Following publication of the original article[1],the authors reported an error in the last author’s name,it was mistakenly written as“Jun Den”.The correct author’s name“Jun Deng”has been updated in this Correction.
Macrophage immunotherapy represents an emerging therapeutic approach aimed at modulating the immune response to alleviate disease symptoms.Nanomaterials(NMs)have been engineered to monitor macrophage metabolism,enabli...Macrophage immunotherapy represents an emerging therapeutic approach aimed at modulating the immune response to alleviate disease symptoms.Nanomaterials(NMs)have been engineered to monitor macrophage metabolism,enabling the evaluation of disease progression and the replication of intricate physiological signal patterns.They achieve this either directly or by delivering regulatory signals,thereby mapping phenotype to effector functions through metabolic repurposing to customize macrophage fate for therapy.However,a comprehensive summary regarding NM-mediated macrophage visualization and coordinated metabolic rewiring to maintain phenotypic equilibrium is currently lacking.This review aims to address this gap by outlining recent advancements in NM-based metabolic immunotherapy.We initially explore the relationship between metabolism,polarization,and disease,before delving into recent NM innovations that visualize macrophage activity to elucidate disease onset and fine-tune its fate through metabolic remodeling for macrophage-centered immunotherapy.Finally,we discuss the prospects and challenges of NM-mediated metabolic immunotherapy,aiming to accelerate clinical translation.We anticipate that this review will serve as a valuable reference for researchers seeking to leverage novel metabolic intervention-matched immunomodulators in macrophages or other fields of immune engineering.展开更多
The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential dis...The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.展开更多
In order to determine whether long-term no-tillage operation in the loess plateau threatens soil fertility and crop yield,a suitable high-yield and efficient tillage technology system was established.In the Changwu lo...In order to determine whether long-term no-tillage operation in the loess plateau threatens soil fertility and crop yield,a suitable high-yield and efficient tillage technology system was established.In the Changwu loess plateau agri-Gecological experiment station of the Northwest A&F University of Changwu County,Shaanxi Province,the no-tillage experimental field for three consecutive years was selected.In September 2015,no-tillage,tillage,and rotary tillage were carried out before winter wheat was sowed.After the harvest of winter wheat in2016,soil organic carbon,total nitrogen and wheat yield in 0-30 cm soil layers under different tillage methods were analyzed.The results showed that the soil organic carbon and total nitrogen contents in the 0-30 cm soil layer decreased along the profile under the three tillage methods.In this study,the soil organic carbon and total nitrogen content in the 0-10 cm soil layer under different tillage methods were no-tillage>rotary tillage>tillage,the actual yield of winter yield in one hectare was tillage>rotary tillage>no-tillage,and there was significant difference in the actual yield of winter wheat only between the no-tillage and tillage.展开更多
In order to find out the effects of long-term no-tillage operation on soil available phosphorus and available potassium in the loess plateau, a suitable high-yield and high-efficiency tillage technology system was est...In order to find out the effects of long-term no-tillage operation on soil available phosphorus and available potassium in the loess plateau, a suitable high-yield and high-efficiency tillage technology system was established. In the Changwu loess plateau agri-ecological experiment station of the Northwest A&F University of Changwu County, Shaanxi Province, the no-tillage experimental field for three consecutive years was selected. In September 2015, no-tillage, tillage, and rotary tillage were carried out before winter wheat was sowed. After the harvest of winter wheat in 2016, the contents of available phosphorus and available potassium in 0-30 cm soil layer under three tillage methods were analyzed. The results showed that in the 0-30 cm soil layer, the soil available phosphorus and available potassium decreased with the increase of the soil depth in the three tillage methods. The content of available phosphorus and available potassium in 10-20 cm soil layer and 20-30 cm soil layer decreased by 16.07%, 32.74%, 15.54% and 27.08%, respectively, and there were significant differences ( P <0.05). Under different tillage methods, the soil available phosphorus content in the 0-10 cm soil layer significantly reduced by 11.31% compared with no-tillage. The soil available potassium content under tillage and rotary tillage significantly reduced by 6.16% and 4.97%, respectively ( P <0.05). Compared with no-tillage, the soil available phosphorus content in the 20-30 cm soil layer significantly reduced by 18.12%. The soil available potassium content under tillage and rotary tillage methods significantly reduced by 17.17% and 9.22%, respectively ( P <0.05). Therefore, in the long-term no-tillage dry loess plateau, it is necessary to conduct proper tillage or rotary tillage.展开更多
[Objectives]This study aimed to provide a basis for the management of nitrogen,phosphorus and potassium nutrients in eum-orthic anthrosols and the fertilization of crops.[Methods]Using the indoor culture method,the co...[Objectives]This study aimed to provide a basis for the management of nitrogen,phosphorus and potassium nutrients in eum-orthic anthrosols and the fertilization of crops.[Methods]Using the indoor culture method,the contents of total nitrogen,available phosphorus and available potassium in eum-orthic anthrosols under three different moisture conditions:long-term drying,long-term logging and alternate drying and logging were analyzed and compared.[Results]The total nitrogen content was higher under the moisture condition of long-term drying.The minimum(0.60 g/kg)appeared on day 30,and the maximum(0.74 g/kg)appeared on day 120,increased by 8.8%compared with the minimum.The available phosphorus content was also higher under the moisture condition of long-term drying.The minimum(16.9 mg/kg)appeared on day 60,and the maximum(22.5 mg/kg)appeared on day 120,increased by 33.1%compared to the minimum.The available potassium content showed a downward trend under long-term logging,and was higher than those under the other two moisture conditions.The maximum(150 mg/kg)appeared on day 30,and the minimum(136 mg/kg)appeared on days 75 and 90,reduced by 9.3%compared with the maximum.[Conclusions]Water plays a positive role in activating nutrients.Different nutrients have different responses to different moisture conditions.展开更多
