Determination of the magnetic structure and confirmation of the presence or absence of inversion(P)and time reversal(Τ)symmetry is imperative for correctly understanding the topological magnetic materials.Here highqu...Determination of the magnetic structure and confirmation of the presence or absence of inversion(P)and time reversal(Τ)symmetry is imperative for correctly understanding the topological magnetic materials.Here highquality single crystals of the layered manganese pnictide CaMnSb_(2)are synthesized using the self-flux method.展开更多
Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy.Because of their nanoscale size,complex biogenesis,and met...Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy.Because of their nanoscale size,complex biogenesis,and methodological limitations related to exosome isolation and detection,advancements in their analysis remain slow.Microfluidic technology offers a better analytic approach compared with conventional methods.Here,we developed a bead-based microarray for exosome isolation and multiplexed tumor marker detection.Using this method,exosomes are isolated by binding to antibodies on the bead surface,and tumor markers on the exosomes are detected through quantum dot(QD)probes.The beads are then uniformly trapped and queued among micropillars in the chip.This design benefits fluorescence observation by dispersing the signals into every single bead,thereby avoiding optical interference and enabling more accurate test results.We analyzed exosomes in the cell culture supernatant of lung cancer and endothelial cell lines,and different lung cancer markers labeled with three QD probes were used to conduct multiplexed detection of exosome surface protein markers.Lung cancer-derived samples showed much higher(~sixfold-tenfold)fluorescence intensity than endothelial cell samples,and different types of lung cancer samples showed distinctive marker expression levels.Additionally,using the chip to detect clinical plasma samples from cancer patients showed good diagnostic power and revealed a well consistency with conventional tests for serological markers.These results provide insight into a promising method for exosome tumor marker detection and early-stage cancer diagnosis.展开更多
First-principles calculations have been performed to study the lithium intercalations in MoS2. The formation energies, changes of volumes, electronic structures and charge densities of the lithium intercalations in Mo...First-principles calculations have been performed to study the lithium intercalations in MoS2. The formation energies, changes of volumes, electronic structures and charge densities of the lithium intercalations in MoS2 are presented. Our calculations show that during lithium intercalations in MoS2, the lithium intercalation formation energies per lithium atom are between 2.5 eV to 3.0 eV. The volume expansions of MoS2 due to lithium intercalations are relatively small展开更多
A membrane bioreactor(MBR)with ordinary aeration(reactor R1)and a MBR with microporous aeration(reactor R2)are conducted in parallel to investigate the characteristics of oily sludge and its effect on membrane fouling...A membrane bioreactor(MBR)with ordinary aeration(reactor R1)and a MBR with microporous aeration(reactor R2)are conducted in parallel to investigate the characteristics of oily sludge and its effect on membrane fouling.The results indicate that the order of membrane fouling rate from high to low is:reactor R1 dissolved oxygen(DO)(1 mg/L)>reactor R2 DO(1 mg/L)>reactor R1 DO(4 mg/L)>reactor R2 DO(4 mg/L).Membrane fouling rate is not related to oily sludge concentration but to oily sludge sedimentation performance and the small particle oily sludge is the key factor to affect the membrane fouling.The soluble microbial products(SMP)are examined by three-dimensional excitation-emission matrix(3DEEM)fluorescence spectra.3DEEM spectra demonstrate that the main organic substances of the SMP in two reactors are tyrosine aromatic protein,fulvic acid-like substances and soluble microbial products under DO are1 mg/L and 4 mg/L,respectively.The proportion sum of fulvic acid-like substances and soluble microbial products is the key factor affecting membrane fouling,and membrane fouling accelerates as the ratio increases.展开更多
