Modern technological lifestyles promote allergic diseases,especially food allergies.The underlying molecular mechanisms remain to be uncovered.Protein acetylation is one of the most important post-translational modifi...Modern technological lifestyles promote allergic diseases,especially food allergies.The underlying molecular mechanisms remain to be uncovered.Protein acetylation is one of the most important post-translational modifications,and it is involved in regulating multiple body metabolic processes.This study aimed to clarify the effects of a high-fat diet(HFD)on allergy risk and the underlying mechanisms.Four-week-old male C57 BL/6 J mice were randomly divided into two groups and fed a normal fat diet(NFD)or HFD for 24 weeks.Then,serum lipids were measured,and skeletal muscle was collected for acetylome analysis.Compared with the findings in the NFD group,HFD-fed mice were obese and hyperlipidemic.Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups.Among these,eight acetylated proteins were upregulated in the HFD group.In addition,13 and 11 proteins were acetylated only in the HFD group and NFD group,respectively.These proteins were mainly involved in regulating energy metabolism and mitochondrial function.This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.展开更多
Spraying N-(2-chloro-4-pyridyl)-N′-phenylurea(CPPU),an exogenous cytokinin(CK)growth regulator,is the conventional method for inducing fruit set during melon(Cucumis melo L.)production;however,the mechanism by which ...Spraying N-(2-chloro-4-pyridyl)-N′-phenylurea(CPPU),an exogenous cytokinin(CK)growth regulator,is the conventional method for inducing fruit set during melon(Cucumis melo L.)production;however,the mechanism by which CPPU induces fruit set is unclear.Through histological and morphological observations,fruit size was comparable between CPPU-induced fruits and normal pollinated fruits because CPPU-induced fruits had higher cell density but smaller cell size compared with normal pollinated fruits.CPPU promotes the accumulation of gibberellin(GA)and auxin and decreases the level of abscisic acid(ABA)during fruit set.Moreover,application of the GA inhibitor paclobutrazol(PAC)partially inhibits CPPU-induced fruit set.Transcriptome analysis revealed that CPPU-induced fruit set specifically induced the GA-related pathway,in which the key synthase encoding gibberellin 20-oxidase 1(CmGA20ox1)was specifically upregulated.Further study indicated that the two-component response regulator 2(CmRR2)of the cytokinin signaling pathway,which is highly expressed at fruit setting,positively regulates the expression of CmGA20ox1.Collectively,our study determined that CPPU-induced melon fruit set is dependent on GA biosynthesis,providing a theoretical basis for the creation of parthenocarpic melon germplasm.展开更多
Barley(Hordeum vulgare L.)is an important economic crop for food,feed and industrial raw materials.In the present research,112 barley landraces from the Shanghai region were genotyped using genotyping-by-sequencing(GB...Barley(Hordeum vulgare L.)is an important economic crop for food,feed and industrial raw materials.In the present research,112 barley landraces from the Shanghai region were genotyped using genotyping-by-sequencing(GBS),and the genetic diversity and population structure were analyzed.The results showed that 210,268 Single Nucleotide Polymorphisms(SNPs)were present in total,and the average poly-morphism information content(PIC)was 0.1642.Genetic diversity and population structure analyses suggested that these barley landraces were differentiated and could be divided into three sub-groups,with morphological traits of row-type and adherence of the hulls the main distinguishing factors between groups.Genotypes with similar or duplicated names were also investigated according to their genetic backgrounds and seed appearances.This study provided valuable information on barley landraces from the Shanghai region,and showed that all these barley landraces should be protected and used for future breeding programs.展开更多
Phrynocephalus vlangalii are widely distributed on Tibetan plateau spanning diverse altitudes and habitats. In the present study, P.vlangalii were exposed to 8% oxygen concentration in a hypoxic chamber for 6 weeks. T...Phrynocephalus vlangalii are widely distributed on Tibetan plateau spanning diverse altitudes and habitats. In the present study, P.vlangalii were exposed to 8% oxygen concentration in a hypoxic chamber for 6 weeks. Then the body temperature(T_b), standard metabolic rate(SMR), heart rate and metabolic enzyme activities of the lizards were measured at 20℃ and 30℃. The results indicated that hypoxia exposure decreased T_b, SMR and heart rate. Lactate dehydrogenase(LDH) activity of 8% O_2 group became significant elevated in liver and skeletal muscle compared with control group at 20℃, but descended significantly in heart. Using electrophoresis we found that LDH contains five isozymes(LDH1, LDH2, LDH3, LDH4 and LDH5) and are expressed specifically in liver, skeletal muscle and heart. Citrate synthase(CS) activity in the liver also decreased at 20℃ and 30℃. No significant difference of CS activity was found between the two groups in skeletal muscle and heart.展开更多
Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologic...Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologically confirmed GA(low-grade:n=154;high-grade:n=438)from January 2008 to March 2018 who were divided into training(n=450)and validation(n=142)sets according to the time of computed tomography(CT)examination.Radiomic features were extracted from the portal venous phase CT images.The Mann-Whitney U test and the least absolute shrinkage and selection operator(LASSO)regression model were used for feature selection,data dimension reduction and radiomics signature construction.Multivariable logistic regression analysis was applied to develop the prediction model.The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram.The performance of the nomogram was assessed with respect to its calibration and discrimination.Results:A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA(P<0.001 for both training and validation sets).A nomogram including the radiomics signature and tumor location as predictors was developed.The model showed both good calibration and good discrimination,in which C-index in the training set,0.752[95%confidence interval(95%CI):0.701-0.803];C-index in the validation set,0.793(95%CI:0.711-0.874).Conclusions:This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures,which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.展开更多