[Objectives]To study the activation effect of hydrochemical energy in regenerative agriculture on the nutrients of arsenic sandstone.[Methods]Starting from common environmental factors,moisture,it studied the mechanis...[Objectives]To study the activation effect of hydrochemical energy in regenerative agriculture on the nutrients of arsenic sandstone.[Methods]Starting from common environmental factors,moisture,it studied the mechanism of the release and activation of N,P,K nutrient elements in arsenic sandstone under different dry and wet environments.[Results]Water played a positive role in activating soil elements.Under the conditions of long-term dryness and alternating dry and wet conditions,the content of total nitrogen,available phosphorus and available potassium coexisted in the 210 d of culture and the element absorption and release,but the overall trend was increasing;under long-term flooding conditions,the content of total nitrogen and available potassium showed an overall increasing trend during the 210 d of culture,but the content of available phosphorus decreased.[Conclusions]Water plays a positive effect on activating soil elements.The research results are expected to provide a certain reference for the application research of water in regenerative agriculture.展开更多
In this paper,the atomic fluorescence(AFS-9760)method used for the determination of total arsenic in soil was verified based on three national quality control samples GSS-8,GSS-25,and GSF-3.Under the conditions of neg...In this paper,the atomic fluorescence(AFS-9760)method used for the determination of total arsenic in soil was verified based on three national quality control samples GSS-8,GSS-25,and GSF-3.Under the conditions of negative pressure of 270 V,carrier gas flow of 300 m L/min,and shield flow of 1000 m L/min,the detection limit of the method was 0.0092 mg/kg;the precision of GSS-8,GSS-25,and GSF-3 was 3.96%,1.47%and 1.08%,and the accuracy was 3.07%,2.13%,2.93%respectively.In addition,the matters needing attention during this experiment,such as reagent factor,instrument conditions,calibration curve,etc.,were summarized.It provides certain reference for the determination of total arsenic content in soil by atomic fluorescence spectrometry.展开更多
Based on previous studies,the research methods and influencing factors of spatial variation of soil nutrients are summarized.It is concluded that the spatial variation of soil nutrients is studied generally by geostat...Based on previous studies,the research methods and influencing factors of spatial variation of soil nutrients are summarized.It is concluded that the spatial variation of soil nutrients is studied generally by geostatistics methods,and the spatial distribution of nutrients is visually observed by using Kriging interpolation method.The influencing factors mainly include topography,sampling method,sampling spacing,sampling density and sampling scale.The influence of random sampling and grid sampling on interpolation is analyzed based on the specific conditions of the actual study area.The influence of sampling density and topography on the spatial variation of soil nutrients cannot be ignored,especially on available nutrients.When samples are collected in a large area(under a small and medium scale),the spatial variation of soil nutrients is large,and they have strong spatial autocorrelation;in a small area(namely under a large scale),the spatial variability of soil nutrients is small,and they have obvious spatial autocorrelation.This study can provide intuitive and convenient reference materials for the following researchers.展开更多
[Objectives]To explore the distribution characteristics of soil organic carbon in degraded forest land in the sandstorm area of Jingbian County,Shaanxi Province.[Methods]The distribution characteristics and abundance ...[Objectives]To explore the distribution characteristics of soil organic carbon in degraded forest land in the sandstorm area of Jingbian County,Shaanxi Province.[Methods]The distribution characteristics and abundance of 0-20 cm shallow soil organic carbon in 5 towns in the sandstorm area in the north of Jingbian County were studied by field sampling and indoor detection.[Results]The average soil organic carbon contents in Hongdunjie Town,Haizetan Town,Huanghaojie Town,Ningtiaoliang Town and Dongkeng Town were 2.93,3.21,2.53,2.54 and 4.08 g/kg,respectively,which were all lower than the national background value(31.00 g/kg).The coefficients of variation of soil organic carbon content in Hongdunjie Town,Huanghaojie Town and Dongkeng Town were 59.04%,35.97%and 47.55%,respectively,with higher coefficients of variation and larger differences in spatial distribution.The organic carbon content of Haizetan Town and Dongkeng Town was above the abundance,accounting for 70%and 50%,which were relatively rich,while the soil organic carbon content of Hongdunjie was relatively scarce.The average content of soil organic carbon in the sandstorm area was 3.03 g/kg,which was also lower than the national background value.The coefficient of variation was 46.53%,showing high coefficient of variation and large difference in spatial distribution.In addition,20.41%of the average content of soil organic carbon in the sandstorm area was in the deficient level,and 79.59%were in the medium or above level.[Conclusions]The study of distribution characteristics of soil organic carbon in degraded forest land in the sandstorm area of Jingbian County will better serve the precise management of soil resources.展开更多
