Vinylene-bridged covalent organic frameworks(V-COFs),as fully conjugated polymer structures,offer promising prospects in optoelectronics.However,challenges such as poor bond reversibility and limited monomer availabil...Vinylene-bridged covalent organic frameworks(V-COFs),as fully conjugated polymer structures,offer promising prospects in optoelectronics.However,challenges such as poor bond reversibility and limited monomer availability persist.In this study,we introduce Ph-DPP-COF,synthesized from a diketopyrrolopyrrole(DPP)core with methyl groups via a Knoevenagel condensation reaction.The resulting material features an AA stacking mode,large nanopores,and broad light absorption across the ultraviolet to near-infrared spectrum.Notably,Ph-DPP-COF achieves a photothermal conversion efficiency of 53%under 660 nm laser irradiation.Its exceptional mechanical processability also offers considerable plasticity for practical applications.These findings suggest that Ph-DPP-COF not only provides a novel approach for developing photothermal conversion materials but also holds promise for future energy conversion and storage technologies.展开更多
Coagulation-based pre-treatment efficiency of high strength digestate of food waste(HSDFW) anaerobic digestion is negated by organic ligand-catalyzed decomposition of coagulants. In this study, an efficient HSDFW pre-...Coagulation-based pre-treatment efficiency of high strength digestate of food waste(HSDFW) anaerobic digestion is negated by organic ligand-catalyzed decomposition of coagulants. In this study, an efficient HSDFW pre-treatment method, magnetic seeds(MS) coagulation, was employed by using highly stable Keggin Al_(30) nanocluster(PAC_(30)), MS and polyacrylamide(PAM), and its operation was optimized by evaluating the performance of removing turbidity, total suspended solids(TSS), chemical oxygen demand(COD), and total phosphorous(TP) phosphate. Results showed that at the optimum dosage of 4.82 g/L, PAC_(30) demonstrated excellent removals as high as 98.93% ± 0.1% of turbidity, 98.04% ± 0.1% of TSS, 58.28% ± 0.3% of total COD, 99.98% ± 0.01% of TP and 99.50% ± 0.01% of dissolved phosphate, respectively. Apparent molecular weight(AMW) and three-dimensional excitation-emission matrix(3 D-EEM) fluorescence spectroscopy analyses demonstrated more efficient removal of dissolved organic matter(DOM), particularly non-biodegradable and hydrophobic components by PAC_(30) than commercial coagulant. The sedimentation was much improved from 40 min by coagulation/flocculation to about 5 min settling by MS coagulation. The PAC_(30) based magnetic coagulation(MC) presents theoretical guidance on a cost-effective and much less footprint pre-treatment alternative for high strength wastewater.展开更多
Visual Cadavers is anemerging study method which promotes medical education and practical applications.It is benefited from other techniques and evaluated as having huge advantages,which is not only accelerating teach...Visual Cadavers is anemerging study method which promotes medical education and practical applications.It is benefited from other techniques and evaluated as having huge advantages,which is not only accelerating teaching and learning,but also improving scientific study,nevertheless,with limited cons.展开更多
Conjugated polymers exhibit exceptional adaptability in flexible thin-film transistors,owing to their inherent flexibility and high charge mobility.Nonetheless,achieving conjugated polymers that demonstrate both high ...Conjugated polymers exhibit exceptional adaptability in flexible thin-film transistors,owing to their inherent flexibility and high charge mobility.Nonetheless,achieving conjugated polymers that demonstrate both high mobility and stability under mechanical stress,such as bending or stretching,remains a significant challenge.In this study,we synthesized an ethylene-bridged conjugated polymer,PDPPVIDT,derived from methyl-side diketopyrrolopyrrole(DPP)and indacenodithiophene(IDT)aldehydes,using an environmentally friendly Knoevenagel condensation reaction under mild conditions,resulting in a moderate yield with promising scalability.Conventional characterization techniques revealed enhanced backbone planarity with stableπ-πstacking,while thin films of PDPPVIDT displayed a nearamorphous nature due to the conformational isomerism of the ethylene bond.This structure enables simultaneous charge transport and flexibility.Consequently,flexible organic thinfilm transistor(OTFT)devices based on PDPPVIDT demonstrated excellent hole mobility(μh)reaching up to 1.70 cm^(2) V^(−1) s^(−1),along with high mechanical bending resilience.This work underscores the potential of vinyl-bridged donor-acceptor conjugated polymers,highlighting the industrial adaptability of their production process and offering new insights for the design and synthesis of future flexible electronic materials.展开更多
