This study uses a T-junction to examine the effects of different parameters(velocity ratio,viscosity,contact angle,and channel size ratio)on the generation of microdroplets,related rate,and size.More specifically,numer...This study uses a T-junction to examine the effects of different parameters(velocity ratio,viscosity,contact angle,and channel size ratio)on the generation of microdroplets,related rate,and size.More specifically,numerical simulations are exploited to investigate situations with a velocity varying from 0.004 to 1.6 m/s for the continuous phase and from 0.004 to 0.8 m/s for the dispersed phase,viscosity ratios(0.668,1,6.689,10,66.899),contact angle 80°<θ<270°and four different canal size ratios(1,1.5,2 and 4).The results show that canal size influences droplet size and the generation rate.The contact angle has an impact on the form and the quality of generated droplets.Moreover,the relationship between velocity and viscosity ratios,droplet size,and generation rate is non-monotonic.展开更多
AIM:To investigate the etiology of esophageal cancer among Taiwan Residents women.METHODS:This is a multi-center,hospital-based,case-control study.Case patients consisted of women who were newly diagnosed and patholog...AIM:To investigate the etiology of esophageal cancer among Taiwan Residents women.METHODS:This is a multi-center,hospital-based,case-control study.Case patients consisted of women who were newly diagnosed and pathology-proven to have esophageal squamous cell carcinoma(ESCC) from three large medical centers(one from Northern and two from Southern Taiwan,respectively)between August 2000 and December 2008.Each ESCC patient was matched with 4 healthy women based on age(within 3 years)and hospital of origin,from the Department of Preventive Medicine in each hospital.A total of 51 case patients and 204 controls,all women,were studied.RESULTS:Frequencies of smokers and drinkers among ESCC patients were 19.6%and 21.6%,respectively,which were significantly higher than smokers(4.4%) and drinkers(4.4%)among controls(OR=4.07,95%CI:1.36-12.16,P=0.01;OR=3.55,95%CI:1.03-12.27,P=0.04).Women who drank an amount of alcohol more than 158 g per week had a 20.58-fold greater risk(95%CI:1.72-245.62,P=0.02)of ESCC than those who never drank alcohol after adjusting for other covariates,although the sample size was small.CONCLUSION:Cigarette smoking and alcohol drinking,especially heavy drinking,are the major risks for developing ESCC in Taiwan Residents women.展开更多
In learning and memory studies on honeybees (Apis mellifera), cold-induced narcosis has been widely used to temporarily immobilize honeybees. In this study, we investigated the effects of cold narcosis on the associ...In learning and memory studies on honeybees (Apis mellifera), cold-induced narcosis has been widely used to temporarily immobilize honeybees. In this study, we investigated the effects of cold narcosis on the associative memories in honeybees by using the proboscis extension response (PER) paradigm. Severe impairments in memory acquisition was found when cold narcosis was performed 30 rain, instead of 1 h before training. Locomotor activities were reduced when honeybees were tested 15 min, instead of 30 rain after cold narcosis. These results indicate that cold narcosis impairs locomotor activities, as well as memory acquisition in a time-dependent manner, but by comparison no such effects on memory retrieval have yet been observed.[0]展开更多
Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties...Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties.The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers,however,tend to be insufficient.Herein,we report a strategy to prepare nucleobase-crosslinked POx nanoparticles(NPs)with enhanced stability and ultra-high paclitaxel(PTX)loading capacity for breast cancer therapy.An amphiphilic amine-functionalized POx(PMBEOx-NH_(2))was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly(2–butyl–2-oxazoline-co-2-butenyl-2-oxazoline)(PMBEOx).Complementary nucleobase-pairs adenine(A)and uracil(U)were subsequently conjugated to PMBEOx-NH2 to give functional POxs(POxA and POxU),respectively.Due to the nucleobase interactions formed between A and U,NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity(38.2%,PTX/POxA@U),excellent stability,and reduced particle size compared to the uncross-linked PTX-loaded NPs(PTX/PMBEOx).Besides the prolonged blood circulation and enhanced tumor accumulation,the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx,thus leading to a higher tumor suppression rate in two murine breast cancer models(E0711 and 4T1).These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.展开更多
