BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contribut...BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.展开更多
In the Acknowledgements section of this article,the grant number"2020YFE0205900"relating to"National Key R&D Program of China"was missing,it has been included and the corrected Acknowledgements...In the Acknowledgements section of this article,the grant number"2020YFE0205900"relating to"National Key R&D Program of China"was missing,it has been included and the corrected Acknowledgements section is given below.展开更多
Objective Non-small cell lung cancer(NSCLC)is a leading cause of cancer-associated mortality.This study aimed to investigate the role of checkpoint kinase 1(CHEK1)in NSCLC progression and its regulatory relationship w...Objective Non-small cell lung cancer(NSCLC)is a leading cause of cancer-associated mortality.This study aimed to investigate the role of checkpoint kinase 1(CHEK1)in NSCLC progression and its regulatory relationship with forkhead box protein M1(FOXM1).Methods Transwell assays were used to evaluate the migration and invasion capabilities of NSCLC cells with either CHEK1 overexpression or knockdown.The expression of epithelial−mesenchymal transition(EMT)markers in NSCLC cells under CHEK1 overexpression or knockdown conditions was analyzed via Western blotting.Proliferative capacity was assessed using CCK-8 assays in NSCLC cells with modulated CHEK1 expression.Additionally,real-time quantitative PCR was employed to measure CHEK1 and FOXM1 expression levels in NSCLC tissues.The effects of CHEK1 knockdown on tumor growth were further validated in animal models.The binding of FOXM1 to the CHEK1 promoter region was examined using dual-luciferase reporter assays and chromatin immunoprecipitation(ChIP)assays.Results FOXM1 and CHEK1 were upregulated in NSCLC tissues.CHEK1 overexpression promoted NSCLC cell proliferation,while its knockdown suppressed proliferation,inhibited EMT,and reduced tumor growth in vivo.FOXM1 was shown to directly bind to CHEK1 promoter,thereby upregulating CHEK1 expression.Conclusion CHEK1 promotes NSCLC cell proliferation and tumor growth,and its expression is regulated by FOXM1.These findings suggest CHEK1 and FOXM1 are potential therapeutic targets for NSCLC treatment.展开更多
BACKGROUND Chylous ascites is an uncommon condition,occurring in less than 1%of ascites cases.It results from traumatic or obstructive disruption of the lymphatic system,causing the leakage of thoracic or intestinal l...BACKGROUND Chylous ascites is an uncommon condition,occurring in less than 1%of ascites cases.It results from traumatic or obstructive disruption of the lymphatic system,causing the leakage of thoracic or intestinal lymph into the abdominal cavity.This leads to the accumulation of a milky,triglyceride-rich fluid.In adults,malignancy and cirrhosis are the primary causes of chylous ascites.Notably,chylous ascites accounts for only 0.5%to 1%of all cirrhosis-related ascites cases.At present,there is a limited understanding of this condition,and effective timely management in clinical practice remains challenging.CASE SUMMARY This case report presents a patient with hepatic cirrhosis complicated by chylous ascites,who had experienced multiple hospitalizations due to abdominal distension.Upon admission,comprehensive examinations and assessments were conducted.The treatment strategy focused on nutritional optimization through a low-sodium,low-fat,and high-protein diet supplemented with medium-chain triglycerides,therapeutic paracentesis,and diuretics.Following a multidiscip-linary discussion and thorough evaluation of the patient’s condition,surgical indications were confirmed.After informing the patient about the benefits and risks,and obtaining consent,a transjugular intrahepatic portosystemic shunt procedure was performed,successfully alleviating the abdominal swelling symptoms.This article details the clinical characteristics and treatment approach for this uncommon case,summarizing current management methods for hepatic cirrhosis complicated by chylous ascites.The aim is to provide valuable insights for clinicians encountering similar situations.CONCLUSION Optimizing nutrition and addressing the underlying cause are essential in the treatment of chylous ascites.When conservative approaches prove ineffective,alternative interventions such as transjugular intrahepatic portosystemic shunt may be considered.展开更多
BACKGROUND Endoscopic submucosal dissection(ESD)is a standardized therapeutic approach for early carcinoma of the digestive tracts.In this regard,the process of histopathological diagnosis requires standardization.How...BACKGROUND Endoscopic submucosal dissection(ESD)is a standardized therapeutic approach for early carcinoma of the digestive tracts.In this regard,the process of histopathological diagnosis requires standardization.However,the uneven development of healthcare in China,especially in eastern and western China,creates challenges for sharing a standardized diagnostic process.AIM To optimize the process of ESD specimen sampling,embedding and slide production,and to provide complete and accurate pathological reports.METHODS We established a practical process of specimen sampling,created standardized reporting templates,and trained pathologists from neighboring hospitals and those in the western region.A training effectiveness survey was conducted,and the collected data were assessed by the corresponding percentages.RESULTS A total of 111 valid feedback forms have been received,among which 58%of the participants obtained photographs during specimen collection,whereas the percentage increased to 79%after training.Only 58%and 62%of the respondents ensured the mucosal tissue strips were flat and their order remained unchanged;after training,these two proportions increased to 95%and 92%,respectively.Approximately half the participants measured the depth of the submucosal infiltration,which significantly increased to 95%after training.The percentage of pathologists who did not evaluate lymphovascular invasion effectively reduced.Only 22%of the participants had fixed clinic-pathological meetings before training,which increased to 49%after training.The number of participants who had a thorough understanding of endoscopic diagnosis also significantly increased.CONCLUSION There have been significant improvements in the process of specimen collection,section quality,and pathology reporting in trained hospitals.Therefore,our study provides valuable insights for others facing similar challenges.展开更多
AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used ...AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.RESULTS Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines(including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 si RNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phosphoIκBα and phosho-p65, were upregulated.CONCLUSION β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation.展开更多
The hot cracking tendency of 7075 semi-solid alloy under different conditions was studied by critical diameter method.The experiment and simulation results show that the dendrite arms of the rod grow from the edge to ...The hot cracking tendency of 7075 semi-solid alloy under different conditions was studied by critical diameter method.The experiment and simulation results show that the dendrite arms of the rod grow from the edge to the center.The smaller the diameter of the rod is,the more obvious the directional growth of dendrite is,and the greater the tendency of hot cracking is.Compared with ordinary melt,for semi-solid slurry,increasing mould temperature or decreasing pouring temperature can significantly decrease hot cracking tendency of 7075 alloy,decreasing hot cracking grade from 256 to 100 mm^2.Furthermore,based on the RDG criterion,the effects of solidification conditions on the hot cracking tendency were discussed combined with simulation.At the same time,the application and development of RDG criterion were also researched.展开更多
Many electrochemical energy storage devices,such as batteries,supercapacitors,and metal ion capacitors,rely on effective and inexpensive electrode materials.Herein,we have developed highly active nitrogen-doped porous...Many electrochemical energy storage devices,such as batteries,supercapacitors,and metal ion capacitors,rely on effective and inexpensive electrode materials.Herein,we have developed highly active nitrogen-doped porous carbon nanofoams(NPCNs-600-N)for sodium-ion capacitors(SICs).NPCNs-600-N have a highly porous framework,extended interlayer spacing(0.41 nm),and lots of surface functional groups.Accordingly,NPCNs-600-N achieves a high reversible capacity(301 mAh·g^(-1)at 0.05 A·g^(-1)),superior rate capability(112 mAh·g^(-1)at 5.00 A·g^(-1)),and ultra-stable cyclability.The excellent rate and cycling performance originate from the abundant active sites and porous architecture of NPCNs-600-N.Further-more,SICs device is constructed by employing the NPCNs-600-N as the battery-like anode and commercial superconductive carbon black as the capacitive cathode,which delivers high energy/power densities of 92 Wh·kg^(-1)/15984 W·kg^(-1)with a remarkable cyclability(93%reten-tion over 5000 cycles at 1.00 A·g^(-1)).The methodology of the work enables the simultaneous tuning of the porous architectures and surface function groups of carbon for high-performance SICs.展开更多
The precipitates and hydrogen permeation behavior in three kinds of hot rolled low carbon heavy plate steels for enameling were analyzed; then, both sides of the steels were enameled. The experimental results show tha...The precipitates and hydrogen permeation behavior in three kinds of hot rolled low carbon heavy plate steels for enameling were analyzed; then, both sides of the steels were enameled. The experimental results show that a large amount of coarse Ti4 Cz $2 and fine Ti（C, N） particles exist in the optimized Ti-bearing steel, quite a lot of fine Ti（C,N） particles exist in the optimized carbon steel, but only a little bit fine Ti（C,N） particles exist in the carbon steel. The fishscaling resistance of the steels can be correlated to the effective hydrogen diffusion coefficient, and a model of correlation between the effective hydrogen diffusion coefficient and the volume fraction of the precipitates was established and verified. The effective hydrogen diffusion coefficient should be lower than 3.96×10-6 cm2/s to avoid fishscaling in heavy plate steels.展开更多
Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic applic...Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV.Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment. To this end, we systematically evaluated the antitumor efficacy of OMV using different loading strategies; this involved varying the in vitro loading duration and loading dose of OMV. We found that improved oncolysis of carrier cells was achieved by a prolonged loading duration in the absence of NAbs. However, the enhanced oncolytic effect was abrogated in the presence of NAbs. Further, we found that the expression of H protein on the surface of carrier cells was predominantly determined by the loading duration rather than the loading dose. Finally, we showed that NAbs blocked viral transfer by targeting H protein prior to the occurrence of cell-to-cell interactions. Our results provide comprehensive information on the determinants of an effective loading strategy for carrier cell-based virotherapy; these results may be useful for guiding the application of OMV as an antitumor agent in clinical practice.展开更多
Animal survival necessitates adaptive behav-iors in volatile environmental contexts.Virtual reality(VR)technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental con-text...Animal survival necessitates adaptive behav-iors in volatile environmental contexts.Virtual reality(VR)technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental con-text by simulating the real world with maximized control of contextual elements.Yet current VR tools for rodents have limited flexibility and performance(e.g.,frame rate)for context-dependent cognitive research.Here,we describe a high-performance VR platform with which to study con-textual behaviors immersed in editable virtual contexts.This platform was assembled from modular hardware and custom-written software with flexibility and upgradability.Using this platform,we trained mice to perform context-dependent cognitive tasks with rules ranging from discrim-ination to delayed-sample-to-match while recording from thousands of hippocampal place cells.By precise manipula-tions of context elements,we found that the context recogni-tion was intact with partial context elements,but impaired by exchanges of context elements.Collectively,our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.展开更多