This paper addresses the critical need for a holistic,evidence-based national strategy to cultivate a world-class artificial intelligence(Al)talent pool.As Al reshapes global economies,labor markets,and the geopolitic...This paper addresses the critical need for a holistic,evidence-based national strategy to cultivate a world-class artificial intelligence(Al)talent pool.As Al reshapes global economies,labor markets,and the geopolitical land-scape,national competitiveness hinges on the ability to develop,attract,and retain Al expertise.Employing a systematic scoping review methodology,this study synthesizes evidence from academic literature,government policy documents,and industry white papers to construct an integrated strategic blueprint.The analysis decon-structs the core components of a comprehensive talent development policy,proposing a multi-pillar framework that integrates a lifelong learning continuum,a differentiated talent pipeline architecture,synergistic public-private enablers,and modernized evaluation paradigms.Through a comparative analysis of divergent nationalstrategies-including the market-driven model of the United States,the governance-first approach of the Eu-ropean Union,and the state-directed models of India,Singapore,the United Arab Emirates,and Canada-this paper illuminates the trade-offs between different philosophical and tactical choices.Key findings reveal the heterogeneous nature of Al's impact on labor,the centrality of public trust as a prerequisite for adoption,and a necessary paradigm shift from credential-based to competency-based talent evaluation.The proposed blueprint,which introduces a novel"Builder-Bridger"talent model,offers a comprehensive,actionable guide for policymakers and academic leaders aiming to build a sustainable and globally competitive national Al talent base capable of navigating the complexities of the Al era.展开更多
Liquid metal(LM)dielectric elastomers with high flexibility and excellent dielectric properties are ideal for flexible capacitive pressure sensors.However,the development of LM dielectric elastomers is hindered by the...Liquid metal(LM)dielectric elastomers with high flexibility and excellent dielectric properties are ideal for flexible capacitive pressure sensors.However,the development of LM dielectric elastomers is hindered by the challenge of unavoidable percolation at high LM fill ratios.Inhomogeneous distribution is an effective strategy to manipulate the percolation threshold.Herein,thermoplastic polyurethane(TPU)fiber mats featuring a unique rapeseed-shaped structure were designed for high LM content filling(up to 90 vol%)and prepared with the aid of an electrospinning technique,in which LM was locally concentrated in the TPU fibers of the composite mats to form isolated clusters,leading to an incredible improvement in the percolation threshold surpassing our calculated theoretical prediction(>90 vol%vs.83 vol%).The LM/TPU-Fiber mats are proven to be recyclable,temperature-insensitive,and waterproof,making them suitable for multiple usage environments.A flexible capacitive sensor prepared with LM/TPU-Fiber mats,capable of exceptional relative capacitance change(Max.ΔC/C_(0)=6.32),an impressive pressure range of 0-550 kPa with a sensitivity of 55 MPa^(−1),and high cyclic stability(>6000 cycles).With these outstanding attributes,the sensor holds great promise for applications in intelligent sorting,pressure distribution monitoring,and human-machine interaction.展开更多
Asphalt mixtures are complex and heterogeneous materials whose performance is governed by their intricate mesostructure and multiphase interactions.Three-dimensional(3D)numerical simulation has emerged as a powerful t...Asphalt mixtures are complex and heterogeneous materials whose performance is governed by their intricate mesostructure and multiphase interactions.Three-dimensional(3D)numerical simulation has emerged as a powerful tool for evaluating the structure and mechanical response of asphalt mixtures.This paper synthesizes recent advances in 3D mesoscopic simulation of asphalt mixtures,distinguishing the distinctions and benefits of image-based and user-defined 3D model generation techniques.This paper identifies the important parameters that affect the reliability of 3D models,encompassing aggregate parameters,asphalt mortar parameters and air void parameters.Furthermore,it outlines the advantages and disadvantages of mainstream 3D simulation methods for asphalt mixtures,along with recent developments in multi-method coupled 3D simulation.Finally,the process and challenges of model validation are discussed.Future research should focus on the precise characterization of aggregate size,morphology,and aggregate-aggregate contact models.The development of reusable digital aggregate libraries is essential to enhance the realism and efficiency of 3D model generation.Improvements in coupled simulation techniques are also needed to ensure interface data consistency and force-displacement synchronization.Moreover,researchers should provide more comprehensive documentation of parameter calibration and iterative optimization processes.展开更多
