Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is...Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.展开更多
Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Alt...Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.展开更多
Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential ...Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.展开更多
Atmospheric models are physical equations based on the ideal gas law. Applied to the atmosphere, this law yields equations for water, vapor (gas), ice, air, humidity, dryness, fire, and heat, thus defining the model o...Atmospheric models are physical equations based on the ideal gas law. Applied to the atmosphere, this law yields equations for water, vapor (gas), ice, air, humidity, dryness, fire, and heat, thus defining the model of key atmospheric parameters. The distribution of these parameters across the entire planet Earth is the origin of the formation of the climatic cycle, which is a normal climatic variation. To do this, the Earth is divided into eight (8) parts according to the number of key parameters to be defined in a physical representation of the model. Following this distribution, numerical models calculate the constants for the formation of water, vapor, ice, dryness, thermal energy (fire), heat, air, and humidity. These models vary in complexity depending on the indirect trigonometric direction and simplicity in the sum of neighboring models. Note that the constants obtained from the equations yield 275.156˚K (2.006˚C) for water, 273.1596˚K (0.00963˚C) for vapor, 273.1633˚K (0.0133˚C) for ice, 0.00365 in/s for atmospheric dryness, 1.996 in<sup>2</sup>/s for humidity, 2.993 in<sup>2</sup>/s for air, 1 J for thermal energy of fire, and 0.9963 J for heat. In summary, this study aims to define the main parameters and natural phenomena contributing to the modification of planetary climate. .展开更多
Life Cycle Cost Analysis (LCCA) provides a systematic approach to assess the total cost associated with owning, operating, and maintaining assets throughout their entire life. BIM empowers architects and designers to ...Life Cycle Cost Analysis (LCCA) provides a systematic approach to assess the total cost associated with owning, operating, and maintaining assets throughout their entire life. BIM empowers architects and designers to perform real-time evaluations to explore various design options. However, when integrated with LCCA, BIM provides a comprehensive economic perspective that helps stakeholders understand the long-term financial implications of design decisions. This study presents a methodology for developing a model that seamlessly integrates BIM and LCCA during the conceptual design stage of buildings. This integration allows for a comprehensive evaluation and analysis of the design process, ensuring that the development aligns with the principles of low carbon emissions by employing modular construction, 3D concrete printing methods, and different building design alternatives. The model considers the initial construction costs in addition to all the long-term operational, maintenance, and salvage values. It combines various tools and data through different modules, including energy analysis, Life Cycle Assessment (LCA), and Life Cycle Cost Analysis (LCCA) to execute a comprehensive assessment of the financial implications of a specific design option throughout the lifecycle of building projects. The development of the said model and its implementation involves the creation of a new plug-in for the BIM tool (i.e., Autodesk Revit) to enhance its functionalities and capabilities in forecasting the life-cycle costs of buildings in addition to generating associated cash flows, creating scenarios, and sensitivity analyses in an automatic manner. This model empowers designers to evaluate and justify their initial investments while designing and selecting potential construction methods for buildings, and enabling stakeholders to make informed decisions by assessing different design alternatives based on long-term financial considerations during the early stages of design.展开更多
Gyllenberg and Yan(Discrete Contin Dyn Syst Ser B 11(2):347–352,2009)presented a system in Zeeman’s class 30 of 3-dimensional Lotka-Volterra(3D LV)competitive systems to admit at least two limit cycles,one of which ...Gyllenberg and Yan(Discrete Contin Dyn Syst Ser B 11(2):347–352,2009)presented a system in Zeeman’s class 30 of 3-dimensional Lotka-Volterra(3D LV)competitive systems to admit at least two limit cycles,one of which is generated by the Hopf bifurcation and the other is obtained by the Poincaré-Bendixson theorem.Yu et al.(J Math Anal Appl 436:521–555,2016,Sect.3.4)recalculated the first Liapunov coefficient of Gyllenberg and Yan’s system to be positive,rather than negative as in Gyllenberg and Yan(2009),and pointed out that the Poincaré-Bendixson theorem is not applicable for that system.Jiang et al.(J Differ Equ 284:183–218,2021,p.213)proposed an open question:“whether Zeeman’s class 30 can be rigorously proved to admit at least two limit cycles by the Hopf theorem and the Poincaré-Bendixson theorem?”This paper provides four systems in Zeeman’s class 30 to admit at least two limit cycles by the Hopf theorem and the Poincaré-Bendixson theorem and gives an answer to the above question.展开更多