Context cognition involves abstractly deriving meaning from situational information in the world and is an important psychological function of higher cognition. However, due to the complexity of contextual information...Context cognition involves abstractly deriving meaning from situational information in the world and is an important psychological function of higher cognition. However, due to the complexity of contextual information processing, along with the lack of relevant technical tools, little remains known about the neural mechanisms and behavioral regulation of context cognition. At present, behavioral training with rodents using virtual reality techniques is considered a potential key for uncovering the neurobiological mechanisms of context cognition. Although virtual reality technology has been preliminarily applied in the study of context cognition in recent years, there remains a lack of virtual scenario integration of multi-sensory information, along with a need for convenient experimental design platforms for researchers who have little programming experience. Therefore, in order to solve problems related to the authenticity, immersion, interaction, and flexibility of rodent virtual reality systems, an immersive virtual reality system based on visual programming was constructed in this study. The system had the ability to flexibly modulate rodent interactive 3 D dynamic experimental environments. The system included a central control unit, virtual perception unit, virtual motion unit, virtual vision unit, and video recording unit. The neural circuit mechanisms in various environments could be effectively studied by combining two-photon imaging and other neural activity recording methods. In addition, to verify the proposed system′s performance, licking experiments were conducted with experimental mice. The results demonstrated that the system could provide a new method and tool for analyzing the neural circuits of the higher cognitive functions in rodents.展开更多
We present a large complex radio burst and its associated fast time structures observed on 2001 April 10 in the frequency range of 0.65-7.6 GHz. The NoRH radio image observation shows very complex radio source structu...We present a large complex radio burst and its associated fast time structures observed on 2001 April 10 in the frequency range of 0.65-7.6 GHz. The NoRH radio image observation shows very complex radio source structures which include preexisting, newly emerging, submerging/cancelling polarities and a bipolar, a tripolar （a ＇bipolar ＋ remote unipolar＇）, and a quadrupolar structure. This suggests that the radio burst is generated from a very complicated loop structure. According to the spectral and image observations, we assume that the beginning of this flare was caused by a single bipolar loop configuration with a ‘Y-type＇ re- connection structure. A composite of radio continuum and fast time structures is contained in this flare. The various fast radio emission phenomena include normal and reverse drifting type Ⅲ bursts, and slowly drifting and no-drift structures. The tripolar configurations may form a double-loop with a ＇three-legged＇ struc- ture, which is an important source of the various types of fast time structures. The two-loop reconnection model can lead simultaneously to electron acceleration and corona heating. We have also analyzed the behaviors of coronal magnetic polarities and the emission processes of different types radio emission qualitatively. Interactions of a bipolar or multi-polar loop are consistent with our observational results. Our observations favor the magnetic reconnection configurations of the ‘inverted Y-type＇ （bipolar） and the ‘three-legged＇ structures （tripolar or quadrupo- lar）.展开更多
Recent advancements in nanotechnology have introduced a myriad of potential applications in dentistry,with nanomaterials playing an increasing role in endodontics.These nanomaterials exhibit distinctive mechanical and...Recent advancements in nanotechnology have introduced a myriad of potential applications in dentistry,with nanomaterials playing an increasing role in endodontics.These nanomaterials exhibit distinctive mechanical and chemical properties,rendering them suitable for various dental applications in endodontics,including obturating materials,sealers,retro-filling agents,and root-repair materials.Certain nanomaterials demonstrate versatile functionalities in endodontics,such as antimicrobial properties that bolster the eradication of bacteria within root canals during endodontic procedures.Moreover,they offer promise in drug delivery,facilitating targeted and controlled release of therapeutic agents to enhance tissue regeneration and repair,which can be used for endodontic tissue repair or regeneration.This review outlines the diverse applications of nanomaterials in endodontics,encompassing endodontic medicaments,irrigants,obturating materials,sealers,retro-filling agents,root-repair materials,as well as pulpal repair and regeneration.The integration of nanomaterials into endodontics stands poised to revolutionize treatment methodologies,presenting substantial potential advancements in the field.Our review aims to provide guidance for the effective translation of nanotechnologies into endodontic practice,serving as an invaluable resource for researchers,clinicians,and professionals in the fields of materials science and dentistry.展开更多
Anxiety disorders such as post-traumatic stress disorder(PTSD)are prevalent mental disorders that disturb millions globally.These disorders often manifest as excessive fear,anxiety,and distress,significantly impacting...Anxiety disorders such as post-traumatic stress disorder(PTSD)are prevalent mental disorders that disturb millions globally.These disorders often manifest as excessive fear,anxiety,and distress,significantly impacting daily life.The fear extinction paradigms in animals were established decades ago and have been widely used in research,providing a scientific basis for exposure therapies for anxiety disorders in humans.展开更多
The China Space Station Telescope(CSST) photometric survey aims to perform a high spatial resolution(~0.″ 15)photometric imaging for the targets that cover a large sky area(~17,500 deg^(2)) and wide wavelength range(...The China Space Station Telescope(CSST) photometric survey aims to perform a high spatial resolution(~0.″ 15)photometric imaging for the targets that cover a large sky area(~17,500 deg^(2)) and wide wavelength range(from NUV to NIR). It expects to explore the properties of dark matter, dark energy, and other important cosmological and astronomical areas. In this work, we evaluate whether the filter design of the Multi-channel Imager(MCI), one of the five instruments of the CSST, can provide accurate photometric redshift(photoz) measurements with its nine medium-band filters to meet the relevant scientific objectives. We generate the mock data based on the COSMOS photometric redshift catalog with astrophysical and instrumental effects. The application of upper limit information of low signal-to-noise ratio data is adopted in the estimation of photoz. We investigate the dependency of photoz accuracy on the filter parameters, such as band position and width. We find that the current MCI filter design can achieve good photoz measurements with accuracy σ_(z)■ 0.017 and outlier fraction f_(c)■ 2.2%. It can effectively improve the photoz measurements of the main CSST survey using the Survey Camera to an accuracy σ_(z)■ 0.015 and outlier fraction f_(c)■ 1.5%. This indicates that the original MCI filters are proper for the photoz calibration.展开更多