Toll-like receptor 3(TLR3),as an important pattern recognition receptor(PRR),dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases.Atherosclerosis is proved as an inflammat...Toll-like receptor 3(TLR3),as an important pattern recognition receptor(PRR),dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases.Atherosclerosis is proved as an inflammatory disease,and inflammatory events involved in the entire process of initiation and deterioration.However,the contribution of TLR3 to atherosclerosis remains unclear.Herein,we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis.Besides,activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules.Conversely,silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation.Given the aberrance in TLR3 functions on atherosclerosis progression,we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy.Therefore,we developed the novel ellipticine derivative SMU-CX24,which specifically inhibited TLR3(IC_(50)=18.87±2.21 nmol/L).In vivo,atherosclerotic burden was alleviated in Western diet fed ApoE^(−/−)mice in response to SMU-CX24 treatment,accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion.Thus,for the first time,we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression,thereby proposing a new strategy and probe for atherosclerosis therapy.展开更多
Objective: Ginsenosides, polysaccharides and phenols, the main active ingredients in Panax ginseng, are not different significantly in content between 3 and 5 years old of ginsengs called Yuan ginseng and more than te...Objective: Ginsenosides, polysaccharides and phenols, the main active ingredients in Panax ginseng, are not different significantly in content between 3 and 5 years old of ginsengs called Yuan ginseng and more than ten years old ones called Shizhu ginseng. The responsible chemical compounds cannot fully explain difference in efficacy between them. According to reports in Lonicerae Japonicae Flos(Jinyinhua in Chinese) and Glycyrrhizae Radix et Rhizoma(Gancao in Chinese), microRNA may play a role in efficacy,so we identified microRNAs in P. ginseng at the different growth years and analyzed their target genes.Methods: Using high-throughput sequencing, the RNA-Seq, small RNA-Seq and degradome databases of P. ginseng were constructed. The differentially expressed microRNAs was identified by qRT-PCR.Results: A total of 63,875 unigenes and 24,154,579 small RNA clean reads were obtained from the roots of P. ginseng. From these small RNAs, 71 miRNA families were identified by bioinformatics target prediction software, including 34 conserved miRNAs, 37 non-conserved miRNA families, as well as 179 target genes of 17 known miRNAs. Through degradome sequencing and computation, we finally verified 13 targets of eight miRNAs involved in transcription, energy metabolism, biological stress and disease resistance, suggesting the significance of miRNAs in the development of P. ginseng. Consistently, major miRNA targets exhibited tissue specificity and complexity in expression patterns.Conclusion: Differential expression microRNAs were found in different growth years of ginsengs(Shizhu ginseng and Yuan ginseng), and the regulatory roles and functional annotations of miRNA targets in P. ginseng need further investigation.展开更多
Nanoparticles(NPs)which are innovation and research focus in drug delivery systems,still have some disadvantages limiting its application in clinical use,such as short circulation time,recognition and clearance by ret...Nanoparticles(NPs)which are innovation and research focus in drug delivery systems,still have some disadvantages limiting its application in clinical use,such as short circulation time,recognition and clearance by reticuloendothelial system(RES)and passive targeting in certain organs.However,the recent combination of natural components and nanotechnology has offered new solutions to address these problems.A novel biomimetic platform consisting of nanoparticle core and membrane shell,such as cell membrane,exosome or vesicle vastly improves properties of nanoparticles.These coated nanoparticles can replicate the unique functions of the membrane,such as prolonged blood circulation,active targeting capability and enhanced internalization.In this review,we focus on the newest development of biological-camouflaged nanoparticles and mainly introduce its application related to cancer therapy and toll-like receptor.展开更多
