Molecular dynamics simulation was adopted to study the interaction between sulfosalicylic acid and aluminum,lanthanum and yttrium,and adsorption on kaolinite surfaces.A complexation reaction occurs between sulfosalicy...Molecular dynamics simulation was adopted to study the interaction between sulfosalicylic acid and aluminum,lanthanum and yttrium,and adsorption on kaolinite surfaces.A complexation reaction occurs between sulfosalicylic acid and aluminum,with an interaction energy of-10472.05 kJ/mol.O—Al covalent bonds are formed with a peak value of 7.93,while there is only weak adsorption between sulfosalicylic acid and rare earth ions.A hydrogen bonding reaction with 13605.82 kJ/mol energy occurs between sulfosalicylic acid and the surface of kaolinite(100).Thus,sulfosalicylic acid can form a complex with free aluminum ions,and can also be adsorbed on kaolinite by hydrogen bonding with aluminum in kaolinite(100)surfaces.Leaching of ion-adsorbed type rare earth ore was performed with aluminum inhibited,results show that when sulfosalicylic acid dosage increases from 0 to 0.15 wt%,aluminum ion concentration in the leaching solution decreases from 273.23 to 47.19 mg/L.And the effect of leaching pH value on the effect of sulfosalicylic acid on aluminum inhibition was studied,the result shows that,when the leaching pH value is 4.0—5.0,the rare earth leaching rate and the aluminum ion concentration basically remain unchanged.The molecular dynamics simulation results were verified by detection and analysis of XPS and SEM.展开更多
Liming is a common strategy applied to attain optimal pH for tea growth in severely acidic soils.Tea however is a calciphobous plant,and the effects of liming on its growth and nutrient uptake remain poorly understand...Liming is a common strategy applied to attain optimal pH for tea growth in severely acidic soils.Tea however is a calciphobous plant,and the effects of liming on its growth and nutrient uptake remain poorly understand.Therefore,it is necessary to better understand the effects of liming on soil chemical properties and tea nutrient content.In this study,a tea plantation that had exhibited large variation in growth after liming was selected as a study site.We categorized plots into two growth condition groups:Plot 1(poor growth)and Plot 2(excellent growth).Tea nutrient levels,and soil chemical properties were then compared between the two groups.Normalized difference vegetation index(NDVI)and transformed vegetation index(TVI)values were significantly higher and lower,respectively,in Plot 2 than in Plot 1.Yield,number of buds per m2,and 100-bud weight were significantly higher in Plot 2.These results were attributed to higher N,K,and Al concentrations and lower Ca concentrations in leaves,and lower pH and available Ca and higher available Al in soil.Leaf concentrations of K and Al were significantly negatively correlated with leaf concentrations of Ca and soil pH.A positive relationship was observed between leaf concentrations of K and Al,indicating inhibited K and Al uptake due to over-liming,restricting tea growth.In conclusion,our results show that tea growth will be restricted by over-liming,as a result of the high soil pH and Ca concentration inhibiting the K and Al uptake.展开更多
In this paper,a novel electrochemiluminescent (ECL) detection approach was developed for highly sensitive detection of ECL inhibitors based on the ECL inhibition of Ru(bpy)32+/2-(Dibutylamino)ethanol (DBAE) system. A ...In this paper,a novel electrochemiluminescent (ECL) detection approach was developed for highly sensitive detection of ECL inhibitors based on the ECL inhibition of Ru(bpy)32+/2-(Dibutylamino)ethanol (DBAE) system. A microfluidic ECL detection cell was fabricated to couple with the capillary electrophoresis system,the electrochemical system and the postcolumn injection system. Both Ru(bpy)32+ and DBAE solutions were injected directly to the working electrode surface by a micro-infusion system to obtain a high and stable ECL signal. The performance of this setup was demonstrated by the analysis of two typical ECL inhibitors,dopamine and epinephrine. Under the optimal conditions,the limit of detection (LOD) for dopamine and epinephrine was 50nM and 5nM respectively. The proposed method was also successfully used for the trace analysis of dopamine and epinephrine in human serum samples.展开更多
Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mai...Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.展开更多
