The main purpose of this survey paper is to point out some very recent developments on Simpson’s inequality for strongly extended s-convex function. Firstly, the concept of strongly extended s-convex function is intr...The main purpose of this survey paper is to point out some very recent developments on Simpson’s inequality for strongly extended s-convex function. Firstly, the concept of strongly extended s-convex function is introduced. Next a new identity is also established. Finally, by this identity and H?lder’s inequality, some new Simpson type for the product of strongly extended s-convex function are obtained.展开更多
Hydrodeoxygenation of furfural(FF)into 2-methylfuran(MF)is a significant biomass utilization route.However,designing efficient and stable non-noble metal catalyst is still a huge challenge.Herein,we reported the N,O c...Hydrodeoxygenation of furfural(FF)into 2-methylfuran(MF)is a significant biomass utilization route.However,designing efficient and stable non-noble metal catalyst is still a huge challenge.Herein,we reported the N,O co-doped carbon anchored with Co nanoparticles(Co-SFB)synthesized by employing the organic ligands with the target heteroatoms.Raman,electron paramagnetic resonance(EPR),electrochemical impedance spectroscopy(EIS),and X-ray photoelectron spectroscopy(XPS)characterizations showed that the co-doping of N and O heteroatoms in the carbon support endows Co-SFB with enriched lone pair electrons,fast electron transfer ability,and strong metal-support interaction.These electronic properties resulted in strong FF adsorption as well as lower apparent reaction activation energy.At last,the obtained N,O co-doped Co/C catalyst showed excellent catalytic activity(nearly 100 mol%FF conversion and 94.6 mol%MF yield)and stability for in-situ dehydrogenation of FF into MF.This N,O co-doping strategy for the synthesis of highly efficient catalytic materials with controllable electronic state will provide an excellent opportunity to better understand the structure-function relationship.展开更多
Three types of scanning strategies,including the chessboard scanning strategy,the zigzag scanning strategy and the remelting scanning strategy,were conducted to study the effects of scanning strategies on surface morp...Three types of scanning strategies,including the chessboard scanning strategy,the zigzag scanning strategy and the remelting scanning strategy,were conducted to study the effects of scanning strategies on surface morphology,microstructure,mechanical properties and the grain orientation of selective laser melted pure tungsten.The results showed that the pores and cracks were main defects in SLM-processed tungsten parts.The pores could be eliminated using the remelting scanning strategy.However,the cracks seemed to be inevitable regardless of the applied scanning strategies.The microstructures of SLM-processed tungsten were columnar grains and showed strong epitaxial growth along the building direction.A compressive strength of 923 MPa with an elongation of 7.7%was obtained when the zigzag scanning strategy was applied,which was the highest among the three scanning strategies.By changing the scanning strategies,the texture of SLM-processed tungsten in the direction of processing could be changed.展开更多
Animals always seek rewards and the related neural basis has been well studied. However, what happens when animals fail to get a reward is largely unknown,although this is commonly seen in behaviors such as predation....Animals always seek rewards and the related neural basis has been well studied. However, what happens when animals fail to get a reward is largely unknown,although this is commonly seen in behaviors such as predation. Here, we set up a behavioral model of repeated failure in reward pursuit(RFRP) in Drosophila larvae. In this model, the larvae were repeatedly prevented from reaching attractants such as yeast and butyl acetate, before finally abandoning further attempts. After giving up, they usually showed a decreased locomotor speed and impaired performance in light avoidance and sugar preference,which were named as phenotypes of RFRP states. In larvae that had developed RFRP phenotypes, the octopamine concentration was greatly elevated, while tbh mutants devoid of octopamine were less likely to develop RFRP phenotypes, and octopamine feeding efficiently restored such defects. By down-regulating tbh in different groups of neurons and imaging neuronal activity, neurons that regulated the development of RFRP states and the behavioral exhibition of RFRP phenotypes were mapped to a small subgroup of non-glutamatergic and glutamatergic octopaminergic neurons in the central larval brain. Our results establish a model for investigating the effect of depriving an expected reward in Drosophila and provide a simplified framework for the associated neural basis.展开更多