Zymography and in situ hybridization were used to investigate matrixmetalloproteinase -2, -9 (MMP -2, MMP-9) activities and expressions of MMP -2, -9 and TIMP1, -2, -3 (tissue inhibitors of matrix metallo-proteinases)...Zymography and in situ hybridization were used to investigate matrixmetalloproteinase -2, -9 (MMP -2, MMP-9) activities and expressions of MMP -2, -9 and TIMP1, -2, -3 (tissue inhibitors of matrix metallo-proteinases) mRNA in the rat uterus during estrouscycle. The relative activity was semiquanted by using densitometric analysis. The MMP-2(67 kDa) activity in every stage during estrpus cycle was detected by zymography. MMP-2activity was highest at proestrus; higher at estrus and metaestrus; lowest at diestrus. Throughin situ hybridization, MMP -2, -9, TIMP -1~ -3 mRNA mainly in hasal stroma cells of uterineendometrium were detected. The positive signals of MMP -2 and -9 mRNAs in hasal stromacells were shown stronger at proestrus, estrus and metaestrus while they showed the weakest atdiestrus. The expression of MMP -2 mRNA coincided with MMP -2 activity change. MMP-2and -9 mRNAs were also highly expressed in uterine circular muscle at estrus. Weak signals ofMMP -9 mRNA were detected in uterine luminal and glandular epithelial cells at estrus.TIMP -1 mRNA in hasal stroma cells was shown as the strongest expression at estrus andmetaestrus; stronger at proestrus and the weakest at diestrus. TIMP-2 mRNA in basal stromacells was stronger at estrus and diestrus; weaker at proestrus and metaestrus. TIMP -1 and -2mRNAs were also highly expressed in uterine luminal and glandular epithelial cells at estrus.TIMP -3 mRNA in hasal stroma cells revealed the strongest expression at estrus; stronger atdiestrus and metaestrus and showed the weakest at proestrus. The mRNA was also highlyexpressed in uterine circular muscle at estrus. In short, our present results provide evidencethat MMP -2, -9 and TIMP -1~ -3 were involved in rat uterine endometrium reconstructionduring estrous cycle.展开更多
To feed an increasing population, large amounts of chemical nitrogen fertilizer have been used to produce much of our food, feed and fiber thereby increasing nitrogen levels in soils, natural waters, crop residues, li...To feed an increasing population, large amounts of chemical nitrogen fertilizer have been used to produce much of our food, feed and fiber thereby increasing nitrogen levels in soils, natural waters, crop residues, livestock wastes,and municipal and agricultural wastes, with national and international concern about its potential adverse effects on environmental quality and public health. To understand these phenomena and problems, first the nitrogen cycle and the environment are described. Then recent trends for nitrogen cycling through the food and feed system, N2O emissions from fertilized upland and paddy soils, and NO-3 pollution in ground water in Japan are reported. Finally, mitigation strategies in Japan for reducing N2O emission and NO-3 pollution are proposed, including nitrification inhibitors, controlled release fertilizers, utilization of plant species that could suppress nitrification, utilizing the toposequence, government policy, and appropriate agricultural practices. Of all the technologies presented, use of nitrification inhibitors and controlled release fertilizers are deemed the most important with further development of these aspects of technologies being expected. These practices, if employed worldwide, could help reduce the load, or environmental deterioration, on the Earth's biosphere.展开更多
ABSTRACT: This paper, with Milanggouwan stratigraphic section as a typical section of the Salawusu River Basin, explores the relation between CaCO3 content distribution and climate change since 150 ka B. P. and conclu...ABSTRACT: This paper, with Milanggouwan stratigraphic section as a typical section of the Salawusu River Basin, explores the relation between CaCO3 content distribution and climate change since 150 ka B. P. and concludes that: 1) The low-high changes of CaCO3 content in the section has a remarkable corresponding relation with the sedimentary cycles of ancient aeolian sand and overlying fluviolacustrine facies or palaeosols. 2) CaCO3 distribution in aeolian sand is relatively meagre, ranging from 0. 8% - 7. 18%, or on an average 2. 50% but relatively enriches in the fluviolacustrine faceis and palaeosols, ranging from 2. 20% - 14. 9% , or on an average 5. 74%. This implies that they have different climatic backgrounds. The former was the product of erosion, transport and deposition by wind under arid and cold climatic conditions, whereas the latter was related to its special low-lying geomorphic position between the Ordos Plateau and Loess Plateau and warm-humid climatic environment. When the climatic became warm and humid, fluviolacustrine and swamp facies developed, soil-forming action strengthened, and low-lying catchment condition was favorable to CaCO3 accumulation. 3) The basic cause responsible for the multicycle of CaCO3 migration and accumulation in the Milanggouwan section may be the multiple alterations of winter and summer monsoons over the Mu Us Desert under the influences of climatic fluctuation of glacial and interglacial periods in the Northern Hemisphere since 150ka B. P. .展开更多