In medical image segmentation,it is often necessary to collect opinions from multiple experts to make the final decision.This clinical routine helps to mitigate individual bias.However,when data is annotated by multip...In medical image segmentation,it is often necessary to collect opinions from multiple experts to make the final decision.This clinical routine helps to mitigate individual bias.However,when data is annotated by multiple experts,standard deep learning models are often not applicable.In this paper,we propose a novel neural network framework called Multi-rater Prism(MrPrism)to learn medical image segmentation from multiple labels.Inspired by iterative half-quadratic optimization,MrPrism combines the task of assigning multi-rater confidences and calibrated segmentation in a recurrent manner.During this process,MrPrism learns inter-observer variability while taking into account the image's semantic properties and finally converges to a self-calibrated segmentation result reflecting inter-observer agreement.Specifically,we propose Converging Prism(ConP)and Diverging Prism(DivP)to iteratively process the two tasks.ConP learns calibrated segmentation based on multi-rater confidence maps estimated by DivP,and DivP generates multi-rater confidence maps based on segmentation masks estimated by ConP.Experimental results show that the two tasks can mutually improve each other through this recurrent process.The final converged segmentation result of MrPrism outperforms state-of-the-art(SOTA)methods for a wide range of medical image segmentation tasks.The code is available at https://github.-com/WuJunde/MrPrism.展开更多
Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The ...Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.展开更多
Atherosclerosis is a chronic multifactorial cardiovascular disease.Western diets have been reported to affect atherosclerosis through regulating adipose function.In high cholesterol diet-fed ApoE^(−/−)mice,adipocyte H...Atherosclerosis is a chronic multifactorial cardiovascular disease.Western diets have been reported to affect atherosclerosis through regulating adipose function.In high cholesterol diet-fed ApoE^(−/−)mice,adipocyte HIF-1αdeficiency or direct inhibition of HIF-1αby the selective pharmacological HIF-1αinhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation,which lowers cholesterol levels and reduces inflammatory responses,resulting in improved dyslipidemia and atherogenesis.Smpd3,the gene encoding neutral sphingomyelinase,is identified as a new target gene directly regulated by HIF-1αthat is involved in ceramide generation.Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-1α-deficient mice.Therefore,HIF-1αinhibition may constitute a novel approach to slow atherosclerotic progression.展开更多
Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathog...Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.展开更多
The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying th...The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system.In this study,two kind of aqueous model drugs with different molecule weight,Congo red and albumin from bovine serum(BSA)were nanoencapsulated in poly(DL-lactic-co-glycolic acid)(PLGA)microspheres by emulsion electrospray.In the preparation process,the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution.The emulsion was then electrosprayed to fabricate drugnanoencapsulated PLGA microspheres.The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase(V_(w)/V_(o))and the molecule weight of model drugs.Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_(w)/V_(o).With the increase of the volume ratio of aqueous drug phase,the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate.Moreover,BSA showed a slower release rate from PLGA microspheres comparing to Congo red,which indicated the drug release rate could be affected by not only V_(w)/V_(o)but also the molecule weight of model drug.In brief,the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple systemto achieve controlled drug release at a desired rate satisfying the need of the practices.展开更多
Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration,which usually demands appropriate carriers like microspheres(MS)to ...Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration,which usually demands appropriate carriers like microspheres(MS)to control drugs releases.Electrospray has been proven an effective technique to prepare MS with uniform particle size and high drug-loading rate.In this study,we applied electrospray to simply and hierarchically fabricate sphere-in-sphere composite microspheres,with smaller poly(lactic-co-glycolic acid)MS(~8-10 lm in diameter)embedded in a larger chitosan MS(~250-300 lm in diameter).The scanning electron microscopy images revealed highly uniform MS that can be accurately controlled by adjusting the nozzle diameter or voltage.Two kinds of model drugs,bovine serum albumin and chlorhexidine acetate,were encapsulated in the microspheres.The fluorescence-labeled rhodamine-fluoresceine isothiocyanate(Rho-FITC)and ultraviolet(UV)spectrophotometry results suggested that loaded drugs got excellent distribution in microspheres,as well as sustained,slow release in vitro.In addition,far-UV circular dichroism and matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS)results indicated original secondary structure and molecular weight of drugs after electrospraying.Generally speaking,our research proposed a modified hierarchically electrospraying technique to prepare sphere-in-sphere composite MS with two different drugs loaded,which could be applied in sequential,multi-modality therapy.展开更多
