Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulatio...Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulation plays an important role in the developmental origins of osteoporosis; however, few studies have investigated the potential of epigenetic therapy to improve or rescue the osteogenic ability of bone marrow mesenchymal stem cells(BMMSCs) under osteoporotic conditions. Here, we investigated pargyline, an inhibitor of lysine-specific demethylase 1(LSD1), which mainly catalyzes the demethylation of the di- and mono-methylation of H3K4. We demonstrated that 1.5 mmol·Lpargyline was the optimal concentration for the osteogenic differentiation of human BMMSCs. Pargyline rescued the osteogenic differentiation ability of mouse BMMSCs under osteoporotic conditions by enhancing the dimethylation level of H3K4 at the promoter regions of osteogenesis-related genes. Moreover, pargyline partially rescued or prevented the osteoporotic conditions in aged or ovariectomized mouse models, respectively. By introducing the concept of epigenetic therapy into the field of osteoporosis, this study demonstrated that LSD1 inhibitors could improve the clinical practice of MSC-based bone tissue engineering and proposes their novel use to treat osteoporosis.展开更多
As a new three-dimensional(3-D)modulation,Polarization Quadrature Amplitude Modulation(PQAM) can be regarded as the combination of Pulse amplitude modulation(PAM) and Quadrature Amplitude Modulation(QAM) Modulation.It...As a new three-dimensional(3-D)modulation,Polarization Quadrature Amplitude Modulation(PQAM) can be regarded as the combination of Pulse amplitude modulation(PAM) and Quadrature Amplitude Modulation(QAM) Modulation.It can better improve the digital communication efficiency and reduce the Symbol error rate(SER) of the system than one-dimensional or two-dimensional modulation scheme.How to design a feasible constellation is the most concerned problem of PQAM currently.This paper first studies the relationship between the SER theoretical value of PQAM and the distribution of M and N,proposes a new M,N allocation scheme.Secondly,a new and straightforward design method of constructing higher-level 3-D signal constellations,which can be matched with the PQAM,and the constellation can divided into three different structures according to the ary for PQAM.Finally,the simulation results show that:in PQAM system,the modulation scheme and the constellation mapping scheme are proposed in this paper which can effectively reduce the system SER and improve the anti-noise performance of the system.展开更多
In this work,a hybrid integrated optical transmitter module was designed and fabricated.A proton-exchanged Mach–Zehnder lithium niobate(LiNbO_(3))modulator chip was chosen to enhance the output extinction ratio.A fib...In this work,a hybrid integrated optical transmitter module was designed and fabricated.A proton-exchanged Mach–Zehnder lithium niobate(LiNbO_(3))modulator chip was chosen to enhance the output extinction ratio.A fiber was used to adjust the rotation of the polarization direction caused by the optical isolator.The whole optical path structure,including the laser chip,lens,fiber,and modulator chip,was simulated to achieve high optical output efficiency.After a series of process improvements,a module with an output extinction ratio of 34 dB and a bandwidth of 20.5 GHz(from 2 GHz)was obtained.The optical output efficiency of the whole module reached approximately 21%.The link performance of the module was also measured.展开更多
MEMS swallowable capsule is a novel technology in the non-invasive surgery. This technology provides a way to diagnose directly into the deep intestinal where the traditional invasive technology implemented, such as X...MEMS swallowable capsule is a novel technology in the non-invasive surgery. This technology provides a way to diagnose directly into the deep intestinal where the traditional invasive technology implemented, such as X-Ray, endoscopy. It is a key for us to locate and track the position of a MEMS capsule in clinical applications. To solve this problem, we implemented a magnetic sensor module based on the scalar form of the magnetic dipole model,which was designed with very small size （5.2 ＊ 2. 1 ＊ 1.2 em） and easy to assemble to satisfy the system requirement. Here we discuss in detail the principle of magnetic dipole model, rules of selecting sensor and functions of the module. Some trials are established to test the characteristic of the module. The results of the Cm experiment demonstrates that the module follows the rules of the new magnetic dipole model form.展开更多
