The current research of sandwich structures under dynamic loading mainly focus on the response characteristic of structure.The micro-topology of core layers would sufficiently influence the property of sandwich struct...The current research of sandwich structures under dynamic loading mainly focus on the response characteristic of structure.The micro-topology of core layers would sufficiently influence the property of sandwich structure.However,the micro deformation and topology mechanism of structural deformation and energy absorption are unclear.In this paper,based on the bi-directional evolutionary structural optimization method and periodic base cell(PBC)technology,a topology optimization frame work is proposed to optimize the core layer of sandwich beams.The objective of the present optimization problem is to maximize shear stiffness of PBC with a volume constraint.The effects of the volume fraction,filter radius,and initial PBC aspect ratio on the micro-topology of the core were discussed.The dynamic response process,core compression,and energy absorption capacity of the sandwich beams under blast impact loading were analyzed by the finite element method.The results demonstrated that the overpressure action stage was coupled with the core compression stage.Under the same loading and mass per unit area,the sandwich beam with a 20%volume fraction core layer had the best blast resistance.The filter radius has a slight effect on the shear stiffness and blast resistances of the sandwich beams.But increasing the filter radius could slightly improve the bending stiffness.Upon changing the initial PBC aspect ratio,there are three ways for PBC evolution:The first is to change the angle between the adjacent bars,the second is to further form holes in the bars,and the third is to combine the first two ways.However,not all three ways can improve the energy absorption capacity of the structure.Changing the aspect ratio of the PBC arbitrarily may lead to worse results.More studies are necessary for further detailed optimization.This research proposes a new topology sandwich beam structure by micro-topology optimization,which has sufficient shear stiffness.The micro mechanism of structural energy absorption is clarified,it is significant for structural energy absorption design.展开更多
The electrochemical oxidation of 5-hydroxymethylfurfural(HMF) represents a significant avenue for sustainable chemical synthesis, owing to its potential to generate high-value derivatives from biomass feedstocks. Tran...The electrochemical oxidation of 5-hydroxymethylfurfural(HMF) represents a significant avenue for sustainable chemical synthesis, owing to its potential to generate high-value derivatives from biomass feedstocks. Transition metal catalysts offer a cost-effective alternative to precious metals for catalyzing HMF oxidation, with transition bimetallic catalysts emerging as particularly promising candidates. In this review, we delve into the intricate reaction pathways and electrochemical mechanisms underlying HMF oxidation, emphasizing the pivotal role of transition bimetallic catalysts in enhancing catalytic efficiency. Subsequently, various types of transition bimetallic catalysts are explored, detailing their synthesis methods and structural modulation strategies. By elucidating the mechanisms behind catalyst modification and performance enhancement, this review sets the stage for upcoming advancements in the field, ultimately advancing the electrochemical HMF conversion and facilitating the transition towards sustainable chemical production.展开更多
Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-neg...Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2−)breast cancer remain unclear.Methods:We retrospectively collected mammography records of an HR+/HER2−breast cancer cohort(n=316)with matched clinicopathological,genomic,transcriptomic,and metabolomic data.On the basis of mammographic images,we grouped tumors by calcification status into calcification-negative tumors,tumors with probably benign calcifications,tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy.We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results:Among the different statuses,tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores,estrogen receptor(ER)pathway activation,lipid metabolism,and sensitivity to endocrine therapy.Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes,elevated lymph node metastasis incidence,Ki-67 staining scores,genomic instability,cell cycle pathway activation,and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Conclusions:Our research established links between tumor calcifications and molecular features,thus proposing potential precision treatment strategies for HR+/HER2−breast cancer.展开更多
[Objectives] To study the anti-inflammatory effect of Wumen Zhike Gancao Decoction (ZKGC) on rats with lumbar disc herniation (LDH) associated with lipid metabolic disorder.[Methods] A rat model of LDH was established...[Objectives] To study the anti-inflammatory effect of Wumen Zhike Gancao Decoction (ZKGC) on rats with lumbar disc herniation (LDH) associated with lipid metabolic disorder.[Methods] A rat model of LDH was established by implantation of the autologous nucleus pulposus from the coccygeal vertebra of each rat tail, and histopathology, immunohistochemistry and biochemistry assays were employed to evaluate the treatment effects of ZKGC. In addition, the metabolic characteristics of LDH and ZKGC treatment were investigated with a liquid-chromatography with time-of-flight mass spectrometer (LC/Q-TOF-MS)-based metabolomics study. Nucleus pulpous tissues from rat models were collected and analyzed by metabolomics.[Results] By metabolism network analysis, lipid metabolism was up-regulated in LDH rat models and the treatment with ZKGC significantly reversed the abnormal up-regulated lipid metabolism. Meanwhile, the treatment of ZKGC also regulated the markers of neuron autophagy and inflammatory response in serum.[Conclusions] These results indicated that a complex mechanism, including abnormal lipid metabolism, associates with the progress of LDH, and multiple pathways might be involved in ZKGC s therapeutic effects on LDH.展开更多
