Facility agriculture is an essential carrier for promoting stable production and supply.In2020,the planting area of facility agriculture in Beijing(290098000 m2)accounted for 29.06%of the total planting area of crops(...Facility agriculture is an essential carrier for promoting stable production and supply.In2020,the planting area of facility agriculture in Beijing(290098000 m2)accounted for 29.06%of the total planting area of crops(998078000 m2),and the output value accounted for 46.56%.In2022,Beijing Agricultural Technology Extension Station organized relevant departments to summarize and evaluate the agricultural facilities in Beijing through consultation materials,interviews,questionnaires,and field trips,combining survey data and statistical data to draw the following conclusions.Facilities play a major supporting role in stabilizing production and ensuring supply.The number of traditional greenhouses is extensive and covers a large area,so special planning and classification upgrades are urgently needed.Facilities are rich in scientific and technological resources,but the mode of production is out of date.It is of great significance to improve the comprehensive production capacity of facility agriculture and promote the healthy and stable development of facility industry in Beijing to increase the utilization rate of facility agriculture land,strengthen the support of facility science and technology,and cultivate the socialized service organization of facility.展开更多
A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cogni...A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients.展开更多
We estimated forest biomass carbon storage and carbon density from 1949 to 2008 based on nine consecutive forest inventories in Henan Province,China.According to the definitions of the forest inventory,Henan forests w...We estimated forest biomass carbon storage and carbon density from 1949 to 2008 based on nine consecutive forest inventories in Henan Province,China.According to the definitions of the forest inventory,Henan forests were categorized into five groups: forest stands,economic forests,bamboo forests,open forests,and shrub forests.We estimated biomass carbon in forest stands for each inventory period by using the continuous biomass expansion factor method.We used the mean biomass density method to estimate carbon stocks in economic,bamboo,open and shrub forests.Over the 60-year period,total forest vegetation carbon storage increased from34.6 Tg(1 Tg = 1×10^(12)g) in 1949 to 80.4 Tg in 2008,a net vegetation carbon increase of 45.8 Tg.By stand type,increases were 39.8 Tg in forest stands,5.5 Tg in economic forests,0.6 Tg in bamboo forests,and-0.1 Tg in open forests combine shrub forests.Carbon storageincreased at an average annual rate of 0.8 Tg carbon over the study period.Carbon was mainly stored in young and middle-aged forests,which together accounted for 70–88%of the total forest carbon storage in different inventory periods.Broad-leaved forest was the main contributor to forest carbon sequestration.From 1998 to 2008,during implementation of national afforestation and reforestation programs,the carbon storage of planted forest increased sharply from 3.9 to 37.9 Tg.Our results show that with the growth of young planted forest,Henan Province forests realized large gains in carbon sequestration over a 60-year period that was characterized in part by a nation-wide tree planting program.展开更多
The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder.Consequently,the norepinephrine transporter gene is an attractive candidate in m...The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder.Consequently,the norepinephrine transporter gene is an attractive candidate in major depressive disorder research.In the present study,we evaluated the depression symptoms of subjects with major depressive disorder,who were all from the North of China and of Han Chinese origin,using the Hamilton Depression Scale.We examined the rela-tionship between two single nucleotide polymorphisms in the norepinephrine transporter,rs2242446 and rs5569,and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program.rs5569 was associated with depressed mood,and the GG genotype may be a risk factor for this;rs2242446 was associated with work and interest,and the TT genotype may be a risk factor for loss of interest.Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Han Chinese population.展开更多
