Objective:Lynch syndrome(LS)predisposes patients to early onset endometrioid endometrial cancer(EEC).However,little is known about LS-related EEC in the Chinese population.The aim of this study was to investigate the ...Objective:Lynch syndrome(LS)predisposes patients to early onset endometrioid endometrial cancer(EEC).However,little is known about LS-related EEC in the Chinese population.The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC.Methods:We applied universal immunohistochemistry screening to detect the expression of mismatch repair(MMR)proteins,which was followed by MLH1 methylation analysis to identify suspected LS cases,next-generation sequencing(NGS)to confirm LS,and microsatellite instability(MSI)analysis to verify LS.Results:We collected 211 samples with EEC.Twenty-seven(27/211,12.8%)EEC cases had a loss of MMR protein expression.After MLH1 methylation analysis,16 EEC cases were suggested to be associated with LS.Finally,through NGS and MSI analysis,we determined that 10 EEC(10/209,4.78%)cases were associated with LS.Among those cases,3 unreported mutations(1 frameshift and 2 nonsense)were identified.M SH6 c.597_597delC,found in 4 patients,is likely to be a founder mutation in China.Conclusions:We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC,by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis.The novel mutations identified in this study expand knowledge of LS.展开更多
Four and a half LIM domains protein 1(FH L1),as the name suggests,contains four and a half LIM domains capable o f interacting with various molecules,including structural proteins,kinases,and transcriptional machinery...Four and a half LIM domains protein 1(FH L1),as the name suggests,contains four and a half LIM domains capable o f interacting with various molecules,including structural proteins,kinases,and transcriptional machinery.FHL1 contains a zinc-finger domain and performs diverse roles in regulation of gene transcription,cytoarchitecture,cell proliferation,and signal transduction.Several studies have validated the importance of FHL1 in muscle development,myopathy,and cardiovascular diseases.Mutations in the FHL1 gene are associated with various myopathies.Recently,FHL1 was identified as a major host factor for chikungunya virus(CHIKV)infection in both humans and mice.Based on more recent findings over the last decade,FHL1 is proposed to play a dual role in cancer progression.On the one hand,FHL1 expression is suppressed in several cancer types,which correlates with increased metastatic disease and decreased survival.Moreover,FHL1 is reported to inhibit tum or cell growth and migration by associating with diverse signals,such as TGF-P and ER,and therefore considered a tumor suppressor.On the other hand,FHL1 can function as an oncogenic protein that promotes tumor progression upon phosphorylation,reflecting complex roles in cancer.This review primarily focuses on the dual role and underlying mechanisms of action of FHL1 in human cancer progression and its clinical relevance.展开更多
The neuroprotective effects of ginkgo biloba extract have been shown in rats following spinal cord injury （SCI）. However, the precise protective mechanisms remain unclear. In the present study, low-acid water-solubl...The neuroprotective effects of ginkgo biloba extract have been shown in rats following spinal cord injury （SCI）. However, the precise protective mechanisms remain unclear. In the present study, low-acid water-soluble extract of ginkgo biloba EGb761 was used to treat rats with SCI. Xanthin oxidase, thiobarbituric acid, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling assay, and immunohistochemistry were utilized to detect lipid peroxidation, neural cell apoptosis, and inducible nitric oxide synthase activity in rats with SCI. Results revealed significantly increased superoxide dismutase activity, decreased malondialdehyde content, apoptotic index, and inducible nitric oxide synthase expression in SCI rats following EGb761 treatment. Therefore, EGb761 suppressed lipid peroxidation following SCI, relieved neural cell apoptosis, inhibited inducible nitric oxide synthase expression, and ultimately exerted protective effects on SCI.展开更多
A new membrane type Al_2O_3 micromachining material is used.We develop an environmental multi-parameter detection micro-system,which implements the detection to temperature,humidity,wind speed,and CO.The test results ...A new membrane type Al_2O_3 micromachining material is used.We develop an environmental multi-parameter detection micro-system,which implements the detection to temperature,humidity,wind speed,and CO.The test results illustrate that the heat-release unit in micro-system intercross greatly affects other sensing units on the temperature.We study the method of etching process,which formed cavity to reduce the heat exchange efficiency and decrease temperature intercross effect.展开更多
