Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently le...Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.展开更多
Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are const...Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are constructed in vitro and comprise cell types highly similar to those in organs or tissues in vivo,thus simulating specific structures and physiological functions of organs.Organoids have been technically developed into an advanced ex vivo disease model used in basic and preclinical research on tumors.Brain organoids,which simulate the brain microenvironment while preserving tumor heterogeneity,have been used to predict patients’therapeutic responses to antitumor drugs,thus enabling a breakthrough in glioma research.GBM organoids provide an effective supplementary model that reflects human tumors’biological characteristics and functions in vitro more directly and accurately than traditional experimental models.Therefore,GBM organoids are widely applicable in disease mechanism research,drug development and screening,and glioma precision treatments.This review focuses on the development of various GBM organoid models and their applications in identifying new individualized therapies against drug-resistant GBM.展开更多
With the continued development of multiple Global Navigation Satellite Systems(GNSS)and the emergence of various frequencies,UnDifferenced and UnCombined(UDUC)data processing has become an increasingly attractive opti...With the continued development of multiple Global Navigation Satellite Systems(GNSS)and the emergence of various frequencies,UnDifferenced and UnCombined(UDUC)data processing has become an increasingly attractive option.In this contribution,we provide an overview of the current status of UDUC GNSS data processing activities in China.These activities encompass the formulation of Precise Point Positioning(PPP)models and PPP-Real-Time Kinematic(PPP-RTK)models for processing single-station and multi-station GNSS data,respectively.Regarding single-station data processing,we discuss the advancements in PPP models,particularly the extension from a single system to multiple systems,and from dual frequencies to single and multiple frequencies.Additionally,we introduce the modified PPP model,which accounts for the time variation of receiver code biases,a departure from the conventional PPP model that typically assumes these biases to be time-constant.In the realm of multi-station PPP-RTK data processing,we introduce the ionosphere-weighted PPP-RTK model,which enhances the model strength by considering the spatial correlation of ionospheric delays.We also review the phase-only PPP-RTK model,designed to mitigate the impact of unmodelled code-related errors.Furthermore,we explore GLONASS PPP-RTK,achieved through the application of the integer-estimable model.For large-scale network data processing,we introduce the all-in-view PPP-RTK model,which alleviates the strict common-view requirement at all receivers.Moreover,we present the decentralized PPP-RTK data processing strategy,designed to improve computational efficiency.Overall,this work highlights the various advancements in UDUC GNSS data processing,providing insights into the state-of-the-art techniques employed in China to achieve precise GNSS applications.展开更多
Technique PPP-RTK combines the advantages of both the Precise Point Positioning(PPP)and the Real-Time Kinematic(RTK)positioning.With the emergence of multi-frequency Global Navigation Satellite System(GNSS)observation...Technique PPP-RTK combines the advantages of both the Precise Point Positioning(PPP)and the Real-Time Kinematic(RTK)positioning.With the emergence of multi-frequency Global Navigation Satellite System(GNSS)observations,it is preferable to formulate PPP-RTK functional models based on original(undiferenced and uncombined)observations.While there exist many variants of the undiferenced and uncombined PPP–RTK models,a unifed theoretical framework needs developing to link these variants.In this contribution,we formulate a class of undiferenced and uncombined PPP-RTK functional models in a systematic way and cast them in a unifed framework.This framework classifes the models into a code-plus-phase category and a phase-only category.Each category covers a variety of measurement scenarios on the network side,ranging from small-,medium-to large-scale networks.For each scenario,special care has been taken of the distinct ionospheric constraints and the diference between Code Division Multiple Access(CDMA)and Frequency Division Multiple Access(FDMA)signals.The key to systematically formulating these models lies in how to deal with the rank defciency problems encountered.We opt for the Singularity-basis(S-basis)theory,giving rise to the full-rank observation equations in which the estimable parameters turn out to be the functions of original parameters and those selected as the S-basis.In the sequel,it becomes straightforward to derive for each scenario the user model as it,more or less,amounts to the single-receiver network model.Benefting from the presented theoretical framework,the relationships and diferences between various undiferenced and uncombined PPP-RTK models become clear,which can lead to the better use of these models in a specifc situation.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172660)Hebei Province Graduate Student Innovation Project(Grant No.CXZZBS2023001)Baoding Natural Science Foundation(Grant No.H2272P015).
文摘Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.