Macroencapsulation has been widely used in cell therapy due to its capability to provide immune-privileged sites for implanted allogeneic or xenogeneic cells.Macroencapsulation also serves to provide mechanical and ph...Macroencapsulation has been widely used in cell therapy due to its capability to provide immune-privileged sites for implanted allogeneic or xenogeneic cells.Macroencapsulation also serves to provide mechanical and physiochemical support for maintaining cell expansion and promoting therapeutic func-tions.Macroencapsulation devices such as membrane-controlled release systems,hydrogels,micronee-dle(MN)array patches,and three-dimensional(3D)stents have shown promising in-lab and preclinical results in the maintenance of long-term cell survival and the strengthening of treatment effi-cacy.Recent studies focus on expanding the applications of these devices to new cell-based areas such as chimeric antigen receptor(CAR)-T cell delivery,cardiovascular disease therapy,and the exploration of new materials,construction methods,and working principles to augment treatment efficacy and prolong therapy duration.Here,we survey innovative platforms and approaches,as well as translation outcomes,for advancing the performance and applications of macrodevices for cell-based therapies.A discussion and critique regarding future opportunities and challenges is also provided.展开更多
Poly(glycidyl methacrylates)(PGMA) was grafted from zinc oxide(ZnO) nanowires via surface-initiated atom transfer radical polymerization(SI-ATRP) technique.Firstly,the ZnO nanowires were synthesized by the one-pot hyd...Poly(glycidyl methacrylates)(PGMA) was grafted from zinc oxide(ZnO) nanowires via surface-initiated atom transfer radical polymerization(SI-ATRP) technique.Firstly,the ZnO nanowires were synthesized by the one-pot hydrothermal technique.Subsequently,the ZnO was functionalized with 3-aminopropyl triethoxysilane,which was converted to macroinitiator by the esterification of them with 2-bromopropionyl bromide.PGMA grafted ZnO nanowires(PGMA-ZnO) were then synthesized in an ATRP of the GMA with CuCl/2,2`-bipyridine as the catalyst system.Kinetics studies revealed an approximate linear increase in weight of polymer with reaction time,indicating that the polymerization process owned some "living" character.The structure and composition of PGMA-ZnO were characterized with scanning electron microscope(SEM),energy-dispersive X-ray(EDX) spectrometer,fourier transform infrared spectroscopy(FT-IR) and thermogravimetric analysis(TGA).展开更多
Leukemia ranks as one of the ten most fatal cancers [1].The mortality and incidence of this disease are associated with multiple factors, including environmental factors,sex, and age. Distinct genetic and chromosomal ...Leukemia ranks as one of the ten most fatal cancers [1].The mortality and incidence of this disease are associated with multiple factors, including environmental factors,sex, and age. Distinct genetic and chromosomal aberrations differentially affect the phenotype and prognosis of individuals with leukemia [2, 3]. The t(8;21)(q22;q22) translocation, which is observed in patients with acute myeloid leukemia with maturation (AML-M2, according to the French-American-British classification system), is characterized by the fusion of AML1 (acute myeloid leukemia factor 1, also referred to as RUNX1 [runt-related transcription factor 1]) on chromosome 21 and ETO (eight-twenty-one, also referred to as RUNX1T1 [runtrelated transcription factor 1, translocated to 1]) on chromosome 8. Although the t(8;21)(q22;q22) translocation is associated with a favorable prognosis, relapse remains the primary cause of treatment failure [4].展开更多
The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity a...The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.展开更多
Magnesium(Mg)alloys,as the lightest metal structural material with good damping capacities,have im-portant application prospects in realizing structural lightweight and vibration reduction.However,their engineering ap...Magnesium(Mg)alloys,as the lightest metal structural material with good damping capacities,have im-portant application prospects in realizing structural lightweight and vibration reduction.However,their engineering application is greatly limited by poor plastic formability.Wire and arc additive manufactur-ing(WAAM)provides a potential approach for fabricating large-scale Mg alloy components with high manufacturing flexibility.In this study,the evolution of the solidification microstructure of a WAAM-processed Mg-Al-based alloy was quantitatively analyzed based on the analytical models;then,the cor-relations between the solidification microstructure and mechanical properties/damping capacities were investigated.The results revealed that the WAAM-processed Mg-Al-based alloy with an equiaxed-grain-dominated microstructure displayed a simultaneous enhancement in mechanical properties and damping capacities compared to those of the cast Mg-Al-based alloy.The good combination of mechanical prop-erties and damping capacities are mainly attributed to the weakened basal texture with a relatively high Schmid factor for basalslip,the twinning-induced plasticity(TWIP)effect associated with the profuse{10-12}tensile twinning,and the relatively high dislocation density caused by the thermal stress during the WAAM process.展开更多
Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,o...Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival.展开更多
Zr modification is an effective method for improving hot-cracking resistance and elevated-temperature mechanical properties during laser powder bed fusion(L-PBF)of traditional medium and high strength wrought aluminum...Zr modification is an effective method for improving hot-cracking resistance and elevated-temperature mechanical properties during laser powder bed fusion(L-PBF)of traditional medium and high strength wrought aluminum alloys.This study investigated the l-PBF processability and elevated-temperature mechanical properties of a Zr-modified 2024Al alloy.It was found that the hot-cracking susceptibility increased with the increased scanning speed,which was in reasonable agreement with the modified Rappaz-Drezet-Gremaud criterion.Furthermore,the primary L1_(2)-Al_(3)Zr precipitates,which acted as ef-ficient nucleation sites,precipitated at the fusion boundary of the melt pool,leading to the formation of a heterogeneous grain structure.The yield strength(YS)of the as-fabricated samples at 150,250,and 350℃was 363,210,and 48 MPa,respectively.Despite the slight decrease to 360 MPa of the YS when tested at 150℃,owing to the additional precipitate strengthening from the L1_(2)-Al_(3)Zr precipitates,the YS achieved yield strengths of 253 and 69 MPa,an increase of 20.5%and 30.4%,when tested at 250 and 350℃,respectively.The yield strengths in both the as-fabricated and T6-treated conditions tested at 150 and 250℃were comparable to those of casting Al-Cu-Mg-Ag alloys and superior to those of traditionally heat-resistant 2219-T6 and 2618-T6 of Al-Cu alloys.展开更多
Prime editing(PE)is a recent gene editing technology that can mediate insertions or deletions and all twelve types of base-tobase conversions.However,its low efficiency hampers the application in creating novel breeds...Prime editing(PE)is a recent gene editing technology that can mediate insertions or deletions and all twelve types of base-tobase conversions.However,its low efficiency hampers the application in creating novel breeds and biomedical models,especially in pigs and other important farm animals.Here,we demonstrate that the pig genome is editable using the PE system,but the editing efficiency was quite low as expected.Therefore,we aimed to enhance PE efficiency by modulating both exogenous PE tools and endogenous pathways in porcine embryonic fibroblasts(PEFs).First,we modified the peg RNA by extending the duplex length and mutating the fourth thymine in a continuous sequence of thymine bases to cytosine,which significantly enhanced PE efficiency by improving the expression of peg RNA and targeted cleavage.Then,we targeted SAMHD1,a deoxynucleoside triphosphate triphosphohydrolase(d NTPase)that impedes the reverse transcription process in retroviruses,and found that treatment with its inhibitor,cephalosporin C zinc salt(CPC),increased PE efficiency up to 29-fold(4-fold on average),presumably by improving the reverse transcription process of Moloney murine leukemia virus reverse transcriptase(M-MLV RT)in the PE system.Moreover,PE efficiency was obviously improved by treatment with a panel of histone deacetylase inhibitors(HDACis).Among the four HDACis tested,panobinostat was the most efficient,with an efficiency up to 122-fold(7-fold on average),partly due to the considerable HDACi-mediated increase in transgene expression.In addition,the synergistic use of the three strategies further enhanced PE efficiency in PEFs.Our study provides novel approaches for optimization of the PE system and broadens the application scope of PE in agriculture and biomedicine.展开更多
