Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune chec...Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.展开更多
The copper disc casting machine is core equipment for producing copper anode plates in the copper metallurgy industry.The copper disc casting machine casting package motion curve(CPMC) is significant for precise casti...The copper disc casting machine is core equipment for producing copper anode plates in the copper metallurgy industry.The copper disc casting machine casting package motion curve(CPMC) is significant for precise casting and efficient production.However,the lack of exact casting modeling and real-time simulation information severely restricts dynamic CPMC optimization.To this end,a liquid copper droplet model describes the casting package copper flow pattern in the casting process.Furthermore,a CPMC optimization model is proposed for the first time.On top of this,a digital twin dual closed-loop self-optimization application framework(DT-DCS) is constructed for optimizing the copper disc casting process to achieve self-optimization of the CPMC and closed-loop feedback of manufacturing information during the casting process.Finally,a case study is carried out based on the proposed methods in the industrial field.展开更多
In this editorial,we discuss the article by Wen et al published.Diabetic foot ulcers are prevalent and serious complications of diabetes,significantly impacting patients’quality of life and often leading to disabilit...In this editorial,we discuss the article by Wen et al published.Diabetic foot ulcers are prevalent and serious complications of diabetes,significantly impacting patients’quality of life and often leading to disability or death,thereby placing a heavy burden on society.Effective diabetic wound healing is hindered by an imbalance in macrophage polarization;many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,which is crucial for tissue remodelling and repair.The wound healing process is both dynamic and complex.Healthy M1 macrophages,which have strong phagocytic abilities,are vital during the inflammatory phase of diabetic wound healing.However,the failure to transition to M2 macrophages during the proliferative phase hinders wound healing.We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase,thereby enhancing the overall healing process.展开更多
The ChatGPT,a lite and conversational variant of Generative Pretrained Transformer 4(GPT-4)developed by OpenAI,is one of the milestone Large Language Models(LLMs)with billions of parameters.LLMs have stirred up much i...The ChatGPT,a lite and conversational variant of Generative Pretrained Transformer 4(GPT-4)developed by OpenAI,is one of the milestone Large Language Models(LLMs)with billions of parameters.LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks,which profoundly impact various fields.This paper mainly discusses the future applications of LLMs in dentistry.We introduce two primary LLM deployment methods in dentistry,including automated dental diagnosis and cross-modal dental diagnosis,and examine their potential applications.Especially,equipped with a cross-modal encoder,a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations.We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application.While LLMs offer significant potential benefits,the challenges,such as data privacy,data quality,and model bias,need further study.Overall,LLMs have the potential to revolutionize dental diagnosis and treatment,which indicates a promising avenue for clinical application and research in dentistry.展开更多
A newly developed digital data acquisition system,which is based on the digital pulse processor Pixie-16 modules by XIA LLC,was tested with the c-ray detector array of the China Institute of Atomic Energy using the cr...A newly developed digital data acquisition system,which is based on the digital pulse processor Pixie-16 modules by XIA LLC,was tested with the c-ray detector array of the China Institute of Atomic Energy using the cray source and in-beam c-rays.A comparison between this digital data acquisition system and the conventional analog data acquisition system was made.At a low count rate,both systems exhibit good and comparable energy resolutions.At a high count rate above 8.8 k/s,while the energy resolution obtained by the analog system deteriorates significantly,the energy resolution obtained by the digital system is nearly unchanged.Meanwhile,experimental data with higher statistics can be collected by the digital system.The advantage of this digital system over the conventional analog system can be ascribed to its excellent capability of handling pile-up pulses at higher count rates,and the fact that it has nearly no dead time in data transmission and conversion.展开更多
Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the ex...Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.展开更多
The intestinal flora is the normal microecosystem of the gastrointestinal tract. The intestinal flora has great complexity, and plays crucial roles in nutrient intake, host metabolism, endocrine signaling, homeostasis...The intestinal flora is the normal microecosystem of the gastrointestinal tract. The intestinal flora has great complexity, and plays crucial roles in nutrient intake, host metabolism, endocrine signaling, homeostasis and immune regulation. Disorders of the intestinal flora can lead to an out-of-balance in immune system, and even results in an increased risk of diseases, including the occurrence and development of malignant tumors. Accumulating evidence shows that intestinal microorganisms may assist in systemic therapy by increasing the “heterogeneity” of the tumor, thereby promoting anti-tumor therapy. Targeting intestinal flora during the treatment of cancer has shown good efficacy. This review focuses on recent advances in research about intestinal flora, the relationship with tumor development, and the potential anti-tumor effects.展开更多
Microstructure evolution and hardening effect of pure tungsten and W-1.5%ZrO_(2) alloy under carbon ion irradiation are investigated by using transmission electron microscopy and nano-indentation.Carbon ion irradiatio...Microstructure evolution and hardening effect of pure tungsten and W-1.5%ZrO_(2) alloy under carbon ion irradiation are investigated by using transmission electron microscopy and nano-indentation.Carbon ion irradiation is performed at 700℃ with irradiation damages ranging from 0.25 dpa to 2.0 dpa.The results show that the irradiation defect clusters are mainly in the form of dislocation loop.The size and density of dislocation loops increase with irradiation damages intensifying.The W-1.5%ZrO_(2) alloy has a smaller dislocation loop size than that of pure tungsten.It is proposed that the phase boundaries have the ability to absorb and annihilate defects and the addition of ZrO_(2) phase improves the sink strength for irradiation defects.It is confirmed that the W-1.5% ZrO_(2) alloy shows a smaller change in hardness than the pure tungsten after being irradiated.From the above results,we conclude that the addition of ZrO_(2) into tungsten can significantly reduce the accumulation of irradiated defects and improve the irradiation resistance behaviors of the tungsten materials.展开更多
Superconducting wire-networks are paradigms to study Cooper pairing issues,vortex dynamics and arrangements.Recently,emergent low-dimensional crystalline superconductors were reported in the minimal-disorder limit,pro...Superconducting wire-networks are paradigms to study Cooper pairing issues,vortex dynamics and arrangements.Recently,emergent low-dimensional crystalline superconductors were reported in the minimal-disorder limit,providing novel platforms to reveal vortices-related physics.Study on superconducting loops with high-crystallinity is thus currently demanded.Here,we report fabrication and transport measurement of finite square-network based on two-dimensional crystalline superconductor Mo_(2)C.We observe oscillations in the resistance as a function of the magnetic flux through the loops.Resistance dips at both matching field and fractional fillings are revealed.Temperature and current evolutions are carried out in magnetoresistance to study vortex dynamics.The amplitude of oscillation is enhanced due to the interaction between thermally activated vortices and the currents induced in the loops.The driving current reduces the effective activation energy for vortex,giving rise to stronger vortex interaction.Moreover,by the thermally activated vortex creep model,we derive the effective potential barrier for vortex dissipation,which shows well-defined correspondence with structures in magnetoresistance.Our work shows that low-dimensional crystalline superconducting network based on Mo_(2)C possesses pronounced potential in studying the modulation of vortex arrangements and dynamics,paving the way for further investigations on crystalline superconducting network with various configurations.展开更多
