Background Hemifacial spasm （HFS） is a facial nerve disorder characterized by episodic involuntary ipsilateral facial muscle contraction.Information on Chinese patients with HFS has not been well-characterized.This ...Background Hemifacial spasm （HFS） is a facial nerve disorder characterized by episodic involuntary ipsilateral facial muscle contraction.Information on Chinese patients with HFS has not been well-characterized.This study aimed to evaluate the clinical feature and the treatment status of HFS across China.Methods A cross-sectional study including 1003 primary HFS patients had been carried out in 15 movement disorder clinics in China in 2012.The investigated information was acquired from questionnaires and medical records including demographic data,site of onset,aggravating and relieving factors,treatments prior to the investigation,etc.Results In this study,the ratio of male to female was 1.0：1.8,the mean age at onset was （46.6±11.5） years.About 1.0％ patients were bilaterally affected.The most often site of initial onset was the orbicularis oculi muscle.The most often affected sites were orbicularis oculi,zygomatic,and orbicularis oris muscles.Stress/anxiety and relaxation were most often aggravating and relieving factors,respectively; 2.3％ patients had family history,28.4％ cases were combined with hypertension,and 1.4％ patients were with trigeminal neuralgia.Botulinum toxin type A （BTX-A） injection was the most commonly used treatment,followed by acupuncture and oral medication.BTX-A maintained the highest repeat treatment ratio （68.7％）,while 98.4％ patients gave up acupuncture.The mean latency of BTX-A effect was （5.0±4.7） days,the mean total duration of the effect was （19.5±11.7） weeks,and 95.9％ patients developed improvements no worse than moderate in both severity and function.The most common side effect was droopy mouth.Conclusions The onset age of HFS in China is earlier than that in western countries.The most often used two treatments are BTX-A injection and acupuncture,while the latter kept the poor repeat treatment ratio because of dissatisfactory therapeutic effect.展开更多
Atherosclerosis is the main cause of ischemic stroke and myocardial infarction diseases.Nanoparticles have shown unique benefits for atherosclerosis treatment by targeting the lesional macrophages of plaques.However,m...Atherosclerosis is the main cause of ischemic stroke and myocardial infarction diseases.Nanoparticles have shown unique benefits for atherosclerosis treatment by targeting the lesional macrophages of plaques.However,most of the nanocarriers are administered intravenously,which is inconvenient and may cause complications.Herein,we developed an oral lipid-polymer based nanoparticles(FA-LNPs)decorated with folic acid,which can not only effectively overcome intestinal mucosal-epithelial barrier by increasing the transmembrane transport through intestinal epithelial and the accumulation in Peyer’s patches but also actively target to the aortic plaque sites and accumulate in lesional macrophages.Subsequently,naringenin(Nrg),one of the antiinflammation drugs,was designed to be the oral nanomedicine(FA-LNPs/Nrg)for the first time via the encapsulation of FALNPs.FA-LNPs/Nrg presented highly anti-atherosclerotic efficacy.After the atherosclerotic ApoE−/−mice were treated by FALNPs/Nrg via oral administration for three months,the aortic lesion area,plaque area,and necrotic core area of the aortic root were significantly decreased.Meanwhile,the lipid-related blood parameters recovered to normal levels.Our study provides a promising approach to atherosclerosis treatment based on the novel oral targeting delivery system.展开更多
Dy^(3+)-doped fluoride fiber lasers have important applications in environment monitoring,real-time sensing,and polymer processing.At present,achieving a high-efficiency and high-power Dy^(3+)-doped fluoride fiber las...Dy^(3+)-doped fluoride fiber lasers have important applications in environment monitoring,real-time sensing,and polymer processing.At present,achieving a high-efficiency and high-power Dy^(3+)-doped fluoride fiber laser in the mid-infrared(mid-IR)region over 3μm is a scientific and technological frontier.Typically,Dy^(3+)-doped fluoride fiber lasers use a unidirectional pumping method,which suffers from the drawback of high thermal loading density on the fiber tips,thus limiting power scalability.In this study,a bi-directional in-band pumping scheme,to address the limitations of output power scaling and to enhance the