Apple replant disease(ARD)negatively affects plant growth and reduces yields in replanted orchards.In this study,biochar was applied to apple replant soil with Fusarium oxysporum.Our aim was to investigate whether bio...Apple replant disease(ARD)negatively affects plant growth and reduces yields in replanted orchards.In this study,biochar was applied to apple replant soil with Fusarium oxysporum.Our aim was to investigate whether biochar could promote plant growth and alleviate apple replant disease by reducing the growth of harmful soil microorganisms,changing soil microbial community structure and improving the soil environment.This experiment included five treatments:apple replant soil(CK),methyl bromide fumigation apple replant soil(FM),replant soil with biochar addition(2%),replant soil with F.oxysporum spore solution(8×10^(7)spores·mL^(-1)),and replant soil with biochar and F.oxysporum spore solution addition.Seedling biomass,the activity of antioxidant enzymes in the leaves and roots,and soil environmental variables were measured.Microbial community composition and community structure were analyzed using 16SrDNA and ITS2 gene sequencing.Biochar significantly reduced the abundance of F.oxysporum and increased soil microbial diversity and richness.Biochar also increased the soil enzyme activities(urease,invertase,neutral phosphatase,and catalase),the biomass(plant height,fresh weight,dry weight)and the activity of antioxidant enzymes(superoxide dismutase,peroxidase,and catalase).The root indexes of apple seedlings was also increased in replant soil by biochar.In sum,biochar promoted the growth of plants,improved the replant soil environment,and alleviated apple replant disease.展开更多
The precise and simultaneous acquisition of multiple beneficial alleles in the genome is in great demand for the development of elite pig breeders. Cytidine base editors(CBEs) that convert C:G to T:A have emerged as p...The precise and simultaneous acquisition of multiple beneficial alleles in the genome is in great demand for the development of elite pig breeders. Cytidine base editors(CBEs) that convert C:G to T:A have emerged as powerful tools for single-nucleotide replacement. Whether CBEs can effectively mediate C-to-T substitution at multiple sites/loci for trait improvement by direct zygote injection has not been verified in large animals. Here, we determined the editing efficiency of four CBE variants in porcine embryonic fibroblast cells and embryos. The findings showed that hA3A-BE3-Y130F and hA3A-eBE-Y130F consistently resulted in increased base-editing efficiency and low toxic effects in embryonic development. Further, we verified that using a one-step approach, direct zygote microinjection of the CBE system can generate pigs harboring multiple point mutations.Our process resulted in a stop codon in CD163 and myostatin(MSTN) and introduced a beneficial allele in insulin-like growth factor-2(IGF2). The pigs showed disrupted expression of CD163 and MSTN and increased expression of IGF2, which significantly improved growth performance and infectious disease resistance. Our approach allows immediate introduction of multiple mutations in transgene-free animals to comprehensively improve economic traits through direct embryo microinjection,providing a potential new route to produce elite pig breeders.展开更多
基金supported by the Rural Revitalization Science and Technology Project of Beijing(No.20221230-01)Beijing Agriculture Innovation Consortium(No.BAIC 2022-1)。
文摘Facility agriculture is an essential carrier for promoting stable production and supply.In2020,the planting area of facility agriculture in Beijing(290098000 m2)accounted for 29.06%of the total planting area of crops(998078000 m2),and the output value accounted for 46.56%.In2022,Beijing Agricultural Technology Extension Station organized relevant departments to summarize and evaluate the agricultural facilities in Beijing through consultation materials,interviews,questionnaires,and field trips,combining survey data and statistical data to draw the following conclusions.Facilities play a major supporting role in stabilizing production and ensuring supply.The number of traditional greenhouses is extensive and covers a large area,so special planning and classification upgrades are urgently needed.Facilities are rich in scientific and technological resources,but the mode of production is out of date.It is of great significance to improve the comprehensive production capacity of facility agriculture and promote the healthy and stable development of facility industry in Beijing to increase the utilization rate of facility agriculture land,strengthen the support of facility science and technology,and cultivate the socialized service organization of facility.
