Titanium(Ti)and its alloys are frequently utilized as critical components in a variety of engineering ap-plications because of their high specific strength and excellent corrosion resistance.Compared to conven-tional ...Titanium(Ti)and its alloys are frequently utilized as critical components in a variety of engineering ap-plications because of their high specific strength and excellent corrosion resistance.Compared to conven-tional surface strengthening technologies,laser shock peening(LSP)has increasingly attracted attention from researchers and industries,since it significantly improves the surface strength,biocompatibility,fa-tigue resistance,and anti-corrosion ability of Ti and its alloys.Despite numerous studies that have been carried out to elucidate the effects of LSP on microstructural evolution and mechanical properties of Ti and its alloys in recent years,a comprehensive review of recent advancements in the field of Ti and its alloys subjected to LSP is still lacking.In this review,the standard LSP and the novel process designs of LSP assisted by thermal,cryogenic,electropulsing and magnetic fields are discussed and compared.Microstructural evolution,with focuses on the dislocation dynamics,deformation twinning,grain refine-ment and surface amorphization,during LSP processing of Ti alloys is reviewed.Furthermore,the en-hanced engineering performance of the L SP-processed(L SPed)Ti alloys,including surface hardness,wear resistance,fatigue life and corrosion resistance are summarized.Finally,this review concludes by present-ing an overview of the current challenges encountered in this field and offering insights into anticipated future trends.展开更多
Nanocarrier-based drug delivery systems(nDDSs)present significant opportunities for improving disease treatment,offering advantages in drug encapsulation,solubilization,stability enhancement,and optimized pharmacokine...Nanocarrier-based drug delivery systems(nDDSs)present significant opportunities for improving disease treatment,offering advantages in drug encapsulation,solubilization,stability enhancement,and optimized pharmacokinetics and biodistribution.n DDSs,comprising lipid,polymeric,protein,and inorganic nanovehicles,can be guided by or respond to biological cues for precise disease treatment and management.Equipping nanocarriers with tissue/celltargeted ligands enables effective navigation in complex environments,while functionalization with stimuli-responsive moieties facilitates site-specific controlled release.These strategies enhance drug delivery efficiency,augment therapeutic efficacy,and reduce side effects.This article reviews recent strategies and ongoing advancements in n DDSs for targeted drug delivery and controlled release,examining lesion-targeted nanomedicines through surface modification with small molecules,peptides,antibodies,carbohydrates,or cell membranes,and controlled-release nanocarriers responding to endogenous signals such as pH,redox conditions,enzymes,or external triggers like light,temperature,and magnetism.The article also discusses perspectives on future developments.展开更多
Marfan syndrome (MFS)(OMIM 154700) is a relatively common autosomal dominant genetic disease that causes skeletal, ocular, and cardiovascular defects and was first described by a French pediatrician in 1896 (Bitterman...Marfan syndrome (MFS)(OMIM 154700) is a relatively common autosomal dominant genetic disease that causes skeletal, ocular, and cardiovascular defects and was first described by a French pediatrician in 1896 (Bitterman and Sponseller, 2017). Its prevalence rate is 1/3000—1/5000, and more than 25% of cases are sporadic (Chiu et al., 2014). Studies have shown that about 90% of MFS is caused by variants in the fibrillin-1 gene (FBN1, OMIM 134797). FBN1, located on chromosome 15q21.1, encodes a macromolecular glycoprotein-fibrin 1, which aggregates to form microfibers in the extracellular matrix and distributes in various human connective tissues, such as periosteum, vessel wall, and crystal suspensor ligament. Variants in FNB1 have been reported in 65 exons, but the relationship between genotype and phenotype remains rather unclear (Sakai et al., 2016). Studies have also shown that patients with MFS and similar diseases may have variants in other related genes such as members of the transforming growth factor beta receptor (TGFBR) family (Mizuguchi et al., 2004;Sakai et al., 2006;Bolar et al., 2012;De Cario et al., 2018). For better prevention and treatment of MFS as well as for suspected MFS patients, there is a strong need for efficient genetic testing for early diagnosis and differential diagnoses of patients with related phenotypes (Aubart et al., 2018).展开更多
Aluminum nitride （AIN） precipitates and microstructure of 4 wt.% （Si＋AI） non-oriented electrical steel were investigated. The 2.0 mm thick cast strips with three different silicon/aluminum （Si/AI） ratios were p...Aluminum nitride （AIN） precipitates and microstructure of 4 wt.% （Si＋AI） non-oriented electrical steel were investigated. The 2.0 mm thick cast strips with three different silicon/aluminum （Si/AI） ratios were produced by twin-roll casting process, then the strips were reheated, warm rolled, cold rolled and annealed. The microstructure and AIN precipitates were characterized using optical microscopy, scanning electron microscopy and transmission electron microscopy. The results showed that with the increase of Si/AI ratio, on the one hand, the casting microstructure changed from columnar grains to equiaxed grains, and the uniformity of annealed microstructure was improved; On the other hand, the number of AIN precipitates in cast strips reduced meanwhile the distribution became dispersed. By the reheat treatment, the size and distribution of the AIN precipitates can be changed. Moreover, the grain size of the annealed strips is in the range of 20-50 #m, at the same time, many AIN precipitates were located at grain boundaries. Therefore, controlling the Si/AI ratio is a simple method to obtain desired microstructure. Then AIN precipitates in non-oriented electrical steel prepared by twin-roll casting process hinder markedly the recrystallized grains growth, A compatible reheat treatment can be an approach worth exploring to control the behavior of AIN precipitates.展开更多
