Photocatalytic conversion of CO_(2)into a special chemical fuel with high yield and selectivity is still a major challenge.Herein,a 3 D hierarchical Ni Al-LDH/Ti_(3)C_(2)MXene(LDH/TC)nanocomposite is constructed throu...Photocatalytic conversion of CO_(2)into a special chemical fuel with high yield and selectivity is still a major challenge.Herein,a 3 D hierarchical Ni Al-LDH/Ti_(3)C_(2)MXene(LDH/TC)nanocomposite is constructed through in situ loading of Ti_(3)C_(2)nanosheets on the Ni Al-LDH scaffold during the hydrothermal process.The formation of a uniform and well-defined 2 D/2 D heterogeneous interface can be realized by optimizing the ratio of Ti_(3)C_(2)and the precursors for Ni Al-LDH.The 3 D hierarchical scaffold with high specific surface area contributes to the favourable photon adsorption and utilization.The intimate contact between Ti_(3)C_(2)and Ni Al-LDH with numerous interfaces effectively promotes the separation of the photoinduced electron-hole pairs in Ni Al-LDH.Together with the highly exposed oxidation-reduction active sites and the enhanced CO_(2)capture and activation.The maximum photocatalytic CO production rate on Ni AlLDH/Ti_(3)C_(2)reaches 11.82 lmol g^(-1)h^(-1)with 92%selectivity and superior stability.This work provides an effective approach for the development of an ideal photocatalyst by collaborative utilization of materials with different dimensionalities.展开更多
In recent years,gesture recognition has been widely used in the fields of intelligent driving,virtual reality,and human-computer interaction.With the development of artificial intelligence,deep learning has achieved r...In recent years,gesture recognition has been widely used in the fields of intelligent driving,virtual reality,and human-computer interaction.With the development of artificial intelligence,deep learning has achieved remarkable success in computer vision.To help researchers better understanding the development status of gesture recognition in video,this article provides a detailed survey of the latest developments in gesture recognition technology for videos based on deep learning.The reviewed methods are broadly categorized into three groups based on the type of neural networks used for recognition:two stream convolutional neural networks,3D convolutional neural networks,and Long-short Term Memory(LSTM)networks.In this review,we discuss the advantages and limitations of existing technologies,focusing on the feature extraction method of the spatiotemporal structure information in a video sequence,and consider future research directions.展开更多
In this paper,the evaluations of metal ablation processes under high temperature,i.e.,the Al plate ablated by a laser and a heat carrier and the reactor pressure vessel ablated by a core melt,are studied by a novel pe...In this paper,the evaluations of metal ablation processes under high temperature,i.e.,the Al plate ablated by a laser and a heat carrier and the reactor pressure vessel ablated by a core melt,are studied by a novel peridynamic method.Above all,the peridynamic formulation for the heat conduction problem is obtained by Taylor’s expansion technique.Then,a simple and efficient moving boundary model in the peridynamic framework is proposed to handle the variable geometries,in which the ablated states of material points are described by an additional scalar field.Next,due to the automatic non-interpenetration properties of peridynamic method,a contact algorithm is established to determine the contact relationship between the ablated system and the additional heat carrier.In addition,the corresponding computational procedure is listed in detail.Finally,several numerical examples are carried out and the results verify the validity and accuracy of the present method.展开更多
Selecting the optimal speed for dynamic obstacle avoidance in complex man–machine environments is a challenging problem for mobile robots inspecting hazardous gases.Consideration of personal space is important,especi...Selecting the optimal speed for dynamic obstacle avoidance in complex man–machine environments is a challenging problem for mobile robots inspecting hazardous gases.Consideration of personal space is important,especially in a relatively narrow man–machine dynamic environments such as warehouses and laboratories.In this study,human and robot behaviors in man–machine environments are analyzed,and a man–machine social force model is established to study the robot obstacle avoidance speed.Four typical man–machine behavior patterns are investigated to design the robot behavior strategy.Based on the social force model and