efficiency of the Dy^(3+)-doped fluoride fiber laser at 3.2μm,is investigated numerically based on rate equations and propagation equations.Detailed simulation results reveal that the optical‒optical efficiency of the bi-directional in-band pumped Dy^(3+)-doped fluoride fiber laser can reach 75.1%,approaching the Stokes limit of 87.3%.The potential for further improvement of the efficiency of the Dy^(3+)-doped fluoride fiber laser is also discussed.The bi-directional pumping scheme offers the intrinsic advantage of mitigating the thermal load on the fiber tips,unlike unidirectional pumping,in addition to its high efficiency.As a result,it is expected to significantly scale the power output of Dy^(3+)-doped fluoride fiber lasers in the mid-IR regime.展开更多
A new dibenzylbutyrolactone lignan named matairesinol 4'-O-β-D-cellobioside(1),together with a known compound(7R,85)-dihydrodehydrodiconiferyl alcohol(2)was isolated from Caulis Trachelospermi.The extract of Caul...A new dibenzylbutyrolactone lignan named matairesinol 4'-O-β-D-cellobioside(1),together with a known compound(7R,85)-dihydrodehydrodiconiferyl alcohol(2)was isolated from Caulis Trachelospermi.The extract of Caulis Trachelospermi,which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography,and its main components trachelogenin(3),nortrachelogenin(4),matairesinol(5)showed moderate inhibiting activities on NF-κB signaling pathway induced by TNFα,with the IC_(50) values of 17.7μg/mL,17.9μM,49.4μM and 29.1μM,respectively.展开更多
As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic mal...As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic malignancies and multiple solid tumors.Numerous evidence has expanded the medical application of CAR-T therapy for the treatment of many other human diseases beyond cancer.In this article,we discuss the principle of CAR-T and enumerate the current application and limitation in oncology.Finally,we provide a comprehensive perspective of current advance and future directions of CAR-T in treating multiple non-tumoral diseases.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by severe synovial inflammation and cartilage damage.Despite great progress in RA therapy,there still lacks the drugs to completely cure RA patients.Herei...Rheumatoid arthritis(RA)is an autoimmune disease characterized by severe synovial inflammation and cartilage damage.Despite great progress in RA therapy,there still lacks the drugs to completely cure RA patients.Herein,we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA(siTNFα)as an alternative anti-inflammatory approach for RA treatment.The loaded siTNFαact as not only the gene therapeutics to inhibit TNFαproduction by macrophages in inflamed synovium,but also the editors to reprogram neutrophils to anti-inflammatory phenotypes.Leveraging the active tendency of neutrophils to inflammation,the reprogrammed siTNFα/neutrophil cytopharmaceuticals(siTNFα/TP/NEs)can rapidly migrate to the inflamed synovium,transfer the loaded siTNFαto macrophages followed by the significant reduction of TNFαexpression,and circumvent the pro-inflammatory activity of neutrophils,thus leading to the alleviated synovial inflammation and improved cartilage protection.Our work provides a promising cytopharmaceutical for RA treatment,and puts forward a living neutrophil-based gene delivery platform.展开更多
In this paper, eleven strains, which were screened strictly from raw royal jelly, soil andhoneycomb etc. by meansof dilution plate and spread plate methods, were cultured at 28℃ for 60 h with shaking. To determine wh...In this paper, eleven strains, which were screened strictly from raw royal jelly, soil andhoneycomb etc. by meansof dilution plate and spread plate methods, were cultured at 28℃ for 60 h with shaking. To determine whether they could yield10-Hydroxy-2-decenoic acid during fermentation, gas chromatography and gas chromatography-mass spectrometry methodswere used. The results showed that the strains BH002 and BH004, were both identified as Crytococcaceae, where BH002was primarily classified into Candida for possessing the abilities. The 10-HDA productivity of Candida BH002 and that ofBH004 were 0.327% and 0.2648% respectively.展开更多