This study proposes a convolutional neural network(CNN)-based identity recognition scheme using electrocardiogram(ECG)at different water temperatures(WTs)during bathing,aiming to explore the impact of ECG length on th...This study proposes a convolutional neural network(CNN)-based identity recognition scheme using electrocardiogram(ECG)at different water temperatures(WTs)during bathing,aiming to explore the impact of ECG length on the recognition rate.ECG data was collected using non-contact electrodes at five different WTs during bathing.Ten young student subjects(seven men and three women)participated in data collection.Three ECG recordings were collected at each preset bathtub WT for each subject.Each recording is 18 min long,with a sampling rate of 200 Hz.In total,150 ECG recordings and 150 WT recordings were collected.The R peaks were detected based on the processed ECG(baseline wandering eliminated,50-Hz hum removed,ECG smoothing and ECG normalization)and the QRS complex waves were segmented.These segmented waves were then transformed into binary images,which served as the datasets.For each subject,the training,validation,and test data were taken from the first,second,and third ECG recordings,respectively.The number of training and validation images was 84297 and 83734,respectively.In the test stage,the preliminary classification results were obtained using the trained CNN model,and the finer classification results were determined using the majority vote method based on the preliminary results.The validation rate was 98.71%.The recognition rates were 95.00%and 98.00%when the number of test heartbeats was 7 and 17,respectively,for each subject.展开更多
The mechanical properties of tissues and cells have proven to be of great importance in biology andmedicine,spawning major research efforts and commercial outcomes,The interplay bet ween mechanical andbiochemical cues...The mechanical properties of tissues and cells have proven to be of great importance in biology andmedicine,spawning major research efforts and commercial outcomes,The interplay bet ween mechanical andbiochemical cues and the mechanical properties of subellar and cellular constituents has come to beappreciated as key to umnderstanding many fundamental aspects of biology as well as the geneis andprogression of disease.展开更多
Spectroscopic measurements and terahertz imaging of the cornea are carried out by using a rapid scanning terahertz time domain spectroscopy(THz-TDS) system.A voice coil motor stage based optical delay line(VCM-ODL...Spectroscopic measurements and terahertz imaging of the cornea are carried out by using a rapid scanning terahertz time domain spectroscopy(THz-TDS) system.A voice coil motor stage based optical delay line(VCM-ODL) is developed to provide a rather simple and robust structure with both the high scanning speed and the large delay length.The developed system is used for THz spectroscopic measurements and imaging of the corneal tissue with different amounts of water content,and the measurement results show the consistence with the reported results,in which the measurement time using VCM-ODL is a factor of 360 shorter than the traditional motorized optical delay line(MDL).With reducing the water content a monotonic decrease of the complex permittivity of the cornea is observed.The two-term Debye relaxation model is employed to explain our experimental results,revealing that the fast relaxation time of a dehydrated cornea is much larger than that of a hydrated cornea and its dielectric behavior can be affected by the presence of the biological macromolecules.These results demonstrate that our THz spectrometer may be a promising candidate for tissue hydration sensing and practical application of THz technology.展开更多
The ability to precisely control activities of engineered designer cells provides a novel strategy for modern precision medicine.Dynamically adjustable gene-and cell-based precision therapies are recognized as next ge...The ability to precisely control activities of engineered designer cells provides a novel strategy for modern precision medicine.Dynamically adjustable gene-and cell-based precision therapies are recognized as next generation medicines.However,the translation of these controllable therapeutics into clinical practice is severely hampered by the lack of safe and highly specific genetic switches controlled by triggers that are nontoxic and side-effect free.Recently,natural products derived from plants have been extensively explored as trigger molecules to control genetic switches and synthetic gene networks for multiple applications.These controlled genetic switches could be further introduced into mammalian cells to obtain synthetic designer cells for adjustable and fine tunable cell-based precision therapy.In this review,we introduce various available natural molecules that were engineered to control genetic switches for controllable transgene expression,complex logic computation,and therapeutic drug delivery to achieve precision therapy.We also discuss current challenges and prospects in translating these natural molecule-controlled genetic switches developed for biomedical applications from the laboratory to the clinic.展开更多