Surface passivation is one of the primary requirements for high efficient silicon solar cells. Though the current existed passivation techniques are effective, expensive equipments are required. In this paper, a compr...Surface passivation is one of the primary requirements for high efficient silicon solar cells. Though the current existed passivation techniques are effective, expensive equipments are required. In this paper, a comprehensive understanding of the SiO2 passivation layer grown by liquid phase deposition （LPD） was presented, which was cost-effective and very simple. It was found that the post-annealing process could significantly enhance the passivation effect of the LPD SiO2 film. Besides, it was revealed that both chemical passivation and field-effect passivation mechanisms played important roles in outstanding passivation effect of the LPD SiO2 film through analyzing the minority carrier lifetime and the surface recombination velocity of n-type and p-type silicon wafers. Although the deposition parameters had little influence on the passivation effect, they affected the deposition rate. Therefore, appropriate deposition para- meters should be carefully chosen based on the compromise of the deposition rate and fabrication cost. By utilizing the LPD SiO2 film as surface passivation layer, a 19.5%-efficient silicon solar cell on a large-scale wafer （156 mm × 156 mm） was fabricated.展开更多
Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse...Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse events has also increased,which can affect tumor treatment.In this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Methods:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed databases.All included trials examined all grade and grades 3–5 cardiac and vascular adverse events.These involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent.The odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel method.Results:Overall,20 trials were included.CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular toxicity.The incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically significant.Conclusion:Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors.In addition,the risk of serious cardiovascular toxic events was independent of the type of adverse event.From these results,physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.展开更多
基金supported by the National Natural Science Foundation of China(NSFC,No.22202024).
文摘Vinylene-bridged covalent organic frameworks(V-COFs),as fully conjugated polymer structures,offer promising prospects in optoelectronics.However,challenges such as poor bond reversibility and limited monomer availability persist.In this study,we introduce Ph-DPP-COF,synthesized from a diketopyrrolopyrrole(DPP)core with methyl groups via a Knoevenagel condensation reaction.The resulting material features an AA stacking mode,large nanopores,and broad light absorption across the ultraviolet to near-infrared spectrum.Notably,Ph-DPP-COF achieves a photothermal conversion efficiency of 53%under 660 nm laser irradiation.Its exceptional mechanical processability also offers considerable plasticity for practical applications.These findings suggest that Ph-DPP-COF not only provides a novel approach for developing photothermal conversion materials but also holds promise for future energy conversion and storage technologies.
基金supported by the National Key Research and Development Program of China (No. 2018YFD1100600)the Program of China-Sri Lanka Joint Center for Water Technology Research and Demonstrationthe Chinese Government Scholarship Program (CSC No. 2018SLJ023250)。
文摘Coagulation-based pre-treatment efficiency of high strength digestate of food waste(HSDFW) anaerobic digestion is negated by organic ligand-catalyzed decomposition of coagulants. In this study, an efficient HSDFW pre-treatment method, magnetic seeds(MS) coagulation, was employed by using highly stable Keggin Al_(30) nanocluster(PAC_(30)), MS and polyacrylamide(PAM), and its operation was optimized by evaluating the performance of removing turbidity, total suspended solids(TSS), chemical oxygen demand(COD), and total phosphorous(TP) phosphate. Results showed that at the optimum dosage of 4.82 g/L, PAC_(30) demonstrated excellent removals as high as 98.93% ± 0.1% of turbidity, 98.04% ± 0.1% of TSS, 58.28% ± 0.3% of total COD, 99.98% ± 0.01% of TP and 99.50% ± 0.01% of dissolved phosphate, respectively. Apparent molecular weight(AMW) and three-dimensional excitation-emission matrix(3 D-EEM) fluorescence spectroscopy analyses demonstrated more efficient removal of dissolved organic matter(DOM), particularly non-biodegradable and hydrophobic components by PAC_(30) than commercial coagulant. The sedimentation was much improved from 40 min by coagulation/flocculation to about 5 min settling by MS coagulation. The PAC_(30) based magnetic coagulation(MC) presents theoretical guidance on a cost-effective and much less footprint pre-treatment alternative for high strength wastewater.
