The rapid development of high-throughput sequencing techniques has led biology into the big-data era.Data analyses using various bioinformatics tools rely on programming and command-line environments,which are challen...The rapid development of high-throughput sequencing techniques has led biology into the big-data era.Data analyses using various bioinformatics tools rely on programming and command-line environments,which are challenging and time-consuming for most wet-lab biologists.Here,we present TBtools(a Toolkit for Biologists integrating various biological data-handling tools),a stand-alone software with a userfriendly interface.The toolkit incorporates over 130 functions,which are designed to meet the increasing demand for big-data analyses,ranging from bulk sequence processing to interactive data visualization.A wide variety of graphs can be prepared in TBtools using a new plotting engine("JIGplot")developed to maximize their interactive ability;this engine allows quick point-and-click modification of almost every graphic feature.TBtools is platform-independent software that can be run under all operating systems with Java Runtime Environment 1.6 or newer.It is freely available to non-commercial users at https://github.com/CJ-Chen/TBtools/releases.展开更多
Genome editing tools such as the clustered regularly interspaced short palindromic repeat （CRISPR）-associated system （Cas） have been widely used to modify genes in model systems including animal zygotes and human ...Genome editing tools such as the clustered regularly interspaced short palindromic repeat （CRISPR）-associated system （Cas） have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear （3PN） zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene （HBB）. However, the efficiency of homologous recombination directed repair （HDR） of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene （HBD）, which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.展开更多
Traditional Chinese medicine （TCM） has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate...Traditional Chinese medicine （TCM） has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate TCM as an area of important medical rediscoveries. This review article briefly introduced the concept, significance, and technology of network pharmacology based on network biology and systems biology. It focused on the theoretical system and potential prospect of TCM network applied in TCM research and development including predicting new drug targets, action mechanism, new drug discovery; evaluating pharmacodynamics, pharmacokinetics, safety, toxicology, quality control, and bioinformatics of drugs. We also discussed the opportunities and challenges in the development and application of network pharmacology in the modernization of TCM research.展开更多
AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto dete...AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.展开更多
Cooperative guidance problems of multiple missiles are considered in this article. A cooperative guidance scheme, where coordination algorithms and local guidance laws are combined together, is proposed. This scheme a...Cooperative guidance problems of multiple missiles are considered in this article. A cooperative guidance scheme, where coordination algorithms and local guidance laws are combined together, is proposed. This scheme actually builds up a hierarchical cooperative guidance architecture, which may provide a general solution to the multimissile cooperative guidance problems. In the case of salvo attacks which require missiles to hit the target simultaneously, both centralized and distributed coordination algorithms are derived based on the impact-time-control guidance （ITCG） law. Numerical simulations are performed to demonstrate the effectiveness of the proposed approaches.展开更多
A growing understanding of the benefits of exercise over the past few decades has prompted researchers to take an interest in the possibilities of exercise therapy.Because each sport has its own set of characteristics...A growing understanding of the benefits of exercise over the past few decades has prompted researchers to take an interest in the possibilities of exercise therapy.Because each sport has its own set of characteristics and physiological complications that tend to occur during exercise training,the effects and underlying mechanisms of exercise remain unclear.Thus,the first step in probing the effects of exercise on different diseases is the selection of an optimal exercise protocol.This review summarizes the latest exercise prescription treatments for 26 different diseases:musculoskeletal system diseases(low back pain,tendon injury,osteoporosis,osteoarthritis,and hip fracture),metabolic system diseases(obesity,type 2 diabetes,type 1 diabetes,and nonalcoholic fatty liver disease),cardio-cerebral vascular system diseases(coronary artery disease,stroke,and chronic heart failure),nervous system diseases(Parkinson’s disease,Huntington’s disease,Alzheimer’s disease,depression,and anxiety disorders),respiratory system diseases(chronic obstructive pulmonary disease,interstitial lung disease,and after lung transplantation),urinary system diseases(chronic kidney disease and after kidney transplantation),and cancers(breast cancer,colon cancer,prostate cancer,and lung cancer).Each exercise prescription is displayed in a corresponding table.The recommended type,intensity,and frequency of exercise prescriptions are summarized,and the effects of exercise therapy on the prevention and rehabilitation of different diseases are discussed.展开更多