Molecular hydrogen is an effective antioxidant.Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases.The possibility of using hydrogen in the treatment of ca...Molecular hydrogen is an effective antioxidant.Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases.The possibility of using hydrogen in the treatment of cancer was first discovered in 1975,and in recent studies,researchers have reported numerous positive effects of hydrogen in cancer therapy,including:1)the alleviation of complications caused by chemotherapy;2)a reduction of complications caused by radiotherapy;3)delays in the progression of cancer;and 4)enhanced efficacy of conventional therapy when used in combination with hydrogen.This article reviews the research progress in the use of hydrogen in the treatment of cancer,and proposes future directions for research in this field.展开更多
Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiven...Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.展开更多
Biomedical polymers are a kind of engineered materials used for disease diagnosis and treatment, tissue fixation,tissue or organ repair, or organ replacement to restore or enhance the related functions in humans.[1]Bi...Biomedical polymers are a kind of engineered materials used for disease diagnosis and treatment, tissue fixation,tissue or organ repair, or organ replacement to restore or enhance the related functions in humans.[1]Biomedical polymers are the earliest developed and most widely used materials in biomedicine and continue to evolve as an essential frontier field of polymer science in the 21century.With the development of molecular biology, cell biology.展开更多
Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient prol...Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.展开更多
Controlled synthesis is central to obtaining polymers with accurate structures and excellent performances.Recent research in the controlled synthesis of polymers has focused on optimizing monomers,initiation systems,a...Controlled synthesis is central to obtaining polymers with accurate structures and excellent performances.Recent research in the controlled synthesis of polymers has focused on optimizing monomers,initiation systems,and reaction conditions.The satisfactory sequence,topological structure,and dispersity have been achieved to satisfy the growing demand for functional polymers.This re-view summarizes the selection of monomers of various types and structures,the innovation of initiation systems,and the optimiza-tion of reaction conditions in the controlled synthesis of polymers and discusses their challenges and opportunities.展开更多
As a revolutionary cancer treatment strategy,immunotherapy has attracted great attention.However,the effect of immunotherapy such as immune checkpoint blockade(ICB)is usually limited by insufficient immune response in...As a revolutionary cancer treatment strategy,immunotherapy has attracted great attention.However,the effect of immunotherapy such as immune checkpoint blockade(ICB)is usually limited by insufficient immune response in the body.Herein,a polycation-based magnetic nanocluster platform was developed to load therapeutic nucleic acids,which could achieve gene therapy-mediated ICB and efficient magnetic hyperthermia therapy(MHT).The silencing of immune checkpoints together with MHT-induced immunogenic cell death(ICD)effectively alleviated the immune escape of cancer cells and significantly enhanced the visibility of cancer cells to the immune system.This combined treatment strategy activated a strong adaptive anti-cancer immune response in vivo,greatly inhibiting tumor growth,metastasis and recurrence.展开更多
Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polyme...Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polymeric nanoparticles(CA4P NPs)consisting of various cholesterol derivatives,and with a drug loading efficacy of 93%.The nanoparticles released CA4P in a sustained manner and achieved a 72%inhibition rate in the murine H22 liver tumor model,which was about 2.9-fold higher than that of free CA4P(24.6%).Furthermore,the carrier components of CA4P NPs were metabolized to arginine,cholesterol,ethanol and poly(ethylene glycol)in vivo;therefore,the CA4P NPs are safe and have significant potential for clinical translation.展开更多