Since the physical and chemical properties of apatite and dolomite can be similar,the separation of these two minerals is difficult.Therefore,when performing this separation using the flotation method,it is necessary ...Since the physical and chemical properties of apatite and dolomite can be similar,the separation of these two minerals is difficult.Therefore,when performing this separation using the flotation method,it is necessary to search for selective depressants.An experimental research was performed on the separation behavior of apatite and dolomite using calcium lignosulfonate as a depressant,and the mechanism by which this occurs was analyzed.The results show that calcium lignosulfonate has a depressant effect on both apatite and dolomite,but the depressant effect on dolomite is stronger at the same dosage.Mechanism analysis shows that the adsorptive capacity of calcium lignosulfonate on dolomite is higher than that of apatite,which is due to the strong reaction between calcium lignosulfonate and the Ca sites on dolomite.In addition,there is a hydrogen bond between calcium lignosulfonate and dolomite,which further prevents the adsorption of sodium oleate to dolomite,thus greatly inhibiting the flotation of dolomite.展开更多
Objective:To systematically explore the effect and mechanism of traditional Chinese herbs in the treatment of allergic rhinitis.Methods:Magnolia flower,xanthium fruit,astragalus root,paniculate cynanchum,scutellaria r...Objective:To systematically explore the effect and mechanism of traditional Chinese herbs in the treatment of allergic rhinitis.Methods:Magnolia flower,xanthium fruit,astragalus root,paniculate cynanchum,scutellaria root,cicada molting,stephania root,small centipeda herb,and licorice root as traditional Chinese herbs are widely used to treat allergic rhinitis.With multiple database integration and entity grammar systems,a molecular interaction network of traditional Chinese herbs for treating allergic rhinitis was established.Bioinformatics approaches were adopted to integrate relevant data and biological information by multiple databases.Molecular interaction network of Chinese herbs for treating allergic rhinitis was constructed based on entity grammar systems model.The network was then used for elucidating the antiallergic rhinitis mechanism of the Chinese herbs on the molecular level.The subnetworks were also extracted to explicitly display the pathway and targets where effective components acted on.Results:Traditional Chinese herbs could influence various pathological aspects in allergic rhinitis including the production of pro-inflammatory substances,such as histamine and cytokine interleukin-4(IL-4),interleukin-13(IL-13),lowering immunoglobulin E(IgE)level or blocking antigen binding,altering the biological processes of IgE,modulating the balance of T helper(Th)or other cells by cell proliferation and differentiation,mediating cellecell signaling and second-messenger-mediated signaling,stabilizing the cell membrane,and affecting regulation of cellular defense response.Conclusion:The research theoretically confirms the mechanism of anti-allergic rhinitis by traditional Chinese herbs,provides important fundamental research information for treatment of allergic rhinitis,and may serve as a reference for new drug development and effective ingredients of compatibility.展开更多
Oil fields present a potential ecological risk to nearby farmland soil. Here we present a new method designed to evaluate the ability of winter wheat(Triticum aestivum) to contribute to the dissipation of polycyclic a...Oil fields present a potential ecological risk to nearby farmland soil. Here we present a new method designed to evaluate the ability of winter wheat(Triticum aestivum) to contribute to the dissipation of polycyclic aromatic hydrocarbons(PAHs), which are priority pollutants in soils contaminated by oily sludge. The influence of different doses of oily sludge on the dissipation of PAHs was studied along with individual PAH profiles in soils after different periods of plant growth. Five soil samples were artificially contaminated with different percentages of oily sludge(0 %, 5 %, 10 %, 15 % and 20 %). Winter wheat grew in the oily sludge–amended soils for 265 days.PAH content in the soils was monitored over the course of the study. The rate of PAH dissipation is related to the properties of different PAHs, period of winter wheat growth, and oily sludge application dose. Analysis for treated soils indicates that the dissipation of PAHs increased significantly over the first 212 days, followed by minimal changes over the final 53 days of treatment. In contrast, PAH dissipation slowed with increasing oily sludge application. For each PAH, the experimental results showed a significant compound-dependent trend. Winter wheat in the present study significantly enhanced the dissipation of PAHs in oily sludge–contaminated soil.展开更多
We present the axial profiles of argon helicon plasma measured by a local optical emission spectroscope(OES) and Langmuir RF-compensated probe. The results show that the emission intensity of the argon atom lines(750 ...We present the axial profiles of argon helicon plasma measured by a local optical emission spectroscope(OES) and Langmuir RF-compensated probe. The results show that the emission intensity of the argon atom lines(750 nm, 811 nm) is proportional to the plasma density determined by the Langmuir probe. The axial profile of helicon plasma depends on the discharge mode which changes with the RF power. Excited by helical antenna, the axial distribution of plasma density is similar to that of the external magnetic field in the capacitive coupled mode(E-mode). As the discharge mode changes into the inductively coupled mode(H-mode), the axial distribution of plasma density in the downstream can still be similar to that of the external magnetic field, but becomes more uniform in the upstream. When the discharge entered wave coupled mode(W-mode), the plasma becomes nearly uniform along the axis, showing a completely different profile from the magnetic field. The W-mode is expected to be a mixed pattern of helicon(H) and Trivelpiece-Gould(TG) waves.展开更多
目的评估养老机构老年人的衰弱程度,并探讨老年人多维度衰弱的风险因素.方法采用横断面调查研究,调查了上海市9个养老机构的218名老年人.使用Tilburg衰弱指数评估老年人的生理、心理和社会维度衰弱,分别使用老年抑郁量表、简易智力状态...目的评估养老机构老年人的衰弱程度,并探讨老年人多维度衰弱的风险因素.方法采用横断面调查研究,调查了上海市9个养老机构的218名老年人.使用Tilburg衰弱指数评估老年人的生理、心理和社会维度衰弱,分别使用老年抑郁量表、简易智力状态检查表(Mini-Mental State Examination,MMSE)、雅典失眠量表和日常生活能力(Activity of Daily Living,ADL)评估老年人抑郁症状、认知功能、睡眠质量和自理能力.结果养老机构老年人生理、心理和社会维度的衰弱程度为中等,不同维度之间呈现高度相关性.老年人的抑郁症状与其衰弱整体和各维度均呈正相关.老年人在养老机构中的实际活动参与和锻炼状况与其衰弱整体、生理和社会维度衰弱呈负相关.结论养老机构中的老年人普遍存在多维度衰弱.在进行衰弱评估时需要进行综合考虑,并采取综合干预措施,为养老机构中的老年人提供整体护理,采取个性化方式提高其活动度,防止衰弱带来的不良后果.展开更多