Background:The hemoglobin glycation index(HGI)was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin(HbA1c)bias.Here,we aimed to...Background:The hemoglobin glycation index(HGI)was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin(HbA1c)bias.Here,we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events(MACEs)by performing a large multicenter cohort study in China.Methods:A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals:a Longitudinal Study(the REACTION study)were divided into five subgroups(Q1-Q5)with the HGI quantiles(≤5th,>5th and≤33.3th,>33.3th and≤66.7th,>66.7th and≤95th,and>95th percentile).A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk.Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups.Results:The total 5-year MACE rate in the nationwide cohort was 6.87%(673/9791).Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors(x^(2)=29.5,P<0.001).After adjustment for potential confounders,subjects with HGIs≤-0.75 or>0.82 showed odds ratios(ORs)for MACE of 1.471(95%confidence interval[CI],1.027-2.069)and 2.222(95%CI,1.641-3.026)compared to subjects with HGIs of>-0.75 and≤-0.20.In the subgroup with non-coronary heart disease,the risk of MACE was significantly higher in subjects with HGIs≤-0.75(OR,1.540[1.039-2.234];P=0.027)and>0.82(OR,2.022[1.392-2.890];P<0.001)compared to those with HGIs of≤-0.75 or>0.82 after adjustment for potential confounders.Conclusions:We found a U-shaped correlation between the HGI values and the risk of 5-year MACE.Both low and high HGIs were associated with an increased risk of MACE.Therefore,the HGI may predict the 5-year MACE risk.展开更多
Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer nanoparticles.In this work,LPNs were applied to encapsulate brin...Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer nanoparticles.In this work,LPNs were applied to encapsulate brinzolamide(Brz-LPNs) for achieving sustained drug release,improving drug corneal permeation and enhancing drug topical therapeutic effect.The structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid(PLGA) nanocore which encapsulated Brz(Brz-NPs) and lipid shell around the core.Brz-LPNs were prepared by a modified thin-film dispersion method.With the parameters optimization of Brz-LPNs,optimal Brz-LPNs showed an average particle size of151.23±1.64 nm with a high encapsulation efficiency(EE) of 86.7%±2.28%.The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy(TEM).Fourier transformed infrared spectra(FTIR) analysis proved that Brz was successfully entrapped into Brz-LPNs.Brz-LPNs exhibited obvious sustained release of Brz,compared with AZOPT^■ and Brz-LPs.Furthermore,the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation(AZOPT^■) in vitro.Moreover,Brz-LPNs(1 mg/mL Brz) showed a more sustained and effective intraocular pressure(IOP) reduction than Brz-LPs(1 mg/mL) and AZOPT^■(10 mg/mL Brz) in vivo.In conclusion,Brz-LPNs,as promising ocular drug delivery systems,are well worth developing in the future for glaucoma treatment.展开更多
Background:Mesencephalic astrocyte-derived neurotrophic factor(MANF)is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress(ER stress).HSP70 family,a chaperon like heat shock pro...Background:Mesencephalic astrocyte-derived neurotrophic factor(MANF)is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress(ER stress).HSP70 family,a chaperon like heat shock protein family,was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells.However,the ER stress relative transcriptome,in MANF signaling cascades is still investigated.The involvement of HSP70,a 70kd member of HSP70 family,need further to be verified.Methods:The cell apoptosis was assayed by MTT,TUNEL staining and western blot of cleaved Caspase-3.The differentially expressed genes in SHSY-5Y cells under different conditions(control,6-OHDA,6-OHDA+MANF)were investigated by RNA-seq.Expression of HSP70 was further confirmed by real-time PCR.RNAi knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling pathway.Results:MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y cells.Six ER stress relative genes(HSP70,GRP78,xbp-1,ATF-4,ATF-6,MAPK)were found enriched in 6-OHDA+MANF treatment group.HSP70 was the most significantly up-regulated gene under 6-OHDA+MANF treatment in SHSY-5Y cells.RNAi knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y cells.Conclusion:MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes,including HSP70 family members.The HSP70 expression level plays a key role in MANFmediated survival pathway.展开更多