Top-down attention mechanisms require the selection of specificobjects or locations;however,the brain mechanism involved when attention is allocated across different modalities is not well understood.The aim of this s...Top-down attention mechanisms require the selection of specificobjects or locations;however,the brain mechanism involved when attention is allocated across different modalities is not well understood.The aim of this study was to use functional magnetic resonance imaging to define the neural mechanisms underlyingdivided and selective spatial attention.A concurrent audiovisual stimulus was used,and subjects were prompted to focus on a visual,auditory and audiovisual stimulus in a Posner paradigm.Ourbehavioral results confirmed the better performance of selectiveattention compared to devided attention.We found differences in the activation level of the frontoparietal network,visual/auditorycortex,the putamen and the salience network under differentattention conditions.We further used Granger causality(GC)toexplore effective connectivity differences between tasks.Differences in GC connectivity between visual and auditory selective tasksreflected the visual dominance effect under spatial attention.In addition,our results supported the role of the putamen inredistributing attention and the functional separation of the saliencenetwork.In summary,we explored the audiovisual top-down allocation of attention and observed the differences in neuralmechanisms under endogenous attention modes,which revealedthe differences in cross-modal expression in visual and auditory attention under attentional modulation.展开更多
Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenge...Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenges.To this end,we developed a cRGD-decorated pH-responsive polyion complex(PIC)micelle for intracellular targeted delivery of doxorubicin(DOX)to upregulate tumor inhibition and reduce toxicity.The PIC micelle was self-assembled via the electrostatic interaction between the positively charged cRGD-modified poly(ethylene glycol)-block-poly(L-lysine)and the anionic acid-sensitive 2,3-dimethylmaleic anhydride-modified doxorubicin(DAD).The decoration of cRGD enhanced the cell internalization of PIC micelle through the specific recognition ofαvβ3 integrin on the membrane of tumor cells.The active DOX was released under intracellular acidic microenvironment after endocytosis following the decomposition of DAD.Moreover,the targeted PIC micelle exhibited enhanced inhibition efficacies toward hepatoma in vitro and in vivo compared with the insensitive controls.The smart multifunctional micelle provides a promising platform for target intracellular delivery of therapeutic agent in cancer therapy.展开更多
文摘This study uses a T-junction to examine the effects of different parameters(velocity ratio,viscosity,contact angle,and channel size ratio)on the generation of microdroplets,related rate,and size.More specifically,numerical simulations are exploited to investigate situations with a velocity varying from 0.004 to 1.6 m/s for the continuous phase and from 0.004 to 0.8 m/s for the dispersed phase,viscosity ratios(0.668,1,6.689,10,66.899),contact angle 80°<θ<270°and four different canal size ratios(1,1.5,2 and 4).The results show that canal size influences droplet size and the generation rate.The contact angle has an impact on the form and the quality of generated droplets.Moreover,the relationship between velocity and viscosity ratios,droplet size,and generation rate is non-monotonic.
基金Supported by Grants from Kaohsiung Medical University Hospital(KMUH96-6G04)National Science Council(NSC 98-2918-I-037-001 and NSC 97-2314-B-037-018-MY3)
文摘AIM:To investigate the etiology of esophageal cancer among Taiwan Residents women.METHODS:This is a multi-center,hospital-based,case-control study.Case patients consisted of women who were newly diagnosed and pathology-proven to have esophageal squamous cell carcinoma(ESCC) from three large medical centers(one from Northern and two from Southern Taiwan,respectively)between August 2000 and December 2008.Each ESCC patient was matched with 4 healthy women based on age(within 3 years)and hospital of origin,from the Department of Preventive Medicine in each hospital.A total of 51 case patients and 204 controls,all women,were studied.RESULTS:Frequencies of smokers and drinkers among ESCC patients were 19.6%and 21.6%,respectively,which were significantly higher than smokers(4.4%) and drinkers(4.4%)among controls(OR=4.07,95%CI:1.36-12.16,P=0.01;OR=3.55,95%CI:1.03-12.27,P=0.04).Women who drank an amount of alcohol more than 158 g per week had a 20.58-fold greater risk(95%CI:1.72-245.62,P=0.02)of ESCC than those who never drank alcohol after adjusting for other covariates,although the sample size was small.CONCLUSION:Cigarette smoking and alcohol drinking,especially heavy drinking,are the major risks for developing ESCC in Taiwan Residents women.
