Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring ...Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring of these events is essential for effective viral surveillance and control.Methods Respiratory specimens were collected from children with ARIs between January 2022 and December 2023.The penton base,hexon,and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type.In cases with inconsistent typing results,genes were cloned into the pGEM-T vector to detect recombination events.Metagenomic next-generation sequencing(mNGS)was performed to characterize the recombinant HAdV genomes.Results Among 6,771 specimens,277(4.09%,277/6,771)were positvie for HAdV,of which 157(56.68%,157/277)were successfully typed,with HAdV-B3 being the dominant type(91.08%,143/157),and 14(5.05%,14/277)exhibited inconsistent typing results,six of which belonged to species B.The penton base genes of these six specimens were classified as HAdV-B7,whereas their hexon and fiber genes were classified as HAdV-B3,resulting in a recombinant genotype designated P7H3F3,which closely resembled HAdV-B114.Additionally,a partial gene encoding L152/55 kD was identified,which originated from HAdV-B16.Conclusion A novel recombinant,P7H3F3,was identified,containing sequences derived from HAdV-B3 and HAdV-B7,which is similar to HAdV-B114,along with additional sequences from HAdV-B16.展开更多
Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the d...Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.展开更多
Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical parts.Layer thickness(LT)is of great significance to the L-PBF process but has not...Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical parts.Layer thickness(LT)is of great significance to the L-PBF process but has not been studied for Mg alloys.In this study,WE43 Mg alloy bulk cubes,porous scaffolds,and thin walls with layer thicknesses of 10,20,30,and 40μm were fabricated.The required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous scaffolds.Porosity tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy input.For thin wall parts,a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used,and the porosity disappeared by reducing the layer thickness or laser energy input.A deeper keyhole penetration was found in all occasions with porosity,explaining the influence of layer thickness,geometrical structure,and laser energy input on the porosity.All the samples achieved a high fusion quality with a relative density of over 99.5%using the optimized laser energy input.The increased layer thickness resulted to more precipitation phases,finer grain sizes and decreased grain texture.With the similar high fusion quality,the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41%with the 10μm layer to 287 MPa and 15.12%with the 40μm layer,in accordance with the microstructural change.The effect of layer thickness on the compressive properties of porous scaffolds was limited.However,the corrosion rate of bulk samples accelerated with increasing the layer thickness,mainly attributed to the increased number of precipitation phases.展开更多
Laser powder bed fusion(L-PBF)has been employed to additively manufacture WE43 magnesium(Mg)alloy biodegradable implants,but WE43 L-PBF samples exhibit excessively rapid corrosion.In this work,dense WE43 L-PBF samples...Laser powder bed fusion(L-PBF)has been employed to additively manufacture WE43 magnesium(Mg)alloy biodegradable implants,but WE43 L-PBF samples exhibit excessively rapid corrosion.In this work,dense WE43 L-PBF samples were built with the relativity density reaching 99.9%.High temperature oxidation was performed on the L-PBF samples in circulating air via various heating temperatures and holding durations.The oxidation and diffusion at the elevated temperature generated a gradient structure composed of an oxide layer at the surface,a transition layer in the middle and the matrix.The oxide layer consisted of rare earth(RE)oxides,and became dense and thick with increasing the holding duration.The matrix was composed ofα-Mg,RE oxides and Mg_(24)RE_(5) precipitates.The precipitates almost disappeared in the transition layer.Enhanced passivation effect was observed in the samples treated by a suitable high temperature oxidation.The original L-PBF samples lost 40%weight after 3-day immersion in Hank’s solution,and broke into fragments after 7-day immersion.The casted and solution treated samples lost roughly half of the weight after 28-day immersion.The high temperature oxidation samples,which were heated at 525℃ for 8 h,kept the structural integrity,and lost only 6.88%weight after 28-day immersion.The substantially improved corrosion resistance was contributed to the gradient structure at the surface.On one hand,the outmost dense layer of RE oxides isolated the corrosive medium;on the other hand,the transition layer considerably inhibited the corrosion owing to the lack of precipitates.Overall,high temperature oxidation provides an efficient,economic and safe approach to inhibit the corrosion of WE43 L-PBF samples,and has promising prospects for future clinical applications.展开更多