[Objectives]To explore the impact of land use changes on physical properties of soil in loess hilly region.[Methods]The methods of field sampling and indoor analysis were adopted.Farmland in a small watershed in the m...[Objectives]To explore the impact of land use changes on physical properties of soil in loess hilly region.[Methods]The methods of field sampling and indoor analysis were adopted.Farmland in a small watershed in the middle of the Loess Plateau,grassland that had been abandoned for 7 years,grassland that had been abandoned for 30 years,jujube orchard and ditch were sampled,and the particle composition(clay,silt and sand)and moisture changes of the soil in the top 0-100 cm were studied.[Results]In the small watershed,the top 0-100 cm of the soil was composed of 14%clay,70%silt and 16%sand.The contents of clay,silt and sand in the grassland that had been abandoned for 30 years varied greatly,while varied little in the land of other use types.The soil moisture content of grassland that had been abandoned for 30 years,jujube orchard,grassland that had been abandoned for 7 years,farmland and ditch increased with the increase of depth,with means of 10.29%,11.66%,10.08%,11.43%and 11.34%,respectively.[Conclusions]This study provides a theoretical basis for the growth of crops of different land use types in the loess hilly region.展开更多
[Objectives]The paper was to investigate the distribution characteristics of soil total nitrogen in low-efficiency forest land in the northern windy desert area of Jingbian County.[Methods]The distribution of soil tot...[Objectives]The paper was to investigate the distribution characteristics of soil total nitrogen in low-efficiency forest land in the northern windy desert area of Jingbian County.[Methods]The distribution of soil total nitrogen in the 0-40 cm soil layer of 5 towns in the northern windy desert area of Jingbian County was studied through field sampling and laboratory detection.[Results]The average soil total nitrogen contents of Hongdunjie Town,Haizetan Town,Huanghaojie Town,Ningtiaoliang Town,Dongkeng Town and windy desert area in the 0-20 cm soil layer were 0.259,0.224,0.242,0.248,0.431 and 0.275 g/kg,respectively.The soil total nitrogen content in Dongkeng Town was higher than those in other towns,while there was little difference among other regions.The average total nitrogen contents in the 20-40 cm soil layer were 0.239,0.285,0.113,0.262,0.349 and 0.241 g/kg,respectively.The soil total nitrogen content in Huanghaojie Town was slightly lower than those in other towns,while that in Dongkeng town was higher.The variation coefficient of soil total nitrogen content in the survey area was greater than 30%,and there was great difference in spatial distribution.With the increase of soil depth,there was little change in soil total nitrogen content,namely the soil total nitrogen contents in 5 towns and windy desert area were not statistically different in the 0-40 cm soil layer.According to the nutrient grading standard of the second national soil survey,the soil total nitrogen content in the survey area was in the deficiency grade.[Conclusions]The research will provide a scientific guidance for the healthy and sustainable development of vegetation in arid regions.展开更多
Based on the experience of soil sampling in Yuanzegou small watershed,several matters needing attention in soil field sampling are summarized.This paper focuses on the layout of sampling points,soil sample collection,...Based on the experience of soil sampling in Yuanzegou small watershed,several matters needing attention in soil field sampling are summarized.This paper focuses on the layout of sampling points,soil sample collection,soil sample preparation and matters needing attention about potential factors in soil field sampling,with a view to providing reference for undergraduates,master students or non-subject experimenters who are about to carry out experiments in this discipline.展开更多
The selection of remediation technology for contaminated site is a key link of the remediation project.It determines the success or failure of the site remediation.The complexity of the types of contaminants in the si...The selection of remediation technology for contaminated site is a key link of the remediation project.It determines the success or failure of the site remediation.The complexity of the types of contaminants in the site determines the diversity of remediation technologies.The experience of many countries in the world shows that the use of scientific and technological means and advanced technology can more effectively carry out the work of soil protection and pollution prevention and control,and achieve obvious results.展开更多
The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage.Numerous studies have demonstrated that intestinal barrier function plays an important ...The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage.Numerous studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease(IBD).Oral administration is the most common route for intestinal diseases.In this study,a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment,which can interrupt the pathological process of IBD,resulting in the significantly improved efficacy of existing treatments.Based on the specific pH values and high reactive oxygen species(ROS)levels in inflammatory sites of IBD,an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed,and confirmed in vitro and in vivo.The anti-inflammatory drug dexamethasone acetate(Dex)and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions(TJs).The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with colitis.In brief,a drug delivery system and a therapeutic strategy for IBD are successfully developed.展开更多
