Tumor blockade therapy inhibits tumor progression by cutting off essential supplies of nutrients,oxygen,and biomolecules from the surrounding microenvironments.Inspired by natural processes,tumor biomineralization has...Tumor blockade therapy inhibits tumor progression by cutting off essential supplies of nutrients,oxygen,and biomolecules from the surrounding microenvironments.Inspired by natural processes,tumor biomineralization has evolved due to its biocompatibility,self-reinforcing capability,and penetrationindependent mechanism.However,the selective induction of tumor biomineralization using synthetic tools presents a significant challenge.Herein,a metabolic glycoengineering-assistant tumor biomineralization strategy was developed.Specifically,the azido group(N_(3))was introduced onto the cytomembrane by incubating tumor cells with glycose analog Ac4ManNAz.In addition,a bisphosphonate-containing polymer,dibenzocyclooctyne-poly(ethylene glycol)-alendronate(DBCO-PEG-ALN,DBPA)was synthesized,which attached to the tumor cell surface via"click chemistry"reaction between DBCO and N_(3).Subsequently,the bisphosphonate group on the cell surface chelated with positively charged ions in the microenvironments,triggering a consecutive process of biomineralization.This physical barrier significantly reduced tumor cell viability and mobility in a calcium ion concentration-dependent manner,suggesting its potential as an effective anti-tumor strategy for in vivo applications.展开更多
BACKGROUND Data suggest that elderly patients may have a lower risk of complications after endoscopic retrograde cholangiopancreatography(ERCP),especially post-ERCP pancreatitis(PEP).AIM To validate these findings in ...BACKGROUND Data suggest that elderly patients may have a lower risk of complications after endoscopic retrograde cholangiopancreatography(ERCP),especially post-ERCP pancreatitis(PEP).AIM To validate these findings in a large,real-world clinical setting.METHODS Clinical,epidemiological,and procedural data collected from a prospectively maintained database were gathered over a 20-year period(2001-2021)from consecutive patients undergoing their first ERCP.Patients were grouped based on age:<80 years and≥80 years.RESULTS A total of 3147 patients were included in the study,with 70.3%<80 years old and 28.7%≥80 years.The most common indication for ERCP was biliary colic with or without elevated liver enzymes(39.6%).Periampullary diverticula were more frequently observed in elderly patients(P<0.001).Successful cannulation of the common bile duct was achieved in 96.1%of cases and did not differ significantly between age groups(P=0.148).Complete common bile duct clearance during the first ERCP was accomplished in 90.1%,and stone size was the only independent predictor of success.Use of antiplatelet or anticoagulant therapy was independently associated with intraprocedural bleeding(odds ratio[OR]=1.333;P=0.03 and OR=1.275;P=0.041,respectively).Overall,post-ERCP complications occurred in 6%of cases,with similar rates between elderly and younger patients.The most common complication was PEP.The incidences of clinical bleeding and PEP did not differ significantly between groups(P=0.290 and P=0.128,respectively).Clinical bleeding was independently associated with anticoagulant use and intraprocedural bleeding.CONCLUSION Our findings highlight that elderly patients do not experience higher complication rates or lower success rates with ERCP,supporting the procedure’s safety and efficacy in this population.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
Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children...Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.展开更多
The development of large-scale cell cultivation and non-invasive cell harvesting is highly desired in various fields,including biological regeneration and pharmaceutical research.When using traditional microcarriers f...The development of large-scale cell cultivation and non-invasive cell harvesting is highly desired in various fields,including biological regeneration and pharmaceutical research.When using traditional microcarriers for cell culture,trypsinization is often necessary during cell collection,leading to partial cells damage.In this work,we developed a thermoresponsive glass microcarrier modified with poly(γ-propargyl-L-glutamate)(PPLG)and poly(N-isopropylacrylamide)(PNIPAM).We utilized these microcarriers for three-dimensional cell culture and enzyme-free cell harvesting,and the results indicated that the prepared microcarriers exhibited excellent non-invasive cell culture performance.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
Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)...Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)of α-amino acid N-carboxyanhydrides(NCAs)by Leuchs and Hermann in 1906.In the past decades,several effective strategies,including the selection of initiators,the adjustment of reaction conditions,and the introduction of catalysts,have been reported to improve the controllability of the ROP of various a-amino acid NCAs to synthesize different polypeptides with precise chemical structures and low polydispersity indexes.In this Review,the strategies,mechanisms,challenges,and opportunities for controlled synthesis of polypeptides by the ROP of differentα-amino acid NCAs have been declared.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
Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to c...Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene co-delivery.PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa ration.All steps could be finished within 30 min.Such simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined treatments.In addition,the pH responsive delivery system reduced the side effects triggered by anti-PD therapy.The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.展开更多
Stimuli-re sponsive polypeptides have been intensively investigated fo r controlled drug release,owing to their favorable biocompatibility and biodegradability.In this work,we designed and synthesized a new kind of po...Stimuli-re sponsive polypeptides have been intensively investigated fo r controlled drug release,owing to their favorable biocompatibility and biodegradability.In this work,we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species(ROS)-responsive drug release.The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization(ROP)of 1,4-dithian-substituted L-glutamate N-carboxyanhydride(DTG-NCA)monomer using an amino-terminated poly(ethylene glycol)methyl ether(mPEG-NH2)as the macro molecular initiator.The resulta nt block copolyme r,mPEG-b-PDTG,could self-assemble into unifo rm micelles in aqueous medium owing to its amphiphilic structure.Then,the H2 O2-triggered oxidation behaviors of the mPEG-b-PDTG micelles were studied by dynamic light scattering(DLS),FT-IR and turbidimetric assay.It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles.Furthermore,the ROS-responsive drug release behavior of the mPEG-b-PDTG micelles was verified by using Nile Red as a model drug.MTT assay also proved that mPEG-b-PDTG was non-toxic in B16 F10 and L929 cells.Therefore,such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery.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
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
Morphine can modulate the processes underlying memory in vertebrates. However, studies have shown various modulations by morphine： positive, negative and even neutral. The honeybee is a potential platform for evaluat...Morphine can modulate the processes underlying memory in vertebrates. However, studies have shown various modulations by morphine： positive, negative and even neutral. The honeybee is a potential platform for evaluating the effects of drugs, especially addictive drugs, on the nervous system. However, the involvement of morphine in learning and memory in insects or other invertebrates is poorly understood. The current work evaluated whether morphine affects memory acquisition, consolidation and retrieval in honeybees, using the proboscis extension response （PER） paradigm. We demonstrated that morphine treatment （5 pg/bee） before training decreased the percentage of correct PERs and the response latency related to aversive rather than rewarding odors when tested after 1 or 24 h. Morphine treatment after training also caused a decrease in this latency when tested after 24 h. Meanwhile, morphine treatment reduced the ambulation distance when tested after 30 min. Our findings suggest that morphine impairs the acquisition of shortand long-term associative memory and slightly disrupts the consolidation of long-term memory in honeybees. These negative effects cannot be explained by reduced locomotion but by impaired memory associated with aversion.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
The effect of exogenous hydroxyl,carboxyl groups and/or Sn^(2+) on pyrolysis reactions of poly(L-lactide)(PLLA)was investigated by thermogravimetric analysis(TGA).The activation energy(fa)of pyrolysis reactions was es...The effect of exogenous hydroxyl,carboxyl groups and/or Sn^(2+) on pyrolysis reactions of poly(L-lactide)(PLLA)was investigated by thermogravimetric analysis(TGA).The activation energy(fa)of pyrolysis reactions was estimated by the Kissinger-Akahira-Sunose method.The kinetic models were also explored by the Malek method,and the random degradation behavior was determined by comparing the plots of ln{-ln[1-(1-w)05]}versus 1/7for experimental data from TGA with model reactions.The pyrolysis reaction rate of PLLA was affected slightly by exogenous hydroxyl and carboxyl groups at lower levels of Sn with 65-70 mg·kg^(-1)but increased appreciably in the presence of extraneous Sn^(2+),-COOH/Sn^(2+),or-OH/Sn^(2+).The Ea values for the pyrolysis reactions of the PLLAs that provided lactide were different under the catalysis of Sn2+in different chemical environments because Sn^(2+) can form the new Sn-carboxylate and Sn-alkoxide with exogenous carboxyl and hydroxyl groups,which were different in steric hindrance for the formation of activated complex between Sn^(2+) and PLLA.Under the catalysis of Sn^(2+),a lactide molecule can be directly eliminated selectively at a random position of PLLA molecular chains,and the molecular chain of PLLA cannot change two PLLA fragments at the elimination site of lactide.However,it was regenerated into a new PLLA molecule with the molecular weight reduced by 144 g·mol^(-1).展开更多