Objective:Radiotherapy has achieved remarkable effects in treating non-small cell lung cancer(NSCLC).However,radioresistance remains the major obstacle to achieving good outcomes.This study aims at identifying potenti...Objective:Radiotherapy has achieved remarkable effects in treating non-small cell lung cancer(NSCLC).However,radioresistance remains the major obstacle to achieving good outcomes.This study aims at identifying potential targets for radiosensitizing NSCLC and elucidating the underlying mechanisms.Methods:Lentivirus-based infection and CRISPR/Cas9 technology were used to modulate the expression of microRNA-384(miR-384).Cell clonogenic formation assays and a xenograft tumor model were used to analyze radiosensitivity in NSCLC cells.Fluorescence-activated cell sorting was used to assess the cell cycle and cell death.Immunofluorescence staining,Comet assays,and homologous recombination or non-homologous end-joining I-SceI/GFP reporter assays were used to study DNA damage and repair.Western blotting and quantitative real-time polymerase chain reaction were used to identify the targets of miR-384.Chromatin immunoprecipitation and polymerase chain reaction were performed to evaluate upstream regulators of miR-384.Results:MiR-384 was downregulated in NSCLC.Overexpression of miR-384 increased the radiosensitivity of NSCLC cells in vitro and in vivo,whereas knockout of miR-384 led to radioresistance.Upregulation of miR-384 radiosensitized NSCLC cells by decreasing G2/M cell cycle arrest,inhibiting DNA damage repair,and consequently increasing cell death;miR-384 depletion had the opposite effects.Further investigation revealed that ATM,Ku70,and Ku80 were direct targets of miR-384.Moreover,miR-384 was repressed by NF-κB.Conclusions:MiR-384 is an ionizing radiation-responsive gene repressed by NF-κB.MiR-384 enhances the radiosensitivity of NSCLC cells via targeting ATM,Ku80,and Ku70,which impairs DNA damage repair.Therefore,miR-384 may serve as a novel radiosensitizer for NSCLC.展开更多
AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorpora...AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorporation. Malondialdehyde (MDA) level in the liver, in vitro response of hepatocyte nuclei nucleotide triphosphatase (NTPase) to free radicals, and nuclear export of total mRNA with 3'-poly A+ were measured respectively. Survival response of HepG2 cells to CCl4 treatment was assessed by methyl thiazolyl tetrazolium. Km and Vmax values of nuclear envelope NTPase activity in liver of rats treated with CCl4 were assayed by a double-reciprocal plot. RESULTS: The protein synthesis was inhibited while the MDA level was signif icantly increased in liver of rats treated with CCl4. In addition, CCl4 decreased the NTPase binding capacity of nuclear envelope (Km value) in cultured HepG2 cells. Moreover, in vitro ferrous radicals from Fenton's system suppressed the NTPase activity of liver nuclear envelope in a dose-dependent manner. Down-regulation of the nuclear envelope NTPase activity indicated a lower energy provision for nucleocytoplasmic transport of mRNA molecules, an evidence in CCl4-treated HepG2 cells correspondingly supported by the nuclear sequestration of poly (A)+ mRNA molecules in morphological hybridization research. CONCLUSION: Inhibition of mRNA transport, suggestive of decreased NTPase activity of the nuclear envelope, may be involved in carbon tetrachloride-inhibited protein synthesis in liver.展开更多
Dicranostigma Leptopodum (Maxim) Fedde (DL- F), which had been previously documented to suppress oxidative hemolysis of erythrocytes and enhance immune functions of murine peri- toneal macrophages, was investigated fo...Dicranostigma Leptopodum (Maxim) Fedde (DL- F), which had been previously documented to suppress oxidative hemolysis of erythrocytes and enhance immune functions of murine peri- toneal macrophages, was investigated for its effect on anti-tumor activity. Of alkaloids extracted from DLF, five have been identified with employment of chromatographic analysis. An antiproliferative role of these alkaloids was determined on SMMC-7721 Human Hepatoma Ce- lls in an apoptosis-inducing manner, through MTT assaying, Trypan blue exclusion assaying and cytometric analysis of cell cycle distribution. To further examine their inhibitory effects on tumor progression, murine H22 cells were inoculated into Kunming mice to determine the role of these alkaloids of DLF in inhibiting tumor growth in the tumor-implanted mice. It was found that these alkaloids of DLF enhanced the tumor shrinkage effectively wherein its tumor inhibitory rate and immunohistochemistry stain- ing of the tumor were determined and profiled, respectively.展开更多
The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory me...The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory mechanisms of HSP60 by mizoribine have not yet been fully understood. In the present study, we investigated the influence of mizoribine on a folding cycle of HSP60 and co-chaperone HSP10. Our results showed that mizoribine inhibited the folding cycle of HSP60/HSP10. The ATPase activity of HSP60/HSP10 was decreased in the presence of mizoribine and the dissociation of HSP10 from HSP-60 was also decreased by mizoribine. The same functions of GroEL and/or GroES were slightly affected by mizoribine. Based on our findings, we discuss the inhibitory mechanisms of HSP60 by mizoribine.展开更多