Transition from mononuclear villous cytotrophoblast into multinuclear syncytiotrophoblast in the human placenta is accompanied by changes in apoptosis-related proteins and an apparent increased resistance to induced a...Transition from mononuclear villous cytotrophoblast into multinuclear syncytiotrophoblast in the human placenta is accompanied by changes in apoptosis-related proteins and an apparent increased resistance to induced apoptosis. We investigated the specific nature and timing of changes in Bcl-2, Bax, p53, and caspases 3 and 8 in forskolin-treated BeWo choriocarcinoma cells, a model for villous cytotrophoblast differentiation. BeWo cells were treated with forskolin or vehicle alone for up to 72 h and evaluated at 24 h intervals for syncytialization and quantitative expression specific apoptosis-related proteins and mRNAs. Syncytialization was quantified using fluorescent staining of intercellular membranes and enumeration of the percentage of nuclei in multinucleate cells, and differential localization of apoptosis-related proteins to multinuclear or mononuclear cells was determined by quantitative immunofluorescence. Forskolin treatment for up to 72 h resulted in 80% syncytialization, increased expression of Bcl-2 protein (P ) and mRNA (P ), and significantly decreased expression of protein and mRNA for Bax, p53, and caspases 3 and 8. Syncytialized cells expressed higher levels of Bcl-2 protein concurrent with increased resistance to cisplatin-induced apoptosis. Thus, syncytialization of BeWo cells was accompanied by altered transcription of apoptotic-related proteins characteristic of increased apoptosis resistance secondary to increased expression of the anti-apoptotic protein Bcl-2 and diminish expression of pro-apoptotic proteins.展开更多
Starvation therapy has been proposed as a new anti-cancer therapy that can starve tumor cells and inhibit tumor growth by limiting the supply of nutrition or varying metabolic pathways. This approach has ignited consi...Starvation therapy has been proposed as a new anti-cancer therapy that can starve tumor cells and inhibit tumor growth by limiting the supply of nutrition or varying metabolic pathways. This approach has ignited considerable interest in medical and scientific communities due to its unparalleled safety. Of note, with the progress made in nano - medicine and nanotechnology, recent state-of-the-art studies have focused on designing smart and precise nanoplatforms capable of realizing and monitoring tumor starvation therapy and establishing starvation therapy-based synergistic strategies. These will be discussed in this review. Moreover, the potential challenges with regard to starvation therapy are also described, aiming to advance the development of starvation therapy in both the clinical and basic research areas.展开更多
The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenyl...The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and species-specificity.Here,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort.Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility.Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the axoneme.Examination of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme.Using an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the flagellum.These findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP transfer.In conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.展开更多
Circular RNAs(circRNAs)are a class of endogenous,singlestranded,covalently closed,mostly non-coding RNAs that are produced by back-splicing that links a downstream splice-donor site with an upstream splice-acceptor si...Circular RNAs(circRNAs)are a class of endogenous,singlestranded,covalently closed,mostly non-coding RNAs that are produced by back-splicing that links a downstream splice-donor site with an upstream splice-acceptor site(Chen,2016;Kristensen et al.,2019).CircRNAs have been reported to have important regulatory functions,such as acting as miRNA(Hansen et al.,2013;Memczak et al.,2013)or protein(Ashwal-Fluss et al.,2014)sponge to regulate gene expression,acting as scaffolds to mediate the formation of complexes(Du et al.,2016),and being translated into small functional peptides(Pamudurti et al.,2017).Notwithstanding,of millions of known circRNAs,those with demonstrated functions are a tiny fraction.展开更多
目的探讨神经外科重症昏迷患者人工气道管理方案的临床应用效果。方法制订神经外科昏迷患者人工气道管理方案,包括综合评估、系统实施、量表督查和落实改进4个方面。收集我院神经重症监护单元收治的283例格拉斯哥昏迷评分(Glasgow Coma ...目的探讨神经外科重症昏迷患者人工气道管理方案的临床应用效果。方法制订神经外科昏迷患者人工气道管理方案,包括综合评估、系统实施、量表督查和落实改进4个方面。收集我院神经重症监护单元收治的283例格拉斯哥昏迷评分(Glasgow Coma Scale,GCS)<6分且建立气管切开人工气道的神经重症昏迷患者的临床资料。其中2013年—2015年的161例患者为对照组,采取常规气道管理模式;2016年—2018年的122例患者为试验组,实施神经外科昏迷患者人工气道管理方案,分别收集两组干预前和干预1周后痰液性状、声门下吸引物性状、肺部感染发生率、ICU住院时间和平均住院日的资料。结果试验组痰液和声门下吸引物显著减少,性状较对照组明显改善(P<0.001);试验组肺部感染发生率为32.8%,较对照组显著下降(P<0.01);试验组ICU住院时间和平均住院日均显著降低(P<0.01和P<0.001)。人工气道工作小组气道综合管理措施执行效果量化评分为(94.6±1.8)分。结论落实神经外科昏迷患者人工气道管理方案,能够改善患者的痰液性状,降低肺部感染发生率,缩短住院日,改善患者预后。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82203539 and 92259102)Provincial Cooperation Project of Science and Technology Department of Sichuan Province(Grant No.2023YFSY0043)the National Key Research and Development Program of China(Grant No.2023YFC3402100).
文摘Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.
