The Sandaowanzi gold deposit is an extremely Au-rich deposit in the Northern Great Hinggan Range in recent years.Zircon U-Pb geochronology,Hf isotope analysis,and the geochemistry of andesites of the Longjiang Formati...The Sandaowanzi gold deposit is an extremely Au-rich deposit in the Northern Great Hinggan Range in recent years.Zircon U-Pb geochronology,Hf isotope analysis,and the geochemistry of andesites of the Longjiang Formation from the Sandaowanzi gold deposit were used to investigate the origin,magmatic evolution as well as mineralization and tectonic setting of the Early Cretaceous epithermal gold deposits in the northern Great Hinggan Range area.Zircon U-Pb dating reveals an emplacement age of 123.4±0.3 Ma,indicating that the andesites of the Sandaowanzi gold deposit was formed during the Early Cretaceous.The andesites are enriched in light rare earth elements relative to heavy rare earth elements and have weak negative Eu anomalies(δEu=0.76-0.90).The rocks are also enriched in large-ion lithophile elements,such as Rb,Ba,Th,U,and K,and depleted in the high-field-strength elements,such as Nb,Ta,and P.These characteristics are typical of volcanic rocks related to subduction.Igneous zircons from the andesite samples have relatively homogeneous Hf isotope ratios,176Hf/177Hf values of 0.282343-0.282502,εHf(t)values of-12.58 to-6.95,and two-stage model ages(TDM2)of 1743-1431 Ma.The characteristics of the andesites of the Longjiang Formation are consistent with derivation from partial melting of enriched mantle wedge metasomatized by subducted-slab-derived fluids.These rocks formed in an extensional environment associated with the closure of the Mongol-Okhotsk Ocean and subduction of the Paleo-Pacific Plate.Mineralization occurred towards the end of volcanism,and the magmatic activity and mineralization are products of the same geodynamic setting.展开更多
Under the background of New Engineering,focusing on talent cultivation,this article explores the teaching reform and innovation of software engineering majors.Starting from the goal of cultivating software engineering...Under the background of New Engineering,focusing on talent cultivation,this article explores the teaching reform and innovation of software engineering majors.Starting from the goal of cultivating software engineering talents in the context of New Engineering,the concept of outcome-based education is introduced to study and explore the construction of innovative talent training models for software engineering majors in universities.Through recent years’application practice,initial results have been achieved,which can provide feasible methods and ideas for the cultivation of innovative talents in other majors.展开更多
The penetration capability of the drug nano-carriers (NCs) in biological hydrogels, such as mucus and tumor interstitial matrix, would typically influence the efficiency of drug delivery. Understanding the effect of t...The penetration capability of the drug nano-carriers (NCs) in biological hydrogels, such as mucus and tumor interstitial matrix, would typically influence the efficiency of drug delivery. Understanding the effect of the physicochemical property of the drug carriers on their diffusion capability in biological hydrogel becomes important for designing and optimizing the nano-carriers. Here, using a coarse-grained molecular dynamics model, we studied how the rigidity of NCs affected their diffusivity in biological hydrogel. The results showed that semi-elastic NCs have higher diffusivity than the hard and the soft NCs. Furthermore, the affinity between the NCs and biological hydrogels and the size ratio between the hydrogel meshes and NCs have also affected the diffusivity of the NCs. Further analysis revealed the mechanism that the deformation of the NCs dominates their diffusivity. These findings demonstrated that the rigidity of NCs is a key parameter in designing efficient NCs for deep penetration into the biological hydrogels.展开更多
The growing complexity of integrated circuits (ICs) is driving the trend of IC testing towards testing based on behavioral descriptions of register-transfer level (RTL). A behavioral description contains an algorithmi...The growing complexity of integrated circuits (ICs) is driving the trend of IC testing towards testing based on behavioral descriptions of register-transfer level (RTL). A behavioral description contains an algorithmic specification of functionality of design. It may contain little or even no information about the design’s cycle-by-cycle behavior or structural implementation. However, it usually has an interior variable to lead the process of its functional phases. This interior variable is named phase variable. The functional behavior of a digital circuit changes according to different values of a phase variable. By analyzing some ITC99 benchmark circuits, this paper presents a way to generate tests for a circuit by tracing the value change of a phase variable in the circuit.展开更多
The paper proposes an ATPG method for the Synchronous Sequential circuits described in synthesizable VHDL behavioral RTL. The method extracts a controlling tree for each process in the behavioral description and forms...The paper proposes an ATPG method for the Synchronous Sequential circuits described in synthesizable VHDL behavioral RTL. The method extracts a controlling tree for each process in the behavioral description and forms a graph to represent the static data-flow for the target circuit. A fault-model is defined at RT-Level. The ATPG method is then presented. Experimental results show that the ATPG method is time effective and can generate tests with fairly good quality, the fault coverage of some circuits is to be enhanced though.展开更多
Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss ...Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.展开更多
Waardenburg syndrome typeⅡ(WS2) is associated with syndromic deafness.A subset of WS2,WS2A,accounting for approximately 15%of patients,is attributed to mutations in the microphthalmia-associated transcription factor(...Waardenburg syndrome typeⅡ(WS2) is associated with syndromic deafness.A subset of WS2,WS2A,accounting for approximately 15%of patients,is attributed to mutations in the microphthalmia-associated transcription factor(MITF) gene.We examined the genetic basis of WS2 in a large Chinese family.All 9 exons of the MITF gene,the single coding exon(exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA(mtDNA) 12S rRNA were sequenced.A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA]in exon 8 of the MITF gene co-segregates with WS2 in the family.The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids.The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G>A]+ [235delC]compound heterozygous pathogenic mutation in the GJB2 gene.No pathogenic mutation was found in mtDNA 12S rRNA in this family.Thus,a novel compound heterozygous mutation,c.[742_743delAAinsT;746_747delCA]in MITF exon 8 was the key genetic reason for WS2 in this family,and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband.展开更多
Hardware Trojans(HTs)have drawn increasing attention in both academia and industry because of their significant potential threat.In this paper,we propose HTDet,a novel HT detection method using information entropybase...Hardware Trojans(HTs)have drawn increasing attention in both academia and industry because of their significant potential threat.In this paper,we propose HTDet,a novel HT detection method using information entropybased clustering.To maintain high concealment,HTs are usually inserted in the regions with low controllability and low observability,which will result in that Trojan logics have extremely low transitions during the simulation.This implies that the regions with the low transitions will provide much more abundant and more important information for HT detection.The HTDet applies information theory technology and a density-based clustering algorithm called Density-Based Spatial Clustering of Applications with Noise(DBSCAN)to detect all suspicious Trojan logics in the circuit under detection.The DBSCAN is an unsupervised learning algorithm,that can improve the applicability of HTDet.In addition,we develop a heuristic test pattern generation method using mutual information to increase the transitions of suspicious Trojan logics.Experiments on circuit benchmarks demonstrate the effectiveness of HTDet.展开更多
Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss.This study aimed to assess the potential effect of the DNA methyltransferase(DNMT)inhibitor RG108 on ci...Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss.This study aimed to assess the potential effect of the DNA methyltransferase(DNMT)inhibitor RG108 on cisplatin-induced ototoxicity.Immunohistochemistry,apoptosis assay,and auditory brainstem response(ABR)were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells(HCs)and spiral ganglion neurons(SGNs).Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential(MMP)assessment.Reactive oxygen species(ROS)amounts were evaluated by Cellrox green and Mitosox-red probes.Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates(OCRs).The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs,and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation.Furthermore,RG108 upregulated BCL-2 and downregulated APAF1,BAX,and BAD in HEI-OC1 cells,and triggered the PI3K/AKT pathway.Decreased expression of low-density lipoprotein receptor-related protein 1(LRP1)and high methylation of the LRP1 promoter were observed after cisplatin treatment.RG108 treatment can increase LRP1expression and decrease LRP1 promoter methylation.In conclusion,RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.展开更多
Astaxanthine(AST) has important biological activities including antioxidant and antiinflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearin...Astaxanthine(AST) has important biological activities including antioxidant and antiinflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss(CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2(NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathwayusing quantitative PCR and Western blotting. The levels of reactive oxygen species(ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction.Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.展开更多