In this work,we demonstrate that an organometallic perovskite(OP)single crystal for effective photodetection can be grown on a gold(Au)-decorated substrate using liquid phase epitaxy.The covered gold could both contro...In this work,we demonstrate that an organometallic perovskite(OP)single crystal for effective photodetection can be grown on a gold(Au)-decorated substrate using liquid phase epitaxy.The covered gold could both control the shape of the epitaxial layer and act as its electrodes.An MAPbCl3 single crystal and an MAPbBr1.5Cl1.5 single crystal were used as the substrate and the epitaxial layer,respectively.The device,with an Au-perovskite-Au structure,can be fully characterized.Due to the high-quality epitaxial layer,the maximum external quantum efficiency(EQE)value is over 60%under the voltage of20 V.In addition,the response speed can reach 200 and 500 ns(ns)rise and fall,respectively.Our work provides an effective and promising method to fabricate efficient perovskite-based photodetectors.展开更多
Effective short-term prediction of regional voltage load is of great significance to the implementation of energy saving and emission reduction policies in China.Accurate prediction of real-time demand voltage can red...Effective short-term prediction of regional voltage load is of great significance to the implementation of energy saving and emission reduction policies in China.Accurate prediction of real-time demand voltage can reduce power waste and carbon emissions,make outstanding contributions to delaying global climate warming,and is conducive to global environmental protection and sustainable development.On the short-term load forecasting of power system,a variant model of RNN-LSTM is tested in this paper.It effectively solves the problem of gradient explosion and disappearance caused by large amount of data input in classical RNN.On the basis of this model,optimization experiments are carried out under different super parameters to achieve better prediction results.The experimental results show that the accuracy of test set reaches 99.8%,which proves that the method proposed in this paper has certain reference value.展开更多
Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012...Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012(eligibility threshold:CD4≤350 cells/μl),2014(CD4≤500 cells/μl),and 2016(treat-all).However,the impact of treat-all policy on HIV care and treatment indicators in China is unknown.We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China.Methods Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019,from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China.We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators:monthly proportion of 30-day ART initiation,mean CD4 counts(cells/μl)at ART initiation,and mean estimated time from infection to diagnosis(year).We built separate models according to gender,age,route of transmission and region.Results Monthly data on ART initiation and collection were available for 75,516 individuals[gender:83.8%males;age:median 39 years,interquartile range(IQR):28-53;region:18.5%Northern China,10.9%Northeastern China,17.5%Southern China,49.2%Southwestern China].In the first month of treat-all,compared with the contemporaneous counterfactual,there was a significant increase in proportion of 30-day ART initiation[+12.6%,incidence rate ratio(IRR)=1.126,95%CI:1.033-1.229;P=0.007]and mean estimated time from infection to diagnosis(+7.0%,IRR=1.070,95%CI:1.021-1.120;P=0.004),while there was no significant change in mean CD4 at ART initiation(IRR=0.990,95%CI:0.956-1.026;P=0.585).By December 2019,the three outcomes were not significantly different from expected levels.In the stratified analysis,compared with the contemporaneous counterfactual,mean CD4 at ART initiation showed significant increases in Northern China(+3.3%,IRR=1.033,95%CI:1.001-1.065;P=0.041)and Northeastern China(+8.0%,IRR=1.080,95%CI:1.003-1.164;P=0.042)in the first month of treat-all;mean estimated time from infection to diagnosis showed significant increases in male(+5.6%,IRR=1.056,95%CI:1.010-1.104;P=0.016),female(+14.8%,IRR=1.148,95%CI:1.062-1.240;P<0.001),aged 26-35(+5.3%,IRR=1.053,95%CI:1.001-1.109;P=0.048)and>50(+7.8%,IRR=1.078,95%CI:1.000-1.161;P=0.046),heterosexual transmission(+12.4%,IRR=1.124,95%CI:1.042-1.213;P=0.002)and Southwestern China(+12.9%,IRR=1.129,95%CI:1.055-1.208;P<0.001)in the first month of treat-all.Conclusions The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes.To advance the work of rapid ART,efforts should be made to streamline the testing and ART initiation process,provide comprehensive support services,and address the issue of uneven distribution of medical resources.展开更多
All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam,which can provide a promising way to overcome the power limitation of a single-fiber laser.One of the key...All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam,which can provide a promising way to overcome the power limitation of a single-fiber laser.One of the key points is combining efficiency,which is determined by various mismatches during fabrication.A theoretical model has been built,and the mismatch error is analyzed numerically for the first time.The mismatch errors have been numerically studied with the beam quality and combining efficiency being chosen as the evaluation criteria.The tolerance of each mismatch error for causing 1%loss is calculated to guide the design of the beam combiners.The simulation results are consistent with the experimental results,which show that the mismatch error of the square-core fiber is the main cause of the efficiency loss.The results can provide useful guidance for the fabrication of all-fiber coherent beam combiners.展开更多