Cycloaddition of CO_(2) and epoxide into cyclic carbonate is one of the most efficient ways for CO_(2) conversion with 100% atom-utilization. Metal–organic frameworks are a kind of potential heterogeneous catalysts, ...Cycloaddition of CO_(2) and epoxide into cyclic carbonate is one of the most efficient ways for CO_(2) conversion with 100% atom-utilization. Metal–organic frameworks are a kind of potential heterogeneous catalysts, however, high temperature, high pressure, and high-purity CO_(2) are still required for the reaction.Here, we report two new Zn(Ⅱ) imidazolate frameworks incoporating MoO_(4)^(2–)or WO_(4)^(2–)units, which can catalyse cycloaddition of CO_(2) and epichlorohydrin at room temperature and atomospheric pressure, giving 95% yield after 24 h in pure CO_(2) and 98% yield after 48 h in simulated flue gas(15% CO_(2)+ 85% N_(2)),respectively. For comparison, the analogic Zn(Ⅱ) imidazolate framework MAF-6 without non-3d metal oxide units showed 71% and 33% yields under the same conditions, respectively. The insightful modulation mechanisms of the MoO_(4)^(2–)unit in optimizing the electronic structure of Zn(Ⅱ) centre, facilitating the rate-determined ring opening process, and minimizing the reaction activation energy, were revealed by X-ray photoelectron spectroscopy, temperature programmed desorption and computational calculations.展开更多
1.设计思路语言学习应以应用为目标,着重培养学生的交际能力,并能解决实际的生活问题。在目前的英语教学里,教师一般会在同一堂课里进行'听'与'说'的技能训练,其中'听'是'说'的前提,'说'是'...1.设计思路语言学习应以应用为目标,着重培养学生的交际能力,并能解决实际的生活问题。在目前的英语教学里,教师一般会在同一堂课里进行'听'与'说'的技能训练,其中'听'是'说'的前提,'说'是'听'的延伸。在听说课里,听力策略和会话技巧是帮助学生实现交流目的和信息沟通的桥梁,这也是教学设计的重点。2.教材分析本课的内容是牛津英语9B Module 2 Unit 3 The environment的听说课。展开更多
As electronic packages become more compact, run at faster speeds and dissipate more heat, package designers need more effective thermal management materials. CVD diamond, because of its high thermal conductivity, low ...As electronic packages become more compact, run at faster speeds and dissipate more heat, package designers need more effective thermal management materials. CVD diamond, because of its high thermal conductivity, low dielectric loss and its great mechanical strength, is an excellent material for three dimensional （319） multichip modules （MCMs） in the next generation compact high speed computers and high power microwave components. In this paper, we have synthesized a large area freestanding diamond films and substrates, and polished diamond substrates, which make MCMs diamond film sink becomes a reality.展开更多
The paradigm of antibody–drug conjugates(ADCs)has successfully transformed oncology,demonstrating that pairing the specificity of an antibody with high potency of a cytotoxic payload is a powerful therapeutic strateg...The paradigm of antibody–drug conjugates(ADCs)has successfully transformed oncology,demonstrating that pairing the specificity of an antibody with high potency of a cytotoxic payload is a powerful therapeutic strategy1,2.To date,approximately 20 ADCs have been approved worldwide,highlighting the success and potential of ADCs as a class of powerful therapeutic modalites3.As researchers contemplate the next generation of ADCs,the field is rapidly evolving beyond traditional toxins to explore novel payloads with new mechanisms of action.展开更多
Degrader–antibody conjugates(DACs)represent a promising drug modality for targeting hematological malignancy,but still lack rational design frameworks.Here,we show the strategies of reasonable antibody-degrader compa...Degrader–antibody conjugates(DACs)represent a promising drug modality for targeting hematological malignancy,but still lack rational design frameworks.Here,we show the strategies of reasonable antibody-degrader compatibility and degradation tail-derived conjugatability through a systematic exploration.Inspired by the success of IKZF1/3 degraders,we sought to explore the potential of cereblon E3 ligase modulators(CELMoDs)in constructing novel conjugates.By combining a modular library with neo-substrate screening and further conjugatable derivation,I034 was identified,a potent CELMoD payload with picomolar degradation activity and antiproliferative effects.Through linker chemistry,I034-based DACs were constructed and demonstrated superior efficacy and safety compared to auristatin-based conjugates both in vitro and in vivo,with the CD38-targeting Dara-VA-I034 achieving complete tumor eradication at low doses.Mechanistic insights revealed distinct positive feedback regulation of CD38 conjugates,highlighting the need for compatibility between payloads and antigens.These results demonstrate that the approach could provide a framework for discovering CELMoD payloads and advancing DACs for treating multiple myeloma and other malignancies.展开更多