As the core of his psychoanalysis,Jacques Lacan’s theory of desire explains the inner workings of activities from individual life to grand society from a relatively essential perspective.This article is intended to r...As the core of his psychoanalysis,Jacques Lacan’s theory of desire explains the inner workings of activities from individual life to grand society from a relatively essential perspective.This article is intended to recapitulate the basic facilitating dynamics of individual mental organs from the perspective of Lacanian psychoanalysis,using the concept of Paradise.On this basis,this article will briefly describe Lacan’s theory of desire and some of its key concepts,such as destitution,jouissance,desire,and explain the special role of the law in this context.Finally,this paper will return to the concept of Paradise with the paradoxes embedded in Lacan’s theory of desire,exploring how it affects the individual and the way the individual copes with it.展开更多
We demonstrate a simple method to obtain accurate optical waveforms with a gigahertz-level programmable modulation bandwidth and a watt-level output power for wideband optical control of free atoms and molecules.Arbit...We demonstrate a simple method to obtain accurate optical waveforms with a gigahertz-level programmable modulation bandwidth and a watt-level output power for wideband optical control of free atoms and molecules.Arbitrary amplitude and phase modulations are transferred from microwave to light with a low-power fiber electro-optical modulator.The sub-milliwatt optical sideband is co-amplified with the optical carrier in a power-balanced fashion through a tapered semiconductor amplifier(TSA).By automatically keeping TSA near saturation in a quasi-continuous manner,typical noise channels associated with pulsed high-gain amplifications are efficiently suppressed.As an example application,we demonstrate interleaved cooling and trapping of two rubidium isotopes with coherent nanosecond pulses.展开更多
The value of big data in science of science for knowledge discovery is that it can reveal deeper information and knowledge, promote knowledge integration in the whole process of scientific research, guide interdiscipl...The value of big data in science of science for knowledge discovery is that it can reveal deeper information and knowledge, promote knowledge integration in the whole process of scientific research, guide interdisciplinary integration, and provide new ideas and new methods for knowledge discovery research. This paper discusses the value and role of big data in science of science in knowledge discovery from five aspects, including exploring the laws of scientific research, revealing scientific structure, analyzing scientific research activities, supporting technical recognition and prediction, and serving science and technology evaluation.展开更多
Chinese as a foreign language (CFL) is a critical language in the United States, and the importance to have competent CFL teachers has been more and more realized. However, the literature does not show sufficient rese...Chinese as a foreign language (CFL) is a critical language in the United States, and the importance to have competent CFL teachers has been more and more realized. However, the literature does not show sufficient research on CFL teacher competency. To fill the gap, a series of exploratory research studies are initiated. As a part of the initiation, this study overviews the professional guidelines, resources, standards and requirements for CFL education in the U.S. at the national and state levels. The findings will be useful for designing teacher education program and teacher training program. In addition, student teachers, pre-service teachers, and in-service teachers can also use them as great references for their academic and/or professional development.展开更多
China has entered a stage of high-quality development in the new era.Especially as it ushers in the beginning of the Fourteenth Five-Year Plan,China is about to embark on a new journey to build a modern and powerful s...China has entered a stage of high-quality development in the new era.Especially as it ushers in the beginning of the Fourteenth Five-Year Plan,China is about to embark on a new journey to build a modern and powerful socialist country in an all-round way.Its population development and social policy changes are also at a critical turning point.As a country with a large population,we urgently need to build a society that is more inclusive of development,attach importance to the support of and tolerance for different population groups.展开更多