Periodontitis is a frequent chronic inflammatory disorder destroying periodontium.Recent studies have revealed the role of bromodomain and extraterminal domain inhibitor(BETi)and microRNA(miR)-130a in regulating macro...Periodontitis is a frequent chronic inflammatory disorder destroying periodontium.Recent studies have revealed the role of bromodomain and extraterminal domain inhibitor(BETi)and microRNA(miR)-130a in regulating macrophage polarization and pro-inflammatory response.However,little is known about whether apabetalone(a novel BETi)and miR-130a are correlated with chronic inflammatory state in periodontitis by regulating macrophage polarization.Here murine RAW264.7 macrophages were applied as an in vitro inflammatory model.After treatment with Porphyromonas gingivalis-derived lipopolysaccharide(Pg LPS)and apabetalone,the expression of macrophage M1 polarization markers and inflammatory cytokines was assessed using real-time PCR,western blot,and enzyme-linked immuno sorbent assay(ELISA).MiR-130a level was assessed using real-time PCR,and the target gene was identified using dual luciferase reporter assay.We demonstrated that apabetalone repressed Pg LPS-induced macrophage M1 polarization in a dose-dependent manner,as evidenced by decreased expression of inducible nitric oxide synthase(iNOS),CD86,and pro-inflammatory cytokines,and increased expression of Arg-1 and CD206.Mechanistically,Pg LPS increased miR-130a expression in macrophages,whereas apabetalone treatment repressed the effect.Functionally,forced expression of miR-130a promoted macrophage M1 polarization,and signal transducer and activator of transcription(STAT)-3 was the direct target gene of miR-130a in the process.Taken together,apabetalone decreases Pg LPS-induced macrophage M1 polarization via regulating miR-130a-3p/STAT3 axis,and may be a promising target for the clinical management of periodontitis.展开更多
Poikilothermic animals living in high-altitude environments can be greatly affected by the anaerobic metabolism and lactate recycling, which are catalyzed by an enzyme called lactate dehydrogenase(LDH). However, the f...Poikilothermic animals living in high-altitude environments can be greatly affected by the anaerobic metabolism and lactate recycling, which are catalyzed by an enzyme called lactate dehydrogenase(LDH). However, the function and possible regulatory mechanisms of their anaerobic glycolysis remained elusive. We compared the difference in LDH between a native high-altitude(4 353 m) lizard, Phrynocephalus erythrurus, and a closely related species, Phrynocephalus przewalskii that lives in intermediate altitude environment(1 400 m). The activity of LDH, the concentration of lactate, the distribution of isoenzyme, and the mRNA amounts of Ldh-A and Ldh-B were determined. In cardiac muscle, the lactate-forming activity of P. erythrurus in LDH was higher than of P. przewalskii LDH at all three temperatures tested(10 °C, 25 °C and 35 °C), while lactate-oxidation activity of LDH was significantly different between the two species only at 25 °C and 35 °C. In skeletal muscle, both lactate-forming and lactate-oxidation rates of P. erythrurus were lower than that of P. przewalskii. There was a higher proportion of H subunit and a significantly higher expression of Ldh-B, with a concomitant decrease of lactate concentration in P. erythrurus. These results indicate that P. erythrurus may have a strong potential for anaerobic metabolism, which is likely adapted to the hypoxic environment at high altitudes. Furthermore, P. erythrurus is capable of oxidizing more lactate than P. przewalskii. The Ldh-A cDNA of the two species consists of a 999 bp open reading frame(ORF), which encodes 332 amino acids, while Ldh-B cDNA consists of a 1 002 bp ORF encoding 333 amino acids. LDHA has the same amino acid sequence between the two species, but three amino acid substitutions(V12 I, N21 S and N318 K) were observed in LDHB. Structure analysis of LDH indicated that the substitutions of residues Val12 and Asp21 in P. erythrurus could be responsible for the highaltitude adaptation. The LDH characteristics of LDH in P. erythrurus suggest unique adaptation strategies of anaerobic metabolism in hypoxia and cold environments at high altitudes for poikilothermic animals.展开更多
A practical method is proposed to search for periodic orbits of elongated asteroids.The method obtains required initial variables of periodic orbits by using the rotating mass dipole with appropriate parameters,and th...A practical method is proposed to search for periodic orbits of elongated asteroids.The method obtains required initial variables of periodic orbits by using the rotating mass dipole with appropriate parameters,and then implement local iterations to obtain the real orbits over an asteroid in the polyhedral model.In this paper the dipole and polyhedral models,and list detailed procedures of the searching method are introduced.A planar single lobe orbit is presented to evaluate the effectiveness of the method,with the asteroid 216 Kleopatra of the triple asteroid system as a representative elongated body.By applying the above method,ten families of periodic orbits around Kleopatra are identified and discussed with respect to their orbital stabilities and periods.One sample of the sombrero orbit is checked by calculating 1000 hours to examine its orbital behavior.Besides the above orbits,the intriguing head-surrounding orbit is also analyzed.展开更多
Sox9 is an important member of Sox family which is involved in a variety of developmental processes including sex determination and gonadal differentiation. The cDNA of Sox9 from multiocellated racerunner E. multiocel...Sox9 is an important member of Sox family which is involved in a variety of developmental processes including sex determination and gonadal differentiation. The cDNA of Sox9 from multiocellated racerunner E. multiocellata was cloned using reverse transcription-polymerase chain reaction(RT-PCR) and rapid amplification of cDNA ends(RACE). The sequence contains a 1497 bp open reading frame, which encodes a 498 amino acid protein with a predicted molecular weight of 55.45 kDa. EmSox9 displays high similarity to those of reptiles, and shows an overall amino acid identity of >82%. We also investigated the tissue-specific expression of EmSox9 mRNA by realtime quantitative PCR. Sox9 mRNA is present in brain, heart, liver, kidney, gonads and muscle tissues of adult E. multiocellata, with the highest expression in brain and testis. The results indicate that Sox9 may play important roles in some tissues during E. multiocellata neural and gonadal development.展开更多
A microwave induced superposition of the 40S_(1/2) and 40P_(1/2) states of a Cs atom has been investigated in detail.Ultralong-range charge migration which spans a region more than 200 nm has been discovered. As far a...A microwave induced superposition of the 40S_(1/2) and 40P_(1/2) states of a Cs atom has been investigated in detail.Ultralong-range charge migration which spans a region more than 200 nm has been discovered. As far as we know, this is the first time to discover charge migration in such a long range. This leads to a large dipole moment which oscillates periodically. The present discovery may stimulate new applications such as quantum simulation of many body physics dominated by periodic interactions. In addition, we find an interesting phenomenon that Cs atoms in the superposition of 40S_(1/2) and 40P_(1/2) have a much larger blockade radius than those of Cs(40S_(1/2))or Cs(40P_(1/2)) atoms.展开更多
