Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological proces...Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.展开更多
Understanding the dominant force responsible for supercontinent breakup is crucial for establishing Earth＇s geodynamic evolution that includes supercontinent cycles and plate tectonics. Conventionally,two forces have...Understanding the dominant force responsible for supercontinent breakup is crucial for establishing Earth＇s geodynamic evolution that includes supercontinent cycles and plate tectonics. Conventionally,two forces have been considered： the push by mantle plumes from the sub-continental mantle which is called the active force for breakup, and the dragging force from oceanic subduction retreat which is called the passive force for breakup. However, the relative importance of these two forces is unclear. Here we model the supercontinent breakup coupled with global mantle convection in order to address this question. Our global model features a spherical harmonic degree-2 structure, which includes a major subduction girdle and two large upwelling（superplume） systems. Based on this global mantle structure,we examine the distribution of extensional stress applied to the supercontinent by both subsupercontinent mantle upwellings and subduction retreat at the supercontinent peripheral. Our results show that：（1） at the center half of the supercontinent, plume push stress is ～3 times larger than the stress induced by subduction retreat;（2） an average hot anomaly of no higher than 50 K beneath the supercontinent can produce a push force strong enough to cause the initialization of supercontinent breakup;（3） the extensional stress induced by subduction retreat concentrates on a ～600 km wide zone on the boundary of the supercontinent, but has far less impact to the interior of the supercontinent. We therefore conclude that although circum-supercontinent subduction retreat assists supercontinent breakup, sub-supercontinent mantle upwelling is the essential force.展开更多
The Internet of Things(IoT)has profoundly impacted our lives and has greatly revolutionized our lifestyle.The terminal devices in an IoT data aggregation application sense real-time data for the remote cloud server to...The Internet of Things(IoT)has profoundly impacted our lives and has greatly revolutionized our lifestyle.The terminal devices in an IoT data aggregation application sense real-time data for the remote cloud server to achieve intelligent decisions.However,the high frequency of collecting user data will raise people concerns about personal privacy.In recent years,many privacy-preserving data aggregation schemes have been proposed.Unfortunately,most existing schemes cannot support either arbitrary aggregation functions,or dynamic user group management,or fault tolerance.In this paper,we propose an efficient and privacy-preserving data aggregation scheme.In the scheme,we design a lightweight encryption method to protect the user privacy by using a ring topology and a random location sequence.On this basis,the proposed scheme supports not only arbitrary aggregation functions,but also flexible dynamic user management.Furthermore,the scheme achieves faulttolerant capabilities by utilizing a future data buffering mechanism.Security analysis reveals that the scheme can achieve the desired security properties,and experimental evaluation results show the scheme's efficiency in terms of computational and communication overhead.展开更多
Lymph node involvement increases the risk of breast cancer recurrence.An accurate non-invasive assessment of nodal involvement is valuable in cancer staging,surgical risk,and cost savings.Radiomics has been proposed t...Lymph node involvement increases the risk of breast cancer recurrence.An accurate non-invasive assessment of nodal involvement is valuable in cancer staging,surgical risk,and cost savings.Radiomics has been proposed to pre-operatively predict sentinel lymph node(SLN)status;however,radiomic models are known to be sensitive to acquisition parameters.The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based(DLB)features and compare its predictive performance to state-of-the-art radiomics.Specifically,this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution.Dynamic contrast-enhancement images from 198 patients(67 positive SLNs)were used in this study.Of these subjects,163 had an in-plane resolution of 0.7×0.7 mm^(2),which were randomly divided into a training set(approximately 67%)and a validation set(approximately 33%).The remaining 35 subjects with a different in-plane resolution(0.78×0.78 mm^(2))were treated as independent testing set for generalizability.Two methods were employed:(1)conventional radiomics(CR),and(2)DLB features which replaced hand-curated features with pre-trained VGG-16 features.The threshold determined using the training set was applied to the independent validation and testing dataset.Same feature reduction,feature selection,model creation procedures were used for both approaches.In the validation set(same resolution as training),the DLB model outperformed the CR model(accuracy 83%vs 80%).Furthermore,in the independent testing set of the dissimilar resolution,the DLB model performed markedly better than the CR model(accuracy 77%vs 71%).The predictive performance of the DLB model outperformed the CR model for this task.More interestingly,these improvements were seen particularly in the independent testing set of dissimilar resolution.This could indicate that DLB features can ultimately result in a more generalizable model.展开更多