Objective: To describe the latest progress in the use of botulinum neurotoxin for post-stroke limb spasm. Methods: This paper looks up the relevant research literatures in recent years in PubMed, Web of Science, Sprin...Objective: To describe the latest progress in the use of botulinum neurotoxin for post-stroke limb spasm. Methods: This paper looks up the relevant research literatures in recent years in PubMed, Web of Science, Springer, Ovid, CNKI, WanFang databases and summarizes them. Results: The latest progress in the use of botulinum neurotoxin for post-stroke limb spasm was studied from the following aspects: the action mechanism of botulinum neurotoxin;efficacy evaluation;injection dose;target muscle selection;guiding technology;combination therapy. Conclusion: Botulinum neurotoxin is the first-line treatment for post-stroke limb spasm. We need to make continuous improvement and progress from the treatment period, injection dose, target muscle selection, guiding technology and efficacy evaluation to improve the quality of life of the majority of post-stroke survivors in China.展开更多
文摘Background Hemifacial spasm （HFS） is a facial nerve disorder characterized by episodic involuntary ipsilateral facial muscle contraction.Information on Chinese patients with HFS has not been well-characterized.This study aimed to evaluate the clinical feature and the treatment status of HFS across China.Methods A cross-sectional study including 1003 primary HFS patients had been carried out in 15 movement disorder clinics in China in 2012.The investigated information was acquired from questionnaires and medical records including demographic data,site of onset,aggravating and relieving factors,treatments prior to the investigation,etc.Results In this study,the ratio of male to female was 1.0：1.8,the mean age at onset was （46.6±11.5） years.About 1.0％ patients were bilaterally affected.The most often site of initial onset was the orbicularis oculi muscle.The most often affected sites were orbicularis oculi,zygomatic,and orbicularis oris muscles.Stress/anxiety and relaxation were most often aggravating and relieving factors,respectively; 2.3％ patients had family history,28.4％ cases were combined with hypertension,and 1.4％ patients were with trigeminal neuralgia.Botulinum toxin type A （BTX-A） injection was the most commonly used treatment,followed by acupuncture and oral medication.BTX-A maintained the highest repeat treatment ratio （68.7％）,while 98.4％ patients gave up acupuncture.The mean latency of BTX-A effect was （5.0±4.7） days,the mean total duration of the effect was （19.5±11.7） weeks,and 95.9％ patients developed improvements no worse than moderate in both severity and function.The most common side effect was droopy mouth.Conclusions The onset age of HFS in China is earlier than that in western countries.The most often used two treatments are BTX-A injection and acupuncture,while the latter kept the poor repeat treatment ratio because of dissatisfactory therapeutic effect.
基金This study was supported by the Youth Fund of National Natural Science Foundation of China(No.82104081)Sichuan Province Science and Technology Support Program(No.2020JDRC0052)+1 种基金the 1.3.5 Project for Disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18020/ZYJC18006)Science and Technology Project of Xinjiang Production and Construction Corps(No.2022AB020).
文摘Atherosclerosis is the main cause of ischemic stroke and myocardial infarction diseases.Nanoparticles have shown unique benefits for atherosclerosis treatment by targeting the lesional macrophages of plaques.However,most of the nanocarriers are administered intravenously,which is inconvenient and may cause complications.Herein,we developed an oral lipid-polymer based nanoparticles(FA-LNPs)decorated with folic acid,which can not only effectively overcome intestinal mucosal-epithelial barrier by increasing the transmembrane transport through intestinal epithelial and the accumulation in Peyer’s patches but also actively target to the aortic plaque sites and accumulate in lesional macrophages.Subsequently,naringenin(Nrg),one of the antiinflammation drugs,was designed to be the oral nanomedicine(FA-LNPs/Nrg)for the first time via the encapsulation of FALNPs.FA-LNPs/Nrg presented highly anti-atherosclerotic efficacy.After the atherosclerotic ApoE−/−mice were treated by FALNPs/Nrg via oral administration for three months,the aortic lesion area,plaque area,and necrotic core area of the aortic root were significantly decreased.Meanwhile,the lipid-related blood parameters recovered to normal levels.Our study provides a promising approach to atherosclerosis treatment based on the novel oral targeting delivery system.
