National Natural Science Fund Research Articles

Polymer Materials Research at CMSE

Polymer Materials Research at CMSE

AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages.

BackgroundMesenchymal stem cell (MSC)-derived exosome administration has been considered as a novel cell-free therapy for liver diseases through cell-cell communication. This study was aimed to determine the effects and mechanisms of AMSC-derived exosomes (AMSC-Exo) for acute liver failure (ALF) treatment.MethodsAMSC-Exo were intravenously administrated into the mice immediately after lipopolysaccharide and D-galactosamine (LPS/GalN)-exposure and their effects were evaluated by liver histological and serum biochemical analysis. To elucidate its mechanisms in ALF therapy, the expression levels of miRNAs and inflammasome-related genes in macrophages were evaluated by qPCR and Western blot analysis, respectively. The exosomes from miR-17-knockdowned AMSCs (AMSC-ExomiR-17-KD) were used for further determine the role of miR-17 in AMSC-Exo-based therapy.FindingsAMSC-Exo administration significantly ameliorated ALF as determined by reduced serum alanine aminotransferase and aspartate aminotransferase levels and hepatic inflammasome activation. Further experiments revealed that AMSC-Exo were colocalized with hepatic macrophages and could reduce inflammatory factor secretion by suppressing inflammasome activation in macrophages. Moreover, miR-17, which can suppress NLRP3 inflammasome activation by targeting TXNIP, was abundant in AMSC-Exo cargo. While, the therapeutic effects of AMSC-ExomiR-17-KD on ALF were significantly abolished as they could not effectively suppress TXNIP expression and consequent inflammasome activation in vitro and in vivo.Interpretation: Exosome-shuttled miR-17 plays an essential role in AMSC-Exo therapy for ALF by targeting TXNIP and suppressing inflammasome activation in hepatic macrophages. AMSC-Exo-based therapy may present as a promising approach for TXNIP/NLRP3 inflammasome-related inflammatory liver diseases.FundKey R&D projects of Zhejiang province (2018C03019) and National Natural Science Fund (81470851 and 81500616).

Testing the variation of the fine structure constant with strongly lensed gravitational waves**Supported by the National Natural Science Fund of China (11775038, 11603005, 11647307)

The possible variation of the electromagnetic fine structure constant, αe, at cosmological scales has aroused great interest in recent years. Strongly lensed gravitational waves (GWs) and their electromagnetic counterparts could be used to test this variation. Under the assumption that the speed of a photon can be modified, whereas the speed of a GW is the same as predicted by general relativity, and they both propagate in a flat Friedman-Robertson-Walker universe, we investigated the difference in time delays of the images and derived the upper bound of the variation of αe. For a typical lensing system in the standard cosmological models, we obtained Bcosθ⩽1.85 × 10−5, where B is the dipolar amplitude and θ is the angle between observation and the preferred direction. Our result is consistent with the most up-to-date observations on αe. In addition, the observations of strongly lensed GWs and their electromagnetic counterparts could be used to test which types of alternative theories of gravity can account for the variation of αe.

In Vitro Culture Expansion Impairs Chondrogenic Differentiation and Therapeutic Effect of Mesenchymal Stem Cells by Regulation of Unfolded Protein Response

In vitro expansion of mesenchymal stem cells (MSCs) has been implicated in loss of multipotency, leading to impaired chondrogenic potential and eventually therapeutic effect, as reported in our previous study. However, the precise regulatory mechanism is still unclear. Here, we demonstrate that endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were highly enriched in in vitro-cultured bone marrow MSCs at passage 3 (P3 BMSCs) vs. flesh P0 BMSCs by microarray analysis. Indeed, RT-PCR and western blot analysis showed significantly lower expression levels of three key UPR-related molecules, ATF4, ATF6 and XBP1 in P3 BMSCs than P0 BMSCs. Further, we found that UPR suppression by 4-phenylbutyrate (4-PBA) impaired chondrogenesis and cartilage repair in P0 BMSCs, and UPR induction by tunicamycin (TM) enhanced chondrogenic differentiation and cartilage regeneration in in vitro-cultured P3 BMSCs. Thus, the decline of chondrogenic potential of stem cells after in vitro culture and expansion may be due to the change of ER stress and UPR pathway. Funding: This study was financially supported by National key research and development program of China (2016YFB0700804), National Natural Science Fund of China (Grant No. 81760326 and 81460345), the Guangxi Scientific Research and Technological Development Foundation (Grant No. GuikeAB16450003) and the Guangxi Science and Technology Major Project (Guike AA17204085), High level innovation teams and outstanding scholars in Guangxi Universities (The third batch), the Distinguished Young Scholars Program of Guangxi Medical University, and the Key scientific research collaboration program of Guangxi Biomedical Collaborative Innovation Center (GCICB-SR-2017002). Declaration of Interest: No conflict of interests exists in this study. Ethical Approval: The experiments were approved by Animal Care and Experiment Committee of Guangxi Medical University (protocol number: 2014-12-3).