基金supported by the National Natural Science Foundation of China,No.30971054,30770770,81171290
文摘A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients.
基金funded by the National Key Research and Development Program of China(2016YFC0501605)the National Sci-Tech Basic Program of China(2014FY210100)+1 种基金the National Natural Science foundation of China(31200332)the University Youth Teacher Training Program by Education Department of Henan Province(2016GGJS-062)
文摘We estimated forest biomass carbon storage and carbon density from 1949 to 2008 based on nine consecutive forest inventories in Henan Province,China.According to the definitions of the forest inventory,Henan forests were categorized into five groups: forest stands,economic forests,bamboo forests,open forests,and shrub forests.We estimated biomass carbon in forest stands for each inventory period by using the continuous biomass expansion factor method.We used the mean biomass density method to estimate carbon stocks in economic,bamboo,open and shrub forests.Over the 60-year period,total forest vegetation carbon storage increased from34.6 Tg(1 Tg = 1×10^(12)g) in 1949 to 80.4 Tg in 2008,a net vegetation carbon increase of 45.8 Tg.By stand type,increases were 39.8 Tg in forest stands,5.5 Tg in economic forests,0.6 Tg in bamboo forests,and-0.1 Tg in open forests combine shrub forests.Carbon storageincreased at an average annual rate of 0.8 Tg carbon over the study period.Carbon was mainly stored in young and middle-aged forests,which together accounted for 70–88%of the total forest carbon storage in different inventory periods.Broad-leaved forest was the main contributor to forest carbon sequestration.From 1998 to 2008,during implementation of national afforestation and reforestation programs,the carbon storage of planted forest increased sharply from 3.9 to 37.9 Tg.Our results show that with the growth of young planted forest,Henan Province forests realized large gains in carbon sequestration over a 60-year period that was characterized in part by a nation-wide tree planting program.
基金supported by the National Natural Science Foundation of China,No. 30770770,30971054,and81171290Science Foundation for the Youth of Shanxi,No.2011021036-1
文摘The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder.Consequently,the norepinephrine transporter gene is an attractive candidate in major depressive disorder research.In the present study,we evaluated the depression symptoms of subjects with major depressive disorder,who were all from the North of China and of Han Chinese origin,using the Hamilton Depression Scale.We examined the rela-tionship between two single nucleotide polymorphisms in the norepinephrine transporter,rs2242446 and rs5569,and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program.rs5569 was associated with depressed mood,and the GG genotype may be a risk factor for this;rs2242446 was associated with work and interest,and the TT genotype may be a risk factor for loss of interest.Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Han Chinese population.
基金supported by the grants from JDRF (2-SRA-2021-1064-M-B)Zhejiang University’s start-up packages+4 种基金the Kunpeng Program grantFundamental Research Funds for the Central Universities (2021FZZX001-46)supported in part by grants from the National Institutes of Health (EB022025 and GM043337)the n Cockrell Family Regents Chair in Engineering(UT Austin) for the Institute for Biomaterials,Drug Delivery,and Regenerative Medicinethe UT-Portugal Collaborative Research Program
文摘Macroencapsulation has been widely used in cell therapy due to its capability to provide immune-privileged sites for implanted allogeneic or xenogeneic cells.Macroencapsulation also serves to provide mechanical and physiochemical support for maintaining cell expansion and promoting therapeutic func-tions.Macroencapsulation devices such as membrane-controlled release systems,hydrogels,micronee-dle(MN)array patches,and three-dimensional(3D)stents have shown promising in-lab and preclinical results in the maintenance of long-term cell survival and the strengthening of treatment effi-cacy.Recent studies focus on expanding the applications of these devices to new cell-based areas such as chimeric antigen receptor(CAR)-T cell delivery,cardiovascular disease therapy,and the exploration of new materials,construction methods,and working principles to augment treatment efficacy and prolong therapy duration.Here,we survey innovative platforms and approaches,as well as translation outcomes,for advancing the performance and applications of macrodevices for cell-based therapies.A discussion and critique regarding future opportunities and challenges is also provided.