Electronic charge of molecules can move on time scales when the nuclei stand practically still,from few hundreds of attoseconds to few femtoseconds.This ultrafast process is called“charge migration”.A typical conseq...Electronic charge of molecules can move on time scales when the nuclei stand practically still,from few hundreds of attoseconds to few femtoseconds.This ultrafast process is called“charge migration”.A typical consequence is rapid change of electronic dipole,which points to the center of charge.Corresponding linear(one-dimensional,1D)and planar(2D)dipolar motions have already been well documented.Here we construct the first case of charge migration which causes chiral 3D dipolar motion,specifically along a helix about oriented iodo-acetylene(HCCI).Quantum dynamics simulations show that this can be induced by well-designed laser pulses.展开更多
An external resonant magnetic perturbation(RMP)field,which is an effective method to mitigate or suppress the edge localized mode(ELM),has been planned to be applied on the ELM control issue in ITER.A new set of magne...An external resonant magnetic perturbation(RMP)field,which is an effective method to mitigate or suppress the edge localized mode(ELM),has been planned to be applied on the ELM control issue in ITER.A new set of magnetic perturbation coils,named as high m coils,has been developed for the EAST tokamak.The magnetic perturbation field of the high m coils is localized in the midplane of the low field side,with the spectral characteristic of high m and wide n,where m and n are the poloidal and toroidal mode numbers,respectively.The high m coils generate a strong localized perturbation field.Edge magnetic topology under the application of high m coils should have either a small or no stochastic region.With the combination of the high m coils and the current RMP coils in the EAST,flexible working scenarios of the magnetic perturbation field are available,which is beneficial for ELM control exploration on EAST.Numerical simulations have been carried out to characterize the high m coil system,including the magnetic spectrum and magnetic topology,which shows a great flexibility of magnetic perturbation variation as a tool to investigate the interaction between ELM and external magnetic perturbation.展开更多
Circular RNAs(circRNAs)are endogenous non-coding RNAs with covalently closed structures,which have important functions in plants.However,their biogenesis,degradation,and function upon treatment with gibberellins(GAs)a...Circular RNAs(circRNAs)are endogenous non-coding RNAs with covalently closed structures,which have important functions in plants.However,their biogenesis,degradation,and function upon treatment with gibberellins(GAs)and auxins(1-naphthaleneacetic acid,NAA)remain unknown.Here,we systematically identified and characterized the expression patterns,evolutionary conservation,genomic features,and internal structures of circRNAs using RNase R-treated libraries from moso bamboo(Phyllostachys edulis)seedlings.Moreover,we investigated the biogenesis of circRNAs dependent on both cis-and trans-regulation.We explored the function of circRNAs,including their roles in regulating microRNA(miRNA)-related genes and modulating the alternative splicing of their linear counterparts.Importantly,we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs.Finally,we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA.Collectively,our study provides insights into the biogenesis,function,and miRNA-mediated degradation of circRNAs in moso bamboo.展开更多
Bioengineering of photorespiratory bypasses is an effective strategy for improving plant productivity by modulating photosynthesis.In previouswork,two photorespiratory bypasses,theGOC andGCGT bypasses,increased photos...Bioengineering of photorespiratory bypasses is an effective strategy for improving plant productivity by modulating photosynthesis.In previouswork,two photorespiratory bypasses,theGOC andGCGT bypasses,increased photosynthetic rates but decreased seed-setting rate in rice(Oryza sativa),probably owing to excess photosynthate accumulation in the stem.To solve this bottleneck,we successfully developed a newsynthetic photorespiratory bypass(called theGMAbypass)in rice chloroplasts by introducing Oryza sativa glycolate oxidase 1(OsGLO1),Cucurbita maxima malate synthase(CmMS),and Oryza sativa ascorbate peroxidase7(OsAPX7)into the rice genome using a high-efficiency transgene stacking system.Unlike the GOC and GCGT bypass genes driven by constitutive promoters,OsGLO1 in GMA plants was driven by a light-inducible Rubisco small subunit promoter(pRbcS);its expression dynamically changed in response to light,producing a more moderate increase in photosynthate.Photosynthetic rates were significantly increased inGMA plants,and grain yieldswere significantly improved under greenhouse and field conditions.Transgenic GMA rice showed no reduction in seed-setting rate under either test condition,unlike previous photorespiratory-bypass rice,probably reflecting proper modulation of the photorespiratory bypass.Together,these results imply that appropriate engineering of the GMA bypass can enhance rice growth and grain yield without affecting seed-setting rate.展开更多
Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjug...Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjugates(ADCs).Phenoxysily based ADC Ate-PPS-CA4 was prepared and its release was systematically investigated by mass spectrometry.Biological evaluation showed that Ate-PPS-CA4 displayed the ability to target delivery and self-immolative release the active payload CA4 on PD-L1 positive cells MDA-MB-231.As the same with its payload CA4,it could arrest the cell cycle to the G2/M phase and induced changes in cell morphology at the dose of its IC_(50).The development of this linker with novel drug release mechanisms will expand the methodology to construct ADCs,especially for non-internalizing ADCs by extracellular cleavage.展开更多
基金funded by the 111 project from the Education Ministry of China(B18053)。
文摘Modern technological lifestyles promote allergic diseases,especially food allergies.The underlying molecular mechanisms remain to be uncovered.Protein acetylation is one of the most important post-translational modifications,and it is involved in regulating multiple body metabolic processes.This study aimed to clarify the effects of a high-fat diet(HFD)on allergy risk and the underlying mechanisms.Four-week-old male C57 BL/6 J mice were randomly divided into two groups and fed a normal fat diet(NFD)or HFD for 24 weeks.Then,serum lipids were measured,and skeletal muscle was collected for acetylome analysis.Compared with the findings in the NFD group,HFD-fed mice were obese and hyperlipidemic.Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups.Among these,eight acetylated proteins were upregulated in the HFD group.In addition,13 and 11 proteins were acetylated only in the HFD group and NFD group,respectively.These proteins were mainly involved in regulating energy metabolism and mitochondrial function.This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.