Presence of higher breast density(BD)and persistence over time are risk factors for breast cancer.A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segme...Presence of higher breast density(BD)and persistence over time are risk factors for breast cancer.A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable.In this study,we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures.Three datasets of volunteers from two clinical trials were included.Breast MR images were acquired on 3T Siemens Biograph mMR,Prisma,and Skyra using 3D Cartesian six-echo GRE sequences with a fat-water separation technique.Two whole-breast segmentation strategies,utiliz-ing image registration and 3D U-Net,were developed.Manual segmentation was performed.A task-based analysis was performed:a previously developed MR-based BD measure,MagDensity,was calculated and assessed using automated and manual segmentation.The mean squared error(MSE)and intraclass correlation coefficient(ICC)between MagDensity were evaluated using the manual segmentation as a reference.The test-retest reproducibility of MagDensity derived from different breast segmentation methods was assessed using the difference between the test and retest measures(Δ_(2-1)),MSE,and ICC.The results showed that MagDensity derived by the registration and deep learning segmentation methods exhibited high concordance with manual segmentation,with ICCs of 0.986(95%CI:0.974-0.993)and 0.983(95%CI:0.961-0.992),respectively.For test-retest analysis,MagDensity derived using the regis-tration algorithm achieved the smallest MSE of 0.370 and highest ICC of 0.993(95%CI:0.982-0.997)when compared to other segmentation methods.In conclusion,the proposed registration and deep learning whole-breast segmentation methods are accurate and reliable for estimating BD.Both methods outperformed a previously developed algorithm and manual segmentation in the test-retest assessment,with the registration exhibiting superior performance for highly reproducible BD measurements.展开更多
Background and aims:The spectral properties of enhanced greenfluorescent protein(EGFP)used in current visualizable animal models for nasopharyngeal carcinoma(NPC)result in a limited imaging depth.Far-redfluorescent pr...Background and aims:The spectral properties of enhanced greenfluorescent protein(EGFP)used in current visualizable animal models for nasopharyngeal carcinoma(NPC)result in a limited imaging depth.Far-redfluorescent proteins have optimal spectral wavelengths that allow deep tissue penetration,thus are well-suited for the imaging of tumor growth and metastases in live animals.This study aims to establish an imageable animal model of NPC using far-redfluorescent proteins.Methods:Eukaryotic expression vectors of far-redfluorescent proteins,mLumin and Katushka S158A,were separately transfected into 5-8F NPC cells,and cell lines stably expressing the far-redfluorescent proteins were obtained.These cells were intraperitoneally or intravenously injected into mice,and their tumorigenic and metastatic potential were examined throughfluorescence imaging.Finally,factors affecting their tumorigenic ability were further assessed through testing side population(SP)cells proportion byflow cytometry.Results:NPC cell line with high tumorigenicity and metastasis(5-8F-mL2)was screened out,which stably expressed far-redfluorescent protein.Intraperitoneal and intravenous injection of 5-8F-mL2 cells resulted in an abdomen metastasis model and a lung metastasis model.In addition,NPC cell line without tumorigenicity(5-8F-Katushka S158A)was screened out.The percentage of SP cells between 5-8F-mL2 and 5-8F-Katushka S158A was found different,suggesting that the SP cell proportion may play a key role in the determination of cell tumorigenic ability.Conclusion:We successfully established animal models for NPC with high tumorigenicity and metastasis using a super-bright far-redfluorescent protein.Owing to the super-brightness and excellent wavelength parameters,these models may be applied as useful tools for intuitive and efficient monitoring of tumor growth and metastasis,as well as assessing the efficacy of nasopharyngeal cancer drugs.展开更多
BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investi...BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investigates the mechanisms involved in the proliferation of human SSC.METHODS The expression of mitogen-activated protein kinase kinase 7(MKK7)in human testis was identified using immunohistochemistry and western blotting(WB).MKK7 was knocked down using small interfering RNA,and cell proliferation and apoptosis were detected by WB,EdU,cell counting kit-8 and fluorescenceactivated cell sorting.After bioinformatic analysis,the interaction of MKK7 with c-Jun N-terminal kinases(JNKs)was verified by protein co-immunoprecipitation and WB.The phosphorylation of JNKs was inhibited by SP600125,and the phenotypic changes were detected by WB,cell counting kit-8 and fluorescenceactivated cell sorting.RESULTS MKK7 is mainly expressed in human SSCs,and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis.MKK7 mediated the phosphorylation of JNKs,and after inhibiting the phosphorylation of JNKs,the phenotypic changes of the cells were similar to those after MKK7 downregulation.The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis,suggesting that abnormal MKK7 may be associated with spermatogenesis impairment.CONCLUSION MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.展开更多