The sensitivity and selectivity of gas sensors are related with not only sensing material,but also their operating temperatures.Applying this property,temperature modulation technique has been proposed to improve the ...The sensitivity and selectivity of gas sensors are related with not only sensing material,but also their operating temperatures.Applying this property,temperature modulation technique has been proposed to improve the selectivity of gas sensors.With a newly developed alumina based micro gas sensor,the sensitivity to CO and CH_4 at different operating temperatures was investigated.By modulating the temperature of the sensor at pulse and sine wave modes with different frequencies and amplitudes,the dynamic responses of the sensor were measured and processed.Results show that the modulating waveshape plays an important role in the improvement of selectivity,while the influence of frequency is small at the suitable sampling frequency in the range of 25 mHz～200 mHz.展开更多
In order to improve the reliability of hydrogen sensor,a novel strategy for full range of hydrogen sensor fault detection and recovery is proposed in this paper. Three kinds of sensors are integrated to realize the me...In order to improve the reliability of hydrogen sensor,a novel strategy for full range of hydrogen sensor fault detection and recovery is proposed in this paper. Three kinds of sensors are integrated to realize the measurement for full range of hydrogen concentration based on relevance vector machine( RVM). Failure detection of hydrogen sensor is carried out by using the variance detection method. When a sensor fault is detected,the other fault-free sensors can recover the fault data in real-time by using RVM predictor accounting for the relevance of sensor data. Analysis,together with both simulated and experimental results,a full-range hydrogen detection and hydrogen sensor self-validating experiment is presented to demonstrate that the proposed strategy is superior at accuracy and runtime compared with the conventional methods. Results show that the proposed methodology provides a better solution to the full range of hydrogen detection and the reliability improvement of hydrogen sensor.展开更多
A new type of semiconductor gas sensor fabricated on an alumina substrate for CO and CH_4 detection has been developed.The alumina substrate was obtained by an anodizing method companying with micromachining to form p...A new type of semiconductor gas sensor fabricated on an alumina substrate for CO and CH_4 detection has been developed.The alumina substrate was obtained by an anodizing method companying with micromachining to form patterned structure.Gas sensitive material was made of nano-sized SnO_2 powder prepared by a chemical precipitation method.Au (0.048wt.%) and Pd (0.3 wt%) were doped to SnO_2 powder to increase sensitivity to CO and CH_4,respectively.The heating power and sensing performance were measured with an automatic test system.The results show that the sensors have remarkable responses and certain selectivity to the target gases.Our study demonstrates that alumina substrate can be successfully applied in sensor micromachining technology.展开更多
The paper presents a new method for fabricating a gas-sensitive micro-sensor based on MEMS.The primary target agents are nitrogen dioxides (NO_2),and DIMP.Past-per-billion concentration levels of these two chemicals c...The paper presents a new method for fabricating a gas-sensitive micro-sensor based on MEMS.The primary target agents are nitrogen dioxides (NO_2),and DIMP.Past-per-billion concentration levels of these two chemicals can be detected.An interdigitated gate electrode field-effect transistor (IGEFET) has been coupled with a chemically-active and electron-beam evaporated copper phthaiocyanine (CuPc) thin film to implement a gas-sensitive micro-sensor.The sensor is excited with voltage pulse.Time and frequency-domain response were measured.The magnitude of the normalized difference Fourier transform is distinct distinguished.展开更多
Integrated gas sensor suspending bridge style micro-structure has been developed on Al_2O_3 new type membrane based on MEMS.CH_4 gas sensing unit and CO gas sensing unit were fabricated separately on 4 unit array styl...Integrated gas sensor suspending bridge style micro-structure has been developed on Al_2O_3 new type membrane based on MEMS.CH_4 gas sensing unit and CO gas sensing unit were fabricated separately on 4 unit array style suspending bridge structure.We have studied on time-sequence modulation form voltage pulse heating method which forms different work temperature展开更多
METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase activity.METTL3 enhances RNA translation independently of its catalytic activity.However,the underlying mechanism is still elusive.Her...METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase activity.METTL3 enhances RNA translation independently of its catalytic activity.However,the underlying mechanism is still elusive.Here,we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by SIRT3.Neither the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at K177.Importantly,acetylation of METTL3 blocks its interaction with EIF3H,a subunit of the translation initiation factor,thereby reducing mRNA translation efficiency.Interestingly,acetylation of METTL3 responds to oxidative stress.Mechanistically,oxidative stress enhances the interaction of PCAF with METTL3,increases METTL3 acetylation,and suppresses the interaction of METTL3 with EIF3H,thereby decreasing the translation efficiency of ribosomes and inhibiting cell proliferation.Altogether,we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.展开更多
