (GEFs) family proteins. T-lymphoma invasion and metastasis factor 1 (Tiam1) is a member of GEFs. Rac1 participates in multiple signaling pathways and regulates various cellular events by interacting with GEFs. Particularly, it is involved in the development and progression of various kinds of tumors. In this paper, we have studied the detailed interaction between Rac1 and Tiam1. Seven residues on Rac1 are predicted to be important for the interaction with Tiam1, i.e. E31, Y32, D38, N39, Y64, D65 and W56. All these residues are located on the switch 1 and 2 domains which are the interface between Rac1 and Tiam1, except W56. In addition, we analyzed how inhibitor NSC23766 interacts with Rac1. Our docking results show that NSC23766 binds to the same region as Tiam1. Several residues, i.e. F37, D38, N39, W56, Y64, L67, L70 and S71, contribute much to binding free energy. These findings are very useful for the structure-based design of inhibitors toward Rac1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2020.625437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884829PMC
February 2021

ROS-Sensitive Nanoparticles Co-delivering Dexamethasone and CDMP-1 for the Treatment of Osteoarthritis Through Chondrogenic Differentiation Induction and Inflammation Inhibition.

Front Bioeng Biotechnol 2021 28;9:608150. Epub 2021 Jan 28.

Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou, China.

Osteoarthritis (OA) is a common subtype of arthritis. To date, treatment of OA focuses primarily on alleviating pain and improving joint function. The lack of a vascular system within synovial joints and the rapid removal of agents due to synovial exchange hinder continuous delivery of OA drugs. However, these obstacles are being addressed by promising nanoscale drugs. We synthesize and assemble a hydrogen peroxide [HO, belongs to the category of active oxygen species (ROS)]-sensitive nanomicelle, which is loaded with the anti-inflammation drug dexamethasone and chondrogenic differentiation factor cartilage-derivedmor-phogeneticprotein-1. The micelle can induce bone marrow mesenchymal stem cells to repair cartilage while inhibiting joint inflammation. The prepared nanoparticles were of uniform size and displayed an obvious core-shell structure. Under HO stimulation, the shell layer could be removed gradually. The drug-loaded micelle effectively inhibited proliferation of activated macrophages, induced macrophage apoptosis with an anti-inflammatory effect, and caused the BMSCs to differentiate into chondrocytes. This work provides an experimental and theoretical basis for further development of a drug-loaded micelle in the healing of osteoarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2021.608150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876336PMC
January 2021

RIP3 facilitates necroptosis through CaMKII and AIF after intracerebral hemorrhage in mice.

Neurosci Lett 2021 04 1;749:135699. Epub 2021 Feb 1.

Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes, Wannan Medical College, Wuhu, 241001, Anhui, China; Non-coding RNA Research Center of Wannan Medical College, Wuhu, 241001, Anhui, China. Electronic address:

Background: Necroptosis-induced neuronal damage after intracerebral hemorrhage (ICH) has been documented recently. Previous studies have reported that RIP3 and its complex are recognized as central mediators of necroptosis. In this study, the role of RIP3 in the activation of CaMKII and AIF was investigated.

Methods: We induced ICH in C57BL/6 mice by injecting collagenase IV into the basal ganglia. ICH mice were pretreated with the mPTP inhibitor CsA and the CAMKII inhibitor Kn-93, RIP3 siRNA or RIP3 rAAV. Brain edema and neurobehavior were evaluated. The expression of RIP3, p-MLKL, AIF, and CaMKII proteins was evaluated by western blotting, immunofluorescence (IF) and immunoprecipitation (IP).

Results: Significant increases in RIP3, p-MLKL, CaMKII and AIF expression were observed in ICH mice, and RIP3-AIF colocalized in the nucleus. Overexpression of RIP3 by rAAV upregulated AIF expression in both the cytoplasm and nucleus, while CaMKII expression was increased in the cytoplasm. The interaction of RIP3-AIF and RIP3-CaMKII was detected after ICH injury. These complexes were inhibited by CsA with Kn-93 or RIP3 siRNA pretreatment, which reduced brain edema and neurological deficits.