基金the Hunan Provincial Natural Science Foundation of China(Nos.2023JJ30596 and 2022JJ30556)the Scientific Research Fund of Hunan Provincial Education Department,China(No.21B0136)+2 种基金the National Natural Science Foundation of China(No.62105209)the Shanghai Pujiang Program,China(No.22PJ1414900)the Shenzhen Government’s Plan of Science and Technology,China(No.RCYX20210609103157071)。
文摘Dy^(3+)-doped fluoride fiber lasers have important applications in environment monitoring,real-time sensing,and polymer processing.At present,achieving a high-efficiency and high-power Dy^(3+)-doped fluoride fiber laser in the mid-infrared(mid-IR)region over 3μm is a scientific and technological frontier.Typically,Dy^(3+)-doped fluoride fiber lasers use a unidirectional pumping method,which suffers from the drawback of high thermal loading density on the fiber tips,thus limiting power scalability.In this study,a bi-directional in-band pumping scheme,to address the limitations of output power scaling and to enhance the efficiency of the Dy^(3+)-doped fluoride fiber laser at 3.2μm,is investigated numerically based on rate equations and propagation equations.Detailed simulation results reveal that the optical‒optical efficiency of the bi-directional in-band pumped Dy^(3+)-doped fluoride fiber laser can reach 75.1%,approaching the Stokes limit of 87.3%.The potential for further improvement of the efficiency of the Dy^(3+)-doped fluoride fiber laser is also discussed.The bi-directional pumping scheme offers the intrinsic advantage of mitigating the thermal load on the fiber tips,unlike unidirectional pumping,in addition to its high efficiency.As a result,it is expected to significantly scale the power output of Dy^(3+)-doped fluoride fiber lasers in the mid-IR regime.
基金Financial support from the“Significant New Drugs Created”National Science and Technology Major Project of China(Nos.2012ZX09301003-001-004 and 2013ZX09102-018)。
文摘A new dibenzylbutyrolactone lignan named matairesinol 4'-O-β-D-cellobioside(1),together with a known compound(7R,85)-dihydrodehydrodiconiferyl alcohol(2)was isolated from Caulis Trachelospermi.The extract of Caulis Trachelospermi,which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography,and its main components trachelogenin(3),nortrachelogenin(4),matairesinol(5)showed moderate inhibiting activities on NF-κB signaling pathway induced by TNFα,with the IC_(50) values of 17.7μg/mL,17.9μM,49.4μM and 29.1μM,respectively.
基金supported by the National Key Research and Development Program of China(Grant no.2019YFA0111400,2022YFE0200100)the National Natural Science Foundation of China(Grant no.32271165,82070144,82270155)the Interdisciplinary Project of Central Universities(Grant no.2022-2-ZD-02).
文摘As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic malignancies and multiple solid tumors.Numerous evidence has expanded the medical application of CAR-T therapy for the treatment of many other human diseases beyond cancer.In this article,we discuss the principle of CAR-T and enumerate the current application and limitation in oncology.Finally,we provide a comprehensive perspective of current advance and future directions of CAR-T in treating multiple non-tumoral diseases.
基金supported by the National Natural Science Foundation of China(81930099,82073785,82130102,92159304,81773664)the Natural Science Foundation of Jiangsu Province(BK20212011,China)+3 种基金“Double First-Class”University project(CPU2018GY47,China)111 Project from the Ministry of Education of Chinathe State Administration of Foreign Expert Affairs of China(No.111-2-07,B17047,China)the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZ202223,China)。
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by severe synovial inflammation and cartilage damage.Despite great progress in RA therapy,there still lacks the drugs to completely cure RA patients.Herein,we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA(siTNFα)as an alternative anti-inflammatory approach for RA treatment.The loaded siTNFαact as not only the gene therapeutics to inhibit TNFαproduction by macrophages in inflamed synovium,but also the editors to reprogram neutrophils to anti-inflammatory phenotypes.Leveraging the active tendency of neutrophils to inflammation,the reprogrammed siTNFα/neutrophil cytopharmaceuticals(siTNFα/TP/NEs)can rapidly migrate to the inflamed synovium,transfer the loaded siTNFαto macrophages followed by the significant reduction of TNFαexpression,and circumvent the pro-inflammatory activity of neutrophils,thus leading to the alleviated synovial inflammation and improved cartilage protection.Our work provides a promising cytopharmaceutical for RA treatment,and puts forward a living neutrophil-based gene delivery platform.
文摘In this paper, eleven strains, which were screened strictly from raw royal jelly, soil andhoneycomb etc. by meansof dilution plate and spread plate methods, were cultured at 28℃ for 60 h with shaking. To determine whether they could yield10-Hydroxy-2-decenoic acid during fermentation, gas chromatography and gas chromatography-mass spectrometry methodswere used. The results showed that the strains BH002 and BH004, were both identified as Crytococcaceae, where BH002was primarily classified into Candida for possessing the abilities. The 10-HDA productivity of Candida BH002 and that ofBH004 were 0.327% and 0.2648% respectively.