Only a few studies have examined how pore geometry affects the mechanical characteristics, biological behavior, and degradation of additively manufactured biodegradable porous magnesium. In this work, the effects of p...Only a few studies have examined how pore geometry affects the mechanical characteristics, biological behavior, and degradation of additively manufactured biodegradable porous magnesium. In this work, the effects of pore geometry on mechanical qualities, degradation,and biological behavior were investigated using three typical porous architectures with the same porosity. The porous structures were found to satisfy bone tissue engineering requirements because they had sufficient degradation resistance and tunable compressive characteristics. All three types of magnesium alloy scaffolds exhibited good biocompatibility. Additionally, the magnesium alloy porous structures influenced the magnesium scaffold material degradation rate and the surrounding environment, impacting the osteogenic differentiation of bone mesenchymal stem cells and bone tissue regeneration. This work offers conceptual support for optimizing pore geometry to alter the mechanical and degradable characteristics of additively manufactured porous magnesium to meet therapeutic demands.展开更多
With the continuous development and improvement of social science and technology,the“learning-oriented”teaching method is proposed,the traditional experimental teaching methods in colleges and universities are insuf...With the continuous development and improvement of social science and technology,the“learning-oriented”teaching method is proposed,the traditional experimental teaching methods in colleges and universities are insufficient to meet the needs of experimental teaching.By studying the role and advantages of digital animation technology in experimental teaching,analyzing the application principle of digital animation in laboratory teaching,it is proposed to strengthen the application of digital animation technology in experimental teaching,give full play to the advantages of digital animation technology,and improve the quality of experimental teaching to promote students’learning efficiency in experimental teaching.展开更多
With the rapid development of computing technology,experimental teaching explores new teaching methods using virtual laboratory and digital laboratory.Based on the characteristics of visualization,continuity and simul...With the rapid development of computing technology,experimental teaching explores new teaching methods using virtual laboratory and digital laboratory.Based on the characteristics of visualization,continuity and simulation,digital animation technology has become an important form of application in experimental teaching reform.This paper analyzes the artistic characteristics of digital animation,and summarizes that digital animation can display the experimental information intuitively,enable students to quickly obtain the cognition of the experimental content,and obtain psychological pleasure through digital animation in experimental learning,thus improving the teaching effect of experimental teaching.展开更多
Chimeric antigen receptor T-cell(CAR-T)therapy has been successfully applied in clinical treatment,especially for hematologic malignancies such as multiple myeloma(MM),but its broad application is limited by cytokine ...Chimeric antigen receptor T-cell(CAR-T)therapy has been successfully applied in clinical treatment,especially for hematologic malignancies such as multiple myeloma(MM),but its broad application is limited by cytokine release syndrome(CRS),a potentially life-threatening complication.Although metabolic alterations are known to accompany CRS,predictive biomarkers for its onset,severity,and associated metabolic remodeling remain unknown,hindering proactive clinical management.Here,we analyzed longitudinal serum metabolic profiles from 19 patients with relapsed/refractory MM receiving CAR-T therapy,with validation in an independent cohort of 23 patients.We observed dysregulated arginine metabolism that progressed alongside clinical CRS.At pre-lymphodepletion(Day–5),over half of differentially abundant metabolites were enriched in unsaturated fatty acid(UFA)synthesis pathways,which were exclusively upregulated in patients who later developed severe CRS.Furthermore,two lysophosphatidylcholines,namely,lysoPC(16:0)and lysoPC(15:0),were significantly associated with delayed CRS onset,with elevated concentrations correlated with a prolonged time to onset;this association was independently validated.These findings revealed that arginine metabolism was a pathological axis in CRS,UFAs were severity predictors,and specific lysoPCs were modulators of onset time.Collectively,they provide proactive CRS management,addressing critical gaps in predictive biomarkers to advance the safe,broad CAR-T application in MM.展开更多