Reciprocal translocation is a chromosomal structural abnormal- ity that arises when two non-homologous chromosomes rearrange and attach with each other, an incidence that occurs in about 1/500 to 1/625 newborns （Mack...Reciprocal translocation is a chromosomal structural abnormal- ity that arises when two non-homologous chromosomes rearrange and attach with each other, an incidence that occurs in about 1/500 to 1/625 newborns （Mackie and Scriven, 2002）. This event typically does not lead to any significant loss of genetic material, thus recip- rocal translocation carriers do not exhibit any severe abnormal phenotypes （Scriven et al., 1998; Zhang et al., 2016）.展开更多
Objective: The effects of arsenic trioxide(As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact rol...Objective: The effects of arsenic trioxide(As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer cells.Methods: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3was detected using immunofluorescence, Western blot assay and transmission electron microscopy.Results: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time-and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression.Furthermore, As2O3treatment induced autophagy in liver cancer cells;this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3on cell viability.Serum starvation increased autophagy and amplified the effect of As2O3on cell death.Conclusion: As2O3induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of As2O3against liver cancer.展开更多
Congenital contractural arachnodactyly(CCA,OMIM:121050),also known as Beals syndrome,belongs to a group of rare autosomal dominant(AD)diseases of connective tissue(Maslen et al.,1997).People with CCA share many distin...Congenital contractural arachnodactyly(CCA,OMIM:121050),also known as Beals syndrome,belongs to a group of rare autosomal dominant(AD)diseases of connective tissue(Maslen et al.,1997).People with CCA share many distinguishing features,such as arachnodactyly,camp tod actyly,multiple joint contractures(especially finger,elbow,and knee joints),crumpled ears,scoliosis,pectus deformities,and muscular hypoplasia(Jurko et al.,2013).It exhibits no specific geographic or ethnic predilection(Frederic et al.,2009).展开更多
Objective： To evaluate correlation between chemosensitivity of tumor cells in vitro and their clinical responsiveness in vivo by comparing the difference of curative effect between chemotherapy of cerebral gliomas di...Objective： To evaluate correlation between chemosensitivity of tumor cells in vitro and their clinical responsiveness in vivo by comparing the difference of curative effect between chemotherapy of cerebral gliomas directed by chemosensitivity test in vitro and its routine chemotherapy. Methods： Sixty-two patients with cerebral gliomas were recruited as the experiment group, who had received total resection or subtotal resection of the tumor. The resected tumor cells were cultured in vitro, followed by chemosensitivity test using colorimetric MTT assay. Finally, chemotherapeutic protocol was made based on the results of the chemosensitivity test. Fifty patients with cerebral gliomas subjected to the routine chemotherapeutic protocol were simultaneously recruited as the control group, whose age, gender, survival functional status and operational fashion were matched with the experiment group. The two groups were equally followed up for the survival functional status, recurrence and death. All data were analyzed using SPSS 10.0 software. Results： At the time of evaluation, KPS values of 64.52 ± 35.84 were seen in the experiment group, and 33.60 ± 36.24 in the control group, showing statistical difference between the two groups （t = 4.5163, P = 0.000）. During 2-4 years of follow up, a recurrence rate of 32.26% was seen in the experimental group, and 60.00% in the control group, showing a statistical difference between the two groups （X^2 = 8.620, P = 0.003）. The fatality was 22.58% in the experiment group, and 48.00% in the control group, showing a statistical difference between the two groups （X^2 = 7.978, P = 0.005）. The survival rate of the experimental group was higher than that of the control group, showing a statistical differences between the two groups （X^2= 7.29, P = 0.0069）. Conclusion： Chemotherapy of glio- mas under the guidance of chemosensitivity test in vitro contributes to obvious improvement on the current survival functional status, a clear decline of the recurrence rates and fatality rate, and raised survival rates of the patients. A close correlation between the chemosensitivity in vitro and clinical responsiveness in vivo is observed.展开更多
Retinal neovascularization is a leading cause of blindness.While current anti-VEGF drugs effectively inhibit pathological angiogenesis,some patients develop resistance or reduced responsiveness to treatments over time...Retinal neovascularization is a leading cause of blindness.While current anti-VEGF drugs effectively inhibit pathological angiogenesis,some patients develop resistance or reduced responsiveness to treatments over time,leading to diminished effectiveness.In this study,we identified high activation of the cGAS-STING signaling pathway,which exacerbated pathological neovascularization and vessel leakage.We developed an injectable thermo-responsive supramolecular hydrogel loaded with an anti-STING drug.The hydrogel,made of Pluronic F127 demonstrated excellent transparency and biocompatibility.Importantly,the thermo-sensitive property allowed for precise spatial release of the drug,extending the effective treatment duration of C-176,which suppressed STING activation in the retina,reduced inflammation and protected retinal tissue.Hydro^(C-176) effectively inhibited microglial cell infiltration and the release of inflammatory angiogenic factors,highlighting its enhanced efficacy.While demonstrating slightly lower effectiveness compared to traditional anti-VEGF therapy,Hydro^(C-176) exhibited more robust capabilities in regulating ocular microenvironmental inflammation.This approach may assist in enhancing the sensitivity and effectiveness of anti-VEGF therapy for reducing ocular inflammation,potentially improving patients’response to traditional treatment.These results have suggested innovative and comprehensive strategies for the management of retinal neovascularization.展开更多