基金This work was supported by the National Natural Science Foundation of China(32225044 to Z.Z.,32130093 to Z.Z.,32102404 to S.C.,32002064 to Y.L.)This work was also supported by the Taishan Scholar Foundation of the People’s Government of Shandong Province and the Natural Science Foundation of Shandong Province(ZR2020QC157).
文摘Spraying N-(2-chloro-4-pyridyl)-N′-phenylurea(CPPU),an exogenous cytokinin(CK)growth regulator,is the conventional method for inducing fruit set during melon(Cucumis melo L.)production;however,the mechanism by which CPPU induces fruit set is unclear.Through histological and morphological observations,fruit size was comparable between CPPU-induced fruits and normal pollinated fruits because CPPU-induced fruits had higher cell density but smaller cell size compared with normal pollinated fruits.CPPU promotes the accumulation of gibberellin(GA)and auxin and decreases the level of abscisic acid(ABA)during fruit set.Moreover,application of the GA inhibitor paclobutrazol(PAC)partially inhibits CPPU-induced fruit set.Transcriptome analysis revealed that CPPU-induced fruit set specifically induced the GA-related pathway,in which the key synthase encoding gibberellin 20-oxidase 1(CmGA20ox1)was specifically upregulated.Further study indicated that the two-component response regulator 2(CmRR2)of the cytokinin signaling pathway,which is highly expressed at fruit setting,positively regulates the expression of CmGA20ox1.Collectively,our study determined that CPPU-induced melon fruit set is dependent on GA biosynthesis,providing a theoretical basis for the creation of parthenocarpic melon germplasm.
基金funded by the Shanghai Agriculture Applied Technology Development Program(Grant No.2019-02-08-00-08-F01109)the Climbing Plan(Grant No.PG22211)and the Ear-Marked Fund for CARS(Grant No.CARS-05-01A-02)N.G.H.is supported at Rothamsted Research by the Biotechnology and Biological Sciences Research Council(BBSRC)via the Designing Future Wheat Programme(BB/P016855/1).
文摘Barley(Hordeum vulgare L.)is an important economic crop for food,feed and industrial raw materials.In the present research,112 barley landraces from the Shanghai region were genotyped using genotyping-by-sequencing(GBS),and the genetic diversity and population structure were analyzed.The results showed that 210,268 Single Nucleotide Polymorphisms(SNPs)were present in total,and the average poly-morphism information content(PIC)was 0.1642.Genetic diversity and population structure analyses suggested that these barley landraces were differentiated and could be divided into three sub-groups,with morphological traits of row-type and adherence of the hulls the main distinguishing factors between groups.Genotypes with similar or duplicated names were also investigated according to their genetic backgrounds and seed appearances.This study provided valuable information on barley landraces from the Shanghai region,and showed that all these barley landraces should be protected and used for future breeding programs.
基金supported by the National Natural Science Foundation of China(Nos.31272313 and 31472005 to Q.CHEN)Fundamental Research Funds for the Central Universities(lzujbky-2015-81 to X,L.Tang)
文摘Phrynocephalus vlangalii are widely distributed on Tibetan plateau spanning diverse altitudes and habitats. In the present study, P.vlangalii were exposed to 8% oxygen concentration in a hypoxic chamber for 6 weeks. Then the body temperature(T_b), standard metabolic rate(SMR), heart rate and metabolic enzyme activities of the lizards were measured at 20℃ and 30℃. The results indicated that hypoxia exposure decreased T_b, SMR and heart rate. Lactate dehydrogenase(LDH) activity of 8% O_2 group became significant elevated in liver and skeletal muscle compared with control group at 20℃, but descended significantly in heart. Using electrophoresis we found that LDH contains five isozymes(LDH1, LDH2, LDH3, LDH4 and LDH5) and are expressed specifically in liver, skeletal muscle and heart. Citrate synthase(CS) activity in the liver also decreased at 20℃ and 30℃. No significant difference of CS activity was found between the two groups in skeletal muscle and heart.
基金supported by the National Key Research and Development Program of China(No.2017YFC 1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Science Foundation of China(No.82071892,81771912,81901910)。
文摘Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologically confirmed GA(low-grade:n=154;high-grade:n=438)from January 2008 to March 2018 who were divided into training(n=450)and validation(n=142)sets according to the time of computed tomography(CT)examination.Radiomic features were extracted from the portal venous phase CT images.The Mann-Whitney U test and the least absolute shrinkage and selection operator(LASSO)regression model were used for feature selection,data dimension reduction and radiomics signature construction.Multivariable logistic regression analysis was applied to develop the prediction model.The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram.The performance of the nomogram was assessed with respect to its calibration and discrimination.Results:A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA(P<0.001 for both training and validation sets).A nomogram including the radiomics signature and tumor location as predictors was developed.The model showed both good calibration and good discrimination,in which C-index in the training set,0.752[95%confidence interval(95%CI):0.701-0.803];C-index in the validation set,0.793(95%CI:0.711-0.874).Conclusions:This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures,which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.
基金financially supported by the National Natural Science Foundation of China(No.52174248)the Natural Science Foundation of Jiangxi Province(No.20202ACBL214010)the Open Foundation of Key Laboratory of Hunan Province for Clean and Efficient Utilization of Strategic Calcium-containing Mineral Resources(No.2018TP1002)。
文摘Since the physical and chemical properties of apatite and dolomite can be similar,the separation of these two minerals is difficult.Therefore,when performing this separation using the flotation method,it is necessary to search for selective depressants.An experimental research was performed on the separation behavior of apatite and dolomite using calcium lignosulfonate as a depressant,and the mechanism by which this occurs was analyzed.The results show that calcium lignosulfonate has a depressant effect on both apatite and dolomite,but the depressant effect on dolomite is stronger at the same dosage.Mechanism analysis shows that the adsorptive capacity of calcium lignosulfonate on dolomite is higher than that of apatite,which is due to the strong reaction between calcium lignosulfonate and the Ca sites on dolomite.In addition,there is a hydrogen bond between calcium lignosulfonate and dolomite,which further prevents the adsorption of sodium oleate to dolomite,thus greatly inhibiting the flotation of dolomite.