Laser powder bed fusion(L-PBF)of magnesium(Mg)alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects.However,one of t...Laser powder bed fusion(L-PBF)of magnesium(Mg)alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects.However,one of the key technical difficulties lies in the poor L-PBF process performance of Mg,contributed by the high susceptibility to oxidation,vaporization,thermal expansion,and powder attachment etc.This work investigated the influence of L-PBF energy input and scanning strategy on the formation quality of porous scaffolds by using WE43 powder,and characterized the microstructure,mechanical properties,biocompatibility,biodegradation and osteogenic effect of the as-built WE43 porous scaffolds.With the customized energy input and scanning strategy,the relative density of struts reached over 99.5%,and the geometrical error between the designed and the fabricated porosity declined to below 10%.Massive secondary phases including intermetallic precipitates and oxides were observed.The compressive strength(4.37-23.49 MPa)and elastic modulus(154.40-873.02 MPa)were comparable to those of cancellous bone.Good biocompatibility was observed by in vitro cell viability and in vivo implantation.The biodegradation of as-built porous scaffolds promoted the osteogenic effect,but the structural integrity devastated after 12 h by the immersion tests in Hank’s solution and after 4 weeks by the implantation in rabbits’femur,indicating an excessively rapid degradation rate.展开更多
The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work...The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work, we found that high temperature oxidation improves the corrosion resistance of magnesium scaffold. And the effects of pore size on the mechanical characteristics and biodegradation of scaffolds, as well as new bone formation, were investigated using magnesium scaffolds with three different pore sizes, namely, 500, 800, and 1400 μm (P500, P800, and P1400). We discovered that the mechanical characteristics of the P500 group were much better than those of the other two groups. In vitro and in vivo investigations showed that WE43 magnesium alloy scaffolds supported the survival of mesenchymal stem cells and did not cause any local toxicity. Due to their larger specific surface area, the scaffolds in the P500 group released more magnesium ions within reasonable range and improved the osteogenic differentiation of bone mesenchymal stem cells compared with the other two scaffolds. In a rabbit femoral condyle defect model, the P500 group demonstrated unique performance in promoting new bone formation, indicating its great potential for use in bone defect regeneration therapy.展开更多
The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine research.Though an altered microenvironme...The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine research.Though an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly understood.Here,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy.Our study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma composition.One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA.Furthermore,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins.Overall,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.展开更多
Two-dimensional(2D)porphyrin(Por)-based covalent organic frameworks(COFs)provide an attractive and effective strategy for photocatalytic CO_(2)reduction,but the layered structure due toπ–πstacking is challenging fo...Two-dimensional(2D)porphyrin(Por)-based covalent organic frameworks(COFs)provide an attractive and effective strategy for photocatalytic CO_(2)reduction,but the layered structure due toπ–πstacking is challenging for the exposure of active sites and transfer of mass and photogenerated carriers.In this study,a series of 2D conjugated porphyrin-based COFs were prepared using porphyrin blocks with linking units having different degrees of twisting.According to the experimental and theoretical calculation results,owing to the large spatial steric hindrance between the two carbazole units connected by the N–N single bond,a greatly undulating layered structure was formed in NN-Por-COF,which enhanced mass transfer and exposed more catalytic sites.The introduction of carbazole also modulated the electronic structure of the porphyrin Co center,which lowered the reaction energy barrier.The optimization of the structural and electronic effects led to the excellent photocatalytic CO_(2)reduction performance of NN-Por-COF,with CO conversion rates as high as 22.38 and 3.02 mmol g−1 h−1 under pure and diluted(10%)CO_(2)atmosphere,respectively,which are superior to those of most of the reported porphyrin-based photocatalysts.展开更多