Aims To clarify whether variation in leaf traits with climate differs with scale,i.e.across species and within a species,and to detect whether plant functional group affects species-specific response.Methods Leaf dry ...Aims To clarify whether variation in leaf traits with climate differs with scale,i.e.across species and within a species,and to detect whether plant functional group affects species-specific response.Methods Leaf dry matter content(LDMC),specific leaf area(SLA),mass-and area-based leaf N(N_(mass),N_(area))and leaf P concentrations(P_(mass),P_(area))and leaf chlorophyll concentration(SPAD)were measured for 92 woody plant species in two botanical gardens in China.The two gardens share plant species in common but differ in climate.Leaf trait variation between the two gardens was examined via mean comparison at three scales:all species together,species grouped into plant functional groups and within a species.A meta-analysis was performed to summarize the species-specific responses.Important Findings At the scale of all species together,LDMC,SLA,P_(mass) and N_(mass) were significantly lower in the dry-cold habitat than in the wet-warm one,whereas N_(area) and SPAD showed an inverse pattern,indicating a significant environmental effect.The meta-analysis showed that the above-mentioned patterns persisted for SLA,N_(area) and SPAD but not for the other variables at the species-specific scale,indicating that intraspecific variation affects the overall pattern of LDMC,P_(mass) and N_(mass) and P_(area).In terms of species-specific response,posi-tive,negative or nonsignificant patterns were observed among the 92 species.Contrary to our prediction,species-specific responses within a functional group were not statistically more similar than those among functional groups.Our results indicated that leaf trait variation captured climatic difference yet species-specific responses were quite diverse irrespective of plant functional group,providing new insights for interpreting trait variability with climate.展开更多
Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the ac...Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the accessibility of immunogenic cell death(ICD)related drugs and immune-related cells.Herein,the strategy of self-oriented deep tumor delivery by circulating monocyte/macrophage was proposed.Briefly,CS-AI including an indoleamine 2,3-dioxygenase(IDO)inhibitor indoximod(IND)and hydrophilic chitosan(CSO)linked with alanine-alanine-asparagine(AAN)was prepared,which could be selectively cleaved by legumain overexpressed in macrophages and promote the collapse in structure.Then,CS-AI was modified with mannose on the surface and further encapsulated the ICD inducer doxorubicin(DOX)to obtain M-CS-AI/DOX.Upon intravenous injection,MCS-AI/DOX was specially recognized and internalized by circulating monocyte in vivo.The formed drugs/monocyte tend to distribute in hypoxia/necrosis region guided by the homing signals released by tumor.Accumulated monocytes then further differentiated into macrophages,up-regulating the expression of legumain and promoting the sensitive-release of chemo-drug DOX,IND,and the mannose-modified CSO(M-CSO).The released IND would specifically regulate immunosuppressive tumor microenvironment,and synergistically inhibit tumor growth with immune activation elements,ICD-induced DOX,and the favorable adjuvant M-CSO.In summary,the self-oriented deep tumor delivery of legumain-cleavable nanovesicles through circulating monocyte makes it possible for reaching tumor regions inaccessible for nanoparticles and provides a novel insight for precise tumor enrichment and immune activation.展开更多
Glial cell line-derived neurotrophic factor(GDNF),a disease-modifying drug for Parkinson’s disease(PD)is in Phase 2 clinical trials(EudraCT number:2011-003866-34),however it is administered by direct intrastriatal de...Glial cell line-derived neurotrophic factor(GDNF),a disease-modifying drug for Parkinson’s disease(PD)is in Phase 2 clinical trials(EudraCT number:2011-003866-34),however it is administered by direct intrastriatal delivery via stereotaxy,which is accompanied with intracranial infection,brain tissue damage,and other complications.In addition,because of complex administration routes,clinical trials of GDNF have yielded contrary results,largely due to differences in dose and concentration brought by intracranial device.Herein,a small molecular agonist SC79 was screened to open blood-brain barrier(BBB)and promote GDNF liposomes to get into brain.SC79 reversibly reduces the expression of claudin-5,one of dominant tight junctions of BBB.Animal study showed SC79 promoted liposomes to enter into brain parenchyma 2.43 times more than that of the control.Motor deficits of PD mice receiving SC79 and brain-targeted GDNF liposomes were recovered by 36.70%and tyrosine hydroxylase positive neurons in striatum were restored by 39.90%.Our combination therapy effectively avoids the side effects such as secondary infection and uneven delivery caused by intracranial injection,improving patients’compliance and providing valuable research ideas for the clinic.展开更多
Researches on indoleamine-2,3-dioxygenase-1(IDO1),a neoplastic pathogenesis-related protein,have provided a new angle of view to regulate malignancy-related immunosuppression.However,the therapeutic efficacy of IDO1 i...Researches on indoleamine-2,3-dioxygenase-1(IDO1),a neoplastic pathogenesis-related protein,have provided a new angle of view to regulate malignancy-related immunosuppression.However,the therapeutic efficacy of IDO1 inhibitors is subject to key limitations as both cancer and dendritic cells tend to be trapped in the IDO1-mediated immune dysfunction,which poses challenges to the inhibitory potency of drug regimens in multiple targets.Here,we report on the fabrication technique of a biomimetic nanocarrier that is endowed with the whole array of cancer cell membrane proteins for encapsulating the most used IDO1 probe indoximod(IND).By fully utilizing the homologous adhesion proteins and antigenic motifs on cytomembrane,these nanoparticulate particles are capable of infiltrating tumors and actively accumulating in cancer and dendritic cells,as well as hitching a ride on dendritic cells to tumor-draining lymph nodes.Ultimately,by increasing the distribution of drugs in both tumor cells and dendritic cells in tumor-draining lymph nodes,these formulations greatly enhance the efficacy of IND without the aid of chemotherapeutic drugs,achieving substantial control of tumor growth.Overall,this leverage of bionanotechnology maximizes the therapeutic potential of IND and can provide a theoretical reference for the clinical application of IDO1 inhibitors.展开更多
文摘Following publication of the original article[1],the authors reported an error in the last author’s name,it was mistakenly written as“Jun Den”.The correct author’s name“Jun Deng”has been updated in this Correction.
