To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-bas...To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.展开更多
The Qarhan Salt Lake(QSL)in western China is K-Sr-Li-B-Br-Rb multi-resource coexisting Quaternary brine deposits.Significant research efforts have been directed to the origin of K-Li resources and evolutionary history...The Qarhan Salt Lake(QSL)in western China is K-Sr-Li-B-Br-Rb multi-resource coexisting Quaternary brine deposits.Significant research efforts have been directed to the origin of K-Li resources and evolutionary history of the QSL.However,the study on the different sources,recharge processes,and differential distribution patterns for these resource elements in brine deposits is still inadequate.Therefore,we measured Li-B concentrations and H-O-Sr-B isotopic compositions of different waters(river,spring,and brine)from the QSL,combined with the reported K-Sr contents and multiple isotopes of waters,to discuss the recharge,source of K-Sr-Li-B and their spatial distributions,by analogy with other evaporite basins in the world.The results show that:(1)the K-Li-B-Sr elemental concentrations of brines and their spatial distribution in the QSL are diverse;(2)high K and Sr values are distributed in Dabuxun and Qarhan sections,respectively,which are controlled by Ca-Cl springs in the northern QSL;on the contrary,Li and B values are enriched in the Bieletan section and are charged by thermal springs in the Kunlun Mountains;(3)the formation and evolution of Ca-Cl and thermal springs constrain fundamentally on the recharge processes of K-Sr and Li-B elements in the terminal salt lakes of the Qaidam Basin(QB);(4)some analogues of recharge processes limit the resource elements of the QSL and other salt lakes(Da Qaidam,Lop Nur,Zhabuye,Atacama,and Guayatayoc)in the world provides a reference for the resource exploration in deep formation waters in the evaporite basins.展开更多
Prussian blue analogues(PBAs) with inherent ordered structures and abundant metal ion sites are widely explored as precursors for various electrochemical applications,including oxygen evolution reaction(OER).Using a r...Prussian blue analogues(PBAs) with inherent ordered structures and abundant metal ion sites are widely explored as precursors for various electrochemical applications,including oxygen evolution reaction(OER).Using a range of characterization techniques including Fourier-transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),X-ray diffraction(XRD) and energy dispersive spectroscopy(EDS),this work discloses the process of replacement of K^(+)by NH4^(+)in the interstitial spaces of the CoFe PBA by a hot aqueous urea solution,which influences the transformation of PBAs under further heat treatment and the OER performance of the deriva tives.After heat treatment at 400℃ under Ar flow,high-resolution transmission electron microscopy(HRTEM) images reveal that CoFe alloy nanoparticles grew on the crystalline cubes of CoFe PBA with K^(+),while CoFe PBA cubes with NH4^(+)become amorphous.Besides,the derivative of CoFe PBA with NH4^(+)(Ar-U-CoFe PBA) performs better than the derivative of CoFe PBA with K^(+)(Ar-CoFe PBA) in OER,registering a lower overpotential of 305 mV at 10 mA cm^(-2),a smaller Tafel slope of 36.1 mV dec^(-1),and better stability over a testing course of 20 h in 1.0 M KOH.A single-cell alkaline electrolyzer,using Ar-U-CoFe PBA and Pt/C for the anodic and cathodic catalyst,respectively,requires an initial cell voltage of 1.66 V to achieve 100 mA cm^(-2)at 80℃,with negligible degradation after100 h.展开更多
In this paper, an analogue correction method of errors (ACE) based on a complicated atmospheric model is further developed and applied to numerical weather prediction (NWP). The analysis shows that the ACE can eff...In this paper, an analogue correction method of errors (ACE) based on a complicated atmospheric model is further developed and applied to numerical weather prediction (NWP). The analysis shows that the ACE can effectively reduce model errors by combining the statistical analogue method with the dynamical model together in order that the information of plenty of historical data is utilized in the current complicated NWP model, Furthermore, in the ACE, the differences of the similarities between different historical analogues and the current initial state are considered as the weights for estimating model errors. The results of daily, decad and monthly prediction experiments on a complicated T63 atmospheric model show that the performance of the ACE by correcting model errors based on the estimation of the errors of 4 historical analogue predictions is not only better than that of the scheme of only introducing the correction of the errors of every single analogue prediction, but is also better than that of the T63 model.展开更多
AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two...AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two hepatitis B envelope antigen(HBeAg)positive CHB patients were enrolled and divided equally into two groups.One group received telbivudine(LDT,600 mg/d),and the other group received lamivudine(LAM,100 mg/d).Clinical,virological and immunological parameters were assessed at the baseline and at 4,12,24,36 and 48 wk.RESULTS:Both groups achieved significant hepatitis B virus(HBV)replication inhibition and alanine aminotransferase normalization at 48 wk.At the baseline,compared to healthy controls,CHB patients had a lower circulating CD8 T cell frequency(29.44%±11.55%vs 37.17%±7.30%,p=0.03)and higher frequencies of programmed death 1 positive CD8 T cells(pD-1+CD8 T)(16.48%±10.82%vs 7.02%±3.62%,p=0.0001)and CD4+CD25+Foxp3+T regulatory cells(Tregs)(23.64%±9.38%vs 13.60%±6.06%,p=0.001).On therapy,at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid(HBV DNA)and HBeAg declining,the frequencies of pD-1+CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups.At treatment week 4,patients treated with LDT had a lower frequency of pD-1+CD8 T cells compared to patients treated with LAM(10.08%±6.83%vs 20.51%±20.96%,p=0.02).The frequency of pD-1+CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level(r=0.45,p=0.01)and HBeAg level(r=0.47,p=0.01)at treatment week 24,but the frequency of Treg cells was only significantly correlated with the HBeAg level(r=0.44,p=0.02).Furthermore,the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.CONCLUSION:NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines.This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.展开更多
