A simulation approach based on a full-wave numerical method is presented to study electromagnetic characteristics by complex targets. How to validate simulation results is considered thoroughly under no analytical and...A simulation approach based on a full-wave numerical method is presented to study electromagnetic characteristics by complex targets. How to validate simulation results is considered thoroughly under no analytical and measured data, where a double-check criterion is designed for our simulation approach. As an example, the scattering of F-117A is studied by using our simulation approach under all polarizations, different frequency bands, incident and scattering directions, etc., some of which, such as cross-polarization, bistatic RCS, have not been considered in the previous literature.展开更多
OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic tar...OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.展开更多
A practical approach for calculating the RCS (Radar Cross Section) of complex targets modeled with wire-grid-frame is presented. A way for generating a polyhedron model (facet-wedge model) with the wire-grid-frame dat...A practical approach for calculating the RCS (Radar Cross Section) of complex targets modeled with wire-grid-frame is presented. A way for generating a polyhedron model (facet-wedge model) with the wire-grid-frame data is described. For storing and reading the data of the polyhedron model in an easy way, a data structure is given.展开更多
The defining neuropathological feature of Parkinson＇s disease （PD） is the loss of nigrostriatal dopaminergic （DA） projections. This results in striatal dopamine levels and a biochemical reduction of movement diso...The defining neuropathological feature of Parkinson＇s disease （PD） is the loss of nigrostriatal dopaminergic （DA） projections. This results in striatal dopamine levels and a biochemical reduction of movement disorders, such as a tremor at rest, rigidity of the limbs, bradykinesia, and postural instability （Kim et al., 2011; Kim et al., 2012; Burke and O＇Malley, 2013; Leem et al., 2014; Namet al., 2014）.展开更多
The mammalian target of rapamycin(mTOR)acts in two structurally and functionally distinct protein complexes,mTOR complex 1(mTORC1)and mTOR complex 2(mTORC2).Upon deregulation,activated mTOR signaling is associated wit...The mammalian target of rapamycin(mTOR)acts in two structurally and functionally distinct protein complexes,mTOR complex 1(mTORC1)and mTOR complex 2(mTORC2).Upon deregulation,activated mTOR signaling is associated with multiple processes involved in tumor growth and metastasis.Compared with mTORC1,much less is known about mTORC2 in cancer,mainly because of the unavailability of a selective inhibitor.However,existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so far.It is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth,cell survival,metabolism,and cytoskeletal organization.It is not only implicated in tumor progression,metastasis,and the tumor microenvironment but also in resistance to therapy.Rictor,the central subunit of mTORC2,was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad prognosis.Moreover,AKT,the main downstream regulator of mTORC2/Rictor,is one of the most highly activated proteins in cancer.Primary and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment,emphasizing the need for further therapeutic options.This review,therefore,summarizes the role of mTORC2/Rictor in cancer,with special focus on primary liver cancer but also on liver metastases.展开更多
A new way of acoustic wave imaging was investigated. By using the Green function theory a system of integral equations,which linked wave number perturbation function with wave field, was firstly deduced. By taking var...A new way of acoustic wave imaging was investigated. By using the Green function theory a system of integral equations,which linked wave number perturbation function with wave field, was firstly deduced. By taking variation on these integral equations an inversion equation,which reflected the relation between the little variation of wave number perturbation function and that of scattering field, was further obtained. Finally, the perturbation functions of some identical targets were reconstructed, and some properties of the novel method including converging speed, inversion accuracy and the abilities to resist random noise and identify complex targets were discussed. Results of numerical simulation show that the method based on the variation principle has great theoretical and applicable value to quantitative nondestructive evaluation.展开更多