Local probes strongly favor ΛCDM against power-law and Rh = ct universe**Supported by National Natural Science Fund of China (11603005, 11775038, 11647307, 11675182, 11690022)

We constrain three cosmological models – the concordance cold dark matter plus cosmological constant (ΛCDM) model, the power-law (PL) model, and the Rh = ct model – using the available local probes, which include the JLA compilation of type-Ia supernovae (SNe Ia), the direct measurement of the Hubble constant (H(z)), and the baryon acoustic oscillations (BAO). For the ΛCDM model, we consider two different cases, i.e. zero and non-zero spatial curvature. We find that by using the JLA alone, the ΛCDM and PL models are indistinguishable, but the Rh = ct model is strongly disfavored. If we combine JLA+H(z), the ΛCDM model is strongly favored over the other two models. The combination of all three datasets supports ΛCDM as the best model. We also use the low-redshift (z<0.2) data to constrain the deceleration parameter using the cosmography method, and find that only the ΛCDM model is consistent with cosmography. However, there is no strong evidence to distinguish between flat and non-flat ΛCDM models by using the local data alone.

SF3B4 is Regulated by microRNA-133b and Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma

MicroRNAs (miRNAs) have been extensively reported and play critical roles in tumorigenesis. SF3B4 acts as a potential oncogene in hepatocellular carcinoma (HCC), however, its regulation by miRNAs is not clear. In our research, it is meant to study the role of SF3B4 in HCC and the regulation mechanism of its expression by miRNAs. Here, we identified the expression of SF3B4 was increased in HCC tissues and cell lines compared with the normal controls and indicated poor prognosis of HCC patients. SF3B4 knockdown could suppress HCC cell proliferation and metastasis in vitro and in vivo. MiRNA-133b was predicted as a regulatory miRNA of SF3B4 in HCC, and negatively regulated SF3B4 expression in HCC. It was further verified that miRNA-133b inhibited proliferation and metastasis of SF3B4 overexpressed HCC cells by regulating SF3B4 associated signal pathway. Collectively, our findings suggested that SF3B4 is regulated by miRNA-133b negatively and plays a crucial role in HCC. Funding Statement: This work was supported by the grants of China National Funds for Distinguished Young Scientists (No.81425019), the State Key Program of National Natural Science Foundation of China (No.81730076), Shanghai Science and Technology Committee Program (No.18XD1405300) and Specially-Appointed Professor Fund of Shanghai (GZ2015009). China National Funds for National Natural Science Fund (No.81672899). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Animal studies were approved by the institutional Ethics Committee on Ethics of Biomedicine, Second Military Medical University.

Quality control and safeguarding measures for the whole-process management of scientific research in tertiary hospitals

Objective Sharing and exploring the efficient development of scientific research management with peers in large tertiary general hospital. Methods This article took the whole process management of scientific research in our hospital during the past five years as example, analyzed and elaborated the quality control and related safeguarding measures. Results According to the comparison between 2012 and 2016, the number of SCI papers published, the number of National Natural Science Funding and other important indicators all have been increased significantly in our hospital. Conclusions The implementation of the whole process quality control management and security measures of scientific research helps hospital to achieve initial and efficient development in research management. Key words: Scientific research; Scientific research management; Quality control of the whole process; Quality control of scientific research

Non-overlapped P- and S-wave Poynting vectors and their solution by the grid method

We thank the National Natural Science Fund of China (under grant 41330316) for supporting this work.