Background Methanesulfonic acid sodium salt （Dipyrone）, an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of t...Background Methanesulfonic acid sodium salt （Dipyrone）, an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy. Methods One hundred mice were assigned randomly into vehicle （V）, methanesulfonic acid sodium salt （D）, light damage model plus vehicle （MV） and light damage model plus methanesulfonic acid sodium salt （MD） groups （n=25 each）. In the MD group, methanesulfonic acid sodium salt （100 mg/kg） was administered by intraperitoneal injection 30 minutes before light exposure. Twenty-four hours after light exposure, hematoxylin and eosin staining and transmission electron microscopy （TEM） were used for histological evaluation. The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 I^m from the optic nerve. Electroretinography （ERG） test was performed to assess the functional change. The morphology of mitochondria was also revealed by TEM. Finally, the expression of cytochrome c （CytC） and the relative apoptotic proteins were detected by Western blotting, and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation. Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group. The thicknesses of the outer plus inner-segment layers and the outer nuclear layer, and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group （P 〈0.05）. TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae. In contrast, the morphology of mitochondria in the MD group was unaffected. Western blotting analysis showed that CytC, apoptosis proteinase activating factor-1 （Apaf-1）, caspase 3, p53, p53-upregulated modulator of apoptosis （PUMA）, Bax, and Bad were increased, whereas the anti-apoptotic proteins Bcl-2 and Bcl-XL were significantly decreased in the MV group than the MD group. Co-immunoprecipitation detection revealed that PUMA immunoreactivity precipitated by Bcl-XL decreased, whereas Bax immunoreactivity precipitated by Bcl-XL increased in the MD group compared to those in the MV group. Conclusion Methanesulfonic acid sodium salt is an effective photoprotective agent against light-induced retinopathy through the inhibition of CytC-mediated mitochondrial impairment.展开更多
We propose and demonstrate a novel variable PDL emulator based on a LiNbO3 modulator. The proposed emulator could vary the PDL values simply by adjusting the bias voltage of modulator. The results show that the propos...We propose and demonstrate a novel variable PDL emulator based on a LiNbO3 modulator. The proposed emulator could vary the PDL values simply by adjusting the bias voltage of modulator. The results show that the proposed PDL emulator could generate a wide range of PDL values (0 ~ 35 dB). The generated PDL value could be maintained within ±0.02 dB for >70 minutes. The wavelength dependency was about 0.03 dB in the range of 1520 nm~ 1590 nm.展开更多
基金supported by grants from the National Natural Science Foundation of China(81200763 to WG and 81070809 to YZ)the Program for New Century Excellent Talents(NCET)at the University from Ministry of Education of China(NCET-11-0026)+1 种基金the PKU School of Stomatology for Talented Young Investigators(PKUSS20150107)the Construction Program for the National Key Clinical Specialty from the National Health and Family Planning Commission of China(2011)
文摘Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulation plays an important role in the developmental origins of osteoporosis; however, few studies have investigated the potential of epigenetic therapy to improve or rescue the osteogenic ability of bone marrow mesenchymal stem cells(BMMSCs) under osteoporotic conditions. Here, we investigated pargyline, an inhibitor of lysine-specific demethylase 1(LSD1), which mainly catalyzes the demethylation of the di- and mono-methylation of H3K4. We demonstrated that 1.5 mmol·Lpargyline was the optimal concentration for the osteogenic differentiation of human BMMSCs. Pargyline rescued the osteogenic differentiation ability of mouse BMMSCs under osteoporotic conditions by enhancing the dimethylation level of H3K4 at the promoter regions of osteogenesis-related genes. Moreover, pargyline partially rescued or prevented the osteoporotic conditions in aged or ovariectomized mouse models, respectively. By introducing the concept of epigenetic therapy into the field of osteoporosis, this study demonstrated that LSD1 inhibitors could improve the clinical practice of MSC-based bone tissue engineering and proposes their novel use to treat osteoporosis.