Sonic hedgehog (Shh) signaling is essential for the proliferation of cerebellar granule neuron progenitors (CGNPs), and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma (MB...Sonic hedgehog (Shh) signaling is essential for the proliferation of cerebellar granule neuron progenitors (CGNPs), and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma (MB). During vertebrate neural development, RNF220, a ubiquitin E3 ligase, is involved in spinal cord patterning by modulating the subcellular location of glioma-associated oncogene homologs (Glis) through ubiquitination. RNF220 is also required for full activation of Shh signaling during cerebellum development in an epigenetic manner through targeting embryonic ectoderm development. ZC4H2 was reported to be involved in spinal cord patterning by acting as an RNF220 stabilizer. Here, we provided evidence to show that ZC4H2 is also required for full activation of Shh signaling in CGNP and MB progression by stabilizing RNF220. In addition, we found that the ubiquitin E3 ligase RING finger LIM domain-binding protein (RLIM) is responsible for ZC4H2 stabilization via direct ubiquitination, through which RNF220 is also thus stabilized. RLIM is a direct target of Shh signaling and is also required for full activation of Shh signaling in CGNP and MB cell proliferation. We further provided clinical evidence to show that the RLIM‒ZC4H2‒RNF220 cascade is involved in Shh-group MB progression. Disease-causative human RLIM and ZC4H2 mutations affect their interaction and regulation. Therefore, our study sheds light on the regulation of Shh signaling during cerebellar development and MB progression and provides insights into neural disorders caused by RLIM or ZC4H2 mutations.展开更多
In the last decade the ns^(2) cations(e.g.,Pb^(2+)and Sn^(2+))-based halides have emerged as one of the most exciting new classes of optoelectronic materials,as exemplified by for instance hybrid perovskite solar abso...In the last decade the ns^(2) cations(e.g.,Pb^(2+)and Sn^(2+))-based halides have emerged as one of the most exciting new classes of optoelectronic materials,as exemplified by for instance hybrid perovskite solar absorbers.These materials not only exhibit unprecedented performance in some cases,but they also appear to break new ground with their unexpected properties,such as extreme tolerance to defects.However,because of the relatively recent emergence of this class of materials,there remain many yet to be fully explored compounds.Here,we assess a series of bismuth/antimony oxyhalides and chalcohalides using consistent first principles methods to ascertain their properties and obtain trends.Based on these calculations,we identify a subset consisting of three types of compounds that may be promising as solar absorbers,transparent conductors,and radiation detectors.Their electronic structure,connection to the crystal geometry,and impact on band-edge dispersion and carrier effective mass are discussed.展开更多
The ability to spontaneously heal injuries is an important survival feature for humans,plants,and animals in nature.Inspired by nature,man-made self-healing materials that are capable of repairing damage and degraded ...The ability to spontaneously heal injuries is an important survival feature for humans,plants,and animals in nature.Inspired by nature,man-made self-healing materials that are capable of repairing damage and degraded properties either autonomously or triggered by external stimuli have been developed to improve the lifetime,safety,and functionality of products[1–3].to date,most self-healing materials are representative soft materials,such as polymers and gels[4–6].Relative to highly elastic and adaptive soft materials,long-range ordered molecular crystals are rigid and unadaptable and are highly vulnerable to stress-induced cracks.Accordingly,the self-healing property is meaningful for ordered molecular crystals as it can endow molecular crystals with the ability to resist the loss of functionality and service lifetime during specific applications。展开更多
TDP43 pathology is seen in a large majority of amyotrophic lateral sclerosis(ALS)cases,suggesting a central pathogenic role of this regulatory protein.Clarifying the molecular mechanism controlling TDP43 stability and...TDP43 pathology is seen in a large majority of amyotrophic lateral sclerosis(ALS)cases,suggesting a central pathogenic role of this regulatory protein.Clarifying the molecular mechanism controlling TDP43 stability and subcellular location might provide important insights into ALS therapy.The ubiquitin E3 ligase RNF220 is involved in different neural developmental processes through various molecular targets in the mouse.Here,we report that the RNF2207 mice showed progressively decreasing mobility to different extents,some of which developed typical ALS pathological characteristics in spinal motor neurons,including TDP43 cytoplasmic accumulation,atrocytosis,muscle denervation,and atrophy.Mechanistically,RNF220 interacts with TDP43 in vitro and in vivo and promotes its polyubiquitination and proteasomal degradation.In conclusion,we propose that RNF220 might be a modifier of TDP43 function in vivo and contribute to TDP43 pathology in neurodegenerative disease like ALS.展开更多
ObjectiveTo investigate the effect of Niraparib,a clinically approved PARP inhibitor on the radiosensitivity of human lung and cervical cancer cells,and preliminarily explore the underlying mechanism.MethodsThe human ...ObjectiveTo investigate the effect of Niraparib,a clinically approved PARP inhibitor on the radiosensitivity of human lung and cervical cancer cells,and preliminarily explore the underlying mechanism.MethodsThe human lung cancer cell line A549 and human cervical cancer cell line Siha were both treated with Niraparib for 1h,or X-ray irradiation with 4y,or Niraparib for 1h combined with X-ray irradiation with 4Gy.The effect was examined via measurements of cell proliferation by the cell counting kit-8 assay,and cell viability was detected by clone formation assays.Cell apoptosis and cell cycle distribution were investigated by flow cytometry.ResultsIn human lung and cervical cancer cell lines,Niraparib combined with radiation therapy significantly inhibited cell proliferation.The proportion of apoptotic cells in cell lines treated with Niraparib plus radiation(the combination group)was significantly higher compared with control,radiation,and Niraparib groups(P<0.05).Additionally,the proportion of A549 cells in the G_(2)/M phase was significantly increased in the combination group compared with the radiation group(P<0.05).ConclusionPARP inhibitor Niraparib increases the radiosensitivity of tumorcells,promotes their apoptosis,and induces cell cycle redistribution.The possible mechanism is associated with the inhibition of radiation-induced DNA damage repair.展开更多