Literature Review of Strategic Transformation—Based on the Literature Supported by the National Natural Science Fund and the National Social Science Fund of China

Chinese enterprises have entered to the speed competition instead of the scale competition; the enterprises can match with the dynamic environment better through strategic transformation. In this paper, we selected 51 literatures about enterprise strategic transformation from the “national natural science fund” and “national social science fund”, and based on this 51 literatures, we analyze these literatures in terms of the concept, motivation, transformation process and the result of strategic transformation, analyze the current research situation and research deficiencies of the existing research, prospect the future research, in order to provide guidance to Chinese enterprises and scholars.

Comorbidities as predictors of inpatient deaths after hip fracture in Chinese elderly patients: analysis of hospital records

BackgroundHip fractures in elderly patients are common and are associated with substantial mortality and variations in outcome. We aimed to describe the type and prevalence of comorbidities in elderly patients (aged 55 years or older) with hip fracture, develop and evaluate multivariable risk-adjustment models for in-hospital mortality, verify if inpatient mortality associated with specific comorbidities is relatively higher in surgical patients compared with those not associated with specific comorbidities, and assess the clinical application of a preoperative risk scoring system for elderly patients with hip fracture. MethodsFrom Jan 1, 2006, to Jan 1, 2010, we used hospitalisation summary reports from the 35 top-rank hospitals in Beijing to identify 14 577 patients aged 55 years or older with hip fracture. We used multivariable regression methods to develop a risk-adjustment model for inpatient mortality in surgical patients. From these models, we obtained a preoperative risk scoring system for elderly patients with hip fracture. Preoperative risk scoring was performed with an evaluation form according to sex, age, and comorbidities. Patients were divided into risk groups according to score: very low risk (score of 0–10), low risk (score of 11–20), moderate risk (score of 21–30), high risk (score of 31–40), and very high risk (score of 41 or more). Postoperative complications and death before discharge from hospital were recorded. FindingsFrom Feb 1, 2014 to Feb 1, 2016, 286 elderly patients with hip fracture who matched the inclusion and exclusion criteria were recruited from Peking University People's hospital. All 286 patients were treated with surgery. The cohort included 175 patients with femoral neck fracture and 111 patients with intertrochanteric fracture. Other than older age and male sex, ten different comorbidities were independently associated with in-hospital mortality, particularly history of pulmonary embolism, respiratory failure, renal failure, and diabetes with complications. The preoperative risk scores of 286 patients ranged from 0 to 69 (mean 24·90 [SD 10·96]). 44 patients had postoperative complications and five patients died during hospitalisation. The frequency of complications was 4% (1/25) in the very low risk group, 4% (3/72) in the low risk group, 15% (17/116) in the moderate risk group, 24% (12/51) in the high risk group, and 50% (11/22) in the very high risk group. InterpretationRisk of inpatient mortality associated with specific comorbidities is relatively higher in surgical patients compared with those without specific comorbidities, particularly pulmonary embolism, respiratory failure, renal failure, and diabetes. The frequency of postoperative complications increased in line with preoperative risk scores in elderly patients with hip fracture, manifesting a positive correlation effect. The preoperative risk scoring system had excellent accuracy for predicting in-hospital mortality and postoperative complications, but further improvement and evaluation of clinical application in a multicentre study is still needed. FundingChinese National Ministry of Science and Technology 973 Project Planning (No. 2014CB542206) and 863 Project Planning (SS2015AA020501), the National Natural Science Fund (31271284, 31171150, 81171146, 31471144, 30971526).