The effect of the architecture of poly(ethylene glycol)/poly(L-lactide)(PEG/PLLA) block copolymers on the non-isothermal crystallization behaviors of PLLA blocks was investigated by differential scanning calorimetry(D...The effect of the architecture of poly(ethylene glycol)/poly(L-lactide)(PEG/PLLA) block copolymers on the non-isothermal crystallization behaviors of PLLA blocks was investigated by differential scanning calorimetry(DSC) and wide angle X-ray diffraction(WAXD). 1-Arm MPEG-b-PLLA and 4-arm PEG-b-PLLA(4PEG-b-PLLA) were synthesized by the ring-opening polymerization of Llactide in the presence of poly(ethylene glycol) methyl ether(MPEG) and 4-arm poly(ethylene glycol)(4PEG). 4-Arm PLLA-b-MPEG(4PLLA-b-PEG) was synthesized by coupling 4-arm PLLA and MPEG. The WAXD results indicated that the crystalline structure of PLLA blocks did not alter due to the different chain architectures. The average values of Avrami index(ˉn) were all above 4, which indicated that the nucleation mechanism of PLLA blocks was heterogeneous nucleation, regardless of the architectures. The overall crystallization rates were decreased markedly as following: MPEG-b-PLLA > 4PEG-b-PLLA > 4PLLA-b-PEG, ascribed to the different confinement by PEG blocks and to the steric hindrance of chain architectures. Therefore, the crystallization of PLLA blocks became more difficult and the crystallization activation energy of the PLLA blocks increased due to the confinement of chain architectures.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
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
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
基金supported by the National Natural Science Foundation of China(Nos.U23A20591 and 52273158)the Science and Technology Development Program of Jilin Province(Nos.20240101002JJ and 20210504001GH).
文摘Tumor blockade therapy inhibits tumor progression by cutting off essential supplies of nutrients,oxygen,and biomolecules from the surrounding microenvironments.Inspired by natural processes,tumor biomineralization has evolved due to its biocompatibility,self-reinforcing capability,and penetrationindependent mechanism.However,the selective induction of tumor biomineralization using synthetic tools presents a significant challenge.Herein,a metabolic glycoengineering-assistant tumor biomineralization strategy was developed.Specifically,the azido group(N_(3))was introduced onto the cytomembrane by incubating tumor cells with glycose analog Ac4ManNAz.In addition,a bisphosphonate-containing polymer,dibenzocyclooctyne-poly(ethylene glycol)-alendronate(DBCO-PEG-ALN,DBPA)was synthesized,which attached to the tumor cell surface via"click chemistry"reaction between DBCO and N_(3).Subsequently,the bisphosphonate group on the cell surface chelated with positively charged ions in the microenvironments,triggering a consecutive process of biomineralization.This physical barrier significantly reduced tumor cell viability and mobility in a calcium ion concentration-dependent manner,suggesting its potential as an effective anti-tumor strategy for in vivo applications.
文摘BACKGROUND Data suggest that elderly patients may have a lower risk of complications after endoscopic retrograde cholangiopancreatography(ERCP),especially post-ERCP pancreatitis(PEP).AIM To validate these findings in a large,real-world clinical setting.METHODS Clinical,epidemiological,and procedural data collected from a prospectively maintained database were gathered over a 20-year period(2001-2021)from consecutive patients undergoing their first ERCP.Patients were grouped based on age:<80 years and≥80 years.RESULTS A total of 3147 patients were included in the study,with 70.3%<80 years old and 28.7%≥80 years.The most common indication for ERCP was biliary colic with or without elevated liver enzymes(39.6%).Periampullary diverticula were more frequently observed in elderly patients(P<0.001).Successful cannulation of the common bile duct was achieved in 96.1%of cases and did not differ significantly between age groups(P=0.148).Complete common bile duct clearance during the first ERCP was accomplished in 90.1%,and stone size was the only independent predictor of success.Use of antiplatelet or anticoagulant therapy was independently associated with intraprocedural bleeding(odds ratio[OR]=1.333;P=0.03 and OR=1.275;P=0.041,respectively).Overall,post-ERCP complications occurred in 6%of cases,with similar rates between elderly and younger patients.The most common complication was PEP.The incidences of clinical bleeding and PEP did not differ significantly between groups(P=0.290 and P=0.128,respectively).Clinical bleeding was independently associated with anticoagulant use and intraprocedural bleeding.CONCLUSION Our findings highlight that elderly patients do not experience higher complication rates or lower success rates with ERCP,supporting the procedure’s safety and efficacy in this population.