The electromagnetic scattering computation has developed rapidly for many years; some computing problems for complex and coated targets cannot be solved by using the existing theory and computing models. A computing m...The electromagnetic scattering computation has developed rapidly for many years; some computing problems for complex and coated targets cannot be solved by using the existing theory and computing models. A computing model based on data is established for making up the insufficiency of theoretic models. Based on the ＂support vector regression method＂, which is formulated on the principle of minimizing a structural risk, a data model to predicate the unknown radar cross section of some appointed targets is given. Comparison between the actual data and the results of this predicting model based on support vector regression method proved that the support vector regression method is workable and with a comparative precision.展开更多
A RCS prediction system named SCTE (Scattering from Complex Target and Environment) for calculating high-frequency electromagnetic scattering from complex target within complex environment is presented. The scattering...A RCS prediction system named SCTE (Scattering from Complex Target and Environment) for calculating high-frequency electromagnetic scattering from complex target within complex environment is presented. The scattering body is described by Computer-Aided-Design (CAD) representations in which the complex body is modeled as NURBS (Non-Uniform Rational B-spline) surfaces. The complex environment (rough surface of sea or ground) is also carefully considered by using fractal function. Scattering fields are calculated by using physical optics and the equivalent currents methods. There is a good agreement between the present results and that from measurements which demonstrates the accuracy of this system.展开更多
BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin co...BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin complex 1(mTORC1)activation.Previous studies have demonstrated the therapeutic effects of BT2 on arthritis,liver cancer,and kidney injury.However,the effects of BT2 on ulcerative colitis(UC)are unknown.AIM To investigate the anti-UC effects of BT2 and the underlying mechanism.METHODS Mouse UC models were created through the administration of 3.5%dextran sodium sulfate(DSS)for 7 d.The mice in the treated groups were administered salazosulfapyridine(300 mg/kg)or BT2(20 mg/kg)orally from day 1 to day 7.At the end of the study,all of the mice were sacrificed,and colon tissues were removed for hematoxylin and eosin staining,immunoblot analyses,and immunohistochemical assays.Cytokine levels were measured by flow cytometry.The contents of BCAAs including valine,leucine,and isoleucine,in mouse serum were detected by liquid chromatography-tandem mass spectrometry,and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.RESULTS Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice.BT2 also reduced the production of the proinflammatory cytokines interleukin 6(IL-6),IL-9,and IL-2 and increased the anti-inflammatory cytokine IL-10 level.In addition,BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice.Furthermore,highthroughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis.Compared with the DSS group,BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and Escherichia-Shigella.CONCLUSION Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.展开更多
During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many peopl...During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many people died before reaching adult- hood, nowadays most people survive. Hence average life ex- pectancy in 1800s was around 30-40, which was barely higher than it had been in Greek and Roman times （Finch, 2010）, but nowadays life expectancy in most modernised economies is around 75 - 80. This demographic shift, which has happened in only 200 years, has created a dramatic change in the causes of mortality. The major killers in the modern world are non- communicable diseases （NCDs）： principally cardiovascular disease, cancer and neurodegenerative disorders such as Alz- heimer＇s disease. A major factor that influences susceptibility to all these diseases is age. As we get older, our risk of developing these NCDs increases enormously. For example, the rate of breast cancer in females at age 15-19 is less than 10 per 100,000 population, but this increases to 100 at age 40-44, 275 at age 55--59 and 450 at age 85 ＋ （http：//www.cancerresearchuk.org/ cancer-info/cancerstats/types/breast/incidence/#age）. Ageing has consequently become a major medical, social and economic burden to many countries.展开更多
This article seeks to outline an integrated and practical geometric optimization design system （GODS） incorporating hybrid graphical electromagnetic computing-wedge modeling （GRECO-WM） scheme and the genetic algor...This article seeks to outline an integrated and practical geometric optimization design system （GODS） incorporating hybrid graphical electromagnetic computing-wedge modeling （GRECO-WM） scheme and the genetic algorithm （GA） for calculating the radar cross section （RCS） and optimizing the geometric parameters of a large and complex target respectively. A new wedge modeling （WM） scheme is presented for calculating the high-frequency RCS of wedge with only one visible facet based on the method of equivalent currents （MEC）. The applications of GODS to 2D cross-section and 3D surface are respectively implemented by choosing an average of monostatic RCS values corresponding to a series of incident angles over a frequency band as the optimum objective function. And the results demonstrate that the RCS can be effectively and conveniently reduced by the GODS presented in this article.展开更多