The repair of infective bone defects is a great challenge in clinical work.It is of vital importance to develop a kind of bone scaffold with good osteogenic properties and long-term antibacterial activity for local an...The repair of infective bone defects is a great challenge in clinical work.It is of vital importance to develop a kind of bone scaffold with good osteogenic properties and long-term antibacterial activity for local anti-infection and bone regeneration.A porous mineralized collagen(MC)scaffold containing poly(D,L-lactide-co-glycolic acid)(PLGA)microspheres loaded with two antibacterial synthetic peptides,Pac-525 or KSL-W was developed and characterized via scanning electron microscopy(SEM),porosity measurement,swelling and mechanical tests.The results showed that the MC scaffold embedded with smooth and compact PLGA microspheres had a positive effect on cell growth and also had antibacterial properties.Through toxicity analysis,cell morphology and proliferation analysis and alkaline phosphatase evaluation,the antibacterial scaffolds showed excellent biocompatibility and osteogenic activity.The antibacterial property evaluated with Staphylococcus aureus and Escherichia coli suggested that the sustained release of Pac-525 or KSL-W from the scaffolds could inhibit the bacterial growth aforementioned in the long term.Our results suggest that the antimicrobial peptides-loaded MC bone scaffold has good antibacterial and osteogenic activities,thus providing a great promise for the treatment of infective bone defects.展开更多
Meat quality is an important trait in the pig industry.To identify genomic regions and haplotype blocks responsible for meat quality traits in pigs,a genome-wide association study was conducted for five traits includi...Meat quality is an important trait in the pig industry.To identify genomic regions and haplotype blocks responsible for meat quality traits in pigs,a genome-wide association study was conducted for five traits including intramuscular fat content,pH at 45 min and 24 h,drip loss within 24 h and water-holding capacity in 231 Yorkshire barrows using illumina porcine 60k SNP chips.The results showed that a total of 344 single nucleotide polymorphisms(SNP)were significantly associated with five meat quality traits(P<1×10^(–4)).Moreover,323 SNPs were within the reported QTL regions,of which 21 were novel.Also,158 SNPs fell into the proximal region of meat quality related genes.In addition,25 haplotype blocks based on 116 SNPs were revealed with SNP combination patterns for five traits.Our study added new SNP information for identification of meat quality traits in pigs and will help elucidate the mechanisms of meat quality in pigs.展开更多
In the present study, we developed a highly sensitive and convenient biosensor consisting of gold nanoparticle (AuNP) probes and a gene chip to detect microRNAs (miRNAs). Specific oligonucleotides were attached to...In the present study, we developed a highly sensitive and convenient biosensor consisting of gold nanoparticle (AuNP) probes and a gene chip to detect microRNAs (miRNAs). Specific oligonucleotides were attached to the glass surface as capture probes for the target miRNAs, which were then detected via hybridization to the AuNP probes. The signal was amplified via the re- duction of HAuCI4 by H202. The use of a single AuNP probe detected 10 pmol L-1 of target miRNA. The recovery rate for miR-126 from fetal bovine serum was 81.5%-109.1%. The biosensor detection of miR-126 in total RNA extracted from lung cancer tissues was consistent with the quantitative PCR (qPCR) results. The use of two AuNP probes further improved the de- tection sensitivity such that even 1 fmol L-t of target miR-125a-5p was detectable. This assay takes less than 1 h to complete and the results can be observed by the naked eye, The platform simultaneously detected lung cancer related miR-126 and miR-125a-5p. Therefore, this low cost, rapid, and convenient technology could be used for ultrasensitive and robust visual miRNA detection.展开更多