Located at the northwest continental slope of the South China Sea, the Qiongdongnan Basin bears valley-shaped bathymetry deepening toward east. It is separated from the Yinggehai Basin through NW-trending Indo-China-R...Located at the northwest continental slope of the South China Sea, the Qiongdongnan Basin bears valley-shaped bathymetry deepening toward east. It is separated from the Yinggehai Basin through NW-trending Indo-China-Red River shear zone, and connected with NW subsea basin through the Xisha Trough. Along with the rapid progress of the deepwater exploration, large amounts of high resolution geophysical and geological data were accumulated. Scientific researches about deepwater basins kept revealing brand new tectonic and sedimentary discoveries. In order to summarize the structural features and main controlling factors of the deepwater Qiongdongnan Basin, a series of researches on basin architecture, fault activities, tectonic deformation and evolution were carried out. In reference to analogue modeling experiments, a tectonic situation and a basin formation mechanism were discussed. The researches indicate that:the northern boundary of the Qiongdongnan Basin is strongly controlled by No. 2 fault. The overlapping control of two stress fields from the east and the west made the central depression zone extremely thinned. Combined with the changed stress field, the segmentation of a preexisting weakness zone made the sags in the east experiencing different rifting histories from the west ones. The NE-trending west segment of the Qiongdongnan Basin experienced strong rifting during Eocene, while the roughly EW-trending sags in the east segment show strong rifting during late Eocene and early Oligocene. Local structures such as NW-trending basal fault and inherited uplifts controlled the lateral segmentation. So first order factors such as regional stress field and preexisting weakness zone controlled the basin zonation, while the second order factors determined the segmentation from east to west.展开更多
Hepatocellular carcinoma(HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus(HBV) infection(CHB) is the most important etiologic factor of this tumor, a...Hepatocellular carcinoma(HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus(HBV) infection(CHB) is the most important etiologic factor of this tumor, accounting for the development of more than50% of the cases in the world. Primary prevention ofHCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204(update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and environmental factors as evaluated in the world literature. Moreover, the benefits of antiviral treatment of CHB with nucleos/tide analogs, which have changed the natural history of the disease and have reduced but not eliminated the risk of HCC are also reviewed.展开更多
The fluvial-tidal transition(FTT)is a complex depositional zone,where fluvial flow is modified by tides as rivers approach a receiving marine basin.Variations in the relative importance of tidal versus fluvial process...The fluvial-tidal transition(FTT)is a complex depositional zone,where fluvial flow is modified by tides as rivers approach a receiving marine basin.Variations in the relative importance of tidal versus fluvial processes lead to a distinctive distribution of sediments that accumulate on channel bars.The FTT generally consists of three broad zones:(1)a freshwater-tidal zone;(2)a tidally influenced freshwater to brackish-water transition:and(3)a zone of relatively sustained brackish-water conditions with stronger tides.A very common type of deposit through the fluvial-tidal transition,especially on the margins of migrating channels,is inclined heterolithic stratification(IHS).At present,a detailed account of changes in the character of IHS across the FIT of a paleo-channel system has not been reported,although a number of modern examples have been documented.To fill this gap,we quantitatively assess the sedimentology and ichnology of IHS from seven cored intervals in three geographic areas situated within the youngest paleovalley("A"Valley)in the Lower Cretaceous McMurray Formation of Alberta.Canada.We compare the data to trends defined along the FTT in the present-day Fraser River in British Columbia.Canada to interpret paleo-depositional position in the ancient fluvial-tidal channels.Analysis determined that the mean mudstone thickness is 8.2 cm in the southern study area(SA).Mean thickness increases to 11 cm in the central study area(CA),and decreases again to 4.4 cm in the northern study area(NA).The proportion of mudstone is 31%in SA,44%in CA,and 27%in NA.Thicknessweighted mean bioturbation intensity in sands varied from 0.29 in SA and CA.to 0.28 in NA.On the other hand,thickness-weighted mean bioturbation intensity(Bl)in mudstone increases from 1.46 in SA.to 1.77 in CA.and is 1.94 in NA.The ichnological diversity also increased from south to north.Sedimentological results show sinilar trends to those of the Fraser River,enabling the identification of a freshwater to brackish-water transition zone with tidal influence.The interpreted position of the transition is underpinned by the bioturbation