man–machine behavior patterns,the fuzzy-PID trajectory tracking control method and the autonomous obstacle avoidance behavior strategy of the mobile robot in inspecting hazardous gases in a relatively narrow man–machine dynamic environment are proposed to determine the optimal robot speed for obstacle avoidance.The simulation analysis results show that compared with the traditional PID control method,the proposed controller has a position error of less than 0.098 m,an angle error of less than 0.088 rad,a smaller steady-state error,and a shorter convergence time.The crossing and encountering pattern experiment results show that the proposed behavior strategy ensures that the robot maintains a safe distance from humans while performing trajectory tracking.This research proposes a combination autonomous behavior strategy for mobile robots inspecting hazardous gases,ensuring that the robot maintains the optimal speed to achieve dynamic obstacle avoidance,reducing human anxiety and increasing comfort in a relatively narrow man–machine environment.展开更多
The treatment of stage Ⅲ non-small cell lung cancer(NSCLC) consisting of the heterogeneous stage subsets remains a challenge. Overall, it has been gradually recognized that radiation therapy(RT) plays a crucial role ...The treatment of stage Ⅲ non-small cell lung cancer(NSCLC) consisting of the heterogeneous stage subsets remains a challenge. Overall, it has been gradually recognized that radiation therapy(RT) plays a crucial role in the management of stage Ⅲ NSCLC. One superior sulcus tumors are the subset for which the trimodality treatments are clearly preferred. One subset of stage Ⅲ NSCLC has a minimal disease burden with microscopic p N2 disease or with discrete p N2 involvement identified preoperatively, thus technically could undergo a surgical resection. For the incidentally found p N2 disease after complete surgery(ⅢA-1, ⅢA-2), the value of postoperative radiotherapy(PORT) has been recognized by a reassessment based on new data. However, doubt persists regarding how to define the clinical target volume for PORT. For the discrete p N2 involvement identified preoperatively(a selected part of ⅢA-3), induction chemoradiation therapy(CRT) before surgery may yield a survival advantage, although the phase Ⅲ randomized trials in this issue are not conclusive. The other major subset of stage Ⅲ NSCLC is the infiltrative stage Ⅲ NSCLC with N2 or N3 nodal disease(ⅢA-3, ⅢA-4, and ⅢB), for which concurrent CRT is considered as the current standard of care. The potential role of radiation dose escalation/acceleration has been proposed; however, the optimal dose fractionation remains an important unresolved question. Additionally, the role of prophylactic cranial irradiation for stage Ⅲ patients with high risk of brain metastasis is worth of further assessment. Moreover, how to integrate molecular targeted therapy with RT, as well as whether they had a role in stage Ⅲ diseases, are other controversies actively under study in ongoing trials. This review specifically describes the updated role of RT in multimodal approach to treat stage Ⅲ NSCLC and the controversies regarding these results in various situations.展开更多
Auditory hair cells(HCs)are the mechanosensory receptors of the cochlea,and HC loss or malfunction can result from genetic defects.Dock4,a member of the Dock180-related protein superfamily,is a guanine nucleotide exch...Auditory hair cells(HCs)are the mechanosensory receptors of the cochlea,and HC loss or malfunction can result from genetic defects.Dock4,a member of the Dock180-related protein superfamily,is a guanine nucleotide exchange factor for Rac1,and previous reports have shown that Dock4 mutations are associated with autism spectrum disorder,myelodysplastic syndromes,and tumorigenesis.Here,we found that Dock4 is highly expressed in the cochlear HCs of mice.However,the role of Dock4 in the inner ear has not yet been investigated.Taking advantage of the piggyBac transposon system,Dock4 knockdown(KD)mice were established to explore the role of Dock4 in the cochlea.Compared to wild-type controls,Dock4 KD mice showed significant hearing impairment from postnatal day 60.Dock4 KD mice showed hair bundle deficits and increased oxidative stress,which eventually led to HC apoptosis,late-onset HC loss,and progressive hearing loss.Furthermore,molecular mechanism studies showed that Rac1/β-catenin signaling was significantly downregulated in Dock4 KD cochleae and that this was the cause for the disorganized stereocilia and increased oxidative stress in HCs.Overall,our work demonstrates that the Dock4/Rac1/β-catenin signaling pathway plays a critical role in the maintenance of auditory HCs and hearing function.展开更多
Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and inflammation.Mitochondria regulate macrophage activation and innate immun...Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and inflammation.Mitochondria regulate macrophage activation and innate immune responses in various inflammatory diseases,including cochlear inflammation.The distribution,number,and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions,including noise exposure,ototoxicity,and age-related degeneration.However,the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains unclear.Here,we summarize the major factors and mitochondrial signaling pathways(e.g.,metabolism,mitochondrial reactive oxygen species,mitochondrial DNA,and the inflammasome)that influence macrophage activation in the innate immune response.In particular,we focus on the properties of cochlear macrophages,activated signaling pathways,and the secretion of inflammatory cytokines after acoustic injury.We hope this review will provide new perspectives and a basis for future research on cochlear inflammation.展开更多
Progressive functional deterioration in the cochlea is associated with age-related hearing loss(ARHL).However,the cellular and molecular basis underlying cochlear aging remains largely unknown.Here,we established a dy...Progressive functional deterioration in the cochlea is associated with age-related hearing loss(ARHL).However,the cellular and molecular basis underlying cochlear aging remains largely unknown.Here,we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging,in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points.Overall,our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging,highlights unexpected age-related transcriptional fluctuations in intermediate ceils localized in the stria vascularis(SV)and demonstrates that upregulation of endoplasmic reticulum(ER)chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging.Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related sVatrophyand hencedelay theprogressionofARHL.展开更多
Tprn encodes the taperin protein,which is concentrated in the tapered region of hair cell stereocilia in the inner ear.In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness(DFNB79)by an unknown mech...Tprn encodes the taperin protein,which is concentrated in the tapered region of hair cell stereocilia in the inner ear.In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness(DFNB79)by an unknown mechanism.To determine the role of Tprn in hearing,we generated Tprn-null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background.We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of Tprn-null mice starting from postnatal day 30.Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts.The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings.Radixin,a protein expressed at stereocilia tapering,was abnormally dispersed along the stereocilia shafts in Tprn-null mice.The expression levels of radixin andβ-actin significantly decreased.We propose that Tprn is critical to the retention of the integrity of the stereociliary rootlet.Loss of Tprn in Tprn-null mice caused the disruption of the stereociliary rootlet,which resulted in damage to stereociliary bundles and hearing impairments.The generated Tprn-null mice are ideal models of human hereditary deafness DFNB79.展开更多
Developing all-solid-state polymer electrolytes(SPEs) with high electrochemical performances and stability is of great importance for exploiting of high energy density and safe batteries. Herein, ether linkage and imi...Developing all-solid-state polymer electrolytes(SPEs) with high electrochemical performances and stability is of great importance for exploiting of high energy density and safe batteries. Herein, ether linkage and imidazolium ionic liquid(ILs) are incorporated into the multi-armed polymer backbone though the series and parallel way. The parallel polymeric ionic liquid(P-P(PEGMA-IM)) maximizes the synergistic effect of ILs and ether linkage, which endowed the material with low crystallinity and high flame retardancy. The P-P(PEGMA-IM) based P-SPE presents a high ionic conductivity of 0.489 m S/cm at 60°C, an excellent lithium-ion transference number of 0.46 and a wide electrochemical window of 4.87 V.The assembled lithium metal battery using P-SPE can deliver a capacity of 151 m Ah/g at 0.2 C, and the capacity retention ratio reaches 82% with a columbic efficiency beyond 99%. The overpotential of P-SPE based symmetric battery is 0.08 V, and there is no apparent magnifying even after 130 h cycling. This new design provides a new avenue for exploitation of advanced SPEs for the next-generation batteries.展开更多