文摘Visual Cadavers is anemerging study method which promotes medical education and practical applications.It is benefited from other techniques and evaluated as having huge advantages,which is not only accelerating teaching and learning,but also improving scientific study,nevertheless,with limited cons.
基金National Natural Science Foundation of China (NSFC)(21404107, 22175081, and 22375080)。
文摘Conjugated polymers exhibit exceptional adaptability in flexible thin-film transistors,owing to their inherent flexibility and high charge mobility.Nonetheless,achieving conjugated polymers that demonstrate both high mobility and stability under mechanical stress,such as bending or stretching,remains a significant challenge.In this study,we synthesized an ethylene-bridged conjugated polymer,PDPPVIDT,derived from methyl-side diketopyrrolopyrrole(DPP)and indacenodithiophene(IDT)aldehydes,using an environmentally friendly Knoevenagel condensation reaction under mild conditions,resulting in a moderate yield with promising scalability.Conventional characterization techniques revealed enhanced backbone planarity with stableπ-πstacking,while thin films of PDPPVIDT displayed a nearamorphous nature due to the conformational isomerism of the ethylene bond.This structure enables simultaneous charge transport and flexibility.Consequently,flexible organic thinfilm transistor(OTFT)devices based on PDPPVIDT demonstrated excellent hole mobility(μh)reaching up to 1.70 cm^(2) V^(−1) s^(−1),along with high mechanical bending resilience.This work underscores the potential of vinyl-bridged donor-acceptor conjugated polymers,highlighting the industrial adaptability of their production process and offering new insights for the design and synthesis of future flexible electronic materials.
文摘This paper addresses the critical need for a holistic,evidence-based national strategy to cultivate a world-class artificial intelligence(Al)talent pool.As Al reshapes global economies,labor markets,and the geopolitical land-scape,national competitiveness hinges on the ability to develop,attract,and retain Al expertise.Employing a systematic scoping review methodology,this study synthesizes evidence from academic literature,government policy documents,and industry white papers to construct an integrated strategic blueprint.The analysis decon-structs the core components of a comprehensive talent development policy,proposing a multi-pillar framework that integrates a lifelong learning continuum,a differentiated talent pipeline architecture,synergistic public-private enablers,and modernized evaluation paradigms.Through a comparative analysis of divergent nationalstrategies-including the market-driven model of the United States,the governance-first approach of the Eu-ropean Union,and the state-directed models of India,Singapore,the United Arab Emirates,and Canada-this paper illuminates the trade-offs between different philosophical and tactical choices.Key findings reveal the heterogeneous nature of Al's impact on labor,the centrality of public trust as a prerequisite for adoption,and a necessary paradigm shift from credential-based to competency-based talent evaluation.The proposed blueprint,which introduces a novel"Builder-Bridger"talent model,offers a comprehensive,actionable guide for policymakers and academic leaders aiming to build a sustainable and globally competitive national Al talent base capable of navigating the complexities of the Al era.
基金supported by NSFC No.52473267 and No.52401249National Key Research and Development Program of China No.2021YFB3501504 and Zhejiang Provincial Key Research and Development Program(2024C01157)Zhejiang University Ningbo“Five in One”Campus Project(K-20213539).