Recent deep-diving expeditions in the South China Sea(SCS)discovered abundant indigenous cold-water corals[1].Cold-water corals,preferentially inhabiting the low-latitude intermediate and deep waters with hard substra...Recent deep-diving expeditions in the South China Sea(SCS)discovered abundant indigenous cold-water corals[1].Cold-water corals,preferentially inhabiting the low-latitude intermediate and deep waters with hard substrates and a cool water temperature,have great potential to be applied in researches of the ocean interior by providing high-resolution records[2,3].展开更多
Group B Streptococcus(GBS)is the major pathogen that causes invasive infectious diseases in neonates and infants.The develop-ment of preventive and therapeutic strategies against GBS infection has been becoming the mo...Group B Streptococcus(GBS)is the major pathogen that causes invasive infectious diseases in neonates and infants.The develop-ment of preventive and therapeutic strategies against GBS infection has been becoming the most pressing subject worldwide.Group B carbohydrate(GBC),the group B-specific polysaccharide that distinguishes GBS with other streptococci species,has been identified as an attractive antigen for diagnosis and vaccine development because of its highly conservative tetra-antennary structure.In this paper,a highly convergent[3+5]glycosylation strategy for efficient synthesis of an octasaccharide derivative related to GBC oligo-saccharide unitⅡhas been developed.In this synthesis,each glycosylation reaction was efficiently constructed with glycosyl im-idates,especially trifluoroacetimidate,as donors,and each glycosidic bond was stereoselectively controlled via the neighboring group participation effect of acyl group on the 2-O-position of imidate donors or the solvent effect of Et_(2)O.Furthermore,the ami-noethylphosphate group was smoothly installed on the 6-O-position of D-glucitoll residue using the phosphoramidite method.After global deprotection,the target octasaccharide was successfully obtained from o-glucitol in 29 steps with an overall yield of 1.37%.The free amino group installed on the aminoethylphosphate spacer of the target molecule enables its modification with functional-ized biomolecules for further biological studies.展开更多
Global warming during the Miocene Climate Optimum(MCO,~17-14 million years ago)is associated with massive carbon emissions sourced from the flood basalt volcanism and ocean crustal production.However,the perturbation ...Global warming during the Miocene Climate Optimum(MCO,~17-14 million years ago)is associated with massive carbon emissions sourced from the flood basalt volcanism and ocean crustal production.However,the perturbation of tectonic carbon degassing on the interaction between climate change and carbon cycle remains unclear.Here,through time-evolutive phase analysis of new and published high-resolution benthic foraminiferal oxygen(δ^(18)O)and carbon(δ^(13)C)isotope records from the global ocean,we find that variations in the marine carbon cycle lead the climate-cryosphere system(δ^(13)Clead-δ^(18)O)on 405,000-year eccentricity timescales during the MCO.This is in contrast to the previously reported climate-lead-carbon(δ^(18)O-lead-δ^(13)C)scenario during most of the Oligo-Miocene(~34-6 million years ago).Further sensitivity analysis and model simulations suggest that the elevated atmospheric CO_(2) concentrations and the resulting greenhouse effect strengthened the low-latitude hydrological cycle during the MCO,accelerating the response of marine carbon cycle to eccentricity forcing.Tropical climate processes played a more important role in regulating carbon-cycle variations when Earth's climate was in a warm regime,as opposed to the dominant influence of polar ice-sheet dynamics during the PlioPleistocene(after~6 million years ago).展开更多
基金supported by the Capital’s Funds for Health Improvement and Research(CFH,shoufa-2022-1G-1131 and shoufa 2022-4G-1133)the High Level Technical Talent Construction Project of Beijing Municipal Health Commission(Discipline Leader-02-20)+1 种基金Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY2023-10)the Pathogen Spectrum and Host Marker Analysis in Children with Respiratory Tract Infections of Children(Grant 2024-0040).