Objective:As a member of the peptidyl arginine deiminase(PAD)family,PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues.However,the role of PADI3 in colon cancer is ...Objective:As a member of the peptidyl arginine deiminase(PAD)family,PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues.However,the role of PADI3 in colon cancer is unclear.In this study,we investigated the function and molecular mechanism of PADI3 in colon cancer tumorigenesis.Methods:Western blot and real-time PCR were used to detect the expression levels of several genes.CCK-8,flow cytometry(FCM)and colony formation assays were used to examine cell proliferation,the cell cycle and colony formation ability.RNAsequencing analysis was used to study the molecular mechanism of PADI3 in tumorigenesis.A truncation mutation experiment was performed to determine the key functional domain of PADI3.Results:PADI3 overexpression inhibited cell proliferation and colony formation and led to G1 phase arrest in both HCT116(originating from primary colon cancer)and LoVo(originating from metastatic tumor nodules of colon cancer)cells.PADI3-expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control cells.PADI3 significantly decreased Sirtuin2(Sirt2)and Snail expression and AKT phosphorylation and increased p21 expression,and Sirt2 overexpression partly reversed the effects induced by PADI3 overexpression.Immunocytochemistry showed that PADI3 is mainly localized in the cytoplasm.Truncation mutation experiments showed that the C-domain is the key domain involved in the antitumor activity of PADI3.Conclusions:PADI3 suppresses Snail expression and AKT phosphorylation and promotes p21 expression by downregulating Sirt2 expression in the cytoplasm,and the C-domain is the key domain for its antitumor activity.展开更多
DDX3X is a highly conserved DEAD-box RNA helicase that participates in RNA transcription, RNA splicing, and mRNA transport, translation, and nucleo-cytoplasmic transport. It is highly expressed in metaphase II （MII）...DDX3X is a highly conserved DEAD-box RNA helicase that participates in RNA transcription, RNA splicing, and mRNA transport, translation, and nucleo-cytoplasmic transport. It is highly expressed in metaphase II （MII） oocytes and is the predominant DDX3 variant in the ovary and embryo. However, whether it is important in mouse early embryo development remains unknown. In this study, we investigated the function of DDX3X in early embryogenesis by cytoplasmic microinjection with its siRNA in zygotes or single blastomeres of 2-cell embryos. Our results showed that knockdown of Ddx3x in zygote cytoplasm led to dramatically diminished blastocyst formarion, reduced cell numbers, and an increase in the number of apoptotic cells in blastocysts. Meanwhile, there was an accumulation of p53 in RNAi blastocysts. In addition, the ratio of cell cycle arrest during 2-cell to 4-cell transition increased following microinjection of Ddx3x siRNA into single blastomeres of 2-cell embryos compared with control. These results suggest that Ddx3x is an essential gene associated with cell survival and cell cycle control in mouse early embryos, and thus plays key roles in normal embryo development.展开更多
La_(4)NiLiO_(8)-coated NCM622 samples were prepared through a sol-gel method,and the electrochemical performance as cathode materials was investigated.It is revealed that part of the introduced La^(3+)ions produce a c...La_(4)NiLiO_(8)-coated NCM622 samples were prepared through a sol-gel method,and the electrochemical performance as cathode materials was investigated.It is revealed that part of the introduced La^(3+)ions produce a coating layer on the surface of NCM622 particles,while the rest occupy the 3b position of the lattice.The optimized sample exhibits a capacity retention of 96.54%after 100 cycles under 1C rate with a discharge specific capacity of 117.54 mAh·g^(-1)under 5C rate,much higher than those of the unmodified sample.The results show that the addition of La^(3+)ion can greatly improve the cyclic stability and the rate performance of NCM622.展开更多
The effect of hot-forging process was investigated on microstructural and mechanical properties of AZ31 B alloy and AZ31 B/1.5 vol.%Al2 O3 nanocomposite under static and cycling loading. The as-cast alloy and composit...The effect of hot-forging process was investigated on microstructural and mechanical properties of AZ31 B alloy and AZ31 B/1.5 vol.%Al2 O3 nanocomposite under static and cycling loading. The as-cast alloy and composite were firstly subjected to a homogenization heat treatment at 450 ℃ and then an open-die forging at 450 ℃. The results indicated that the presence of reinforcing particles led to grain refinement and improvement of dynamic recrystallization. The forging process was more effective to eliminate the porosity in the cast alloy workpiece. Microhardness of the forged composite was increased by up to 80% and 16%, in comparison with those of the cast and forged alloy samples, respectively. Ultimate tensile strength and maximum tensile strain of the composite were improved by up to 45% and 23%, compared with those of the forged alloy in similar regions. These enhancements were respectively 50% and 37% in the compression test. The composite exhibited a fatigue life improvement in the region with low applied strain;however, a degradation was observed in the high applied strain region. Unlike AZ31 B samples, tensile, compressive and high cycle fatigue behaviors of the composite showed less sensitivity to the applied strain, which can be attributed to the amount of porosity in the samples before and after the hot-forging.展开更多