intensity and trace-fossil diversity trends,indicating periodic brackish-water conditions throughout SA in the McMurray Formation during low river flow conditions.Together,these data suggest that a broad FTT existed in the"A"Valley,with fluvial-dominated channels to the south that experienced seasonal brackish-water inundation during base flow,and channels experiencing increasing brackish-water influence lying further north towards a turbidity maximun zone.The FIT zone appears to have extended for several hundred kilometers fron south to north.Based on the sedimentological and ichnological data,as well as estimations of lateral accretion rates,we refute the colmonly applied Mississippi River depositional analogue for McMurray Formation channels.Rather,we show that while not a perfect fit,the tidally influenced Fraser River shows much greater agreement with the depositional character recorded in McMurray Formation IHS.Future work on the McMurray system should focus on characterizing tide-dominatecl deltaic and estuarine systems,such as the Ganges-Brahmaputra,and on forward-modeling the evolution of tide-dominated and tideinfluenced river systems.展开更多
Abstract Elements and natural radionuclides in the contact zone of two granites with different ages would migrate from one to the other because of the difference in their chemical contents and later water-rock interac...Abstract Elements and natural radionuclides in the contact zone of two granites with different ages would migrate from one to the other because of the difference in their chemical contents and later water-rock interactions. This migration could serve as an analogue for the near-field process of radwastes in a high-level radwaste deep geological disposal repository.展开更多
Rapid global population growth has caused an increasing need for products containing protein.Meat products are the most common high-protein food source,but impact the environment,cause animal welfare issues,and raise ...Rapid global population growth has caused an increasing need for products containing protein.Meat products are the most common high-protein food source,but impact the environment,cause animal welfare issues,and raise public health concerns.Consumer health and food safety are paramount to the food industry.Both the scientists and food industry are actively seeking plant proteins to substitute for animal-sourced proteins.Plant proteins have a well-balanced amino acid composition,and exhibit great potential for replacing meat via the development of healthy,high-protein,low-saturated fat,cholesterol-free,and nutritionally similar meat-like products.Generally,meat analogue formulations are specially designed and processing conditions are optimized to obtain the texture and bite of real animal meat.This article focuses on plant-based meat analogues,and covers aspects regarding processing,products,quality,and nutritional and structural modifications.Product safety consciousness and consumer acceptance are also discussed.Challenges and perspectives for future research concerning nonmeat products are presented.展开更多
In the applications of large-scale energy storage,aqueous batteries are considered as rivals for organic batteries due to their environmentally friendly and low-cost nature.However,carrier ions always exhibit huge hyd...In the applications of large-scale energy storage,aqueous batteries are considered as rivals for organic batteries due to their environmentally friendly and low-cost nature.However,carrier ions always exhibit huge hydrated radius in aqueous electrolyte,which brings difficulty to find suitable host materials that can achieve highly reversible insertion and extraction of cations.Owing to open threedimensional rigid framework and facile synthesis,Prussian blue analogues(PBAs)receive the most extensive attention among various host candidates in aqueous system.Herein,a comprehensive review on recent progresses of PBAs in aqueous batteries is presented.Based on the application in different aqueous systems,the relationship between electrochemical behaviors(redox potential,capacity,cycling stability and rate performance)and structural characteristics(preparation method,structure type,particle size,morphology,crystallinity,defect,metal atom in highspin state and chemical composition)is analyzed and summarized thoroughly.It can be concluded that the required type of PBAs is different for various carrier ions.In particular,the desalination batteries worked with the same mechanism as aqueous batteries are also discussed in detail to introduce the application of PBAs in aqueous systems comprehensively.This report can help the readers to understand the relationship between physical/chemical characteristics and electrochemical properties for PBAs and find a way to fabricate high-performance PBAs in aqueous batteries and desalination batteries.展开更多
Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cu...Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups.展开更多
Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donor...Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.展开更多
In civil and mining operations that involve ground excavation and support, the loads are distributed between the ground and support depending on their relative stiffness. This paper presents the development of concept...In civil and mining operations that involve ground excavation and support, the loads are distributed between the ground and support depending on their relative stiffness. This paper presents the development of conceptual single-degree-of-freedom models, which are used to derive equations for estimating displacements and stresses for ground-support interaction problems encountered in pillars in room-andpillar mining(natural support system), and liners for circular vertical shafts(artificial support systems).For pillar assessment, mine-pillar interaction curves can be constructed using a double spring analogy.Additionally, the effectiveness of different support systems can be evaluated depending on their effect upon the mine-pillar system. For shaft design, an initial estimation of the required lining strength and thickness can be readily made based on a double ring analogue. For both problems, the results from the proposed approach compare well with those obtained by finite element numerical simulations.展开更多