基金financially supported by the National Natural Science Foundation of China(Nos.92168106 and 82222039).
文摘Macrophage immunotherapy represents an emerging therapeutic approach aimed at modulating the immune response to alleviate disease symptoms.Nanomaterials(NMs)have been engineered to monitor macrophage metabolism,enabling the evaluation of disease progression and the replication of intricate physiological signal patterns.They achieve this either directly or by delivering regulatory signals,thereby mapping phenotype to effector functions through metabolic repurposing to customize macrophage fate for therapy.However,a comprehensive summary regarding NM-mediated macrophage visualization and coordinated metabolic rewiring to maintain phenotypic equilibrium is currently lacking.This review aims to address this gap by outlining recent advancements in NM-based metabolic immunotherapy.We initially explore the relationship between metabolism,polarization,and disease,before delving into recent NM innovations that visualize macrophage activity to elucidate disease onset and fine-tune its fate through metabolic remodeling for macrophage-centered immunotherapy.Finally,we discuss the prospects and challenges of NM-mediated metabolic immunotherapy,aiming to accelerate clinical translation.We anticipate that this review will serve as a valuable reference for researchers seeking to leverage novel metabolic intervention-matched immunomodulators in macrophages or other fields of immune engineering.
基金National Natural Science Foundation of China(grant nos.81973267)Natural Science Foundation of Zhejiang Province(grant nos.LD19H300001).
文摘The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.
文摘In order to determine whether long-term no-tillage operation in the loess plateau threatens soil fertility and crop yield,a suitable high-yield and efficient tillage technology system was established.In the Changwu loess plateau agri-Gecological experiment station of the Northwest A&F University of Changwu County,Shaanxi Province,the no-tillage experimental field for three consecutive years was selected.In September 2015,no-tillage,tillage,and rotary tillage were carried out before winter wheat was sowed.After the harvest of winter wheat in2016,soil organic carbon,total nitrogen and wheat yield in 0-30 cm soil layers under different tillage methods were analyzed.The results showed that the soil organic carbon and total nitrogen contents in the 0-30 cm soil layer decreased along the profile under the three tillage methods.In this study,the soil organic carbon and total nitrogen content in the 0-10 cm soil layer under different tillage methods were no-tillage>rotary tillage>tillage,the actual yield of winter yield in one hectare was tillage>rotary tillage>no-tillage,and there was significant difference in the actual yield of winter wheat only between the no-tillage and tillage.
文摘In order to find out the effects of long-term no-tillage operation on soil available phosphorus and available potassium in the loess plateau, a suitable high-yield and high-efficiency tillage technology system was established. In the Changwu loess plateau agri-ecological experiment station of the Northwest A&F University of Changwu County, Shaanxi Province, the no-tillage experimental field for three consecutive years was selected. In September 2015, no-tillage, tillage, and rotary tillage were carried out before winter wheat was sowed. After the harvest of winter wheat in 2016, the contents of available phosphorus and available potassium in 0-30 cm soil layer under three tillage methods were analyzed. The results showed that in the 0-30 cm soil layer, the soil available phosphorus and available potassium decreased with the increase of the soil depth in the three tillage methods. The content of available phosphorus and available potassium in 10-20 cm soil layer and 20-30 cm soil layer decreased by 16.07%, 32.74%, 15.54% and 27.08%, respectively, and there were significant differences ( P <0.05). Under different tillage methods, the soil available phosphorus content in the 0-10 cm soil layer significantly reduced by 11.31% compared with no-tillage. The soil available potassium content under tillage and rotary tillage significantly reduced by 6.16% and 4.97%, respectively ( P <0.05). Compared with no-tillage, the soil available phosphorus content in the 20-30 cm soil layer significantly reduced by 18.12%. The soil available potassium content under tillage and rotary tillage methods significantly reduced by 17.17% and 9.22%, respectively ( P <0.05). Therefore, in the long-term no-tillage dry loess plateau, it is necessary to conduct proper tillage or rotary tillage.