Magnetic resonance imaging(MRI),as a noninvasive and powerful method in modern diagnostics,has been advancing in leaps and bounds.Conventional methods to improve MRI based on increasing the static magnetic field stren...Magnetic resonance imaging(MRI),as a noninvasive and powerful method in modern diagnostics,has been advancing in leaps and bounds.Conventional methods to improve MRI based on increasing the static magnetic field strength are restricted by safety concerns,cost issues,and the impact on patient experience;as such,innovative approaches are required.It has been suggested that metamaterials featuring subwavelength unit cells can be used to take full control of electromagnetic waves and redistribute electromagnetic fields,achieve abundant counterintuitive phenomena,and construct versatile devices.Recently,metamaterials with exotic effective electromagnetic parameters,peculiar dispersion relations,or tailored field distribution of resonant modes have shown promising capabilities in MRI.Herein,we outline the principle of the MRI process,review recent advances in enhancing MRI by employing the unique physical mechanisms of metamaterials,and demystify ways in which metamaterial designs could improve MRI,such as by enhancing the imaging quality,reducing the scanning time,alleviating field inhomogeneities,and increasing patient safety.We conclude by providing our vision for the future of improving MRI with metamaterials.展开更多
Fusion welding easily causes microstructural coarsening in the heat-affected zone(HAZ) of a thick-gauge pipeline steel joint. This is most significant in the inter-critically coarse-grained HAZ(ICCGHAZ), which conside...Fusion welding easily causes microstructural coarsening in the heat-affected zone(HAZ) of a thick-gauge pipeline steel joint. This is most significant in the inter-critically coarse-grained HAZ(ICCGHAZ), which considerably deteriorates the toughness of the joint. In the present work, 11-mm thick pipeline steel was joined by preheating and double-sided friction stir welding(FSW). A comparative study on the microstructure and toughness in the ICCGHAZs for FSW and gas metal arc welding(GMAW) was performed. The toughness in the ICCGHAZ for FSW was improved significantly than that in the ICCGHAZ for GMAW. Generally, the nugget zone(NZ) has a coarse microstructure in the FSW steel joint formed at the highest peak temperature. However, in the current study, the microstructure in the one-pass NZ was remarkably refined owing to the static recrystallization of ferrite. An excellent toughness was achieved in the NZ of the pipeline steel joint that employed FSW.展开更多
Comprehensive experiments including monotonic tension and monotonic compression of specimens taken from a rolled AZ31B Mg thick plate along five different material orientations with respect to the rolled direction(RD)...Comprehensive experiments including monotonic tension and monotonic compression of specimens taken from a rolled AZ31B Mg thick plate along five different material orientations with respect to the rolled direction(RD),and free-end torsion of a tubular specimen machined along the thickness direction(ND)were conducted.The experimental results were used to evaluate an elastic-viscoplastic self-consistent model with the consideration of twinning and detwinning(EVPSC-TDT)on magnesium(Mg)alloys.The EVPSC-TDT model provides stress-strain curves and the hardening rates in close agreement with the experimental results of all the 11 loading cases.The model adequately predicts the textures after fracture of all the 11 loading cases and the evolutions of tension twins with increasing strains for tension in the ND,compression in the RD,and torsion along the ND.The Swift effect was observed in the experiment and was properly simulated by the model.展开更多
Magnetic resonance coupling plays an important role in the non-radiative wireless power transfer without cables.However,the basic near-field coupling also has some key limitations on the resonance wireless power trans...Magnetic resonance coupling plays an important role in the non-radiative wireless power transfer without cables.However,the basic near-field coupling also has some key limitations on the resonance wireless power transfer(WPT).On the one hand,when the transfer distance is short,the eigenfrequencies of the WPT system will split because of the strong near-field coupling between the resonance transmitter and receiver.On the other hand,although the working frequency is fixed for the long-distance case,the transfer efficiency will be significantly dropped for the weak coupling strength.Therefore,a long-captivated problem of the resonance WPT systems is that it is difficult to balance the fixed working frequency and high efficiency of the devices.In this work,we put forward the composite transmitter with a pair of resonance coils of different size.By assisting the rotational degrees of freedom in the composite transmitter,a high-order parity-time-symmetric non-Hermitian system can be established.Especially,in contrast to the conventional resonance WPT scheme,the robust WPT can maintain fixed working frequency and efficiency over a varying transfer distance in the optimized WPT system with composite transmitter,since this eigenfrequency is insensitive to the operational conditions.Our findings demonstrate that the composite transmitter possesses better performance for WPT than its single counterpart,offering the opportunities for engineering novel designer electromagnetic transfer states with unique robustness.展开更多