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(82171001,82222015)Research Funding from West China School/Hospital of Stomatology Sichuan University(RCDWJS2023-1)Align Technology Specialized Scientific Research Fund(21H0922).
文摘Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.
基金supported by the name of National Key Research and Development Program of China(No.2021YFB3800900)the National Natural Science Foundation of China(Nos.51925305,51873208,1833010,51973217,52373161)Jilin Province Science and Technology Development Program(No.20200201075JC)。
文摘The development of large-scale cell cultivation and non-invasive cell harvesting is highly desired in various fields,including biological regeneration and pharmaceutical research.When using traditional microcarriers for cell culture,trypsinization is often necessary during cell collection,leading to partial cells damage.In this work,we developed a thermoresponsive glass microcarrier modified with poly(γ-propargyl-L-glutamate)(PPLG)and poly(N-isopropylacrylamide)(PNIPAM).We utilized these microcarriers for three-dimensional cell culture and enzyme-free cell harvesting,and the results indicated that the prepared microcarriers exhibited excellent non-invasive cell culture performance.
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.
基金the financial support from the National Natural Science Foundation of China(Nos.51973216,51873207,51803006,51833010,51673190 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Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)of α-amino acid N-carboxyanhydrides(NCAs)by Leuchs and Hermann in 1906.In the past decades,several effective strategies,including the selection of initiators,the adjustment of reaction conditions,and the introduction of catalysts,have been reported to improve the controllability of the ROP of various a-amino acid NCAs to synthesize different polypeptides with precise chemical structures and low polydispersity indexes.In this Review,the strategies,mechanisms,challenges,and opportunities for controlled synthesis of polypeptides by the ROP of differentα-amino acid NCAs have been declared.
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.
基金The authors are thankful to the National Natural Science Foundation of China(Nos.51925305,51803210,51520105004,51873208,51973217 and 51833010)Jilin province science and technology development program(Nos.20200201075JC,20180414027GH)National Science and Technology Major Projects for Major New Drugs Innovation and Development(No.2018ZX09711003-012).
文摘Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene co-delivery.PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa ration.All steps could be finished within 30 min.Such simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined treatments.In addition,the pH responsive delivery system reduced the side effects triggered by anti-PD therapy.The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.
基金financially supported by National Key Research and Development Program of China(No.2016YFC1100701)the National Natural Science Foundation of China(Nos.51573184,51520105004 and 51833010)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2017266)。
文摘Stimuli-re sponsive polypeptides have been intensively investigated fo r controlled drug release,owing to their favorable biocompatibility and biodegradability.In this work,we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species(ROS)-responsive drug release.The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization(ROP)of 1,4-dithian-substituted L-glutamate N-carboxyanhydride(DTG-NCA)monomer using an amino-terminated poly(ethylene glycol)methyl ether(mPEG-NH2)as the macro molecular initiator.The resulta nt block copolyme r,mPEG-b-PDTG,could self-assemble into unifo rm micelles in aqueous medium owing to its amphiphilic structure.Then,the H2 O2-triggered oxidation behaviors of the mPEG-b-PDTG micelles were studied by dynamic light scattering(DLS),FT-IR and turbidimetric assay.It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles.Furthermore,the ROS-responsive drug release behavior of the mPEG-b-PDTG micelles was verified by using Nile Red as a model drug.MTT assay also proved that mPEG-b-PDTG was non-toxic in B16 F10 and L929 cells.Therefore,such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery.