Conclusions: Our findings revealed that ICH induced necroptotic neuronal death through the RIP3-CaMKII complex and the RIP3-AIF signaling pathway. Moreover, blockade of mPTP opening could suppress the pathogenesis of necroptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2021.135699DOI Listing
April 2021

Carbon ion triggered immunogenic necroptosis of nasopharyngeal carcinoma cells involving necroptotic inhibitor BCL-x.

J Cancer 2021 1;12(5):1520-1530. Epub 2021 Jan 1.

Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China.

To explore the potential and mechanisms of necroptosis, a form of immunogenic cell death, induced by carbon ion as compared to photon beams in established photon resistant- (PR-) and sensitive nasopharyngeal carcinoma (NPC) cells. MLKL is considered a central executor of necroptosis and phosphorylation of MLKL (p-MLKL) was a critical event of necroptosis. The clonogenic survival and DNA microarray demonstrated that after repeated photon irradiation, radiosensitive NPC cells became apoptosis-resistant but could be effectively inhibited by carbon ion irradiation. The relative biologic effectiveness (RBE) at D10 and D37 were 2.15 and 2.78 for PR-NPC cells. Carbon ion induced delayed DNA damage repair, cell cycle arrest, cytogenetic damage, morphological change and cell necrosis, indicating the possibility of necroptosis in both PR- and sensitive NPC cell types. The lower expression of necroptotic inhibitors (caspase-8 and Bcl-x) and higher level of MLKL in PR-NPC cells showed it was relatively more predisposed to necroptosis compared to the sensitive cells. Subsequent experiments demonstrated the significant upregulation of p-MLKL in the PR-NPC cells treated by carbon ion (4 Gy) compared with photon irradiation at both physical (4 Gy) and RBE (10 Gy) doses (P≤0.0001). Moreover, carbon ion induced a robust (up to 28 folds) p-MLKL in the PR-NPC cells as well as sensitive cells (up to 6-fold) coupled with a lower level of BCL-x expression and increased GM-CSF implicated in resculputure of immune system. These results suggested that carbon ion could induce necroptosis of NPC cells, especially in PR-NPC cells, and its mechanisms involve BCL-x.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.46316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847655PMC
January 2021

A colloidal gold test strip assay for the detection of African swine fever virus based on two monoclonal antibodies against P30.

Arch Virol 2021 Mar 26;166(3):871-879. Epub 2021 Jan 26.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China.

African swine fever (ASF), caused by African swine fever virus (ASFV), was first reported in Kenya in 1921, but an effective vaccine or antiviral drug is still not available for ASFV control. Rapid and effective diagnostics are key steps in managing ASF. We generated two monoclonal antibodies (MAbs) against the ASFV phosphoprotein P30 and designated these as 3H7A7 and 6H9A10. Epitope mapping revealed that MAb 3H7A7 and 6H9A10 recognized aa 144-154 and aa 12-18 of P30, respectively. A signal-amplified sandwich colloidal gold test strip for rapid detection of ASFV was developed based using these MAbs. Sensitivity and specificity analysis showed that the detection limit of the strip was 2.16 ng of P30. The strip only reacted with ASFV and did not react with other common porcine viruses. In detection tests using 153 clinical field samples including sera, plasma, anticoagulant-treated blood, and tissue, the strip had 95.42% concordance with real-time PCR. The new MAbs specific for P30 and the rapid colloidal gold test strip helped to reveal novel B cell epitopes in P30 and provide an efficient diagnostic test for on-site clinical detection of ASF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-020-04915-wDOI Listing
March 2021

Quasi- quantification of Cu(II) ions in Cu-SSZ-13 catalyst by an NH temperature-programmed reduction method.

Chem Commun (Camb) 2021 Feb;57(15):1891-1894

The Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China. and Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.

A quasi-operando NH3 temperature-programmed reduction method (NH3-TPR), with N2:Cu = 1:1, is developed to quantify total Cu(ii) ions in Cu-SSZ-13 quenched from SCR-relevant reactions, and its accuracy is confirmed by in situ EPR. [Cu(OH)]+-Z and Cu2+-2Z can be further distinguished by NH3 reduction temperatures, and their different reducibility in SCR is revealed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc07346fDOI Listing
February 2021

Variations of Concentration Characteristics of Rainfall Runoff Pollutants in Typical Urban Living Areas.

Bull Environ Contam Toxicol 2021 Apr 25;106(4):608-613. Epub 2021 Jan 25.