基金supported by the National Science Foundation of China(91132307)the K.C.Wong Education Foundation,Hong Kong
文摘In learning and memory studies on honeybees (Apis mellifera), cold-induced narcosis has been widely used to temporarily immobilize honeybees. In this study, we investigated the effects of cold narcosis on the associative memories in honeybees by using the proboscis extension response (PER) paradigm. Severe impairments in memory acquisition was found when cold narcosis was performed 30 rain, instead of 1 h before training. Locomotor activities were reduced when honeybees were tested 15 min, instead of 30 rain after cold narcosis. These results indicate that cold narcosis impairs locomotor activities, as well as memory acquisition in a time-dependent manner, but by comparison no such effects on memory retrieval have yet been observed.[0]
基金financially supported by the National Natural Science Foundation of China (51973215, 52025035, 52103194, 22105199, 51829302)Bureau of International Cooperation Chinese Academy of Science (121522KYSB20200029)the Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)
文摘Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties.The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers,however,tend to be insufficient.Herein,we report a strategy to prepare nucleobase-crosslinked POx nanoparticles(NPs)with enhanced stability and ultra-high paclitaxel(PTX)loading capacity for breast cancer therapy.An amphiphilic amine-functionalized POx(PMBEOx-NH_(2))was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly(2–butyl–2-oxazoline-co-2-butenyl-2-oxazoline)(PMBEOx).Complementary nucleobase-pairs adenine(A)and uracil(U)were subsequently conjugated to PMBEOx-NH2 to give functional POxs(POxA and POxU),respectively.Due to the nucleobase interactions formed between A and U,NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity(38.2%,PTX/POxA@U),excellent stability,and reduced particle size compared to the uncross-linked PTX-loaded NPs(PTX/PMBEOx).Besides the prolonged blood circulation and enhanced tumor accumulation,the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx,thus leading to a higher tumor suppression rate in two murine breast cancer models(E0711 and 4T1).These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.
基金This study is supported in part by the University of Aizu’s Competitive Research Fund(2020-P-24)。
文摘This study proposes a convolutional neural network(CNN)-based identity recognition scheme using electrocardiogram(ECG)at different water temperatures(WTs)during bathing,aiming to explore the impact of ECG length on the recognition rate.ECG data was collected using non-contact electrodes at five different WTs during bathing.Ten young student subjects(seven men and three women)participated in data collection.Three ECG recordings were collected at each preset bathtub WT for each subject.Each recording is 18 min long,with a sampling rate of 200 Hz.In total,150 ECG recordings and 150 WT recordings were collected.The R peaks were detected based on the processed ECG(baseline wandering eliminated,50-Hz hum removed,ECG smoothing and ECG normalization)and the QRS complex waves were segmented.These segmented waves were then transformed into binary images,which served as the datasets.For each subject,the training,validation,and test data were taken from the first,second,and third ECG recordings,respectively.The number of training and validation images was 84297 and 83734,respectively.In the test stage,the preliminary classification results were obtained using the trained CNN model,and the finer classification results were determined using the majority vote method based on the preliminary results.The validation rate was 98.71%.The recognition rates were 95.00%and 98.00%when the number of test heartbeats was 7 and 17,respectively,for each subject.
文摘The mechanical properties of tissues and cells have proven to be of great importance in biology andmedicine,spawning major research efforts and commercial outcomes,The interplay bet ween mechanical andbiochemical cues and the mechanical properties of subellar and cellular constituents has come to beappreciated as key to umnderstanding many fundamental aspects of biology as well as the geneis andprogression of disease.
基金Project supported by the National Natural Science Foundation of China(Grant No.61205101)the Shenzhen Municipal Research Foundation,China(Grant Nos.GJHZ201404171134305 and JCYJ20140417113130693)the Marie Curie Actions-International Research Staff Exchange Scheme(IRSES)(Grant No.FP7 PIRSES-2013-612267)
文摘Spectroscopic measurements and terahertz imaging of the cornea are carried out by using a rapid scanning terahertz time domain spectroscopy(THz-TDS) system.A voice coil motor stage based optical delay line(VCM-ODL) is developed to provide a rather simple and robust structure with both the high scanning speed and the large delay length.The developed system is used for THz spectroscopic measurements and imaging of the corneal tissue with different amounts of water content,and the measurement results show the consistence with the reported results,in which the measurement time using VCM-ODL is a factor of 360 shorter than the traditional motorized optical delay line(MDL).With reducing the water content a monotonic decrease of the complex permittivity of the cornea is observed.The two-term Debye relaxation model is employed to explain our experimental results,revealing that the fast relaxation time of a dehydrated cornea is much larger than that of a hydrated cornea and its dielectric behavior can be affected by the presence of the biological macromolecules.These results demonstrate that our THz spectrometer may be a promising candidate for tissue hydration sensing and practical application of THz technology.