文摘Background:The hemoglobin glycation index(HGI)was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin(HbA1c)bias.Here,we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events(MACEs)by performing a large multicenter cohort study in China.Methods:A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals:a Longitudinal Study(the REACTION study)were divided into five subgroups(Q1-Q5)with the HGI quantiles(≤5th,>5th and≤33.3th,>33.3th and≤66.7th,>66.7th and≤95th,and>95th percentile).A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk.Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups.Results:The total 5-year MACE rate in the nationwide cohort was 6.87%(673/9791).Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors(x^(2)=29.5,P<0.001).After adjustment for potential confounders,subjects with HGIs≤-0.75 or>0.82 showed odds ratios(ORs)for MACE of 1.471(95%confidence interval[CI],1.027-2.069)and 2.222(95%CI,1.641-3.026)compared to subjects with HGIs of>-0.75 and≤-0.20.In the subgroup with non-coronary heart disease,the risk of MACE was significantly higher in subjects with HGIs≤-0.75(OR,1.540[1.039-2.234];P=0.027)and>0.82(OR,2.022[1.392-2.890];P<0.001)compared to those with HGIs of≤-0.75 or>0.82 after adjustment for potential confounders.Conclusions:We found a U-shaped correlation between the HGI values and the risk of 5-year MACE.Both low and high HGIs were associated with an increased risk of MACE.Therefore,the HGI may predict the 5-year MACE risk.
基金financially supported by Sichuan Province Science and Technology Support Program(Nos.16ZC2698 and 2018JY0582)the National Natural Science Foundation of China(No.81872821)。
文摘Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer nanoparticles.In this work,LPNs were applied to encapsulate brinzolamide(Brz-LPNs) for achieving sustained drug release,improving drug corneal permeation and enhancing drug topical therapeutic effect.The structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid(PLGA) nanocore which encapsulated Brz(Brz-NPs) and lipid shell around the core.Brz-LPNs were prepared by a modified thin-film dispersion method.With the parameters optimization of Brz-LPNs,optimal Brz-LPNs showed an average particle size of151.23±1.64 nm with a high encapsulation efficiency(EE) of 86.7%±2.28%.The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy(TEM).Fourier transformed infrared spectra(FTIR) analysis proved that Brz was successfully entrapped into Brz-LPNs.Brz-LPNs exhibited obvious sustained release of Brz,compared with AZOPT^■ and Brz-LPs.Furthermore,the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation(AZOPT^■) in vitro.Moreover,Brz-LPNs(1 mg/mL Brz) showed a more sustained and effective intraocular pressure(IOP) reduction than Brz-LPs(1 mg/mL) and AZOPT^■(10 mg/mL Brz) in vivo.In conclusion,Brz-LPNs,as promising ocular drug delivery systems,are well worth developing in the future for glaucoma treatment.
基金This study is supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development(2014ZX09102043-003)National Natural Science Foundation of China(81371403)+1 种基金Shanghai Science and Technology Commission(13JC1401102)Natural Science Foundation of Jiangsu Province of China(BK20140275).
文摘Background:Mesencephalic astrocyte-derived neurotrophic factor(MANF)is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress(ER stress).HSP70 family,a chaperon like heat shock protein family,was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells.However,the ER stress relative transcriptome,in MANF signaling cascades is still investigated.The involvement of HSP70,a 70kd member of HSP70 family,need further to be verified.Methods:The cell apoptosis was assayed by MTT,TUNEL staining and western blot of cleaved Caspase-3.The differentially expressed genes in SHSY-5Y cells under different conditions(control,6-OHDA,6-OHDA+MANF)were investigated by RNA-seq.Expression of HSP70 was further confirmed by real-time PCR.RNAi knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling pathway.Results:MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y cells.Six ER stress relative genes(HSP70,GRP78,xbp-1,ATF-4,ATF-6,MAPK)were found enriched in 6-OHDA+MANF treatment group.HSP70 was the most significantly up-regulated gene under 6-OHDA+MANF treatment in SHSY-5Y cells.RNAi knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y cells.Conclusion:MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes,including HSP70 family members.The HSP70 expression level plays a key role in MANFmediated survival pathway.