In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes melli...In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes mellitus were generated by a single injection of streptozotocin.At 8 weeks after streptozotocin injection,the Morris water maze test and western blot assays confirmed that the diabetic model rats had learning and memory deficits,insulin resistance,and Sirtuin 1 expression could be detected in the hippocampus.Insulin and the insulin receptor inhibitor S961 were intranasally administered to investigate the regulatory effects of insulin signaling on Sirtuin 1.The results showed that insulin administration improved the impaired cognitive function of diabetic model rats and increased the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1 in the hippocampus.Conversely,S961 administration resulted in more severe cognitive dysfunction and reduced the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1.The Sirtuin 1 activator SRT2104 and the inhibitor Sirtinol were injected into the lateral ventricle,which revealed that the activation of Sirtuin 1 increased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor.Hippocampal dendritic length and spine density also increased in response to Sirtuin 1 activation.In contrast,Sirtinol decreased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor and damaged the dendritic structure.These findings suggest that the Sirtuin 1 signaling pathway plays an important role in the development of insulin resistance-related cognitive deficits in diabetic rats.This study was approved by the Animal Ethics Welfare Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine(approval No.ZYFY201811207)in November 2018.展开更多
This paper presents a new method for computation of the monostatic radar cross section (RCS) of electrically large conducting objects. Compared with the traditional Z-buffer technique, the improved one can record not ...This paper presents a new method for computation of the monostatic radar cross section (RCS) of electrically large conducting objects. Compared with the traditional Z-buffer technique, the improved one can record not only the illuminated surface of the body, but also the information about the shadowed part. So multi-scattering and RCS of cavity can be calculated. The second advantage of it is using dual representation, of the target's facet surface, in which the illuminated part is treated as bicubic patches for RCS calculation, and is simplified to flat facet when ray tracing is done. Excellent agreement with the experiment has been obtained.展开更多
Background:Autophagy dysfunction plays a crucial role in tau accumulation and neurodegeneration in Alzheimer’s disease(AD).This study aimed to investigate whether and how the accumulating tau may in turn affect autop...Background:Autophagy dysfunction plays a crucial role in tau accumulation and neurodegeneration in Alzheimer’s disease(AD).This study aimed to investigate whether and how the accumulating tau may in turn affect autophagy.Methods:The primary hippocampal neurons,N2a and HEK293T cells with tau overexpression were respectively starved and treated with vinblastine to study the effects of tau on the initiating steps of autophagy,which was analysed by Student’s two-tailed t-test.The rapamycin and concanamycin A were employed to inhibit the mammalian target of rapamycin kinase complex 1(mTORC1)activity and the vacuolar H+-ATPase(v-ATPase)activity,respectively,which were analysed by One-way ANOVA with post hoc tests.The Western blotting,co-immunoprecipitation and immunofuorescence staining were conducted to gain insight into the mechanisms underlying the tau effects of mTORC1 signaling alterations,as analysed by Student’s two-tailed t-test or One-way ANOVA with post hoc tests.The autophagosome formation was detected by immunofuorescence staining and transmission electron microscopy.The amino acids(AA)levels were detected by high performance liquid chromatography(HPLC).Results:We observed that overexpressing human full-length wild-type tau to mimic AD-like tau accumulation induced autophagy deficits.Further studies revealed that the increased tau could bind to the prion-related domain of T cell intracellular antigen 1(PRD-TIA1)and this association significantly increased the intercellular level of amino acids(Leucine,P=0.0038;Glutamic acid,P=0.0348;Alanine,P=0.0037;Glycine,P=0.0104),with concordant upregulation of mTORC1 activity[phosphorylated eukaryotic translation initiation factor 4E-binding protein 1(p-4EBP1),P<0.0001;phosphorylated 70 kD ribosomal protein S6 kinase 1(p-p70S6K1),P=0.0001,phosphorylated unc-51-like autophagyactivating kinase 1(p-ULK1),P=0.0015]and inhibition of autophagosome formation[microtubuleassociated