基金the National Natural Science Foundation of China(NSFC:no.32250010,no.31971346,no.32261160373)the Science and Technology Commission of Shanghai Municipality(no.22N31900300)the Fundamental Research Funds for the Central Universities to H.Y.
文摘The ability to precisely control activities of engineered designer cells provides a novel strategy for modern precision medicine.Dynamically adjustable gene-and cell-based precision therapies are recognized as next generation medicines.However,the translation of these controllable therapeutics into clinical practice is severely hampered by the lack of safe and highly specific genetic switches controlled by triggers that are nontoxic and side-effect free.Recently,natural products derived from plants have been extensively explored as trigger molecules to control genetic switches and synthetic gene networks for multiple applications.These controlled genetic switches could be further introduced into mammalian cells to obtain synthetic designer cells for adjustable and fine tunable cell-based precision therapy.In this review,we introduce various available natural molecules that were engineered to control genetic switches for controllable transgene expression,complex logic computation,and therapeutic drug delivery to achieve precision therapy.We also discuss current challenges and prospects in translating these natural molecule-controlled genetic switches developed for biomedical applications from the laboratory to the clinic.
基金supported by the Major State Basic Research Development Program(2015CB856302,2015CB553602)the National Natural Science Foundation of China(31870848,81741110,81802787)the Natural Science Foundation of Shaanxi(2018JZ3005).
文摘Molecular hydrogen is an effective antioxidant.Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases.The possibility of using hydrogen in the treatment of cancer was first discovered in 1975,and in recent studies,researchers have reported numerous positive effects of hydrogen in cancer therapy,including:1)the alleviation of complications caused by chemotherapy;2)a reduction of complications caused by radiotherapy;3)delays in the progression of cancer;and 4)enhanced efficacy of conventional therapy when used in combination with hydrogen.This article reviews the research progress in the use of hydrogen in the treatment of cancer,and proposes future directions for research in this field.
基金supported by the National Natural Science Foundation of China (22222509, 52025035, 52103194, and 22105199)The Ministry of Science and Technology of China (2022YFE0110200)+3 种基金Bureau of International Cooperation Chinese Academy of Sciences (121522KYSB20200029)Jilin Province Science and Technology Development Plan (YDZJ202101ZYTS131, 20220402037GH, and 20210508049RQ)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (20210504001GH)The Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)。
文摘Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.
文摘Biomedical polymers are a kind of engineered materials used for disease diagnosis and treatment, tissue fixation,tissue or organ repair, or organ replacement to restore or enhance the related functions in humans.[1]Biomedical polymers are the earliest developed and most widely used materials in biomedicine and continue to evolve as an essential frontier field of polymer science in the 21century.With the development of molecular biology, cell biology.
基金supported by the National Natural Science Foundation of China(Nos.52025035,51873206 and 52203198)the Project of Health research talents Project of Jilin Province(No.2020SCZ06)+1 种基金the Project of Jilin Province Development and Reform Commission(No.2021C043-6)the Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(No.20210504001GH).
文摘Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.
基金financially supported by the National Natural Science Foundation of China(52222307,51803072,and 51833010)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(20210504001GH)。
基金supported by the National Key Research and Development Program(Nos.2022YFC2603500,2021YFC2400600)the National Natural Science Foundation of China(Nos.52273158,U21A2099,52022095,52073280,51973216)+2 种基金the Science and Technology Development Program of Jjilin Province(Nos.20220204018YY,20210509005RQ,20210504001GH,20200404182YY)the Special Project for City-Academy Scientific and Technological Innovation Cooperation of Changchun(No.21SH14)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2019230).
文摘Controlled synthesis is central to obtaining polymers with accurate structures and excellent performances.Recent research in the controlled synthesis of polymers has focused on optimizing monomers,initiation systems,and reaction conditions.The satisfactory sequence,topological structure,and dispersity have been achieved to satisfy the growing demand for functional polymers.This re-view summarizes the selection of monomers of various types and structures,the innovation of initiation systems,and the optimiza-tion of reaction conditions in the controlled synthesis of polymers and discusses their challenges and opportunities.