Two unknown states can be unambiguously distinguished by a universal programmable discriminator, which has been widely discussed in previous works and the optimal solution has also been obtained. In this paper, we inv...Two unknown states can be unambiguously distinguished by a universal programmable discriminator, which has been widely discussed in previous works and the optimal solution has also been obtained. In this paper, we investigate the programmable unambiguous discriminator between two unknown "latitudinal" states, which lie in a subspace of the total state space. By equivalence of unknown pure states to known average mixed states, the optimal solution for this problem is systematically derived, and the analytical success probabilities for the optimal unambiguous discrimination are obtained. It is beyond one's expectation that the optimal setting for the programmable unambiguous discrimination between two unknown "latitudinal" states is the same as that for the universal ones. The results in this work can be used for the realization of the programmable discriminator in laboratory.展开更多
The self-imaging effect in a square core fiber has been investigated, and an integrated all-fiber combiner has been proposed based on a large mode area double clad fiber, which can be employed to construct high power ...The self-imaging effect in a square core fiber has been investigated, and an integrated all-fiber combiner has been proposed based on a large mode area double clad fiber, which can be employed to construct high power coherent beam combining sources in the all-fiber format. The influence of various parameters on beam quality(M^(2)) and efficiency of the all-fiber coherent beam combiner has been studied numerically, which reveals that the near diffraction-limited laser beam can be achieved. A principle demonstration of the self-imaging effect has been carried out experimentally in a square core fiber, which proves the feasibility of beam combining with the square fiber, and that it is a promising way to develop high power coherent beam combination sources.展开更多
Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinat...Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib(SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4(GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.展开更多
A multifunctional nanocomposite of AgNPs@GQDs is prepared by synergistic in-situ growth of silver nanoparticles(AgNPs)on the complex of tannic acid(TA)and graphene quantum dots(GQDs)for the construction of dual-mode b...A multifunctional nanocomposite of AgNPs@GQDs is prepared by synergistic in-situ growth of silver nanoparticles(AgNPs)on the complex of tannic acid(TA)and graphene quantum dots(GQDs)for the construction of dual-mode biosensing platform and cancer theranostics.The nanocomposite exhibits a hydrogen peroxide(H_(2)O_(2))-responsive degradation,in which Ag^(0)is oxidized to Ag^(+)along with the release of oxidized TA and GQDs.The degradation induces the decreased absorbance and enhanced fluorescence(FL)intensity due to the suppression of Forster resonance ene rgy transfer(FRET)in AgNPs@GQDs,which is employed for colorimetric/fluorescence dual-mode sensing of H_(2)O_(2).The intrinsic peroxidase-like activity of GQDs nanozyme can effectively catalyze the oxidation reaction,enhancing the detection sensitivity significantly.Based on the generation of H_(2)O_(2)from the oxidation of glucose with the catalysis of glucose oxidase(GOx),this nanoprobe is versatilely used for the determination of glucose in human serum.Further,through combining the H_(2)O_(2)-responsive degradation of AgNPs@GQDs with high H_(2)O_(2)level in cancer cells,the nanocomposites exhibit good performance in cancer cell recognition and therapy,in which the synergistic anticancer effect of Ag^(+)and oxidized TA contribute to effective cell death,and the liberated GQDs are used to monitor the therapeutic effect by cell imaging.展开更多
基金Supported by National Natural Science Foundation of China (Grant Nos.12072219,12202303,12272254)Shanxi Provincial Excellent Talents Science and Technology Innovation Project of China (Grant No.201805D211033)。
文摘The current research of sandwich structures under dynamic loading mainly focus on the response characteristic of structure.The micro-topology of core layers would sufficiently influence the property of sandwich structure.However,the micro deformation and topology mechanism of structural deformation and energy absorption are unclear.In this paper,based on the bi-directional evolutionary structural optimization method and periodic base cell(PBC)technology,a topology optimization frame work is proposed to optimize the core layer of sandwich beams.The objective of the present optimization problem is to maximize shear stiffness of PBC with a volume constraint.The effects of the volume fraction,filter radius,and initial PBC aspect ratio on the micro-topology of the core were discussed.The dynamic response process,core compression,and energy absorption capacity of the sandwich beams under blast impact loading were analyzed by the finite element method.The results demonstrated that the overpressure action stage was coupled with the core compression stage.Under the same loading and mass per unit area,the sandwich beam with a 20%volume fraction core layer had the best blast resistance.The filter radius has a slight effect on the shear stiffness and blast resistances of the sandwich beams.But increasing the filter radius could slightly improve the bending stiffness.Upon changing the initial PBC aspect ratio,there are three ways for PBC evolution:The first is to change the angle between the adjacent bars,the second is to further form holes in the bars,and the third is to combine the first two ways.However,not all three ways can improve the energy absorption capacity of the structure.Changing the aspect ratio of the PBC arbitrarily may lead to worse results.More studies are necessary for further detailed optimization.This research proposes a new topology sandwich beam structure by micro-topology optimization,which has sufficient shear stiffness.The micro mechanism of structural energy absorption is clarified,it is significant for structural energy absorption design.