Spike number is one of three yield-related factors and is closely related to wheat yield. In the present study, we found that the inhibited and normal tillers of the 3558 line presented phenotypic differences at the e...Spike number is one of three yield-related factors and is closely related to wheat yield. In the present study, we found that the inhibited and normal tillers of the 3558 line presented phenotypic differences at the elongation stage by morphological and anatomical analysis. We then initiated a proteomic study using two-dimensional electrophoresis （2-DE） and nano- scale liquid chromatography-high-definition tandem mass spectroscopy, to isolate and identify the key proteins and metabolic pathways related to spike-development inhibition. A total of 31 differentially expressed proteins （DEPs）, which were mainly involved in cell cycle regulation, photosynthesis, glycolysis, stress response, and oxidation-reduction reactions, were isolated and identified. 14-3-3-1ike proteins and proliferating cell nuclear antigen （PCNA）, involved in cell-cycle regulation, were dramatically down-regulated in inhibited tillers compared to normal tillers. Six spots corresponding to degraded Rubisco large subunits, involved in photosynthesis, were detected in different locations of the 2-DE gels and were up-regulated in inhibited tillers. In addition, the relative levels of DEPs involved in glycolysis and oxidation- reduction reactions changed dramatically. Development was blocked or delayed at the elongation stage in the inhibited tillers of 3558. Weakened energy metabolism might be one reason that the inhibited tillers could not joint and develop into spikes. These DEPs and related metabolic pathways are significant for understanding the mechanism of spike-development inhibition and studying the spike-development process in wheat.展开更多
The thermokinetic reduced extent equations of reversible inhibitions for Michaiels-Menten enzymatic reaction were deduced, and then the criteria for distingushing inhibition type was given and the methods for calculat...The thermokinetic reduced extent equations of reversible inhibitions for Michaiels-Menten enzymatic reaction were deduced, and then the criteria for distingushing inhibition type was given and the methods for calculating kinetic parameters, KM,Ki and Urn were suggested. This theory was applied to inverstigate the inhibited thermokinetics of laccase-catalyzed oxidation of o-dihydroxybenzene by m-dihydroxybenzene. The experimental results show the inhibition belongs to reversible competitive type, KM=6.224×10-3 mol L-1, Ki=2. 363 × 10-2 mol. L-1.展开更多
This study presents an innovative urea detection method utilizing pH-controlled Fenton etching of gold nanobipyramids(AuNBPs),offering a multicolor visual response.By leveraging the urease-catalyzed hydrolysis of urea...This study presents an innovative urea detection method utilizing pH-controlled Fenton etching of gold nanobipyramids(AuNBPs),offering a multicolor visual response.By leveraging the urease-catalyzed hydrolysis of urea,which releases ammonia and raises pH,the Fenton reaction is inhibited,reducing the etching of AuNBPs.This approach enables a highly sensitive and distinct multichromatic response across a wide range of urea concentrations,particularly at low target levels.The solution-based sensor achieved an exceptionally low detection limit of 0.098μM,surpassing existing colorimetric urea biosensors.Furthermore,embedding the sensor in an agarose hydrogel matrix to create a solid-state format resulted in a detection limit of 0.2μM.Real-world validation demonstrated high recovery rates in urine samples,further affirming the sensor’s reliability.This multicolor biosensing platform offers a robust tool for point-of-care diagnostics,facilitating accurate and user-friendly urea detection.展开更多