Licorice is a common herb which has been used in traditional Chinese medicine for centuries.More than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. Recent studies have shown that these m...Licorice is a common herb which has been used in traditional Chinese medicine for centuries.More than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. Recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral,antimicrobial, anti-inflammatory, antitumor and other activities. This paper provides a summary of the antiviral and antimicrobial activities of licorice. The active components and the possible mechanisms for these activities are summarized in detail. This review will be helpful for the further studies of licorice for its potential therapeutic effects as an antiviral or an antimicrobial agent.展开更多
With the rapid development of nuclear power in China, the disposal of high-level radioactive waste（HLW） has become an important issue for nuclear safety and environmental protection. Deep geological disposal is inte...With the rapid development of nuclear power in China, the disposal of high-level radioactive waste（HLW） has become an important issue for nuclear safety and environmental protection. Deep geological disposal is internationally accepted as a feasible and safe way to dispose of HLW, and underground research laboratories（URLs） play an important and multi-faceted role in the development of HLW repositories. This paper introduces the overall planning and the latest progress for China＇s URL. On the basis of the proposed strategy to build an area-specific URL in combination with a comprehensive evaluation of the site selection results obtained during the last 33 years, the Xinchang site in the Beishan area,located in Gansu Province of northwestern China, has been selected as the final site for China＇s first URL built in granite. In the process of characterizing the Xinchang URL site, a series of investigations,including borehole drilling,geological mapping, geophysical surveying,hydraulic testing and in situ stress measurements, has been conducted. The investigation results indicate that the geological,hydrogeological, engineering geological and geochemical conditions of the Xinchang site are very suitable for URL construction. Meanwhile, to validate and develop construction technologies for the Beishan URL, the Beishan exploration tunnel（BET）, which is a 50-m-deep facility in the Jiujing sub-area, has been constructed and several in situ tests, such as drill-and-blast tests, characterization of the excavation damaged zone（EDZ）, and long-term deformation monitoring of surrounding rocks, have been performed in the BET. The methodologies and technologies established in the BET will serve for URL construction.According to the achievements of the characterization of the URL site, a preliminary design of the URL with a maximum depth of 560 m is proposed and necessary in situ tests in the URL are planned.展开更多
Gaseous emission （N2O, CH4 and NH3） from composting can be an important source of anthropogenic greenhouse gas and air pollution. A laboratory scale orthogonal experiment was conducted to estimate the effects of C/N...Gaseous emission （N2O, CH4 and NH3） from composting can be an important source of anthropogenic greenhouse gas and air pollution. A laboratory scale orthogonal experiment was conducted to estimate the effects of C/N ratio, aeration rate and initial moisture content on gaseous emission during the composting of pig faeces from Chinese Ganqinfen system. The results showed that about 23.9% to 45.6% of total organic carbon （TOC） was lost in the form of CO2 and 0.8% to 7.5% of TOC emitted as CH4. Most of the nitrogen was lost in the form of NH3, which account for 9.6% to 32.4% of initial nitrogen. N20 was also an important way of nitrogen losses and 1.5% to 7.3% of initial total nitrogen was lost as it. Statistic analysis showed that the aeration rate is the most important factor which could affect the NH3 （p = 0.0189）, CH4 （p = 0.0113） and N20 （p = 0.0493） emissions significantly. Higher aeration rates reduce the CH4 emission but increase the NH3 and N20 losses. C/N ratio could affect the NH3 （p = 0.0442） and CH4 （p = 0.0246） emissions significantly, but not the N20. Lower C/N ratio caused higher NH3 and CH4 emissions. The initial moisture content can not influence the gaseous emission significantly. Most treatments were matured after 37 days, except a trial with high moisture content and a low C/N ratio.展开更多
Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherap...Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells （iPSCs）, and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice （GMP） facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.展开更多
Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD）...Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and 展开更多
The reentry trajectory optimization for hypersonic vehicle（HV）is a current problem of great interest.Some complex constraints,such as waypoints for reconnaissance and no-fly zones for threat avoidance,are inevitably...The reentry trajectory optimization for hypersonic vehicle（HV）is a current problem of great interest.Some complex constraints,such as waypoints for reconnaissance and no-fly zones for threat avoidance,are inevitably involved in a global strike mission.Of the many direct methods,Gauss pseudospectral method（GPM）has been demonstrated as an effective tool to solve the trajectory optimization problem with typical constraints.However,a series of diffculties arises for complex constraints,such as the uncertainty of passage time for waypoints and the inaccuracy of approximate trajectory near no-fly zones.The research herein proposes a multi-phase technique based on the GPM to generate an optimal reentry trajectory for HV satisfying waypoint and nofly zone constraints.Three kinds of specifc breaks are introduced to divide the full trajectory into multiple phases.The continuity conditions are presented to ensure a smooth connection between each pair of phases.Numerical examples for reentry trajectory optimization in free-space flight and with complex constraints are used to demonstrate the proposed technique.Simulation results show the feasible application of multi-phase technique in reentry trajectory optimization with waypoint and no-fly zone constraints.展开更多
Permafrost on the Qinghai-Tibet Plateau (QTP) is widespread, thin, and thermally unstable. Under a warming climate during the past few decades, it has been degrading extensively with generally rising ground temperatur...Permafrost on the Qinghai-Tibet Plateau (QTP) is widespread, thin, and thermally unstable. Under a warming climate during the past few decades, it has been degrading extensively with generally rising ground temperatures, the deepening of the maximum summer thaw, and with lessening of the winter frost penetration. The permafrost has degraded downward, upward and laterally. Permafrost has thinned or, in some areas, has totally disappeared. The modes of permafrost degradation have great significance in geocryology, in cold regions engineering and in cold regions environmental management. Permafrost in the interior of the QTP is well represented along the Qing-hai-Tibet Highway (QTH), which crosses the Plateau through north to south and traverses 560 km of permafrost-impacted ground. Horizontally, the degradation of permafrost occurs more visibly in the sporadic permafrost zone in the vicinity of the lower limit of permafrost (LLP), along the margins of taliks, and around permafrost islands. Downward degradation develops when the maximum depth of seasonal thaw exceeds the maximum depth of seasonal frost, and it generally results in the formation of a layered talik disconnecting the permafrost from the seasonal frost layer. The downward degrada- tion is divided into four stages: 1) initial degradation, 2) accelerated degradation, 3) layered talik and 4) finally the conversion of permafrost to seasonally frozen ground (SFG). The upward degradation occurs when the geothermal gradient in permafrost drops to less than the geothermal gradients in the underlying thawed soil layers. Three types of permafrost temperature curves (stable, degrading, and phase-changing transitory permafrost) illustrate these modes. Although strong differentiations in local conditions and permafrost types exist, the various combinations of the three degradation modes will ultimately transform permafrost into SFG. Along the QTH, the downward degradation has been proceeding at annual rates of 6 to 25 cm, upward degradation at 12 to 30 cm, and later展开更多
Background:As reported by the World Health Organization,a novel coronavirus(2019-nCoV)was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January,2020.The virus was...Background:As reported by the World Health Organization,a novel coronavirus(2019-nCoV)was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January,2020.The virus was named as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)by International Committee on Taxonomy of Viruses on 11 February,2020.This study aimed to develop a mathematical model for calculating the transmissibility of the virus.Methods:In this study,we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source(probably be bats)to the human infection.Since the Bats-HostsReservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market(reservoir)to people,we simplified the model as Reservoir-People(RP)transmission network model.The next generation matrix approach was adopted to calculate the basic reproduction number(R0)from the RP model to assess the transmissibility of the SARS-CoV-2.Results:The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58.Conclusions:Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries,similar to severe acute respiratory syndrome,but lower than MERS in the Republic of Korea.展开更多