基金Hubei Provincial Natural Science Foundation of China (2023AFB0049)Scientific Research Fund Project of Wuhan Institute of Technology (K202232 and K2023028)Graduate Education Innovation Fund of Wuhan Institute of Technology (CX2023091)。
文摘The electrochemical oxidation of 5-hydroxymethylfurfural(HMF) represents a significant avenue for sustainable chemical synthesis, owing to its potential to generate high-value derivatives from biomass feedstocks. Transition metal catalysts offer a cost-effective alternative to precious metals for catalyzing HMF oxidation, with transition bimetallic catalysts emerging as particularly promising candidates. In this review, we delve into the intricate reaction pathways and electrochemical mechanisms underlying HMF oxidation, emphasizing the pivotal role of transition bimetallic catalysts in enhancing catalytic efficiency. Subsequently, various types of transition bimetallic catalysts are explored, detailing their synthesis methods and structural modulation strategies. By elucidating the mechanisms behind catalyst modification and performance enhancement, this review sets the stage for upcoming advancements in the field, ultimately advancing the electrochemical HMF conversion and facilitating the transition towards sustainable chemical production.
基金supported by grants from the National Key Research and Development Project of China(Grant No.2020YFA0112304)the National Natural Science Foundation of China(Grant Nos.81922048,82072922,91959207,and 92159301)+3 种基金the Program of Shanghai Academic/Technology Research Leader(Grant No.20XD1421100)the Shanghai Key Laboratory of Breast Cancer(Grant No.12DZ2260100)the Clinical Research Plan of SHDC(Grant Nos.SHDC2020CR4002 and SHDC2020CR5005)the SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals(Grant No.SHDC12021103).
文摘Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2−)breast cancer remain unclear.Methods:We retrospectively collected mammography records of an HR+/HER2−breast cancer cohort(n=316)with matched clinicopathological,genomic,transcriptomic,and metabolomic data.On the basis of mammographic images,we grouped tumors by calcification status into calcification-negative tumors,tumors with probably benign calcifications,tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy.We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results:Among the different statuses,tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores,estrogen receptor(ER)pathway activation,lipid metabolism,and sensitivity to endocrine therapy.Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes,elevated lymph node metastasis incidence,Ki-67 staining scores,genomic instability,cell cycle pathway activation,and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Conclusions:Our research established links between tumor calcifications and molecular features,thus proposing potential precision treatment strategies for HR+/HER2−breast cancer.
基金Supported by the Special Clinical Diagnosis and Treatment Technology Foundation of Suzhou(LCZX201513)Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine(FY201708)Youth Medical Talents Project of Jiangsu Province(QNRC2016252)
文摘[Objectives] To study the anti-inflammatory effect of Wumen Zhike Gancao Decoction (ZKGC) on rats with lumbar disc herniation (LDH) associated with lipid metabolic disorder.[Methods] A rat model of LDH was established by implantation of the autologous nucleus pulposus from the coccygeal vertebra of each rat tail, and histopathology, immunohistochemistry and biochemistry assays were employed to evaluate the treatment effects of ZKGC. In addition, the metabolic characteristics of LDH and ZKGC treatment were investigated with a liquid-chromatography with time-of-flight mass spectrometer (LC/Q-TOF-MS)-based metabolomics study. Nucleus pulpous tissues from rat models were collected and analyzed by metabolomics.[Results] By metabolism network analysis, lipid metabolism was up-regulated in LDH rat models and the treatment with ZKGC significantly reversed the abnormal up-regulated lipid metabolism. Meanwhile, the treatment of ZKGC also regulated the markers of neuron autophagy and inflammatory response in serum.[Conclusions] These results indicated that a complex mechanism, including abnormal lipid metabolism, associates with the progress of LDH, and multiple pathways might be involved in ZKGC s therapeutic effects on LDH.
基金the National Key R&D Program of China(2017YFC0111500 and 2016YFB0401600)the National Natural Science Foundation Project(61775034,61571124,and 61674029)+1 种基金the Taizhou Key Technology R&D Program(TS201716)the NSFC Research Fund for International Young Scientists(61750110537).
文摘In this work,we demonstrate that an organometallic perovskite(OP)single crystal for effective photodetection can be grown on a gold(Au)-decorated substrate using liquid phase epitaxy.The covered gold could both control the shape of the epitaxial layer and act as its electrodes.An MAPbCl3 single crystal and an MAPbBr1.5Cl1.5 single crystal were used as the substrate and the epitaxial layer,respectively.The device,with an Au-perovskite-Au structure,can be fully characterized.Due to the high-quality epitaxial layer,the maximum external quantum efficiency(EQE)value is over 60%under the voltage of20 V.In addition,the response speed can reach 200 and 500 ns(ns)rise and fall,respectively.Our work provides an effective and promising method to fabricate efficient perovskite-based photodetectors.