As an important advanced technique in the field of Earth observations,Synthetic Aperture Radar(SAR)plays a key role in the study of global environmental change,resources exploration,disaster mitigation,urban environme...As an important advanced technique in the field of Earth observations,Synthetic Aperture Radar(SAR)plays a key role in the study of global environmental change,resources exploration,disaster mitigation,urban environments,and even lunar exploration.However,studies on imaging,image processing,and Earth factor inversions have often been conducted independently for a long time,which significantly limits the application effectiveness of SAR remote sensing due to the lack of an overall integrated design scheme and integrated information processing.Focusing on this SAR application issue,this paper proposes and describes a new SAR data processing methodology–SAR data integrated processing(DIP)oriented on Earth environment factor inversions.The simple definition,typical integrated modes and overall implementation ideas are introduced.Finally,focusing on building information extraction(man-made targets)and sea ice classification(natural targets)applications,three SAR DIP methods and experiments are conducted.Improved results are obtained under the guidance of the SAR DIP framework.Therefore,the SAR DIP theoretical framework and methodology represent a new SAR science application mode that has the capability to improve the SAR remote sensing quantitative application level and promote the development of new theories and methodologies.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant Nos.12074023,12304053,and 12174018)the Large Scientific Facility Open Subject of Songshan Lake(Dongguan,Guangdong)the Fundamental Research Funds for the Central Universities in China。
文摘Determination of the magnetic structure and confirmation of the presence or absence of inversion(P)and time reversal(Τ)symmetry is imperative for correctly understanding the topological magnetic materials.Here highquality single crystals of the layered manganese pnictide CaMnSb_(2)are synthesized using the self-flux method.
基金supported by Grants from National Key Research and Development Program of China(Nos.2018YFA0108202 and 2017YFA0205300)National Science Foundation of China(Nos.61571429,61571077,61801464,and 61801465)+1 种基金the STS Project of the Chinese Academy of Sciences(No.KFJ-STS-SCYD-120)the Science and Technology Commission of Shanghai Municipality(Nos.16410711800 and 4391901900).
文摘Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy.Because of their nanoscale size,complex biogenesis,and methodological limitations related to exosome isolation and detection,advancements in their analysis remain slow.Microfluidic technology offers a better analytic approach compared with conventional methods.Here,we developed a bead-based microarray for exosome isolation and multiplexed tumor marker detection.Using this method,exosomes are isolated by binding to antibodies on the bead surface,and tumor markers on the exosomes are detected through quantum dot(QD)probes.The beads are then uniformly trapped and queued among micropillars in the chip.This design benefits fluorescence observation by dispersing the signals into every single bead,thereby avoiding optical interference and enabling more accurate test results.We analyzed exosomes in the cell culture supernatant of lung cancer and endothelial cell lines,and different lung cancer markers labeled with three QD probes were used to conduct multiplexed detection of exosome surface protein markers.Lung cancer-derived samples showed much higher(~sixfold-tenfold)fluorescence intensity than endothelial cell samples,and different types of lung cancer samples showed distinctive marker expression levels.Additionally,using the chip to detect clinical plasma samples from cancer patients showed good diagnostic power and revealed a well consistency with conventional tests for serological markers.These results provide insight into a promising method for exosome tumor marker detection and early-stage cancer diagnosis.
基金This work was supported by the National Natural Science Foundation of China under Grant No.10374076by the Natural Science Foundation of Fujian Province under Grant Nos.E0410025 and E032001.
文摘First-principles calculations have been performed to study the lithium intercalations in MoS2. The formation energies, changes of volumes, electronic structures and charge densities of the lithium intercalations in MoS2 are presented. Our calculations show that during lithium intercalations in MoS2, the lithium intercalation formation energies per lithium atom are between 2.5 eV to 3.0 eV. The volume expansions of MoS2 due to lithium intercalations are relatively small
基金National Natural Science Foundation of China(No.21173026)Key Program of the Natural Science Foundation of Hubei Province(No.2013CFA107).