Aiming at regional services,the space segment of COMPASS (Phase I) satellite navigation system is a constellation of Geostationary Earth Orbit (GEO),Inclined Geostationary Earth Orbit (IGSO) and Medium Earth Orbit (ME...Aiming at regional services,the space segment of COMPASS (Phase I) satellite navigation system is a constellation of Geostationary Earth Orbit (GEO),Inclined Geostationary Earth Orbit (IGSO) and Medium Earth Orbit (MEO) satellites.Precise orbit determination (POD) for the satellites is limited by the geographic distribution of regional tracking stations.Independent time synchronization (TS) system is developed to supplement the regional tracking network,and satellite clock errors and orbit data may be obtained by simultaneously processing both tracking data and TS data.Consequently,inconsistency between tracking system and TS system caused by remaining instrumental errors not calibrated may decrease navigation accuracy.On the other hand,POD for the mixed constellation of GEO/IGSO/MEO with the regional tracking network leads to parameter estimations that are highly correlated.Notorious example of correlation is found between GEO's orbital elements and its clock errors.We estimate orbital elements and clock errors for a 3GEO+2IGSO constellation in this study using a multi-satellite precise orbit determination (MPOD) strategy,with which clock error elimination algorithm is applied to separate orbital and clock estimates to improve numerical efficiency.Satellite Laser Ranging (SLR) data are used to evaluate User Ranging Error (URE),which is the orbital error projected on a receiver's line-of-sight direction.Two-way radio-wave time transfer measurements are used to evaluate clock errors.Experimenting with data from the regional tracking network,we conclude that the fitting of code data is better than 1 m in terms of Root-Mean-Square (RMS),and fitting of carrier phase is better than 1 cm.For orbital evaluation,difference between computed receiver-satellite ranging based on estimated orbits and SLR measurements is better than 1 m (RMS).For clock estimates evaluation,2-hour linear-fitting shows that the satellite clock rates are about 1.E-10 s/s,while receiver clock rates are about 1×10 13-1×10 12 s/s.For the 72-hour P展开更多
BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for prevent...BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSC展开更多
Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most pre...Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.展开更多
In China, volatile organic compound（VOC） control directives have been continuously released and implemented for important sources and regions to tackle air pollution. The corresponding control requirements were base...In China, volatile organic compound（VOC） control directives have been continuously released and implemented for important sources and regions to tackle air pollution. The corresponding control requirements were based on VOC emission amounts（EA）, but never considered the significant differentiation of VOC species in terms of atmospheric chemical reactivity. This will adversely influence the effect of VOC reduction on air quality improvement. Therefore,this study attempted to develop a comprehensive classification method for typical VOC sources in the Beijing–Tianjin–Hebei region（BTH）, by combining the VOC emission amounts with the chemical reactivities of VOC species. Firstly, we obtained the VOC chemical profiles by measuring 5 key sources in the BTH region and referencing another 10 key sources, and estimated the ozone formation potential（OFP） per ton VOC emission for these sources by using the maximum incremental reactivity（MIR） index as the characteristic of source reactivity（SR）. Then, we applied the data normalization method to respectively convert EA and SR to normalized EA（NEA） and normalized SR（NSR） for various sources in the BTH region.Finally, the control index（CI） was calculated, and these sources were further classified into four grades based on the normalized CI（NCI）. The study results showed that in the BTH region,furniture coating, automobile coating, and road vehicles are characterized by high NCI and need to be given more attention; however, the petro-chemical industry, which was designated as an important control source by air quality managers, has a lower NCI.展开更多
基金This work was funded by the National Key Research and Developmental Program of China(2018YFD1000104)This work is also supported by awards to R.X.,Y.H.,and H.C.from the National Key Research and Developmental Program of China(2017YFD0101702,2018YFD1000500,2019YFD1000500)+4 种基金the National Science Foundation of China(#31872063)the Special Support Program of Guangdong Province(2019TX05N193)the Key-Area Research and Development Program of Guangdong Province(2018B020202011)the Guangzhou Science and Technology Key Project(201804020063)Support to M.H.F.comes from the NSF Faculty Early Career Development Program(IOS-1942437).