With the advent of the era of big data,the Provenance Method of electronic archives based on knowledge graph under the environment of big data has produced a large number of electronic archives due to the development ...With the advent of the era of big data,the Provenance Method of electronic archives based on knowledge graph under the environment of big data has produced a large number of electronic archives due to the development of science and technology.How to guarantee the credential characteristics of electronic archives in the big data environment has attracted wide attention of the academic community.Provenance is an important technical means to guarantee the certification of electronic archives.In this paper,knowledge graph technology is used to provide the concept provenance of electronic archives in large data environment.It not only enriches the provenance method,but also guarantees the certification of electronic archives in the large data environment.展开更多
Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity.However,these data are still lacking for the Chinese population.In this study,we constructed ...Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity.However,these data are still lacking for the Chinese population.In this study,we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese individuals.In total,1,577,513 variants(including 331,610 novel variants)were identified among 3,538 pharmacogenes related to 2,086 drugs.We found that the variant spectrum in the Chinese population differed among the seven major regions.Regional differences also exist among provinces in China.The average numbers of drug enzyme,transporter,and receptor variants were 258,557,and 632,respectively.Subsequent correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer variants.Among the 16 categories of drugs,we found that nervous system,cardiovascular system,and genitourinary system/sex hormone drugs were more likely to be affected by variants of pharmacogenes.Characteristics of the variants in the enzyme,transporter,and receptor subfamilies showed specificity.To explore the clinical utility of these data,a genetic association study was conducted on 1,019 lung cancer patients.Two novel variants,AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C,were identified as novel platinum response biomarkers.Finally,a pharmacogenomic database,named the Chinese Pharmacogenomic Knowledge Base(CNPKB:http://www.cnpkb.com.cn/),was constructed to collect all the data.In summary,a pharmacogenomic landscape and database for the Chinese population were constructed in this study,which could support personalized Chinese medicine in the future.展开更多
The synergistic approach of combining photodynamic immunotherapy with endogenous clearance of PD-L1 immune checkpoint blockade therapy holds promise for enhancing survival outcomes in glioblastoma(GBM)patients.The obs...The synergistic approach of combining photodynamic immunotherapy with endogenous clearance of PD-L1 immune checkpoint blockade therapy holds promise for enhancing survival outcomes in glioblastoma(GBM)patients.The observed upregulation of O-GlcNAc glycolysis in tumors may contribute to the stabilization of endogenous PD-L1 protein,facilitating tumor immune evasion.This study presents a pH-adapted excited state intramolecular proton transfer(ESIPT)-isomerizedβ-ketoamide-based covalent organic framework(COF)nanoplatform(denoted as OT@COF-RVG).Temozolomide(TMZ)and OSMI-4(O-GlcNAc transferase inhibitor)were integrated into COF cavities,then modified on the surface with polyethylene glycol and the rabies virus peptide RVG-29,showing potential for sensitizing TMZ chemotherapy and initiating photodynamic therapy(PDT).By inhibiting O-GlcNAc and promoting lysosomal degradation of PD-L1,OT@COF-RVG enhanced the effectiveness of immune checkpoint blockade(ICB)therapy.Additionally,treatment with OT@COF-RVG led to a notable elevation in reactive oxygen species(ROS)levels,thereby re-establishing an immunostimulatory state,inducing immunogenic cell death(ICD).In summary,our research unveiled a correlation between O-GlcNAc in GBM and the evasion of immune responses by tumors,while showcasing the potential of OT@COF-RVG in reshaping the immunosuppressive microenvironment of GBM and offering a more effective approach to immunotherapy in clinical settings.展开更多
Dental pulp stem cells(DPSCs)have demonstrated remarkable potential in enhancing peripheral nerve regeneration,though the precise mechanisms remain largely unknown.This study investigates how DPSCs alleviate Schwann c...Dental pulp stem cells(DPSCs)have demonstrated remarkable potential in enhancing peripheral nerve regeneration,though the precise mechanisms remain largely unknown.This study investigates how DPSCs alleviate Schwann cell pyroptosis and restore mitochondrial homeostasis through intercellular mitochondrial transfer.In a crab-eating macaque model,we first observed that DPSC-loaded nerve conduits significantly promoted long-term nerve regeneration,facilitating tissue proliferation and myelin recovery.We further established a rat facial nerve injury(FNI)model and found that DPSC treatment reduced pyroptosis and mitochondrial ROS production in Schwann cells.A pivotal mitochondrial protective mechanism,resembling the effects of a ROS-targeted inhibitor,involved the transfer of mitochondria from DPSCs to pyroptosis-induced Schwann cells via tunneling nanotubes,while blocking intercellular junctions or mitochondrial function diminished the therapeutic effects.TNFαsecreted by pyroptosis-induced Schwann cells activated the NF-κB pathway in DPSCs,enhancing mitochondrial transfer and adaptive stress responses,thereby promoting mitochondrial protection against pyroptosis in Schwann cells,as reflected in the improved therapeutic efficacy of TNF α-preconditioned DPSCs in the FNI model.These findings unveil a mechanism through which DPSCs foster nerve regeneration via mitochondrial transfer,presenting a promising strategy for enhancing stem cell-based therapies for nerve injuries.展开更多
文摘BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.
文摘In the Acknowledgements section of this article,the grant number"2020YFE0205900"relating to"National Key R&D Program of China"was missing,it has been included and the corrected Acknowledgements section is given below.
基金funded by the Suqian Science and Technology Program Project(No.K202008).