基金supported in part by the National Major Scientific Research Equipment of China (61927803)the National Natural Science Foundation of China Basic Science Center Project (61988101)+1 种基金Science and Technology Innovation Program of Hunan Province (2021RC4054)the China Postdoctoral Science Foundation (2021M691681)。
文摘The copper disc casting machine is core equipment for producing copper anode plates in the copper metallurgy industry.The copper disc casting machine casting package motion curve(CPMC) is significant for precise casting and efficient production.However,the lack of exact casting modeling and real-time simulation information severely restricts dynamic CPMC optimization.To this end,a liquid copper droplet model describes the casting package copper flow pattern in the casting process.Furthermore,a CPMC optimization model is proposed for the first time.On top of this,a digital twin dual closed-loop self-optimization application framework(DT-DCS) is constructed for optimizing the copper disc casting process to achieve self-optimization of the CPMC and closed-loop feedback of manufacturing information during the casting process.Finally,a case study is carried out based on the proposed methods in the industrial field.
基金Supported by Key Project of the Huzhou City Science and Technology Plan,No.2023GZ83.
文摘In this editorial,we discuss the article by Wen et al published.Diabetic foot ulcers are prevalent and serious complications of diabetes,significantly impacting patients’quality of life and often leading to disability or death,thereby placing a heavy burden on society.Effective diabetic wound healing is hindered by an imbalance in macrophage polarization;many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,which is crucial for tissue remodelling and repair.The wound healing process is both dynamic and complex.Healthy M1 macrophages,which have strong phagocytic abilities,are vital during the inflammatory phase of diabetic wound healing.However,the failure to transition to M2 macrophages during the proliferative phase hinders wound healing.We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase,thereby enhancing the overall healing process.
基金supported by the Research and Development Program,West China Hospital of Stomatology,Sichuan University(RD-02-202107)Sichuan Province Science and Technology Support Program(2022NSFSC0743)Sichuan Postdoctoral Science Foundation(TB2022005)grant to H.Huang.
文摘The ChatGPT,a lite and conversational variant of Generative Pretrained Transformer 4(GPT-4)developed by OpenAI,is one of the milestone Large Language Models(LLMs)with billions of parameters.LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks,which profoundly impact various fields.This paper mainly discusses the future applications of LLMs in dentistry.We introduce two primary LLM deployment methods in dentistry,including automated dental diagnosis and cross-modal dental diagnosis,and examine their potential applications.Especially,equipped with a cross-modal encoder,a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations.We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application.While LLMs offer significant potential benefits,the challenges,such as data privacy,data quality,and model bias,need further study.Overall,LLMs have the potential to revolutionize dental diagnosis and treatment,which indicates a promising avenue for clinical application and research in dentistry.
基金supported by the National Key R&D Program of China(No.2018YFA0404403)the National Natural Science Foundation of China(Nos.12035001,12075006,11675003)the State Key Laboratory of Nuclear Physics and Technology,PKU(No.NPT2020KFY18)。
文摘A newly developed digital data acquisition system,which is based on the digital pulse processor Pixie-16 modules by XIA LLC,was tested with the c-ray detector array of the China Institute of Atomic Energy using the cray source and in-beam c-rays.A comparison between this digital data acquisition system and the conventional analog data acquisition system was made.At a low count rate,both systems exhibit good and comparable energy resolutions.At a high count rate above 8.8 k/s,while the energy resolution obtained by the analog system deteriorates significantly,the energy resolution obtained by the digital system is nearly unchanged.Meanwhile,experimental data with higher statistics can be collected by the digital system.The advantage of this digital system over the conventional analog system can be ascribed to its excellent capability of handling pile-up pulses at higher count rates,and the fact that it has nearly no dead time in data transmission and conversion.
基金supported by the National Key Research and Development Program of China (Grant No.2023YFC3402100)the National Natural Science Foundation of China (Grant No.92259102)。
文摘Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.