FRMD6,a member of the 4.1 ezrin-radixin-moesin domain-containing protein family,has been reported to inhibit tumor progression in multiple cancers.Here,we demonstrate the involvement of FRMD6 in lung cancer progressio...FRMD6,a member of the 4.1 ezrin-radixin-moesin domain-containing protein family,has been reported to inhibit tumor progression in multiple cancers.Here,we demonstrate the involvement of FRMD6 in lung cancer progression.We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues.In addition,the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma(n=75,P=0.0054)and lung adenocarcinoma(n=94,P=0.0330).Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6.Mechanistically,FRMD6 interacts and colocalizes with mTOR and S6K,which are the key molecules of the mTOR signaling pathway.FRMD6 markedly enhances the interaction between mTOR and S6K,subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells.Furthermore,knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^(−/−)gene KO MEFs and mice.Altogether,our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.展开更多
Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a...Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a Kindlin-2 transgenic mouse model using a mammary gland-specific promoter, mammary tumor virus(MMTV) long terminal repeat(LTR). Kindlin-2 was overexpressed in the epithelial cells of the transgenic mice. The mammary gland ductal trees were found to grow faster in MMTV-Kindlin-2 transgenic mice than in control mice during puberty. Kindlin-2 promoted mammary gland growth as indicated by more numerous duct branches and larger lumens, and more alveoli were formed in the mammary glands during pregnancy under Kindlin-2 overexpression. Importantly, mammary gland-specific expression of Kindlin-2 induced tumor formation at the age of 55 weeks on average. Additionally, the levels of estrogen receptor and progesterone receptor were decreased, whereas human epidermal growth factor receptor 2 and β-catenin were upregulated in the Kindlin-2-induced mammary tumors. These findings demonstrated that Kindlin-2 induces mammary tumor formation via activation of the Wnt signaling pathway.展开更多
Slug,a member of the Snail family of transcriptional repressors,plays a key role in cancer progression,cellular plasticity,and epithelial to mesenchymal transition(EMT).Slug is a fast-turnover protein and its stabilit...Slug,a member of the Snail family of transcriptional repressors,plays a key role in cancer progression,cellular plasticity,and epithelial to mesenchymal transition(EMT).Slug is a fast-turnover protein and its stability is controlled by post-translational modifications.Here,we identified that Slug is acetylated by acetyltransferase CREB-binding protein(CBP)in breast cancer cells.CBP directly interacts with the C-terminal domain of Slug through its catalytic histone acetyltransferase(HAT)domain,leading to acetylation of Slug at lysines 166 and 211.Analysis with acetylation-specific antibodies revealed that Slug is highly acetylated in metastatic breast cancer cells.Notably,Slug acetylation,mediated by CBP at lysines 166 and 211,doubles its halflife and increases its stability.Further,acetylated Slug downregulates the expression of E-cadherin,the epithelial marker,and upregulates the expression of N-cadherin and vimentin,thereby promoting breast cancer cell migration.In conclusion,the present study demonstrates that CBP-mediated Slug acetylation increases its stability,promoting EMT and migration of breast cancer cells.展开更多
PH20 is a member of the human hyaluronidase family that degrades hyaluronan in the extracellular matrix and controls tumor progression.Inhibition of DNA methyltransferases(DNMTs)leads to elevated hyaluronan levels;how...PH20 is a member of the human hyaluronidase family that degrades hyaluronan in the extracellular matrix and controls tumor progression.Inhibition of DNA methyltransferases(DNMTs)leads to elevated hyaluronan levels;however,whether DNMT inhibitors control PH20 remains unclear.Here,we report that the DNMT1 inhibitor,decitabine,suppresses PH20 expression by activating the long non-coding RNA PHACTR2-AS1(PAS1).PAS1 forms a tripartite complex with the RNA-binding protein vigilin and histone methyltransferase SUV39H1.The interaction between PAS1 and vigilin maintains the stability of PAS1.Meanwhile,PAS1 recruits SUV39H1 to trigger the H3K9 methylation of PH20,resulting in its silencing.Functionally,PAS1 inhibits breast cancer growth and metastasis,at least partially,by suppressing PH20.Combination therapy of decitabine and PAS1-30nt-RNA,which directly binds to SUV39H1,effectively blocked breast cancer growth and metastasis in mice.Taken together,DNMT1,PAS1,and PH20 comprise a regulatory axis to control breast cancer growth and metastasis.These findings reveal that the DNMT1-PAS1-PH20 axis is a potential therapeutic target for breast cancer.展开更多
Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-l...Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-like breast cancer development remain largely unknown.Here,we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients.In human TCGA database,C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3,two transcription factors that regulate mammary gland stem cell fate.Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5;depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3.These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3.Taken together,we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.展开更多
LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains uncl...LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains unclear. This study aimed to clarify whether the expression level of LGR6 is correlated with colon adenocarcinoma progression. Immunohistochemistry was used to detect LGR6 expression in colon adenoma tissues (n = 21), colon adenocarcinoma tissues (n = 156), and adjacent normal tissues (n = 124). The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues (P < 0.001). Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma (log-rank test, P = 0.016). Univariate and multivariate survival analyses showed that, in addition to N and M classification, LGR6 expression served as an independent prognostic factor. Thus, low expression of LGR6 can be used as an independent prognostic parameter in patients with colon adenocarcinoma.展开更多
Large tumor suppressor 1(LATS1)is the key kinase controlling activation of Hippo signalling pathway.Post-translational modifications of LATS1 modulate its kinase activity.However,detailed mechanism underlying LATS1 st...Large tumor suppressor 1(LATS1)is the key kinase controlling activation of Hippo signalling pathway.Post-translational modifications of LATS1 modulate its kinase activity.However,detailed mechanism underlying LATS1 stability and activation remains elusive.Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4.Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation.Mechanistically,LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation,leading to increased YAP nucleus translocation and promoted target gene expression.Functionally,LATS1-K751 Q,the acetylation mimic mutant potentiated lung cancer cell migration,invasion and tumor growth,whereas LATS1-K751 R,the acetylation deficient mutant inhibited these functions.Taken together,we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1.展开更多
The emergence of multidrug-resistant bacteria, or'superbugs,' has become an urgent and worldwide concern.Antibiotic-resistant bacteria (ARB) cause significant morbidity and mortality (O’Neill, 2016). It has b...The emergence of multidrug-resistant bacteria, or'superbugs,' has become an urgent and worldwide concern.Antibiotic-resistant bacteria (ARB) cause significant morbidity and mortality (O’Neill, 2016). It has been estimated that ARB cause at least 23,000 deaths annually in the United States alone and hundreds of thousands of deaths in developing countries (Bougnom and Piddock, 2017).展开更多
Colorectal cancer(CRC) progression is associated with cancer cell dedifferentiation and stemness acquisition. Several methods have been developed to identify stemness signatures in CRCs. However, studies that directly...Colorectal cancer(CRC) progression is associated with cancer cell dedifferentiation and stemness acquisition. Several methods have been developed to identify stemness signatures in CRCs. However, studies that directly measured the degree of dedifferentiation in CRC tissues are limited. It is unclear how the differentiation states change during CRC progression. To address this, we develop a method to analyze the tissue differentiation spectrum in colorectal cancer using normal gastrointestinal singlecell transcriptome data. Applying this method on 281 tumor samples from The Cancer Genome Atlas Colon Adenocarcinoma dataset, we identified three major CRC subtypes with distinct tissue differentiation pattern. We observed that differentiation states are closely correlated with anti-tumor immune response and patient outcomes in CRC. Highly dedifferentiated CRC samples escaped the immune surveillance and exhibited poor outcomes;mildly dedifferentiated CRC samples showed resistance to anti-tumor immune responses and had a worse survival rate;well-differentiated CRC samples showed sustained anti-tumor immune responses and had a good prognosis. Overall, the spectrum of tissue differentiation observed in CRCs can be used for future clinical risk stratification and subtype-based therapy selection.展开更多
基金grants from the National Key Research and Development Program of China to CL(grant No.2018 YFC1004002)National Natural Science Foundation of China(grant Nos.81730071,81472734 and 81321003 to HZ and 81402388 to CR)+3 种基金Natural Science Foundation of Beijing Municipality(grant No.7162102 to YW and 7171005 to HZ)Ministry of Science and Technology of China(grant No.2016 YFC 1302103 to HZ)Leading Academic Discipline Project of Beijing Education Bureau(grant No.BMU 20110254 to CR)the 111 Project of the Ministry of Education,Peking University(grant No.BMU 2018 JC004 to HZ and BMU 20150492 to CR).