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 grants from the Training Program for Young Backbone Teachers of Yunnan University, the Research Foundation of Yunnan University (2011YB22)the Natural Science Foundation of Yunnan Province, China (2011FZ012)+5 种基金the Special Fund of the "211" Third Phase Project of Yunnan University (21134018)a National Project (2007ZDGGKVST003)a Provincial National Project (2008CA012-5)National Basic Research Development Program (973 program) of China (2012CB825500, 2011CB70780)National Natural Science Foundation of China (31271168)"Strategic Priority Research Program" of the Chinese Acedemy of Sciences, China (XD B02020500)
文摘Morphine can modulate the processes underlying memory in vertebrates. However, studies have shown various modulations by morphine： positive, negative and even neutral. The honeybee is a potential platform for evaluating the effects of drugs, especially addictive drugs, on the nervous system. However, the involvement of morphine in learning and memory in insects or other invertebrates is poorly understood. The current work evaluated whether morphine affects memory acquisition, consolidation and retrieval in honeybees, using the proboscis extension response （PER） paradigm. We demonstrated that morphine treatment （5 pg/bee） before training decreased the percentage of correct PERs and the response latency related to aversive rather than rewarding odors when tested after 1 or 24 h. Morphine treatment after training also caused a decrease in this latency when tested after 24 h. Meanwhile, morphine treatment reduced the ambulation distance when tested after 30 min. Our findings suggest that morphine impairs the acquisition of shortand long-term associative memory and slightly disrupts the consolidation of long-term memory in honeybees. These negative effects cannot be explained by reduced locomotion but by impaired memory associated with aversion.
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the National Key Research and Development Program of China(No.2016YFB0302500)the National Natural Science Foundation of China(Nos.51873209,51873210,51773194 and 51973219)Jilin Scientific and Technological Development Program,China(No.20200403022SF).
文摘The effect of exogenous hydroxyl,carboxyl groups and/or Sn^(2+) on pyrolysis reactions of poly(L-lactide)(PLLA)was investigated by thermogravimetric analysis(TGA).The activation energy(fa)of pyrolysis reactions was estimated by the Kissinger-Akahira-Sunose method.The kinetic models were also explored by the Malek method,and the random degradation behavior was determined by comparing the plots of ln{-ln[1-(1-w)05]}versus 1/7for experimental data from TGA with model reactions.The pyrolysis reaction rate of PLLA was affected slightly by exogenous hydroxyl and carboxyl groups at lower levels of Sn with 65-70 mg·kg^(-1)but increased appreciably in the presence of extraneous Sn^(2+),-COOH/Sn^(2+),or-OH/Sn^(2+).The Ea values for the pyrolysis reactions of the PLLAs that provided lactide were different under the catalysis of Sn2+in different chemical environments because Sn^(2+) can form the new Sn-carboxylate and Sn-alkoxide with exogenous carboxyl and hydroxyl groups,which were different in steric hindrance for the formation of activated complex between Sn^(2+) and PLLA.Under the catalysis of Sn^(2+),a lactide molecule can be directly eliminated selectively at a random position of PLLA molecular chains,and the molecular chain of PLLA cannot change two PLLA fragments at the elimination site of lactide.However,it was regenerated into a new PLLA molecule with the molecular weight reduced by 144 g·mol^(-1).
基金financially supported by the National Natural Science Foundation of China(Nos.51303176,51873209,51573178,and 51773194)the National Key Research and Development Program of China(No.2016YFB0302500)
文摘The effect of the architecture of poly(ethylene glycol)/poly(L-lactide)(PEG/PLLA) block copolymers on the non-isothermal crystallization behaviors of PLLA blocks was investigated by differential scanning calorimetry(DSC) and wide angle X-ray diffraction(WAXD). 1-Arm MPEG-b-PLLA and 4-arm PEG-b-PLLA(4PEG-b-PLLA) were synthesized by the ring-opening polymerization of Llactide in the presence of poly(ethylene glycol) methyl ether(MPEG) and 4-arm poly(ethylene glycol)(4PEG). 4-Arm PLLA-b-MPEG(4PLLA-b-PEG) was synthesized by coupling 4-arm PLLA and MPEG. The WAXD results indicated that the crystalline structure of PLLA blocks did not alter due to the different chain architectures. The average values of Avrami index(ˉn) were all above 4, which indicated that the nucleation mechanism of PLLA blocks was heterogeneous nucleation, regardless of the architectures. The overall crystallization rates were decreased markedly as following: MPEG-b-PLLA > 4PEG-b-PLLA > 4PLLA-b-PEG, ascribed to the different confinement by PEG blocks and to the steric hindrance of chain architectures. Therefore, the crystallization of PLLA blocks became more difficult and the crystallization activation energy of the PLLA blocks increased due to the confinement of chain architectures.
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.
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.
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.
