Xanthomonas spp. cause severe bacterial diseases. However, effective strategies for prevention and management of these diseases are scarce. Thus, it is necessary to improve the efficiency of control of diseases caused...Xanthomonas spp. cause severe bacterial diseases. However, effective strategies for prevention and management of these diseases are scarce. Thus, it is necessary to improve the efficiency of control of diseases caused by Xanthomonas. In this study, Xanthomonas oryzae pv. oryzae(Xoo), which causes rice bacterial leaf blight, has been studied as a representative. A transposon insertion library of Xoo, comprising approximately 200,000 individual insertion mutants, was generated. Transposon sequencing data indicated that the mariner C9 transposase mapped at 35.7–36.4% of all potential insertion sites, revealing 491 essential genes required for the growth of Xoo in rich media. The results show that, compared to the functions of essential genes of other bacteria, the functions of some essential genes of Xoo are unknown, 25 genes might be dangerous for the Xanthomonas group, and 3 are specific to Xanthomonas. High-priority candidates for developing broad-spectrum, Xanthomonas-specific, and environment-friendly bactericides were identified in this study. In addition, this study revealed the possible targets of dioctyldiethylenetriamine using surface plasmon resonance(SPR) in combination with high performance liquid chromatography–mass spectrometry(HPLC–MS). The study also provided references for the research of some certain bactericides with unknown anti-bacterial mode of action. In conclusion, this study urged a better understanding of Xanthomonas,provided meaningful data for the management of bacterial leaf blight, and disclosed selected targets of a novel bactericide.展开更多
Great Wall Motor(GWM),a leading automotive manufacturer,places a strong emphasis on environmental sustainability and social responsibility.The company focuses on comprehensively evaluating and enhancing its supply cha...Great Wall Motor(GWM),a leading automotive manufacturer,places a strong emphasis on environmental sustainability and social responsibility.The company focuses on comprehensively evaluating and enhancing its supply chain to align with these objectives.This evaluation spans the entire product life cycle,encompassing design,manufacturing,packaging,distribution,usage,and recycling and disposal processes.Key areas of focus include optimizing raw material selection,improving product recyclability,reducing energy consumption and waste emissions,and minimizing carbon emissions during transportation.Through these endeavors,GWM not only enhances its environmental performance by reducing carbon emissions and resource consumption but also bolsters its brand image and competitiveness in the market.GWM’s dedication to environmental innovation and technological leadership serves as a driving force behind sustainable development and social responsibility within the industry.展开更多
Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has...Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.展开更多
A novel strategy was developed to fabricate FeNx-doped carbon quantum dots(Fe-N-CQDs)to detect Cu^(2+) ions selectively as a fluorescence probe.The Fe-N-CQDs were synthesized by an efficient electrolysis of a carbon c...A novel strategy was developed to fabricate FeNx-doped carbon quantum dots(Fe-N-CQDs)to detect Cu^(2+) ions selectively as a fluorescence probe.The Fe-N-CQDs were synthesized by an efficient electrolysis of a carbon cloth electrode,which was coated with monoatomic ironanchored nitrogen-doped carbon(Fe-N-C).The obtained Fe-N-CQDs emitted blue fluorescence and possessed a quantum yield(QY)of 7.5%.An extremely wide linear relationship between the Cu^(2+) concentration and the fluorescence intensity was obtained in the range from 100 nmol L^(-1) to 1000 nmol L^(-1)(R^(2)=0.997),and the detection limit was calculated as 59 nmol L^(-1).Moreover,the Fe-N-CQDs demonstrated wide range pH compatibility between 2 and 13 due to the coordination between pyridine nitrogen and Fe^(3+),which dramatically reduced the affection of the protonation and deprotonation process between H^(+) and Fe-N-CQDs.It is notable that the Fe-N-CQDs exhibited a rapid response in Cu^(2+) detection,where stable quenching can be completed in 7 s.The mechanism of excellent selective detection of Cu^(2+) was revealed by energy level simulation that the LUMO level of Fe-N-CQDs(-4.37 eV)was close to the redox potential of Cu^(2+),thus facilitating the electron transport from Fe-N-CQDs to Cu^(2+).展开更多