Autophagy,a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway,is an important mechanism for cellular self-protection in eukaryotes.Autophagy plays essential roles in cell s...Autophagy,a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway,is an important mechanism for cellular self-protection in eukaryotes.Autophagy plays essential roles in cell survival,renewal,material reuse and the maintenance of homeostasis.This paper reviews recent advances in understanding the physiological function of autophagy and its possible roles in auditory diseases.We focused our review on original publications on animal models,drug models,and molecular mechanisms of hearing impairment involved in the dysregulation of autophagy.As research on the mechanisms of autophagy has deepened,it has become obvious that autophagy plays essential roles not only in cell survival,but the occurrence and development of a variety of auditory-related disorder,including aminoglycoside-induced hearing loss,age-related hearing loss,and noise-induced hearing loss.While clinical treatment of such conditions via regulation of the development of autophagy is a novel idea,more time is needed to fully elucidate the specific regulatory pathways and modes of autophagy in auditory diseases.The continued study of the mechanisms and regulation of autophagy in auditory diseases will be of great significance for the future treatment and prevention of these conditions.展开更多
基金the National Natural Science Foundation of China(51303083)the National Natural Science Foundation of China for Excellent Young Scholars(51922050)+2 种基金the Natural Science Foundation of Jiangsu Province(BK20191293)the China Postdoctoral Science Foundation(2017m621708)the Fundamental Research Funds for the Central Universities(30920021123)for financial support。
文摘Photocatalytic conversion of CO_(2)into a special chemical fuel with high yield and selectivity is still a major challenge.Herein,a 3 D hierarchical Ni Al-LDH/Ti_(3)C_(2)MXene(LDH/TC)nanocomposite is constructed through in situ loading of Ti_(3)C_(2)nanosheets on the Ni Al-LDH scaffold during the hydrothermal process.The formation of a uniform and well-defined 2 D/2 D heterogeneous interface can be realized by optimizing the ratio of Ti_(3)C_(2)and the precursors for Ni Al-LDH.The 3 D hierarchical scaffold with high specific surface area contributes to the favourable photon adsorption and utilization.The intimate contact between Ti_(3)C_(2)and Ni Al-LDH with numerous interfaces effectively promotes the separation of the photoinduced electron-hole pairs in Ni Al-LDH.Together with the highly exposed oxidation-reduction active sites and the enhanced CO_(2)capture and activation.The maximum photocatalytic CO production rate on Ni AlLDH/Ti_(3)C_(2)reaches 11.82 lmol g^(-1)h^(-1)with 92%selectivity and superior stability.This work provides an effective approach for the development of an ideal photocatalyst by collaborative utilization of materials with different dimensionalities.
基金the National Key R&D Program of China(2018YFC0807500)the National Natural Science Foundation of China(61772396,61772392,62002271,61902296)+3 种基金the Fundamental Research Funds for the Central Universities(JBF180301,XJS210310,XJS190307)Xi'an Key Laboratory of Big Data and Intelligent Vision(201805053ZD4CG37)the National Natural Science Foundation of Shaanxi Province(2020JQ-330,2020JM-195)the China Postdoctoral Science Foundation(2019M663640).
文摘In recent years,gesture recognition has been widely used in the fields of intelligent driving,virtual reality,and human-computer interaction.With the development of artificial intelligence,deep learning has achieved remarkable success in computer vision.To help researchers better understanding the development status of gesture recognition in video,this article provides a detailed survey of the latest developments in gesture recognition technology for videos based on deep learning.The reviewed methods are broadly categorized into three groups based on the type of neural networks used for recognition:two stream convolutional neural networks,3D convolutional neural networks,and Long-short Term Memory(LSTM)networks.In this review,we discuss the advantages and limitations of existing technologies,focusing on the feature extraction method of the spatiotemporal structure information in a video sequence,and consider future research directions.
基金supported by the National Natural Science Foundation of China(No.12102416).