文摘Liquid metal(LM)dielectric elastomers with high flexibility and excellent dielectric properties are ideal for flexible capacitive pressure sensors.However,the development of LM dielectric elastomers is hindered by the challenge of unavoidable percolation at high LM fill ratios.Inhomogeneous distribution is an effective strategy to manipulate the percolation threshold.Herein,thermoplastic polyurethane(TPU)fiber mats featuring a unique rapeseed-shaped structure were designed for high LM content filling(up to 90 vol%)and prepared with the aid of an electrospinning technique,in which LM was locally concentrated in the TPU fibers of the composite mats to form isolated clusters,leading to an incredible improvement in the percolation threshold surpassing our calculated theoretical prediction(>90 vol%vs.83 vol%).The LM/TPU-Fiber mats are proven to be recyclable,temperature-insensitive,and waterproof,making them suitable for multiple usage environments.A flexible capacitive sensor prepared with LM/TPU-Fiber mats,capable of exceptional relative capacitance change(Max.ΔC/C_(0)=6.32),an impressive pressure range of 0-550 kPa with a sensitivity of 55 MPa^(−1),and high cyclic stability(>6000 cycles).With these outstanding attributes,the sensor holds great promise for applications in intelligent sorting,pressure distribution monitoring,and human-machine interaction.
基金supported by the National Natural Science Foundation of China(Grant No.52378459).
文摘Asphalt mixtures are complex and heterogeneous materials whose performance is governed by their intricate mesostructure and multiphase interactions.Three-dimensional(3D)numerical simulation has emerged as a powerful tool for evaluating the structure and mechanical response of asphalt mixtures.This paper synthesizes recent advances in 3D mesoscopic simulation of asphalt mixtures,distinguishing the distinctions and benefits of image-based and user-defined 3D model generation techniques.This paper identifies the important parameters that affect the reliability of 3D models,encompassing aggregate parameters,asphalt mortar parameters and air void parameters.Furthermore,it outlines the advantages and disadvantages of mainstream 3D simulation methods for asphalt mixtures,along with recent developments in multi-method coupled 3D simulation.Finally,the process and challenges of model validation are discussed.Future research should focus on the precise characterization of aggregate size,morphology,and aggregate-aggregate contact models.The development of reusable digital aggregate libraries is essential to enhance the realism and efficiency of 3D model generation.Improvements in coupled simulation techniques are also needed to ensure interface data consistency and force-displacement synchronization.Moreover,researchers should provide more comprehensive documentation of parameter calibration and iterative optimization processes.
基金supported by National Natural Science Foundation of China (Nos. 81773558, 82073689 (KC), and 1825702 (HY))National Natural Science Foundation of Guangdong Province (Nos. 2020A151501518, 2018B030312010, China)Science and Technology Program of Guangzhou (No. 201904010380, China)
文摘Toll-like receptor 3(TLR3),as an important pattern recognition receptor(PRR),dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases.Atherosclerosis is proved as an inflammatory disease,and inflammatory events involved in the entire process of initiation and deterioration.However,the contribution of TLR3 to atherosclerosis remains unclear.Herein,we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis.Besides,activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules.Conversely,silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation.Given the aberrance in TLR3 functions on atherosclerosis progression,we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy.Therefore,we developed the novel ellipticine derivative SMU-CX24,which specifically inhibited TLR3(IC_(50)=18.87±2.21 nmol/L).In vivo,atherosclerotic burden was alleviated in Western diet fed ApoE^(−/−)mice in response to SMU-CX24 treatment,accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion.Thus,for the first time,we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression,thereby proposing a new strategy and probe for atherosclerosis therapy.