protein light chain 3 II(LC3 II),P=0.0073;LC3 puncta,P<0.0001].As expected,this tau-induced deficit of autophagosome formation in turn aggravated tau accumulation.Importantly,we also found that blocking TIA1 and tau interaction by overexpressing PRD-TIA1,downregulating the endogenous TIA1 expression by shRNA,or downregulating tau protein level by a small proteolysis targeting chimera(PROTAC)could remarkably attenuate tau-induced autophagy impairment.Conclusions:Our findings reveal that AD-like tau accumulation inhibits autophagosome formation and induces autophagy deficits by activating the TIA1/amino acid/mTORC1 pathway,and thus this work reveals new insight into tau-associated neurodegeneration and provides evidence supporting the use of new therapeutic targets for AD treat-ment and that of related tauopathies.展开更多
The mechanistic target of rapamycin complex 1(mTORC1)controls cell growth and metabolism in response to various environmental inputs,especially amino acids.In fact,the activity of mTORC1 is highly sensitive to changes...The mechanistic target of rapamycin complex 1(mTORC1)controls cell growth and metabolism in response to various environmental inputs,especially amino acids.In fact,the activity of mTORC1 is highly sensitive to changes in amino acid levels.Over past decades,a variety of proteins have been identified as participating in the mTORC1 pathway regulated by amino acids.Classically,the Rag guanosine triphosphatases(GTPases),which reside on the lysosome,transmit amino acid availability to the mTORC1 pathway and recruit mTORC1 to the lysosome upon amino acid sufficiency.Recently,several sensors of leucine,arginine,and S-adenosylmethionine for the amino acidstimulated mTORC1 pathway have been coming to light.Characterization of these sensors is requisite for understanding how cells adjust amino acid sensing pathways to their different needs.In this review,we summarize recent advances in amino acid sensing mechanisms that regulate mTORC1 activity and highlight these identified sensors that accurately transmit specific amino acid signals to the mTORC1 pathway.展开更多
Radio recombination lines（RRLs） are the best tracers of ionized gas. Simultaneous observations of multi-transitions of RRLs can significantly improve survey sensitivity. We conducted pilot RRL observations near the ...Radio recombination lines（RRLs） are the best tracers of ionized gas. Simultaneous observations of multi-transitions of RRLs can significantly improve survey sensitivity. We conducted pilot RRL observations near the Sagittarius Arm tangent by using the 65-m Shanghai Tian Ma Radio Telescope（TMRT） equipped with broadband feeds and a digital backend. Six hydrogen RRLs（H96α-H101α）at C band（6289 MHz-7319 MHz） were observed simultaneously toward a sky area of 2°× 1.2° by using on-the-fly mapping mode. These transitions were then stacked together for detection of ionized gas. Star forming complexes G48.6＋0.1 and G49.5-0.3 were detected in the integrated intensity map.We found agreements between our measured centroid velocities and previous results for the 21 known HII regions in the mapped area. For more than 80 cataloged HII region candidates without previous RRL measurements, we obtained new RRL spectra at 30 targeted positions. In addition, we detected 25 new discrete RRL sources with spectral S/N 〉 5σ, and they were not listed in the catalogs of previously known HII regions. The distances for 44 out of these 55 new RRL sources were estimated.展开更多
Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets...Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin.Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales,from nanometers to micrometers.Single molecule localization microscopy(SMLM)methods,such as STORM,are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization.Multi-label imaging of chromatin is necessary to unpack its structural complexity.However,these efforts are challenged by the high-density nuclear environment,which can affect antibody binding affinities,diffusivity and non-specific interactions.Optimizing buffer conditions,fluorophore stability,and antibody specificity is crucial for achieving effective antibody conjugates.Here,we demonstrate a sequential immunolabeling protocol that reliably enables three-color studies within the dense nuclear environment.This protocol couples multiplexed localization datasets with a robust analysis algorithm,which utilizes localizations from one target as seed points for distance,density and multi-label joint affinity measurements to explore complex organization of all three targets.Applying this multiplexed algorithm to analyze distance and joint density reveals that heterochromatin and euchromatin are not-distinct territories,but that localization of transcription and euchromatin couple with the periphery of heterochromatic clusters.This work is a crucial step in molecular imaging of the dense nuclear environment as multi-label capacity enables for investigation of complex multi-component systems like chromatin with enhanced accuracy.展开更多