文摘In this paper,the evaluations of metal ablation processes under high temperature,i.e.,the Al plate ablated by a laser and a heat carrier and the reactor pressure vessel ablated by a core melt,are studied by a novel peridynamic method.Above all,the peridynamic formulation for the heat conduction problem is obtained by Taylor’s expansion technique.Then,a simple and efficient moving boundary model in the peridynamic framework is proposed to handle the variable geometries,in which the ablated states of material points are described by an additional scalar field.Next,due to the automatic non-interpenetration properties of peridynamic method,a contact algorithm is established to determine the contact relationship between the ablated system and the additional heat carrier.In addition,the corresponding computational procedure is listed in detail.Finally,several numerical examples are carried out and the results verify the validity and accuracy of the present method.
基金Research and Development Program of Xi’an Modern Chemistry Research Institute of Chnia(Grant No.204J201916234/6)Key Project of Liuzhou Science and Technology Bureau of China(Grant No.2020PAAA0601).
文摘Selecting the optimal speed for dynamic obstacle avoidance in complex man–machine environments is a challenging problem for mobile robots inspecting hazardous gases.Consideration of personal space is important,especially in a relatively narrow man–machine dynamic environments such as warehouses and laboratories.In this study,human and robot behaviors in man–machine environments are analyzed,and a man–machine social force model is established to study the robot obstacle avoidance speed.Four typical man–machine behavior patterns are investigated to design the robot behavior strategy.Based on the social force model and man–machine behavior patterns,the fuzzy-PID trajectory tracking control method and the autonomous obstacle avoidance behavior strategy of the mobile robot in inspecting hazardous gases in a relatively narrow man–machine dynamic environment are proposed to determine the optimal robot speed for obstacle avoidance.The simulation analysis results show that compared with the traditional PID control method,the proposed controller has a position error of less than 0.098 m,an angle error of less than 0.088 rad,a smaller steady-state error,and a shorter convergence time.The crossing and encountering pattern experiment results show that the proposed behavior strategy ensures that the robot maintains a safe distance from humans while performing trajectory tracking.This research proposes a combination autonomous behavior strategy for mobile robots inspecting hazardous gases,ensuring that the robot maintains the optimal speed to achieve dynamic obstacle avoidance,reducing human anxiety and increasing comfort in a relatively narrow man–machine environment.
文摘The treatment of stage Ⅲ non-small cell lung cancer(NSCLC) consisting of the heterogeneous stage subsets remains a challenge. Overall, it has been gradually recognized that radiation therapy(RT) plays a crucial role in the management of stage Ⅲ NSCLC. One superior sulcus tumors are the subset for which the trimodality treatments are clearly preferred. One subset of stage Ⅲ NSCLC has a minimal disease burden with microscopic p N2 disease or with discrete p N2 involvement identified preoperatively, thus technically could undergo a surgical resection. For the incidentally found p N2 disease after complete surgery(ⅢA-1, ⅢA-2), the value of postoperative radiotherapy(PORT) has been recognized by a reassessment based on new data. However, doubt persists regarding how to define the clinical target volume for PORT. For the discrete p N2 involvement identified preoperatively(a selected part of ⅢA-3), induction chemoradiation therapy(CRT) before surgery may yield a survival advantage, although the phase Ⅲ randomized trials in this issue are not conclusive. The other major subset of stage Ⅲ NSCLC is the infiltrative stage Ⅲ NSCLC with N2 or N3 nodal disease(ⅢA-3, ⅢA-4, and ⅢB), for which concurrent CRT is considered as the current standard of care. The potential role of radiation dose escalation/acceleration has been proposed; however, the optimal dose fractionation remains an important unresolved question. Additionally, the role of prophylactic cranial irradiation for stage Ⅲ patients with high risk of brain metastasis is worth of further assessment. Moreover, how to integrate molecular targeted therapy with RT, as well as whether they had a role in stage Ⅲ diseases, are other controversies actively under study in ongoing trials. This review specifically describes the updated role of RT in multimodal approach to treat stage Ⅲ NSCLC and the controversies regarding these results in various situations.
