Efficient distribution of therapeutics to the targeted site,particularly internal organs,is essential for their therapeutic success.Here,we developed a therapeutic delivery system targeting internal organs,which featu...Efficient distribution of therapeutics to the targeted site,particularly internal organs,is essential for their therapeutic success.Here,we developed a therapeutic delivery system targeting internal organs,which features a mechanism akin to a snake’s jaw for grasping and deploying detachable microneedles(MNs)embedded with therapeutics.This solves the current challenges of delivering microneedle patches without open chest or abdominal wall surgery.We showed an example of this technology via delivering exosomes derived from mesenchymal stem cells(MSCs)directly to the heart’s damaged regions via percutaneous minimally invasive surgery.The shell of MNs is fabricated from methacrylated hyaluronic acid(MeHA),which ensures mechanical strength for myocardium penetration,while the hyaluronic acid(HA)core allows a sustained release of exo-somes.In a rat model of myocardial infarction(MI),the delivery of exosomes-loaded microneedles(XOs-MNs)resulted in angiomyogenesis and promoted cardiac function.The feasibility of this microneedle delivery method was also confirmed in a pig model.With its capability to encapsulate a wide range of therapeutic formulations,our system presents a versatile platform for the minimally invasive administration of treatments to internal organs.展开更多
Current gravitational-wave detectors have achieved remarkable sensitivity around 100 Hz,enabling ground-breaking discoveries.Enhancing sensitivity at higher frequencies in the kilohertz(kHz)range promises access to ri...Current gravitational-wave detectors have achieved remarkable sensitivity around 100 Hz,enabling ground-breaking discoveries.Enhancing sensitivity at higher frequencies in the kilohertz(kHz)range promises access to rich physics,particularly the extreme conditions during the merger stage of binary neutron stars.However,the high-frequency sensitivity of Michelson-based interferometers is fundamentally limited by their linear optical cavities,which are optimized for low-frequency signal enhancement.A new configuration employing an L-shaped optical resonator was proposed to overcome this limitation,offering exceptional sensitivity in the kHz band.As a pathfinder,the 12-meter prototype at Beijing Normal University is designed to demonstrate the sensing and control schemes of this new kHz detector configuration and to explore its performance in the high-power regime with suspended optics.Beyond its primary scientific goal,the prototype also offers potential sensitivity in the megahertz(MHz)range,potentially enabling constraints on exotic sources.This paper presents an overview of the prototype,including its optical design and current development status of key components.展开更多
Anaerobic process is regarded as a green and sustainable process due to low carbon emission and minimal energy consumption in wastewater treatment plants(WWTPs).However,some water quality metrics are not measurable in...Anaerobic process is regarded as a green and sustainable process due to low carbon emission and minimal energy consumption in wastewater treatment plants(WWTPs).However,some water quality metrics are not measurable in real time,thus influencing the judgment of the operators and may increase energy consumption and carbon emission.One of the solutions is using a soft-sensor prediction technique.This article introduces a water quality soft-sensor prediction method based on Bidirectional Gated Recurrent Unit(BiGRU)combined with Gaussian Progress Regression(GPR)optimized by Tree-structured Parzen Estimator(TPE).TPE automatically optimizes the hyperparameters of BiGRU,and BiGRU is trained to obtain the point prediction with GPR for the interval prediction.Then,a case study applying this prediction method for an actual anaerobic process(2500 m^(3)/d)is carried out.Results show that TPE effectively optimizes the hyperparameters of BiGRU.For point prediction of CODeff and biogas yield,R^(2)values of BiGRU,which are 0.973 and 0.939,respectively,are increased by 1.03%–7.61%and 1.28%–10.33%,compared with those of other models,and the valid prediction interval can be obtained.Besides,the proposed model is assessed as a reliable model for anaerobic process through the probability prediction and reliable evaluation.It is expected to provide high accuracy and reliable water quality prediction to offer basis for operators in WWTPs to control the reactor and minimize carbon emission and energy consumption.展开更多