文摘Objective Non-small cell lung cancer(NSCLC)is a leading cause of cancer-associated mortality.This study aimed to investigate the role of checkpoint kinase 1(CHEK1)in NSCLC progression and its regulatory relationship with forkhead box protein M1(FOXM1).Methods Transwell assays were used to evaluate the migration and invasion capabilities of NSCLC cells with either CHEK1 overexpression or knockdown.The expression of epithelial−mesenchymal transition(EMT)markers in NSCLC cells under CHEK1 overexpression or knockdown conditions was analyzed via Western blotting.Proliferative capacity was assessed using CCK-8 assays in NSCLC cells with modulated CHEK1 expression.Additionally,real-time quantitative PCR was employed to measure CHEK1 and FOXM1 expression levels in NSCLC tissues.The effects of CHEK1 knockdown on tumor growth were further validated in animal models.The binding of FOXM1 to the CHEK1 promoter region was examined using dual-luciferase reporter assays and chromatin immunoprecipitation(ChIP)assays.Results FOXM1 and CHEK1 were upregulated in NSCLC tissues.CHEK1 overexpression promoted NSCLC cell proliferation,while its knockdown suppressed proliferation,inhibited EMT,and reduced tumor growth in vivo.FOXM1 was shown to directly bind to CHEK1 promoter,thereby upregulating CHEK1 expression.Conclusion CHEK1 promotes NSCLC cell proliferation and tumor growth,and its expression is regulated by FOXM1.These findings suggest CHEK1 and FOXM1 are potential therapeutic targets for NSCLC treatment.
文摘BACKGROUND Chylous ascites is an uncommon condition,occurring in less than 1%of ascites cases.It results from traumatic or obstructive disruption of the lymphatic system,causing the leakage of thoracic or intestinal lymph into the abdominal cavity.This leads to the accumulation of a milky,triglyceride-rich fluid.In adults,malignancy and cirrhosis are the primary causes of chylous ascites.Notably,chylous ascites accounts for only 0.5%to 1%of all cirrhosis-related ascites cases.At present,there is a limited understanding of this condition,and effective timely management in clinical practice remains challenging.CASE SUMMARY This case report presents a patient with hepatic cirrhosis complicated by chylous ascites,who had experienced multiple hospitalizations due to abdominal distension.Upon admission,comprehensive examinations and assessments were conducted.The treatment strategy focused on nutritional optimization through a low-sodium,low-fat,and high-protein diet supplemented with medium-chain triglycerides,therapeutic paracentesis,and diuretics.Following a multidiscip-linary discussion and thorough evaluation of the patient’s condition,surgical indications were confirmed.After informing the patient about the benefits and risks,and obtaining consent,a transjugular intrahepatic portosystemic shunt procedure was performed,successfully alleviating the abdominal swelling symptoms.This article details the clinical characteristics and treatment approach for this uncommon case,summarizing current management methods for hepatic cirrhosis complicated by chylous ascites.The aim is to provide valuable insights for clinicians encountering similar situations.CONCLUSION Optimizing nutrition and addressing the underlying cause are essential in the treatment of chylous ascites.When conservative approaches prove ineffective,alternative interventions such as transjugular intrahepatic portosystemic shunt may be considered.
基金Supported by the Medical Education Research Project from Nanjing Drum Tower Hospital,No.2021-7the Clinical Trials Fund from Nanjing Drum Tower Hospital,No.2022-YXZX-XH-04National Natural Science Foundation of China,No.82203063.
文摘BACKGROUND Endoscopic submucosal dissection(ESD)is a standardized therapeutic approach for early carcinoma of the digestive tracts.In this regard,the process of histopathological diagnosis requires standardization.However,the uneven development of healthcare in China,especially in eastern and western China,creates challenges for sharing a standardized diagnostic process.AIM To optimize the process of ESD specimen sampling,embedding and slide production,and to provide complete and accurate pathological reports.METHODS We established a practical process of specimen sampling,created standardized reporting templates,and trained pathologists from neighboring hospitals and those in the western region.A training effectiveness survey was conducted,and the collected data were assessed by the corresponding percentages.RESULTS A total of 111 valid feedback forms have been received,among which 58%of the participants obtained photographs during specimen collection,whereas the percentage increased to 79%after training.Only 58%and 62%of the respondents ensured the mucosal tissue strips were flat and their order remained unchanged;after training,these two proportions increased to 95%and 92%,respectively.Approximately half the participants measured the depth of the submucosal infiltration,which significantly increased to 95%after training.The percentage of pathologists who did not evaluate lymphovascular invasion effectively reduced.Only 22%of the participants had fixed clinic-pathological meetings before training,which increased to 49%after training.The number of participants who had a thorough understanding of endoscopic diagnosis also significantly increased.CONCLUSION There have been significant improvements in the process of specimen collection,section quality,and pathology reporting in trained hospitals.Therefore,our study provides valuable insights for others facing similar challenges.
基金Supported by the National Natural Science Foundation of China,No.81470848the Breeding Foundation for Young Pioneers’Research of Sun Yat-sen University,No.14ykpy27
文摘AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.RESULTS Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines(including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 si RNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phosphoIκBα and phosho-p65, were upregulated.CONCLUSION β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation.