文摘Objective:Lynch syndrome(LS)predisposes patients to early onset endometrioid endometrial cancer(EEC).However,little is known about LS-related EEC in the Chinese population.The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC.Methods:We applied universal immunohistochemistry screening to detect the expression of mismatch repair(MMR)proteins,which was followed by MLH1 methylation analysis to identify suspected LS cases,next-generation sequencing(NGS)to confirm LS,and microsatellite instability(MSI)analysis to verify LS.Results:We collected 211 samples with EEC.Twenty-seven(27/211,12.8%)EEC cases had a loss of MMR protein expression.After MLH1 methylation analysis,16 EEC cases were suggested to be associated with LS.Finally,through NGS and MSI analysis,we determined that 10 EEC(10/209,4.78%)cases were associated with LS.Among those cases,3 unreported mutations(1 frameshift and 2 nonsense)were identified.M SH6 c.597_597delC,found in 4 patients,is likely to be a founder mutation in China.Conclusions:We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC,by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis.The novel mutations identified in this study expand knowledge of LS.
基金grants from the National Natural Science Foundation of China(Grant No.81730071,81472734,and 81670626)Ministry of Science and Technology of China(Grant No.2016YFC1302103,and 2015CB553906)+1 种基金Beijing Natural Science Foundation grants(Grant No.7171005,7202084,and 7202080)Peking University grants(Grant No.BMU2018JC004 and BMU20120314)to H.Z.
文摘Four and a half LIM domains protein 1(FH L1),as the name suggests,contains four and a half LIM domains capable o f interacting with various molecules,including structural proteins,kinases,and transcriptional machinery.FHL1 contains a zinc-finger domain and performs diverse roles in regulation of gene transcription,cytoarchitecture,cell proliferation,and signal transduction.Several studies have validated the importance of FHL1 in muscle development,myopathy,and cardiovascular diseases.Mutations in the FHL1 gene are associated with various myopathies.Recently,FHL1 was identified as a major host factor for chikungunya virus(CHIKV)infection in both humans and mice.Based on more recent findings over the last decade,FHL1 is proposed to play a dual role in cancer progression.On the one hand,FHL1 expression is suppressed in several cancer types,which correlates with increased metastatic disease and decreased survival.Moreover,FHL1 is reported to inhibit tum or cell growth and migration by associating with diverse signals,such as TGF-P and ER,and therefore considered a tumor suppressor.On the other hand,FHL1 can function as an oncogenic protein that promotes tumor progression upon phosphorylation,reflecting complex roles in cancer.This review primarily focuses on the dual role and underlying mechanisms of action of FHL1 in human cancer progression and its clinical relevance.
基金the Science and Technology Promotion Project for Livelihood of the People of Yixing City in 2008,No.Yikeji[2008]56,Yicaiqi[2008]33,Yifagaifu[2008]100
文摘The neuroprotective effects of ginkgo biloba extract have been shown in rats following spinal cord injury （SCI）. However, the precise protective mechanisms remain unclear. In the present study, low-acid water-soluble extract of ginkgo biloba EGb761 was used to treat rats with SCI. Xanthin oxidase, thiobarbituric acid, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling assay, and immunohistochemistry were utilized to detect lipid peroxidation, neural cell apoptosis, and inducible nitric oxide synthase activity in rats with SCI. Results revealed significantly increased superoxide dismutase activity, decreased malondialdehyde content, apoptotic index, and inducible nitric oxide synthase expression in SCI rats following EGb761 treatment. Therefore, EGb761 suppressed lipid peroxidation following SCI, relieved neural cell apoptosis, inhibited inducible nitric oxide synthase expression, and ultimately exerted protective effects on SCI.
文摘A new membrane type Al_2O_3 micromachining material is used.We develop an environmental multi-parameter detection micro-system,which implements the detection to temperature,humidity,wind speed,and CO.The test results illustrate that the heat-release unit in micro-system intercross greatly affects other sensing units on the temperature.We study the method of etching process,which formed cavity to reduce the heat exchange efficiency and decrease temperature intercross effect.
文摘The sensitivity and selectivity of gas sensors are related with not only sensing material,but also their operating temperatures.Applying this property,temperature modulation technique has been proposed to improve the selectivity of gas sensors.With a newly developed alumina based micro gas sensor,the sensitivity to CO and CH_4 at different operating temperatures was investigated.By modulating the temperature of the sensor at pulse and sine wave modes with different frequencies and amplitudes,the dynamic responses of the sensor were measured and processed.Results show that the modulating waveshape plays an important role in the improvement of selectivity,while the influence of frequency is small at the suitable sampling frequency in the range of 25 mHz～200 mHz.