基金supported by the National Natural Science Foundation for Young Scholars of China (No. 81403195)。
文摘Objective: Ginsenosides, polysaccharides and phenols, the main active ingredients in Panax ginseng, are not different significantly in content between 3 and 5 years old of ginsengs called Yuan ginseng and more than ten years old ones called Shizhu ginseng. The responsible chemical compounds cannot fully explain difference in efficacy between them. According to reports in Lonicerae Japonicae Flos(Jinyinhua in Chinese) and Glycyrrhizae Radix et Rhizoma(Gancao in Chinese), microRNA may play a role in efficacy,so we identified microRNAs in P. ginseng at the different growth years and analyzed their target genes.Methods: Using high-throughput sequencing, the RNA-Seq, small RNA-Seq and degradome databases of P. ginseng were constructed. The differentially expressed microRNAs was identified by qRT-PCR.Results: A total of 63,875 unigenes and 24,154,579 small RNA clean reads were obtained from the roots of P. ginseng. From these small RNAs, 71 miRNA families were identified by bioinformatics target prediction software, including 34 conserved miRNAs, 37 non-conserved miRNA families, as well as 179 target genes of 17 known miRNAs. Through degradome sequencing and computation, we finally verified 13 targets of eight miRNAs involved in transcription, energy metabolism, biological stress and disease resistance, suggesting the significance of miRNAs in the development of P. ginseng. Consistently, major miRNA targets exhibited tissue specificity and complexity in expression patterns.Conclusion: Differential expression microRNAs were found in different growth years of ginsengs(Shizhu ginseng and Yuan ginseng), and the regulatory roles and functional annotations of miRNA targets in P. ginseng need further investigation.
基金We thank the financial support from the National Natural Science Foundation of China(No.81773558)the Natural Science Foundation of Guangdong Province(Nos.2020A 151501518 and 2018B 030312010)the Science and Technology Program of Guangzhou(No.201904010380)for this work.
文摘Nanoparticles(NPs)which are innovation and research focus in drug delivery systems,still have some disadvantages limiting its application in clinical use,such as short circulation time,recognition and clearance by reticuloendothelial system(RES)and passive targeting in certain organs.However,the recent combination of natural components and nanotechnology has offered new solutions to address these problems.A novel biomimetic platform consisting of nanoparticle core and membrane shell,such as cell membrane,exosome or vesicle vastly improves properties of nanoparticles.These coated nanoparticles can replicate the unique functions of the membrane,such as prolonged blood circulation,active targeting capability and enhanced internalization.In this review,we focus on the newest development of biological-camouflaged nanoparticles and mainly introduce its application related to cancer therapy and toll-like receptor.
基金Acknowledgements This work was supported by the National Natural Science Foundation of China （Grant Nos. 61234005 and 11474201）, and Shanghai Municipal Project （No. 14DZ1201000）.
文摘Surface passivation is one of the primary requirements for high efficient silicon solar cells. Though the current existed passivation techniques are effective, expensive equipments are required. In this paper, a comprehensive understanding of the SiO2 passivation layer grown by liquid phase deposition （LPD） was presented, which was cost-effective and very simple. It was found that the post-annealing process could significantly enhance the passivation effect of the LPD SiO2 film. Besides, it was revealed that both chemical passivation and field-effect passivation mechanisms played important roles in outstanding passivation effect of the LPD SiO2 film through analyzing the minority carrier lifetime and the surface recombination velocity of n-type and p-type silicon wafers. Although the deposition parameters had little influence on the passivation effect, they affected the deposition rate. Therefore, appropriate deposition para- meters should be carefully chosen based on the compromise of the deposition rate and fabrication cost. By utilizing the LPD SiO2 film as surface passivation layer, a 19.5%-efficient silicon solar cell on a large-scale wafer （156 mm × 156 mm） was fabricated.
基金National Natural Science Foundation of China,Grant/Award Number:81870254Science and Technology Programs of Guangdong Province,Grant/Award Number:2019B020230004+1 种基金National Key Research and Development Project,Grant/Award Number:2018YFC1312502Guangdong Special Funds for Science and Technology Innovation Strategy,China(Stability support for scientific research institutions affiliated to Guangdong Province,GDCI 2021)。
文摘Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse events has also increased,which can affect tumor treatment.In this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Methods:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed databases.All included trials examined all grade and grades 3–5 cardiac and vascular adverse events.These involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent.The odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel method.Results:Overall,20 trials were included.CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular toxicity.The incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically significant.Conclusion:Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors.In addition,the risk of serious cardiovascular toxic events was independent of the type of adverse event.From these results,physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.