基金the National Natural Science Foundation of China (No.50730008 and 30772434)Shanghai Science & Technology Committee (No.09JC1407400 and 1052nm02000)
文摘Poly(glycidyl methacrylates)(PGMA) was grafted from zinc oxide(ZnO) nanowires via surface-initiated atom transfer radical polymerization(SI-ATRP) technique.Firstly,the ZnO nanowires were synthesized by the one-pot hydrothermal technique.Subsequently,the ZnO was functionalized with 3-aminopropyl triethoxysilane,which was converted to macroinitiator by the esterification of them with 2-bromopropionyl bromide.PGMA grafted ZnO nanowires(PGMA-ZnO) were then synthesized in an ATRP of the GMA with CuCl/2,2`-bipyridine as the catalyst system.Kinetics studies revealed an approximate linear increase in weight of polymer with reaction time,indicating that the polymerization process owned some "living" character.The structure and composition of PGMA-ZnO were characterized with scanning electron microscope(SEM),energy-dispersive X-ray(EDX) spectrometer,fourier transform infrared spectroscopy(FT-IR) and thermogravimetric analysis(TGA).
基金supported by the National Natural Science Foundation of China (No.11374180)
文摘Leukemia ranks as one of the ten most fatal cancers [1].The mortality and incidence of this disease are associated with multiple factors, including environmental factors,sex, and age. Distinct genetic and chromosomal aberrations differentially affect the phenotype and prognosis of individuals with leukemia [2, 3]. The t(8;21)(q22;q22) translocation, which is observed in patients with acute myeloid leukemia with maturation (AML-M2, according to the French-American-British classification system), is characterized by the fusion of AML1 (acute myeloid leukemia factor 1, also referred to as RUNX1 [runt-related transcription factor 1]) on chromosome 21 and ETO (eight-twenty-one, also referred to as RUNX1T1 [runtrelated transcription factor 1, translocated to 1]) on chromosome 8. Although the t(8;21)(q22;q22) translocation is associated with a favorable prognosis, relapse remains the primary cause of treatment failure [4].
基金This work was supported by the National Postdoctoral Foundation of China(No.2023M730375)Liaoning Province Department of Education Project(No.LJKMZ20221365,China)+3 种基金the State Key Laboratory of Natural and Biomimetic Drugs(No.K202215,China)the National Natural Science Foundation of China(No.82173766)Liaoning Province Applied Basic Research Program(No.2022JH2/101300097,China)the Natural Science Foundation of Shandong Province(No.ZR2021QH084,China)。
文摘The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.
基金supported by the National Key Research and Development Program of China (No.2021YFB3701100)the National Natural Science Foundation of China (Nos.U20A20234,51874062)+1 种基金the Postdoctoral Science Foundation of China (No.2022M710503)the Chongqing Foundation and Advanced Research Project (No.cstc2019jcyj-zdxmX0010).
文摘Magnesium(Mg)alloys,as the lightest metal structural material with good damping capacities,have im-portant application prospects in realizing structural lightweight and vibration reduction.However,their engineering application is greatly limited by poor plastic formability.Wire and arc additive manufactur-ing(WAAM)provides a potential approach for fabricating large-scale Mg alloy components with high manufacturing flexibility.In this study,the evolution of the solidification microstructure of a WAAM-processed Mg-Al-based alloy was quantitatively analyzed based on the analytical models;then,the cor-relations between the solidification microstructure and mechanical properties/damping capacities were investigated.The results revealed that the WAAM-processed Mg-Al-based alloy with an equiaxed-grain-dominated microstructure displayed a simultaneous enhancement in mechanical properties and damping capacities compared to those of the cast Mg-Al-based alloy.The good combination of mechanical prop-erties and damping capacities are mainly attributed to the weakened basal texture with a relatively high Schmid factor for basalslip,the twinning-induced plasticity(TWIP)effect associated with the profuse{10-12}tensile twinning,and the relatively high dislocation density caused by the thermal stress during the WAAM process.