School of Environment and Surveying Engineering, Suzhou University, Suzhou City, 234000, China.

Based on a typical residential area, this paper studies the characteristics of pollutant concentration changes in two rainfall runoffs and the first flush effect of rainfall. In rainfall runoff, the concentrations of seven pollutants (COD, TN, DTN, NH-N, TP, DTP, and PO) increased during the initial rainfall period and decreased in the later period. Rainfall causes the erosion of pollutants on the underlying surface so that water pollution begins when rainfall runoff occurs, and the pollution level drops over time. The seven pollutants all experience this first flush effect, of which, rainfall has the strongest scouring effect on NH-N produced by domestic sewage. The significant excess of pollutants in rainfall runoff should be considered by management departments. In addition, the existence of the first flush effect makes it possible in theory to partially intercept rainfall runoff to control water pollution, thereby reducing the cost of pollution control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00128-021-03110-0DOI Listing
April 2021

Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.

BMC Med 2021 01 21;19(1):23. Epub 2021 Jan 21.

Department of Acute Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification.

Methods: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models.

Results: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites.

Conclusions: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12916-020-01893-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817348PMC
January 2021

Optimized Nanointerface Engineering of Micro/Nanostructured Titanium Implants to Enhance Cell-Nanotopography Interactions and Osseointegration.

ACS Biomater Sci Eng 2020 02 23;6(2):969-983. Epub 2020 Jan 23.

Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P. R. China.

The success of orthopedic implants requires rapid and complete osseointegration which relies on an implant surface with optimal features. To enhance cellular function in response to the implant surface, micro- and nanoscale topography have been suggested as essential. The aim of this study was to identify an optimized Ti nanostructure and to introduce it onto a titanium plasma-sprayed titanium implant (denoted NTPS-Ti) to confer enhanced immunomodulatory properties for optimal osseointegration. To this end, three types of titania nanostructures, namely, nanowires, nanonests, and nanoflakes, were achieved on hydrothermally prepared Ti substrates. The nanowire surface modulated protein conformation and directed integrin binding and specificity in such a way as to augment the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and induce a desirable osteoimmune response of RAW264.7 macrophages. In a coculture system, BMSCs on the optimized micro/nanosurface exerted enhanced effects on nonactivated or lipopolysaccharide-stimulated macrophages, causing them to adopt a less inflammatory macrophage profile. The enhanced immunomodulatory properties of BMSCs grown on NTPS-Ti depended on a ROCK-medicated cyclooxygenase-2 (COX2) pathway to increase prostaglandin E2 (PGE2) production, as evidenced by decreased production of PGE2 and concurrent inhibition of immunomodulatory properties after treatment with ROCK or COX2 inhibitors. evaluation showed that the NTPS-Ti implant resulted in enhanced osseointegration compared with the TPS-Ti and Ti implants. The results obtained in our study may provide a prospective approach for enhancing osseointegration and supporting the application of micro/nanostructured Ti implants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsbiomaterials.9b01717DOI Listing
February 2020

Reducing human activity promotes environmental restoration in arid and semi-arid regions: A case study in Northwest China.

Sci Total Environ 2021 May 7;768:144525. Epub 2021 Jan 7.

Cryosphere Research Station on the Qinghai-Tibet Plateau, State Key Laboratory of Cryospheric Science, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Science, Lanzhou 730070, China; University of Chinese Academy Sciences, Beijing 100049, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), 511458, China.