Dynamically tunable laser sources are highly promising for realizing visionary concepts of integrated photonic circuits and other applications. In this paper, a Ga N-based laser with an integrated PN junction heater o...Dynamically tunable laser sources are highly promising for realizing visionary concepts of integrated photonic circuits and other applications. In this paper, a Ga N-based laser with an integrated PN junction heater on Si is fabricated.The photoluminescence properties of the Ga N beam cavity are controlled by temperature, and the Joule heater provides electrically driven regulation of temperature. These two features of the cavity make it possible to realize convenient tuning of the lasing properties. The multi-functional Ga N beam cavity achieves optically pumped lasing with a single mode near 362.4 nm with a high Q-factor of 1394. The temperature of this device increases by 0–5℃ under the Joule heating effect. Then, electrical control of the lasing mode is demonstrated. The lasing resonant peak shows a continuous redshift of about 0.5 nm and the device also exhibits dynamic switching of its lasing mode. The lasing modulation can be ascribed to temperature-induced reduction of the bandgap. Our work may be of benefit for external optical modulation in future chip-based optoelectronic devices.展开更多
The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/re...The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.展开更多
Background:Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract.The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD patholog...Background:Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract.The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD pathology.Growing evidence indicated that epithelial cell ferroptosis is linked to IBD and is considered a target process.Methods:RAS-selective lethal 3(RSL3)was used to induce ferroptosis in intestinal epithelial cell line No.6(IEC-6)cells,and cell ferroptosis and the effects of tanshinone IIA(Tan IIA)were determined by cell counting kit-8(CCK-8),reactive oxygen species(ROS)staining,Giemsa staining and transmission electron microscope(TEM).The cell viability of natural product library compounds was determined by CCK-8.The expression of ferroptosis-related genes were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blot.Results:Treatment of IEC-6 cells results in the accumulation of ROS and typical morphological characteristics of ferroptosis.RSL3 treatment caused rapid cellular cytotoxicity which could be reversed by ferrostatin-1(Fer-1)in IEC-6 cells.Natural product library screening revealed that Tan IIA is a potent inhibitor of IEC-6 cell ferroptosis.Tan IIA could significantly protect the RSL3-induced ferroptosis of IEC-6 cells.Furthermore,the ferroptosis suppressors,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and miR-17-92 were found to be early response genes in RSL3-treated cells.Treatment of IEC-6 cells with Tan IIA resulted in upregulation of GPX4,SLC7A11,and miR-17-92.Conclusion:Our study demonstrated that Tan IIA protects IEC-6 cells from ferroptosis through the upregulation of GPX4,SLC7A11,and miR-17-92.The findings might provide a theoretical grounding for the future application of Tan IIA to treat or prevent IBD.展开更多
Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in ...Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further probed.Methods:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)data.Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out.The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves.The CLEC5A expression pattern in OC was validated using immunohistochemistry.The CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO cohort.Finally,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also compared.Results:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor.The CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in it.While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was lower.Conclusion:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.展开更多
Mesenchymal stem cells(MSCs)have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation,differentiation,and immune regulation.However,during in vitro expansion,MSCs a...Mesenchymal stem cells(MSCs)have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation,differentiation,and immune regulation.However,during in vitro expansion,MSCs are prone to aging,which largely limits their application.Prostaglandin E-2(PGE-2)is a key effector secreted by MSCs to exert immunomodulatory effects.By screening the compound library for PGE-2 secretion,the antioxidant trolox was verified as a stimulator of MSCs to secrete PGE-2.The effect of antioxidant trolox on biological characteristics of MSCS,including aging,proliferation,and gene expression,was examined.The results demonstrated that trolox can resist aging,promote proliferation,and enhance PGE-2 secretion of MSCs without affecting their surface marker expression.Furthermore,trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects.Thus,trolox addition might be beneficial for MSCs expansion and their application.展开更多