Cell division is precisely regulated and highly tissue-specific;studies have suggested that diverse signals in the epidermis,especially the epidermal brassinosteroids(BRs),can regulate root growth.However,the underlyi...Cell division is precisely regulated and highly tissue-specific;studies have suggested that diverse signals in the epidermis,especially the epidermal brassinosteroids(BRs),can regulate root growth.However,the underlying molecular mechanisms that integrate hormonal cues such as BR signaling with other endogenous,tissue-specific developmental programs to regulate epidermal cell proliferation remain unclear.In this study,we used molecular and biochemical approaches,microscopic imaging and genetic analysis to investigate the function and mechanisms of a P-type cyclin in root growth regulation.We found that CYCP3;1,specifically expressed in the root meristem epidermis and lateral root cap,can regulate meristem cell division.Mitotic analyses and biochemical studies demonstrated that CYCP3;1 promotes cell division at the G2-M duration by associating and activating cyclin-dependent kinase B2-1(CDKB2;i).Furthermore,we found that CYCP^;1 expression was inhibited by BR signaling through BRI1-EMS-SUPPRESSOR1(BES1),a positive downstream transcription factor in the BR signaling pathway.These findings not only provide a mechanism of how root epidermal-specific regulators modulate root growth,but also reveal why the excess of BRs or enhanced BR signaling inhibits cell division in the meristem to negatively regulate root growth.展开更多
Heterogeneous nuclear ribonucleoprotein K(hnRNPK)is a predominantly nuclear RNA-binding protein that can bind to DNA or RNA through three KH domains and interact with multiple proteins by interactive region.These bind...Heterogeneous nuclear ribonucleoprotein K(hnRNPK)is a predominantly nuclear RNA-binding protein that can bind to DNA or RNA through three KH domains and interact with multiple proteins by interactive region.These binding activities enable hnRNPK to link the function in a wide array of diverse cellular processes,such as chromatin remodeling,gene transcription,RNA metabolism,protein translation,DNA repair,and cell signal transduction,thereby playing crucial roles in many biological processes,including development,axonal regeneration,spermatogenesis,cell cycle,apoptosis,differentiation,and carcinogenesis.展开更多
Oxidized low density lipoprotein (LDL) has been shown to inhibit the activity of platelet plasma mambrane Ca^2+ ATPase, and induce changes of factin in endothelial cells. Since the deformability of human erythrocyt...Oxidized low density lipoprotein (LDL) has been shown to inhibit the activity of platelet plasma mambrane Ca^2+ ATPase, and induce changes of factin in endothelial cells. Since the deformability of human erythrocytes are closely related to the calcium metabolism and the stability of cytoskeleton, the influence of oxidized LDL on plasma membrane Ca^2+ ATPase and plasma membrane fluidity were studied in human erythrocytes. Our in vitro experiments demonstrated that oxidized LDL, but not native LDL, inhibits the activity of Platelet Research Unit, Institute of Anatomy, University of Münster, Germany (Zhao B, Filler TJ and Dierichs R) Shanghai Fourth People's Hospital, Shanghai, China (Yu H) Department of Biochemistry, University of Louisville, Kentucky, USA (Dean W)Ca^2+ ATPase in purified erythrocyte plasma membrane (P<0.01). Since no change in the membrane fluidity was detected in the erythrocyte plasma membrane exposed to native LDL and oxidized LDL as estimated by steady state by trimthylammonium diphenylhexatriene (TMA DPH) anisotropy, oxidized LDL did not affect the Ca^2+ ATPase by grossly changing the erythrocyte deformability probably by interfering the cytosolic calcium and then altering the cytoskeleton. The deformability of erythrocytes is important in microcirculation. A better understanding of the interactions between oxidized LDL, erythrocytes, platelets and endothelial cells can prevent cardiovascular diseases.展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Rese...In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Research(Ding et al.,2025),the title was incorrectly presented due to an error during the language polishing process.展开更多
The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble dif...The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.展开更多
Objective To investigate the underlying molecular mechanisms of metformin in inhibiting hepatic gluconeogenesis.Methods Primary hepatocytes of mice were isolated by a modified version of the collagenase method.The eff...Objective To investigate the underlying molecular mechanisms of metformin in inhibiting hepatic gluconeogenesis.Methods Primary hepatocytes of mice were isolated by a modified version of the collagenase method.The effect of metformin on glucose production in primary hepatocytes was detected by glucose oxidation method.展开更多
Objective To observe the effect of Bushen Huoxue Recipe(BHR)on inhibiting vascular calcification(VC)in chronic renal failure(CRF)rats by regulating BMP-2/Runx2/Osterix signal pathway,and to explore its possible mechan...Objective To observe the effect of Bushen Huoxue Recipe(BHR)on inhibiting vascular calcification(VC)in chronic renal failure(CRF)rats by regulating BMP-2/Runx2/Osterix signal pathway,and to explore its possible mechanism.Methods Thirty SD rats were randomly divided into the normal group,the model group,and the BHR group,10 in each group.Rats in the model group and the BHR group were administered with 250展开更多