Current contraceptive methods come with a number of drawbacks,including low efficacy,in the case of commercial contraceptive gels,and a reduction in the quality of sexual intercourse,in the case of condoms.Adding phar...Current contraceptive methods come with a number of drawbacks,including low efficacy,in the case of commercial contraceptive gels,and a reduction in the quality of sexual intercourse,in the case of condoms.Adding pharmacologically-active agents to contraceptive gels holds the potential to improve sexual experience,and hardbor safety and hygiene.In this study,we fabricated a carbomer-based contraceptive gel consisting of three agents:tenofovir,gossypol acetate,and nitroglycerin(TGN),with pH adjusted to 4.5(to be compatible with the vagina).In vitro,the gossypol component of the contraceptive gel proved to be an effective spermicide.When the concentration of gossypol acetate was 10 mg/ml,the spermicidal ability reached 100%after 30 s.In addition,tenofovir in the gel significantly inhibited lentiviral transfection efficiency in cell-containing media.In 6 pairs of rats,the gel successfully prevented all females from conceiving after successful mating.Moreover,increased sexual frequency and enhanced erection,which were promoted by the nitroglycerin in the components,were observed in male rats that had the gel applied to their penises.This novel TGN contraceptive gel yielded a higher contraceptive success rate than that of the commercial contraceptive gel(Contragel®).In addition,it has the added benefits to prevent sexually transmitted diseases and improve male libido and erectile function during sexual intercourse.Combining three FDA-approved and marketed agents together,our trifunctional TGN gel has a great potential for further translation and commercialization.展开更多
Myocardial infarction(MI),commonly known as a heart attack,remains a leading cause of death worldwide.Standard treatments,such as coronary stent placement or coronary artery bypass graft surgery,aim to restore blood f...Myocardial infarction(MI),commonly known as a heart attack,remains a leading cause of death worldwide.Standard treatments,such as coronary stent placement or coronary artery bypass graft surgery,aim to restore blood flow to ischemic myocardial tissue.However,a significant complication of these procedures is ischemia/reperfusion(I/R)injury,which occurs when blood flow is restored,triggering oxidative stress,inflammation,and calcium overload that can further damage the heart.To limit the I/R injury following the coronary recanalization of an MI heart,we designed stromal-platelet membrane-inspired nanoparticles(SPINs)that consist of a poly(lactic-co-glycolic acid)(PLGA)core,decorated by a dual membrane coating:a platelet membrane for precise adhesion to the damaged endothelium area and a stromal cell membrane to enhance receptor-ligand interactions and immune-evasiveness.This unique dual-membrane configuration synergistically reduces fibrosis and inflammation while promoting angiomyogenesis.This combination integrates the vascular injury targeting and immune-evasive properties of the nanoparticle,making this dual-membrane design a promising add-on intervention to augment post-percutaneous coronary intervention recovery,enhancing outcomes and offering potential improved cardiac repair.展开更多
Primary ovarian insufficiency(POI)is an ovarian dysfunction that affects more than 1%of women and is characterized by hormone imbalances that afflict women before the age of 40.The typical perimenopausal symptoms resu...Primary ovarian insufficiency(POI)is an ovarian dysfunction that affects more than 1%of women and is characterized by hormone imbalances that afflict women before the age of 40.The typical perimenopausal symptoms result from abnormal levels of sex hormones,especially estrogen.The most prevalent treatment is hormone replacement therapy(HRT),which can relieve symptoms and improve quality of life.However,HRT cannot restore ovarian functions,including secretion,ovulation,and fertility.Recently,as part of a developing field of regenerative medicine,stem cell therapy has been proposed for the treatment of POI.Thus,we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment,and sum up the underlying mechanisms of action.A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies.展开更多
Extracellular vesicles(EVs)generated from mesenchymal stem cells(MSCs)play an essential role in modulating cell–cell communication and tissue regeneration.The clinical translation of EVs is constrained by the poor yi...Extracellular vesicles(EVs)generated from mesenchymal stem cells(MSCs)play an essential role in modulating cell–cell communication and tissue regeneration.The clinical translation of EVs is constrained by the poor yield of EVs.Extrusion has recently become an effective technique for producing a large scale of nanovesicles(NVs).In this study,we systematically compared MSC NVs(from extrusion)and EVs(from natural secretion).Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs.Additionally,microRNAs in NVs are related to cardiac repair,fibrosis repression,angiogenesis.Lastly,intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction.展开更多
Our Moon is by far the easiest natural, extraterrestrial celestial object for us to reach, and many space agencies, in particular the China National Space Administration, have publicized plans for manned missions ther...Our Moon is by far the easiest natural, extraterrestrial celestial object for us to reach, and many space agencies, in particular the China National Space Administration, have publicized plans for manned missions there. Such high-profile projects must yield commensurate scientific outputs to justify their cost to the taxpayers. An important criterion for the selection of candidate experiments is the extent to which the Moon plays an integral and irreplaceable role, as opposed to offering only marginal advantages over Earth-orbit, space-based alternatives. In this study, we propose an experiment that excels in this regard, which considers the Moon as part of the experimental apparatus. Specifically, the Moon acts as a Weber bar-style resonant mass that responds to deci-Hertz gravitational waves(GWs). GW-excited lunar vibrations can be picked up by an array of(prefabricated on Earth and easy to transport to the Moon) small laser interferometric seismometers yielding GW detection. Such a setup would plug a gap in the GW frequency range already covered by the existing or underdevelopment detectors, and it can inform us on important astrophysics topics, such as the progenitors of Type Ia supernovae(SNe Ia) or intermediate mass black holes. We provide the instrument design as well as its deployment strategy, and we also summarize relevant science cases according to the estimated viable sensitivity.展开更多