文摘[Objectives]This study aimed to provide a basis for the management of nitrogen,phosphorus and potassium nutrients in eum-orthic anthrosols and the fertilization of crops.[Methods]Using the indoor culture method,the contents of total nitrogen,available phosphorus and available potassium in eum-orthic anthrosols under three different moisture conditions:long-term drying,long-term logging and alternate drying and logging were analyzed and compared.[Results]The total nitrogen content was higher under the moisture condition of long-term drying.The minimum(0.60 g/kg)appeared on day 30,and the maximum(0.74 g/kg)appeared on day 120,increased by 8.8%compared with the minimum.The available phosphorus content was also higher under the moisture condition of long-term drying.The minimum(16.9 mg/kg)appeared on day 60,and the maximum(22.5 mg/kg)appeared on day 120,increased by 33.1%compared to the minimum.The available potassium content showed a downward trend under long-term logging,and was higher than those under the other two moisture conditions.The maximum(150 mg/kg)appeared on day 30,and the minimum(136 mg/kg)appeared on days 75 and 90,reduced by 9.3%compared with the maximum.[Conclusions]Water plays a positive role in activating nutrients.Different nutrients have different responses to different moisture conditions.
文摘[Objectives]To study the activation effect of hydrochemical energy in regenerative agriculture on the nutrients of arsenic sandstone.[Methods]Starting from common environmental factors,moisture,it studied the mechanism of the release and activation of N,P,K nutrient elements in arsenic sandstone under different dry and wet environments.[Results]Water played a positive role in activating soil elements.Under the conditions of long-term dryness and alternating dry and wet conditions,the content of total nitrogen,available phosphorus and available potassium coexisted in the 210 d of culture and the element absorption and release,but the overall trend was increasing;under long-term flooding conditions,the content of total nitrogen and available potassium showed an overall increasing trend during the 210 d of culture,but the content of available phosphorus decreased.[Conclusions]Water plays a positive effect on activating soil elements.The research results are expected to provide a certain reference for the application research of water in regenerative agriculture.
文摘In this paper,the atomic fluorescence(AFS-9760)method used for the determination of total arsenic in soil was verified based on three national quality control samples GSS-8,GSS-25,and GSF-3.Under the conditions of negative pressure of 270 V,carrier gas flow of 300 m L/min,and shield flow of 1000 m L/min,the detection limit of the method was 0.0092 mg/kg;the precision of GSS-8,GSS-25,and GSF-3 was 3.96%,1.47%and 1.08%,and the accuracy was 3.07%,2.13%,2.93%respectively.In addition,the matters needing attention during this experiment,such as reagent factor,instrument conditions,calibration curve,etc.,were summarized.It provides certain reference for the determination of total arsenic content in soil by atomic fluorescence spectrometry.
文摘Based on previous studies,the research methods and influencing factors of spatial variation of soil nutrients are summarized.It is concluded that the spatial variation of soil nutrients is studied generally by geostatistics methods,and the spatial distribution of nutrients is visually observed by using Kriging interpolation method.The influencing factors mainly include topography,sampling method,sampling spacing,sampling density and sampling scale.The influence of random sampling and grid sampling on interpolation is analyzed based on the specific conditions of the actual study area.The influence of sampling density and topography on the spatial variation of soil nutrients cannot be ignored,especially on available nutrients.When samples are collected in a large area(under a small and medium scale),the spatial variation of soil nutrients is large,and they have strong spatial autocorrelation;in a small area(namely under a large scale),the spatial variability of soil nutrients is small,and they have obvious spatial autocorrelation.This study can provide intuitive and convenient reference materials for the following researchers.
基金Supported by the Scientific Research Project of Shaanxi Provincial Land Engineering Construction Group(DJNY2022-21)Shaanxi Province Youth Talent Promotion Program(YKJ202228).
文摘[Objectives]To explore the distribution characteristics of soil organic carbon in degraded forest land in the sandstorm area of Jingbian County,Shaanxi Province.[Methods]The distribution characteristics and abundance of 0-20 cm shallow soil organic carbon in 5 towns in the sandstorm area in the north of Jingbian County were studied by field sampling and indoor detection.[Results]The average soil organic carbon contents in Hongdunjie Town,Haizetan Town,Huanghaojie Town,Ningtiaoliang Town and Dongkeng Town were 2.93,3.21,2.53,2.54 and 4.08 g/kg,respectively,which were all lower than the national background value(31.00 g/kg).The coefficients of variation of soil organic carbon content in Hongdunjie Town,Huanghaojie Town and Dongkeng Town were 59.04%,35.97%and 47.55%,respectively,with higher coefficients of variation and larger differences in spatial distribution.The organic carbon content of Haizetan Town and Dongkeng Town was above the abundance,accounting for 70%and 50%,which were relatively rich,while the soil organic carbon content of Hongdunjie was relatively scarce.The average content of soil organic carbon in the sandstorm area was 3.03 g/kg,which was also lower than the national background value.The coefficient of variation was 46.53%,showing high coefficient of variation and large difference in spatial distribution.In addition,20.41%of the average content of soil organic carbon in the sandstorm area was in the deficient level,and 79.59%were in the medium or above level.[Conclusions]The study of distribution characteristics of soil organic carbon in degraded forest land in the sandstorm area of Jingbian County will better serve the precise management of soil resources.
基金Fund of Shaanxi Provincial Land Engineering Construction Group(DJNY-2021-15).