文摘Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring of these events is essential for effective viral surveillance and control.Methods Respiratory specimens were collected from children with ARIs between January 2022 and December 2023.The penton base,hexon,and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type.In cases with inconsistent typing results,genes were cloned into the pGEM-T vector to detect recombination events.Metagenomic next-generation sequencing(mNGS)was performed to characterize the recombinant HAdV genomes.Results Among 6,771 specimens,277(4.09%,277/6,771)were positvie for HAdV,of which 157(56.68%,157/277)were successfully typed,with HAdV-B3 being the dominant type(91.08%,143/157),and 14(5.05%,14/277)exhibited inconsistent typing results,six of which belonged to species B.The penton base genes of these six specimens were classified as HAdV-B7,whereas their hexon and fiber genes were classified as HAdV-B3,resulting in a recombinant genotype designated P7H3F3,which closely resembled HAdV-B114.Additionally,a partial gene encoding L152/55 kD was identified,which originated from HAdV-B16.Conclusion A novel recombinant,P7H3F3,was identified,containing sequences derived from HAdV-B3 and HAdV-B7,which is similar to HAdV-B114,along with additional sequences from HAdV-B16.
基金supported by the Shandong Province Medical and Health Technology Project(202303111442).
文摘Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.
基金funded by the National Key Research and Development Program of China(2018YFE0104200)National Natural Science Foundation of China(51875310,52175274,82172065)Tsinghua Precision Medicine Foundation.
文摘Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical parts.Layer thickness(LT)is of great significance to the L-PBF process but has not been studied for Mg alloys.In this study,WE43 Mg alloy bulk cubes,porous scaffolds,and thin walls with layer thicknesses of 10,20,30,and 40μm were fabricated.The required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous scaffolds.Porosity tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy input.For thin wall parts,a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used,and the porosity disappeared by reducing the layer thickness or laser energy input.A deeper keyhole penetration was found in all occasions with porosity,explaining the influence of layer thickness,geometrical structure,and laser energy input on the porosity.All the samples achieved a high fusion quality with a relative density of over 99.5%using the optimized laser energy input.The increased layer thickness resulted to more precipitation phases,finer grain sizes and decreased grain texture.With the similar high fusion quality,the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41%with the 10μm layer to 287 MPa and 15.12%with the 40μm layer,in accordance with the microstructural change.The effect of layer thickness on the compressive properties of porous scaffolds was limited.However,the corrosion rate of bulk samples accelerated with increasing the layer thickness,mainly attributed to the increased number of precipitation phases.
基金funded by the National Key Research and Development Program of China (2018YFE0104200)National Natural Science Foundation of China (51875310, 52175274, 82172065)Tsinghua Precision Medicine Foundation
文摘Laser powder bed fusion(L-PBF)has been employed to additively manufacture WE43 magnesium(Mg)alloy biodegradable implants,but WE43 L-PBF samples exhibit excessively rapid corrosion.In this work,dense WE43 L-PBF samples were built with the relativity density reaching 99.9%.High temperature oxidation was performed on the L-PBF samples in circulating air via various heating temperatures and holding durations.The oxidation and diffusion at the elevated temperature generated a gradient structure composed of an oxide layer at the surface,a transition layer in the middle and the matrix.The oxide layer consisted of rare earth(RE)oxides,and became dense and thick with increasing the holding duration.The matrix was composed ofα-Mg,RE oxides and Mg_(24)RE_(5) precipitates.The precipitates almost disappeared in the transition layer.Enhanced passivation effect was observed in the samples treated by a suitable high temperature oxidation.The original L-PBF samples lost 40%weight after 3-day immersion in Hank’s solution,and broke into fragments after 7-day immersion.The casted and solution treated samples lost roughly half of the weight after 28-day immersion.The high temperature oxidation samples,which were heated at 525℃ for 8 h,kept the structural integrity,and lost only 6.88%weight after 28-day immersion.The substantially improved corrosion resistance was contributed to the gradient structure at the surface.On one hand,the outmost dense layer of RE oxides isolated the corrosive medium;on the other hand,the transition layer considerably inhibited the corrosion owing to the lack of precipitates.Overall,high temperature oxidation provides an efficient,economic and safe approach to inhibit the corrosion of WE43 L-PBF samples,and has promising prospects for future clinical applications.