基金This work was supported by grants from National Key R&D Program of China(2021YFA1101300,2020YFA0112503,2020YFA0113600)the Strategic Priority Research Program of the Chinese Academy of Science(XDA16010303)+5 种基金the National Natural Science Foundation of China(82030029,81970882,82071013,81870721,92149304,82000984)the Natural Science Foundation of Jiangsu Province(BE2019711)the Science and Technology Department of Sichuan Province(2021YFS0371)the Shenzhen Fundamental Research Program(JCYJ20190814093401920,JCYJ20210324125608022)the China National Postdoctoral Program for Innovative Talents(BX20200082)the Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University(SKLGE-2109).
文摘Auditory hair cells(HCs)are the mechanosensory receptors of the cochlea,and HC loss or malfunction can result from genetic defects.Dock4,a member of the Dock180-related protein superfamily,is a guanine nucleotide exchange factor for Rac1,and previous reports have shown that Dock4 mutations are associated with autism spectrum disorder,myelodysplastic syndromes,and tumorigenesis.Here,we found that Dock4 is highly expressed in the cochlear HCs of mice.However,the role of Dock4 in the inner ear has not yet been investigated.Taking advantage of the piggyBac transposon system,Dock4 knockdown(KD)mice were established to explore the role of Dock4 in the cochlea.Compared to wild-type controls,Dock4 KD mice showed significant hearing impairment from postnatal day 60.Dock4 KD mice showed hair bundle deficits and increased oxidative stress,which eventually led to HC apoptosis,late-onset HC loss,and progressive hearing loss.Furthermore,molecular mechanism studies showed that Rac1/β-catenin signaling was significantly downregulated in Dock4 KD cochleae and that this was the cause for the disorganized stereocilia and increased oxidative stress in HCs.Overall,our work demonstrates that the Dock4/Rac1/β-catenin signaling pathway plays a critical role in the maintenance of auditory HCs and hearing function.
基金supported by the China Postdoctoral Science Foundation(2022M712892)the Joint project Henan Province Medical Science and Technology Project(LHGJ20210297).
文摘Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and inflammation.Mitochondria regulate macrophage activation and innate immune responses in various inflammatory diseases,including cochlear inflammation.The distribution,number,and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions,including noise exposure,ototoxicity,and age-related degeneration.However,the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains unclear.Here,we summarize the major factors and mitochondrial signaling pathways(e.g.,metabolism,mitochondrial reactive oxygen species,mitochondrial DNA,and the inflammasome)that influence macrophage activation in the innate immune response.In particular,we focus on the properties of cochlear macrophages,activated signaling pathways,and the secretion of inflammatory cytokines after acoustic injury.We hope this review will provide new perspectives and a basis for future research on cochlear inflammation.
基金supported by the National Key Research and Development Program of China(No.2020YFA0804000)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16000000)+12 种基金the National Natural Science Foundation of China(Nos.82192863,81921006,92149301,92168201,91949209,92049304,82125011,82122024,82071588,92049116,32121001,32000500,82030029,81970882,31900523,82271600,32200610,and 81861168034)the National Key Research and Development Program of China(Nos.2018YFC2000100,2021ZD0202400,2020YFA0112200,2018YFA0107203,2021YFF1201005,and2019YFA0110100)the Program of the Beijing Natural Science Foundation(No.Z190019)CAS Project for Young Scientists in Basic Research(No.YSBR-076 and YSBR-012)the Key Research Program of the Chinese Academy of Sciences(No.KFZD-SW-221)K.C.Wong Education Foundation(Nos.GJTD-2019-06 and GJTD-2019-08)Youth Innovation Promotion Association of CAS(Nos.2021078,2022083,and E1CAZW0401)Young Elite Scientists Sponsorship Program by CAST(Nos.YESS20200012 and YESS20210002)the State Key Laboratory of Stem Cell and Reproductive Biology,the State Key Laboratory of Membrane Biology,the Tencent Foundation(No.2021-1045)the Informatization Plan of Chinese Academy of Sciences(Nos.CAS-WX2021SF-0301 and CASWX2022SDC-XK14)the Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(No.11000022T000000461062)Natural Science Foundation from Jiangsu Province(No.BE2019711),Shenzhen Fundamental Research Program(No.JCYJ20190814093401920)Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University(No.SKLGE-2109).