基金Project(17YF1407100)supported by the Shanghai Sailing Program of ChinaProject(17PJ1408600)supported by Shanghai Pujiang Program of China
文摘The hot cracking tendency of 7075 semi-solid alloy under different conditions was studied by critical diameter method.The experiment and simulation results show that the dendrite arms of the rod grow from the edge to the center.The smaller the diameter of the rod is,the more obvious the directional growth of dendrite is,and the greater the tendency of hot cracking is.Compared with ordinary melt,for semi-solid slurry,increasing mould temperature or decreasing pouring temperature can significantly decrease hot cracking tendency of 7075 alloy,decreasing hot cracking grade from 256 to 100 mm^2.Furthermore,based on the RDG criterion,the effects of solidification conditions on the hot cracking tendency were discussed combined with simulation.At the same time,the application and development of RDG criterion were also researched.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No. BK20170549)the National Natural Science Foundation of China (Nos. 21706103 and 22075109)+2 种基金Nanjing Tech University Research Start-Up Fund (No. 38274017111)Zhongyan Jilantai Chlor-Alkali Chemical Co., Ltd (No. FZ2019-RWS-027)the Open Fund of the Key Laboratory of Fine Chemical Application Technology of Luzhou (No. HYJH-2101-B)
文摘Many electrochemical energy storage devices,such as batteries,supercapacitors,and metal ion capacitors,rely on effective and inexpensive electrode materials.Herein,we have developed highly active nitrogen-doped porous carbon nanofoams(NPCNs-600-N)for sodium-ion capacitors(SICs).NPCNs-600-N have a highly porous framework,extended interlayer spacing(0.41 nm),and lots of surface functional groups.Accordingly,NPCNs-600-N achieves a high reversible capacity(301 mAh·g^(-1)at 0.05 A·g^(-1)),superior rate capability(112 mAh·g^(-1)at 5.00 A·g^(-1)),and ultra-stable cyclability.The excellent rate and cycling performance originate from the abundant active sites and porous architecture of NPCNs-600-N.Further-more,SICs device is constructed by employing the NPCNs-600-N as the battery-like anode and commercial superconductive carbon black as the capacitive cathode,which delivers high energy/power densities of 92 Wh·kg^(-1)/15984 W·kg^(-1)with a remarkable cyclability(93%reten-tion over 5000 cycles at 1.00 A·g^(-1)).The methodology of the work enables the simultaneous tuning of the porous architectures and surface function groups of carbon for high-performance SICs.
文摘The precipitates and hydrogen permeation behavior in three kinds of hot rolled low carbon heavy plate steels for enameling were analyzed; then, both sides of the steels were enameled. The experimental results show that a large amount of coarse Ti4 Cz $2 and fine Ti（C, N） particles exist in the optimized Ti-bearing steel, quite a lot of fine Ti（C,N） particles exist in the optimized carbon steel, but only a little bit fine Ti（C,N） particles exist in the carbon steel. The fishscaling resistance of the steels can be correlated to the effective hydrogen diffusion coefficient, and a model of correlation between the effective hydrogen diffusion coefficient and the volume fraction of the precipitates was established and verified. The effective hydrogen diffusion coefficient should be lower than 3.96×10-6 cm2/s to avoid fishscaling in heavy plate steels.
基金supported in part by the National Natural Science Foundation of China (81472820, 81773255, 81071860 and 81602702)Jiangsu Special Program for Clinical Medical Science and Technology (BL2014054)+2 种基金the Natural Science Foundation of Jiangsu Province of China (BK20160126)the Fundamental Research Funds for the Central Universities (021414380223 and 14380336/1-2)Six talent peaks project in Jiangsu Province to JW
文摘Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV.Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment. To this end, we systematically evaluated the antitumor efficacy of OMV using different loading strategies; this involved varying the in vitro loading duration and loading dose of OMV. We found that improved oncolysis of carrier cells was achieved by a prolonged loading duration in the absence of NAbs. However, the enhanced oncolytic effect was abrogated in the presence of NAbs. Further, we found that the expression of H protein on the surface of carrier cells was predominantly determined by the loading duration rather than the loading dose. Finally, we showed that NAbs blocked viral transfer by targeting H protein prior to the occurrence of cell-to-cell interactions. Our results provide comprehensive information on the determinants of an effective loading strategy for carrier cell-based virotherapy; these results may be useful for guiding the application of OMV as an antitumor agent in clinical practice.
基金supported by the National Science and Technology Innovation 2030 Major Program(2022ZD0205000)the National Key R&D Program of China,the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010105,XDBS01010100)+3 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)Lingang Lab(LG202104-01-08)the National Natural Science Foundation of China(31771180 and 91732106)an International Collaborative Project of the Shanghai Science and Technology Committee(201978677).
文摘Animal survival necessitates adaptive behav-iors in volatile environmental contexts.Virtual reality(VR)technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental con-text by simulating the real world with maximized control of contextual elements.Yet current VR tools for rodents have limited flexibility and performance(e.g.,frame rate)for context-dependent cognitive research.Here,we describe a high-performance VR platform with which to study con-textual behaviors immersed in editable virtual contexts.This platform was assembled from modular hardware and custom-written software with flexibility and upgradability.Using this platform,we trained mice to perform context-dependent cognitive tasks with rules ranging from discrim-ination to delayed-sample-to-match while recording from thousands of hippocampal place cells.By precise manipula-tions of context elements,we found that the context recogni-tion was intact with partial context elements,but impaired by exchanges of context elements.Collectively,our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.
文摘Context cognition involves abstractly deriving meaning from situational information in the world and is an important psychological function of higher cognition. However, due to the complexity of contextual information processing, along with the lack of relevant technical tools, little remains known about the neural mechanisms and behavioral regulation of context cognition. At present, behavioral training with rodents using virtual reality techniques is considered a potential key for uncovering the neurobiological mechanisms of context cognition. Although virtual reality technology has been preliminarily applied in the study of context cognition in recent years, there remains a lack of virtual scenario integration of multi-sensory information, along with a need for convenient experimental design platforms for researchers who have little programming experience. Therefore, in order to solve problems related to the authenticity, immersion, interaction, and flexibility of rodent virtual reality systems, an immersive virtual reality system based on visual programming was constructed in this study. The system had the ability to flexibly modulate rodent interactive 3 D dynamic experimental environments. The system included a central control unit, virtual perception unit, virtual motion unit, virtual vision unit, and video recording unit. The neural circuit mechanisms in various environments could be effectively studied by combining two-photon imaging and other neural activity recording methods. In addition, to verify the proposed system′s performance, licking experiments were conducted with experimental mice. The results demonstrated that the system could provide a new method and tool for analyzing the neural circuits of the higher cognitive functions in rodents.