Radiomic analysis has exponentially increased the amount of quantitative data that can be extracted from a single image.These imaging biomarkers can aid in the generation of prediction models aimed to further personal...Radiomic analysis has exponentially increased the amount of quantitative data that can be extracted from a single image.These imaging biomarkers can aid in the generation of prediction models aimed to further personalized medicine.However,the generalizability of the model is dependent on the robustness of these features.The purpose of this study is to review the current literature regarding robustness of radiomic features on magnetic resonance imaging.Additionally,a phantom study is performed to systematically evaluate the behavior of radiomic features under various conditions(signal to noise ratio,region of interest delineation,voxel size change and normalization methods)using intraclass correlation coefficients.The features extracted in this phantom study include first order,shape,gray level cooccurrence matrix and gray level run length matrix.Many features are found to be non-robust to changing parameters.Feature robustness assessment prior to feature selection,especially in the case of combining multi-institutional data,may be warranted.Further investigation is needed in this area of research.展开更多
Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of activity.However,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug resistance.To address the...Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of activity.However,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug resistance.To address these issues,semi-synthetic approaches for modifying natural AGs have generated new generations of AGs,however,with limited types of modification due to significant challenges in synthesis.This study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid AGs.This was achieved by glycodiversification of gentamicins via swapping the glycosyltransferase(GT)in their producer with the GT from kanamycins biosynthetic pathway and resulted in the creation of a series of novel AGs,therefore referred to as genkamicins(GKs).The manipulation of the hybrid biosynthetic pathway enabled the targeted accumulation of different GK species and the isolation and characterization of six GK components.These compounds display retained antimicrobial activity against a panel of World Health Organization(WHO)critical priority pathogens,and GK-C2a,in particular,demonstrates low ototoxicity compared to clinical drugs in zebrafish embryos.This study provides a new strategy for diversifying the structure of AGs and a potential avenue for developing less toxic AG drugs to combat infectious diseases.展开更多
Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains debated.The screening criteria of sperm banks are rarely mentioned to individuals with...Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains debated.The screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as controls.In addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm morphology.Results showed that inv(9)did not significantly increase reproductive risks overall.Despite detecting ROSlevel differences,the clinical impact may be insignificant.This study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.展开更多
Resonant beam communications (RBCom), which adopts oscillating photons between two separate retroreflectors for information transmission, exhibits potential advantages over other types of wireless optical communicatio...Resonant beam communications (RBCom), which adopts oscillating photons between two separate retroreflectors for information transmission, exhibits potential advantages over other types of wireless optical communications (WOC). However, echo interference generated by the modulated beam reflected from the receiver affects the transmission of the desired information. To tackle this challenge, a synchronization-based point-to-point RBCom system is proposed to eliminate the echo interference, and the design for the transmitter and receiver is discussed. Subsequently,the performance of the proposed RBCom is evaluated and compared with that of visible light communications(VLC)and free space optical communications (FOC). Finally, future research directions are outlined and several implementation challenges of RBCom systems are highlighted.展开更多
This paper studies the fundamental limit of semantic communications over the discrete memoryless channel.We consider the scenario to send a semantic source consisting of an observation state and its corresponding sema...This paper studies the fundamental limit of semantic communications over the discrete memoryless channel.We consider the scenario to send a semantic source consisting of an observation state and its corresponding semantic state,both of which are recovered at the receiver.To derive the performance limitation,we adopt the semantic rate-distortion function(SRDF)to study the relationship among the minimum compression rate,observation distortion,semantic distortion,and channel capacity.For the case with unknown semantic source distribution,while only a set of the source samples is available,we propose a neural-network-based method by leveraging the generative networks to learn the semantic source distribution.Furthermore,for a special case where the semantic state is a deterministic function of the observation,we design a cascade neural network to estimate the SRDF.For the case with perfectly known semantic source distribution,we propose a general Blahut-Arimoto(BA)algorithm to effectively compute the SRDE.Finally,experimental results validate our proposed algorithms for the scenarios with ideal Gaussian semantic source and some practical datasets.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32270601 and 32070633(to CH)the Chongqing Talents Plan for Young Talents No.cstc2022ycjh-bgzxm0140(to CH)+1 种基金the Innovation Support Program for Overseas Returned Scholars of Chongqing,China,No.cx2019142(to CH)the Natural Science Foundation of Chongqing of China,No.cstc2021jcyj-bshX0121(to MZ)。
文摘Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.