文摘The rapid development of high-throughput sequencing techniques has led biology into the big-data era.Data analyses using various bioinformatics tools rely on programming and command-line environments,which are challenging and time-consuming for most wet-lab biologists.Here,we present TBtools(a Toolkit for Biologists integrating various biological data-handling tools),a stand-alone software with a userfriendly interface.The toolkit incorporates over 130 functions,which are designed to meet the increasing demand for big-data analyses,ranging from bulk sequence processing to interactive data visualization.A wide variety of graphs can be prepared in TBtools using a new plotting engine("JIGplot")developed to maximize their interactive ability;this engine allows quick point-and-click modification of almost every graphic feature.TBtools is platform-independent software that can be run under all operating systems with Java Runtime Environment 1.6 or newer.It is freely available to non-commercial users at https://github.com/CJ-Chen/TBtools/releases.
基金This study was supported by the National Basic Research Program （973 Program） （Nos. 2010CB945401 and 2012CB911201）, the National Natural Science Foundation of China （Grant Nos. 91019020, 81330055, and 31371508）.
文摘Genome editing tools such as the clustered regularly interspaced short palindromic repeat （CRISPR）-associated system （Cas） have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear （3PN） zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene （HBB）. However, the efficiency of homologous recombination directed repair （HDR） of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene （HBD）, which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
基金National Natural Science Foundation of China(81430096)China Drug Innovation Plan(2014ZX09507005,2014ZX09507005-003,2012ZX09304002,2012ZX09505001)
文摘Traditional Chinese medicine （TCM） has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate TCM as an area of important medical rediscoveries. This review article briefly introduced the concept, significance, and technology of network pharmacology based on network biology and systems biology. It focused on the theoretical system and potential prospect of TCM network applied in TCM research and development including predicting new drug targets, action mechanism, new drug discovery; evaluating pharmacodynamics, pharmacokinetics, safety, toxicology, quality control, and bioinformatics of drugs. We also discussed the opportunities and challenges in the development and application of network pharmacology in the modernization of TCM research.
文摘AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.
基金Foundation items： National Natural Science Foundation of China （60674103） Aeronautical Science Foundation of China （2006ZC51026）
文摘Cooperative guidance problems of multiple missiles are considered in this article. A cooperative guidance scheme, where coordination algorithms and local guidance laws are combined together, is proposed. This scheme actually builds up a hierarchical cooperative guidance architecture, which may provide a general solution to the multimissile cooperative guidance problems. In the case of salvo attacks which require missiles to hit the target simultaneously, both centralized and distributed coordination algorithms are derived based on the impact-time-control guidance （ITCG） law. Numerical simulations are performed to demonstrate the effectiveness of the proposed approaches.
基金supported by Natural Science Foundation of China (No. 31671242)the National Key R&D Program of China (No. 2018YFC1314701)
文摘A growing understanding of the benefits of exercise over the past few decades has prompted researchers to take an interest in the possibilities of exercise therapy.Because each sport has its own set of characteristics and physiological complications that tend to occur during exercise training,the effects and underlying mechanisms of exercise remain unclear.Thus,the first step in probing the effects of exercise on different diseases is the selection of an optimal exercise protocol.This review summarizes the latest exercise prescription treatments for 26 different diseases:musculoskeletal system diseases(low back pain,tendon injury,osteoporosis,osteoarthritis,and hip fracture),metabolic system diseases(obesity,type 2 diabetes,type 1 diabetes,and nonalcoholic fatty liver disease),cardio-cerebral vascular system diseases(coronary artery disease,stroke,and chronic heart failure),nervous system diseases(Parkinson’s disease,Huntington’s disease,Alzheimer’s disease,depression,and anxiety disorders),respiratory system diseases(chronic obstructive pulmonary disease,interstitial lung disease,and after lung transplantation),urinary system diseases(chronic kidney disease and after kidney transplantation),and cancers(breast cancer,colon cancer,prostate cancer,and lung cancer).Each exercise prescription is displayed in a corresponding table.The recommended type,intensity,and frequency of exercise prescriptions are summarized,and the effects of exercise therapy on the prevention and rehabilitation of different diseases are discussed.