The Grainyhead-like 3（GRHL3） is involved in epidermal barrier formation, neural tube closure and wound repair. Previous studies have suggested that GRHL3 has been linked to many different types of cancers. However, ...The Grainyhead-like 3（GRHL3） is involved in epidermal barrier formation, neural tube closure and wound repair. Previous studies have suggested that GRHL3 has been linked to many different types of cancers. However, to date, its effects on human colorectal cancer（CRC） has not been clarified yet. Our microarray analysis has indicated predominant GRHL3 expression in CRC. The purpose of this study was to investigate the expression and significance of GRHL3 in CRC tumorigenesis using CRC tissues and paired paracancerous tissues, as well as using distinct CRC cell lines（HT29 and DLD1）. We observed increased GRHL3 expression at both m RNA and protein levels in CRC tissues and CRC cell lines using quantitative real-time polymerase chain reaction（q RT-PCR） and Western blotting. Moreover, silencing GRHL3 with si RNA could suppress CRC cell proliferation, viability and migration in vitro. We also found that knockdown of GRHL3 could promote cell cycle arrest at G0/G1 phase in HT29 cells and DLD1 cells, and induce cell apoptosis in HT29 cells. Together, our study revealed the down-regulation of GRHL3 in vitro could inhibit CRC cell activity and trigger cell cycle arrest at G0/G1 phase and apoptosis.展开更多
HCC(Hepatocellular Carcinoma)is a critical health issue worldwide.Our previous animal experiment has confirmed that blueberry malvidin-3-galactoside(M3G)can regulate the progression of HCC.In this study,feces samples ...HCC(Hepatocellular Carcinoma)is a critical health issue worldwide.Our previous animal experiment has confirmed that blueberry malvidin-3-galactoside(M3G)can regulate the progression of HCC.In this study,feces samples from the same batch of mice were collected to explore the regulatory mechanism of M3G on intestinal microbiota and microbial TCA cycle metabolism KEGG pathway in HCC mice based on 16S rRNA sequencing and metagenomics.Our results showed that blueberry M3G increased the microbial diversity and regulated the structure of intestinal microbiota in mice,such as increasing the abundance of Clostridia(butyric acid-producing bacteria),Oscillospira and Ruminococcus,and reducing the abundance of pathogenic Erysipelotrichi.Compared with the group of liver cancer and 5-fluorouracil,blueberry M3G significantly regulated microbial TCA cycle KEGG pathway via improving the expression of key proteins(porA,DLAT,aceE,PC and OGDH).Additionally,we found which the abundance of Muribaculum intestinale increased by blueberry M3G may be an important factor affecting the microbial TCA cycle KEGG pathway via the pearson correlation(R)analysis of protein and microbiota.Taken together,these results demonstrate that the blueberry M3G has the potential to be an intestinal microbiota regulator and an adjuvant to HCC therapy.展开更多
Summary： The effects of RNAi-mediated gene silencing of LR1G3 expression on cell cycle and survival of human glioma cell line GL15 and the possible mechanisms were explored. The plasmids pGenesil2-LRIG3-shRNA1 and pG...Summary： The effects of RNAi-mediated gene silencing of LR1G3 expression on cell cycle and survival of human glioma cell line GL15 and the possible mechanisms were explored. The plasmids pGenesil2-LRIG3-shRNA1 and pGenesil2-LRIG3-shRNA2 were transfected into GLI 5 glioma cells respectively by using Metafectine, and the transfected cells that stably suppressed LR1G3 expression were selected by G418. The control cells were transfected with negative control shRNA. The changes in LRIG3 mRNA and protein levels were measured by RT-PCR and Western blot. The apoptosis rate and cell cycle were analyzed by flow cytometry. As compared with the negative shRNA-transfected GL 15 cells, LRIG3 mRNA expression in GLI 5 cells transfected with pGenesil2-LRIG3-shRNA 1 and pGenesil2-LRlG3-shRNA2 was silenced by 52.4%, 63.8%, and LRIG3 protein expression was reduced by 50.9% and 67.4% respectively. The LRIG3-specific siRNA transfected cells had higher proliferation rate than control cells. Cell cycle analysis showed that silencing LRIG3 increased the percentage of G2/M phase cells and the proliferation index significantly （P〈0.01）. Silencing LRIG3 could inhibit the apoptosis of GL15 cells （P〈0.05）. These findings suggest that the siRNA targeting LRIG3 gene shows a dramatic inhibitory effect on RNA transcription and protein expression, then promoting the proliferation of GL15 cells, arresting GL15 cells in G2/M phase, and suppressing apoptosis of GL15 cells.展开更多
基金supported by the Science and Technology Innovation Program of Hunan Province(Grant Numbers:2021SK1014 and 2022WZ1027)the Colleges and Universities of Hunan Province(Grant Number:HNJG 20200440)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department(Grant Number:21B0411)the Scientific Research Project of Changsha Central Hospital(Number:YNKY202201).