In a recent study published in Science,Chen and colleagues unveiled the mechanism by which hepatic alkylation repair homolog protein 5(ALKBH5)regulates the glucagon receptor(GCGR)and mechanistic target of rapamycin co...In a recent study published in Science,Chen and colleagues unveiled the mechanism by which hepatic alkylation repair homolog protein 5(ALKBH5)regulates the glucagon receptor(GCGR)and mechanistic target of rapamycin complex 1(mTORC1)signaling pathways via two independent mechanisms,thereby integrating the modulation of glucose and lipid metabolism homeostasis.1 This research explores the regulation of metabolic homeostasis and the pathogenesis of metabolic diseases from the perspective of RNAbinding proteins,offering new drug targets for alleviating metabolicassociated fatty liver disease(MAFLD)and metabolic disorders.展开更多
With the support by the National Natural Science Foundation of China and the Chinese Academy of Sciences,the research team led by Prof.Li Junbai(李峻柏)at the CAS Key Lab of Colloid,Interface and Thermodynamics,Instit...With the support by the National Natural Science Foundation of China and the Chinese Academy of Sciences,the research team led by Prof.Li Junbai(李峻柏)at the CAS Key Lab of Colloid,Interface and Thermodynamics,Institute of Chemistry,Chinese Academy of Sciences,revealed the distribution of proteins in the transformation of inorganic/protein hybrid crystals by super-resolution microscopy,which展开更多
The intake of sugars,especially glucose and fructose,has significantly increased with the change of lifestyle.Excessive intake of sugar has been proven to be associated with tumors and inflammatory diseases.Fructose d...The intake of sugars,especially glucose and fructose,has significantly increased with the change of lifestyle.Excessive intake of sugar has been proven to be associated with tumors and inflammatory diseases.Fructose directly mediates innate immune responses;however,whether it can directly regulate T-cell immunity remains unknown.We show that high fructose consumption accelerates the development of inflammatory bowel disease(IBD)by promoting the generation of T helper 1(Th1)and T helper 17(Th17)cells.It was demonstrated that fructose promotes the differentiation of Th1 and Th17 cells directly by enhancing mechanistic target of rapamycin complex 1(mTORC1)activation through the glutamine metabolism-dependent pathway.Reactive oxygen species(ROS)-induced activation of transforming growth factor-β(TGF-β)is also involved in fructose-induced Th17 cell generation.Moreover,metformin can reverse Th1 and Th17 cell generation induced by fructose by suppressing mTORC1 activation and reducing ROS-mediated TGF-βactivation.Finally,we identified metformin as an in vivo therapeutic drug for relieving high fructose consumption-induced T-cell inflammation and colitis aggravation.Our study revealed a previously unknown adverse effect of high fructose consumption in disrupting immune homeostasis and exacerbating IBD by directly promoting T-cell immunity,and showed metformin is a potential therapeutic for reversing the T cell immune imbalance caused by long-term high fructose consumption.展开更多
文摘A simulation approach based on a full-wave numerical method is presented to study electromagnetic characteristics by complex targets. How to validate simulation results is considered thoroughly under no analytical and measured data, where a double-check criterion is designed for our simulation approach. As an example, the scattering of F-117A is studied by using our simulation approach under all polarizations, different frequency bands, incident and scattering directions, etc., some of which, such as cross-polarization, bistatic RCS, have not been considered in the previous literature.
基金Supported by Guangzhou Science and Technology Bureau Research Fund:the Mechanism of Action of Huangqi Guizhi Decoction on Precancerous Lesions in Cag Rats was Studied based on the Phosphatidylinositol 3-Kinase-Protein Kinase B-Mechanistic Target of Rapamycin Complex 2 Pathway(No.202102080643)Guangzhou Traditional Chinese Medicine and Integrative Medicine Research Project:Observation on the Therapeutic Effect of Wenyang Jianpi Ointment on Chronic Atrophic Gastritis of Spleen and Stomach Weakness Type and Study on its Regulatory Effect on Transforming Growth Factor Beta 3(No.20222A010079)Panyu District Science and Technology Project:the Mechanism by which the Modified Huangqi Guizhi Decoction Regulates the Transforming Growth Factor-β3 Signaling Pathway to Improve Precancerous Lesions in Rats with Chronic Atrophic Gastritis(No.2020-Z04-025)。
文摘OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.
文摘A practical approach for calculating the RCS (Radar Cross Section) of complex targets modeled with wire-grid-frame is presented. A way for generating a polyhedron model (facet-wedge model) with the wire-grid-frame data is described. For storing and reading the data of the polyhedron model in an easy way, a data structure is given.