Phase structure of sputtered Ta coating in the negative glow space and LPH effect were explored.The whole coating/substrate system is substrate→physically gas-absorbed Fe surface→oxygen-enriched TaOx layer→amorphou...Phase structure of sputtered Ta coating in the negative glow space and LPH effect were explored.The whole coating/substrate system is substrate→physically gas-absorbed Fe surface→oxygen-enriched TaOx layer→amorphous Ta→αandβdual phase→singleαphase.After LPH course,micro structure of Ta coating shows intact,only a few cracks emerge after 100 laser pulses,exhibiting thin HAZ but thick Fe/Ta ICZ,without martensitic transformation.For the electrodeposited Cr coating,continuous thermal stresses produce many extra micro-crack,substrate oxidation and martensitic transformation,leading to crack propagations and final bulk delamination,without any ICZ.展开更多
CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-...CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.展开更多
PbI2/MoS2,as a typical van der Waals(vdW)heterostructure,has attracted intensive attention owing to its remarkable electronic and optoelectronic properties.In this work,the effect of defects on the electronic structur...PbI2/MoS2,as a typical van der Waals(vdW)heterostructure,has attracted intensive attention owing to its remarkable electronic and optoelectronic properties.In this work,the effect of defects on the electronic structures of a PbI2/MoS2 heterointerface has been systematically investigated.The manner in which the defects modulate the band structure of PbI2/MoS2,including the band gap,band edge,band alignment,and defect energy-level density within the band gap is discussed herein.It is shown that sulfur defects tune the band gaps,iodine defects shift the positions of the band edge and Fermi level,and lead defects realize the conversions between the straddling-gap band alignment and valence-band-aligned gap,thus enhancing the light-absorption ability of the material.展开更多
Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections(otitis medi...Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections(otitis media and otitis externa),cerumen obstruction,and injuries,congenital structural defects are uncommon for significant etiologies to recognize.Stapes ankylosis is characterized by conductive hearing loss.It may be difficult to differentiate from otosclerosis,the most common cause of progressive conductive hearing loss,by audiologic evaluation,when the diagnosis is delayed.Skeletal anomalies may be subtle,such that the syndrome may not be recognized(Brown et al.,2002).展开更多
To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort,we conducted a multicentric and retrospective study in the cardiology and otorhino...To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort,we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments.Records of patients with primary complaint of throat discomfort,absence of chest pain at onset,and an ultimate diagnosis of acute coronary syndrome,as well as patients with pharyngitis(as controls)were collected from May 2015 to April 2016.The patients’main manifestations were compared.Logistic regression results showed that chest tightness,dyspnea,perspiring,and exertional throat symptoms were significantly associated with acute coronary syndrome,with odds ratios of 8.3(95%CI 2.2–31.5),10.9(95%CI 1.8–66.9),25.4(95%CI 3.6–179.9),and 81.2(95%CI 13.0–506.7).A total of 25(56.82%)out of 44 acute coronary syndrome patients,who were first admitted to the otorhinolaryngology department,were misdiagnosed,with a 12%(3/25)mortality rate.Throat discomfort can be the principal manifestation of acute coronary syndrome.Such patients exhibit high misdiagnosis and mortality rates.Exertional throat symptoms,chest tightness,perspiring,and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort.The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.展开更多
基金funded by the National Natural Science Foundation of China (No. 41272093)Natural Science Foundation of Jilin Province (No. 20180101089JC)Key Projects of Science and Technology Development Plan of Jilin Province (No. 20100445)。
文摘The Sandaowanzi gold deposit is an extremely Au-rich deposit in the Northern Great Hinggan Range in recent years.Zircon U-Pb geochronology,Hf isotope analysis,and the geochemistry of andesites of the Longjiang Formation from the Sandaowanzi gold deposit were used to investigate the origin,magmatic evolution as well as mineralization and tectonic setting of the Early Cretaceous epithermal gold deposits in the northern Great Hinggan Range area.Zircon U-Pb dating reveals an emplacement age of 123.4±0.3 Ma,indicating that the andesites of the Sandaowanzi gold deposit was formed during the Early Cretaceous.The andesites are enriched in light rare earth elements relative to heavy rare earth elements and have weak negative Eu anomalies(δEu=0.76-0.90).The rocks are also enriched in large-ion lithophile elements,such as Rb,Ba,Th,U,and K,and depleted in the high-field-strength elements,such as Nb,Ta,and P.These characteristics are typical of volcanic rocks related to subduction.Igneous zircons from the andesite samples have relatively homogeneous Hf isotope ratios,176Hf/177Hf values of 0.282343-0.282502,εHf(t)values of-12.58 to-6.95,and two-stage model ages(TDM2)of 1743-1431 Ma.The characteristics of the andesites of the Longjiang Formation are consistent with derivation from partial melting of enriched mantle wedge metasomatized by subducted-slab-derived fluids.These rocks formed in an extensional environment associated with the closure of the Mongol-Okhotsk Ocean and subduction of the Paleo-Pacific Plate.Mineralization occurred towards the end of volcanism,and the magmatic activity and mineralization are products of the same geodynamic setting.