基金Project supported by the National Natural Science Foundation of China,(51674125,51604128)Outstanding Doctoral Dissertation Project Fund of JXUST(YB2016001)
文摘Molecular dynamics simulation was adopted to study the interaction between sulfosalicylic acid and aluminum,lanthanum and yttrium,and adsorption on kaolinite surfaces.A complexation reaction occurs between sulfosalicylic acid and aluminum,with an interaction energy of-10472.05 kJ/mol.O—Al covalent bonds are formed with a peak value of 7.93,while there is only weak adsorption between sulfosalicylic acid and rare earth ions.A hydrogen bonding reaction with 13605.82 kJ/mol energy occurs between sulfosalicylic acid and the surface of kaolinite(100).Thus,sulfosalicylic acid can form a complex with free aluminum ions,and can also be adsorbed on kaolinite by hydrogen bonding with aluminum in kaolinite(100)surfaces.Leaching of ion-adsorbed type rare earth ore was performed with aluminum inhibited,results show that when sulfosalicylic acid dosage increases from 0 to 0.15 wt%,aluminum ion concentration in the leaching solution decreases from 273.23 to 47.19 mg/L.And the effect of leaching pH value on the effect of sulfosalicylic acid on aluminum inhibition was studied,the result shows that,when the leaching pH value is 4.0—5.0,the rare earth leaching rate and the aluminum ion concentration basically remain unchanged.The molecular dynamics simulation results were verified by detection and analysis of XPS and SEM.
基金the National Key R and D Program of China(2020YFD1000701)the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2014-TRICAAS)the Funds for Science and Technology Innovation Project from the Chinese Academy of Agricultural Sciences(CAASXTCX2016015).
文摘Liming is a common strategy applied to attain optimal pH for tea growth in severely acidic soils.Tea however is a calciphobous plant,and the effects of liming on its growth and nutrient uptake remain poorly understand.Therefore,it is necessary to better understand the effects of liming on soil chemical properties and tea nutrient content.In this study,a tea plantation that had exhibited large variation in growth after liming was selected as a study site.We categorized plots into two growth condition groups:Plot 1(poor growth)and Plot 2(excellent growth).Tea nutrient levels,and soil chemical properties were then compared between the two groups.Normalized difference vegetation index(NDVI)and transformed vegetation index(TVI)values were significantly higher and lower,respectively,in Plot 2 than in Plot 1.Yield,number of buds per m2,and 100-bud weight were significantly higher in Plot 2.These results were attributed to higher N,K,and Al concentrations and lower Ca concentrations in leaves,and lower pH and available Ca and higher available Al in soil.Leaf concentrations of K and Al were significantly negatively correlated with leaf concentrations of Ca and soil pH.A positive relationship was observed between leaf concentrations of K and Al,indicating inhibited K and Al uptake due to over-liming,restricting tea growth.In conclusion,our results show that tea growth will be restricted by over-liming,as a result of the high soil pH and Ca concentration inhibiting the K and Al uptake.
基金supported by the National Natural Science Foundation of China (NSFC) (20735002,20877019)the Key Natural SciencesFoundation of Fujian Province,China (D0520001)the Key Program of Science and Technology Department of Fujian Province,China(2007Y0026)
文摘In this paper,a novel electrochemiluminescent (ECL) detection approach was developed for highly sensitive detection of ECL inhibitors based on the ECL inhibition of Ru(bpy)32+/2-(Dibutylamino)ethanol (DBAE) system. A microfluidic ECL detection cell was fabricated to couple with the capillary electrophoresis system,the electrochemical system and the postcolumn injection system. Both Ru(bpy)32+ and DBAE solutions were injected directly to the working electrode surface by a micro-infusion system to obtain a high and stable ECL signal. The performance of this setup was demonstrated by the analysis of two typical ECL inhibitors,dopamine and epinephrine. Under the optimal conditions,the limit of detection (LOD) for dopamine and epinephrine was 50nM and 5nM respectively. The proposed method was also successfully used for the trace analysis of dopamine and epinephrine in human serum samples.
基金supported by grants from the NIH(P01DK113954,R01DK115761,R01DK117281,R01DK125480 and R01DK120858 to YXR01DK129548 to YH)+1 种基金USDA/CRIS(51000-064-01S to YX)Postdoctoral Fellowship(2020AHA000POST000204188)to LT。
文摘Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.