基金This study was supported by the National Natural Science Foundation of China(81373985,and 81430094).
文摘Objective:To systematically explore the effect and mechanism of traditional Chinese herbs in the treatment of allergic rhinitis.Methods:Magnolia flower,xanthium fruit,astragalus root,paniculate cynanchum,scutellaria root,cicada molting,stephania root,small centipeda herb,and licorice root as traditional Chinese herbs are widely used to treat allergic rhinitis.With multiple database integration and entity grammar systems,a molecular interaction network of traditional Chinese herbs for treating allergic rhinitis was established.Bioinformatics approaches were adopted to integrate relevant data and biological information by multiple databases.Molecular interaction network of Chinese herbs for treating allergic rhinitis was constructed based on entity grammar systems model.The network was then used for elucidating the antiallergic rhinitis mechanism of the Chinese herbs on the molecular level.The subnetworks were also extracted to explicitly display the pathway and targets where effective components acted on.Results:Traditional Chinese herbs could influence various pathological aspects in allergic rhinitis including the production of pro-inflammatory substances,such as histamine and cytokine interleukin-4(IL-4),interleukin-13(IL-13),lowering immunoglobulin E(IgE)level or blocking antigen binding,altering the biological processes of IgE,modulating the balance of T helper(Th)or other cells by cell proliferation and differentiation,mediating cellecell signaling and second-messenger-mediated signaling,stabilizing the cell membrane,and affecting regulation of cellular defense response.Conclusion:The research theoretically confirms the mechanism of anti-allergic rhinitis by traditional Chinese herbs,provides important fundamental research information for treatment of allergic rhinitis,and may serve as a reference for new drug development and effective ingredients of compatibility.
基金jointly supported by National Natural Science Foundation of China(41541025)Open Research Fund Program of Shandong Provincial Key Laboratory of Eco-Environmental Science for Yellow River Delta(Binzhou University)(2015KFJJ01)
文摘Oil fields present a potential ecological risk to nearby farmland soil. Here we present a new method designed to evaluate the ability of winter wheat(Triticum aestivum) to contribute to the dissipation of polycyclic aromatic hydrocarbons(PAHs), which are priority pollutants in soils contaminated by oily sludge. The influence of different doses of oily sludge on the dissipation of PAHs was studied along with individual PAH profiles in soils after different periods of plant growth. Five soil samples were artificially contaminated with different percentages of oily sludge(0 %, 5 %, 10 %, 15 % and 20 %). Winter wheat grew in the oily sludge–amended soils for 265 days.PAH content in the soils was monitored over the course of the study. The rate of PAH dissipation is related to the properties of different PAHs, period of winter wheat growth, and oily sludge application dose. Analysis for treated soils indicates that the dissipation of PAHs increased significantly over the first 212 days, followed by minimal changes over the final 53 days of treatment. In contrast, PAH dissipation slowed with increasing oily sludge application. For each PAH, the experimental results showed a significant compound-dependent trend. Winter wheat in the present study significantly enhanced the dissipation of PAHs in oily sludge–contaminated soil.
基金supported by National Natural Science Foundation of China (Nos. 11475131, 11805011)
文摘We present the axial profiles of argon helicon plasma measured by a local optical emission spectroscope(OES) and Langmuir RF-compensated probe. The results show that the emission intensity of the argon atom lines(750 nm, 811 nm) is proportional to the plasma density determined by the Langmuir probe. The axial profile of helicon plasma depends on the discharge mode which changes with the RF power. Excited by helical antenna, the axial distribution of plasma density is similar to that of the external magnetic field in the capacitive coupled mode(E-mode). As the discharge mode changes into the inductively coupled mode(H-mode), the axial distribution of plasma density in the downstream can still be similar to that of the external magnetic field, but becomes more uniform in the upstream. When the discharge entered wave coupled mode(W-mode), the plasma becomes nearly uniform along the axis, showing a completely different profile from the magnetic field. The W-mode is expected to be a mixed pattern of helicon(H) and Trivelpiece-Gould(TG) waves.
基金This work was supported by the Fudan University Nursing Research Foundation(Fund#FNF201706).
文摘目的评估养老机构老年人的衰弱程度,并探讨老年人多维度衰弱的风险因素.方法采用横断面调查研究,调查了上海市9个养老机构的218名老年人.使用Tilburg衰弱指数评估老年人的生理、心理和社会维度衰弱,分别使用老年抑郁量表、简易智力状态检查表(Mini-Mental State Examination,MMSE)、雅典失眠量表和日常生活能力(Activity of Daily Living,ADL)评估老年人抑郁症状、认知功能、睡眠质量和自理能力.结果养老机构老年人生理、心理和社会维度的衰弱程度为中等,不同维度之间呈现高度相关性.老年人的抑郁症状与其衰弱整体和各维度均呈正相关.老年人在养老机构中的实际活动参与和锻炼状况与其衰弱整体、生理和社会维度衰弱呈负相关.结论养老机构中的老年人普遍存在多维度衰弱.在进行衰弱评估时需要进行综合考虑,并采取综合干预措施,为养老机构中的老年人提供整体护理,采取个性化方式提高其活动度,防止衰弱带来的不良后果.
基金This work was supported by the National Natural Science Foundation for Young Scientists of China(Grant No.81901004)the Youth Program Shanghai Municipal Health and Family Planning Commission grant(Grant No.20194Y0227)Shanghai Stomatological Hospital Science Foundation(Grant No.SSDC-2018-02).