基金supported by Australian Research Council Australian Laureate Fellowship grant to ZXL (FL150100133)by China’s Thousand Talents Plan (2015)+2 种基金NSFC41674098 to NZsupported by resources provided by the High-performance Computing Platform of Peking Universitythe Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia
文摘Understanding the dominant force responsible for supercontinent breakup is crucial for establishing Earth＇s geodynamic evolution that includes supercontinent cycles and plate tectonics. Conventionally,two forces have been considered： the push by mantle plumes from the sub-continental mantle which is called the active force for breakup, and the dragging force from oceanic subduction retreat which is called the passive force for breakup. However, the relative importance of these two forces is unclear. Here we model the supercontinent breakup coupled with global mantle convection in order to address this question. Our global model features a spherical harmonic degree-2 structure, which includes a major subduction girdle and two large upwelling（superplume） systems. Based on this global mantle structure,we examine the distribution of extensional stress applied to the supercontinent by both subsupercontinent mantle upwellings and subduction retreat at the supercontinent peripheral. Our results show that：（1） at the center half of the supercontinent, plume push stress is ～3 times larger than the stress induced by subduction retreat;（2） an average hot anomaly of no higher than 50 K beneath the supercontinent can produce a push force strong enough to cause the initialization of supercontinent breakup;（3） the extensional stress induced by subduction retreat concentrates on a ～600 km wide zone on the boundary of the supercontinent, but has far less impact to the interior of the supercontinent. We therefore conclude that although circum-supercontinent subduction retreat assists supercontinent breakup, sub-supercontinent mantle upwelling is the essential force.
文摘背景与目的间质性肺病(interstitial lung disease,ILD)是一组主要累及肺间质和肺泡腔导致肺泡-毛细血管功能单位丧失的弥漫性肺疾病,常导致限制性通气功能障碍和弥散功能障碍。ILD基础上肺癌发病率增高,肺癌合并间质性肺病(lung cancer combined with ILD,LC-ILD)的手术风险明显增加。本研究旨在探讨LC-ILD外科治疗的安全性,总结围术期诊治经验。方法回顾性分析2012年1月-2019年12月北京医院胸外科收治的LC-ILD行肺切除术的患者资料,总结其临床表现、影像、病理、手术安全性、围术期并发症和诊治经验。结果本研究共纳入23例患者,男性20例(87.0%),平均年龄(69.1±7.8)岁,吸烟者19例(82.6%)。ILD类型包括特发性肺纤维化14例(60.9%)、特发性非特异性间质性肺炎7例(30.4%)、结缔组织病相关ILD 2例(8.7%)。肺癌病理包括腺癌7例(30.4%)、小细胞癌7例(30.4%)、鳞癌6例(26.1%)、小细胞癌混合鳞癌1例(4.3%)、大细胞癌2例(8.7%)。手术入路包括经电视胸腔镜16例(69.6%)和前外侧开胸7例(30.4%),切除方式包括肺叶切除13例(56.5%)、双肺叶切除1例(4.3%)和亚肺叶切除9例(39.1%)。术后90 d并发症11例(47.8%),其中肺部并发症8例(34.8%),ILD急性加重(acute exacerbation of ILD,AE-ILD)4例(17.4%),心房纤颤6例(26.1%),急性左心功能不全1例(4.3%)。术后90 d死亡2例(8.7%),死因均为AE-ILD。结论LC-ILD以合并症多、肺功能差的高龄患者居多,手术风险明显增高。术前应充分控制ILD病情,术中尽量降低手术创伤,术后应特别关注肺部并发症和AE-ILD。AEILD预后差,治疗难度大,糖皮质激素有助于改善病情,早诊早治是治疗关键。
基金supported by the Natural Science Foundation of Fujian Province(2018J01782)the National Natural Science Foundation of China(U1905211)the Educational scientific research project of Fujian Provincial Department of Education(JAT210291)。
文摘The Internet of Things(IoT)has profoundly impacted our lives and has greatly revolutionized our lifestyle.The terminal devices in an IoT data aggregation application sense real-time data for the remote cloud server to achieve intelligent decisions.However,the high frequency of collecting user data will raise people concerns about personal privacy.In recent years,many privacy-preserving data aggregation schemes have been proposed.Unfortunately,most existing schemes cannot support either arbitrary aggregation functions,or dynamic user group management,or fault tolerance.In this paper,we propose an efficient and privacy-preserving data aggregation scheme.In the scheme,we design a lightweight encryption method to protect the user privacy by using a ring topology and a random location sequence.On this basis,the proposed scheme supports not only arbitrary aggregation functions,but also flexible dynamic user management.Furthermore,the scheme achieves faulttolerant capabilities by utilizing a future data buffering mechanism.Security analysis reveals that the scheme can achieve the desired security properties,and experimental evaluation results show the scheme's efficiency in terms of computational and communication overhead.