文摘A membrane bioreactor(MBR)with ordinary aeration(reactor R1)and a MBR with microporous aeration(reactor R2)are conducted in parallel to investigate the characteristics of oily sludge and its effect on membrane fouling.The results indicate that the order of membrane fouling rate from high to low is:reactor R1 dissolved oxygen(DO)(1 mg/L)>reactor R2 DO(1 mg/L)>reactor R1 DO(4 mg/L)>reactor R2 DO(4 mg/L).Membrane fouling rate is not related to oily sludge concentration but to oily sludge sedimentation performance and the small particle oily sludge is the key factor to affect the membrane fouling.The soluble microbial products(SMP)are examined by three-dimensional excitation-emission matrix(3DEEM)fluorescence spectra.3DEEM spectra demonstrate that the main organic substances of the SMP in two reactors are tyrosine aromatic protein,fulvic acid-like substances and soluble microbial products under DO are1 mg/L and 4 mg/L,respectively.The proportion sum of fulvic acid-like substances and soluble microbial products is the key factor affecting membrane fouling,and membrane fouling accelerates as the ratio increases.
基金supported by the Excellent Young Science and Technology Talent Cultivation Special Project of China Academy of Chinese Medical Sciences(CI2023D006)the National Natural Science Foundation of China(82121003 and 82022076)+2 种基金Beijing Natural Science Foundation(2190023)Shenzhen Fundamental Research Program(JCYJ20220818103207015)Guangdong Provincial Key Laboratory of Human Digital Twin(2022B1212010004)。
文摘In medical image segmentation,it is often necessary to collect opinions from multiple experts to make the final decision.This clinical routine helps to mitigate individual bias.However,when data is annotated by multiple experts,standard deep learning models are often not applicable.In this paper,we propose a novel neural network framework called Multi-rater Prism(MrPrism)to learn medical image segmentation from multiple labels.Inspired by iterative half-quadratic optimization,MrPrism combines the task of assigning multi-rater confidences and calibrated segmentation in a recurrent manner.During this process,MrPrism learns inter-observer variability while taking into account the image's semantic properties and finally converges to a self-calibrated segmentation result reflecting inter-observer agreement.Specifically,we propose Converging Prism(ConP)and Diverging Prism(DivP)to iteratively process the two tasks.ConP learns calibrated segmentation based on multi-rater confidence maps estimated by DivP,and DivP generates multi-rater confidence maps based on segmentation masks estimated by ConP.Experimental results show that the two tasks can mutually improve each other through this recurrent process.The final converged segmentation result of MrPrism outperforms state-of-the-art(SOTA)methods for a wide range of medical image segmentation tasks.The code is available at https://github.-com/WuJunde/MrPrism.
基金supported by the National Key Research and Development Program of China(grant No.SQ2018YFC100236)the National Natural Science Foundation of China(grant Nos.91857115,81522007,81470554,31401011,and 81700010)+1 种基金the Fundamental Research Funds for the Central Universities:Clinical Medicine Plus X-Young Scholars Project of Peking University(grant No.PKU2018LCXQ013,China)Beijing Nova Program(grant No.Z161100004916056,China)
文摘Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.
基金This work was supported by the National Key Research and Development Program of China(2018YFA0800700 and 2018YFC1003900)the National Natural Science Foundation of China(Nos.91857115,31925021,82022028 and 81921001).
文摘Atherosclerosis is a chronic multifactorial cardiovascular disease.Western diets have been reported to affect atherosclerosis through regulating adipose function.In high cholesterol diet-fed ApoE^(−/−)mice,adipocyte HIF-1αdeficiency or direct inhibition of HIF-1αby the selective pharmacological HIF-1αinhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation,which lowers cholesterol levels and reduces inflammatory responses,resulting in improved dyslipidemia and atherogenesis.Smpd3,the gene encoding neutral sphingomyelinase,is identified as a new target gene directly regulated by HIF-1αthat is involved in ceramide generation.Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-1α-deficient mice.Therefore,HIF-1αinhibition may constitute a novel approach to slow atherosclerotic progression.