With the progress of deep learning research, convolutional neural networks have become the most important method in feature extraction. How to effectively classify and recognize the extracted features will directly af...With the progress of deep learning research, convolutional neural networks have become the most important method in feature extraction. How to effectively classify and recognize the extracted features will directly affect the performance of the entire network. Traditional processing methods include classification models such as fully connected network models and support vector machines. In order to solve the problem that the traditional convolutional neural network is prone to over-fitting for the classification of small samples, a CNN-TWSVM hybrid model was proposed by fusing the twin support vector machine (TWSVM) with higher computational efficiency as the CNN classifier, and it was applied to the traffic sign recognition task. In order to improve the generalization ability of the model, the wavelet kernel function is introduced to deal with the nonlinear classification task. The method uses the network initialized from the ImageNet dataset to fine-tune the specific domain and intercept the inner layer of the network to extract the high abstract features of the traffic sign image. Finally, the TWSVM based on wavelet kernel function is used to identify the traffic signs, so as to effectively solve the over-fitting problem of traffic signs classification. On GTSRB and BELGIUMTS datasets, the validity and generalization ability of the improved model is verified by comparing with different kernel functions and different SVM classifiers.展开更多
The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family- CNTNA...The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family- CNTNAP1 (Casprl), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Casprl-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Casprl participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.展开更多
基金This study was supported by the National Natural Science Foundation of China(32272587 and 32202342)the Programs for the Scientific Research Activities of Academic and Technical Leaders of Anhui Province,China(2020D251)+3 种基金the Development Fund for Talent Personnel of Anhui Agricultural University,China(rc342006)the University Synergy Innovation Program of Anhui Province,China(GXXT-2021-059)the Key Project of the Natural Science Foundation of Anhui Provincial Department of Education,China(2023AH040129)Anhui Province Agricultural Eco-Environmental Protection and Quality Safety Industry Technology System,China。
文摘Xanthomonas spp. cause severe bacterial diseases. However, effective strategies for prevention and management of these diseases are scarce. Thus, it is necessary to improve the efficiency of control of diseases caused by Xanthomonas. In this study, Xanthomonas oryzae pv. oryzae(Xoo), which causes rice bacterial leaf blight, has been studied as a representative. A transposon insertion library of Xoo, comprising approximately 200,000 individual insertion mutants, was generated. Transposon sequencing data indicated that the mariner C9 transposase mapped at 35.7–36.4% of all potential insertion sites, revealing 491 essential genes required for the growth of Xoo in rich media. The results show that, compared to the functions of essential genes of other bacteria, the functions of some essential genes of Xoo are unknown, 25 genes might be dangerous for the Xanthomonas group, and 3 are specific to Xanthomonas. High-priority candidates for developing broad-spectrum, Xanthomonas-specific, and environment-friendly bactericides were identified in this study. In addition, this study revealed the possible targets of dioctyldiethylenetriamine using surface plasmon resonance(SPR) in combination with high performance liquid chromatography–mass spectrometry(HPLC–MS). The study also provided references for the research of some certain bactericides with unknown anti-bacterial mode of action. In conclusion, this study urged a better understanding of Xanthomonas,provided meaningful data for the management of bacterial leaf blight, and disclosed selected targets of a novel bactericide.
文摘Great Wall Motor(GWM),a leading automotive manufacturer,places a strong emphasis on environmental sustainability and social responsibility.The company focuses on comprehensively evaluating and enhancing its supply chain to align with these objectives.This evaluation spans the entire product life cycle,encompassing design,manufacturing,packaging,distribution,usage,and recycling and disposal processes.Key areas of focus include optimizing raw material selection,improving product recyclability,reducing energy consumption and waste emissions,and minimizing carbon emissions during transportation.Through these endeavors,GWM not only enhances its environmental performance by reducing carbon emissions and resource consumption but also bolsters its brand image and competitiveness in the market.GWM’s dedication to environmental innovation and technological leadership serves as a driving force behind sustainable development and social responsibility within the industry.