Human activities have adversely impacted grassland net primary productivity (NPP) across the world, and quantitative estimations of the anthropogenic impacts on NPP (HNPP) can be helpful to improve environmental protection and climate adaptation measures. However, disentangling the effects of climate variability and human activities on NPP is problematic and requires the calculation of potential net primary productivity (PNPP). In this study, we assessed the anthropogenic impacts on NPP in the Shiyang River basin-a typical arid and semi-arid region. We used the seasonal changes in NPP to identify the grids that were not affected by human activity and then proposed a method to calculate PNPP based on the leaf area index (LAI). We estimated the actual net primary productivity (ANPP) using the Carnegie-Ames-Stanford Approach (CASA) model, and the HNPP was then calculated as the difference between ANPP and PNPP. Our results showed that this method for PNPP calculation was reliable. From 2001 to 2016, the positive (90.85 gC·m·a) and negative effects (-130.21 gC·m·a) of human activities on NPP accounted for 32.68% and 46.84% of the ANPP, respectively, and the overall average HNPP was -39.36 g C·m·a. The implementation of ecological and environmental protection projects gradually mitigated the negative effects of human activity on NPP at a rate of 4.55 gC·m·a; however, negative HNPP values still occupied 55.39% of the entire region in 2016. In contrast with the prevailing views that climate change is the main factor accounting for vegetation recovery in arid and semi-arid regions, our results suggest that reducing human activities can significantly promote environmental restoration. The findings of this study suggest that policy makers and stakeholders can restore grassland ecosystems and promote environmental protection by reducing anthropogenic activities in arid and semi-arid regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.144525DOI Listing
May 2021

Boron-incorporated micro/nano-topographical calcium silicate coating dictates osteo/angio-genesis and inflammatory response toward enhanced osseointegration.

Biol Trace Elem Res 2021 Jan 6. Epub 2021 Jan 6.

Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People's Republic of China.

Orthopedic implant coatings with optimal surface features to achieve favorable osteo/angio-genesis and inflammatory response would be of great importance. However, to date, few coatings are capable of fully satisfying these requirements. In this work, to take advantage of the structural complexity of micro/nano-topography and benefits of biological trace elements, two types of boron-containing nanostructures (nanoflakes and nanolamellars) were introduced onto plasma-sprayed calcium silicate (F-BCS and L-BCS) coatings via hydrothermal treatment. The C-CS coating using deionized water as hydrothermal medium served as control. Boron-incorporated CS coating stimulated osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Specifically, the combination of β1 integrin-vinculin-mediated cell spreading and activation of bone morphogenetic protein signaling pathway acted synergistically to cause significant upregulation of runt-related transcription factor 2 (RUNX2) protein and Runx2 gene expression in BMSCs on the F-BCS coating surface, which induced the transcription of downstream osteogenic differentiation marker genes. F-BCS coating allowed specific boron ion release, which favored angiogenesis as evidenced by the enhanced migration and tube formation of human umbilical vein endothelial cells in the coating extract. Boron-incorporated coatings significantly suppressed the expression of toll-like receptor adaptor genes in RAW264.7 macrophages and subsequently the degradation of nuclear factor-κB inhibitor α, accompanied by the inactivation of the downstream pro-inflammatory genes. In vivo experiments confirmed that F-BCS-coated Ti implant possessed enhanced osseointegration compared with L-BCS- and C-CS-coated implants. These data highlighted the synergistic effect of specific nanotopography and boron release from orthopedic implant coating on improvement of osseointegration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-020-02517-wDOI Listing
January 2021

Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group.

Radiat Res 2020 12;194(6):665-677

Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington 98195.

The limits of radiation tolerance, which often deter the use of large doses, have been a major challenge to the treatment of bulky primary and metastatic cancers. A novel technique using spatial modulation of megavoltage therapy beams, commonly referred to as spatially fractionated radiation therapy (SFRT) (e.g., GRID radiation therapy), which purposefully maintains a high degree of dose heterogeneity across the treated tumor volume, has shown promise in clinical studies as a method to improve treatment response of advanced, bulky tumors. Compared to conventional uniform-dose radiotherapy, the complexities of megavoltage GRID therapy include its highly heterogeneous dose distribution, very high prescription doses, and the overall lack of experience among physicists and clinicians. Since only a few centers have used GRID radiation therapy in the clinic, wide and effective use of this technique has been hindered. To date, the mechanisms underlying the observed high tumor response and low toxicity are still not well understood. To advance SFRT technology and planning, the Physics Working Group of the Radiosurgery Society (RSS) GRID/Lattice, Microbeam and Flash Radiotherapy Working Groups, was established after an RSS-NCI Workshop. One of the goals of the Physics Working Group was to develop consensus recommendations to standardize dose prescription, treatment planning approach, response modeling and dose reporting in GRID therapy. The objective of this report is to present the results of the Physics Working Group's consensus that includes recommendations on GRID therapy as an SFRT technology, field dosimetric properties, techniques for generating GRID fields, the GRID therapy planning methods, documentation metrics and clinical practice recommendations. Such understanding is essential for clinical patient care, effective comparisons of outcome results, and for the design of rigorous clinical trials in the area of SFRT. The results of well-conducted GRID radiation therapy studies have the potential to advance the clinical management of bulky and advanced tumors by providing improved treatment response, and to further develop our current radiobiology models and parameters of radiation therapy design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1667/RADE-20-00047.1DOI Listing
December 2020

Biological Guided Carbon-Ion Microporous Radiation to Tumor Hypoxia Area Triggers Robust Abscopal Effects as Open Field Radiation.