文摘The defining neuropathological feature of Parkinson＇s disease （PD） is the loss of nigrostriatal dopaminergic （DA） projections. This results in striatal dopamine levels and a biochemical reduction of movement disorders, such as a tremor at rest, rigidity of the limbs, bradykinesia, and postural instability （Kim et al., 2011; Kim et al., 2012; Burke and O＇Malley, 2013; Leem et al., 2014; Namet al., 2014）.
文摘The mammalian target of rapamycin(mTOR)acts in two structurally and functionally distinct protein complexes,mTOR complex 1(mTORC1)and mTOR complex 2(mTORC2).Upon deregulation,activated mTOR signaling is associated with multiple processes involved in tumor growth and metastasis.Compared with mTORC1,much less is known about mTORC2 in cancer,mainly because of the unavailability of a selective inhibitor.However,existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so far.It is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth,cell survival,metabolism,and cytoskeletal organization.It is not only implicated in tumor progression,metastasis,and the tumor microenvironment but also in resistance to therapy.Rictor,the central subunit of mTORC2,was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad prognosis.Moreover,AKT,the main downstream regulator of mTORC2/Rictor,is one of the most highly activated proteins in cancer.Primary and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment,emphasizing the need for further therapeutic options.This review,therefore,summarizes the role of mTORC2/Rictor in cancer,with special focus on primary liver cancer but also on liver metastases.
文摘A new way of acoustic wave imaging was investigated. By using the Green function theory a system of integral equations,which linked wave number perturbation function with wave field, was firstly deduced. By taking variation on these integral equations an inversion equation,which reflected the relation between the little variation of wave number perturbation function and that of scattering field, was further obtained. Finally, the perturbation functions of some identical targets were reconstructed, and some properties of the novel method including converging speed, inversion accuracy and the abilities to resist random noise and identify complex targets were discussed. Results of numerical simulation show that the method based on the variation principle has great theoretical and applicable value to quantitative nondestructive evaluation.
文摘The electromagnetic scattering computation has developed rapidly for many years; some computing problems for complex and coated targets cannot be solved by using the existing theory and computing models. A computing model based on data is established for making up the insufficiency of theoretic models. Based on the ＂support vector regression method＂, which is formulated on the principle of minimizing a structural risk, a data model to predicate the unknown radar cross section of some appointed targets is given. Comparison between the actual data and the results of this predicting model based on support vector regression method proved that the support vector regression method is workable and with a comparative precision.
文摘A RCS prediction system named SCTE (Scattering from Complex Target and Environment) for calculating high-frequency electromagnetic scattering from complex target within complex environment is presented. The scattering body is described by Computer-Aided-Design (CAD) representations in which the complex body is modeled as NURBS (Non-Uniform Rational B-spline) surfaces. The complex environment (rough surface of sea or ground) is also carefully considered by using fractal function. Scattering fields are calculated by using physical optics and the equivalent currents methods. There is a good agreement between the present results and that from measurements which demonstrates the accuracy of this system.
基金Supported by National Natural Science Foundation of ChinaNo. 82074241+1 种基金Project of Jiangsu Province Hospital of Traditional Chinese Medicine Peak TalentNo. y2021rc36
文摘BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin complex 1(mTORC1)activation.Previous studies have demonstrated the therapeutic effects of BT2 on arthritis,liver cancer,and kidney injury.However,the effects of BT2 on ulcerative colitis(UC)are unknown.AIM To investigate the anti-UC effects of BT2 and the underlying mechanism.METHODS Mouse UC models were created through the administration of 3.5%dextran sodium sulfate(DSS)for 7 d.The mice in the treated groups were administered salazosulfapyridine(300 mg/kg)or BT2(20 mg/kg)orally from day 1 to day 7.At the end of the study,all of the mice were sacrificed,and colon tissues were removed for hematoxylin and eosin staining,immunoblot analyses,and immunohistochemical assays.Cytokine levels were measured by flow cytometry.The contents of BCAAs including valine,leucine,and isoleucine,in mouse serum were detected by liquid chromatography-tandem mass spectrometry,and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.RESULTS Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice.BT2 also reduced the production of the proinflammatory cytokines interleukin 6(IL-6),IL-9,and IL-2 and increased the anti-inflammatory cytokine IL-10 level.In addition,BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice.Furthermore,highthroughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis.Compared with the DSS group,BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and Escherichia-Shigella.CONCLUSION Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.