文摘Progressive functional deterioration in the cochlea is associated with age-related hearing loss(ARHL).However,the cellular and molecular basis underlying cochlear aging remains largely unknown.Here,we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging,in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points.Overall,our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging,highlights unexpected age-related transcriptional fluctuations in intermediate ceils localized in the stria vascularis(SV)and demonstrates that upregulation of endoplasmic reticulum(ER)chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging.Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related sVatrophyand hencedelay theprogressionofARHL.
文摘Tprn encodes the taperin protein,which is concentrated in the tapered region of hair cell stereocilia in the inner ear.In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness(DFNB79)by an unknown mechanism.To determine the role of Tprn in hearing,we generated Tprn-null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background.We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of Tprn-null mice starting from postnatal day 30.Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts.The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings.Radixin,a protein expressed at stereocilia tapering,was abnormally dispersed along the stereocilia shafts in Tprn-null mice.The expression levels of radixin andβ-actin significantly decreased.We propose that Tprn is critical to the retention of the integrity of the stereociliary rootlet.Loss of Tprn in Tprn-null mice caused the disruption of the stereociliary rootlet,which resulted in damage to stereociliary bundles and hearing impairments.The generated Tprn-null mice are ideal models of human hereditary deafness DFNB79.
基金National Natural Science Foundation of China (No. 51303083)the Natural Science Foundation of Jiangsu Province (No. BK20191293)the Fundamental Research Funds for the Central Universities (No. 30920021123) for financial support。
文摘Developing all-solid-state polymer electrolytes(SPEs) with high electrochemical performances and stability is of great importance for exploiting of high energy density and safe batteries. Herein, ether linkage and imidazolium ionic liquid(ILs) are incorporated into the multi-armed polymer backbone though the series and parallel way. The parallel polymeric ionic liquid(P-P(PEGMA-IM)) maximizes the synergistic effect of ILs and ether linkage, which endowed the material with low crystallinity and high flame retardancy. The P-P(PEGMA-IM) based P-SPE presents a high ionic conductivity of 0.489 m S/cm at 60°C, an excellent lithium-ion transference number of 0.46 and a wide electrochemical window of 4.87 V.The assembled lithium metal battery using P-SPE can deliver a capacity of 151 m Ah/g at 0.2 C, and the capacity retention ratio reaches 82% with a columbic efficiency beyond 99%. The overpotential of P-SPE based symmetric battery is 0.08 V, and there is no apparent magnifying even after 130 h cycling. This new design provides a new avenue for exploitation of advanced SPEs for the next-generation batteries.
文摘Autophagy,a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway,is an important mechanism for cellular self-protection in eukaryotes.Autophagy plays essential roles in cell survival,renewal,material reuse and the maintenance of homeostasis.This paper reviews recent advances in understanding the physiological function of autophagy and its possible roles in auditory diseases.We focused our review on original publications on animal models,drug models,and molecular mechanisms of hearing impairment involved in the dysregulation of autophagy.As research on the mechanisms of autophagy has deepened,it has become obvious that autophagy plays essential roles not only in cell survival,but the occurrence and development of a variety of auditory-related disorder,including aminoglycoside-induced hearing loss,age-related hearing loss,and noise-induced hearing loss.While clinical treatment of such conditions via regulation of the development of autophagy is a novel idea,more time is needed to fully elucidate the specific regulatory pathways and modes of autophagy in auditory diseases.The continued study of the mechanisms and regulation of autophagy in auditory diseases will be of great significance for the future treatment and prevention of these conditions.