基金National Key R&D Program of China(No.2021YFA0909900)Zhejiang Provincial Natural Science Foundation of China(No.LY23C100001)+2 种基金National Natural Science Foundation of China(Nos.51973214 and 51503003)Kunpeng Program from Zhejiang Province,Zhejiang University's start-up packages,Fundamental Research Funds for the Central Universities(No.2021FZZX001-46)the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University(No.SN-ZJU-SIAS-009).
文摘Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival.
基金The work was financially supported by the National Key R&D Program of China(No.2016YFB1100100)the Research Fund of the State Key Laboratory of Solidification Processing(NPU),China(No.2020-TZ-02)+3 种基金the Advance Research Projects in the Field of Manned Spaceflight(No.040302)the Shanghai Aerospace Science and Technology Innovation Fund Project(No.SAST2018-066)This work was also supported by the“Fundamental Research Funds for the Central Universities”(No.G2021KY05104)the“Natural Science Basis Research Plan in Shaanxi Province of China”(No.2022JQ-479).We would like to thank Editage(www.editage.com)for En-glish language editing.
文摘Zr modification is an effective method for improving hot-cracking resistance and elevated-temperature mechanical properties during laser powder bed fusion(L-PBF)of traditional medium and high strength wrought aluminum alloys.This study investigated the l-PBF processability and elevated-temperature mechanical properties of a Zr-modified 2024Al alloy.It was found that the hot-cracking susceptibility increased with the increased scanning speed,which was in reasonable agreement with the modified Rappaz-Drezet-Gremaud criterion.Furthermore,the primary L1_(2)-Al_(3)Zr precipitates,which acted as ef-ficient nucleation sites,precipitated at the fusion boundary of the melt pool,leading to the formation of a heterogeneous grain structure.The yield strength(YS)of the as-fabricated samples at 150,250,and 350℃was 363,210,and 48 MPa,respectively.Despite the slight decrease to 360 MPa of the YS when tested at 150℃,owing to the additional precipitate strengthening from the L1_(2)-Al_(3)Zr precipitates,the YS achieved yield strengths of 253 and 69 MPa,an increase of 20.5%and 30.4%,when tested at 250 and 350℃,respectively.The yield strengths in both the as-fabricated and T6-treated conditions tested at 150 and 250℃were comparable to those of casting Al-Cu-Mg-Ag alloys and superior to those of traditionally heat-resistant 2219-T6 and 2618-T6 of Al-Cu alloys.
基金supported by the National Key Research and Development Program of China (2020YFA0509503,2022YFF0710703,2021YFA0805902)the National Science Fund for Distinguished Young Scholars (31925036,32025034)+3 种基金the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2019QNRC001)the National Natural Science Foundation of China (31801031)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030304)Lingnan Modern Agriculture Project (NT2021005)。
文摘Prime editing(PE)is a recent gene editing technology that can mediate insertions or deletions and all twelve types of base-tobase conversions.However,its low efficiency hampers the application in creating novel breeds and biomedical models,especially in pigs and other important farm animals.Here,we demonstrate that the pig genome is editable using the PE system,but the editing efficiency was quite low as expected.Therefore,we aimed to enhance PE efficiency by modulating both exogenous PE tools and endogenous pathways in porcine embryonic fibroblasts(PEFs).First,we modified the peg RNA by extending the duplex length and mutating the fourth thymine in a continuous sequence of thymine bases to cytosine,which significantly enhanced PE efficiency by improving the expression of peg RNA and targeted cleavage.Then,we targeted SAMHD1,a deoxynucleoside triphosphate triphosphohydrolase(d NTPase)that impedes the reverse transcription process in retroviruses,and found that treatment with its inhibitor,cephalosporin C zinc salt(CPC),increased PE efficiency up to 29-fold(4-fold on average),presumably by improving the reverse transcription process of Moloney murine leukemia virus reverse transcriptase(M-MLV RT)in the PE system.Moreover,PE efficiency was obviously improved by treatment with a panel of histone deacetylase inhibitors(HDACis).Among the four HDACis tested,panobinostat was the most efficient,with an efficiency up to 122-fold(7-fold on average),partly due to the considerable HDACi-mediated increase in transgene expression.In addition,the synergistic use of the three strategies further enhanced PE efficiency in PEFs.Our study provides novel approaches for optimization of the PE system and broadens the application scope of PE in agriculture and biomedicine.