Transformer-based neural-network quantum states(NNQS)have shown great promise in representing quantum manybody ground states,offering high flexibility and accuracy.However,the interpretability of such models remains l...Transformer-based neural-network quantum states(NNQS)have shown great promise in representing quantum manybody ground states,offering high flexibility and accuracy.However,the interpretability of such models remains limited,especially in terms of connecting network components to physically meaningful quantities.We propose that the attention mechanism—a central module in transformer architectures—explicitly models the conditional information flow between orbitals.Intuitively,as the transformer learns to predict orbital configurations by optimizing an energy functional,it approximates the conditional probability distribution p(xn|x_(1),...,x_(n-1)),implicitly encoding conditional mutual information(CMI)among orbitals.This suggests a natural correspondence between attention maps and CMI structures in quantum systems.To probe this idea,we compare weighted attention scores from trained transformer wavefunction ansatze with CMI matrices across several representative small molecules.In most cases,we observe a positive rank-level correlation(Kendall's tau)between attention and CMI,suggesting that the learned attention can reflect physically relevant orbital dependencies.This study provides a quantitative link between transformer attention and conditional mutual information in the NNQS setting.Our results provide a step toward explainable deep learning in quantum chemistry,pointing to opportunities in interpreting attention as a proxy for physical correlations.展开更多
Tryptophan 2,3-dioxygnease 2(TDO2) is specific for metabolizing tryptophan to kynurenine(KYN),which plays a critical role in mediating immune escape of cancer.Although accumulating evidence demonstrates that TDO2 over...Tryptophan 2,3-dioxygnease 2(TDO2) is specific for metabolizing tryptophan to kynurenine(KYN),which plays a critical role in mediating immune escape of cancer.Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers,its tumor-promoting role in esophageal squamous cell carcinoma(ESCC) remains unclear.Here,we observed that TDO2 was overexpressed in ESCC tis sues and correlated significantly with lymph node metastasis,advanced clinical stage,and unfavorable prognosis.Functional experiments showed that TDO2 promoted tumor cell proliferation,migration,and colony formation,which could be prevented by inhibition of TDO2 and aryl hydrocarb on receptor(AHR).Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model,tumor burden of C57 BL/6 mice with ESCC induced by 4-NQO,enhance the expression of phosphorylated AKT,with subsequent pho sphorylation of GSK3β,and polarization of M2 macrophages by upregulating interleukin-8(IL-8) to accelerate tumor progression in the tumor microenvironment(TME).Collectively,our results discovered that TDO2 could upregulate IL-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC,and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC.展开更多
The interaction of PD-1/PD-L1 allows tumor cells to escape from immune surveillance.Clinical success of the antibody drugs has proven that blockade of PD-1/PD-L1 pathway is a promising strategy for cancer immunotherap...The interaction of PD-1/PD-L1 allows tumor cells to escape from immune surveillance.Clinical success of the antibody drugs has proven that blockade of PD-1/PD-L1 pathway is a promising strategy for cancer immunotherapy.Here,we developed a cyclic peptide C8 by using Ph.D.-C7 C phage display technology.C8 showed high binding affinity with h PD-1 and could effectively interfere the interaction of PD-1/PD-L1.Furthermore,C8 could stimulate CD8^(+)T cell activation in human peripheral blood mononuclear cells(PBMCs).We also observed that C8 could suppress tumor growth in CT26 and B16-OVA,as well as anti-PD-1 antibody resistant B16 mouse model.CD8^(+)T cells infiltration significantly increased in tumor microenvironment,and IFN-γsecretion by CD8^(+)T cells in draining lymph nodes also increased.Simultaneously,we exploited T cells depletion models and confirmed that C8 exerted anti-tumor effects via activating CD8^(+)T cells dependent manner.The interaction model of C8 with h PD-1 was simulated and confirmed by alanine scanning.In conclusion,C8 shows anti-tumor capability by blockade of PD-1/PD-L1 interaction,and C8 may provide an alternative candidate for cancer immunotherapy.展开更多