文摘The intestinal flora is the normal microecosystem of the gastrointestinal tract. The intestinal flora has great complexity, and plays crucial roles in nutrient intake, host metabolism, endocrine signaling, homeostasis and immune regulation. Disorders of the intestinal flora can lead to an out-of-balance in immune system, and even results in an increased risk of diseases, including the occurrence and development of malignant tumors. Accumulating evidence shows that intestinal microorganisms may assist in systemic therapy by increasing the “heterogeneity” of the tumor, thereby promoting anti-tumor therapy. Targeting intestinal flora during the treatment of cancer has shown good efficacy. This review focuses on recent advances in research about intestinal flora, the relationship with tumor development, and the potential anti-tumor effects.
基金Project supported by the President's Foundation of the ChinaAcademy of Engineering Physics(Grant No.YZJJLX2018003)the National Natural Science Foundation of China(Grant Nos.U2004180 and 12105261)the Program for Changjiang Scholars and Innovative Research Team in Universities,China(Grant No.IRT1234).
文摘Microstructure evolution and hardening effect of pure tungsten and W-1.5%ZrO_(2) alloy under carbon ion irradiation are investigated by using transmission electron microscopy and nano-indentation.Carbon ion irradiation is performed at 700℃ with irradiation damages ranging from 0.25 dpa to 2.0 dpa.The results show that the irradiation defect clusters are mainly in the form of dislocation loop.The size and density of dislocation loops increase with irradiation damages intensifying.The W-1.5%ZrO_(2) alloy has a smaller dislocation loop size than that of pure tungsten.It is proposed that the phase boundaries have the ability to absorb and annihilate defects and the addition of ZrO_(2) phase improves the sink strength for irradiation defects.It is confirmed that the W-1.5% ZrO_(2) alloy shows a smaller change in hardness than the pure tungsten after being irradiated.From the above results,we conclude that the addition of ZrO_(2) into tungsten can significantly reduce the accumulation of irradiated defects and improve the irradiation resistance behaviors of the tungsten materials.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11974026,11774005,and 51802314)the National Key Research and Development Program of China(Grant No.2017YFA0303304)+1 种基金Science Foundation of Jihua Laboratory(Grant No.2021B0301030003-03)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB30000000)。
文摘Superconducting wire-networks are paradigms to study Cooper pairing issues,vortex dynamics and arrangements.Recently,emergent low-dimensional crystalline superconductors were reported in the minimal-disorder limit,providing novel platforms to reveal vortices-related physics.Study on superconducting loops with high-crystallinity is thus currently demanded.Here,we report fabrication and transport measurement of finite square-network based on two-dimensional crystalline superconductor Mo_(2)C.We observe oscillations in the resistance as a function of the magnetic flux through the loops.Resistance dips at both matching field and fractional fillings are revealed.Temperature and current evolutions are carried out in magnetoresistance to study vortex dynamics.The amplitude of oscillation is enhanced due to the interaction between thermally activated vortices and the currents induced in the loops.The driving current reduces the effective activation energy for vortex,giving rise to stronger vortex interaction.Moreover,by the thermally activated vortex creep model,we derive the effective potential barrier for vortex dissipation,which shows well-defined correspondence with structures in magnetoresistance.Our work shows that low-dimensional crystalline superconducting network based on Mo_(2)C possesses pronounced potential in studying the modulation of vortex arrangements and dynamics,paving the way for further investigations on crystalline superconducting network with various configurations.
文摘Transition from mononuclear villous cytotrophoblast into multinuclear syncytiotrophoblast in the human placenta is accompanied by changes in apoptosis-related proteins and an apparent increased resistance to induced apoptosis. We investigated the specific nature and timing of changes in Bcl-2, Bax, p53, and caspases 3 and 8 in forskolin-treated BeWo choriocarcinoma cells, a model for villous cytotrophoblast differentiation. BeWo cells were treated with forskolin or vehicle alone for up to 72 h and evaluated at 24 h intervals for syncytialization and quantitative expression specific apoptosis-related proteins and mRNAs. Syncytialization was quantified using fluorescent staining of intercellular membranes and enumeration of the percentage of nuclei in multinucleate cells, and differential localization of apoptosis-related proteins to multinuclear or mononuclear cells was determined by quantitative immunofluorescence. Forskolin treatment for up to 72 h resulted in 80% syncytialization, increased expression of Bcl-2 protein (P ) and mRNA (P ), and significantly decreased expression of protein and mRNA for Bax, p53, and caspases 3 and 8. Syncytialized cells expressed higher levels of Bcl-2 protein concurrent with increased resistance to cisplatin-induced apoptosis. Thus, syncytialization of BeWo cells was accompanied by altered transcription of apoptotic-related proteins characteristic of increased apoptosis resistance secondary to increased expression of the anti-apoptotic protein Bcl-2 and diminish expression of pro-apoptotic proteins.