基金supported by the National Natural Science Foundation of China (81625001, 81700010)National Key Research & Development Program of China (2018YFC1312700, 2018YFC1312701)
文摘Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.
基金This work is partly supported by Tsinghua University Initiative Scientific Research Program(20161080091,20131089199)China Postdoctoral Science Foundation(No.2016M591075)the National Natural Science Foundation of China(51572144).
文摘The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system.In this study,two kind of aqueous model drugs with different molecule weight,Congo red and albumin from bovine serum(BSA)were nanoencapsulated in poly(DL-lactic-co-glycolic acid)(PLGA)microspheres by emulsion electrospray.In the preparation process,the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution.The emulsion was then electrosprayed to fabricate drugnanoencapsulated PLGA microspheres.The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase(V_(w)/V_(o))and the molecule weight of model drugs.Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_(w)/V_(o).With the increase of the volume ratio of aqueous drug phase,the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate.Moreover,BSA showed a slower release rate from PLGA microspheres comparing to Congo red,which indicated the drug release rate could be affected by not only V_(w)/V_(o)but also the molecule weight of model drug.In brief,the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple systemto achieve controlled drug release at a desired rate satisfying the need of the practices.
基金supported by National Natural Science Foundation of China(nos.31771056,81671827 and 51572144).
文摘Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration,which usually demands appropriate carriers like microspheres(MS)to control drugs releases.Electrospray has been proven an effective technique to prepare MS with uniform particle size and high drug-loading rate.In this study,we applied electrospray to simply and hierarchically fabricate sphere-in-sphere composite microspheres,with smaller poly(lactic-co-glycolic acid)MS(~8-10 lm in diameter)embedded in a larger chitosan MS(~250-300 lm in diameter).The scanning electron microscopy images revealed highly uniform MS that can be accurately controlled by adjusting the nozzle diameter or voltage.Two kinds of model drugs,bovine serum albumin and chlorhexidine acetate,were encapsulated in the microspheres.The fluorescence-labeled rhodamine-fluoresceine isothiocyanate(Rho-FITC)and ultraviolet(UV)spectrophotometry results suggested that loaded drugs got excellent distribution in microspheres,as well as sustained,slow release in vitro.In addition,far-UV circular dichroism and matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS)results indicated original secondary structure and molecular weight of drugs after electrospraying.Generally speaking,our research proposed a modified hierarchically electrospraying technique to prepare sphere-in-sphere composite MS with two different drugs loaded,which could be applied in sequential,multi-modality therapy.
基金sponsored by the National Natural Science Foundation of China(Grant Nos 31771056,81671827,51572144,61571077,61871068)the National Key R&D Program of China(No.2018YFB0704304).
文摘The repair of infective bone defects is a great challenge in clinical work.It is of vital importance to develop a kind of bone scaffold with good osteogenic properties and long-term antibacterial activity for local anti-infection and bone regeneration.A porous mineralized collagen(MC)scaffold containing poly(D,L-lactide-co-glycolic acid)(PLGA)microspheres loaded with two antibacterial synthetic peptides,Pac-525 or KSL-W was developed and characterized via scanning electron microscopy(SEM),porosity measurement,swelling and mechanical tests.The results showed that the MC scaffold embedded with smooth and compact PLGA microspheres had a positive effect on cell growth and also had antibacterial properties.Through toxicity analysis,cell morphology and proliferation analysis and alkaline phosphatase evaluation,the antibacterial scaffolds showed excellent biocompatibility and osteogenic activity.The antibacterial property evaluated with Staphylococcus aureus and Escherichia coli suggested that the sustained release of Pac-525 or KSL-W from the scaffolds could inhibit the bacterial growth aforementioned in the long term.Our results suggest that the antimicrobial peptides-loaded MC bone scaffold has good antibacterial and osteogenic activities,thus providing a great promise for the treatment of infective bone defects.