Porous hollow Co3O4 microspheres have been synthesized from a mixed cobalt nitrate and urea solution through spray pyrolysis followed by calcination at 600 ℃ in air. This porous hollow Co3O4 is assembled by nanoparti...Porous hollow Co3O4 microspheres have been synthesized from a mixed cobalt nitrate and urea solution through spray pyrolysis followed by calcination at 600 ℃ in air. This porous hollow Co3O4 is assembled by nanoparticles and exhibits variable porosity depending on the amount of gas in the system. In pyrolysis process, urea continuously decomposes into gaseous components, which act as a template to control the porous structure. The amount of gas escaping from precursor droplets can directly influence the porosity of the microspheres and the size of the nanoparticles controlled by the ratio of urea to cobalt nitrate. Electrochemical measurements show that the performance of the porous hollow Co3O4 microspheres is related to the porosity and size of the nanopartides. The sample with optimal porosity delivers a high first charge capacity of 1,417.9 mAh·g^-1 at 0.2C （1C = 890 mA·g^-1）, and superior charge cycle performance of 1,012.7 mAh.g-1 after 100 cycles. In addition, the optimized material displays satisfactory rate performance of 1,012.4 mAh.g-1 at 1C after 50 cycles and 881.3 mAh·g^-1 at 2C after 300 cycles. Superior charge/discharge capacity, excellent rate performance and high yield achieved in this study is promising for the development of high-performance Co3O4 anode materials for lithium-ion batteries.展开更多
Aside from antibodies,peptides show great potential as immune checkpoint inhibitors(ICIs)due to several advantages,such as better tumor penetration and lower cost.Lymphocyte-activation gene 3(LAG-3)is an immune checkp...Aside from antibodies,peptides show great potential as immune checkpoint inhibitors(ICIs)due to several advantages,such as better tumor penetration and lower cost.Lymphocyte-activation gene 3(LAG-3)is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1(FGL1).Here,we found that LAG-3 expression was higher than programmed cell death protein 1(PD-1)in multiple human cancers by TCGA databases,and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning,which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II.Subsequently,D-amino acids were introduced to substitute the N-and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1,which restores T cell function in vitro and inhibits tumor growth in vivo.Further,a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1blocking peptide OPBP-1(8-12),which activates T cell with enhanced proliferation and IFN-γ production.More importantly,LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response.In conclusion,we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function,and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.展开更多
The deformability and high degree of freedom of mollusks bring challenges in mathematical modeling and synthesis of motions.Traditional analytical and statistical models are limited by either rigid skeleton assumption...The deformability and high degree of freedom of mollusks bring challenges in mathematical modeling and synthesis of motions.Traditional analytical and statistical models are limited by either rigid skeleton assumptions or model capacity,and have difficulty in generating realistic and multi-pattern mollusk motions.In this work,we present a large-scale dynamic pose dataset of Drosophila larvae and propose a motion synthesis model named Path2Pose to generate a pose sequence given the initial poses and the subsequent guiding path.The Path2Pose model is further used to synthesize long pose sequences of various motion patterns through a recursive generation method.Evaluation analysis results demonstrate that our novel model synthesizes highly realistic mollusk motions and achieves state-of-the-art performance.Our work proves high performance of deep neural networks for mollusk motion synthesis and the feasibility of long pose sequence synthesis based on the customized body shape and guiding path.展开更多
Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome(PCOS)and androgen receptor(AR)in ovarian granulosa cells(GCs)functions as an important element to the accumulation of androgens.This ...Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome(PCOS)and androgen receptor(AR)in ovarian granulosa cells(GCs)functions as an important element to the accumulation of androgens.This study verified the existence of alternative splicing variant of AR(AR-SVs)in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs.And compared to the normal individuals,the expression of Serine/arginine-rich splicing factor 2(SRSF2)was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs.More importantly,we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183,and testostrone(T)concentrations in the culture medium were increased.The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated,while the expression of AR significantly increased;however,the function of AR was also inhibited when T concentration in the culture medium was increased.This study has proved that SRSFs are regulated by corresponding miRNAs,and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR,leading to the accumulation of androgens in the ovary.展开更多