基金supported by the Natural Science Foundation of China under Grant 62171325Experimental Technology Project of Wuhan University under Grant WHU-2022-SYJS-11。
文摘Under the background of New Engineering,focusing on talent cultivation,this article explores the teaching reform and innovation of software engineering majors.Starting from the goal of cultivating software engineering talents in the context of New Engineering,the concept of outcome-based education is introduced to study and explore the construction of innovative talent training models for software engineering majors in universities.Through recent years’application practice,initial results have been achieved,which can provide feasible methods and ideas for the cultivation of innovative talents in other majors.
基金the National Natural Science Foundation of China (Grands 11422215, 11272327, and 11672079)partly supported by the Opening Fund of State Key Laboratory of Nonlinear Mechanics and the Natural Science Foundation of Zhejiang Province (Grant LQ17B030003).
文摘The penetration capability of the drug nano-carriers (NCs) in biological hydrogels, such as mucus and tumor interstitial matrix, would typically influence the efficiency of drug delivery. Understanding the effect of the physicochemical property of the drug carriers on their diffusion capability in biological hydrogel becomes important for designing and optimizing the nano-carriers. Here, using a coarse-grained molecular dynamics model, we studied how the rigidity of NCs affected their diffusivity in biological hydrogel. The results showed that semi-elastic NCs have higher diffusivity than the hard and the soft NCs. Furthermore, the affinity between the NCs and biological hydrogels and the size ratio between the hydrogel meshes and NCs have also affected the diffusivity of the NCs. Further analysis revealed the mechanism that the deformation of the NCs dominates their diffusivity. These findings demonstrated that the rigidity of NCs is a key parameter in designing efficient NCs for deep penetration into the biological hydrogels.
文摘The growing complexity of integrated circuits (ICs) is driving the trend of IC testing towards testing based on behavioral descriptions of register-transfer level (RTL). A behavioral description contains an algorithmic specification of functionality of design. It may contain little or even no information about the design’s cycle-by-cycle behavior or structural implementation. However, it usually has an interior variable to lead the process of its functional phases. This interior variable is named phase variable. The functional behavior of a digital circuit changes according to different values of a phase variable. By analyzing some ITC99 benchmark circuits, this paper presents a way to generate tests for a circuit by tracing the value change of a phase variable in the circuit.
基金supported by National Natural Science Foundation of China under grant No.69733010.
文摘The paper proposes an ATPG method for the Synchronous Sequential circuits described in synthesizable VHDL behavioral RTL. The method extracts a controlling tree for each process in the behavioral description and forms a graph to represent the static data-flow for the target circuit. A fault-model is defined at RT-Level. The ATPG method is then presented. Experimental results show that the ATPG method is time effective and can generate tests with fairly good quality, the fault coverage of some circuits is to be enhanced though.
基金supported by the STI2030-Major Projects(2022ZD0205400)the National Natural Science Foundation of China(82192861,81922018,82271170,and 82101218)+3 种基金the Foundation from Science and Technology Commission of Shanghai Municipality(22140900800 and 20JC1419500)the Foundation from Shanghai Municipal Health Commission(20234Z0007)the China Postdoctoral Science Foundation(2021M700824 and 2022T150133)the Shanghai Super Postdoctoral Incentive Program.
文摘Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.