基金supported by Beijing Project for Young Talents (YETP0819)
文摘Licorice is a common herb which has been used in traditional Chinese medicine for centuries.More than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. Recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral,antimicrobial, anti-inflammatory, antitumor and other activities. This paper provides a summary of the antiviral and antimicrobial activities of licorice. The active components and the possible mechanisms for these activities are summarized in detail. This review will be helpful for the further studies of licorice for its potential therapeutic effects as an antiviral or an antimicrobial agent.
基金support from the China Atomic Energy Authority (CAEA) for China's URL Development Program and the Geological Disposal ProgramThe International Atomic Energy Agency is specially thanked for its support for China's geological disposal program through its Technical Cooperation Projects
文摘With the rapid development of nuclear power in China, the disposal of high-level radioactive waste（HLW） has become an important issue for nuclear safety and environmental protection. Deep geological disposal is internationally accepted as a feasible and safe way to dispose of HLW, and underground research laboratories（URLs） play an important and multi-faceted role in the development of HLW repositories. This paper introduces the overall planning and the latest progress for China＇s URL. On the basis of the proposed strategy to build an area-specific URL in combination with a comprehensive evaluation of the site selection results obtained during the last 33 years, the Xinchang site in the Beishan area,located in Gansu Province of northwestern China, has been selected as the final site for China＇s first URL built in granite. In the process of characterizing the Xinchang URL site, a series of investigations,including borehole drilling,geological mapping, geophysical surveying,hydraulic testing and in situ stress measurements, has been conducted. The investigation results indicate that the geological,hydrogeological, engineering geological and geochemical conditions of the Xinchang site are very suitable for URL construction. Meanwhile, to validate and develop construction technologies for the Beishan URL, the Beishan exploration tunnel（BET）, which is a 50-m-deep facility in the Jiujing sub-area, has been constructed and several in situ tests, such as drill-and-blast tests, characterization of the excavation damaged zone（EDZ）, and long-term deformation monitoring of surrounding rocks, have been performed in the BET. The methodologies and technologies established in the BET will serve for URL construction.According to the achievements of the characterization of the URL site, a preliminary design of the URL with a maximum depth of 560 m is proposed and necessary in situ tests in the URL are planned.
基金part of the Sino-German cooperation project of the Recycling of Organic Residues from Agricultural and Municipal Residues in China (http://www.organicresidues.de) and the National Natural Science Foundation of China (No. 40971177)
文摘Gaseous emission （N2O, CH4 and NH3） from composting can be an important source of anthropogenic greenhouse gas and air pollution. A laboratory scale orthogonal experiment was conducted to estimate the effects of C/N ratio, aeration rate and initial moisture content on gaseous emission during the composting of pig faeces from Chinese Ganqinfen system. The results showed that about 23.9% to 45.6% of total organic carbon （TOC） was lost in the form of CO2 and 0.8% to 7.5% of TOC emitted as CH4. Most of the nitrogen was lost in the form of NH3, which account for 9.6% to 32.4% of initial nitrogen. N20 was also an important way of nitrogen losses and 1.5% to 7.3% of initial total nitrogen was lost as it. Statistic analysis showed that the aeration rate is the most important factor which could affect the NH3 （p = 0.0189）, CH4 （p = 0.0113） and N20 （p = 0.0493） emissions significantly. Higher aeration rates reduce the CH4 emission but increase the NH3 and N20 losses. C/N ratio could affect the NH3 （p = 0.0442） and CH4 （p = 0.0246） emissions significantly, but not the N20. Lower C/N ratio caused higher NH3 and CH4 emissions. The initial moisture content can not influence the gaseous emission significantly. Most treatments were matured after 37 days, except a trial with high moisture content and a low C/N ratio.