Lattice thermal conductivity is important for many applications,but experimental measurements or first principles calculations including three-phonon and four-phonon scattering are expensive or even unaffordable.Machi...Lattice thermal conductivity is important for many applications,but experimental measurements or first principles calculations including three-phonon and four-phonon scattering are expensive or even unaffordable.Machine learning approaches that can achieve similar accuracy have been a long-standing open question.Despite recent progress,machine learning models using structural information as descriptors fall short of experimental or first principles accuracy.This study presents a machine learning approach that predicts phonon scattering rates and thermal conductivity with experimental and first principles accuracy.The success of our approach is enabled by mitigating computational challenges associated with the high skewness of phonon scattering rates and their complex contributions to the total thermal resistance.Transfer learning between different orders of phonon scattering can further improve the model performance.Our surrogates offer up to two orders of magnitude acceleration compared to first principles calculations and would enable large-scale thermal transport informatics.展开更多
文摘The main purpose of this survey paper is to point out some very recent developments on Simpson’s inequality for strongly extended s-convex function. Firstly, the concept of strongly extended s-convex function is introduced. Next a new identity is also established. Finally, by this identity and H?lder’s inequality, some new Simpson type for the product of strongly extended s-convex function are obtained.
基金supported by the National Key R&D Program of China(2021YFC2103704)the National Natural Science Foundation of China(22022812,21978259)+1 种基金Key R&D Program of Zhejiang(2022C01208)Institute of Zhejiang University-Quzhou S&T Planed Projects(IZQ2021KJ1001)。
文摘Hydrodeoxygenation of furfural(FF)into 2-methylfuran(MF)is a significant biomass utilization route.However,designing efficient and stable non-noble metal catalyst is still a huge challenge.Herein,we reported the N,O co-doped carbon anchored with Co nanoparticles(Co-SFB)synthesized by employing the organic ligands with the target heteroatoms.Raman,electron paramagnetic resonance(EPR),electrochemical impedance spectroscopy(EIS),and X-ray photoelectron spectroscopy(XPS)characterizations showed that the co-doping of N and O heteroatoms in the carbon support endows Co-SFB with enriched lone pair electrons,fast electron transfer ability,and strong metal-support interaction.These electronic properties resulted in strong FF adsorption as well as lower apparent reaction activation energy.At last,the obtained N,O co-doped Co/C catalyst showed excellent catalytic activity(nearly 100 mol%FF conversion and 94.6 mol%MF yield)and stability for in-situ dehydrogenation of FF into MF.This N,O co-doping strategy for the synthesis of highly efficient catalytic materials with controllable electronic state will provide an excellent opportunity to better understand the structure-function relationship.
基金the financial support by Science Challenge Project(Nos.TZ2018006-0301-02 and TZ2018006-0303-03)National Natural Science Foundation of China(No.51735005)National Natural Science Foundation of China for Creative Research Groups(Grant No.51921003)。
文摘Three types of scanning strategies,including the chessboard scanning strategy,the zigzag scanning strategy and the remelting scanning strategy,were conducted to study the effects of scanning strategies on surface morphology,microstructure,mechanical properties and the grain orientation of selective laser melted pure tungsten.The results showed that the pores and cracks were main defects in SLM-processed tungsten parts.The pores could be eliminated using the remelting scanning strategy.However,the cracks seemed to be inevitable regardless of the applied scanning strategies.The microstructures of SLM-processed tungsten were columnar grains and showed strong epitaxial growth along the building direction.A compressive strength of 923 MPa with an elongation of 7.7%was obtained when the zigzag scanning strategy was applied,which was the highest among the three scanning strategies.By changing the scanning strategies,the texture of SLM-processed tungsten in the direction of processing could be changed.