基金This work was supported by grants from the National Basic Research Program of China （973 Program, No. 2015CB965000）, National Natural Science Foundation of China （Nos. 81400463, 81570911, 81470692, 81230019, 81371094, 81500790, 81570921, 31500852, and 31501194）, J iangsu Province Natural Science Foundation （Nos. BK20150022, BK20140620, and BK20150598）, Fundamental Research Funds for the Central Universities （Nos. 2242014R- 30022 and 021414380037）, the Yingdong Huo Education Founda- tion, the Open Research Funds of the State Key Laboratory of Genetic Engineering, Fudan University （No. SKLGE-1407）, Major Program of Shanghai Committee of Science and Technology （Nos. 14DJ1400203 and 11441901000）, Doctoral Fund of Chinese Ministry of Education （No. 20120071110077）, and China Post- doctoral Science Foundation Funded Project （No. 2014M551328）.
基金This work was supported by grants from the National Basic Research Program of China （973 Program, No. 2015CB965000）, the National Natural Science Foundation of China （Nos. 81570911, 81470692, 81371094, 81230019, 81500790, 81570921, 31500852, and 31501194）, the Jiangsu Province Natural Science Foundation （Nos. BK20150022, BK20140620, and BK20150598）, the Fundamental Research Funds for the Central Universities （Nos. 2242014R30022 and 021414380037）, the Yingdong Huo Education Foundation, and the Open Research Funds of the State Key Laboratory of Genetic Engineering, Fudan University （No. SKLGE-1407）.
基金supported by the grants from the National Basic Research Program of China(Nos.2011CB504500, 2011CB504506 and 2010CB945503)the National Basic Research Program of China(No.2011504502)+1 种基金the Shanghai Municipal Commission of Science and Technology Program (No.09DJ140061)the National Natural Science Foundation of China(No.81070793)
文摘Waardenburg syndrome typeⅡ(WS2) is associated with syndromic deafness.A subset of WS2,WS2A,accounting for approximately 15%of patients,is attributed to mutations in the microphthalmia-associated transcription factor(MITF) gene.We examined the genetic basis of WS2 in a large Chinese family.All 9 exons of the MITF gene,the single coding exon(exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA(mtDNA) 12S rRNA were sequenced.A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA]in exon 8 of the MITF gene co-segregates with WS2 in the family.The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids.The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G>A]+ [235delC]compound heterozygous pathogenic mutation in the GJB2 gene.No pathogenic mutation was found in mtDNA 12S rRNA in this family.Thus,a novel compound heterozygous mutation,c.[742_743delAAinsT;746_747delCA]in MITF exon 8 was the key genetic reason for WS2 in this family,and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband.
文摘Hardware Trojans(HTs)have drawn increasing attention in both academia and industry because of their significant potential threat.In this paper,we propose HTDet,a novel HT detection method using information entropybased clustering.To maintain high concealment,HTs are usually inserted in the regions with low controllability and low observability,which will result in that Trojan logics have extremely low transitions during the simulation.This implies that the regions with the low transitions will provide much more abundant and more important information for HT detection.The HTDet applies information theory technology and a density-based clustering algorithm called Density-Based Spatial Clustering of Applications with Noise(DBSCAN)to detect all suspicious Trojan logics in the circuit under detection.The DBSCAN is an unsupervised learning algorithm,that can improve the applicability of HTDet.In addition,we develop a heuristic test pattern generation method using mutual information to increase the transitions of suspicious Trojan logics.Experiments on circuit benchmarks demonstrate the effectiveness of HTDet.
基金was supported by grants from the National Key R&D Program of China(No.2017YFA0103900)the National Natural Science Foundation of China(Nos.82071045,81870728,81830029,and 81970875)Shanghai Rising-Star Program(19QA1401800)。
文摘Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss.This study aimed to assess the potential effect of the DNA methyltransferase(DNMT)inhibitor RG108 on cisplatin-induced ototoxicity.Immunohistochemistry,apoptosis assay,and auditory brainstem response(ABR)were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells(HCs)and spiral ganglion neurons(SGNs).Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential(MMP)assessment.Reactive oxygen species(ROS)amounts were evaluated by Cellrox green and Mitosox-red probes.Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates(OCRs).The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs,and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation.Furthermore,RG108 upregulated BCL-2 and downregulated APAF1,BAX,and BAD in HEI-OC1 cells,and triggered the PI3K/AKT pathway.Decreased expression of low-density lipoprotein receptor-related protein 1(LRP1)and high methylation of the LRP1 promoter were observed after cisplatin treatment.RG108 treatment can increase LRP1expression and decrease LRP1 promoter methylation.In conclusion,RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.