文摘Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.
基金supported by the National Natural Science Foundation of China(52173143 and 82371108)Natural Science Foundation of Henan Province(232300421176)Basic Science Key Project of Henan Eye Hospital(20JCZD002 and 23JCZD003).
文摘Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.
文摘Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.
文摘Atmospheric models are physical equations based on the ideal gas law. Applied to the atmosphere, this law yields equations for water, vapor (gas), ice, air, humidity, dryness, fire, and heat, thus defining the model of key atmospheric parameters. The distribution of these parameters across the entire planet Earth is the origin of the formation of the climatic cycle, which is a normal climatic variation. To do this, the Earth is divided into eight (8) parts according to the number of key parameters to be defined in a physical representation of the model. Following this distribution, numerical models calculate the constants for the formation of water, vapor, ice, dryness, thermal energy (fire), heat, air, and humidity. These models vary in complexity depending on the indirect trigonometric direction and simplicity in the sum of neighboring models. Note that the constants obtained from the equations yield 275.156˚K (2.006˚C) for water, 273.1596˚K (0.00963˚C) for vapor, 273.1633˚K (0.0133˚C) for ice, 0.00365 in/s for atmospheric dryness, 1.996 in<sup>2</sup>/s for humidity, 2.993 in<sup>2</sup>/s for air, 1 J for thermal energy of fire, and 0.9963 J for heat. In summary, this study aims to define the main parameters and natural phenomena contributing to the modification of planetary climate. .
文摘Life Cycle Cost Analysis (LCCA) provides a systematic approach to assess the total cost associated with owning, operating, and maintaining assets throughout their entire life. BIM empowers architects and designers to perform real-time evaluations to explore various design options. However, when integrated with LCCA, BIM provides a comprehensive economic perspective that helps stakeholders understand the long-term financial implications of design decisions. This study presents a methodology for developing a model that seamlessly integrates BIM and LCCA during the conceptual design stage of buildings. This integration allows for a comprehensive evaluation and analysis of the design process, ensuring that the development aligns with the principles of low carbon emissions by employing modular construction, 3D concrete printing methods, and different building design alternatives. The model considers the initial construction costs in addition to all the long-term operational, maintenance, and salvage values. It combines various tools and data through different modules, including energy analysis, Life Cycle Assessment (LCA), and Life Cycle Cost Analysis (LCCA) to execute a comprehensive assessment of the financial implications of a specific design option throughout the lifecycle of building projects. The development of the said model and its implementation involves the creation of a new plug-in for the BIM tool (i.e., Autodesk Revit) to enhance its functionalities and capabilities in forecasting the life-cycle costs of buildings in addition to generating associated cash flows, creating scenarios, and sensitivity analyses in an automatic manner. This model empowers designers to evaluate and justify their initial investments while designing and selecting potential construction methods for buildings, and enabling stakeholders to make informed decisions by assessing different design alternatives based on long-term financial considerations during the early stages of design.
基金the National Natural Science Foundation of China(NSFC)under Grant No.12171321.
文摘Gyllenberg and Yan(Discrete Contin Dyn Syst Ser B 11(2):347–352,2009)presented a system in Zeeman’s class 30 of 3-dimensional Lotka-Volterra(3D LV)competitive systems to admit at least two limit cycles,one of which is generated by the Hopf bifurcation and the other is obtained by the Poincaré-Bendixson theorem.Yu et al.(J Math Anal Appl 436:521–555,2016,Sect.3.4)recalculated the first Liapunov coefficient of Gyllenberg and Yan’s system to be positive,rather than negative as in Gyllenberg and Yan(2009),and pointed out that the Poincaré-Bendixson theorem is not applicable for that system.Jiang et al.(J Differ Equ 284:183–218,2021,p.213)proposed an open question:“whether Zeeman’s class 30 can be rigorously proved to admit at least two limit cycles by the Hopf theorem and the Poincaré-Bendixson theorem?”This paper provides four systems in Zeeman’s class 30 to admit at least two limit cycles by the Hopf theorem and the Poincaré-Bendixson theorem and gives an answer to the above question.