基金supported by National Basic Research Development Program of China (973 Program, 2013CB945603)the National Natural Science Foundation of China (31070944, 31271147, 31471063, 31671074)+1 种基金the Natural Science Foundation of Zhejiang Province (LR13C090001)the Fundamental Research Funds for the Central Universities, China (No. 2017FZA7003)
文摘Animals always seek rewards and the related neural basis has been well studied. However, what happens when animals fail to get a reward is largely unknown,although this is commonly seen in behaviors such as predation. Here, we set up a behavioral model of repeated failure in reward pursuit(RFRP) in Drosophila larvae. In this model, the larvae were repeatedly prevented from reaching attractants such as yeast and butyl acetate, before finally abandoning further attempts. After giving up, they usually showed a decreased locomotor speed and impaired performance in light avoidance and sugar preference,which were named as phenotypes of RFRP states. In larvae that had developed RFRP phenotypes, the octopamine concentration was greatly elevated, while tbh mutants devoid of octopamine were less likely to develop RFRP phenotypes, and octopamine feeding efficiently restored such defects. By down-regulating tbh in different groups of neurons and imaging neuronal activity, neurons that regulated the development of RFRP states and the behavioral exhibition of RFRP phenotypes were mapped to a small subgroup of non-glutamatergic and glutamatergic octopaminergic neurons in the central larval brain. Our results establish a model for investigating the effect of depriving an expected reward in Drosophila and provide a simplified framework for the associated neural basis.
基金supported by the National Natural Science Foundation of China(Grant No.T2222026)the CAS Project for Young Scientists in Basic Research(Grant No.YSBR-034)the Robotic AIScientist Platform of the Chinese Academy of Sciences。
文摘Transformer-based neural-network quantum states(NNQS)have shown great promise in representing quantum manybody ground states,offering high flexibility and accuracy.However,the interpretability of such models remains limited,especially in terms of connecting network components to physically meaningful quantities.We propose that the attention mechanism—a central module in transformer architectures—explicitly models the conditional information flow between orbitals.Intuitively,as the transformer learns to predict orbital configurations by optimizing an energy functional,it approximates the conditional probability distribution p(xn|x_(1),...,x_(n-1)),implicitly encoding conditional mutual information(CMI)among orbitals.This suggests a natural correspondence between attention maps and CMI structures in quantum systems.To probe this idea,we compare weighted attention scores from trained transformer wavefunction ansatze with CMI matrices across several representative small molecules.In most cases,we observe a positive rank-level correlation(Kendall's tau)between attention and CMI,suggesting that the learned attention can reflect physically relevant orbital dependencies.This study provides a quantitative link between transformer attention and conditional mutual information in the NNQS setting.Our results provide a step toward explainable deep learning in quantum chemistry,pointing to opportunities in interpreting attention as a proxy for physical correlations.
基金supported by the National Natural Science Foundation of China(Nos.U1604286,81822043,and 81901687)Shenzhen Science and Technology Program(3000531,China)the Key Incubation Fund of SYSU(19ykzd29,China)
文摘Tryptophan 2,3-dioxygnease 2(TDO2) is specific for metabolizing tryptophan to kynurenine(KYN),which plays a critical role in mediating immune escape of cancer.Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers,its tumor-promoting role in esophageal squamous cell carcinoma(ESCC) remains unclear.Here,we observed that TDO2 was overexpressed in ESCC tis sues and correlated significantly with lymph node metastasis,advanced clinical stage,and unfavorable prognosis.Functional experiments showed that TDO2 promoted tumor cell proliferation,migration,and colony formation,which could be prevented by inhibition of TDO2 and aryl hydrocarb on receptor(AHR).Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model,tumor burden of C57 BL/6 mice with ESCC induced by 4-NQO,enhance the expression of phosphorylated AKT,with subsequent pho sphorylation of GSK3β,and polarization of M2 macrophages by upregulating interleukin-8(IL-8) to accelerate tumor progression in the tumor microenvironment(TME).Collectively,our results discovered that TDO2 could upregulate IL-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC,and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC.