基金Supported by the National Natural Science Foundation of China.
文摘We present a large complex radio burst and its associated fast time structures observed on 2001 April 10 in the frequency range of 0.65-7.6 GHz. The NoRH radio image observation shows very complex radio source structures which include preexisting, newly emerging, submerging/cancelling polarities and a bipolar, a tripolar （a ＇bipolar ＋ remote unipolar＇）, and a quadrupolar structure. This suggests that the radio burst is generated from a very complicated loop structure. According to the spectral and image observations, we assume that the beginning of this flare was caused by a single bipolar loop configuration with a ‘Y-type＇ re- connection structure. A composite of radio continuum and fast time structures is contained in this flare. The various fast radio emission phenomena include normal and reverse drifting type Ⅲ bursts, and slowly drifting and no-drift structures. The tripolar configurations may form a double-loop with a ＇three-legged＇ struc- ture, which is an important source of the various types of fast time structures. The two-loop reconnection model can lead simultaneously to electron acceleration and corona heating. We have also analyzed the behaviors of coronal magnetic polarities and the emission processes of different types radio emission qualitatively. Interactions of a bipolar or multi-polar loop are consistent with our observational results. Our observations favor the magnetic reconnection configurations of the ‘inverted Y-type＇ （bipolar） and the ‘three-legged＇ structures （tripolar or quadrupo- lar）.
文摘Recent advancements in nanotechnology have introduced a myriad of potential applications in dentistry,with nanomaterials playing an increasing role in endodontics.These nanomaterials exhibit distinctive mechanical and chemical properties,rendering them suitable for various dental applications in endodontics,including obturating materials,sealers,retro-filling agents,and root-repair materials.Certain nanomaterials demonstrate versatile functionalities in endodontics,such as antimicrobial properties that bolster the eradication of bacteria within root canals during endodontic procedures.Moreover,they offer promise in drug delivery,facilitating targeted and controlled release of therapeutic agents to enhance tissue regeneration and repair,which can be used for endodontic tissue repair or regeneration.This review outlines the diverse applications of nanomaterials in endodontics,encompassing endodontic medicaments,irrigants,obturating materials,sealers,retro-filling agents,root-repair materials,as well as pulpal repair and regeneration.The integration of nanomaterials into endodontics stands poised to revolutionize treatment methodologies,presenting substantial potential advancements in the field.Our review aims to provide guidance for the effective translation of nanotechnologies into endodontic practice,serving as an invaluable resource for researchers,clinicians,and professionals in the fields of materials science and dentistry.
基金supported by the National Natural Science Foundation of China(31872764 and 82171090)the Shanghai Science and Technology Committee Rising-Star Program(19QA1401600)+1 种基金the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)the ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Anxiety disorders such as post-traumatic stress disorder(PTSD)are prevalent mental disorders that disturb millions globally.These disorders often manifest as excessive fear,anxiety,and distress,significantly impacting daily life.The fear extinction paradigms in animals were established decades ago and have been widely used in research,providing a scientific basis for exposure therapies for anxiety disorders in humans.
基金the support of NSFC-11822305, NSFC-11773031, NSFC-11633004, MOST-2018YFE0120800, MOST-2020SKA0110402, and CAS Interdisciplinary Innovation Teamsupported by the science research grants from the China Manned Space Project with NO.CMSCSST-2021-B01 and CMS-CSST-2021-A01. Z.Y.Z+1 种基金support by the National Natural Science Foundation of China (11773051 and 12022303)the CAS Pioneer Hundred Talents Program。
文摘The China Space Station Telescope(CSST) photometric survey aims to perform a high spatial resolution(~0.″ 15)photometric imaging for the targets that cover a large sky area(~17,500 deg^(2)) and wide wavelength range(from NUV to NIR). It expects to explore the properties of dark matter, dark energy, and other important cosmological and astronomical areas. In this work, we evaluate whether the filter design of the Multi-channel Imager(MCI), one of the five instruments of the CSST, can provide accurate photometric redshift(photoz) measurements with its nine medium-band filters to meet the relevant scientific objectives. We generate the mock data based on the COSMOS photometric redshift catalog with astrophysical and instrumental effects. The application of upper limit information of low signal-to-noise ratio data is adopted in the estimation of photoz. We investigate the dependency of photoz accuracy on the filter parameters, such as band position and width. We find that the current MCI filter design can achieve good photoz measurements with accuracy σ_(z)■ 0.017 and outlier fraction f_(c)■ 2.2%. It can effectively improve the photoz measurements of the main CSST survey using the Survey Camera to an accuracy σ_(z)■ 0.015 and outlier fraction f_(c)■ 1.5%. This indicates that the original MCI filters are proper for the photoz calibration.
基金This work is supported by the NSFC[Grant No.61772280]the National Training Programs of Innovation and Entrepreneurship for Undergraduates[Grant Nos.201910300123Y,201810300165]the PAPD Fund from NUIST.
文摘With the advent of the era of big data,the Provenance Method of electronic archives based on knowledge graph under the environment of big data has produced a large number of electronic archives due to the development of science and technology.How to guarantee the credential characteristics of electronic archives in the big data environment has attracted wide attention of the academic community.Provenance is an important technical means to guarantee the certification of electronic archives.In this paper,knowledge graph technology is used to provide the concept provenance of electronic archives in large data environment.It not only enriches the provenance method,but also guarantees the certification of electronic archives in the large data environment.