基金supported by the National Key Research and Development Plan,China(Grant No.:2022YFC3500202)the Natural Science Foundation of China(Grant Nos.:82172558,and 82205024)+4 种基金the Scientific and Technological Innovation Action Plan of Natural Science Foundation Project of Shanghai,China(Grant No.:22ZR1447400)the Scientific and Technological Innovation Action Plan,China(Grant No.:22ZR1447400)the Fundamental Research Funds for the Central Universities,China(Grant Nos.:020814380179,020814380174)the Distinguished Young Scholars of Nanjing,China(Grant No.:JQX20008)the School of Life Science(NJU)-Sipimo Joint Funds and Mountain Climbing Talents Project of Nanjing University,China(Grant No.:2015018).
文摘Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.
基金supported partially by a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) of the Korean government (2021R1A3B1068304)。
基金the National Natural Science Foundation of China(Nos.21776302 and 21776308)the Science Foundation of China University of Petroleum,Beijing(No.2462020YXZZ033).
文摘A novel strategy was developed to fabricate FeNx-doped carbon quantum dots(Fe-N-CQDs)to detect Cu^(2+) ions selectively as a fluorescence probe.The Fe-N-CQDs were synthesized by an efficient electrolysis of a carbon cloth electrode,which was coated with monoatomic ironanchored nitrogen-doped carbon(Fe-N-C).The obtained Fe-N-CQDs emitted blue fluorescence and possessed a quantum yield(QY)of 7.5%.An extremely wide linear relationship between the Cu^(2+) concentration and the fluorescence intensity was obtained in the range from 100 nmol L^(-1) to 1000 nmol L^(-1)(R^(2)=0.997),and the detection limit was calculated as 59 nmol L^(-1).Moreover,the Fe-N-CQDs demonstrated wide range pH compatibility between 2 and 13 due to the coordination between pyridine nitrogen and Fe^(3+),which dramatically reduced the affection of the protonation and deprotonation process between H^(+) and Fe-N-CQDs.It is notable that the Fe-N-CQDs exhibited a rapid response in Cu^(2+) detection,where stable quenching can be completed in 7 s.The mechanism of excellent selective detection of Cu^(2+) was revealed by energy level simulation that the LUMO level of Fe-N-CQDs(-4.37 eV)was close to the redox potential of Cu^(2+),thus facilitating the electron transport from Fe-N-CQDs to Cu^(2+).
基金the Natural Science Foundation of Jiangsu Province, China (Grant No. BK20210593)the Foundation of Jiangsu Provincial Double Innovation Doctor Program (Grant No. 30644)+2 种基金the National Natural Science Foundation of China (Grant No. 62204127)State Key Laboratory of Luminescence and Applications (Grant No. SKLA 202104)open research fund of Key Lab of Broadband Wireless Communication and Sensor Network Technology (Nanjing University of Posts and Telecommunications, Ministry of Education)。
文摘Dynamically tunable laser sources are highly promising for realizing visionary concepts of integrated photonic circuits and other applications. In this paper, a Ga N-based laser with an integrated PN junction heater on Si is fabricated.The photoluminescence properties of the Ga N beam cavity are controlled by temperature, and the Joule heater provides electrically driven regulation of temperature. These two features of the cavity make it possible to realize convenient tuning of the lasing properties. The multi-functional Ga N beam cavity achieves optically pumped lasing with a single mode near 362.4 nm with a high Q-factor of 1394. The temperature of this device increases by 0–5℃ under the Joule heating effect. Then, electrical control of the lasing mode is demonstrated. The lasing resonant peak shows a continuous redshift of about 0.5 nm and the device also exhibits dynamic switching of its lasing mode. The lasing modulation can be ascribed to temperature-induced reduction of the bandgap. Our work may be of benefit for external optical modulation in future chip-based optoelectronic devices.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81970245,82270357,and 81770432)the Scientific Research Project of Shaanxi Administration of Traditional Chinese Medicine,China(Grant Nos.:2021-04-ZZ-001,2021-QYPT-003,and 2022-SLRH-YQ-004)+1 种基金the Project of Science and Technology Department of Shaanxi Province in China(Project No.:2022YWZX-PG-01)the Natural Science Basic Research Program of Shaanxi Province in China(Grant No.:2023-JC-JQ-61).