基金Supported by Natural Science Foundation of Hunan Province(2020JJ4306)"Scientific Innovation Plan"of the Chinese Academy of Sciences(20194001882)。
文摘Effective short-term prediction of regional voltage load is of great significance to the implementation of energy saving and emission reduction policies in China.Accurate prediction of real-time demand voltage can reduce power waste and carbon emissions,make outstanding contributions to delaying global climate warming,and is conducive to global environmental protection and sustainable development.On the short-term load forecasting of power system,a variant model of RNN-LSTM is tested in this paper.It effectively solves the problem of gradient explosion and disappearance caused by large amount of data input in classical RNN.On the basis of this model,optimization experiments are carried out under different super parameters to achieve better prediction results.The experimental results show that the accuracy of test set reaches 99.8%,which proves that the method proposed in this paper has certain reference value.
基金This study was supported by the Shenzhen Science and Technology Innovation Commission Basic Research Program[JCYJ20190807155409373]the Natural Science Foundation of China Excellent Young Scientists Fund[82022064]+6 种基金Natural Science Foundation of China International/Regional Research Collaboration Project[72061137001]the Sanming Project of Medicine in Shenzhen[SZSM201811071]the High Level Project of Medicine in Longhua,Shenzhen[HLPM201907020105]Special Support Plan for High-Level Talents of Guangdong Province[2019TQ05Y230]the Fundamental Research Funds for the Central Universities[58000-31620005]Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences[2020-JKCS-030]All funding parties did not have any role in the design of the study or in the explanation of the data.
文摘Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012(eligibility threshold:CD4≤350 cells/μl),2014(CD4≤500 cells/μl),and 2016(treat-all).However,the impact of treat-all policy on HIV care and treatment indicators in China is unknown.We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China.Methods Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019,from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China.We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators:monthly proportion of 30-day ART initiation,mean CD4 counts(cells/μl)at ART initiation,and mean estimated time from infection to diagnosis(year).We built separate models according to gender,age,route of transmission and region.Results Monthly data on ART initiation and collection were available for 75,516 individuals[gender:83.8%males;age:median 39 years,interquartile range(IQR):28-53;region:18.5%Northern China,10.9%Northeastern China,17.5%Southern China,49.2%Southwestern China].In the first month of treat-all,compared with the contemporaneous counterfactual,there was a significant increase in proportion of 30-day ART initiation[+12.6%,incidence rate ratio(IRR)=1.126,95%CI:1.033-1.229;P=0.007]and mean estimated time from infection to diagnosis(+7.0%,IRR=1.070,95%CI:1.021-1.120;P=0.004),while there was no significant change in mean CD4 at ART initiation(IRR=0.990,95%CI:0.956-1.026;P=0.585).By December 2019,the three outcomes were not significantly different from expected levels.In the stratified analysis,compared with the contemporaneous counterfactual,mean CD4 at ART initiation showed significant increases in Northern China(+3.3%,IRR=1.033,95%CI:1.001-1.065;P=0.041)and Northeastern China(+8.0%,IRR=1.080,95%CI:1.003-1.164;P=0.042)in the first month of treat-all;mean estimated time from infection to diagnosis showed significant increases in male(+5.6%,IRR=1.056,95%CI:1.010-1.104;P=0.016),female(+14.8%,IRR=1.148,95%CI:1.062-1.240;P<0.001),aged 26-35(+5.3%,IRR=1.053,95%CI:1.001-1.109;P=0.048)and>50(+7.8%,IRR=1.078,95%CI:1.000-1.161;P=0.046),heterosexual transmission(+12.4%,IRR=1.124,95%CI:1.042-1.213;P=0.002)and Southwestern China(+12.9%,IRR=1.129,95%CI:1.055-1.208;P<0.001)in the first month of treat-all.Conclusions The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes.To advance the work of rapid ART,efforts should be made to streamline the testing and ART initiation process,provide comprehensive support services,and address the issue of uneven distribution of medical resources.
文摘All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam,which can provide a promising way to overcome the power limitation of a single-fiber laser.One of the key points is combining efficiency,which is determined by various mismatches during fabrication.A theoretical model has been built,and the mismatch error is analyzed numerically for the first time.The mismatch errors have been numerically studied with the beam quality and combining efficiency being chosen as the evaluation criteria.The tolerance of each mismatch error for causing 1%loss is calculated to guide the design of the beam combiners.The simulation results are consistent with the experimental results,which show that the mismatch error of the square-core fiber is the main cause of the efficiency loss.The results can provide useful guidance for the fabrication of all-fiber coherent beam combiners.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000 to B.M.)the National Natural Science Foundation of China(32170965 to P.M.and 82060292 to S.Z.)+1 种基金Yunnan Basic Research Program(202001AS070036 to B.M.)the open project of State Key Laboratory of Genetic Resources and Evolution(GREKF20-07 to S.Z.and GREKF18-12 to Yan Li).P.M.was supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences.