Wireless power transfer(WPT)offers significant advantages,particularly due to its flexibility,enabling diverse applications.However,conventional single-transmitter,single-receiver systems are limited by their sensitiv...Wireless power transfer(WPT)offers significant advantages,particularly due to its flexibility,enabling diverse applications.However,conventional single-transmitter,single-receiver systems are limited by their sensitivity to lateral disturbances,frequency instability,and strict distance constraints.Recently,multiple-transmitter,single-receiver(MTSR)systems have gained attention for their potential to enhance system flexibility and reliability.In this work,we propose an efficient second-order anti-parity‒time(anti-PT)symmetry by introducing two transmitters that simultaneously exchange energy with the external channel.This concept is further extended to third-order anti-PT symmetry for efficient WPT in MTSR systems.By leveraging interference between shared sources,we construct virtual coupling instead of relying on traditional resistive losses.Remarkably,our system maintains frequency stability,broad bandwidth,and robust high-efficiency power transfer even when the resonant frequencies of the transmitter and receiver coils are mismatched.This innovation challenges conventional understanding and opens new directions for WPT technology.展开更多
To improve energy efficiency and protect the environment,the integrated energy system(IES)becomes a significant direction of energy structure adjustment.This paper innovatively proposes a wavelet neural network(WNN)mo...To improve energy efficiency and protect the environment,the integrated energy system(IES)becomes a significant direction of energy structure adjustment.This paper innovatively proposes a wavelet neural network(WNN)model optimized by the improved particle swarm optimization(IPSO)and chaos optimization algorithm(COA)for short-term load prediction of IES.The proposed model overcomes the disadvantages of the slow convergence and the tendency to fall into the local optimum in traditional WNN models.First,the Pearson correlation coefficient is employed to select the key influencing factors of load prediction.Then,the traditional particle swarm optimization(PSO)is improved by the dynamic particle inertia weight.To jump out of the local optimum,the COA is employed to search for individual optimal particles in IPSO.In the iteration,the parameters of WNN are continually optimized by IPSO-COA.Meanwhile,the feedback link is added to the proposed model,where the output error is adopted to modify the prediction results.Finally,the proposed model is employed for load prediction.The experimental simulation verifies that the proposed model significantly improves the prediction accuracy and operation efficiency compared with the artificial neural network(ANN),WNN,and PSO-WNN.展开更多
Birth defects are caused by multiple factors,such as chromosome abnormality,environmental factors,and maternal factors.In this study,we focused on exploring the genetic causes of a non-consanguineous couple who suffer...Birth defects are caused by multiple factors,such as chromosome abnormality,environmental factors,and maternal factors.In this study,we focused on exploring the genetic causes of a non-consanguineous couple who suffered from four times of unsuccessful pregnancy due to unexplained recurrent fetal malformations with similar symptoms and normal chromosome copy number variations.Using trio-whole exome sequencing(trio-WES) for this couple and one of the affected fetuses,we found a mutation,c.1996 delC on the maternal imprinted gene MAGEL2 that was carried by the affected fetus and husband,leading to Schaaf-Yang syndrome.To screen this mutation,we further performed preimplantation genetic diagnosis(PGD) strategy followed by a gene pedigree validation and pathogenicity analysis.After the transfer of a PGD-screened embryo,a normal newborn without previous abnormal symptoms was born(February 15,2019).We present the first data that identified a pathogenic gene(MAGEL2 c.1996 delC) in a fetus with Schaaf-Yang syndrome in the EAS(East Asian) database and overcame this genetic defect by using processed PGD for this couple based on the WES results.展开更多
Although previous studies have demonstrated that endosperm development is influenced by its parental genome constitution, the genetic basis and molecular mechanisms that control parent-of-origin effects require furthe...Although previous studies have demonstrated that endosperm development is influenced by its parental genome constitution, the genetic basis and molecular mechanisms that control parent-of-origin effects require further elucidation. Here we show that the Ras-related nuclear protein 1 （RAN1） regulates endosperm development in Arabidopsis thaliana. Reciprocal crosses between wild-type （WT） and transgenic lines misexpressing RAN1 （msRAN1） gave rise to small F1 seeds when RAN1 down-regulated/up-regulated individuals were used as a male/female parent; in contrast, F1 seeds were aborted when RAN1 down-regulated/up-regulated plants were used as a female/male parent, suggesting that seed development is affected by the parental genome ratio of RAN1. Whereas RAN1 expression in wild-type plants is reduced before the onset of endosperm cellularization, F1 seeds from reciprocal crosses between WT and msRAN1 showed abnormal endosperm cellularization and ectopic expression of RAN1. The expression of MINISEED3 （MINI3）-a gene that also controls endosperm cellularization-was also affected in these reciprocal crosses, and the misregulation of MINI3 activity rescued F1 seeds when msRAN1 plants were used in reciprocal crosses. Taken together, our results suggest that the parental ratio of RAN1 regulates the onset of endosperm cellularization through its genetic interaction with MINI3.展开更多
Radiotherapy remains the mainstay for treatment of various types of human cancer;however,the clinical efficacy is often limited by radioresistance,in which the underlying mechanism is largely unknown.Here,using esopha...Radiotherapy remains the mainstay for treatment of various types of human cancer;however,the clinical efficacy is often limited by radioresistance,in which the underlying mechanism is largely unknown.Here,using esophageal squamous cell carcinoma(ESCC)as a model,we demonstrate that guanine nucleotide exchange factor 2(VAV2),which is overexpressed in most human cancers,plays an important role in primary and secondary radioresistance.We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation.展开更多
基金supported by the National Key R&D Plan of China(No.2022YFB3705603)the National Natural Science Foundation of China(No.52101046)+1 种基金the Excellent Youth Overseas Project of National Science and Natural Foundation of China,the Baowu Special Metallurgy Cooperation Limited(No.22H010101336)the Medicine-Engineering Interdisciplinary Project of Shanghai Jiao Tong University(No.YG2022QN076).