基金Sponsored by the National Natural Science Foundation of China(Grant No.61201306 and No.61473095)
文摘In order to improve the reliability of hydrogen sensor,a novel strategy for full range of hydrogen sensor fault detection and recovery is proposed in this paper. Three kinds of sensors are integrated to realize the measurement for full range of hydrogen concentration based on relevance vector machine( RVM). Failure detection of hydrogen sensor is carried out by using the variance detection method. When a sensor fault is detected,the other fault-free sensors can recover the fault data in real-time by using RVM predictor accounting for the relevance of sensor data. Analysis,together with both simulated and experimental results,a full-range hydrogen detection and hydrogen sensor self-validating experiment is presented to demonstrate that the proposed strategy is superior at accuracy and runtime compared with the conventional methods. Results show that the proposed methodology provides a better solution to the full range of hydrogen detection and the reliability improvement of hydrogen sensor.
文摘A new type of semiconductor gas sensor fabricated on an alumina substrate for CO and CH_4 detection has been developed.The alumina substrate was obtained by an anodizing method companying with micromachining to form patterned structure.Gas sensitive material was made of nano-sized SnO_2 powder prepared by a chemical precipitation method.Au (0.048wt.%) and Pd (0.3 wt%) were doped to SnO_2 powder to increase sensitivity to CO and CH_4,respectively.The heating power and sensing performance were measured with an automatic test system.The results show that the sensors have remarkable responses and certain selectivity to the target gases.Our study demonstrates that alumina substrate can be successfully applied in sensor micromachining technology.
基金This project was supported by National Science Foundation of the U.S. under fund cite NSF 03-512. And it is supported by National Science Foundation of China+1 种基金 under fund cite NSFC 60272002. National ‘863 Project＇ of China under fund cite A05106AA5114.
文摘The paper presents a new method for fabricating a gas-sensitive micro-sensor based on MEMS.The primary target agents are nitrogen dioxides (NO_2),and DIMP.Past-per-billion concentration levels of these two chemicals can be detected.An interdigitated gate electrode field-effect transistor (IGEFET) has been coupled with a chemically-active and electron-beam evaporated copper phthaiocyanine (CuPc) thin film to implement a gas-sensitive micro-sensor.The sensor is excited with voltage pulse.Time and frequency-domain response were measured.The magnitude of the normalized difference Fourier transform is distinct distinguished.
文摘Integrated gas sensor suspending bridge style micro-structure has been developed on Al_2O_3 new type membrane based on MEMS.CH_4 gas sensing unit and CO gas sensing unit were fabricated separately on 4 unit array style suspending bridge structure.We have studied on time-sequence modulation form voltage pulse heating method which forms different work temperature
基金supported by the National Key Research and Development Program of China(2022YFA1104003,2021YFC2501003)the National Natural Science Foundation of China(82230094,81972616,81730071)+1 种基金Peking University Medicine Sailing Program for Young Scholars'Scientific&Technological Innovation(BMU2024YFJHPY004)the Fundamental Research Funds for the Central Universities。
文摘METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase activity.METTL3 enhances RNA translation independently of its catalytic activity.However,the underlying mechanism is still elusive.Here,we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by SIRT3.Neither the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at K177.Importantly,acetylation of METTL3 blocks its interaction with EIF3H,a subunit of the translation initiation factor,thereby reducing mRNA translation efficiency.Interestingly,acetylation of METTL3 responds to oxidative stress.Mechanistically,oxidative stress enhances the interaction of PCAF with METTL3,increases METTL3 acetylation,and suppresses the interaction of METTL3 with EIF3H,thereby decreasing the translation efficiency of ribosomes and inhibiting cell proliferation.Altogether,we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.
基金supported by grants from the National Natural Science Foundation of China(Nos.82172972,81972609,81472734,31170711,81773199,81730071,81972616,81230051,and 81670626)the Beijing Natural Science Foundation(Nos.202084,7171005,7120002,and 7202080).
文摘FRMD6,a member of the 4.1 ezrin-radixin-moesin domain-containing protein family,has been reported to inhibit tumor progression in multiple cancers.Here,we demonstrate the involvement of FRMD6 in lung cancer progression.We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues.In addition,the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma(n=75,P=0.0054)and lung adenocarcinoma(n=94,P=0.0330).Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6.Mechanistically,FRMD6 interacts and colocalizes with mTOR and S6K,which are the key molecules of the mTOR signaling pathway.FRMD6 markedly enhances the interaction between mTOR and S6K,subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells.Furthermore,knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^(−/−)gene KO MEFs and mice.Altogether,our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.