文摘The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.
基金supported by the National Key Research and Development Program(Grant Number:2017YFA0105303)the Natural Science Foundation of Shandong Province(Grant Number:ZR2020MH327).
文摘Background:Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract.The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD pathology.Growing evidence indicated that epithelial cell ferroptosis is linked to IBD and is considered a target process.Methods:RAS-selective lethal 3(RSL3)was used to induce ferroptosis in intestinal epithelial cell line No.6(IEC-6)cells,and cell ferroptosis and the effects of tanshinone IIA(Tan IIA)were determined by cell counting kit-8(CCK-8),reactive oxygen species(ROS)staining,Giemsa staining and transmission electron microscope(TEM).The cell viability of natural product library compounds was determined by CCK-8.The expression of ferroptosis-related genes were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blot.Results:Treatment of IEC-6 cells results in the accumulation of ROS and typical morphological characteristics of ferroptosis.RSL3 treatment caused rapid cellular cytotoxicity which could be reversed by ferrostatin-1(Fer-1)in IEC-6 cells.Natural product library screening revealed that Tan IIA is a potent inhibitor of IEC-6 cell ferroptosis.Tan IIA could significantly protect the RSL3-induced ferroptosis of IEC-6 cells.Furthermore,the ferroptosis suppressors,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and miR-17-92 were found to be early response genes in RSL3-treated cells.Treatment of IEC-6 cells with Tan IIA resulted in upregulation of GPX4,SLC7A11,and miR-17-92.Conclusion:Our study demonstrated that Tan IIA protects IEC-6 cells from ferroptosis through the upregulation of GPX4,SLC7A11,and miR-17-92.The findings might provide a theoretical grounding for the future application of Tan IIA to treat or prevent IBD.
基金funded by a grant from the National Natural Science Foundation of China(81873045)the Natural Science Foundation of Fujian Province of China(2020J011115)+1 种基金the Medicine Innovation Project of Fujian Province of China(2020CXB007)the Joint Funds for the Innovation of Science and Technology(2021Y9209).
文摘Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further probed.Methods:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)data.Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out.The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves.The CLEC5A expression pattern in OC was validated using immunohistochemistry.The CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO cohort.Finally,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also compared.Results:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor.The CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in it.While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was lower.Conclusion:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.
基金supported by the Natural Science Foundation of Shandong Province(ZR2020MH327)Hebei Key Research and Development Program(19272405D)Jilin Scientific and Technological Development Program(Grant No.20190304041YY).
文摘Mesenchymal stem cells(MSCs)have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation,differentiation,and immune regulation.However,during in vitro expansion,MSCs are prone to aging,which largely limits their application.Prostaglandin E-2(PGE-2)is a key effector secreted by MSCs to exert immunomodulatory effects.By screening the compound library for PGE-2 secretion,the antioxidant trolox was verified as a stimulator of MSCs to secrete PGE-2.The effect of antioxidant trolox on biological characteristics of MSCS,including aging,proliferation,and gene expression,was examined.The results demonstrated that trolox can resist aging,promote proliferation,and enhance PGE-2 secretion of MSCs without affecting their surface marker expression.Furthermore,trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects.Thus,trolox addition might be beneficial for MSCs expansion and their application.