文摘[Objectives]To explore the impact of land use changes on physical properties of soil in loess hilly region.[Methods]The methods of field sampling and indoor analysis were adopted.Farmland in a small watershed in the middle of the Loess Plateau,grassland that had been abandoned for 7 years,grassland that had been abandoned for 30 years,jujube orchard and ditch were sampled,and the particle composition(clay,silt and sand)and moisture changes of the soil in the top 0-100 cm were studied.[Results]In the small watershed,the top 0-100 cm of the soil was composed of 14%clay,70%silt and 16%sand.The contents of clay,silt and sand in the grassland that had been abandoned for 30 years varied greatly,while varied little in the land of other use types.The soil moisture content of grassland that had been abandoned for 30 years,jujube orchard,grassland that had been abandoned for 7 years,farmland and ditch increased with the increase of depth,with means of 10.29%,11.66%,10.08%,11.43%and 11.34%,respectively.[Conclusions]This study provides a theoretical basis for the growth of crops of different land use types in the loess hilly region.
基金Supported by Internal Scientific Research Project of Shaanxi Provincial Land Engineering Construction Group Co.,Ltd.(DJNY2022-21)Shaanxi Provincial Youth Talent Promotion Program(NYKJ202228)+1 种基金Technology Innovation Center for Land Engineering and Human Settlements,Shaanxi Provincial Land Engineering Construction Group Co.,Ltd.and Xi an Jiaotong University(2021WHZ0094)Shaanxi Provincial Enterprise Innovation Striving for the First Young Talents Support Program Project(2021-1-2).
文摘[Objectives]The paper was to investigate the distribution characteristics of soil total nitrogen in low-efficiency forest land in the northern windy desert area of Jingbian County.[Methods]The distribution of soil total nitrogen in the 0-40 cm soil layer of 5 towns in the northern windy desert area of Jingbian County was studied through field sampling and laboratory detection.[Results]The average soil total nitrogen contents of Hongdunjie Town,Haizetan Town,Huanghaojie Town,Ningtiaoliang Town,Dongkeng Town and windy desert area in the 0-20 cm soil layer were 0.259,0.224,0.242,0.248,0.431 and 0.275 g/kg,respectively.The soil total nitrogen content in Dongkeng Town was higher than those in other towns,while there was little difference among other regions.The average total nitrogen contents in the 20-40 cm soil layer were 0.239,0.285,0.113,0.262,0.349 and 0.241 g/kg,respectively.The soil total nitrogen content in Huanghaojie Town was slightly lower than those in other towns,while that in Dongkeng town was higher.The variation coefficient of soil total nitrogen content in the survey area was greater than 30%,and there was great difference in spatial distribution.With the increase of soil depth,there was little change in soil total nitrogen content,namely the soil total nitrogen contents in 5 towns and windy desert area were not statistically different in the 0-40 cm soil layer.According to the nutrient grading standard of the second national soil survey,the soil total nitrogen content in the survey area was in the deficiency grade.[Conclusions]The research will provide a scientific guidance for the healthy and sustainable development of vegetation in arid regions.
文摘Based on the experience of soil sampling in Yuanzegou small watershed,several matters needing attention in soil field sampling are summarized.This paper focuses on the layout of sampling points,soil sample collection,soil sample preparation and matters needing attention about potential factors in soil field sampling,with a view to providing reference for undergraduates,master students or non-subject experimenters who are about to carry out experiments in this discipline.
基金the Technology Innovation Leading Program of Shaanxi Province(2021CGBX-03).
文摘The selection of remediation technology for contaminated site is a key link of the remediation project.It determines the success or failure of the site remediation.The complexity of the types of contaminants in the site determines the diversity of remediation technologies.The experience of many countries in the world shows that the use of scientific and technological means and advanced technology can more effectively carry out the work of soil protection and pollution prevention and control,and achieve obvious results.
基金the National Natural Science Foundation of China(No.81973267)the Zhejiang Provincial Natural Science Foundation of China(No.LZ22H060001).
文摘The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage.Numerous studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease(IBD).Oral administration is the most common route for intestinal diseases.In this study,a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment,which can interrupt the pathological process of IBD,resulting in the significantly improved efficacy of existing treatments.Based on the specific pH values and high reactive oxygen species(ROS)levels in inflammatory sites of IBD,an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed,and confirmed in vitro and in vivo.The anti-inflammatory drug dexamethasone acetate(Dex)and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions(TJs).The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with colitis.In brief,a drug delivery system and a therapeutic strategy for IBD are successfully developed.
基金Chinese National Basic Research Program(2014CB954201)National Natural Science Foundation of China(30870398).