基金supported by grants from the Ministry of Science and Technology of China (2016YFC1302103, 2015CB553906, and 2013CB910501)the National Natural Science Foundation of China (81730071, 81230051, 81472734, and 31170711)+3 种基金the Beijing Natural Science Foundation (7120002 and 7171005)the 111 Project of the Ministry of Education, grants from Peking University (BMU20120314 and BMU20130364)a Leading Academic Discipline Project of Beijing Education Bureau to H.Z.supported by a grant from the National Natural Science Foundation of China (81773199) to J.Z
文摘Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a Kindlin-2 transgenic mouse model using a mammary gland-specific promoter, mammary tumor virus(MMTV) long terminal repeat(LTR). Kindlin-2 was overexpressed in the epithelial cells of the transgenic mice. The mammary gland ductal trees were found to grow faster in MMTV-Kindlin-2 transgenic mice than in control mice during puberty. Kindlin-2 promoted mammary gland growth as indicated by more numerous duct branches and larger lumens, and more alveoli were formed in the mammary glands during pregnancy under Kindlin-2 overexpression. Importantly, mammary gland-specific expression of Kindlin-2 induced tumor formation at the age of 55 weeks on average. Additionally, the levels of estrogen receptor and progesterone receptor were decreased, whereas human epidermal growth factor receptor 2 and β-catenin were upregulated in the Kindlin-2-induced mammary tumors. These findings demonstrated that Kindlin-2 induces mammary tumor formation via activation of the Wnt signaling pathway.
基金supported by grants from Ministry of Science and Technology of the People's Republic of China(2016YFC1302103)National Natural Science Foundation of China(81621063,81730071,81972616,81670626)+2 种基金Natural Science Foundation of Beijing Municipality(7171005)Peking University Medical Sciences Grant(BMU 2018JC004)the Beijing Natural Science Foundation(7202080)。
文摘Slug,a member of the Snail family of transcriptional repressors,plays a key role in cancer progression,cellular plasticity,and epithelial to mesenchymal transition(EMT).Slug is a fast-turnover protein and its stability is controlled by post-translational modifications.Here,we identified that Slug is acetylated by acetyltransferase CREB-binding protein(CBP)in breast cancer cells.CBP directly interacts with the C-terminal domain of Slug through its catalytic histone acetyltransferase(HAT)domain,leading to acetylation of Slug at lysines 166 and 211.Analysis with acetylation-specific antibodies revealed that Slug is highly acetylated in metastatic breast cancer cells.Notably,Slug acetylation,mediated by CBP at lysines 166 and 211,doubles its halflife and increases its stability.Further,acetylated Slug downregulates the expression of E-cadherin,the epithelial marker,and upregulates the expression of N-cadherin and vimentin,thereby promoting breast cancer cell migration.In conclusion,the present study demonstrates that CBP-mediated Slug acetylation increases its stability,promoting EMT and migration of breast cancer cells.
基金grants from Ministry of Science and Technology of the People’s Republic of China 2021YFC2501000National Natural Science Foundation of China 82073076,81972616,81730071,81621063,81572839Natural Science Foundation of Beijing Municipality 7192092,7171005,PKU2021LCXQ015.
文摘PH20 is a member of the human hyaluronidase family that degrades hyaluronan in the extracellular matrix and controls tumor progression.Inhibition of DNA methyltransferases(DNMTs)leads to elevated hyaluronan levels;however,whether DNMT inhibitors control PH20 remains unclear.Here,we report that the DNMT1 inhibitor,decitabine,suppresses PH20 expression by activating the long non-coding RNA PHACTR2-AS1(PAS1).PAS1 forms a tripartite complex with the RNA-binding protein vigilin and histone methyltransferase SUV39H1.The interaction between PAS1 and vigilin maintains the stability of PAS1.Meanwhile,PAS1 recruits SUV39H1 to trigger the H3K9 methylation of PH20,resulting in its silencing.Functionally,PAS1 inhibits breast cancer growth and metastasis,at least partially,by suppressing PH20.Combination therapy of decitabine and PAS1-30nt-RNA,which directly binds to SUV39H1,effectively blocked breast cancer growth and metastasis in mice.Taken together,DNMT1,PAS1,and PH20 comprise a regulatory axis to control breast cancer growth and metastasis.These findings reveal that the DNMT1-PAS1-PH20 axis is a potential therapeutic target for breast cancer.