基金This work was supported in part by National Cancer Institute,No.R03CA223052Walk-for-Beauty Foundation and Baldwin Carol M.Baldwin Breast Cancer Research Awards。
文摘Lymph node involvement increases the risk of breast cancer recurrence.An accurate non-invasive assessment of nodal involvement is valuable in cancer staging,surgical risk,and cost savings.Radiomics has been proposed to pre-operatively predict sentinel lymph node(SLN)status;however,radiomic models are known to be sensitive to acquisition parameters.The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based(DLB)features and compare its predictive performance to state-of-the-art radiomics.Specifically,this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution.Dynamic contrast-enhancement images from 198 patients(67 positive SLNs)were used in this study.Of these subjects,163 had an in-plane resolution of 0.7×0.7 mm^(2),which were randomly divided into a training set(approximately 67%)and a validation set(approximately 33%).The remaining 35 subjects with a different in-plane resolution(0.78×0.78 mm^(2))were treated as independent testing set for generalizability.Two methods were employed:(1)conventional radiomics(CR),and(2)DLB features which replaced hand-curated features with pre-trained VGG-16 features.The threshold determined using the training set was applied to the independent validation and testing dataset.Same feature reduction,feature selection,model creation procedures were used for both approaches.In the validation set(same resolution as training),the DLB model outperformed the CR model(accuracy 83%vs 80%).Furthermore,in the independent testing set of the dissimilar resolution,the DLB model performed markedly better than the CR model(accuracy 77%vs 71%).The predictive performance of the DLB model outperformed the CR model for this task.More interestingly,these improvements were seen particularly in the independent testing set of dissimilar resolution.This could indicate that DLB features can ultimately result in a more generalizable model.
基金This work is partially supported by the National Institute of Health R03CA223052The sulindac trial was supported by R01CA161534The metformin trial was supported by R01CA172444 and P30CA023074。
文摘Presence of higher breast density(BD)and persistence over time are risk factors for breast cancer.A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable.In this study,we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures.Three datasets of volunteers from two clinical trials were included.Breast MR images were acquired on 3T Siemens Biograph mMR,Prisma,and Skyra using 3D Cartesian six-echo GRE sequences with a fat-water separation technique.Two whole-breast segmentation strategies,utiliz-ing image registration and 3D U-Net,were developed.Manual segmentation was performed.A task-based analysis was performed:a previously developed MR-based BD measure,MagDensity,was calculated and assessed using automated and manual segmentation.The mean squared error(MSE)and intraclass correlation coefficient(ICC)between MagDensity were evaluated using the manual segmentation as a reference.The test-retest reproducibility of MagDensity derived from different breast segmentation methods was assessed using the difference between the test and retest measures(Δ_(2-1)),MSE,and ICC.The results showed that MagDensity derived by the registration and deep learning segmentation methods exhibited high concordance with manual segmentation,with ICCs of 0.986(95%CI:0.974-0.993)and 0.983(95%CI:0.961-0.992),respectively.For test-retest analysis,MagDensity derived using the regis-tration algorithm achieved the smallest MSE of 0.370 and highest ICC of 0.993(95%CI:0.982-0.997)when compared to other segmentation methods.In conclusion,the proposed registration and deep learning whole-breast segmentation methods are accurate and reliable for estimating BD.Both methods outperformed a previously developed algorithm and manual segmentation in the test-retest assessment,with the registration exhibiting superior performance for highly reproducible BD measurements.