文摘Zymography and in situ hybridization were used to investigate matrixmetalloproteinase -2, -9 (MMP -2, MMP-9) activities and expressions of MMP -2, -9 and TIMP1, -2, -3 (tissue inhibitors of matrix metallo-proteinases) mRNA in the rat uterus during estrouscycle. The relative activity was semiquanted by using densitometric analysis. The MMP-2(67 kDa) activity in every stage during estrpus cycle was detected by zymography. MMP-2activity was highest at proestrus; higher at estrus and metaestrus; lowest at diestrus. Throughin situ hybridization, MMP -2, -9, TIMP -1~ -3 mRNA mainly in hasal stroma cells of uterineendometrium were detected. The positive signals of MMP -2 and -9 mRNAs in hasal stromacells were shown stronger at proestrus, estrus and metaestrus while they showed the weakest atdiestrus. The expression of MMP -2 mRNA coincided with MMP -2 activity change. MMP-2and -9 mRNAs were also highly expressed in uterine circular muscle at estrus. Weak signals ofMMP -9 mRNA were detected in uterine luminal and glandular epithelial cells at estrus.TIMP -1 mRNA in hasal stroma cells was shown as the strongest expression at estrus andmetaestrus; stronger at proestrus and the weakest at diestrus. TIMP-2 mRNA in basal stromacells was stronger at estrus and diestrus; weaker at proestrus and metaestrus. TIMP -1 and -2mRNAs were also highly expressed in uterine luminal and glandular epithelial cells at estrus.TIMP -3 mRNA in hasal stroma cells revealed the strongest expression at estrus; stronger atdiestrus and metaestrus and showed the weakest at proestrus. The mRNA was also highlyexpressed in uterine circular muscle at estrus. In short, our present results provide evidencethat MMP -2, -9 and TIMP -1~ -3 were involved in rat uterine endometrium reconstructionduring estrous cycle.
基金Project supported by the Canadian International Development Agency, Canada and the Chinese Academy of Scicences, China (No. KZCX2-413)
文摘To feed an increasing population, large amounts of chemical nitrogen fertilizer have been used to produce much of our food, feed and fiber thereby increasing nitrogen levels in soils, natural waters, crop residues, livestock wastes,and municipal and agricultural wastes, with national and international concern about its potential adverse effects on environmental quality and public health. To understand these phenomena and problems, first the nitrogen cycle and the environment are described. Then recent trends for nitrogen cycling through the food and feed system, N2O emissions from fertilized upland and paddy soils, and NO-3 pollution in ground water in Japan are reported. Finally, mitigation strategies in Japan for reducing N2O emission and NO-3 pollution are proposed, including nitrification inhibitors, controlled release fertilizers, utilization of plant species that could suppress nitrification, utilizing the toposequence, government policy, and appropriate agricultural practices. Of all the technologies presented, use of nitrification inhibitors and controlled release fertilizers are deemed the most important with further development of these aspects of technologies being expected. These practices, if employed worldwide, could help reduce the load, or environmental deterioration, on the Earth's biosphere.
基金Under the auspices of the National Natural Science Foundation of China(No.49971009) State Key Laboratory ofLoess and Quaternary Geology,Institute of Earth Environment,the Chinese Academy of sciences(SKLLQG0088)and National KeyProject for Basic Re
文摘ABSTRACT: This paper, with Milanggouwan stratigraphic section as a typical section of the Salawusu River Basin, explores the relation between CaCO3 content distribution and climate change since 150 ka B. P. and concludes that: 1) The low-high changes of CaCO3 content in the section has a remarkable corresponding relation with the sedimentary cycles of ancient aeolian sand and overlying fluviolacustrine facies or palaeosols. 2) CaCO3 distribution in aeolian sand is relatively meagre, ranging from 0. 8% - 7. 18%, or on an average 2. 50% but relatively enriches in the fluviolacustrine faceis and palaeosols, ranging from 2. 20% - 14. 9% , or on an average 5. 74%. This implies that they have different climatic backgrounds. The former was the product of erosion, transport and deposition by wind under arid and cold climatic conditions, whereas the latter was related to its special low-lying geomorphic position between the Ordos Plateau and Loess Plateau and warm-humid climatic environment. When the climatic became warm and humid, fluviolacustrine and swamp facies developed, soil-forming action strengthened, and low-lying catchment condition was favorable to CaCO3 accumulation. 3) The basic cause responsible for the multicycle of CaCO3 migration and accumulation in the Milanggouwan section may be the multiple alterations of winter and summer monsoons over the Mu Us Desert under the influences of climatic fluctuation of glacial and interglacial periods in the Northern Hemisphere since 150ka B. P. .