基金supported by the Ministry of Science and Technology of China (2016YFC1302103 and 2015CB553906)the National Natural Science Foundation of China (81230051, 81472734,31170711, 81321003, and 30830048)+3 种基金the Beijing Natural Science Foundation (7120002)the 111 Project of the Ministry of Education, Peking University (BMU2018JC004, BMU20120314, and BMU20130364)a Leading Academic Discipline Project of Beijing Education Bureau to H.Za grant from the National Natural Science Foundation of China (81773199) to J.Z
文摘Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-like breast cancer development remain largely unknown.Here,we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients.In human TCGA database,C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3,two transcription factors that regulate mammary gland stem cell fate.Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5;depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3.These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3.Taken together,we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.
基金This study was supported by grants from the Ministry of Science and Technology ofChina (Nos. 2016YFC1302103,2015CB553906, and 2013CB910501)the National Natural Science Foundation of China (Nos. 81230051, 81472734, 31170711, 81321003, and 30830048)+2 种基金the Beijing Natural Science Foundation (No. 7120002)the 111 Project of the Ministry of Education, Peking University (Nos. BMU20120314 and BMU20130364)and the Leading Academic Discipline Project of Beijing Education Bureau to Hongquan Zhang.
文摘LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains unclear. This study aimed to clarify whether the expression level of LGR6 is correlated with colon adenocarcinoma progression. Immunohistochemistry was used to detect LGR6 expression in colon adenoma tissues (n = 21), colon adenocarcinoma tissues (n = 156), and adjacent normal tissues (n = 124). The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues (P < 0.001). Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma (log-rank test, P = 0.016). Univariate and multivariate survival analyses showed that, in addition to N and M classification, LGR6 expression served as an independent prognostic factor. Thus, low expression of LGR6 can be used as an independent prognostic parameter in patients with colon adenocarcinoma.
基金supported by the National Natural Science Foundation of China(81730071,81972616,81230051,81472734,31170711 and 81773199)the Ministry of Science and Technology of China(2016YFC1302103 and 2015CB553906)+1 种基金Beijing Natural Science Foundation(7120002 and 7171005)Peking University(BMU2018JC004,BMU20120314 and BMU20130364)。
文摘Large tumor suppressor 1(LATS1)is the key kinase controlling activation of Hippo signalling pathway.Post-translational modifications of LATS1 modulate its kinase activity.However,detailed mechanism underlying LATS1 stability and activation remains elusive.Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4.Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation.Mechanistically,LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation,leading to increased YAP nucleus translocation and promoted target gene expression.Functionally,LATS1-K751 Q,the acetylation mimic mutant potentiated lung cancer cell migration,invasion and tumor growth,whereas LATS1-K751 R,the acetylation deficient mutant inhibited these functions.Taken together,we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1.
文摘The emergence of multidrug-resistant bacteria, or'superbugs,' has become an urgent and worldwide concern.Antibiotic-resistant bacteria (ARB) cause significant morbidity and mortality (O’Neill, 2016). It has been estimated that ARB cause at least 23,000 deaths annually in the United States alone and hundreds of thousands of deaths in developing countries (Bougnom and Piddock, 2017).
基金supported in part by the National Key R&D Program of China(2017YFC0910400)the National Natural Science Foundation of China(61721003)+1 种基金Tsinghua-Fuzhou Institute for Data Technology(TFIDT2018006)China Postdoctoral Science Foundation(2020M670297).
文摘Colorectal cancer(CRC) progression is associated with cancer cell dedifferentiation and stemness acquisition. Several methods have been developed to identify stemness signatures in CRCs. However, studies that directly measured the degree of dedifferentiation in CRC tissues are limited. It is unclear how the differentiation states change during CRC progression. To address this, we develop a method to analyze the tissue differentiation spectrum in colorectal cancer using normal gastrointestinal singlecell transcriptome data. Applying this method on 281 tumor samples from The Cancer Genome Atlas Colon Adenocarcinoma dataset, we identified three major CRC subtypes with distinct tissue differentiation pattern. We observed that differentiation states are closely correlated with anti-tumor immune response and patient outcomes in CRC. Highly dedifferentiated CRC samples escaped the immune surveillance and exhibited poor outcomes;mildly dedifferentiated CRC samples showed resistance to anti-tumor immune responses and had a worse survival rate;well-differentiated CRC samples showed sustained anti-tumor immune responses and had a good prognosis. Overall, the spectrum of tissue differentiation observed in CRCs can be used for future clinical risk stratification and subtype-based therapy selection.