基金supported by the National Natural Science Foundation of China(Grant Nos.82170758,82373085,81974364,and 82172674)the Natural Science Foundation of Tianjin Municipal Science and Technology Commission(Grant No.16JCQNJC10000)+2 种基金the Foundation of Tianjin Medical University Cancer Institute and Hospital(Grant No.B2211)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2023KJ095)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A)。
文摘Objective:Radiotherapy has achieved remarkable effects in treating non-small cell lung cancer(NSCLC).However,radioresistance remains the major obstacle to achieving good outcomes.This study aims at identifying potential targets for radiosensitizing NSCLC and elucidating the underlying mechanisms.Methods:Lentivirus-based infection and CRISPR/Cas9 technology were used to modulate the expression of microRNA-384(miR-384).Cell clonogenic formation assays and a xenograft tumor model were used to analyze radiosensitivity in NSCLC cells.Fluorescence-activated cell sorting was used to assess the cell cycle and cell death.Immunofluorescence staining,Comet assays,and homologous recombination or non-homologous end-joining I-SceI/GFP reporter assays were used to study DNA damage and repair.Western blotting and quantitative real-time polymerase chain reaction were used to identify the targets of miR-384.Chromatin immunoprecipitation and polymerase chain reaction were performed to evaluate upstream regulators of miR-384.Results:MiR-384 was downregulated in NSCLC.Overexpression of miR-384 increased the radiosensitivity of NSCLC cells in vitro and in vivo,whereas knockout of miR-384 led to radioresistance.Upregulation of miR-384 radiosensitized NSCLC cells by decreasing G2/M cell cycle arrest,inhibiting DNA damage repair,and consequently increasing cell death;miR-384 depletion had the opposite effects.Further investigation revealed that ATM,Ku70,and Ku80 were direct targets of miR-384.Moreover,miR-384 was repressed by NF-κB.Conclusions:MiR-384 is an ionizing radiation-responsive gene repressed by NF-κB.MiR-384 enhances the radiosensitivity of NSCLC cells via targeting ATM,Ku80,and Ku70,which impairs DNA damage repair.Therefore,miR-384 may serve as a novel radiosensitizer for NSCLC.
基金Supported by The National Natural Science Foundation of China,No.30470846
文摘AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorporation. Malondialdehyde (MDA) level in the liver, in vitro response of hepatocyte nuclei nucleotide triphosphatase (NTPase) to free radicals, and nuclear export of total mRNA with 3'-poly A+ were measured respectively. Survival response of HepG2 cells to CCl4 treatment was assessed by methyl thiazolyl tetrazolium. Km and Vmax values of nuclear envelope NTPase activity in liver of rats treated with CCl4 were assayed by a double-reciprocal plot. RESULTS: The protein synthesis was inhibited while the MDA level was signif icantly increased in liver of rats treated with CCl4. In addition, CCl4 decreased the NTPase binding capacity of nuclear envelope (Km value) in cultured HepG2 cells. Moreover, in vitro ferrous radicals from Fenton's system suppressed the NTPase activity of liver nuclear envelope in a dose-dependent manner. Down-regulation of the nuclear envelope NTPase activity indicated a lower energy provision for nucleocytoplasmic transport of mRNA molecules, an evidence in CCl4-treated HepG2 cells correspondingly supported by the nuclear sequestration of poly (A)+ mRNA molecules in morphological hybridization research. CONCLUSION: Inhibition of mRNA transport, suggestive of decreased NTPase activity of the nuclear envelope, may be involved in carbon tetrachloride-inhibited protein synthesis in liver.
文摘Dicranostigma Leptopodum (Maxim) Fedde (DL- F), which had been previously documented to suppress oxidative hemolysis of erythrocytes and enhance immune functions of murine peri- toneal macrophages, was investigated for its effect on anti-tumor activity. Of alkaloids extracted from DLF, five have been identified with employment of chromatographic analysis. An antiproliferative role of these alkaloids was determined on SMMC-7721 Human Hepatoma Ce- lls in an apoptosis-inducing manner, through MTT assaying, Trypan blue exclusion assaying and cytometric analysis of cell cycle distribution. To further examine their inhibitory effects on tumor progression, murine H22 cells were inoculated into Kunming mice to determine the role of these alkaloids of DLF in inhibiting tumor growth in the tumor-implanted mice. It was found that these alkaloids of DLF enhanced the tumor shrinkage effectively wherein its tumor inhibitory rate and immunohistochemistry stain- ing of the tumor were determined and profiled, respectively.