基金The authors are thankful to National Natural Science Foundation of China(Nos.51925305,51873208,51833010,and 52203183)the National Key Research and Development Program of China(No.2021YFB3800900)the talent cultivation project Funds for the Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(No.HRTP-[2022]52).
文摘As a revolutionary cancer treatment strategy,immunotherapy has attracted great attention.However,the effect of immunotherapy such as immune checkpoint blockade(ICB)is usually limited by insufficient immune response in the body.Herein,a polycation-based magnetic nanocluster platform was developed to load therapeutic nucleic acids,which could achieve gene therapy-mediated ICB and efficient magnetic hyperthermia therapy(MHT).The silencing of immune checkpoints together with MHT-induced immunogenic cell death(ICD)effectively alleviated the immune escape of cancer cells and significantly enhanced the visibility of cancer cells to the immune system.This combined treatment strategy activated a strong adaptive anti-cancer immune response in vivo,greatly inhibiting tumor growth,metastasis and recurrence.
基金financially supported by the Ministry of Science and Technology of China(No.2022YFE0110200)the Natural Science Foundation of Hunan Province of China(No.2021JJ30680)the National Natural Science Foundation of China(Nos.52203198,52025035 and 52103195)。
文摘Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polymeric nanoparticles(CA4P NPs)consisting of various cholesterol derivatives,and with a drug loading efficacy of 93%.The nanoparticles released CA4P in a sustained manner and achieved a 72%inhibition rate in the murine H22 liver tumor model,which was about 2.9-fold higher than that of free CA4P(24.6%).Furthermore,the carrier components of CA4P NPs were metabolized to arginine,cholesterol,ethanol and poly(ethylene glycol)in vivo;therefore,the CA4P NPs are safe and have significant potential for clinical translation.
基金The study was supported by the National Natural Science Foundation of China(Grant Nos.62171300,61727807).
文摘Top-down attention mechanisms require the selection of specificobjects or locations;however,the brain mechanism involved when attention is allocated across different modalities is not well understood.The aim of this study was to use functional magnetic resonance imaging to define the neural mechanisms underlyingdivided and selective spatial attention.A concurrent audiovisual stimulus was used,and subjects were prompted to focus on a visual,auditory and audiovisual stimulus in a Posner paradigm.Ourbehavioral results confirmed the better performance of selectiveattention compared to devided attention.We found differences in the activation level of the frontoparietal network,visual/auditorycortex,the putamen and the salience network under differentattention conditions.We further used Granger causality(GC)toexplore effective connectivity differences between tasks.Differences in GC connectivity between visual and auditory selective tasksreflected the visual dominance effect under spatial attention.In addition,our results supported the role of the putamen inredistributing attention and the functional separation of the saliencenetwork.In summary,we explored the audiovisual top-down allocation of attention and observed the differences in neuralmechanisms under endogenous attention modes,which revealedthe differences in cross-modal expression in visual and auditory attention under attentional modulation.
基金financially supported by the National Natural Science Foundation of China(Nos.51973216,51873207,51833010,51703225,51673190,51673187,51603204 and 51520105004)the Science and Technology Development Program of Jilin Province(No.20190201068JC)+2 种基金the National Key Research and Development Program of China(No.2016YFC1100701)the Youth Talents Promotion Project of Jilin Province(No.181909)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019005)。
文摘Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenges.To this end,we developed a cRGD-decorated pH-responsive polyion complex(PIC)micelle for intracellular targeted delivery of doxorubicin(DOX)to upregulate tumor inhibition and reduce toxicity.The PIC micelle was self-assembled via the electrostatic interaction between the positively charged cRGD-modified poly(ethylene glycol)-block-poly(L-lysine)and the anionic acid-sensitive 2,3-dimethylmaleic anhydride-modified doxorubicin(DAD).The decoration of cRGD enhanced the cell internalization of PIC micelle through the specific recognition ofαvβ3 integrin on the membrane of tumor cells.The active DOX was released under intracellular acidic microenvironment after endocytosis following the decomposition of DAD.Moreover,the targeted PIC micelle exhibited enhanced inhibition efficacies toward hepatoma in vitro and in vivo compared with the insensitive controls.The smart multifunctional micelle provides a promising platform for target intracellular delivery of therapeutic agent in cancer therapy.