Chemotherapy-induced cardiotoxicity with subsequent heart failure(HF)is a major cause of morbidity and mortality in cancer survivors worldwide.Chemotherapy-induced HF is exceptionally challenging as it generally manif...Chemotherapy-induced cardiotoxicity with subsequent heart failure(HF)is a major cause of morbidity and mortality in cancer survivors worldwide.Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation.To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF,we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive(MISA)that could be delivered locally through an endoscope-guided intrapericardial injection.To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients,we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections.In vitro,we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability,but also inhibited their apoptosis.In vivo,we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation,angiogenesis,and mitochondrial respiration.Additionally,we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system.In general,our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.展开更多
This paper"Detecting gravitational wave with an interferometric seismometer array on lunar nearside"[1]was published in SCIENCE CHINA Physics,Mechanics&Astronomy(66,109513(2023),doi:10.1007/s11433-023-21...This paper"Detecting gravitational wave with an interferometric seismometer array on lunar nearside"[1]was published in SCIENCE CHINA Physics,Mechanics&Astronomy(66,109513(2023),doi:10.1007/s11433-023-2179-9).Due to an oversight on our part,some errors were made in the originally published paper.We apologize for these errors and offer the corresponding explanations and corrections for the readers.展开更多
基金supported by grants from the National Institutes of Health(NIH)of the United States(nos.HL123920,HL137093,HL144002,HL146153,HL147357 and HL149940 to K.C.)funded in part through the NIH/NCI Cancer Center Support grant no.P30CA013696.
文摘Efficient distribution of therapeutics to the targeted site,particularly internal organs,is essential for their therapeutic success.Here,we developed a therapeutic delivery system targeting internal organs,which features a mechanism akin to a snake’s jaw for grasping and deploying detachable microneedles(MNs)embedded with therapeutics.This solves the current challenges of delivering microneedle patches without open chest or abdominal wall surgery.We showed an example of this technology via delivering exosomes derived from mesenchymal stem cells(MSCs)directly to the heart’s damaged regions via percutaneous minimally invasive surgery.The shell of MNs is fabricated from methacrylated hyaluronic acid(MeHA),which ensures mechanical strength for myocardium penetration,while the hyaluronic acid(HA)core allows a sustained release of exo-somes.In a rat model of myocardial infarction(MI),the delivery of exosomes-loaded microneedles(XOs-MNs)resulted in angiomyogenesis and promoted cardiac function.The feasibility of this microneedle delivery method was also confirmed in a pig model.With its capability to encapsulate a wide range of therapeutic formulations,our system presents a versatile platform for the minimally invasive administration of treatments to internal organs.
基金supported by the National Key Research and Development Program of China(Grant Nos.2024YFC2208000,and 2023YFC2205800)the National Natural Science Foundation of China(Grant Nos.12021003,12474481,and 123B1015)+1 种基金the Fundamental Research Funds for the Central Universities(Grant Nos.310432103,and 310400209522)the JST ASPIRE Program of Japan(Grant No.JPMJAP2320)。
文摘Current gravitational-wave detectors have achieved remarkable sensitivity around 100 Hz,enabling ground-breaking discoveries.Enhancing sensitivity at higher frequencies in the kilohertz(kHz)range promises access to rich physics,particularly the extreme conditions during the merger stage of binary neutron stars.However,the high-frequency sensitivity of Michelson-based interferometers is fundamentally limited by their linear optical cavities,which are optimized for low-frequency signal enhancement.A new configuration employing an L-shaped optical resonator was proposed to overcome this limitation,offering exceptional sensitivity in the kHz band.As a pathfinder,the 12-meter prototype at Beijing Normal University is designed to demonstrate the sensing and control schemes of this new kHz detector configuration and to explore its performance in the high-power regime with suspended optics.Beyond its primary scientific goal,the prototype also offers potential sensitivity in the megahertz(MHz)range,potentially enabling constraints on exotic sources.This paper presents an overview of the prototype,including its optical design and current development status of key components.