Some new inequalities involving improper integrals are established in the paper which generalize the related results due to Pachpatte and Rodrigues.Discrete analogues of the integral inequalities obtained are also der...Some new inequalities involving improper integrals are established in the paper which generalize the related results due to Pachpatte and Rodrigues.Discrete analogues of the integral inequalities obtained are also derived.An example is given to show that the bound in Theorem 1 is not improvable.展开更多
Peptides are one of the indispensable substances in life. The use of computer aided drug design(CADD) methods to design peptides and peptiodmimetics can short the design cycle, save research funding, improve the level...Peptides are one of the indispensable substances in life. The use of computer aided drug design(CADD) methods to design peptides and peptiodmimetics can short the design cycle, save research funding, improve the level of whole research to a large extent and guide the discovery of new drugs. In this paper, Melittin and amoebapore three-dimensional quantitative structureactivity relationship(3D-QSAR) models were established by using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA) method. The result shows that, the correlation coefficient(q^2) was 0.583 and non-cross-validation correlation coefficient(r^2) was 0.972 for the melittin CoMFA model. The q^2 and r^2 were 0.630 and 0.995 for the best CoMSIA model, 0.645 and 0.993 for the amoebapore CoMFA model, and 0.738 and 0.996 for the best CoMSIA model. The statistical parameters demonstrated that the CoMFA and CoMSIA models had both good predictive ability and high statistical stability, and can provide theoretical basis for designing new high activity polypeptide drugs.展开更多
The Two-dimensional Quantitative Structure-activity Relationship (2D-QSAR) of a series of novel norcantharidin analogues, which exhibit hnhibitory activities of protein phosphatase 1 and 2A (PP1 and PP2A), has bee...The Two-dimensional Quantitative Structure-activity Relationship (2D-QSAR) of a series of novel norcantharidin analogues, which exhibit hnhibitory activities of protein phosphatase 1 and 2A (PP1 and PP2A), has been studied with a combined method of ab initio (I/F), molecular mechanics (MM+) and statistics. The established 2D-QSAR model (Eq. 1) for PP1 shows a reasonable regressive performance (R2= 0.749), and the hydrophobic property of this molecule plays a decisive role in determining the inhibitory activity of PP1. In addition, the established 2D-QSAR model (Eq. 2) for PP2A also shows an acceptable regressive performance (R2= 0.701), and the dipole moment of the molecule determines the inhibitory activity of PP2A.展开更多
Significant advances have been made in nucleos(t)ideanalogue(NA) therapy to treat chronic hepatitis B,and this therapy reduces the risk of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) in somepatients.H...Significant advances have been made in nucleos(t)ideanalogue(NA) therapy to treat chronic hepatitis B,and this therapy reduces the risk of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) in somepatients.However,whether NAs can also prevent recurrence after radical resection of HBV-related HCC remains controversial and is an important question,giventhat most patients will experience recurrence within afew years of curative surgery.Here we systematicallyreviewed the literature since 2004 on outcomes afteradministering NAs to patients with HBV-related HCCfollowing radical resection.We focused on treatmentindications,duration,effects on recurrence-free survivaland overall survival,and the management of NA resistance.We find that patients with HCC should stronglyconsider NA therapy if they are positive for HBV-DNA,and that the available evidence suggests that postoperative NA therapy can increase both recurrence-free andoverall survival.To minimize drug resistance,cliniciansshould opt for potent analogues with higher resistancebarriers,and they should monitor the patient carefully for emergence of NA-resistant HBV.展开更多
Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bi...Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.展开更多
The Yinggehai basin lies in the northwestern shelf of the South China Sea. The maximum depth of the Cenozoic sediments is 17 km. Present gas exploration was mainly in the Neogene strata. But it is estimated that the P...The Yinggehai basin lies in the northwestern shelf of the South China Sea. The maximum depth of the Cenozoic sediments is 17 km. Present gas exploration was mainly in the Neogene strata. But it is estimated that the Paleocene sediments (~8 km in thickness) has productive potential. So research on the Paleogene rifting structure will greatly enlarge the exploration area. 3D scaled sandbox is the analogue model for the Yinggehai basin. Comparing modeling with the basin by the positions and movement of depocenters, the geometric similarity, we aim to summarize the dynamic situation of Yinggehai basin during the rifting stage and to cast an objective prediction on the structures in the areas without data.展开更多
基金supported by Jiangsu Innovative Group of Meat Nutrition,Health and Biotechnologythe Postgraduate Research&Practice Innovation Program of Jiangsu Province(grant number:KYCX21_0575)。
文摘To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.