文摘Sonic hedgehog (Shh) signaling is essential for the proliferation of cerebellar granule neuron progenitors (CGNPs), and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma (MB). During vertebrate neural development, RNF220, a ubiquitin E3 ligase, is involved in spinal cord patterning by modulating the subcellular location of glioma-associated oncogene homologs (Glis) through ubiquitination. RNF220 is also required for full activation of Shh signaling during cerebellum development in an epigenetic manner through targeting embryonic ectoderm development. ZC4H2 was reported to be involved in spinal cord patterning by acting as an RNF220 stabilizer. Here, we provided evidence to show that ZC4H2 is also required for full activation of Shh signaling in CGNP and MB progression by stabilizing RNF220. In addition, we found that the ubiquitin E3 ligase RING finger LIM domain-binding protein (RLIM) is responsible for ZC4H2 stabilization via direct ubiquitination, through which RNF220 is also thus stabilized. RLIM is a direct target of Shh signaling and is also required for full activation of Shh signaling in CGNP and MB cell proliferation. We further provided clinical evidence to show that the RLIM‒ZC4H2‒RNF220 cascade is involved in Shh-group MB progression. Disease-causative human RLIM and ZC4H2 mutations affect their interaction and regulation. Therefore, our study sheds light on the regulation of Shh signaling during cerebellar development and MB progression and provides insights into neural disorders caused by RLIM or ZC4H2 mutations.
基金The authors acknowledge funding support from the National Natural Science Foundation of China(under Grant Nos.61722403 and 11674121)National Key Research and Development Program of China(under Grant No.2016YFB0201204)Program for JLU Science and Technology Innovative Research Team,and the Recruitment Program of Global Youth Experts in China.Work at the University of Missouri was supported by the Department of Energy through the S3TEC Energy Frontier Research Center,award DE-SC0001299.K.B.acknowledges support from US Department of Homeland Security under Grant Award Number,2014-DN-077-ARI075.Part of the calculations was performed at the High Performance Computing Center of Jilin University.
文摘In the last decade the ns^(2) cations(e.g.,Pb^(2+)and Sn^(2+))-based halides have emerged as one of the most exciting new classes of optoelectronic materials,as exemplified by for instance hybrid perovskite solar absorbers.These materials not only exhibit unprecedented performance in some cases,but they also appear to break new ground with their unexpected properties,such as extreme tolerance to defects.However,because of the relatively recent emergence of this class of materials,there remain many yet to be fully explored compounds.Here,we assess a series of bismuth/antimony oxyhalides and chalcohalides using consistent first principles methods to ascertain their properties and obtain trends.Based on these calculations,we identify a subset consisting of three types of compounds that may be promising as solar absorbers,transparent conductors,and radiation detectors.Their electronic structure,connection to the crystal geometry,and impact on band-edge dispersion and carrier effective mass are discussed.
基金supported by the National Natural Science Foundation of China (21725304,11774120 and 11904010)Chang Jiang Scholars Program of China (T2016051)+3 种基金Changbai Mountain Scholars Program (2013007)the Natural Science Foundation of Hebei Province (A2019409043 and A2020409002)the Foundation of Hebei Educational Committee (QN2020108)the Open Project of the State Key Laboratory of Superhard Materials,Jilin University (201915)。
文摘The ability to spontaneously heal injuries is an important survival feature for humans,plants,and animals in nature.Inspired by nature,man-made self-healing materials that are capable of repairing damage and degraded properties either autonomously or triggered by external stimuli have been developed to improve the lifetime,safety,and functionality of products[1–3].to date,most self-healing materials are representative soft materials,such as polymers and gels[4–6].Relative to highly elastic and adaptive soft materials,long-range ordered molecular crystals are rigid and unadaptable and are highly vulnerable to stress-induced cracks.Accordingly,the self-healing property is meaningful for ordered molecular crystals as it can endow molecular crystals with the ability to resist the loss of functionality and service lifetime during specific applications。
基金This work was supported by the National Natural Science Foundation of China(31671521 and 31871483 to B.M.)Yunnan Basic Research Program(202001AS070036 to B.M.).
文摘TDP43 pathology is seen in a large majority of amyotrophic lateral sclerosis(ALS)cases,suggesting a central pathogenic role of this regulatory protein.Clarifying the molecular mechanism controlling TDP43 stability and subcellular location might provide important insights into ALS therapy.The ubiquitin E3 ligase RNF220 is involved in different neural developmental processes through various molecular targets in the mouse.Here,we report that the RNF2207 mice showed progressively decreasing mobility to different extents,some of which developed typical ALS pathological characteristics in spinal motor neurons,including TDP43 cytoplasmic accumulation,atrocytosis,muscle denervation,and atrophy.Mechanistically,RNF220 interacts with TDP43 in vitro and in vivo and promotes its polyubiquitination and proteasomal degradation.In conclusion,we propose that RNF220 might be a modifier of TDP43 function in vivo and contribute to TDP43 pathology in neurodegenerative disease like ALS.