基金This research was supported by the National Natural Science Foundation of China(Nos.41977300 and 41907297)the Science and Technology Program of Guangzhou(China)(No.202002020055)the Fujian Provincial Natural Science Foundation(China)(No.2020I1001).
文摘Anaerobic process is regarded as a green and sustainable process due to low carbon emission and minimal energy consumption in wastewater treatment plants(WWTPs).However,some water quality metrics are not measurable in real time,thus influencing the judgment of the operators and may increase energy consumption and carbon emission.One of the solutions is using a soft-sensor prediction technique.This article introduces a water quality soft-sensor prediction method based on Bidirectional Gated Recurrent Unit(BiGRU)combined with Gaussian Progress Regression(GPR)optimized by Tree-structured Parzen Estimator(TPE).TPE automatically optimizes the hyperparameters of BiGRU,and BiGRU is trained to obtain the point prediction with GPR for the interval prediction.Then,a case study applying this prediction method for an actual anaerobic process(2500 m^(3)/d)is carried out.Results show that TPE effectively optimizes the hyperparameters of BiGRU.For point prediction of CODeff and biogas yield,R^(2)values of BiGRU,which are 0.973 and 0.939,respectively,are increased by 1.03%–7.61%and 1.28%–10.33%,compared with those of other models,and the valid prediction interval can be obtained.Besides,the proposed model is assessed as a reliable model for anaerobic process through the probability prediction and reliable evaluation.It is expected to provide high accuracy and reliable water quality prediction to offer basis for operators in WWTPs to control the reactor and minimize carbon emission and energy consumption.
文摘Current contraceptive methods come with a number of drawbacks,including low efficacy,in the case of commercial contraceptive gels,and a reduction in the quality of sexual intercourse,in the case of condoms.Adding pharmacologically-active agents to contraceptive gels holds the potential to improve sexual experience,and hardbor safety and hygiene.In this study,we fabricated a carbomer-based contraceptive gel consisting of three agents:tenofovir,gossypol acetate,and nitroglycerin(TGN),with pH adjusted to 4.5(to be compatible with the vagina).In vitro,the gossypol component of the contraceptive gel proved to be an effective spermicide.When the concentration of gossypol acetate was 10 mg/ml,the spermicidal ability reached 100%after 30 s.In addition,tenofovir in the gel significantly inhibited lentiviral transfection efficiency in cell-containing media.In 6 pairs of rats,the gel successfully prevented all females from conceiving after successful mating.Moreover,increased sexual frequency and enhanced erection,which were promoted by the nitroglycerin in the components,were observed in male rats that had the gel applied to their penises.This novel TGN contraceptive gel yielded a higher contraceptive success rate than that of the commercial contraceptive gel(Contragel®).In addition,it has the added benefits to prevent sexually transmitted diseases and improve male libido and erectile function during sexual intercourse.Combining three FDA-approved and marketed agents together,our trifunctional TGN gel has a great potential for further translation and commercialization.
基金supported by grants from the National Institute of Health(1R01HL175373-01 to K.H.)the American Heart Association(21CDA855570 to K.H.)(24CDA1277521 to D.Z).
文摘Myocardial infarction(MI),commonly known as a heart attack,remains a leading cause of death worldwide.Standard treatments,such as coronary stent placement or coronary artery bypass graft surgery,aim to restore blood flow to ischemic myocardial tissue.However,a significant complication of these procedures is ischemia/reperfusion(I/R)injury,which occurs when blood flow is restored,triggering oxidative stress,inflammation,and calcium overload that can further damage the heart.To limit the I/R injury following the coronary recanalization of an MI heart,we designed stromal-platelet membrane-inspired nanoparticles(SPINs)that consist of a poly(lactic-co-glycolic acid)(PLGA)core,decorated by a dual membrane coating:a platelet membrane for precise adhesion to the damaged endothelium area and a stromal cell membrane to enhance receptor-ligand interactions and immune-evasiveness.This unique dual-membrane configuration synergistically reduces fibrosis and inflammation while promoting angiomyogenesis.This combination integrates the vascular injury targeting and immune-evasive properties of the nanoparticle,making this dual-membrane design a promising add-on intervention to augment post-percutaneous coronary intervention recovery,enhancing outcomes and offering potential improved cardiac repair.