Hospitalisation cost analysis of hip fracture in China: a cross-sectional, multicenter study

BackgroundHip fracture is common, with high morbidity and expense, which becomes a major health-care problem. Very few multicenter studies of the cost of care for hip fracture in China have been done. The aim of this study was to describe and analyse the hospitalisation cost associated with hip fractures, to compare the hospitalisation cost with the local income level, and to provide rational proposals for Chinese national medical insurance policy. MethodsIn this multicenter, cross-sectional study, we collected and analysed data from Chinese National Medical Data Center Database. The inclusion criteria were based on the main diagnosis of femoral neck or intertrochanteric fracture and a discharge date between Dec 30, 2013, and Dec 31, 2015. Hospitalisation costs, age, diagnosis, treating methods, hospitalisation provinces, and hospitalisation length of stay were collected and analysed using SPSS 23.0. We excluded any datasets that did not have the full complement of information listed above. The gross domestic product (GDP) per capita and average annual disposable income were obtained from National Bureau of Statistics of the People's Republic of China. The effect of various factors on the cost of hospitalisation was investigated using ANOVA analysis and multivariable linear regression analysis. The level of significance was set at p<0·05. The choropleth maps of the hospitalisation cost, GDP per capita, and average annual disposable income was made using Excel 2007 to compare the distribution characteristics. Findings27 205 cases from 73 central hospitals in 24 provinces were included in the study. The average cost of all patients was ¥53 440 (median ¥51158, SD ¥35 238), which was more than the GDP per capita in 2014 (¥46 629) and 2·65 times the average annual disposable income of 2014 (¥20 167). According to the multiple linear regression analysis, the diagnosis, treatment methods, and length of hospital stay had a statistically significant effect on hospitalisation costs. Furthermore, some age groups (0–19 years, 60–69 years) also had significant effects. The average cost of care for patients with femoral neck fractures was ¥12 284·22 less than for the care of patients with intertrochanteric fractures, with the standardised coefficient of 0·263; the average cost of hip replacement was ¥18560·65 higher than that of internal fixation, with the standardised coefficient of 0·263, which indicated a strong effect of the surgical approach to cost. The length of hospital stay was the most important factor, and the hospitalisation cost increased with increasing number of days spent at hospitals. The distribution of average hospitalisation cost of hip fracture patients varied a lot across different provinces, presenting a multicenter, radicalised distribution pattern, which did not match with the local income level. InterpretationThe regional economic and medical development is highly inconsistent, and the hospitalisation cost of hip fracture has become a great burden to many patients' families, especially those living in economically underdeveloped regions with high medical expense. However, the medical insurance now only covers the hospitalisation cost to a limited extent. Thus, we call for further enhancement of the Chinese medical insurance policy, which should be implemented according to the distribution characteristics of hospitalisation cost and local income levels. FundingChinese National Ministry of Science and Technology 973 Project (2014CB542201) and 863 project (SS2015AA020501), the National Natural Science Fund (31571235, 31571236, 31271284).

Role of entropy generation minimization in thermal optimization**Project supported by the National Natural Science Foundation of China (Grant No. 51376101) and the National Natural Science Fund for Creative Research Groups, China (Grant No. 51621062).

Thermal optimization is very important for improving the performances of thermal systems. In engineering, the entropy generation minimization (EGM) has been widely used to optimize and evaluate the performances of thermal systems. However, the consistency between the EGM and the optimization objective should be specified when the EGM is used. In this paper, we discuss the view angle of irreversibility of entropy generation, and show that entropy generation directly reflects the exergy destruction or the ability loss of doing work. As the design objective in a thermal system is not often consistent with the view angle of irreversibility of entropy generation, the EGM may not lead to the optimal value of the design objective. In heat transfer and heat-work conversion, the inconsistence between the design objectives and the EGM is shown with some examples, and the applicability of the EGM is found to be conditional. The “entropy generation paradox” in heat exchanger analyses is also discussed, and it is shown that there is no direct monotonic relation between the minimum entropy generation rate and the best heat transfer performance of heat exchangers.

P38 Immunoregulatory effects and mechanisms of four Milk-borne probiotics in immunocompromised Balb/c mice