Front Oncol 2020 19;10:597702. Epub 2020 Nov 19.

Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, China.

Recently, a growing number of studies focus on partial tumor irradiation to induce the stronger non-target effects. However, the value of partial volume carbon ion radiotherapy (CIRT) targeting hypoxic region of a tumor under imaging guidance as well as its effect of inducing radiation induced abscopal effects (RIAEs) have not been well investigated. Herein, we developed a technique of carbon ion microporous radiation (CI-MPR), guided by F-FMISO PET/computerized tomography (CT), for partial volume radiation targeting the hypoxia area of a tumor and investigated its capability of inducing abscopal effects. Tumor-bearing mice were inoculated subcutaneously with breast cancer 4T1 cells into the flanks of both hind legs of mouse. Mice were assigned to three groups: group I: control group with no treatment; group II: carbon ion open field radiation (CI-OFR group) targeting the entire tumor; group III: partial volume carbon ion microporous radiation (CI-MPR group) targeting the hypoxia region. The tumors on the left hind legs of mice were irradiated with single fraction of 20 Gy of CIRT. Mice treated with CI-MPR or CI-OFR showed that significant growth delay on both the irradiated and unirradiated of tumor as compared to the control groups. Tumor regression of left tumor irradiated with CI-OFR was more prominent as compared to the tumor treated with CI-MPR, while the regression of the unirradiated tumor in both CI-MPR and CI-OFR group was similar. Biological-guided CIRT using the newly developed microporous technique targeting tumor hypoxia region could induce robust abscopal effects similar to CIRT covering the entire tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.597702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713593PMC
November 2020

Pericarpium protects against isoproterenol-induced chronic heart failure via activation of PPARγ.

Ann Transl Med 2020 Nov;8(21):1396

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

Background: Accumulated clinical trials and animal studies showed that Qiliqiangxin (QLQX), a traditional Chinese medicine formula containing extracts of 11 herbs, exerts beneficial effects on chronic heart failure (HF). Pericarpium (CRP), one herbal medicine in QLQX, has been widely used in treatment against digestive, respiratory and cardiovascular diseases (CVDs) in China. However, the cardiac protective effects and mechanisms of CRP are still unclear.

Methods: The effects of CRP were investigated in isoproterenol (ISO)-induced chronic HF mice model and neonatal rat ventricular cardiomyocytes (NRVMs) treated with ISO. Echocardiography was used to determine cardiac function. Hematoxylin-eosin (HE) staining and α-actinin immunofluorescent staining were used to measure cardiomyocyte size. Cardiac fibrosis was evaluated by Masson's trichrome staining. The expression of atrial natriuretic polypeptide (ANP) and brain natriuretic polypeptide (BNP) were determined by quantitative real time PCR (qRT-PCR). Western blot was applied to examine the expression of peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1α (PGC-1α), fibrosis-related and apoptosis-related proteins.

Results: We found that CRP could significantly attenuate ISO-induced cardiac dysfunction, inhibit cardiac pathological hypertrophy and alleviate myocardial fibrosis and apoptosis. Mechanistically, the downregulation of PPARγ and PGC-1α in ISO-injected mice hearts and ISO-treated NRVMs could be reversed by CRP treatment. The beneficial effects of CRP against ISO-induced HF were abolished by PPARγ inhibitor (T0070907), suggesting that CRP-mediated PPARγ upregulation was essential for the preventive effect of CRP on ISO-induced cardiac dysfunction.

Conclusions: In conclusion, our study demonstrated that CRP attenuates ISO-induced cardiac remodeling via PPARγ activation, which represents a new application for CRP in the prevention of chronic HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-2200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723657PMC
November 2020