基金Supported by the Second Tibetan Plateau Scientific Expedition and Research Program(No.2019 QZKK 0805)the National Natural Science Foundation of China(No.U 21 A 2018)the Foundation of Department of Qinghai Science&Technology(No.2020-ZJ-T 06)。
文摘The Qarhan Salt Lake(QSL)in western China is K-Sr-Li-B-Br-Rb multi-resource coexisting Quaternary brine deposits.Significant research efforts have been directed to the origin of K-Li resources and evolutionary history of the QSL.However,the study on the different sources,recharge processes,and differential distribution patterns for these resource elements in brine deposits is still inadequate.Therefore,we measured Li-B concentrations and H-O-Sr-B isotopic compositions of different waters(river,spring,and brine)from the QSL,combined with the reported K-Sr contents and multiple isotopes of waters,to discuss the recharge,source of K-Sr-Li-B and their spatial distributions,by analogy with other evaporite basins in the world.The results show that:(1)the K-Li-B-Sr elemental concentrations of brines and their spatial distribution in the QSL are diverse;(2)high K and Sr values are distributed in Dabuxun and Qarhan sections,respectively,which are controlled by Ca-Cl springs in the northern QSL;on the contrary,Li and B values are enriched in the Bieletan section and are charged by thermal springs in the Kunlun Mountains;(3)the formation and evolution of Ca-Cl and thermal springs constrain fundamentally on the recharge processes of K-Sr and Li-B elements in the terminal salt lakes of the Qaidam Basin(QB);(4)some analogues of recharge processes limit the resource elements of the QSL and other salt lakes(Da Qaidam,Lop Nur,Zhabuye,Atacama,and Guayatayoc)in the world provides a reference for the resource exploration in deep formation waters in the evaporite basins.
基金Financial support from the China Scholarship Council(201806220068,201806650009) to F.Dthe Villum Experiment(grant No.35844) to X.X.
文摘Prussian blue analogues(PBAs) with inherent ordered structures and abundant metal ion sites are widely explored as precursors for various electrochemical applications,including oxygen evolution reaction(OER).Using a range of characterization techniques including Fourier-transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),X-ray diffraction(XRD) and energy dispersive spectroscopy(EDS),this work discloses the process of replacement of K^(+)by NH4^(+)in the interstitial spaces of the CoFe PBA by a hot aqueous urea solution,which influences the transformation of PBAs under further heat treatment and the OER performance of the deriva tives.After heat treatment at 400℃ under Ar flow,high-resolution transmission electron microscopy(HRTEM) images reveal that CoFe alloy nanoparticles grew on the crystalline cubes of CoFe PBA with K^(+),while CoFe PBA cubes with NH4^(+)become amorphous.Besides,the derivative of CoFe PBA with NH4^(+)(Ar-U-CoFe PBA) performs better than the derivative of CoFe PBA with K^(+)(Ar-CoFe PBA) in OER,registering a lower overpotential of 305 mV at 10 mA cm^(-2),a smaller Tafel slope of 36.1 mV dec^(-1),and better stability over a testing course of 20 h in 1.0 M KOH.A single-cell alkaline electrolyzer,using Ar-U-CoFe PBA and Pt/C for the anodic and cathodic catalyst,respectively,requires an initial cell voltage of 1.66 V to achieve 100 mA cm^(-2)at 80℃,with negligible degradation after100 h.
基金Project supported by the National Natural Science Foundation of China (Grant Nos 40575036 and 40325015).Acknowledgement The authors thank Drs Zhang Pei-Qun and Bao Ming very much for their valuable comments on the present paper.
文摘In this paper, an analogue correction method of errors (ACE) based on a complicated atmospheric model is further developed and applied to numerical weather prediction (NWP). The analysis shows that the ACE can effectively reduce model errors by combining the statistical analogue method with the dynamical model together in order that the information of plenty of historical data is utilized in the current complicated NWP model, Furthermore, in the ACE, the differences of the similarities between different historical analogues and the current initial state are considered as the weights for estimating model errors. The results of daily, decad and monthly prediction experiments on a complicated T63 atmospheric model show that the performance of the ACE by correcting model errors based on the estimation of the errors of 4 historical analogue predictions is not only better than that of the scheme of only introducing the correction of the errors of every single analogue prediction, but is also better than that of the T63 model.