基金supported by grants from the National Key Basic Research Program of China(2012CB124702)National Outstanding Youth Foundation of the National Natural Science Foundation of China(31025026)the Fundamental Research Funds for the Central Universities.
文摘Meat quality is an important trait in the pig industry.To identify genomic regions and haplotype blocks responsible for meat quality traits in pigs,a genome-wide association study was conducted for five traits including intramuscular fat content,pH at 45 min and 24 h,drip loss within 24 h and water-holding capacity in 231 Yorkshire barrows using illumina porcine 60k SNP chips.The results showed that a total of 344 single nucleotide polymorphisms(SNP)were significantly associated with five meat quality traits(P<1×10^(–4)).Moreover,323 SNPs were within the reported QTL regions,of which 21 were novel.Also,158 SNPs fell into the proximal region of meat quality related genes.In addition,25 haplotype blocks based on 116 SNPs were revealed with SNP combination patterns for five traits.Our study added new SNP information for identification of meat quality traits in pigs and will help elucidate the mechanisms of meat quality in pigs.
基金supported by the National Basic Research Program of China (2012CB933303)the National Natural Science Foundation of China (61571429, 61571077, 61401442)+2 种基金the Innovation Team of Henan University of Science and Technology (2015XTD003)the Science and Technology Commission of Shanghai Municipality (12441902600, 1402H233900)the Shanghai Clinical Center/Shanghai Xuhui Central Hospital, Chinese Academic of Sciences (BRC2012002)
文摘In the present study, we developed a highly sensitive and convenient biosensor consisting of gold nanoparticle (AuNP) probes and a gene chip to detect microRNAs (miRNAs). Specific oligonucleotides were attached to the glass surface as capture probes for the target miRNAs, which were then detected via hybridization to the AuNP probes. The signal was amplified via the re- duction of HAuCI4 by H202. The use of a single AuNP probe detected 10 pmol L-1 of target miRNA. The recovery rate for miR-126 from fetal bovine serum was 81.5%-109.1%. The biosensor detection of miR-126 in total RNA extracted from lung cancer tissues was consistent with the quantitative PCR (qPCR) results. The use of two AuNP probes further improved the de- tection sensitivity such that even 1 fmol L-t of target miR-125a-5p was detectable. This assay takes less than 1 h to complete and the results can be observed by the naked eye, The platform simultaneously detected lung cancer related miR-126 and miR-125a-5p. Therefore, this low cost, rapid, and convenient technology could be used for ultrasensitive and robust visual miRNA detection.
基金This study was supported by the Key project of National Natural Science Foundation of China(No.61132006)the Major project of National Natural Science Foundation of China(No.41590852).
文摘As an important advanced technique in the field of Earth observations,Synthetic Aperture Radar(SAR)plays a key role in the study of global environmental change,resources exploration,disaster mitigation,urban environments,and even lunar exploration.However,studies on imaging,image processing,and Earth factor inversions have often been conducted independently for a long time,which significantly limits the application effectiveness of SAR remote sensing due to the lack of an overall integrated design scheme and integrated information processing.Focusing on this SAR application issue,this paper proposes and describes a new SAR data processing methodology–SAR data integrated processing(DIP)oriented on Earth environment factor inversions.The simple definition,typical integrated modes and overall implementation ideas are introduced.Finally,focusing on building information extraction(man-made targets)and sea ice classification(natural targets)applications,three SAR DIP methods and experiments are conducted.Improved results are obtained under the guidance of the SAR DIP framework.Therefore,the SAR DIP theoretical framework and methodology represent a new SAR science application mode that has the capability to improve the SAR remote sensing quantitative application level and promote the development of new theories and methodologies.