基金National Key Research and Development Program of China (2018YFE0104200)Youth Innovation Promotion Association CAS (2019031)National Natural Science Foundation of China (51875310,52175274, 82172065)。
文摘Only a few studies have examined how pore geometry affects the mechanical characteristics, biological behavior, and degradation of additively manufactured biodegradable porous magnesium. In this work, the effects of pore geometry on mechanical qualities, degradation,and biological behavior were investigated using three typical porous architectures with the same porosity. The porous structures were found to satisfy bone tissue engineering requirements because they had sufficient degradation resistance and tunable compressive characteristics. All three types of magnesium alloy scaffolds exhibited good biocompatibility. Additionally, the magnesium alloy porous structures influenced the magnesium scaffold material degradation rate and the surrounding environment, impacting the osteogenic differentiation of bone mesenchymal stem cells and bone tissue regeneration. This work offers conceptual support for optimizing pore geometry to alter the mechanical and degradable characteristics of additively manufactured porous magnesium to meet therapeutic demands.
文摘With the continuous development and improvement of social science and technology,the“learning-oriented”teaching method is proposed,the traditional experimental teaching methods in colleges and universities are insufficient to meet the needs of experimental teaching.By studying the role and advantages of digital animation technology in experimental teaching,analyzing the application principle of digital animation in laboratory teaching,it is proposed to strengthen the application of digital animation technology in experimental teaching,give full play to the advantages of digital animation technology,and improve the quality of experimental teaching to promote students’learning efficiency in experimental teaching.
基金Research on the Unique Role of Digital Animation in Energy Science Experimental Teaching.
文摘With the rapid development of computing technology,experimental teaching explores new teaching methods using virtual laboratory and digital laboratory.Based on the characteristics of visualization,continuity and simulation,digital animation technology has become an important form of application in experimental teaching reform.This paper analyzes the artistic characteristics of digital animation,and summarizes that digital animation can display the experimental information intuitively,enable students to quickly obtain the cognition of the experimental content,and obtain psychological pleasure through digital animation in experimental learning,thus improving the teaching effect of experimental teaching.
基金supported by the State Key Laboratory of Medical Genomics,the Double First-Class Project(No.WF510162602)from the Ministry of EducationOverseas Expertise Introduction Project for Discipline Innovation(111 Project,No.B17029)+2 种基金National Natural Science Foundation of China(Nos.82230006,82470206,32170663,32470681,and 81770124)Innovative Research Team of High-level Local Universities in Shanghai and CAMS Innovation Fund for Medical Sciences(No.CIFMS 2021-I2M-5-010)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(No.RC20210190).
文摘Chimeric antigen receptor T-cell(CAR-T)therapy has been successfully applied in clinical treatment,especially for hematologic malignancies such as multiple myeloma(MM),but its broad application is limited by cytokine release syndrome(CRS),a potentially life-threatening complication.Although metabolic alterations are known to accompany CRS,predictive biomarkers for its onset,severity,and associated metabolic remodeling remain unknown,hindering proactive clinical management.Here,we analyzed longitudinal serum metabolic profiles from 19 patients with relapsed/refractory MM receiving CAR-T therapy,with validation in an independent cohort of 23 patients.We observed dysregulated arginine metabolism that progressed alongside clinical CRS.At pre-lymphodepletion(Day–5),over half of differentially abundant metabolites were enriched in unsaturated fatty acid(UFA)synthesis pathways,which were exclusively upregulated in patients who later developed severe CRS.Furthermore,two lysophosphatidylcholines,namely,lysoPC(16:0)and lysoPC(15:0),were significantly associated with delayed CRS onset,with elevated concentrations correlated with a prolonged time to onset;this association was independently validated.These findings revealed that arginine metabolism was a pathological axis in CRS,UFAs were severity predictors,and specific lysoPCs were modulators of onset time.Collectively,they provide proactive CRS management,addressing critical gaps in predictive biomarkers to advance the safe,broad CAR-T application in MM.