文摘Titanium(Ti)and its alloys are frequently utilized as critical components in a variety of engineering ap-plications because of their high specific strength and excellent corrosion resistance.Compared to conven-tional surface strengthening technologies,laser shock peening(LSP)has increasingly attracted attention from researchers and industries,since it significantly improves the surface strength,biocompatibility,fa-tigue resistance,and anti-corrosion ability of Ti and its alloys.Despite numerous studies that have been carried out to elucidate the effects of LSP on microstructural evolution and mechanical properties of Ti and its alloys in recent years,a comprehensive review of recent advancements in the field of Ti and its alloys subjected to LSP is still lacking.In this review,the standard LSP and the novel process designs of LSP assisted by thermal,cryogenic,electropulsing and magnetic fields are discussed and compared.Microstructural evolution,with focuses on the dislocation dynamics,deformation twinning,grain refine-ment and surface amorphization,during LSP processing of Ti alloys is reviewed.Furthermore,the en-hanced engineering performance of the L SP-processed(L SPed)Ti alloys,including surface hardness,wear resistance,fatigue life and corrosion resistance are summarized.Finally,this review concludes by present-ing an overview of the current challenges encountered in this field and offering insights into anticipated future trends.
基金supported by the National Natural Science Foundation of China(No.82273876)the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China(No.171028)+1 种基金the Project of State Key Laboratory of Advanced Drug Delivery and Release Systems(No.DSQZZD-200301)the Fundamental Research Fund for the Central Universities(No.2632022YC02)。
文摘Nanocarrier-based drug delivery systems(nDDSs)present significant opportunities for improving disease treatment,offering advantages in drug encapsulation,solubilization,stability enhancement,and optimized pharmacokinetics and biodistribution.n DDSs,comprising lipid,polymeric,protein,and inorganic nanovehicles,can be guided by or respond to biological cues for precise disease treatment and management.Equipping nanocarriers with tissue/celltargeted ligands enables effective navigation in complex environments,while functionalization with stimuli-responsive moieties facilitates site-specific controlled release.These strategies enhance drug delivery efficiency,augment therapeutic efficacy,and reduce side effects.This article reviews recent strategies and ongoing advancements in n DDSs for targeted drug delivery and controlled release,examining lesion-targeted nanomedicines through surface modification with small molecules,peptides,antibodies,carbohydrates,or cell membranes,and controlled-release nanocarriers responding to endogenous signals such as pH,redox conditions,enzymes,or external triggers like light,temperature,and magnetism.The article also discusses perspectives on future developments.
基金supported by the National Key R&D Program of China (2018YFC1002302, 2016YFC0900103)National Natural Science Foundation of China (81671458)+1 种基金Beijing Lab for Cardiovascular Precision Medicine (PXM2018_014226_000013)supported by the Reproduction Center Biobank at Peking University Third Hospital
文摘Marfan syndrome (MFS)(OMIM 154700) is a relatively common autosomal dominant genetic disease that causes skeletal, ocular, and cardiovascular defects and was first described by a French pediatrician in 1896 (Bitterman and Sponseller, 2017). Its prevalence rate is 1/3000—1/5000, and more than 25% of cases are sporadic (Chiu et al., 2014). Studies have shown that about 90% of MFS is caused by variants in the fibrillin-1 gene (FBN1, OMIM 134797). FBN1, located on chromosome 15q21.1, encodes a macromolecular glycoprotein-fibrin 1, which aggregates to form microfibers in the extracellular matrix and distributes in various human connective tissues, such as periosteum, vessel wall, and crystal suspensor ligament. Variants in FNB1 have been reported in 65 exons, but the relationship between genotype and phenotype remains rather unclear (Sakai et al., 2016). Studies have also shown that patients with MFS and similar diseases may have variants in other related genes such as members of the transforming growth factor beta receptor (TGFBR) family (Mizuguchi et al., 2004;Sakai et al., 2006;Bolar et al., 2012;De Cario et al., 2018). For better prevention and treatment of MFS as well as for suspected MFS patients, there is a strong need for efficient genetic testing for early diagnosis and differential diagnoses of patients with related phenotypes (Aubart et al., 2018).
基金financially supported by the National Natural Science Foundation of China(Nos.50734001 and 51004035)
文摘Aluminum nitride （AIN） precipitates and microstructure of 4 wt.% （Si＋AI） non-oriented electrical steel were investigated. The 2.0 mm thick cast strips with three different silicon/aluminum （Si/AI） ratios were produced by twin-roll casting process, then the strips were reheated, warm rolled, cold rolled and annealed. The microstructure and AIN precipitates were characterized using optical microscopy, scanning electron microscopy and transmission electron microscopy. The results showed that with the increase of Si/AI ratio, on the one hand, the casting microstructure changed from columnar grains to equiaxed grains, and the uniformity of annealed microstructure was improved; On the other hand, the number of AIN precipitates in cast strips reduced meanwhile the distribution became dispersed. By the reheat treatment, the size and distribution of the AIN precipitates can be changed. Moreover, the grain size of the annealed strips is in the range of 20-50 #m, at the same time, many AIN precipitates were located at grain boundaries. Therefore, controlling the Si/AI ratio is a simple method to obtain desired microstructure. Then AIN precipitates in non-oriented electrical steel prepared by twin-roll casting process hinder markedly the recrystallized grains growth, A compatible reheat treatment can be an approach worth exploring to control the behavior of AIN precipitates.