文摘During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many people died before reaching adult- hood, nowadays most people survive. Hence average life ex- pectancy in 1800s was around 30-40, which was barely higher than it had been in Greek and Roman times （Finch, 2010）, but nowadays life expectancy in most modernised economies is around 75 - 80. This demographic shift, which has happened in only 200 years, has created a dramatic change in the causes of mortality. The major killers in the modern world are non- communicable diseases （NCDs）： principally cardiovascular disease, cancer and neurodegenerative disorders such as Alz- heimer＇s disease. A major factor that influences susceptibility to all these diseases is age. As we get older, our risk of developing these NCDs increases enormously. For example, the rate of breast cancer in females at age 15-19 is less than 10 per 100,000 population, but this increases to 100 at age 40-44, 275 at age 55--59 and 450 at age 85 ＋ （http：//www.cancerresearchuk.org/ cancer-info/cancerstats/types/breast/incidence/#age）. Ageing has consequently become a major medical, social and economic burden to many countries.
基金National Natural Science Foundation of China （20095251024）
文摘This article seeks to outline an integrated and practical geometric optimization design system （GODS） incorporating hybrid graphical electromagnetic computing-wedge modeling （GRECO-WM） scheme and the genetic algorithm （GA） for calculating the radar cross section （RCS） and optimizing the geometric parameters of a large and complex target respectively. A new wedge modeling （WM） scheme is presented for calculating the high-frequency RCS of wedge with only one visible facet based on the method of equivalent currents （MEC）. The applications of GODS to 2D cross-section and 3D surface are respectively implemented by choosing an average of monostatic RCS values corresponding to a series of incident angles over a frequency band as the optimum objective function. And the results demonstrate that the RCS can be effectively and conveniently reduced by the GODS presented in this article.
基金This study was supported by the National Natural Science Foundation of China,No.81874464(to YHW)the Natural Science Foundation of Hunan Province of China,No.2019JJ50464(to HY)the Open Fund of the Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine,No.2018ZYX46(to HY).
文摘In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes mellitus were generated by a single injection of streptozotocin.At 8 weeks after streptozotocin injection,the Morris water maze test and western blot assays confirmed that the diabetic model rats had learning and memory deficits,insulin resistance,and Sirtuin 1 expression could be detected in the hippocampus.Insulin and the insulin receptor inhibitor S961 were intranasally administered to investigate the regulatory effects of insulin signaling on Sirtuin 1.The results showed that insulin administration improved the impaired cognitive function of diabetic model rats and increased the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1 in the hippocampus.Conversely,S961 administration resulted in more severe cognitive dysfunction and reduced the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1.The Sirtuin 1 activator SRT2104 and the inhibitor Sirtinol were injected into the lateral ventricle,which revealed that the activation of Sirtuin 1 increased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor.Hippocampal dendritic length and spine density also increased in response to Sirtuin 1 activation.In contrast,Sirtinol decreased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor and damaged the dendritic structure.These findings suggest that the Sirtuin 1 signaling pathway plays an important role in the development of insulin resistance-related cognitive deficits in diabetic rats.This study was approved by the Animal Ethics Welfare Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine(approval No.ZYFY201811207)in November 2018.
文摘This paper presents a new method for computation of the monostatic radar cross section (RCS) of electrically large conducting objects. Compared with the traditional Z-buffer technique, the improved one can record not only the illuminated surface of the body, but also the information about the shadowed part. So multi-scattering and RCS of cavity can be calculated. The second advantage of it is using dual representation, of the target's facet surface, in which the illuminated part is treated as bicubic patches for RCS calculation, and is simplified to flat facet when ray tracing is done. Excellent agreement with the experiment has been obtained.