基金the National Natural Science Foundation of China (Grant No. 81771836,81501473)the Guangxi Collaborative Innovation Center of Biomedicine (Grant No. GCICB-SR-201703)the Fostering Project of Shanghai Municipal Commission of Health and Family Planning for Excellent Young Medical Scholars (Grant No. 2018YQ31).
文摘Starvation therapy has been proposed as a new anti-cancer therapy that can starve tumor cells and inhibit tumor growth by limiting the supply of nutrition or varying metabolic pathways. This approach has ignited considerable interest in medical and scientific communities due to its unparalleled safety. Of note, with the progress made in nano - medicine and nanotechnology, recent state-of-the-art studies have focused on designing smart and precise nanoplatforms capable of realizing and monitoring tumor starvation therapy and establishing starvation therapy-based synergistic strategies. These will be discussed in this review. Moreover, the potential challenges with regard to starvation therapy are also described, aiming to advance the development of starvation therapy in both the clinical and basic research areas.
基金supported by National Key Research and Development Program of China(2022YFC2702702,2021YFC2700901)the National Natural Science Foundation of China(81971441,82171607,32000584)+3 种基金the University Outstanding Young Talents Support Program(gxyq2021174)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310002)Anhui Provincial Natural Science Foundation(2208085Y31)the Natural Science Foundation of Jiangsu Province(BK20230004).
文摘The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and species-specificity.Here,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort.Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility.Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the axoneme.Examination of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme.Using an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the flagellum.These findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP transfer.In conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.
基金supported by the National Natural Science Foundation of China(32270704,32100518 and 32472630)National Science and Technology Innovation 2030(2022ZD0214400)+1 种基金Engineering Shanghai Jiao Tong University(YG2022QN084)the U.S.National Institutes of Health(R35GM139484 to J.Z.)。
文摘Circular RNAs(circRNAs)are a class of endogenous,singlestranded,covalently closed,mostly non-coding RNAs that are produced by back-splicing that links a downstream splice-donor site with an upstream splice-acceptor site(Chen,2016;Kristensen et al.,2019).CircRNAs have been reported to have important regulatory functions,such as acting as miRNA(Hansen et al.,2013;Memczak et al.,2013)or protein(Ashwal-Fluss et al.,2014)sponge to regulate gene expression,acting as scaffolds to mediate the formation of complexes(Du et al.,2016),and being translated into small functional peptides(Pamudurti et al.,2017).Notwithstanding,of millions of known circRNAs,those with demonstrated functions are a tiny fraction.
文摘目的探讨神经外科重症昏迷患者人工气道管理方案的临床应用效果。方法制订神经外科昏迷患者人工气道管理方案,包括综合评估、系统实施、量表督查和落实改进4个方面。收集我院神经重症监护单元收治的283例格拉斯哥昏迷评分(Glasgow Coma Scale,GCS)<6分且建立气管切开人工气道的神经重症昏迷患者的临床资料。其中2013年—2015年的161例患者为对照组,采取常规气道管理模式;2016年—2018年的122例患者为试验组,实施神经外科昏迷患者人工气道管理方案,分别收集两组干预前和干预1周后痰液性状、声门下吸引物性状、肺部感染发生率、ICU住院时间和平均住院日的资料。结果试验组痰液和声门下吸引物显著减少,性状较对照组明显改善(P<0.001);试验组肺部感染发生率为32.8%,较对照组显著下降(P<0.01);试验组ICU住院时间和平均住院日均显著降低(P<0.01和P<0.001)。人工气道工作小组气道综合管理措施执行效果量化评分为(94.6±1.8)分。结论落实神经外科昏迷患者人工气道管理方案,能够改善患者的痰液性状,降低肺部感染发生率,缩短住院日,改善患者预后。