基金Supported by The Shanghai Natural Science Fund,No.09ZR1400500the National Natural Science Foundation of China,No.30972600+1 种基金the GuangHui Fund of Hepatitis Prevention Fund Committee China,No.GHZ20100204the Shanghai Health Bureau Fund,No.2012092
文摘AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two hepatitis B envelope antigen(HBeAg)positive CHB patients were enrolled and divided equally into two groups.One group received telbivudine(LDT,600 mg/d),and the other group received lamivudine(LAM,100 mg/d).Clinical,virological and immunological parameters were assessed at the baseline and at 4,12,24,36 and 48 wk.RESULTS:Both groups achieved significant hepatitis B virus(HBV)replication inhibition and alanine aminotransferase normalization at 48 wk.At the baseline,compared to healthy controls,CHB patients had a lower circulating CD8 T cell frequency(29.44%±11.55%vs 37.17%±7.30%,p=0.03)and higher frequencies of programmed death 1 positive CD8 T cells(pD-1+CD8 T)(16.48%±10.82%vs 7.02%±3.62%,p=0.0001)and CD4+CD25+Foxp3+T regulatory cells(Tregs)(23.64%±9.38%vs 13.60%±6.06%,p=0.001).On therapy,at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid(HBV DNA)and HBeAg declining,the frequencies of pD-1+CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups.At treatment week 4,patients treated with LDT had a lower frequency of pD-1+CD8 T cells compared to patients treated with LAM(10.08%±6.83%vs 20.51%±20.96%,p=0.02).The frequency of pD-1+CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level(r=0.45,p=0.01)and HBeAg level(r=0.47,p=0.01)at treatment week 24,but the frequency of Treg cells was only significantly correlated with the HBeAg level(r=0.44,p=0.02).Furthermore,the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.CONCLUSION:NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines.This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.
基金The Major National Science and Technology Programs of China under contract No.2011ZX05025-003-005the Joint Program of the National Science Foundation and Guangdong Province under contract No.U1301233
文摘Located at the northwest continental slope of the South China Sea, the Qiongdongnan Basin bears valley-shaped bathymetry deepening toward east. It is separated from the Yinggehai Basin through NW-trending Indo-China-Red River shear zone, and connected with NW subsea basin through the Xisha Trough. Along with the rapid progress of the deepwater exploration, large amounts of high resolution geophysical and geological data were accumulated. Scientific researches about deepwater basins kept revealing brand new tectonic and sedimentary discoveries. In order to summarize the structural features and main controlling factors of the deepwater Qiongdongnan Basin, a series of researches on basin architecture, fault activities, tectonic deformation and evolution were carried out. In reference to analogue modeling experiments, a tectonic situation and a basin formation mechanism were discussed. The researches indicate that:the northern boundary of the Qiongdongnan Basin is strongly controlled by No. 2 fault. The overlapping control of two stress fields from the east and the west made the central depression zone extremely thinned. Combined with the changed stress field, the segmentation of a preexisting weakness zone made the sags in the east experiencing different rifting histories from the west ones. The NE-trending west segment of the Qiongdongnan Basin experienced strong rifting during Eocene, while the roughly EW-trending sags in the east segment show strong rifting during late Eocene and early Oligocene. Local structures such as NW-trending basal fault and inherited uplifts controlled the lateral segmentation. So first order factors such as regional stress field and preexisting weakness zone controlled the basin zonation, while the second order factors determined the segmentation from east to west.
文摘Hepatocellular carcinoma(HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus(HBV) infection(CHB) is the most important etiologic factor of this tumor, accounting for the development of more than50% of the cases in the world. Primary prevention ofHCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204(update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and environmental factors as evaluated in the world literature. Moreover, the benefits of antiviral treatment of CHB with nucleos/tide analogs, which have changed the natural history of the disease and have reduced but not eliminated the risk of HCC are also reviewed.
基金The Natural Sciences and Engineering Research Council of Canada and Carbon Management Canada funded the rock record portion of this study
文摘The fluvial-tidal transition(FTT)is a complex depositional zone,where fluvial flow is modified by tides as rivers approach a receiving marine basin.Variations in the relative importance of tidal versus fluvial processes lead to a distinctive distribution of sediments that accumulate on channel bars.The FTT generally consists of three broad zones:(1)a freshwater-tidal zone;(2)a tidally influenced freshwater to brackish-water transition:and(3)a zone of relatively sustained brackish-water conditions with stronger tides.A very common type of deposit through the fluvial-tidal transition,especially on the margins of migrating channels,is inclined heterolithic stratification(IHS).At present,a detailed account of changes in the character of IHS across the FIT of a paleo-channel system has not been reported,although a number of modern examples have been documented.To fill this gap,we quantitatively assess the sedimentology and ichnology of IHS from seven cored intervals in three geographic areas situated within the youngest paleovalley("A"Valley)in the Lower Cretaceous McMurray Formation of Alberta.Canada.We compare the data to trends defined along the FTT in the present-day Fraser River in British Columbia.Canada to interpret paleo-depositional