基金supported by the National Natural Science Foundation of China(82073943,82373962,and 82450103 to J-Y.Y. and 82204533 to J.J.C.)a Scientific Research Project of the Furong Laboratory of Central South University (2023SK2083 to J-Y.Y.)+4 种基金the Natural Science Foundation of Hunan Province(2023JJ40931 to JJ.C 2023JU50251 to J.-C.W,and 2024JJ6633 to Y.W.)the Postdoctoral Fellowship Programof CPSF (GZB20240878 to Y.W.)the Hunan Innovation platform and talent program(2020RC3086 to C.-P.L)the Non-profit Central Research Institute Fund of the Chinese Academyof Medical Scienoes (2020 PT320-004to J.-G.L)the Open Fund for ScientificResearch ofNHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyn-geal Carcinoma (2021NPCK01 to J.-Y.Y.).
文摘Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity.However,these data are still lacking for the Chinese population.In this study,we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese individuals.In total,1,577,513 variants(including 331,610 novel variants)were identified among 3,538 pharmacogenes related to 2,086 drugs.We found that the variant spectrum in the Chinese population differed among the seven major regions.Regional differences also exist among provinces in China.The average numbers of drug enzyme,transporter,and receptor variants were 258,557,and 632,respectively.Subsequent correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer variants.Among the 16 categories of drugs,we found that nervous system,cardiovascular system,and genitourinary system/sex hormone drugs were more likely to be affected by variants of pharmacogenes.Characteristics of the variants in the enzyme,transporter,and receptor subfamilies showed specificity.To explore the clinical utility of these data,a genetic association study was conducted on 1,019 lung cancer patients.Two novel variants,AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C,were identified as novel platinum response biomarkers.Finally,a pharmacogenomic database,named the Chinese Pharmacogenomic Knowledge Base(CNPKB:http://www.cnpkb.com.cn/),was constructed to collect all the data.In summary,a pharmacogenomic landscape and database for the Chinese population were constructed in this study,which could support personalized Chinese medicine in the future.
基金supported by grants from the Natural Science Foundation of Jiangxi Province(No.20232BAB206085 and 20224BAB216074 for TFY,No.20232BAB216084 for LY)Postdoctoral Research Foundation of China(No.2022M721452 for TFY)。
文摘The synergistic approach of combining photodynamic immunotherapy with endogenous clearance of PD-L1 immune checkpoint blockade therapy holds promise for enhancing survival outcomes in glioblastoma(GBM)patients.The observed upregulation of O-GlcNAc glycolysis in tumors may contribute to the stabilization of endogenous PD-L1 protein,facilitating tumor immune evasion.This study presents a pH-adapted excited state intramolecular proton transfer(ESIPT)-isomerizedβ-ketoamide-based covalent organic framework(COF)nanoplatform(denoted as OT@COF-RVG).Temozolomide(TMZ)and OSMI-4(O-GlcNAc transferase inhibitor)were integrated into COF cavities,then modified on the surface with polyethylene glycol and the rabies virus peptide RVG-29,showing potential for sensitizing TMZ chemotherapy and initiating photodynamic therapy(PDT).By inhibiting O-GlcNAc and promoting lysosomal degradation of PD-L1,OT@COF-RVG enhanced the effectiveness of immune checkpoint blockade(ICB)therapy.Additionally,treatment with OT@COF-RVG led to a notable elevation in reactive oxygen species(ROS)levels,thereby re-establishing an immunostimulatory state,inducing immunogenic cell death(ICD).In summary,our research unveiled a correlation between O-GlcNAc in GBM and the evasion of immune responses by tumors,while showcasing the potential of OT@COF-RVG in reshaping the immunosuppressive microenvironment of GBM and offering a more effective approach to immunotherapy in clinical settings.
基金supported by the National Natural Science Foundation of China(U22A20314)the State Key Project Ministry of Science and Technology of China(2022YFC2504200)+3 种基金the Key Research and Development Project of Hubei Province(2022BCA029)the Fundamental Research Funds for the Central Universities(2042023kf0198)the Chutian Researcher Project(X22020024)Noel Martin foundation at the University of Sydney(NMVC-2024Ye)。
文摘Dental pulp stem cells(DPSCs)have demonstrated remarkable potential in enhancing peripheral nerve regeneration,though the precise mechanisms remain largely unknown.This study investigates how DPSCs alleviate Schwann cell pyroptosis and restore mitochondrial homeostasis through intercellular mitochondrial transfer.In a crab-eating macaque model,we first observed that DPSC-loaded nerve conduits significantly promoted long-term nerve regeneration,facilitating tissue proliferation and myelin recovery.We further established a rat facial nerve injury(FNI)model and found that DPSC treatment reduced pyroptosis and mitochondrial ROS production in Schwann cells.A pivotal mitochondrial protective mechanism,resembling the effects of a ROS-targeted inhibitor,involved the transfer of mitochondria from DPSCs to pyroptosis-induced Schwann cells via tunneling nanotubes,while blocking intercellular junctions or mitochondrial function diminished the therapeutic effects.TNFαsecreted by pyroptosis-induced Schwann cells activated the NF-κB pathway in DPSCs,enhancing mitochondrial transfer and adaptive stress responses,thereby promoting mitochondrial protection against pyroptosis in Schwann cells,as reflected in the improved therapeutic efficacy of TNF α-preconditioned DPSCs in the FNI model.These findings unveil a mechanism through which DPSCs foster nerve regeneration via mitochondrial transfer,presenting a promising strategy for enhancing stem cell-based therapies for nerve injuries.