基金financial support by the National Natural Science Foundation of China(82000980)。
文摘Astaxanthine(AST) has important biological activities including antioxidant and antiinflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss(CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2(NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathwayusing quantitative PCR and Western blotting. The levels of reactive oxygen species(ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction.Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.
基金financial support of the project from the National Natural Science Foundation of China(No.51701223)。
文摘Phase structure of sputtered Ta coating in the negative glow space and LPH effect were explored.The whole coating/substrate system is substrate→physically gas-absorbed Fe surface→oxygen-enriched TaOx layer→amorphous Ta→αandβdual phase→singleαphase.After LPH course,micro structure of Ta coating shows intact,only a few cracks emerge after 100 laser pulses,exhibiting thin HAZ but thick Fe/Ta ICZ,without martensitic transformation.For the electrodeposited Cr coating,continuous thermal stresses produce many extra micro-crack,substrate oxidation and martensitic transformation,leading to crack propagations and final bulk delamination,without any ICZ.
基金the National Natural Science Foundation of China(82171148,51873107,81770999)National Key Research and Development Program of China(2020YFA0908201)+3 种基金Science and Technology Commission of Shanghai Municipality(21S11905100)National Genetically Modified Organisms Breeding Major Projects of China(2016ZX08009003-006)Clinic Research Plan of SHDC(No.SHDC2020CR4083),“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG08)National Research Facility for Phenotypic and Genotypic Analysis of Model Animals(Beijing).
文摘CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.
基金National Natural Science Foundation of China(Grant No.11672079)the National Science Foundation of Beijing(Grant No.2184130)。
文摘PbI2/MoS2,as a typical van der Waals(vdW)heterostructure,has attracted intensive attention owing to its remarkable electronic and optoelectronic properties.In this work,the effect of defects on the electronic structures of a PbI2/MoS2 heterointerface has been systematically investigated.The manner in which the defects modulate the band structure of PbI2/MoS2,including the band gap,band edge,band alignment,and defect energy-level density within the band gap is discussed herein.It is shown that sulfur defects tune the band gaps,iodine defects shift the positions of the band edge and Fermi level,and lead defects realize the conversions between the straddling-gap band alignment and valence-band-aligned gap,thus enhancing the light-absorption ability of the material.
基金funded in part by the National Nature Science Foundation of China(81771013,81822011,and 81570914)Science and Technology Commission of Shanghai Municipality(17ZR1448600 and 18410712400)the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health in the United States(R03DC013866 and R01DC015052)
文摘Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections(otitis media and otitis externa),cerumen obstruction,and injuries,congenital structural defects are uncommon for significant etiologies to recognize.Stapes ankylosis is characterized by conductive hearing loss.It may be difficult to differentiate from otosclerosis,the most common cause of progressive conductive hearing loss,by audiologic evaluation,when the diagnosis is delayed.Skeletal anomalies may be subtle,such that the syndrome may not be recognized(Brown et al.,2002).
基金supported by the National Natural Science Foundation of China(Nos.81822011 and 81771013)Clinical Research Plan of SHDC(No.SHDC2020CR4083).
文摘To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort,we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments.Records of patients with primary complaint of throat discomfort,absence of chest pain at onset,and an ultimate diagnosis of acute coronary syndrome,as well as patients with pharyngitis(as controls)were collected from May 2015 to April 2016.The patients’main manifestations were compared.Logistic regression results showed that chest tightness,dyspnea,perspiring,and exertional throat symptoms were significantly associated with acute coronary syndrome,with odds ratios of 8.3(95%CI 2.2–31.5),10.9(95%CI 1.8–66.9),25.4(95%CI 3.6–179.9),and 81.2(95%CI 13.0–506.7).A total of 25(56.82%)out of 44 acute coronary syndrome patients,who were first admitted to the otorhinolaryngology department,were misdiagnosed,with a 12%(3/25)mortality rate.Throat discomfort can be the principal manifestation of acute coronary syndrome.Such patients exhibit high misdiagnosis and mortality rates.Exertional throat symptoms,chest tightness,perspiring,and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort.The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.