文摘With the progress of deep learning research, convolutional neural networks have become the most important method in feature extraction. How to effectively classify and recognize the extracted features will directly affect the performance of the entire network. Traditional processing methods include classification models such as fully connected network models and support vector machines. In order to solve the problem that the traditional convolutional neural network is prone to over-fitting for the classification of small samples, a CNN-TWSVM hybrid model was proposed by fusing the twin support vector machine (TWSVM) with higher computational efficiency as the CNN classifier, and it was applied to the traffic sign recognition task. In order to improve the generalization ability of the model, the wavelet kernel function is introduced to deal with the nonlinear classification task. The method uses the network initialized from the ImageNet dataset to fine-tune the specific domain and intercept the inner layer of the network to extract the high abstract features of the traffic sign image. Finally, the TWSVM based on wavelet kernel function is used to identify the traffic signs, so as to effectively solve the over-fitting problem of traffic signs classification. On GTSRB and BELGIUMTS datasets, the validity and generalization ability of the improved model is verified by comparing with different kernel functions and different SVM classifiers.
基金Project(51674304)supported by the National Natural Science Foundation of ChinaProject(2018JJ3677)supported by Natural Science Foundation of Hunan Province,China。
基金supported by a grant from the Instructional Program of Science and Technology Bureau of Wuxi City of China,No.0302B010507130039PB
文摘The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family- CNTNAP1 (Casprl), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Casprl-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Casprl participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20160936,BK20160938)the National Natural Science Foundation of China(51708297)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)~~
文摘近几年过一硫酸盐(PMS)活化技术备受关注,其中利用太阳能活化PMS具有可持续和环保的优势,但PMS本身不吸收可见光.因此,本文提出利用具有可见光响应的石墨相氮化碳(g-C3N4)激发产生光电子进而活化PMS.首先利用三聚氰胺前驱体通过热缩聚法制备g-C3N4,通过X射线衍射(XRD)、傅里叶变换红外光谱(FT-IR)、紫外-可见光漫反射(UV-Vis)、荧光光谱(PL)、透射电镜(TEM)、N2吸附脱附测试(BET)、电化学等一系列方法对g-C3N4进行表征,研究其表面性质及光学性能.结果显示, g-C3N4具有典型的片层结构和可见光活性,禁带宽度为2.7 e V.本文选取光惰性的内分泌干扰物邻苯二甲酸二甲酯(DMP)为目标污染物,系统地研究了其降解动力学和降解机理.研究发现,在短波紫外光(254和300nm)照射下,直接光解和·OH参与的反应机理能实现DMP的光降解,而在可见光照射下g-C3N4介导的光催化过程不能使DMP分解;但当添加PMS时,体系主导自由基由·O2–转化为SO4·–和·OH,从而实现DMP的有效降解和矿化.研究还发现,高浓度的PMS和高剂量的g-C3N4均可以提高PMS的活化量和相应的DMP降解效率,但提高催化剂剂量的方式能更充分的利用PMS.尽管高浓度的DMP阻碍了PMS和光催化剂g-C3N4的有效接触,但可以提高PMS的利用率.当p H低于零电荷点(5.4)时, DMP的降解效率较高.此外,使用两种淬灭剂(乙醇和叔丁醇)与DMP进行竞争性实验,结合电子自旋共振检测,表明SO4·–和·OH都是体系主要的自由基.此外,还对g-C3N4的可持续性能进行考察,四次循环实验结果显示,该催化剂具有良好的可重复利用性.对DMP降解进行总有机碳测定,发现降低了19%.最后,利用液相色谱质谱联用对DMP降解产物进行定性定量分析,发现DMP主要通过SO4·–和·OH对苯环的攻击以及脂肪族链的氧化断键这两种途径进行降解.综上可见,利用可见光激发g-C3N4产生的光电子能有效活化PMS降解顽固型有机污染物,可为实现太阳能活化PMS技术提供有力的技术参考.