Objective: We demonstrated that immune active peptides isolated from shubat could promote the proliferation of mice spleen lymphocytes. This effect was related to regulation of the Th1/Th2 balance. We wanted to investigate four probiotics from Xinjiang traditional fermented camel milk (shubat) and cheese whey, to examine their immunoregulatory mechanisms and determine their signalling pathways. Methods: 1. The four probiotics were cultured and suspensions prepared. 2. An immunocompromised model (Balb/c mice) was induced with cyclophosphamide. 3. Mice were randomly divided into eleven groups, given high and low dose suspensions of four probiotics. 4. Determination index: calculate indexes of spleen, thymus, colon. Detect spleen lymphocyte activity, serum ALT, AST, CREA, and UREA. 5. Detect serum cytokine levels with CBA kit. 5. Gene expression: use RT-PCR to detect the mRNA expression of five genes. Results: 1. The spleen index was significantly increased. 2. The levels of AST, ALT and UREA were reduced. 3. Probiotic groups had significantly increased levels of IL-2, IFN-γ, significantly reduced IL-6, IL-10, IL-17A. 4. RT-PCR results: the probiotic groups were significantly decreased. Conclusion: The four probiotics can increase the body weight, maintain normal liver and kidney function and improves the spleen index, (lymphocyte activity). We concluded that probiotics from shubat can work through a MyD88-dependent TLR-7 signal pathway and have some protective effects. Acknowledgements Funding from The National Natural Science Fund of China (81160344).

Improved high-frequency equivalent circuit model based on distributed effects for SiGe HBTs with CBE layout**Project supported by the National Natural Science Funds of China (Grant Nos. 61574056 and 61504156), the Natural Science Foundation of Shanghai, China (Grant No. 14ZR1412000), Shanghai Sailing Program, China (Grant No. 17YF1404700), and the Science and Technology Commission of Shanghai Municipality, China (Grant No. 14DZ2260800).

In this paper, we present an improved high-frequency equivalent circuit for SiGe heterojunction bipolar transistors (HBTs) with a CBE layout, where we consider the distributed effects along the base region. The actual device structure is divided into three parts: a link base region under a spacer oxide, an intrinsic transistor region under the emitter window, and an extrinsic base region. Each region is considered as a two-port network, and is composed of a distributed resistance and capacitance. We solve the admittance parameters by solving the transmission-line equation. Then, we obtain the small-signal equivalent circuit depending on the reasonable approximations. Unlike previous compact models, in our proposed model, we introduce an additional internal base node, and the intrinsic base resistance is shifted into this internal base node, which can theoretically explain the anomalous change in the intrinsic bias-dependent collector resistance in the conventional compact model.

Interventional Radiology in China: Current Status and Future Prospects.

Interventional Radiology in China: Current Status and Future Prospects.

Allosteric Mechanism of Calmodulin Revealed by Targeted Molecular Dynamics Simulation**Supported by the Natural Science Fund for Distinguished Young Scholars of Hebei Province under Grant Nos C2015202340 and C2013202244, the Fund for Outstanding Talents of Hebei Province under Grant No C201400305, the National Natural Science Fund of China under Grant Nos 11247010, 11175055, 11475053, 11347017, 31600594, 31400711 and 11647121, the Fund

Calmodulin (CaM) is involved in the regulation of a variety of cellular signaling pathways. To accomplish its physiological functions, CaM binds with Ca2+ at its EF-hand Ca2+ binding sites which induce the conformational switching of CaM. However, the molecular mechanism by which Ca2+ binds with CaM and induces conformational switching is still obscure. Here we combine molecular dynamics with targeted molecular dynamics simulation and achieve the state-transition pathway of CaM. Our data show that Ca2+ binding speeds up the conformational transition of CaM by weakening the interactions which stabilize the closed state. It spends about 6.5 ns and 5.25 ns for transition from closed state to open state for apo and holo CaM, respectively. Regarding the contribution of two EF-hands, our data indicate that the first EF-hand triggers the conformational transition and is followed by the second one. We determine that there are two interaction networks which contribute to stabilize the closed and open states, respectively.

Spatial and temporal variations of the fine-structure constant in the Finslerian universe**Supported by Fundamental Research Funds for Central Universities (106112016CDJCR301206), National Natural Science Fund of China (11305181, 11547035, 11603005), and Open Project Program of State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, China (Y5KF181CJ1).