文摘Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells （iPSCs）, and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice （GMP） facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.
文摘Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and
基金supported by Aviation Science Foundation of China(No.2011ZC13001 and 2013ZA18001)National Natural Science Foundation of China(Nos:60975073,61273349,61175109 and 61203223)Innovation Foundation of BUAA for PhD Graduates
文摘The reentry trajectory optimization for hypersonic vehicle（HV）is a current problem of great interest.Some complex constraints,such as waypoints for reconnaissance and no-fly zones for threat avoidance,are inevitably involved in a global strike mission.Of the many direct methods,Gauss pseudospectral method（GPM）has been demonstrated as an effective tool to solve the trajectory optimization problem with typical constraints.However,a series of diffculties arises for complex constraints,such as the uncertainty of passage time for waypoints and the inaccuracy of approximate trajectory near no-fly zones.The research herein proposes a multi-phase technique based on the GPM to generate an optimal reentry trajectory for HV satisfying waypoint and nofly zone constraints.Three kinds of specifc breaks are introduced to divide the full trajectory into multiple phases.The continuity conditions are presented to ensure a smooth connection between each pair of phases.Numerical examples for reentry trajectory optimization in free-space flight and with complex constraints are used to demonstrate the proposed technique.Simulation results show the feasible application of multi-phase technique in reentry trajectory optimization with waypoint and no-fly zone constraints.
基金This work was supprted by CAS Hundred Talents Progam"Stability of linear engineering foundations in warm permafrost regions under a changing cimte"(2004)CAS Knowledge Inovation Key Programs(Grant Nos.KZCX1-SW-04,KZCX3-SW-345 and KZCX3-SW-339-3).
文摘Permafrost on the Qinghai-Tibet Plateau (QTP) is widespread, thin, and thermally unstable. Under a warming climate during the past few decades, it has been degrading extensively with generally rising ground temperatures, the deepening of the maximum summer thaw, and with lessening of the winter frost penetration. The permafrost has degraded downward, upward and laterally. Permafrost has thinned or, in some areas, has totally disappeared. The modes of permafrost degradation have great significance in geocryology, in cold regions engineering and in cold regions environmental management. Permafrost in the interior of the QTP is well represented along the Qing-hai-Tibet Highway (QTH), which crosses the Plateau through north to south and traverses 560 km of permafrost-impacted ground. Horizontally, the degradation of permafrost occurs more visibly in the sporadic permafrost zone in the vicinity of the lower limit of permafrost (LLP), along the margins of taliks, and around permafrost islands. Downward degradation develops when the maximum depth of seasonal thaw exceeds the maximum depth of seasonal frost, and it generally results in the formation of a layered talik disconnecting the permafrost from the seasonal frost layer. The downward degrada- tion is divided into four stages: 1) initial degradation, 2) accelerated degradation, 3) layered talik and 4) finally the conversion of permafrost to seasonally frozen ground (SFG). The upward degradation occurs when the geothermal gradient in permafrost drops to less than the geothermal gradients in the underlying thawed soil layers. Three types of permafrost temperature curves (stable, degrading, and phase-changing transitory permafrost) illustrate these modes. Although strong differentiations in local conditions and permafrost types exist, the various combinations of the three degradation modes will ultimately transform permafrost into SFG. Along the QTH, the downward degradation has been proceeding at annual rates of 6 to 25 cm, upward degradation at 12 to 30 cm, and later
基金This study was supported by Xiamen New Coronavirus Prevention and Control Emergency Tackling Special Topic Program(No:3502Z2020YJ03).