基金supported by the National Natural Science Foundation of China (No. 31522034)Ministry of Science and Technology of China (2016YFC0900103)the National High Technology Research and Development Program Grant (2015AA020407)
文摘Reciprocal translocation is a chromosomal structural abnormal- ity that arises when two non-homologous chromosomes rearrange and attach with each other, an incidence that occurs in about 1/500 to 1/625 newborns （Mackie and Scriven, 2002）. This event typically does not lead to any significant loss of genetic material, thus recip- rocal translocation carriers do not exhibit any severe abnormal phenotypes （Scriven et al., 1998; Zhang et al., 2016）.
基金supported by the grants from National Natural Science Foundation of China(No. 82074203, 82274328 and 81673655)。
文摘Objective: The effects of arsenic trioxide(As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer cells.Methods: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3was detected using immunofluorescence, Western blot assay and transmission electron microscopy.Results: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time-and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression.Furthermore, As2O3treatment induced autophagy in liver cancer cells;this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3on cell viability.Serum starvation increased autophagy and amplified the effect of As2O3on cell death.Conclusion: As2O3induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of As2O3against liver cancer.
基金supported by the National High Technology Research and Development Program(Nos.2018YFC1002904,2018YFC1004000 and 2017YFA0103801)。
文摘Congenital contractural arachnodactyly(CCA,OMIM:121050),also known as Beals syndrome,belongs to a group of rare autosomal dominant(AD)diseases of connective tissue(Maslen et al.,1997).People with CCA share many distinguishing features,such as arachnodactyly,camp tod actyly,multiple joint contractures(especially finger,elbow,and knee joints),crumpled ears,scoliosis,pectus deformities,and muscular hypoplasia(Jurko et al.,2013).It exhibits no specific geographic or ethnic predilection(Frederic et al.,2009).
文摘Objective： To evaluate correlation between chemosensitivity of tumor cells in vitro and their clinical responsiveness in vivo by comparing the difference of curative effect between chemotherapy of cerebral gliomas directed by chemosensitivity test in vitro and its routine chemotherapy. Methods： Sixty-two patients with cerebral gliomas were recruited as the experiment group, who had received total resection or subtotal resection of the tumor. The resected tumor cells were cultured in vitro, followed by chemosensitivity test using colorimetric MTT assay. Finally, chemotherapeutic protocol was made based on the results of the chemosensitivity test. Fifty patients with cerebral gliomas subjected to the routine chemotherapeutic protocol were simultaneously recruited as the control group, whose age, gender, survival functional status and operational fashion were matched with the experiment group. The two groups were equally followed up for the survival functional status, recurrence and death. All data were analyzed using SPSS 10.0 software. Results： At the time of evaluation, KPS values of 64.52 ± 35.84 were seen in the experiment group, and 33.60 ± 36.24 in the control group, showing statistical difference between the two groups （t = 4.5163, P = 0.000）. During 2-4 years of follow up, a recurrence rate of 32.26% was seen in the experimental group, and 60.00% in the control group, showing a statistical difference between the two groups （X^2 = 8.620, P = 0.003）. The fatality was 22.58% in the experiment group, and 48.00% in the control group, showing a statistical difference between the two groups （X^2 = 7.978, P = 0.005）. The survival rate of the experimental group was higher than that of the control group, showing a statistical differences between the two groups （X^2= 7.29, P = 0.0069）. Conclusion： Chemotherapy of glio- mas under the guidance of chemosensitivity test in vitro contributes to obvious improvement on the current survival functional status, a clear decline of the recurrence rates and fatality rate, and raised survival rates of the patients. A close correlation between the chemosensitivity in vitro and clinical responsiveness in vivo is observed.
基金This study was supported by grants from the National Natural Science Foundation of China(No.82271054,ZL,No.U20A20363,JH).
文摘Retinal neovascularization is a leading cause of blindness.While current anti-VEGF drugs effectively inhibit pathological angiogenesis,some patients develop resistance or reduced responsiveness to treatments over time,leading to diminished effectiveness.In this study,we identified high activation of the cGAS-STING signaling pathway,which exacerbated pathological neovascularization and vessel leakage.We developed an injectable thermo-responsive supramolecular hydrogel loaded with an anti-STING drug.The hydrogel,made of Pluronic F127 demonstrated excellent transparency and biocompatibility.Importantly,the thermo-sensitive property allowed for precise spatial release of the drug,extending the effective treatment duration of C-176,which suppressed STING activation in the retina,reduced inflammation and protected retinal tissue.Hydro^(C-176) effectively inhibited microglial cell infiltration and the release of inflammatory angiogenic factors,highlighting its enhanced efficacy.While demonstrating slightly lower effectiveness compared to traditional anti-VEGF therapy,Hydro^(C-176) exhibited more robust capabilities in regulating ocular microenvironmental inflammation.This approach may assist in enhancing the sensitivity and effectiveness of anti-VEGF therapy for reducing ocular inflammation,potentially improving patients’response to traditional treatment.These results have suggested innovative and comprehensive strategies for the management of retinal neovascularization.