文摘As the core of his psychoanalysis,Jacques Lacan’s theory of desire explains the inner workings of activities from individual life to grand society from a relatively essential perspective.This article is intended to recapitulate the basic facilitating dynamics of individual mental organs from the perspective of Lacanian psychoanalysis,using the concept of Paradise.On this basis,this article will briefly describe Lacan’s theory of desire and some of its key concepts,such as destitution,jouissance,desire,and explain the special role of the law in this context.Finally,this paper will return to the concept of Paradise with the paradoxes embedded in Lacan’s theory of desire,exploring how it affects the individual and the way the individual copes with it.
基金supported by the National Key Research and Development Program of China(Nos.2016YFA0302000 and 2017YFA0304204)the National Natural Science Foundation of China(NSFC)(No.12074083)the National Key Scientific Instrument and Equipment Development Project(No.12027806)。
文摘We demonstrate a simple method to obtain accurate optical waveforms with a gigahertz-level programmable modulation bandwidth and a watt-level output power for wideband optical control of free atoms and molecules.Arbitrary amplitude and phase modulations are transferred from microwave to light with a low-power fiber electro-optical modulator.The sub-milliwatt optical sideband is co-amplified with the optical carrier in a power-balanced fashion through a tapered semiconductor amplifier(TSA).By automatically keeping TSA near saturation in a quasi-continuous manner,typical noise channels associated with pulsed high-gain amplifications are efficiently suppressed.As an example application,we demonstrate interleaved cooling and trapping of two rubidium isotopes with coherent nanosecond pulses.
基金National Social Science Foundation of China--Research on the Hybrid Network for Scientific Structure Analysis(Grant No.19XTQ012)。
文摘The value of big data in science of science for knowledge discovery is that it can reveal deeper information and knowledge, promote knowledge integration in the whole process of scientific research, guide interdisciplinary integration, and provide new ideas and new methods for knowledge discovery research. This paper discusses the value and role of big data in science of science in knowledge discovery from five aspects, including exploring the laws of scientific research, revealing scientific structure, analyzing scientific research activities, supporting technical recognition and prediction, and serving science and technology evaluation.
文摘Chinese as a foreign language (CFL) is a critical language in the United States, and the importance to have competent CFL teachers has been more and more realized. However, the literature does not show sufficient research on CFL teacher competency. To fill the gap, a series of exploratory research studies are initiated. As a part of the initiation, this study overviews the professional guidelines, resources, standards and requirements for CFL education in the U.S. at the national and state levels. The findings will be useful for designing teacher education program and teacher training program. In addition, student teachers, pre-service teachers, and in-service teachers can also use them as great references for their academic and/or professional development.
文摘China has entered a stage of high-quality development in the new era.Especially as it ushers in the beginning of the Fourteenth Five-Year Plan,China is about to embark on a new journey to build a modern and powerful socialist country in an all-round way.Its population development and social policy changes are also at a critical turning point.As a country with a large population,we urgently need to build a society that is more inclusive of development,attach importance to the support of and tolerance for different population groups.
文摘Objective: To describe the latest progress in the use of botulinum neurotoxin for post-stroke limb spasm. Methods: This paper looks up the relevant research literatures in recent years in PubMed, Web of Science, Springer, Ovid, CNKI, WanFang databases and summarizes them. Results: The latest progress in the use of botulinum neurotoxin for post-stroke limb spasm was studied from the following aspects: the action mechanism of botulinum neurotoxin;efficacy evaluation;injection dose;target muscle selection;guiding technology;combination therapy. Conclusion: Botulinum neurotoxin is the first-line treatment for post-stroke limb spasm. We need to make continuous improvement and progress from the treatment period, injection dose, target muscle selection, guiding technology and efficacy evaluation to improve the quality of life of the majority of post-stroke survivors in China.