基金supported in part by the National Natural Science Foundation of China (61561039, 61271177, and 61461044)
文摘As a new three-dimensional(3-D)modulation,Polarization Quadrature Amplitude Modulation(PQAM) can be regarded as the combination of Pulse amplitude modulation(PAM) and Quadrature Amplitude Modulation(QAM) Modulation.It can better improve the digital communication efficiency and reduce the Symbol error rate(SER) of the system than one-dimensional or two-dimensional modulation scheme.How to design a feasible constellation is the most concerned problem of PQAM currently.This paper first studies the relationship between the SER theoretical value of PQAM and the distribution of M and N,proposes a new M,N allocation scheme.Secondly,a new and straightforward design method of constructing higher-level 3-D signal constellations,which can be matched with the PQAM,and the constellation can divided into three different structures according to the ary for PQAM.Finally,the simulation results show that:in PQAM system,the modulation scheme and the constellation mapping scheme are proposed in this paper which can effectively reduce the system SER and improve the anti-noise performance of the system.
基金This work was supported by National Key Research and Development Program of China(2018YFB2201101)the Strategic Priority Research Program of Chinese Academy of Sciences,Grant No.XDB43000000Beijing Municipal Science&Technology Commission,Administrative Commission of Zhongguancun Science Park No.Z201100004020004。
文摘In this work,a hybrid integrated optical transmitter module was designed and fabricated.A proton-exchanged Mach–Zehnder lithium niobate(LiNbO_(3))modulator chip was chosen to enhance the output extinction ratio.A fiber was used to adjust the rotation of the polarization direction caused by the optical isolator.The whole optical path structure,including the laser chip,lens,fiber,and modulator chip,was simulated to achieve high optical output efficiency.After a series of process improvements,a module with an output extinction ratio of 34 dB and a bandwidth of 20.5 GHz(from 2 GHz)was obtained.The optical output efficiency of the whole module reached approximately 21%.The link performance of the module was also measured.
文摘MEMS swallowable capsule is a novel technology in the non-invasive surgery. This technology provides a way to diagnose directly into the deep intestinal where the traditional invasive technology implemented, such as X-Ray, endoscopy. It is a key for us to locate and track the position of a MEMS capsule in clinical applications. To solve this problem, we implemented a magnetic sensor module based on the scalar form of the magnetic dipole model,which was designed with very small size （5.2 ＊ 2. 1 ＊ 1.2 em） and easy to assemble to satisfy the system requirement. Here we discuss in detail the principle of magnetic dipole model, rules of selecting sensor and functions of the module. Some trials are established to test the characteristic of the module. The results of the Cm experiment demonstrates that the module follows the rules of the new magnetic dipole model form.
基金supported by the National Natural Science Foundation of China (Nos. 22090061, 21731007, 21890380 and 22161021)the Guangdong Pearl River Talents Program (No. 2017BT01C161)the support of Jiangxi Province (No. jxsq2018106041)。
文摘Cycloaddition of CO_(2) and epoxide into cyclic carbonate is one of the most efficient ways for CO_(2) conversion with 100% atom-utilization. Metal–organic frameworks are a kind of potential heterogeneous catalysts, however, high temperature, high pressure, and high-purity CO_(2) are still required for the reaction.Here, we report two new Zn(Ⅱ) imidazolate frameworks incoporating MoO_(4)^(2–)or WO_(4)^(2–)units, which can catalyse cycloaddition of CO_(2) and epichlorohydrin at room temperature and atomospheric pressure, giving 95% yield after 24 h in pure CO_(2) and 98% yield after 48 h in simulated flue gas(15% CO_(2)+ 85% N_(2)),respectively. For comparison, the analogic Zn(Ⅱ) imidazolate framework MAF-6 without non-3d metal oxide units showed 71% and 33% yields under the same conditions, respectively. The insightful modulation mechanisms of the MoO_(4)^(2–)unit in optimizing the electronic structure of Zn(Ⅱ) centre, facilitating the rate-determined ring opening process, and minimizing the reaction activation energy, were revealed by X-ray photoelectron spectroscopy, temperature programmed desorption and computational calculations.
文摘1.设计思路语言学习应以应用为目标,着重培养学生的交际能力,并能解决实际的生活问题。在目前的英语教学里,教师一般会在同一堂课里进行'听'与'说'的技能训练,其中'听'是'说'的前提,'说'是'听'的延伸。在听说课里,听力策略和会话技巧是帮助学生实现交流目的和信息沟通的桥梁,这也是教学设计的重点。2.教材分析本课的内容是牛津英语9B Module 2 Unit 3 The environment的听说课。
基金Supported by National Natural Science Foundation of China (No.60371006)
文摘As electronic packages become more compact, run at faster speeds and dissipate more heat, package designers need more effective thermal management materials. CVD diamond, because of its high thermal conductivity, low dielectric loss and its great mechanical strength, is an excellent material for three dimensional （319） multichip modules （MCMs） in the next generation compact high speed computers and high power microwave components. In this paper, we have synthesized a large area freestanding diamond films and substrates, and polished diamond substrates, which make MCMs diamond film sink becomes a reality.