基金The authors thank Prof.Yi-Xin Zeng and Prof.Mu-Sheng Zeng(Sun Yat-sen University Cancer Center,Guangzhou,China)for providing the 5-8F cell line.This work was supported by National Natural Science Foundation of China(Grant No.81172153)National Science and Technology Support Program of China(Grant No.2012BAI23B02).
文摘Background and aims:The spectral properties of enhanced greenfluorescent protein(EGFP)used in current visualizable animal models for nasopharyngeal carcinoma(NPC)result in a limited imaging depth.Far-redfluorescent proteins have optimal spectral wavelengths that allow deep tissue penetration,thus are well-suited for the imaging of tumor growth and metastases in live animals.This study aims to establish an imageable animal model of NPC using far-redfluorescent proteins.Methods:Eukaryotic expression vectors of far-redfluorescent proteins,mLumin and Katushka S158A,were separately transfected into 5-8F NPC cells,and cell lines stably expressing the far-redfluorescent proteins were obtained.These cells were intraperitoneally or intravenously injected into mice,and their tumorigenic and metastatic potential were examined throughfluorescence imaging.Finally,factors affecting their tumorigenic ability were further assessed through testing side population(SP)cells proportion byflow cytometry.Results:NPC cell line with high tumorigenicity and metastasis(5-8F-mL2)was screened out,which stably expressed far-redfluorescent protein.Intraperitoneal and intravenous injection of 5-8F-mL2 cells resulted in an abdomen metastasis model and a lung metastasis model.In addition,NPC cell line without tumorigenicity(5-8F-Katushka S158A)was screened out.The percentage of SP cells between 5-8F-mL2 and 5-8F-Katushka S158A was found different,suggesting that the SP cell proportion may play a key role in the determination of cell tumorigenic ability.Conclusion:We successfully established animal models for NPC with high tumorigenicity and metastasis using a super-bright far-redfluorescent protein.Owing to the super-brightness and excellent wavelength parameters,these models may be applied as useful tools for intuitive and efficient monitoring of tumor growth and metastasis,as well as assessing the efficacy of nasopharyngeal cancer drugs.
基金Supported by China Postdoctoral Science Foundation,No.2019M661521and National Natural Science Foundation of China,No.82001634.
文摘BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investigates the mechanisms involved in the proliferation of human SSC.METHODS The expression of mitogen-activated protein kinase kinase 7(MKK7)in human testis was identified using immunohistochemistry and western blotting(WB).MKK7 was knocked down using small interfering RNA,and cell proliferation and apoptosis were detected by WB,EdU,cell counting kit-8 and fluorescenceactivated cell sorting.After bioinformatic analysis,the interaction of MKK7 with c-Jun N-terminal kinases(JNKs)was verified by protein co-immunoprecipitation and WB.The phosphorylation of JNKs was inhibited by SP600125,and the phenotypic changes were detected by WB,cell counting kit-8 and fluorescenceactivated cell sorting.RESULTS MKK7 is mainly expressed in human SSCs,and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis.MKK7 mediated the phosphorylation of JNKs,and after inhibiting the phosphorylation of JNKs,the phenotypic changes of the cells were similar to those after MKK7 downregulation.The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis,suggesting that abnormal MKK7 may be associated with spermatogenesis impairment.CONCLUSION MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.
基金This work is in part funded by Walk-for-Beauty Foundation and Carol M.Baldwin Breast Cancer Research Foundation.
文摘Radiomic analysis has exponentially increased the amount of quantitative data that can be extracted from a single image.These imaging biomarkers can aid in the generation of prediction models aimed to further personalized medicine.However,the generalizability of the model is dependent on the robustness of these features.The purpose of this study is to review the current literature regarding robustness of radiomic features on magnetic resonance imaging.Additionally,a phantom study is performed to systematically evaluate the behavior of radiomic features under various conditions(signal to noise ratio,region of interest delineation,voxel size change and normalization methods)using intraclass correlation coefficients.The features extracted in this phantom study include first order,shape,gray level cooccurrence matrix and gray level run length matrix.Many features are found to be non-robust to changing parameters.Feature robustness assessment prior to feature selection,especially in the case of combining multi-institutional data,may be warranted.Further investigation is needed in this area of research.