基金funded by the National Key Research and Development Program of China(2018YFE0104200)National Natural Science Foundation of China(51875310,52175274,82172065)and AO Foundation(AOTAP21-47).
文摘Laser powder bed fusion(L-PBF)of magnesium(Mg)alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects.However,one of the key technical difficulties lies in the poor L-PBF process performance of Mg,contributed by the high susceptibility to oxidation,vaporization,thermal expansion,and powder attachment etc.This work investigated the influence of L-PBF energy input and scanning strategy on the formation quality of porous scaffolds by using WE43 powder,and characterized the microstructure,mechanical properties,biocompatibility,biodegradation and osteogenic effect of the as-built WE43 porous scaffolds.With the customized energy input and scanning strategy,the relative density of struts reached over 99.5%,and the geometrical error between the designed and the fabricated porosity declined to below 10%.Massive secondary phases including intermetallic precipitates and oxides were observed.The compressive strength(4.37-23.49 MPa)and elastic modulus(154.40-873.02 MPa)were comparable to those of cancellous bone.Good biocompatibility was observed by in vitro cell viability and in vivo implantation.The biodegradation of as-built porous scaffolds promoted the osteogenic effect,but the structural integrity devastated after 12 h by the immersion tests in Hank’s solution and after 4 weeks by the implantation in rabbits’femur,indicating an excessively rapid degradation rate.
文摘The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work, we found that high temperature oxidation improves the corrosion resistance of magnesium scaffold. And the effects of pore size on the mechanical characteristics and biodegradation of scaffolds, as well as new bone formation, were investigated using magnesium scaffolds with three different pore sizes, namely, 500, 800, and 1400 μm (P500, P800, and P1400). We discovered that the mechanical characteristics of the P500 group were much better than those of the other two groups. In vitro and in vivo investigations showed that WE43 magnesium alloy scaffolds supported the survival of mesenchymal stem cells and did not cause any local toxicity. Due to their larger specific surface area, the scaffolds in the P500 group released more magnesium ions within reasonable range and improved the osteogenic differentiation of bone mesenchymal stem cells compared with the other two scaffolds. In a rabbit femoral condyle defect model, the P500 group demonstrated unique performance in promoting new bone formation, indicating its great potential for use in bone defect regeneration therapy.
基金supported by the State Key Laboratory of Medical Genomics,the Double First-Class Project(No.WF510162602)from the Ministry of Educationthe Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01)+5 种基金the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,No.B17029)the National Natural Science Foundation of China(Nos.82230006 and 32170663)the Shanghai Clinical Research Center for Hematological disease(No.19MC1910700)the Shanghai Shenkang Hospital Development Center(No.SHDC2020CR5002)the Shanghai Major Project for Clinical Medicine(No.2017ZZ01002)the Innovative Research Team of High-level Local Universities in Shanghai and the Yangfan Program of the Science and Technology Commission of Shanghai Municipality(No.22YF1425500)。
文摘The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine research.Though an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly understood.Here,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy.Our study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma composition.One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA.Furthermore,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins.Overall,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.
基金supported by the National Natural Science Foundation of China(22235001,22175020,and 22271012)the Fundamental Research Funds for the Central Universities(FRF-IDRY-23-021,FRF-BR-23-02B,and FRF-TP-24-014A)+1 种基金University of Science and Technology Beijingsupported by the User Experiment Assist System of Shanghai Synchrotron Radiation Facility.
文摘Two-dimensional(2D)porphyrin(Por)-based covalent organic frameworks(COFs)provide an attractive and effective strategy for photocatalytic CO_(2)reduction,but the layered structure due toπ–πstacking is challenging for the exposure of active sites and transfer of mass and photogenerated carriers.In this study,a series of 2D conjugated porphyrin-based COFs were prepared using porphyrin blocks with linking units having different degrees of twisting.According to the experimental and theoretical calculation results,owing to the large spatial steric hindrance between the two carbazole units connected by the N–N single bond,a greatly undulating layered structure was formed in NN-Por-COF,which enhanced mass transfer and exposed more catalytic sites.The introduction of carbazole also modulated the electronic structure of the porphyrin Co center,which lowered the reaction energy barrier.The optimization of the structural and electronic effects led to the excellent photocatalytic CO_(2)reduction performance of NN-Por-COF,with CO conversion rates as high as 22.38 and 3.02 mmol g−1 h−1 under pure and diluted(10%)CO_(2)atmosphere,respectively,which are superior to those of most of the reported porphyrin-based photocatalysts.