文摘Periodontitis is a frequent chronic inflammatory disorder destroying periodontium.Recent studies have revealed the role of bromodomain and extraterminal domain inhibitor(BETi)and microRNA(miR)-130a in regulating macrophage polarization and pro-inflammatory response.However,little is known about whether apabetalone(a novel BETi)and miR-130a are correlated with chronic inflammatory state in periodontitis by regulating macrophage polarization.Here murine RAW264.7 macrophages were applied as an in vitro inflammatory model.After treatment with Porphyromonas gingivalis-derived lipopolysaccharide(Pg LPS)and apabetalone,the expression of macrophage M1 polarization markers and inflammatory cytokines was assessed using real-time PCR,western blot,and enzyme-linked immuno sorbent assay(ELISA).MiR-130a level was assessed using real-time PCR,and the target gene was identified using dual luciferase reporter assay.We demonstrated that apabetalone repressed Pg LPS-induced macrophage M1 polarization in a dose-dependent manner,as evidenced by decreased expression of inducible nitric oxide synthase(iNOS),CD86,and pro-inflammatory cytokines,and increased expression of Arg-1 and CD206.Mechanistically,Pg LPS increased miR-130a expression in macrophages,whereas apabetalone treatment repressed the effect.Functionally,forced expression of miR-130a promoted macrophage M1 polarization,and signal transducer and activator of transcription(STAT)-3 was the direct target gene of miR-130a in the process.Taken together,apabetalone decreases Pg LPS-induced macrophage M1 polarization via regulating miR-130a-3p/STAT3 axis,and may be a promising target for the clinical management of periodontitis.
基金supported by the National Natural Science Foundation of China (No. 31501860 to Xiaolong TANG, No. 31272313 and No. 31472005 to Qiang CHEN) Fundamental Research Funds for the Central Universities (lzujbky-2017-150 to Xiaolong TANG)Natural Science Foundation of Gansu Province: 1506RJYA243
文摘Poikilothermic animals living in high-altitude environments can be greatly affected by the anaerobic metabolism and lactate recycling, which are catalyzed by an enzyme called lactate dehydrogenase(LDH). However, the function and possible regulatory mechanisms of their anaerobic glycolysis remained elusive. We compared the difference in LDH between a native high-altitude(4 353 m) lizard, Phrynocephalus erythrurus, and a closely related species, Phrynocephalus przewalskii that lives in intermediate altitude environment(1 400 m). The activity of LDH, the concentration of lactate, the distribution of isoenzyme, and the mRNA amounts of Ldh-A and Ldh-B were determined. In cardiac muscle, the lactate-forming activity of P. erythrurus in LDH was higher than of P. przewalskii LDH at all three temperatures tested(10 °C, 25 °C and 35 °C), while lactate-oxidation activity of LDH was significantly different between the two species only at 25 °C and 35 °C. In skeletal muscle, both lactate-forming and lactate-oxidation rates of P. erythrurus were lower than that of P. przewalskii. There was a higher proportion of H subunit and a significantly higher expression of Ldh-B, with a concomitant decrease of lactate concentration in P. erythrurus. These results indicate that P. erythrurus may have a strong potential for anaerobic metabolism, which is likely adapted to the hypoxic environment at high altitudes. Furthermore, P. erythrurus is capable of oxidizing more lactate than P. przewalskii. The Ldh-A cDNA of the two species consists of a 999 bp open reading frame(ORF), which encodes 332 amino acids, while Ldh-B cDNA consists of a 1 002 bp ORF encoding 333 amino acids. LDHA has the same amino acid sequence between the two species, but three amino acid substitutions(V12 I, N21 S and N318 K) were observed in LDHB. Structure analysis of LDH indicated that the substitutions of residues Val12 and Asp21 in P. erythrurus could be responsible for the highaltitude adaptation. The LDH characteristics of LDH in P. erythrurus suggest unique adaptation strategies of anaerobic metabolism in hypoxia and cold environments at high altitudes for poikilothermic animals.
基金Supported by the National Natural Science Foundation of China(11602019)。
文摘A practical method is proposed to search for periodic orbits of elongated asteroids.The method obtains required initial variables of periodic orbits by using the rotating mass dipole with appropriate parameters,and then implement local iterations to obtain the real orbits over an asteroid in the polyhedral model.In this paper the dipole and polyhedral models,and list detailed procedures of the searching method are introduced.A planar single lobe orbit is presented to evaluate the effectiveness of the method,with the asteroid 216 Kleopatra of the triple asteroid system as a representative elongated body.By applying the above method,ten families of periodic orbits around Kleopatra are identified and discussed with respect to their orbital stabilities and periods.One sample of the sombrero orbit is checked by calculating 1000 hours to examine its orbital behavior.Besides the above orbits,the intriguing head-surrounding orbit is also analyzed.
基金supported by the National Natural Science Foundation of China (No. 30670263)
文摘Sox9 is an important member of Sox family which is involved in a variety of developmental processes including sex determination and gonadal differentiation. The cDNA of Sox9 from multiocellated racerunner E. multiocellata was cloned using reverse transcription-polymerase chain reaction(RT-PCR) and rapid amplification of cDNA ends(RACE). The sequence contains a 1497 bp open reading frame, which encodes a 498 amino acid protein with a predicted molecular weight of 55.45 kDa. EmSox9 displays high similarity to those of reptiles, and shows an overall amino acid identity of >82%. We also investigated the tissue-specific expression of EmSox9 mRNA by realtime quantitative PCR. Sox9 mRNA is present in brain, heart, liver, kidney, gonads and muscle tissues of adult E. multiocellata, with the highest expression in brain and testis. The results indicate that Sox9 may play important roles in some tissues during E. multiocellata neural and gonadal development.
基金supported by the National Key Research and Development Program of China (Grant No. 2017YFA0304203)the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (Grant No.IRT 17R70)+3 种基金the National Natural Science Foundation of China (Grant No. 11904215)the 111 Project(Grant No. D18001)the Fund for Shanxi “1331 Project”the Hundred Talent Program of Shanxi Province。
文摘A microwave induced superposition of the 40S_(1/2) and 40P_(1/2) states of a Cs atom has been investigated in detail.Ultralong-range charge migration which spans a region more than 200 nm has been discovered. As far as we know, this is the first time to discover charge migration in such a long range. This leads to a large dipole moment which oscillates periodically. The present discovery may stimulate new applications such as quantum simulation of many body physics dominated by periodic interactions. In addition, we find an interesting phenomenon that Cs atoms in the superposition of 40S_(1/2) and 40P_(1/2) have a much larger blockade radius than those of Cs(40S_(1/2))or Cs(40P_(1/2)) atoms.