基金the National Key R&D Program of China(2018YFA0903200)the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China(31920103001).
文摘Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of activity.However,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug resistance.To address these issues,semi-synthetic approaches for modifying natural AGs have generated new generations of AGs,however,with limited types of modification due to significant challenges in synthesis.This study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid AGs.This was achieved by glycodiversification of gentamicins via swapping the glycosyltransferase(GT)in their producer with the GT from kanamycins biosynthetic pathway and resulted in the creation of a series of novel AGs,therefore referred to as genkamicins(GKs).The manipulation of the hybrid biosynthetic pathway enabled the targeted accumulation of different GK species and the isolation and characterization of six GK components.These compounds display retained antimicrobial activity against a panel of World Health Organization(WHO)critical priority pathogens,and GK-C2a,in particular,demonstrates low ototoxicity compared to clinical drugs in zebrafish embryos.This study provides a new strategy for diversifying the structure of AGs and a potential avenue for developing less toxic AG drugs to combat infectious diseases.
基金financial supported by National Natural Science Foundationof China(No.82001634)the China Postdoctoral Science Foundation(No.2019M661521).
文摘Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains debated.The screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as controls.In addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm morphology.Results showed that inv(9)did not significantly increase reproductive risks overall.Despite detecting ROSlevel differences,the clinical impact may be insignificant.This study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.
基金supported in part by the Natural Science Foundation of China under Grant 62341112in part by the Basic Research Project of Hetao Shenzhen-HK S&T Cooperation Zone under Grant HZQBKCZYZ-2021067+3 种基金in part by the Key Project of Shenzhen under Grant JCYJ20220818103006013in part by Shenzhen High-Tech Zone Project under Grant KC2022KCCX0041in part by Guangdong Provincial Key Laboratory of Future Networks of Intelligence under Grant 2022B1212010001in part by Shenzhen Key Laboratory of Big Data and Artificial Intelligence under Grant ZDSYS201707251409055.
文摘Resonant beam communications (RBCom), which adopts oscillating photons between two separate retroreflectors for information transmission, exhibits potential advantages over other types of wireless optical communications (WOC). However, echo interference generated by the modulated beam reflected from the receiver affects the transmission of the desired information. To tackle this challenge, a synchronization-based point-to-point RBCom system is proposed to eliminate the echo interference, and the design for the transmitter and receiver is discussed. Subsequently,the performance of the proposed RBCom is evaluated and compared with that of visible light communications(VLC)and free space optical communications (FOC). Finally, future research directions are outlined and several implementation challenges of RBCom systems are highlighted.
基金supported in part by the Natural Science Foundation of China under Grants 62022070,62341112,62293480,and 62293481,in part by Shenzhen high-tech zone project under Grant KC2022KCCX0041,in part by the key project of Shenzhen under Grant JCYJ20220818103006013,in part by the Shenzhen Outstanding Talents Training Fund 202002,in part by the Guangdong Provincial Key Laboratory of Future Networks of Intelligence under Grant 2022B1212010001,and in part by the Shenzhen Key Laboratory of Big Data and Artificial Intelligence under Grant ZDSYS201707251409055.
文摘This paper studies the fundamental limit of semantic communications over the discrete memoryless channel.We consider the scenario to send a semantic source consisting of an observation state and its corresponding semantic state,both of which are recovered at the receiver.To derive the performance limitation,we adopt the semantic rate-distortion function(SRDF)to study the relationship among the minimum compression rate,observation distortion,semantic distortion,and channel capacity.For the case with unknown semantic source distribution,while only a set of the source samples is available,we propose a neural-network-based method by leveraging the generative networks to learn the semantic source distribution.Furthermore,for a special case where the semantic state is a deterministic function of the observation,we design a cascade neural network to estimate the SRDF.For the case with perfectly known semantic source distribution,we propose a general Blahut-Arimoto(BA)algorithm to effectively compute the SRDE.Finally,experimental results validate our proposed algorithms for the scenarios with ideal Gaussian semantic source and some practical datasets.