基金supported by the National Natural Science Foundation of China(81822043,U1604286)Key Scientific Research Projects of Henan Higher Education Institutions(18A180033,16A180037)the Key Incubation Fund of SYSU(19ykzd29)。
文摘The interaction of PD-1/PD-L1 allows tumor cells to escape from immune surveillance.Clinical success of the antibody drugs has proven that blockade of PD-1/PD-L1 pathway is a promising strategy for cancer immunotherapy.Here,we developed a cyclic peptide C8 by using Ph.D.-C7 C phage display technology.C8 showed high binding affinity with h PD-1 and could effectively interfere the interaction of PD-1/PD-L1.Furthermore,C8 could stimulate CD8^(+)T cell activation in human peripheral blood mononuclear cells(PBMCs).We also observed that C8 could suppress tumor growth in CT26 and B16-OVA,as well as anti-PD-1 antibody resistant B16 mouse model.CD8^(+)T cells infiltration significantly increased in tumor microenvironment,and IFN-γsecretion by CD8^(+)T cells in draining lymph nodes also increased.Simultaneously,we exploited T cells depletion models and confirmed that C8 exerted anti-tumor effects via activating CD8^(+)T cells dependent manner.The interaction model of C8 with h PD-1 was simulated and confirmed by alanine scanning.In conclusion,C8 shows anti-tumor capability by blockade of PD-1/PD-L1 interaction,and C8 may provide an alternative candidate for cancer immunotherapy.
基金This work was supported by the National Natural Science Foundation of China （NSFC） （Nos. 21471006 and 21271009）, the Programs for Science and Technology Development of Anhui Province （No. 1501021019）, the Recruitment Program for Leading Talent Team of Anhui Province, the Program for Innova- tive Research Team of Anhui Education Committee, and the Research Foundation for Science and Technology Leaders and Candidates of Anhui Province.
文摘Porous hollow Co3O4 microspheres have been synthesized from a mixed cobalt nitrate and urea solution through spray pyrolysis followed by calcination at 600 ℃ in air. This porous hollow Co3O4 is assembled by nanoparticles and exhibits variable porosity depending on the amount of gas in the system. In pyrolysis process, urea continuously decomposes into gaseous components, which act as a template to control the porous structure. The amount of gas escaping from precursor droplets can directly influence the porosity of the microspheres and the size of the nanoparticles controlled by the ratio of urea to cobalt nitrate. Electrochemical measurements show that the performance of the porous hollow Co3O4 microspheres is related to the porosity and size of the nanopartides. The sample with optimal porosity delivers a high first charge capacity of 1,417.9 mAh·g^-1 at 0.2C （1C = 890 mA·g^-1）, and superior charge cycle performance of 1,012.7 mAh.g-1 after 100 cycles. In addition, the optimized material displays satisfactory rate performance of 1,012.4 mAh.g-1 at 1C after 50 cycles and 881.3 mAh·g^-1 at 2C after 300 cycles. Superior charge/discharge capacity, excellent rate performance and high yield achieved in this study is promising for the development of high-performance Co3O4 anode materials for lithium-ion batteries.