基金supported by grants from the Hebei Natural Science Foundation(Grant No.H2022201062)The Science and Technology Program of Hebei(Grant No.223777115D)+1 种基金Hebei Provincial Central Leading Local Science and Technology Development Fund Project(Grant No.216Z7711G)Postgraduate’s Innovation Fund Project of Hebei Province(Grant No.CXZZBS2023002)。
文摘Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are constructed in vitro and comprise cell types highly similar to those in organs or tissues in vivo,thus simulating specific structures and physiological functions of organs.Organoids have been technically developed into an advanced ex vivo disease model used in basic and preclinical research on tumors.Brain organoids,which simulate the brain microenvironment while preserving tumor heterogeneity,have been used to predict patients’therapeutic responses to antitumor drugs,thus enabling a breakthrough in glioma research.GBM organoids provide an effective supplementary model that reflects human tumors’biological characteristics and functions in vitro more directly and accurately than traditional experimental models.Therefore,GBM organoids are widely applicable in disease mechanism research,drug development and screening,and glioma precision treatments.This review focuses on the development of various GBM organoid models and their applications in identifying new individualized therapies against drug-resistant GBM.
基金National Natural Science Foundation of China(No.42022025)。
文摘With the continued development of multiple Global Navigation Satellite Systems(GNSS)and the emergence of various frequencies,UnDifferenced and UnCombined(UDUC)data processing has become an increasingly attractive option.In this contribution,we provide an overview of the current status of UDUC GNSS data processing activities in China.These activities encompass the formulation of Precise Point Positioning(PPP)models and PPP-Real-Time Kinematic(PPP-RTK)models for processing single-station and multi-station GNSS data,respectively.Regarding single-station data processing,we discuss the advancements in PPP models,particularly the extension from a single system to multiple systems,and from dual frequencies to single and multiple frequencies.Additionally,we introduce the modified PPP model,which accounts for the time variation of receiver code biases,a departure from the conventional PPP model that typically assumes these biases to be time-constant.In the realm of multi-station PPP-RTK data processing,we introduce the ionosphere-weighted PPP-RTK model,which enhances the model strength by considering the spatial correlation of ionospheric delays.We also review the phase-only PPP-RTK model,designed to mitigate the impact of unmodelled code-related errors.Furthermore,we explore GLONASS PPP-RTK,achieved through the application of the integer-estimable model.For large-scale network data processing,we introduce the all-in-view PPP-RTK model,which alleviates the strict common-view requirement at all receivers.Moreover,we present the decentralized PPP-RTK data processing strategy,designed to improve computational efficiency.Overall,this work highlights the various advancements in UDUC GNSS data processing,providing insights into the state-of-the-art techniques employed in China to achieve precise GNSS applications.
基金This work was partially funded by the National Natural Science Foundation of China(Grant Nos.41774042,42174034)the Key Research and Development Plan of Hubei Province(Grant No.2020BHB014)+1 种基金the Scientifc Instrument Developing Project of the Chinese Academy of Sciences(Grant No.YJKYYQ20190063)The frst author is supported by the CAS Pioneer Hundred Talents Program。
文摘Technique PPP-RTK combines the advantages of both the Precise Point Positioning(PPP)and the Real-Time Kinematic(RTK)positioning.With the emergence of multi-frequency Global Navigation Satellite System(GNSS)observations,it is preferable to formulate PPP-RTK functional models based on original(undiferenced and uncombined)observations.While there exist many variants of the undiferenced and uncombined PPP–RTK models,a unifed theoretical framework needs developing to link these variants.In this contribution,we formulate a class of undiferenced and uncombined PPP-RTK functional models in a systematic way and cast them in a unifed framework.This framework classifes the models into a code-plus-phase category and a phase-only category.Each category covers a variety of measurement scenarios on the network side,ranging from small-,medium-to large-scale networks.For each scenario,special care has been taken of the distinct ionospheric constraints and the diference between Code Division Multiple Access(CDMA)and Frequency Division Multiple Access(FDMA)signals.The key to systematically formulating these models lies in how to deal with the rank defciency problems encountered.We opt for the Singularity-basis(S-basis)theory,giving rise to the full-rank observation equations in which the estimable parameters turn out to be the functions of original parameters and those selected as the S-basis.In the sequel,it becomes straightforward to derive for each scenario the user model as it,more or less,amounts to the single-receiver network model.Benefting from the presented theoretical framework,the relationships and diferences between various undiferenced and uncombined PPP-RTK models become clear,which can lead to the better use of these models in a specifc situation.