基金supported by the earmarked fund for National Natural Science Foundation of China(Grant No.31801816)National Modern Agro-industry Technology Research System(Grant No.CARS-27)Taishan scholar funded project(Grant No.TS20190923)。
文摘Apple replant disease(ARD)negatively affects plant growth and reduces yields in replanted orchards.In this study,biochar was applied to apple replant soil with Fusarium oxysporum.Our aim was to investigate whether biochar could promote plant growth and alleviate apple replant disease by reducing the growth of harmful soil microorganisms,changing soil microbial community structure and improving the soil environment.This experiment included five treatments:apple replant soil(CK),methyl bromide fumigation apple replant soil(FM),replant soil with biochar addition(2%),replant soil with F.oxysporum spore solution(8×10^(7)spores·mL^(-1)),and replant soil with biochar and F.oxysporum spore solution addition.Seedling biomass,the activity of antioxidant enzymes in the leaves and roots,and soil environmental variables were measured.Microbial community composition and community structure were analyzed using 16SrDNA and ITS2 gene sequencing.Biochar significantly reduced the abundance of F.oxysporum and increased soil microbial diversity and richness.Biochar also increased the soil enzyme activities(urease,invertase,neutral phosphatase,and catalase),the biomass(plant height,fresh weight,dry weight)and the activity of antioxidant enzymes(superoxide dismutase,peroxidase,and catalase).The root indexes of apple seedlings was also increased in replant soil by biochar.In sum,biochar promoted the growth of plants,improved the replant soil environment,and alleviated apple replant disease.
基金supported by the National Natural Science Foundation for Distinguished Young Scholars (31925036)the National Key Research and Development Program of China (2020YFC1316602)+2 种基金the National Natural Science Foundation of China (81671274, 31272440, and 31801031)the National Transgenic Project of China (2016ZX08009003-006-007)the Elite Youth Program of the Chinese Academy of Agricultural Sciences (ASTIP-IAS05)
文摘The precise and simultaneous acquisition of multiple beneficial alleles in the genome is in great demand for the development of elite pig breeders. Cytidine base editors(CBEs) that convert C:G to T:A have emerged as powerful tools for single-nucleotide replacement. Whether CBEs can effectively mediate C-to-T substitution at multiple sites/loci for trait improvement by direct zygote injection has not been verified in large animals. Here, we determined the editing efficiency of four CBE variants in porcine embryonic fibroblast cells and embryos. The findings showed that hA3A-BE3-Y130F and hA3A-eBE-Y130F consistently resulted in increased base-editing efficiency and low toxic effects in embryonic development. Further, we verified that using a one-step approach, direct zygote microinjection of the CBE system can generate pigs harboring multiple point mutations.Our process resulted in a stop codon in CD163 and myostatin(MSTN) and introduced a beneficial allele in insulin-like growth factor-2(IGF2). The pigs showed disrupted expression of CD163 and MSTN and increased expression of IGF2, which significantly improved growth performance and infectious disease resistance. Our approach allows immediate introduction of multiple mutations in transgene-free animals to comprehensively improve economic traits through direct embryo microinjection,providing a potential new route to produce elite pig breeders.