基金supported financially by the National Key Research&Development Program of China(2018YFE0202401)the Science and Technology Commission of Shanghai Municipalitythe National Natural Science Foundation of China(91958208 and 42076061)。
文摘Recent deep-diving expeditions in the South China Sea(SCS)discovered abundant indigenous cold-water corals[1].Cold-water corals,preferentially inhabiting the low-latitude intermediate and deep waters with hard substrates and a cool water temperature,have great potential to be applied in researches of the ocean interior by providing high-resolution records[2,3].
基金This work was supported by grants from the National Natural Science Foundation of China(Grant number 21877074)the Shandong Provincial Natural Science Foundation(Grant number ZR2019BM007).
文摘Group B Streptococcus(GBS)is the major pathogen that causes invasive infectious diseases in neonates and infants.The develop-ment of preventive and therapeutic strategies against GBS infection has been becoming the most pressing subject worldwide.Group B carbohydrate(GBC),the group B-specific polysaccharide that distinguishes GBS with other streptococci species,has been identified as an attractive antigen for diagnosis and vaccine development because of its highly conservative tetra-antennary structure.In this paper,a highly convergent[3+5]glycosylation strategy for efficient synthesis of an octasaccharide derivative related to GBC oligo-saccharide unitⅡhas been developed.In this synthesis,each glycosylation reaction was efficiently constructed with glycosyl im-idates,especially trifluoroacetimidate,as donors,and each glycosidic bond was stereoselectively controlled via the neighboring group participation effect of acyl group on the 2-O-position of imidate donors or the solvent effect of Et_(2)O.Furthermore,the ami-noethylphosphate group was smoothly installed on the 6-O-position of D-glucitoll residue using the phosphoramidite method.After global deprotection,the target octasaccharide was successfully obtained from o-glucitol in 29 steps with an overall yield of 1.37%.The free amino group installed on the aminoethylphosphate spacer of the target molecule enables its modification with functional-ized biomolecules for further biological studies.
基金supported by the National Natural Science Foundation of China(42122042,42030403,and 42188102)the Fundamental Research Funds for the Central Universities(22120220531)+1 种基金the Shanghai Pilot Program for Basic Researchthe Netherlands Earth System Science Centre(024.002.001)。
文摘Global warming during the Miocene Climate Optimum(MCO,~17-14 million years ago)is associated with massive carbon emissions sourced from the flood basalt volcanism and ocean crustal production.However,the perturbation of tectonic carbon degassing on the interaction between climate change and carbon cycle remains unclear.Here,through time-evolutive phase analysis of new and published high-resolution benthic foraminiferal oxygen(δ^(18)O)and carbon(δ^(13)C)isotope records from the global ocean,we find that variations in the marine carbon cycle lead the climate-cryosphere system(δ^(13)Clead-δ^(18)O)on 405,000-year eccentricity timescales during the MCO.This is in contrast to the previously reported climate-lead-carbon(δ^(18)O-lead-δ^(13)C)scenario during most of the Oligo-Miocene(~34-6 million years ago).Further sensitivity analysis and model simulations suggest that the elevated atmospheric CO_(2) concentrations and the resulting greenhouse effect strengthened the low-latitude hydrological cycle during the MCO,accelerating the response of marine carbon cycle to eccentricity forcing.Tropical climate processes played a more important role in regulating carbon-cycle variations when Earth's climate was in a warm regime,as opposed to the dominant influence of polar ice-sheet dynamics during the PlioPleistocene(after~6 million years ago).