position in the ancient fluvial-tidal channels.Analysis determined that the mean mudstone thickness is 8.2 cm in the southern study area(SA).Mean thickness increases to 11 cm in the central study area(CA),and decreases again to 4.4 cm in the northern study area(NA).The proportion of mudstone is 31%in SA,44%in CA,and 27%in NA.Thicknessweighted mean bioturbation intensity in sands varied from 0.29 in SA and CA.to 0.28 in NA.On the other hand,thickness-weighted mean bioturbation intensity(Bl)in mudstone increases from 1.46 in SA.to 1.77 in CA.and is 1.94 in NA.The ichnological diversity also increased from south to north.Sedimentological results show sinilar trends to those of the Fraser River,enabling the identification of a freshwater to brackish-water transition zone with tidal influence.The interpreted position of the transition is underpinned by the bioturbation intensity and trace-fossil diversity trends,indicating periodic brackish-water conditions throughout SA in the McMurray Formation during low river flow conditions.Together,these data suggest that a broad FTT existed in the"A"Valley,with fluvial-dominated channels to the south that experienced seasonal brackish-water inundation during base flow,and channels experiencing increasing brackish-water influence lying further north towards a turbidity maximun zone.The FIT zone appears to have extended for several hundred kilometers fron south to north.Based on the sedimentological and ichnological data,as well as estimations of lateral accretion rates,we refute the colmonly applied Mississippi River depositional analogue for McMurray Formation channels.Rather,we show that while not a perfect fit,the tidally influenced Fraser River shows much greater agreement with the depositional character recorded in McMurray Formation IHS.Future work on the McMurray system should focus on characterizing tide-dominatecl deltaic and estuarine systems,such as the Ganges-Brahmaputra,and on forward-modeling the evolution of tide-dominated and tideinfluenced river systems.
文摘Abstract Elements and natural radionuclides in the contact zone of two granites with different ages would migrate from one to the other because of the difference in their chemical contents and later water-rock interactions. This migration could serve as an analogue for the near-field process of radwastes in a high-level radwaste deep geological disposal repository.
基金This research was sponsored by a grant from the National Natural Science Foundation of China(31901641 and 31972023)by a grant from the Shanghai Science and Technology Committee(18JC1410801 and 19YF1422400)+1 种基金by the Startup Fund for Youngman Research at Shanghai Jiao Tong University(18X100040057)by the 20th Innovative Practice Plan for College Students at SJTU(IPP20192).
文摘Rapid global population growth has caused an increasing need for products containing protein.Meat products are the most common high-protein food source,but impact the environment,cause animal welfare issues,and raise public health concerns.Consumer health and food safety are paramount to the food industry.Both the scientists and food industry are actively seeking plant proteins to substitute for animal-sourced proteins.Plant proteins have a well-balanced amino acid composition,and exhibit great potential for replacing meat via the development of healthy,high-protein,low-saturated fat,cholesterol-free,and nutritionally similar meat-like products.Generally,meat analogue formulations are specially designed and processing conditions are optimized to obtain the texture and bite of real animal meat.This article focuses on plant-based meat analogues,and covers aspects regarding processing,products,quality,and nutritional and structural modifications.Product safety consciousness and consumer acceptance are also discussed.Challenges and perspectives for future research concerning nonmeat products are presented.
基金This work was sponsored by NSAF Joint Fund(U1830106)Science and Technology Innovation 2025 Major Program of Ningbo(2018B10061)K.C.Wong Magna Fund in Ningbo University.
文摘In the applications of large-scale energy storage,aqueous batteries are considered as rivals for organic batteries due to their environmentally friendly and low-cost nature.However,carrier ions always exhibit huge hydrated radius in aqueous electrolyte,which brings difficulty to find suitable host materials that can achieve highly reversible insertion and extraction of cations.Owing to open threedimensional rigid framework and facile synthesis,Prussian blue analogues(PBAs)receive the most extensive attention among various host candidates in aqueous system.Herein,a comprehensive review on recent progresses of PBAs in aqueous batteries is presented.Based on the application in different aqueous systems,the relationship between electrochemical behaviors(redox potential,capacity,cycling stability and rate performance)and structural characteristics(preparation method,structure type,particle size,morphology,crystallinity,defect,metal atom in highspin state and chemical composition)is analyzed and summarized thoroughly.It can be concluded that the required type of PBAs is different for various carrier ions.In particular,the desalination batteries worked with the same mechanism as aqueous batteries are also discussed in detail to introduce the application of PBAs in aqueous systems comprehensively.This report can help the readers to understand the relationship between physical/chemical characteristics and electrochemical properties for PBAs and find a way to fabricate high-performance PBAs in aqueous batteries and desalination batteries.
基金Supported by grants from the “Instituto de Salud Carlos Ⅲ”,Spain and the “European Regional Development Fund(ERDF),a way of making Europe”,No.PI12/00130 and No.PI15/00074the “Gilead Spain & Instituto de Salud Carlos Ⅲ”,No.GLD14_00217 and No.GLD16_00014
文摘Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups.