基金This work was supported by the Beijing Dongcheng Department of Science,Technology,and Information(BJ-2019-103 to Shaowei Wang).
文摘Primary ovarian insufficiency(POI)is an ovarian dysfunction that affects more than 1%of women and is characterized by hormone imbalances that afflict women before the age of 40.The typical perimenopausal symptoms result from abnormal levels of sex hormones,especially estrogen.The most prevalent treatment is hormone replacement therapy(HRT),which can relieve symptoms and improve quality of life.However,HRT cannot restore ovarian functions,including secretion,ovulation,and fertility.Recently,as part of a developing field of regenerative medicine,stem cell therapy has been proposed for the treatment of POI.Thus,we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment,and sum up the underlying mechanisms of action.A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies.
基金NC State University,the National Natural Science Foundation of China(No.82200276)the Grant of Key Research and Development Program of Hebei Province(No.203777117D)+1 种基金the Key Project of Hebei Provincial Health Commission(Nos.20201159 and 20180224)the Natural Science Foundation of Hebei Province(Nos.H2021206399 and H2022206295)。
文摘Extracellular vesicles(EVs)generated from mesenchymal stem cells(MSCs)play an essential role in modulating cell–cell communication and tissue regeneration.The clinical translation of EVs is constrained by the poor yield of EVs.Extrusion has recently become an effective technique for producing a large scale of nanovesicles(NVs).In this study,we systematically compared MSC NVs(from extrusion)and EVs(from natural secretion).Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs.Additionally,microRNAs in NVs are related to cardiac repair,fibrosis repression,angiogenesis.Lastly,intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.310432103)the National Natural Science Foundation of China(Grant Nos.12073005,12021003,12021003,11920101003,and 11633001)+1 种基金the Interdiscipline Research Funds of Beijing Normal Universitythe Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB23000000)。
文摘Our Moon is by far the easiest natural, extraterrestrial celestial object for us to reach, and many space agencies, in particular the China National Space Administration, have publicized plans for manned missions there. Such high-profile projects must yield commensurate scientific outputs to justify their cost to the taxpayers. An important criterion for the selection of candidate experiments is the extent to which the Moon plays an integral and irreplaceable role, as opposed to offering only marginal advantages over Earth-orbit, space-based alternatives. In this study, we propose an experiment that excels in this regard, which considers the Moon as part of the experimental apparatus. Specifically, the Moon acts as a Weber bar-style resonant mass that responds to deci-Hertz gravitational waves(GWs). GW-excited lunar vibrations can be picked up by an array of(prefabricated on Earth and easy to transport to the Moon) small laser interferometric seismometers yielding GW detection. Such a setup would plug a gap in the GW frequency range already covered by the existing or underdevelopment detectors, and it can inform us on important astrophysics topics, such as the progenitors of Type Ia supernovae(SNe Ia) or intermediate mass black holes. We provide the instrument design as well as its deployment strategy, and we also summarize relevant science cases according to the estimated viable sensitivity.
基金supported by the American Heart Association(21CDA855570 to KH)JY is supported by Suzhou Youth Science and Technology Project(KJXW2023012 to JY)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20231198)the Jiangsu Province Health Care Development Special Fund(M2022038)。
文摘Chemotherapy-induced cardiotoxicity with subsequent heart failure(HF)is a major cause of morbidity and mortality in cancer survivors worldwide.Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation.To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF,we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive(MISA)that could be delivered locally through an endoscope-guided intrapericardial injection.To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients,we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections.In vitro,we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability,but also inhibited their apoptosis.In vivo,we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation,angiogenesis,and mitochondrial respiration.Additionally,we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system.In general,our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.
文摘This paper"Detecting gravitational wave with an interferometric seismometer array on lunar nearside"[1]was published in SCIENCE CHINA Physics,Mechanics&Astronomy(66,109513(2023),doi:10.1007/s11433-023-2179-9).Due to an oversight on our part,some errors were made in the originally published paper.We apologize for these errors and offer the corresponding explanations and corrections for the readers.