Recent observations show that the electromagnetic fine-structure constant, αe, may vary with space and time. In the framework of Finsler spacetime, we propose here an anisotropic cosmological model, in which both spatial and temporal variations of αe are allowed. Our model naturally leads to the dipole structure of αe, and predicts that the dipole amplitude increases with time. We fit our model to the most up-to-date measurements of αe from the quasar absorption lines. It is found that the dipole direction points towards (l,b) = (330.2°±7.3°,−13.0°±5.6°) in galactic coordinates, and the anisotropic parameter is b0 = (0.47±0.09) × 10−5, which corresponds to a dipole amplitude (7.2±1.4)×10−8 at redshift z = 0.015. This is consistent with the upper limit of the variation of αe measured in the Milky Way. We also fit our model to Union2.1 type Ia supernovae, and find that the preferred direction of Union2.1 is consistent with the dipole direction of αe.

Overview of research projects funding in traditional Chinese medicine oncology field supported by National Natural Science Foundation of China

In this paper, the funding situation of traditional Chinese medicine oncology research projects supported by National Natural Science Fund from 1986-2016 was reviewed. The characteristics of funded projects were summarized from funding amount, funding expenses, funding category, and the main research contents of projects, etc. At the same time, the main problems in the projects were analyzed in this paper, in order to provide reference for the relevant fund applicants.

Comparing dark matter models, modified Newtonian dynamics and modified gravity in accounting for galaxy rotation curves**Supported by Fundamental Research Funds for the Central Universities (106112016CDJCR301206), National Natural Science Fund of China (11305181, 11547305 and 11603005), and Open Project Program of State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, China (Y5KF181CJ1)

We compare six models (including the baryonic model, two dark matter models, two modified Newtonian dynamics models and one modified gravity model) in accounting for galaxy rotation curves. For the dark matter models, we assume NFW profile and core-modified profile for the dark halo, respectively. For the modified Newtonian dynamics models, we discuss Milgrom’s MOND theory with two different interpolation functions, the standard and the simple interpolation functions. For the modified gravity, we focus on Moffat’s MSTG theory. We fit these models to the observed rotation curves of 9 high-surface brightness and 9 low-surface brightness galaxies. We apply the Bayesian Information Criterion and the Akaike Information Criterion to test the goodness-of-fit of each model. It is found that none of the six models can fit all the galaxy rotation curves well. Two galaxies can be best fitted by the baryonic model without involving nonluminous dark matter. MOND can fit the largest number of galaxies, and only one galaxy can be best fitted by the MSTG model. Core-modified model fits about half the LSB galaxies well, but no HSB galaxies, while the NFW model fits only a small fraction of HSB galaxies but no LSB galaxies. This may imply that the oversimplified NFW and core-modified profiles cannot model the postulated dark matter haloes well.

Effect of Excess Iron Intake on Growth and Intestinal Inflammatory Injury in Rats

ObjectiveTo study the effects of excess iron intake on growth and development, and determine the possible mechanism.MethodsFourty eight male Wistar rats were randomly divided into 4 groups: low iron group, normal group, medium iron group, and high iron group, and received daily iron intake of 7mg/kg, 16.8mg/kg, 35mg/kg, and 70mg/kg in diet, and deionized water, respectively, for 8 weeks. The general condition, body weight, and food intake were documented during the study. Serum levels of Ferritin, IL‐6, IL‐10, and sIgA were measured using enzyme‐linked immunosorbent assay(ELISA).ResultsDuring the process of iron intervention, the high iron group had lower growth compared with the other three groups (p&lt;0.05). In addition, the levels of IL‐6 (108.60pg/ml) in small intestine were higher in the high iron group compared to the normal iron group (84.68pg/ml, P&lt;0.05), while serum levels of IL‐10 (50.47 pg/ml) in small intestine in the high iron group was lower than that in the normal iron group (71.69 pg/ml, (P&lt;0.05). Serum levels of sIgA (62.3pg/ml) in small intestine with the high iron group is lower than that in the normal iron group (67.1 pg/ml, P&lt;0.05). The histopathology showed normal morphology in the low iron and normal iron groups, however the rats in medium iron group showed slightly damaged mucosa, and lost apical microvilli. Irregular shape of microvilli and necrosis were found in a few epithelial cells of intestinal mucosa in the high iron group rats.ConclusionExcessive dietary iron intake has a negative affect on the normal growth and development of rats, and results in inflammatory injury in intestinal tract of rats.Support or Funding InformationThe National Natural Science Fund (No. 81373000)