基金Supported by National High Technology Research and Development Program(863 Program)of China,Grant No.2012AA021001
文摘Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.
文摘In civil and mining operations that involve ground excavation and support, the loads are distributed between the ground and support depending on their relative stiffness. This paper presents the development of conceptual single-degree-of-freedom models, which are used to derive equations for estimating displacements and stresses for ground-support interaction problems encountered in pillars in room-andpillar mining(natural support system), and liners for circular vertical shafts(artificial support systems).For pillar assessment, mine-pillar interaction curves can be constructed using a double spring analogy.Additionally, the effectiveness of different support systems can be evaluated depending on their effect upon the mine-pillar system. For shaft design, an initial estimation of the required lining strength and thickness can be readily made based on a double ring analogue. For both problems, the results from the proposed approach compare well with those obtained by finite element numerical simulations.
基金Supported by the Natural Science Foundation of Guangdong Pronvince( 0 1 1 471 ) and Education Bu-reau( 0 1 76)
文摘Some new inequalities involving improper integrals are established in the paper which generalize the related results due to Pachpatte and Rodrigues.Discrete analogues of the integral inequalities obtained are also derived.An example is given to show that the bound in Theorem 1 is not improvable.
基金Supported by the National Natural Science Foundation of China(21475081)Natural Science Foundation of Shaanxi Province of China(2015JM2057)Graduate Innovation Fund of Shaanxi University of Science and Technology
文摘Peptides are one of the indispensable substances in life. The use of computer aided drug design(CADD) methods to design peptides and peptiodmimetics can short the design cycle, save research funding, improve the level of whole research to a large extent and guide the discovery of new drugs. In this paper, Melittin and amoebapore three-dimensional quantitative structureactivity relationship(3D-QSAR) models were established by using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA) method. The result shows that, the correlation coefficient(q^2) was 0.583 and non-cross-validation correlation coefficient(r^2) was 0.972 for the melittin CoMFA model. The q^2 and r^2 were 0.630 and 0.995 for the best CoMSIA model, 0.645 and 0.993 for the amoebapore CoMFA model, and 0.738 and 0.996 for the best CoMSIA model. The statistical parameters demonstrated that the CoMFA and CoMSIA models had both good predictive ability and high statistical stability, and can provide theoretical basis for designing new high activity polypeptide drugs.
基金supported by the China Scholarship Council (CSC [2006] No. 3085)
文摘The Two-dimensional Quantitative Structure-activity Relationship (2D-QSAR) of a series of novel norcantharidin analogues, which exhibit hnhibitory activities of protein phosphatase 1 and 2A (PP1 and PP2A), has been studied with a combined method of ab initio (I/F), molecular mechanics (MM+) and statistics. The established 2D-QSAR model (Eq. 1) for PP1 shows a reasonable regressive performance (R2= 0.749), and the hydrophobic property of this molecule plays a decisive role in determining the inhibitory activity of PP1. In addition, the established 2D-QSAR model (Eq. 2) for PP2A also shows an acceptable regressive performance (R2= 0.701), and the dipole moment of the molecule determines the inhibitory activity of PP2A.
文摘Significant advances have been made in nucleos(t)ideanalogue(NA) therapy to treat chronic hepatitis B,and this therapy reduces the risk of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) in somepatients.However,whether NAs can also prevent recurrence after radical resection of HBV-related HCC remains controversial and is an important question,giventhat most patients will experience recurrence within afew years of curative surgery.Here we systematicallyreviewed the literature since 2004 on outcomes afteradministering NAs to patients with HBV-related HCCfollowing radical resection.We focused on treatmentindications,duration,effects on recurrence-free survivaland overall survival,and the management of NA resistance.We find that patients with HCC should stronglyconsider NA therapy if they are positive for HBV-DNA,and that the available evidence suggests that postoperative NA therapy can increase both recurrence-free andoverall survival.To minimize drug resistance,cliniciansshould opt for potent analogues with higher resistancebarriers,and they should monitor the patient carefully for emergence of NA-resistant HBV.
基金the Project for Sci-ence and Technology Plan of Liaoning Province(No.2011225020).
文摘Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.
基金the MarginalSeaOpenL aboratory!(No.KZ951-B1-406-02)Mineral Resources Quantitive Prediction Explorative Evaluation Open L
文摘The Yinggehai basin lies in the northwestern shelf of the South China Sea. The maximum depth of the Cenozoic sediments is 17 km. Present gas exploration was mainly in the Neogene strata. But it is estimated that the Paleocene sediments (~8 km in thickness) has productive potential. So research on the Paleogene rifting structure will greatly enlarge the exploration area. 3D scaled sandbox is the analogue model for the Yinggehai basin. Comparing modeling with the basin by the positions and movement of depocenters, the geometric similarity, we aim to summarize the dynamic situation of Yinggehai basin during the rifting stage and to cast an objective prediction on the structures in the areas without data.