文摘The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory mechanisms of HSP60 by mizoribine have not yet been fully understood. In the present study, we investigated the influence of mizoribine on a folding cycle of HSP60 and co-chaperone HSP10. Our results showed that mizoribine inhibited the folding cycle of HSP60/HSP10. The ATPase activity of HSP60/HSP10 was decreased in the presence of mizoribine and the dissociation of HSP10 from HSP-60 was also decreased by mizoribine. The same functions of GroEL and/or GroES were slightly affected by mizoribine. Based on our findings, we discuss the inhibitory mechanisms of HSP60 by mizoribine.
基金supported by the National High Technology Research and Development Program of China (2011AA100102 and 2006AA10Z174)
文摘Spike number is one of three yield-related factors and is closely related to wheat yield. In the present study, we found that the inhibited and normal tillers of the 3558 line presented phenotypic differences at the elongation stage by morphological and anatomical analysis. We then initiated a proteomic study using two-dimensional electrophoresis （2-DE） and nano- scale liquid chromatography-high-definition tandem mass spectroscopy, to isolate and identify the key proteins and metabolic pathways related to spike-development inhibition. A total of 31 differentially expressed proteins （DEPs）, which were mainly involved in cell cycle regulation, photosynthesis, glycolysis, stress response, and oxidation-reduction reactions, were isolated and identified. 14-3-3-1ike proteins and proliferating cell nuclear antigen （PCNA）, involved in cell-cycle regulation, were dramatically down-regulated in inhibited tillers compared to normal tillers. Six spots corresponding to degraded Rubisco large subunits, involved in photosynthesis, were detected in different locations of the 2-DE gels and were up-regulated in inhibited tillers. In addition, the relative levels of DEPs involved in glycolysis and oxidation- reduction reactions changed dramatically. Development was blocked or delayed at the elongation stage in the inhibited tillers of 3558. Weakened energy metabolism might be one reason that the inhibited tillers could not joint and develop into spikes. These DEPs and related metabolic pathways are significant for understanding the mechanism of spike-development inhibition and studying the spike-development process in wheat.
文摘The thermokinetic reduced extent equations of reversible inhibitions for Michaiels-Menten enzymatic reaction were deduced, and then the criteria for distingushing inhibition type was given and the methods for calculating kinetic parameters, KM,Ki and Urn were suggested. This theory was applied to inverstigate the inhibited thermokinetics of laccase-catalyzed oxidation of o-dihydroxybenzene by m-dihydroxybenzene. The experimental results show the inhibition belongs to reversible competitive type, KM=6.224×10-3 mol L-1, Ki=2. 363 × 10-2 mol. L-1.
基金supported by the Institute for Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korea government(MSIT)(RS-2023-00228994),RS-2024-00346003the National Research Foundation of Korea(2020R1A5A1018052)and(RS-2024-00410209).
文摘This study presents an innovative urea detection method utilizing pH-controlled Fenton etching of gold nanobipyramids(AuNBPs),offering a multicolor visual response.By leveraging the urease-catalyzed hydrolysis of urea,which releases ammonia and raises pH,the Fenton reaction is inhibited,reducing the etching of AuNBPs.This approach enables a highly sensitive and distinct multichromatic response across a wide range of urea concentrations,particularly at low target levels.The solution-based sensor achieved an exceptionally low detection limit of 0.098μM,surpassing existing colorimetric urea biosensors.Furthermore,embedding the sensor in an agarose hydrogel matrix to create a solid-state format resulted in a detection limit of 0.2μM.Real-world validation demonstrated high recovery rates in urine samples,further affirming the sensor’s reliability.This multicolor biosensing platform offers a robust tool for point-of-care diagnostics,facilitating accurate and user-friendly urea detection.
基金We thank Peter Doerner for providing the marker line pCYCBi,1:GUS,Cangjin Yang for helping with design the experiments of genetic analysis,Shenglong Qiao and Meijing Wang for helping with transient expression assays in protoplasts,and H.Saiyin for assistance on preparing root sections.This work was supported by grants(31430046 and 31661143024 to X.W.)of the National Natural Science Foundation of China.