基金supported by the National Natural Science Foundation for the Youth of China (Grant No. 81802422 and 81702440)the Shandong Provincial Key R & D Program (Nos. 2019GSF108115, 2017GSF218102)+2 种基金Jinan Science and Technology Development Program (Nos. 201907116)Shandong Science and Technology Development Plan (Grant No. 2017GFS18195)Shandong Traditional Chinese Medicine Science and Technology Development Programs (Grant No. 2017-173)
文摘Objective:As a member of the peptidyl arginine deiminase(PAD)family,PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues.However,the role of PADI3 in colon cancer is unclear.In this study,we investigated the function and molecular mechanism of PADI3 in colon cancer tumorigenesis.Methods:Western blot and real-time PCR were used to detect the expression levels of several genes.CCK-8,flow cytometry(FCM)and colony formation assays were used to examine cell proliferation,the cell cycle and colony formation ability.RNAsequencing analysis was used to study the molecular mechanism of PADI3 in tumorigenesis.A truncation mutation experiment was performed to determine the key functional domain of PADI3.Results:PADI3 overexpression inhibited cell proliferation and colony formation and led to G1 phase arrest in both HCT116(originating from primary colon cancer)and LoVo(originating from metastatic tumor nodules of colon cancer)cells.PADI3-expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control cells.PADI3 significantly decreased Sirtuin2(Sirt2)and Snail expression and AKT phosphorylation and increased p21 expression,and Sirt2 overexpression partly reversed the effects induced by PADI3 overexpression.Immunocytochemistry showed that PADI3 is mainly localized in the cytoplasm.Truncation mutation experiments showed that the C-domain is the key domain involved in the antitumor activity of PADI3.Conclusions:PADI3 suppresses Snail expression and AKT phosphorylation and promotes p21 expression by downregulating Sirt2 expression in the cytoplasm,and the C-domain is the key domain for its antitumor activity.
文摘DDX3X is a highly conserved DEAD-box RNA helicase that participates in RNA transcription, RNA splicing, and mRNA transport, translation, and nucleo-cytoplasmic transport. It is highly expressed in metaphase II （MII） oocytes and is the predominant DDX3 variant in the ovary and embryo. However, whether it is important in mouse early embryo development remains unknown. In this study, we investigated the function of DDX3X in early embryogenesis by cytoplasmic microinjection with its siRNA in zygotes or single blastomeres of 2-cell embryos. Our results showed that knockdown of Ddx3x in zygote cytoplasm led to dramatically diminished blastocyst formarion, reduced cell numbers, and an increase in the number of apoptotic cells in blastocysts. Meanwhile, there was an accumulation of p53 in RNAi blastocysts. In addition, the ratio of cell cycle arrest during 2-cell to 4-cell transition increased following microinjection of Ddx3x siRNA into single blastomeres of 2-cell embryos compared with control. These results suggest that Ddx3x is an essential gene associated with cell survival and cell cycle control in mouse early embryos, and thus plays key roles in normal embryo development.
基金Funded by the Guangdong Key R&D Program(Nos.2020B 0909040001 and 2019B090909003)。
文摘La_(4)NiLiO_(8)-coated NCM622 samples were prepared through a sol-gel method,and the electrochemical performance as cathode materials was investigated.It is revealed that part of the introduced La^(3+)ions produce a coating layer on the surface of NCM622 particles,while the rest occupy the 3b position of the lattice.The optimized sample exhibits a capacity retention of 96.54%after 100 cycles under 1C rate with a discharge specific capacity of 117.54 mAh·g^(-1)under 5C rate,much higher than those of the unmodified sample.The results show that the addition of La^(3+)ion can greatly improve the cyclic stability and the rate performance of NCM622.
文摘The effect of hot-forging process was investigated on microstructural and mechanical properties of AZ31 B alloy and AZ31 B/1.5 vol.%Al2 O3 nanocomposite under static and cycling loading. The as-cast alloy and composite were firstly subjected to a homogenization heat treatment at 450 ℃ and then an open-die forging at 450 ℃. The results indicated that the presence of reinforcing particles led to grain refinement and improvement of dynamic recrystallization. The forging process was more effective to eliminate the porosity in the cast alloy workpiece. Microhardness of the forged composite was increased by up to 80% and 16%, in comparison with those of the cast and forged alloy samples, respectively. Ultimate tensile strength and maximum tensile strain of the composite were improved by up to 45% and 23%, compared with those of the forged alloy in similar regions. These enhancements were respectively 50% and 37% in the compression test. The composite exhibited a fatigue life improvement in the region with low applied strain;however, a degradation was observed in the high applied strain region. Unlike AZ31 B samples, tensile, compressive and high cycle fatigue behaviors of the composite showed less sensitivity to the applied strain, which can be attributed to the amount of porosity in the samples before and after the hot-forging.