文摘The paradigm of antibody–drug conjugates(ADCs)has successfully transformed oncology,demonstrating that pairing the specificity of an antibody with high potency of a cytotoxic payload is a powerful therapeutic strategy1,2.To date,approximately 20 ADCs have been approved worldwide,highlighting the success and potential of ADCs as a class of powerful therapeutic modalites3.As researchers contemplate the next generation of ADCs,the field is rapidly evolving beyond traditional toxins to explore novel payloads with new mechanisms of action.
基金supported by the National Natural Science Foundation of China[82173660(Xiaowu Dong),82273951(Yubo Zhou),82404655(Hanlin Wang),92253306(Jia Li)]China Postdoctoral Science Foundation 2024M750708(Jingyu Zhang)Shanghai Science and Technology Development Foundation 24YF275530(Hanlin Wang).
文摘Degrader–antibody conjugates(DACs)represent a promising drug modality for targeting hematological malignancy,but still lack rational design frameworks.Here,we show the strategies of reasonable antibody-degrader compatibility and degradation tail-derived conjugatability through a systematic exploration.Inspired by the success of IKZF1/3 degraders,we sought to explore the potential of cereblon E3 ligase modulators(CELMoDs)in constructing novel conjugates.By combining a modular library with neo-substrate screening and further conjugatable derivation,I034 was identified,a potent CELMoD payload with picomolar degradation activity and antiproliferative effects.Through linker chemistry,I034-based DACs were constructed and demonstrated superior efficacy and safety compared to auristatin-based conjugates both in vitro and in vivo,with the CD38-targeting Dara-VA-I034 achieving complete tumor eradication at low doses.Mechanistic insights revealed distinct positive feedback regulation of CD38 conjugates,highlighting the need for compatibility between payloads and antigens.These results demonstrate that the approach could provide a framework for discovering CELMoD payloads and advancing DACs for treating multiple myeloma and other malignancies.
文摘Background Methanesulfonic acid sodium salt （Dipyrone）, an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy. Methods One hundred mice were assigned randomly into vehicle （V）, methanesulfonic acid sodium salt （D）, light damage model plus vehicle （MV） and light damage model plus methanesulfonic acid sodium salt （MD） groups （n=25 each）. In the MD group, methanesulfonic acid sodium salt （100 mg/kg） was administered by intraperitoneal injection 30 minutes before light exposure. Twenty-four hours after light exposure, hematoxylin and eosin staining and transmission electron microscopy （TEM） were used for histological evaluation. The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 I^m from the optic nerve. Electroretinography （ERG） test was performed to assess the functional change. The morphology of mitochondria was also revealed by TEM. Finally, the expression of cytochrome c （CytC） and the relative apoptotic proteins were detected by Western blotting, and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation. Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group. The thicknesses of the outer plus inner-segment layers and the outer nuclear layer, and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group （P 〈0.05）. TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae. In contrast, the morphology of mitochondria in the MD group was unaffected. Western blotting analysis showed that CytC, apoptosis proteinase activating factor-1 （Apaf-1）, caspase 3, p53, p53-upregulated modulator of apoptosis （PUMA）, Bax, and Bad were increased, whereas the anti-apoptotic proteins Bcl-2 and Bcl-XL were significantly decreased in the MV group than the MD group. Co-immunoprecipitation detection revealed that PUMA immunoreactivity precipitated by Bcl-XL decreased, whereas Bax immunoreactivity precipitated by Bcl-XL increased in the MD group compared to those in the MV group. Conclusion Methanesulfonic acid sodium salt is an effective photoprotective agent against light-induced retinopathy through the inhibition of CytC-mediated mitochondrial impairment.
文摘We propose and demonstrate a novel variable PDL emulator based on a LiNbO3 modulator. The proposed emulator could vary the PDL values simply by adjusting the bias voltage of modulator. The results show that the proposed PDL emulator could generate a wide range of PDL values (0 ~ 35 dB). The generated PDL value could be maintained within ±0.02 dB for >70 minutes. The wavelength dependency was about 0.03 dB in the range of 1520 nm~ 1590 nm.