基金supported by the National Key R&D Program of China(Grant Nos.2021YFA1400602 and 2023YFA1407600)the National Natural Science Foundation of China(Grant Nos.91850206,12374294,and 12004284)the Chenguang Program of Shanghai(Grant No.21CGA22).
文摘Magnetic resonance imaging(MRI),as a noninvasive and powerful method in modern diagnostics,has been advancing in leaps and bounds.Conventional methods to improve MRI based on increasing the static magnetic field strength are restricted by safety concerns,cost issues,and the impact on patient experience;as such,innovative approaches are required.It has been suggested that metamaterials featuring subwavelength unit cells can be used to take full control of electromagnetic waves and redistribute electromagnetic fields,achieve abundant counterintuitive phenomena,and construct versatile devices.Recently,metamaterials with exotic effective electromagnetic parameters,peculiar dispersion relations,or tailored field distribution of resonant modes have shown promising capabilities in MRI.Herein,we outline the principle of the MRI process,review recent advances in enhancing MRI by employing the unique physical mechanisms of metamaterials,and demystify ways in which metamaterial designs could improve MRI,such as by enhancing the imaging quality,reducing the scanning time,alleviating field inhomogeneities,and increasing patient safety.We conclude by providing our vision for the future of improving MRI with metamaterials.
基金financially supported by the National Nature Science Foundation of China (No. 51774085)Liaoning Province Excellent Youth Foundation (No. 2020-YQ03)the Open Research Fund from the State Key Laboratory of Rolling and Automation, Northeastern University (No. 2020RALKFKT009)。
文摘Fusion welding easily causes microstructural coarsening in the heat-affected zone(HAZ) of a thick-gauge pipeline steel joint. This is most significant in the inter-critically coarse-grained HAZ(ICCGHAZ), which considerably deteriorates the toughness of the joint. In the present work, 11-mm thick pipeline steel was joined by preheating and double-sided friction stir welding(FSW). A comparative study on the microstructure and toughness in the ICCGHAZs for FSW and gas metal arc welding(GMAW) was performed. The toughness in the ICCGHAZ for FSW was improved significantly than that in the ICCGHAZ for GMAW. Generally, the nugget zone(NZ) has a coarse microstructure in the FSW steel joint formed at the highest peak temperature. However, in the current study, the microstructure in the one-pass NZ was remarkably refined owing to the static recrystallization of ferrite. An excellent toughness was achieved in the NZ of the pipeline steel joint that employed FSW.
基金supported by the U.S.National Science Foundation(CMMI-1762312)the support of China Scholarship Council(CSC).
文摘Comprehensive experiments including monotonic tension and monotonic compression of specimens taken from a rolled AZ31B Mg thick plate along five different material orientations with respect to the rolled direction(RD),and free-end torsion of a tubular specimen machined along the thickness direction(ND)were conducted.The experimental results were used to evaluate an elastic-viscoplastic self-consistent model with the consideration of twinning and detwinning(EVPSC-TDT)on magnesium(Mg)alloys.The EVPSC-TDT model provides stress-strain curves and the hardening rates in close agreement with the experimental results of all the 11 loading cases.The model adequately predicts the textures after fracture of all the 11 loading cases and the evolutions of tension twins with increasing strains for tension in the ND,compression in the RD,and torsion along the ND.The Swift effect was observed in the experiment and was properly simulated by the model.
基金supported by the National Key R&D Program of China(2021YFA1400602)the National Natural Science Foundation of China(12004284)+1 种基金the Fundamental Research Funds for the Central Universities(22120210579)the Chenguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(21CGA22).
文摘Magnetic resonance coupling plays an important role in the non-radiative wireless power transfer without cables.However,the basic near-field coupling also has some key limitations on the resonance wireless power transfer(WPT).On the one hand,when the transfer distance is short,the eigenfrequencies of the WPT system will split because of the strong near-field coupling between the resonance transmitter and receiver.On the other hand,although the working frequency is fixed for the long-distance case,the transfer efficiency will be significantly dropped for the weak coupling strength.Therefore,a long-captivated problem of the resonance WPT systems is that it is difficult to balance the fixed working frequency and high efficiency of the devices.In this work,we put forward the composite transmitter with a pair of resonance coils of different size.By assisting the rotational degrees of freedom in the composite transmitter,a high-order parity-time-symmetric non-Hermitian system can be established.Especially,in contrast to the conventional resonance WPT scheme,the robust WPT can maintain fixed working frequency and efficiency over a varying transfer distance in the optimized WPT system with composite transmitter,since this eigenfrequency is insensitive to the operational conditions.Our findings demonstrate that the composite transmitter possesses better performance for WPT than its single counterpart,offering the opportunities for engineering novel designer electromagnetic transfer states with unique robustness.
基金supported by the National Key R&D Program of China(Nos.2021YFA1400602 and 2023YFA1407600)the National Natural Science Foundation of China(Nos.12374294 and 52477014)the Chenguang Program of Shanghai(No.21CGA22).