基金supported by the grants from National Science Foundation of China(U20A20369)“Pearl River Talent Plan”Innovation and Entrepreneurship Team Project of Guangdong Province(2019ZT08Y464,China)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2022B1515120085,China)Shenzhen Science and Technology Program(KQTD20190929173853397,China)Henan Provincial Key R&D and Promotion Special(Scientific Problem Tackling)(222102310344,China)。
文摘Aside from antibodies,peptides show great potential as immune checkpoint inhibitors(ICIs)due to several advantages,such as better tumor penetration and lower cost.Lymphocyte-activation gene 3(LAG-3)is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1(FGL1).Here,we found that LAG-3 expression was higher than programmed cell death protein 1(PD-1)in multiple human cancers by TCGA databases,and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning,which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II.Subsequently,D-amino acids were introduced to substitute the N-and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1,which restores T cell function in vitro and inhibits tumor growth in vivo.Further,a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1blocking peptide OPBP-1(8-12),which activates T cell with enhanced proliferation and IFN-γ production.More importantly,LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response.In conclusion,we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function,and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.
基金supported by the Zhejiang Lab,China(No.2020KB0AC02)the Zhejiang Provincial Key R&D Program,China(Nos.2022C01022,2022C01119,and 2021C03003)+2 种基金the National Natural Science Foundation of China(Nos.T2293723 and 61972347)the Zhejiang Provincial Natural Science Foundation,China(No.LR19F020005)the Fundamental Research Funds for the Central Universities,China(No.226-2022-00051)。
文摘The deformability and high degree of freedom of mollusks bring challenges in mathematical modeling and synthesis of motions.Traditional analytical and statistical models are limited by either rigid skeleton assumptions or model capacity,and have difficulty in generating realistic and multi-pattern mollusk motions.In this work,we present a large-scale dynamic pose dataset of Drosophila larvae and propose a motion synthesis model named Path2Pose to generate a pose sequence given the initial poses and the subsequent guiding path.The Path2Pose model is further used to synthesize long pose sequences of various motion patterns through a recursive generation method.Evaluation analysis results demonstrate that our novel model synthesizes highly realistic mollusk motions and achieves state-of-the-art performance.Our work proves high performance of deep neural networks for mollusk motion synthesis and the feasibility of long pose sequence synthesis based on the customized body shape and guiding path.
文摘Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome(PCOS)and androgen receptor(AR)in ovarian granulosa cells(GCs)functions as an important element to the accumulation of androgens.This study verified the existence of alternative splicing variant of AR(AR-SVs)in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs.And compared to the normal individuals,the expression of Serine/arginine-rich splicing factor 2(SRSF2)was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs.More importantly,we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183,and testostrone(T)concentrations in the culture medium were increased.The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated,while the expression of AR significantly increased;however,the function of AR was also inhibited when T concentration in the culture medium was increased.This study has proved that SRSFs are regulated by corresponding miRNAs,and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR,leading to the accumulation of androgens in the ovary.
基金Z.G.,D.F.,and X.R.acknowledge partial support from the US National Science Foundation through award 2102645Z.H.and X.R.acknowledge partial support from the US National Science Foundation through award 2015946+1 种基金Z.G.acknowledges the Ross Fellowship from Purdue University.L.G.acknowledges the support from the National Science Foundation(DMS-1555072,DMS-2053746,and DMS-2134209)U.S.Department of Energy(DOE)Office of Science Advanced Scientific Computing Research program DE-SC0021142 and DE-SC0023161.
文摘Lattice thermal conductivity is important for many applications,but experimental measurements or first principles calculations including three-phonon and four-phonon scattering are expensive or even unaffordable.Machine learning approaches that can achieve similar accuracy have been a long-standing open question.Despite recent progress,machine learning models using structural information as descriptors fall short of experimental or first principles accuracy.This study presents a machine learning approach that predicts phonon scattering rates and thermal conductivity with experimental and first principles accuracy.The success of our approach is enabled by mitigating computational challenges associated with the high skewness of phonon scattering rates and their complex contributions to the total thermal resistance.Transfer learning between different orders of phonon scattering can further improve the model performance.Our surrogates offer up to two orders of magnitude acceleration compared to first principles calculations and would enable large-scale thermal transport informatics.