文摘Aims To clarify whether variation in leaf traits with climate differs with scale,i.e.across species and within a species,and to detect whether plant functional group affects species-specific response.Methods Leaf dry matter content(LDMC),specific leaf area(SLA),mass-and area-based leaf N(N_(mass),N_(area))and leaf P concentrations(P_(mass),P_(area))and leaf chlorophyll concentration(SPAD)were measured for 92 woody plant species in two botanical gardens in China.The two gardens share plant species in common but differ in climate.Leaf trait variation between the two gardens was examined via mean comparison at three scales:all species together,species grouped into plant functional groups and within a species.A meta-analysis was performed to summarize the species-specific responses.Important Findings At the scale of all species together,LDMC,SLA,P_(mass) and N_(mass) were significantly lower in the dry-cold habitat than in the wet-warm one,whereas N_(area) and SPAD showed an inverse pattern,indicating a significant environmental effect.The meta-analysis showed that the above-mentioned patterns persisted for SLA,N_(area) and SPAD but not for the other variables at the species-specific scale,indicating that intraspecific variation affects the overall pattern of LDMC,P_(mass) and N_(mass) and P_(area).In terms of species-specific response,posi-tive,negative or nonsignificant patterns were observed among the 92 species.Contrary to our prediction,species-specific responses within a functional group were not statistically more similar than those among functional groups.Our results indicated that leaf trait variation captured climatic difference yet species-specific responses were quite diverse irrespective of plant functional group,providing new insights for interpreting trait variability with climate.
基金supported by Zhejiang Provincial Natural Science Foundation of China(No.D19H300001).
文摘Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the accessibility of immunogenic cell death(ICD)related drugs and immune-related cells.Herein,the strategy of self-oriented deep tumor delivery by circulating monocyte/macrophage was proposed.Briefly,CS-AI including an indoleamine 2,3-dioxygenase(IDO)inhibitor indoximod(IND)and hydrophilic chitosan(CSO)linked with alanine-alanine-asparagine(AAN)was prepared,which could be selectively cleaved by legumain overexpressed in macrophages and promote the collapse in structure.Then,CS-AI was modified with mannose on the surface and further encapsulated the ICD inducer doxorubicin(DOX)to obtain M-CS-AI/DOX.Upon intravenous injection,MCS-AI/DOX was specially recognized and internalized by circulating monocyte in vivo.The formed drugs/monocyte tend to distribute in hypoxia/necrosis region guided by the homing signals released by tumor.Accumulated monocytes then further differentiated into macrophages,up-regulating the expression of legumain and promoting the sensitive-release of chemo-drug DOX,IND,and the mannose-modified CSO(M-CSO).The released IND would specifically regulate immunosuppressive tumor microenvironment,and synergistically inhibit tumor growth with immune activation elements,ICD-induced DOX,and the favorable adjuvant M-CSO.In summary,the self-oriented deep tumor delivery of legumain-cleavable nanovesicles through circulating monocyte makes it possible for reaching tumor regions inaccessible for nanoparticles and provides a novel insight for precise tumor enrichment and immune activation.
基金supported by the National Natural Science Foundation of China(No.81973267)Natural Science Foundation of Zhejiang Province(No.LD19H300001).
文摘Glial cell line-derived neurotrophic factor(GDNF),a disease-modifying drug for Parkinson’s disease(PD)is in Phase 2 clinical trials(EudraCT number:2011-003866-34),however it is administered by direct intrastriatal delivery via stereotaxy,which is accompanied with intracranial infection,brain tissue damage,and other complications.In addition,because of complex administration routes,clinical trials of GDNF have yielded contrary results,largely due to differences in dose and concentration brought by intracranial device.Herein,a small molecular agonist SC79 was screened to open blood-brain barrier(BBB)and promote GDNF liposomes to get into brain.SC79 reversibly reduces the expression of claudin-5,one of dominant tight junctions of BBB.Animal study showed SC79 promoted liposomes to enter into brain parenchyma 2.43 times more than that of the control.Motor deficits of PD mice receiving SC79 and brain-targeted GDNF liposomes were recovered by 36.70%and tyrosine hydroxylase positive neurons in striatum were restored by 39.90%.Our combination therapy effectively avoids the side effects such as secondary infection and uneven delivery caused by intracranial injection,improving patients’compliance and providing valuable research ideas for the clinic.
基金support from the National Natural Science Foundation of China(Nos.81773648 and 81973267)the Zhejiang Provincial Natural Science Foundation of China(Nos.LD19H300001 and LQ20H300004).
文摘Researches on indoleamine-2,3-dioxygenase-1(IDO1),a neoplastic pathogenesis-related protein,have provided a new angle of view to regulate malignancy-related immunosuppression.However,the therapeutic efficacy of IDO1 inhibitors is subject to key limitations as both cancer and dendritic cells tend to be trapped in the IDO1-mediated immune dysfunction,which poses challenges to the inhibitory potency of drug regimens in multiple targets.Here,we report on the fabrication technique of a biomimetic nanocarrier that is endowed with the whole array of cancer cell membrane proteins for encapsulating the most used IDO1 probe indoximod(IND).By fully utilizing the homologous adhesion proteins and antigenic motifs on cytomembrane,these nanoparticulate particles are capable of infiltrating tumors and actively accumulating in cancer and dendritic cells,as well as hitching a ride on dendritic cells to tumor-draining lymph nodes.Ultimately,by increasing the distribution of drugs in both tumor cells and dendritic cells in tumor-draining lymph nodes,these formulations greatly enhance the efficacy of IND without the aid of chemotherapeutic drugs,achieving substantial control of tumor growth.Overall,this leverage of bionanotechnology maximizes the therapeutic potential of IND and can provide a theoretical reference for the clinical application of IDO1 inhibitors.