文摘Wireless power transfer(WPT)offers significant advantages,particularly due to its flexibility,enabling diverse applications.However,conventional single-transmitter,single-receiver systems are limited by their sensitivity to lateral disturbances,frequency instability,and strict distance constraints.Recently,multiple-transmitter,single-receiver(MTSR)systems have gained attention for their potential to enhance system flexibility and reliability.In this work,we propose an efficient second-order anti-parity‒time(anti-PT)symmetry by introducing two transmitters that simultaneously exchange energy with the external channel.This concept is further extended to third-order anti-PT symmetry for efficient WPT in MTSR systems.By leveraging interference between shared sources,we construct virtual coupling instead of relying on traditional resistive losses.Remarkably,our system maintains frequency stability,broad bandwidth,and robust high-efficiency power transfer even when the resonant frequencies of the transmitter and receiver coils are mismatched.This innovation challenges conventional understanding and opens new directions for WPT technology.
基金supported in part by the National Key Research and Development Program of China(No.2018YFB1500800)the National Natural Science Foundation of China(No.51807134)the State Key Laboratory of Reliability and Intelligence of Electrical Equipment,Hebei University of Technology(No.EERI_KF20200014)。
文摘To improve energy efficiency and protect the environment,the integrated energy system(IES)becomes a significant direction of energy structure adjustment.This paper innovatively proposes a wavelet neural network(WNN)model optimized by the improved particle swarm optimization(IPSO)and chaos optimization algorithm(COA)for short-term load prediction of IES.The proposed model overcomes the disadvantages of the slow convergence and the tendency to fall into the local optimum in traditional WNN models.First,the Pearson correlation coefficient is employed to select the key influencing factors of load prediction.Then,the traditional particle swarm optimization(PSO)is improved by the dynamic particle inertia weight.To jump out of the local optimum,the COA is employed to search for individual optimal particles in IPSO.In the iteration,the parameters of WNN are continually optimized by IPSO-COA.Meanwhile,the feedback link is added to the proposed model,where the output error is adopted to modify the prediction results.Finally,the proposed model is employed for load prediction.The experimental simulation verifies that the proposed model significantly improves the prediction accuracy and operation efficiency compared with the artificial neural network(ANN),WNN,and PSO-WNN.
基金supported by the National Natural Science Foundation of China(31522034,81521002,81730038)the National High Technology Research and Development Program(2015AA020407)
文摘Birth defects are caused by multiple factors,such as chromosome abnormality,environmental factors,and maternal factors.In this study,we focused on exploring the genetic causes of a non-consanguineous couple who suffered from four times of unsuccessful pregnancy due to unexplained recurrent fetal malformations with similar symptoms and normal chromosome copy number variations.Using trio-whole exome sequencing(trio-WES) for this couple and one of the affected fetuses,we found a mutation,c.1996 delC on the maternal imprinted gene MAGEL2 that was carried by the affected fetus and husband,leading to Schaaf-Yang syndrome.To screen this mutation,we further performed preimplantation genetic diagnosis(PGD) strategy followed by a gene pedigree validation and pathogenicity analysis.After the transfer of a PGD-screened embryo,a normal newborn without previous abnormal symptoms was born(February 15,2019).We present the first data that identified a pathogenic gene(MAGEL2 c.1996 delC) in a fetus with Schaaf-Yang syndrome in the EAS(East Asian) database and overcame this genetic defect by using processed PGD for this couple based on the WES results.
文摘Although previous studies have demonstrated that endosperm development is influenced by its parental genome constitution, the genetic basis and molecular mechanisms that control parent-of-origin effects require further elucidation. Here we show that the Ras-related nuclear protein 1 （RAN1） regulates endosperm development in Arabidopsis thaliana. Reciprocal crosses between wild-type （WT） and transgenic lines misexpressing RAN1 （msRAN1） gave rise to small F1 seeds when RAN1 down-regulated/up-regulated individuals were used as a male/female parent; in contrast, F1 seeds were aborted when RAN1 down-regulated/up-regulated plants were used as a female/male parent, suggesting that seed development is affected by the parental genome ratio of RAN1. Whereas RAN1 expression in wild-type plants is reduced before the onset of endosperm cellularization, F1 seeds from reciprocal crosses between WT and msRAN1 showed abnormal endosperm cellularization and ectopic expression of RAN1. The expression of MINISEED3 （MINI3）-a gene that also controls endosperm cellularization-was also affected in these reciprocal crosses, and the misregulation of MINI3 activity rescued F1 seeds when msRAN1 plants were used in reciprocal crosses. Taken together, our results suggest that the parental ratio of RAN1 regulates the onset of endosperm cellularization through its genetic interaction with MINI3.
基金This project was supported by National Science Fund for Distinguished Young Scholars(81725015 to C.W.)Medical and Health Technology Innovation Project of Chinese Academy of Medical Sciences(2016-I2M-3-019 to D.L.,2016-I2M-4-002 to C.W.,2019-I2M-2-001 to D.L.and C.W.,2016-I2M-1-001 and 2019-12M-1-003 to W.T.)+1 种基金Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023027 to C.W.)National Natural Science Foundation of China(81988101 to D.L and C.W.).
文摘Radiotherapy remains the mainstay for treatment of various types of human cancer;however,the clinical efficacy is often limited by radioresistance,in which the underlying mechanism is largely unknown.Here,using esophageal squamous cell carcinoma(ESCC)as a model,we demonstrate that guanine nucleotide exchange factor 2(VAV2),which is overexpressed in most human cancers,plays an important role in primary and secondary radioresistance.We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation.