文摘ObjectiveTo investigate the effect of Niraparib,a clinically approved PARP inhibitor on the radiosensitivity of human lung and cervical cancer cells,and preliminarily explore the underlying mechanism.MethodsThe human lung cancer cell line A549 and human cervical cancer cell line Siha were both treated with Niraparib for 1h,or X-ray irradiation with 4y,or Niraparib for 1h combined with X-ray irradiation with 4Gy.The effect was examined via measurements of cell proliferation by the cell counting kit-8 assay,and cell viability was detected by clone formation assays.Cell apoptosis and cell cycle distribution were investigated by flow cytometry.ResultsIn human lung and cervical cancer cell lines,Niraparib combined with radiation therapy significantly inhibited cell proliferation.The proportion of apoptotic cells in cell lines treated with Niraparib plus radiation(the combination group)was significantly higher compared with control,radiation,and Niraparib groups(P<0.05).Additionally,the proportion of A549 cells in the G_(2)/M phase was significantly increased in the combination group compared with the radiation group(P<0.05).ConclusionPARP inhibitor Niraparib increases the radiosensitivity of tumorcells,promotes their apoptosis,and induces cell cycle redistribution.The possible mechanism is associated with the inhibition of radiation-induced DNA damage repair.
基金supported by the National Natural Science Foundation of China(Grants Nos.11405136 and 11547311)the Fundamental Research Funds for the Central Universities of China(Grants Nos.2682016CX059 and 2682014BR056)
文摘Two unknown states can be unambiguously distinguished by a universal programmable discriminator, which has been widely discussed in previous works and the optimal solution has also been obtained. In this paper, we investigate the programmable unambiguous discriminator between two unknown "latitudinal" states, which lie in a subspace of the total state space. By equivalence of unknown pure states to known average mixed states, the optimal solution for this problem is systematically derived, and the analytical success probabilities for the optimal unambiguous discrimination are obtained. It is beyond one's expectation that the optimal setting for the programmable unambiguous discrimination between two unknown "latitudinal" states is the same as that for the universal ones. The results in this work can be used for the realization of the programmable discriminator in laboratory.
基金National Key Research and Development Program of China (2017YFB1104401)National Natural Science Foundation of China (61905226)。
文摘The self-imaging effect in a square core fiber has been investigated, and an integrated all-fiber combiner has been proposed based on a large mode area double clad fiber, which can be employed to construct high power coherent beam combining sources in the all-fiber format. The influence of various parameters on beam quality(M^(2)) and efficiency of the all-fiber coherent beam combiner has been studied numerically, which reveals that the near diffraction-limited laser beam can be achieved. A principle demonstration of the self-imaging effect has been carried out experimentally in a square core fiber, which proves the feasibility of beam combining with the square fiber, and that it is a promising way to develop high power coherent beam combination sources.
基金supported by grants from the National Natural Science Foundation of China (No. 51903062)Guangdong Basic and Applied Basic Research Foundation (No.2020A1515011320)+1 种基金Science and Technology Projects of Guangzhou(No. 202102020757)Subject Construction Project of Basic Medical Sciences of Guangzhou Medical University (Nos.JCXKJS2021B07, JCXKJS2021D09)。
文摘Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib(SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4(GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.
基金supported by the National Natural Science Foundation of China(Nos.21722505 and 21705086)the Special Funds of the Taishan Scholar Program of Shandong Province(No.tsqn20161028)+4 种基金the Youth Innovation Technology Program of Shandong Province(No.2019KJC029)the Natural Science Foundation of Shandong Province(No.ZR2017JL009)the Collaborative Innovation Program of Jinan(No.2018GXRC033)the Open Project of Shandong Key Laboratory of Tumor Marker Detection Technology(Nos.KLDTTM2019-4,KLDTTM2019-5)the Open Project of Chemistry Department of Qingdao University of Science and Technology(No.QUSTHX201928)。
文摘A multifunctional nanocomposite of AgNPs@GQDs is prepared by synergistic in-situ growth of silver nanoparticles(AgNPs)on the complex of tannic acid(TA)and graphene quantum dots(GQDs)for the construction of dual-mode biosensing platform and cancer theranostics.The nanocomposite exhibits a hydrogen peroxide(H_(2)O_(2))-responsive degradation,in which Ag^(0)is oxidized to Ag^(+)along with the release of oxidized TA and GQDs.The degradation induces the decreased absorbance and enhanced fluorescence(FL)intensity due to the suppression of Forster resonance ene rgy transfer(FRET)in AgNPs@GQDs,which is employed for colorimetric/fluorescence dual-mode sensing of H_(2)O_(2).The intrinsic peroxidase-like activity of GQDs nanozyme can effectively catalyze the oxidation reaction,enhancing the detection sensitivity significantly.Based on the generation of H_(2)O_(2)from the oxidation of glucose with the catalysis of glucose oxidase(GOx),this nanoprobe is versatilely used for the determination of glucose in human serum.Further,through combining the H_(2)O_(2)-responsive degradation of AgNPs@GQDs with high H_(2)O_(2)level in cancer cells,the nanocomposites exhibit good performance in cancer cell recognition and therapy,in which the synergistic anticancer effect of Ag^(+)and oxidized TA contribute to effective cell death,and the liberated GQDs are used to monitor the therapeutic effect by cell imaging.