文摘Background:As reported by the World Health Organization,a novel coronavirus(2019-nCoV)was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January,2020.The virus was named as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)by International Committee on Taxonomy of Viruses on 11 February,2020.This study aimed to develop a mathematical model for calculating the transmissibility of the virus.Methods:In this study,we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source(probably be bats)to the human infection.Since the Bats-HostsReservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market(reservoir)to people,we simplified the model as Reservoir-People(RP)transmission network model.The next generation matrix approach was adopted to calculate the basic reproduction number(R0)from the RP model to assess the transmissibility of the SARS-CoV-2.Results:The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58.Conclusions:Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries,similar to severe acute respiratory syndrome,but lower than MERS in the Republic of Korea.
基金supported by the Shanghai Committee of Science and Technology,China (Grant No.11ZR1443500)the National Natural Science Foundation of China (Grant No.11033004)
文摘Aiming at regional services,the space segment of COMPASS (Phase I) satellite navigation system is a constellation of Geostationary Earth Orbit (GEO),Inclined Geostationary Earth Orbit (IGSO) and Medium Earth Orbit (MEO) satellites.Precise orbit determination (POD) for the satellites is limited by the geographic distribution of regional tracking stations.Independent time synchronization (TS) system is developed to supplement the regional tracking network,and satellite clock errors and orbit data may be obtained by simultaneously processing both tracking data and TS data.Consequently,inconsistency between tracking system and TS system caused by remaining instrumental errors not calibrated may decrease navigation accuracy.On the other hand,POD for the mixed constellation of GEO/IGSO/MEO with the regional tracking network leads to parameter estimations that are highly correlated.Notorious example of correlation is found between GEO's orbital elements and its clock errors.We estimate orbital elements and clock errors for a 3GEO+2IGSO constellation in this study using a multi-satellite precise orbit determination (MPOD) strategy,with which clock error elimination algorithm is applied to separate orbital and clock estimates to improve numerical efficiency.Satellite Laser Ranging (SLR) data are used to evaluate User Ranging Error (URE),which is the orbital error projected on a receiver's line-of-sight direction.Two-way radio-wave time transfer measurements are used to evaluate clock errors.Experimenting with data from the regional tracking network,we conclude that the fitting of code data is better than 1 m in terms of Root-Mean-Square (RMS),and fitting of carrier phase is better than 1 cm.For orbital evaluation,difference between computed receiver-satellite ranging based on estimated orbits and SLR measurements is better than 1 m (RMS).For clock estimates evaluation,2-hour linear-fitting shows that the satellite clock rates are about 1.E-10 s/s,while receiver clock rates are about 1×10 13-1×10 12 s/s.For the 72-hour P
文摘BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSC
文摘Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.
基金supported by the National Key Technology Support Program of China(Nos.2014BAC23B05&2014BAC23B02)the Natural Sciences Foundation of China(No.51478017)+1 种基金the Youth Individual Project of Beijing Talents Training Fund(No.2015000021733G170)the Ministry of Environmental Protection Special Funds for Scientific Research on Public Causes(No.201409016)
文摘In China, volatile organic compound（VOC） control directives have been continuously released and implemented for important sources and regions to tackle air pollution. The corresponding control requirements were based on VOC emission amounts（EA）, but never considered the significant differentiation of VOC species in terms of atmospheric chemical reactivity. This will adversely influence the effect of VOC reduction on air quality improvement. Therefore,this study attempted to develop a comprehensive classification method for typical VOC sources in the Beijing–Tianjin–Hebei region（BTH）, by combining the VOC emission amounts with the chemical reactivities of VOC species. Firstly, we obtained the VOC chemical profiles by measuring 5 key sources in the BTH region and referencing another 10 key sources, and estimated the ozone formation potential（OFP） per ton VOC emission for these sources by using the maximum incremental reactivity（MIR） index as the characteristic of source reactivity（SR）. Then, we applied the data normalization method to respectively convert EA and SR to normalized EA（NEA） and normalized SR（NSR） for various sources in the BTH region.Finally, the control index（CI） was calculated, and these sources were further classified into four grades based on the normalized CI（NCI）. The study results showed that in the BTH region,furniture coating, automobile coating, and road vehicles are characterized by high NCI and need to be given more attention; however, the petro-chemical industry, which was designated as an important control source by air quality managers, has a lower NCI.