基金supported by grants from National Natural Science Foundation of China(No.81072152)Natural Science Foundation of Hubei Province(No.2015CFA027)+1 种基金Research Foundation of Health and Family Planning Commission of Hubei Province(No.WJ2015MA010 and No.WJ2017M249)Clinical Medical Research Center of Peritoneal Cancer of Wuhan(No.2015060911020462)
文摘The Grainyhead-like 3（GRHL3） is involved in epidermal barrier formation, neural tube closure and wound repair. Previous studies have suggested that GRHL3 has been linked to many different types of cancers. However, to date, its effects on human colorectal cancer（CRC） has not been clarified yet. Our microarray analysis has indicated predominant GRHL3 expression in CRC. The purpose of this study was to investigate the expression and significance of GRHL3 in CRC tumorigenesis using CRC tissues and paired paracancerous tissues, as well as using distinct CRC cell lines（HT29 and DLD1）. We observed increased GRHL3 expression at both m RNA and protein levels in CRC tissues and CRC cell lines using quantitative real-time polymerase chain reaction（q RT-PCR） and Western blotting. Moreover, silencing GRHL3 with si RNA could suppress CRC cell proliferation, viability and migration in vitro. We also found that knockdown of GRHL3 could promote cell cycle arrest at G0/G1 phase in HT29 cells and DLD1 cells, and induce cell apoptosis in HT29 cells. Together, our study revealed the down-regulation of GRHL3 in vitro could inhibit CRC cell activity and trigger cell cycle arrest at G0/G1 phase and apoptosis.
基金supported by the National Natural Science Foundation of China(31972090)LiaoNing Revitalization Talents Program(XLYC1807127)+3 种基金Liaoning BaiQianWan Talents Program(2018-B-21)Tianzhu Mountain Scholar Support Project(2018)the Innovative Talent Support Program for Institution of Higher Learning of Liaoning Province(LR2017038)the project of“double hundred”for major scientific and technological achievements transformating of Shenyang Science and Technology Bureau(Z19-3-012).
文摘HCC(Hepatocellular Carcinoma)is a critical health issue worldwide.Our previous animal experiment has confirmed that blueberry malvidin-3-galactoside(M3G)can regulate the progression of HCC.In this study,feces samples from the same batch of mice were collected to explore the regulatory mechanism of M3G on intestinal microbiota and microbial TCA cycle metabolism KEGG pathway in HCC mice based on 16S rRNA sequencing and metagenomics.Our results showed that blueberry M3G increased the microbial diversity and regulated the structure of intestinal microbiota in mice,such as increasing the abundance of Clostridia(butyric acid-producing bacteria),Oscillospira and Ruminococcus,and reducing the abundance of pathogenic Erysipelotrichi.Compared with the group of liver cancer and 5-fluorouracil,blueberry M3G significantly regulated microbial TCA cycle KEGG pathway via improving the expression of key proteins(porA,DLAT,aceE,PC and OGDH).Additionally,we found which the abundance of Muribaculum intestinale increased by blueberry M3G may be an important factor affecting the microbial TCA cycle KEGG pathway via the pearson correlation(R)analysis of protein and microbiota.Taken together,these results demonstrate that the blueberry M3G has the potential to be an intestinal microbiota regulator and an adjuvant to HCC therapy.
基金supported by a grant from National Natu-ral Sciences Foundation of China (No. 3.500521 No. 30872653).
文摘Summary： The effects of RNAi-mediated gene silencing of LR1G3 expression on cell cycle and survival of human glioma cell line GL15 and the possible mechanisms were explored. The plasmids pGenesil2-LRIG3-shRNA1 and pGenesil2-LRIG3-shRNA2 were transfected into GLI 5 glioma cells respectively by using Metafectine, and the transfected cells that stably suppressed LR1G3 expression were selected by G418. The control cells were transfected with negative control shRNA. The changes in LRIG3 mRNA and protein levels were measured by RT-PCR and Western blot. The apoptosis rate and cell cycle were analyzed by flow cytometry. As compared with the negative shRNA-transfected GL 15 cells, LRIG3 mRNA expression in GLI 5 cells transfected with pGenesil2-LRIG3-shRNA 1 and pGenesil2-LRlG3-shRNA2 was silenced by 52.4%, 63.8%, and LRIG3 protein expression was reduced by 50.9% and 67.4% respectively. The LRIG3-specific siRNA transfected cells had higher proliferation rate than control cells. Cell cycle analysis showed that silencing LRIG3 increased the percentage of G2/M phase cells and the proliferation index significantly （P〈0.01）. Silencing LRIG3 could inhibit the apoptosis of GL15 cells （P〈0.05）. These findings suggest that the siRNA targeting LRIG3 gene shows a dramatic inhibitory effect on RNA transcription and protein expression, then promoting the proliferation of GL15 cells, arresting GL15 cells in G2/M phase, and suppressing apoptosis of GL15 cells.