基金supported by the National Key Research and Development Program of China(Grant No.2017YFA0304203)the Program for Changjiang Scholars and Innovative Research Team(Grant No.IRT17R70)+4 种基金the National Natural Science Foundation of China(Grant Nos.12004193 and 11904215)the 111 Project(Grant No.D18001)the Fund for Shanxi 1331 Project Key Subjects Constructionthe Hundred Talent Program of Shanxi ProvinceNJUPT-SF(Grant No.NY220089)。
文摘Electronic charge of molecules can move on time scales when the nuclei stand practically still,from few hundreds of attoseconds to few femtoseconds.This ultrafast process is called“charge migration”.A typical consequence is rapid change of electronic dipole,which points to the center of charge.Corresponding linear(one-dimensional,1D)and planar(2D)dipolar motions have already been well documented.Here we construct the first case of charge migration which causes chiral 3D dipolar motion,specifically along a helix about oriented iodo-acetylene(HCCI).Quantum dynamics simulations show that this can be induced by well-designed laser pulses.
基金supported by National Magnetic Confined Fusion Energy R&D Program of China(Nos.2017YFE0301100,2019YFE03040000 and 2017YFE0301300)National Natural Science Foundation of China(No.11875294)+1 种基金the Science Foundation of Institute of Plasma Physics,Chinese Academy of Sciences(No.DSJJ-2021-01)the Collaborative Innovation Program of Hefei Science Center,CAS(No.2021HSC-CIP019)。
文摘An external resonant magnetic perturbation(RMP)field,which is an effective method to mitigate or suppress the edge localized mode(ELM),has been planned to be applied on the ELM control issue in ITER.A new set of magnetic perturbation coils,named as high m coils,has been developed for the EAST tokamak.The magnetic perturbation field of the high m coils is localized in the midplane of the low field side,with the spectral characteristic of high m and wide n,where m and n are the poloidal and toroidal mode numbers,respectively.The high m coils generate a strong localized perturbation field.Edge magnetic topology under the application of high m coils should have either a small or no stochastic region.With the combination of the high m coils and the current RMP coils in the EAST,flexible working scenarios of the magnetic perturbation field are available,which is beneficial for ELM control exploration on EAST.Numerical simulations have been carried out to characterize the high m coil system,including the magnetic spectrum and magnetic topology,which shows a great flexibility of magnetic perturbation variation as a tool to investigate the interaction between ELM and external magnetic perturbation.
基金supported by the National Natural Science Foundation of China(Grant Nos.31971734 and 31800566)the National Key R&D Program of China(Grant No.2021YFD2200505)+2 种基金the Distinguished Young Scholar Program of Fujian Agriculture and Forestry University(Grant No.xjq202017)the Scientific Research Foundation of Graduate School of Fujian Agriculture and Forestry University(Grant No.324-1122yb061)the Forestry Peak Discipline Construction Project of Fujian Agriculture and Forestry University(Grant No.72202200205),China。
文摘Circular RNAs(circRNAs)are endogenous non-coding RNAs with covalently closed structures,which have important functions in plants.However,their biogenesis,degradation,and function upon treatment with gibberellins(GAs)and auxins(1-naphthaleneacetic acid,NAA)remain unknown.Here,we systematically identified and characterized the expression patterns,evolutionary conservation,genomic features,and internal structures of circRNAs using RNase R-treated libraries from moso bamboo(Phyllostachys edulis)seedlings.Moreover,we investigated the biogenesis of circRNAs dependent on both cis-and trans-regulation.We explored the function of circRNAs,including their roles in regulating microRNA(miRNA)-related genes and modulating the alternative splicing of their linear counterparts.Importantly,we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs.Finally,we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA.Collectively,our study provides insights into the biogenesis,function,and miRNA-mediated degradation of circRNAs in moso bamboo.
基金supported by the National Natural Science Foundation of China(3110019,32271757)the Natural Science Foundation of Henan Province(21010338)the Gansu Provincial Science and Technology Major Projects(22ZD6NA007).
文摘Bioengineering of photorespiratory bypasses is an effective strategy for improving plant productivity by modulating photosynthesis.In previouswork,two photorespiratory bypasses,theGOC andGCGT bypasses,increased photosynthetic rates but decreased seed-setting rate in rice(Oryza sativa),probably owing to excess photosynthate accumulation in the stem.To solve this bottleneck,we successfully developed a newsynthetic photorespiratory bypass(called theGMAbypass)in rice chloroplasts by introducing Oryza sativa glycolate oxidase 1(OsGLO1),Cucurbita maxima malate synthase(CmMS),and Oryza sativa ascorbate peroxidase7(OsAPX7)into the rice genome using a high-efficiency transgene stacking system.Unlike the GOC and GCGT bypass genes driven by constitutive promoters,OsGLO1 in GMA plants was driven by a light-inducible Rubisco small subunit promoter(pRbcS);its expression dynamically changed in response to light,producing a more moderate increase in photosynthate.Photosynthetic rates were significantly increased inGMA plants,and grain yieldswere significantly improved under greenhouse and field conditions.Transgenic GMA rice showed no reduction in seed-setting rate under either test condition,unlike previous photorespiratory-bypass rice,probably reflecting proper modulation of the photorespiratory bypass.Together,these results imply that appropriate engineering of the GMA bypass can enhance rice growth and grain yield without affecting seed-setting rate.
基金supported by Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at Shanghai Tech University。
文摘Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjugates(ADCs).Phenoxysily based ADC Ate-PPS-CA4 was prepared and its release was systematically investigated by mass spectrometry.Biological evaluation showed that Ate-PPS-CA4 displayed the ability to target delivery and self-immolative release the active payload CA4 on PD-L1 positive cells MDA-MB-231.As the same with its payload CA4,it could arrest the cell cycle to the G2/M phase and induced changes in cell morphology at the dose of its IC_(50).The development of this linker with novel drug release mechanisms will expand the methodology to construct ADCs,especially for non-internalizing ADCs by extracellular cleavage.