文摘Cell division is precisely regulated and highly tissue-specific;studies have suggested that diverse signals in the epidermis,especially the epidermal brassinosteroids(BRs),can regulate root growth.However,the underlying molecular mechanisms that integrate hormonal cues such as BR signaling with other endogenous,tissue-specific developmental programs to regulate epidermal cell proliferation remain unclear.In this study,we used molecular and biochemical approaches,microscopic imaging and genetic analysis to investigate the function and mechanisms of a P-type cyclin in root growth regulation.We found that CYCP3;1,specifically expressed in the root meristem epidermis and lateral root cap,can regulate meristem cell division.Mitotic analyses and biochemical studies demonstrated that CYCP3;1 promotes cell division at the G2-M duration by associating and activating cyclin-dependent kinase B2-1(CDKB2;i).Furthermore,we found that CYCP^;1 expression was inhibited by BR signaling through BRI1-EMS-SUPPRESSOR1(BES1),a positive downstream transcription factor in the BR signaling pathway.These findings not only provide a mechanism of how root epidermal-specific regulators modulate root growth,but also reveal why the excess of BRs or enhanced BR signaling inhibits cell division in the meristem to negatively regulate root growth.
基金supported by the National Natural Science Foundation of China(No.31972537,32202654)the Department of Science and Technology in Henan Province,China(No.222102110013)+1 种基金the Natural Science Foundation of Henan Province,China(No.222300420272,212300410230)the Nanhu Scholars Program of Xinyang Normal University(Henan,China).
文摘Heterogeneous nuclear ribonucleoprotein K(hnRNPK)is a predominantly nuclear RNA-binding protein that can bind to DNA or RNA through three KH domains and interact with multiple proteins by interactive region.These binding activities enable hnRNPK to link the function in a wide array of diverse cellular processes,such as chromatin remodeling,gene transcription,RNA metabolism,protein translation,DNA repair,and cell signal transduction,thereby playing crucial roles in many biological processes,including development,axonal regeneration,spermatogenesis,cell cycle,apoptosis,differentiation,and carcinogenesis.
文摘Oxidized low density lipoprotein (LDL) has been shown to inhibit the activity of platelet plasma mambrane Ca^2+ ATPase, and induce changes of factin in endothelial cells. Since the deformability of human erythrocytes are closely related to the calcium metabolism and the stability of cytoskeleton, the influence of oxidized LDL on plasma membrane Ca^2+ ATPase and plasma membrane fluidity were studied in human erythrocytes. Our in vitro experiments demonstrated that oxidized LDL, but not native LDL, inhibits the activity of Platelet Research Unit, Institute of Anatomy, University of Münster, Germany (Zhao B, Filler TJ and Dierichs R) Shanghai Fourth People's Hospital, Shanghai, China (Yu H) Department of Biochemistry, University of Louisville, Kentucky, USA (Dean W)Ca^2+ ATPase in purified erythrocyte plasma membrane (P<0.01). Since no change in the membrane fluidity was detected in the erythrocyte plasma membrane exposed to native LDL and oxidized LDL as estimated by steady state by trimthylammonium diphenylhexatriene (TMA DPH) anisotropy, oxidized LDL did not affect the Ca^2+ ATPase by grossly changing the erythrocyte deformability probably by interfering the cytosolic calcium and then altering the cytoskeleton. The deformability of erythrocytes is important in microcirculation. A better understanding of the interactions between oxidized LDL, erythrocytes, platelets and endothelial cells can prevent cardiovascular diseases.
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
文摘In the article titled“Inhibiting SHP2 reduces glycolysis,promotes microglial M1 polarization,and alleviates secondary inflammation following spinal cord injury in a mouse model,”published in Neural Regeneration Research(Ding et al.,2025),the title was incorrectly presented due to an error during the language polishing process.
基金supported by FATALSDrug Project [Progetti di Ricerca@CNR SAC.AD002.173.058] from National Research Council,Italy (to CV)。
文摘The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.
文摘Objective To investigate the underlying molecular mechanisms of metformin in inhibiting hepatic gluconeogenesis.Methods Primary hepatocytes of mice were isolated by a modified version of the collagenase method.The effect of metformin on glucose production in primary hepatocytes was detected by glucose oxidation method.
文摘Objective To observe the effect of Bushen Huoxue Recipe(BHR)on inhibiting vascular calcification(VC)in chronic renal failure(CRF)rats by regulating BMP-2/Runx2/Osterix signal pathway,and to explore its possible mechanism.Methods Thirty SD rats were randomly divided into the normal group,the model group,and the BHR group,10 in each group.Rats in the model group and the BHR group were administered with 250