基金supported by grants from the Natural Science Foundation of China(91949205,31730035,81721005)the Science and Technology Committee of China(2016YFC1305800)+1 种基金the Special Project of Technological Innovation of Hubei Province(2018ACA142)Guangdong Provincial Key S&T Program(2018B030336001)。
文摘Background:Autophagy dysfunction plays a crucial role in tau accumulation and neurodegeneration in Alzheimer’s disease(AD).This study aimed to investigate whether and how the accumulating tau may in turn affect autophagy.Methods:The primary hippocampal neurons,N2a and HEK293T cells with tau overexpression were respectively starved and treated with vinblastine to study the effects of tau on the initiating steps of autophagy,which was analysed by Student’s two-tailed t-test.The rapamycin and concanamycin A were employed to inhibit the mammalian target of rapamycin kinase complex 1(mTORC1)activity and the vacuolar H+-ATPase(v-ATPase)activity,respectively,which were analysed by One-way ANOVA with post hoc tests.The Western blotting,co-immunoprecipitation and immunofuorescence staining were conducted to gain insight into the mechanisms underlying the tau effects of mTORC1 signaling alterations,as analysed by Student’s two-tailed t-test or One-way ANOVA with post hoc tests.The autophagosome formation was detected by immunofuorescence staining and transmission electron microscopy.The amino acids(AA)levels were detected by high performance liquid chromatography(HPLC).Results:We observed that overexpressing human full-length wild-type tau to mimic AD-like tau accumulation induced autophagy deficits.Further studies revealed that the increased tau could bind to the prion-related domain of T cell intracellular antigen 1(PRD-TIA1)and this association significantly increased the intercellular level of amino acids(Leucine,P=0.0038;Glutamic acid,P=0.0348;Alanine,P=0.0037;Glycine,P=0.0104),with concordant upregulation of mTORC1 activity[phosphorylated eukaryotic translation initiation factor 4E-binding protein 1(p-4EBP1),P<0.0001;phosphorylated 70 kD ribosomal protein S6 kinase 1(p-p70S6K1),P=0.0001,phosphorylated unc-51-like autophagyactivating kinase 1(p-ULK1),P=0.0015]and inhibition of autophagosome formation[microtubuleassociated protein light chain 3 II(LC3 II),P=0.0073;LC3 puncta,P<0.0001].As expected,this tau-induced deficit of autophagosome formation in turn aggravated tau accumulation.Importantly,we also found that blocking TIA1 and tau interaction by overexpressing PRD-TIA1,downregulating the endogenous TIA1 expression by shRNA,or downregulating tau protein level by a small proteolysis targeting chimera(PROTAC)could remarkably attenuate tau-induced autophagy impairment.Conclusions:Our findings reveal that AD-like tau accumulation inhibits autophagosome formation and induces autophagy deficits by activating the TIA1/amino acid/mTORC1 pathway,and thus this work reveals new insight into tau-associated neurodegeneration and provides evidence supporting the use of new therapeutic targets for AD treat-ment and that of related tauopathies.
基金National Natural Science Foundation of China(Nos.31520103915,31730090,and 31322053)the Hubei Provincial Natural Science Foundation of China(No.2018CFA020)
文摘The mechanistic target of rapamycin complex 1(mTORC1)controls cell growth and metabolism in response to various environmental inputs,especially amino acids.In fact,the activity of mTORC1 is highly sensitive to changes in amino acid levels.Over past decades,a variety of proteins have been identified as participating in the mTORC1 pathway regulated by amino acids.Classically,the Rag guanosine triphosphatases(GTPases),which reside on the lysosome,transmit amino acid availability to the mTORC1 pathway and recruit mTORC1 to the lysosome upon amino acid sufficiency.Recently,several sensors of leucine,arginine,and S-adenosylmethionine for the amino acidstimulated mTORC1 pathway have been coming to light.Characterization of these sensors is requisite for understanding how cells adjust amino acid sensing pathways to their different needs.In this review,we summarize recent advances in amino acid sensing mechanisms that regulate mTORC1 activity and highlight these identified sensors that accurately transmit specific amino acid signals to the mTORC1 pathway.
基金supported by the National Natural Science Foundation of China (11303035, 11473034, 11503033 and 11503070)supported by the Key Research Program of the Chinese Academy of Sciences, Grant No. QYZDJSSW-SLH021+1 种基金additionally supported by the FAST Fellowshipthe Young Researchers Grant of National Astronomical Observatories, Chinese Academy of Sciences
文摘Radio recombination lines（RRLs） are the best tracers of ionized gas. Simultaneous observations of multi-transitions of RRLs can significantly improve survey sensitivity. We conducted pilot RRL observations near the Sagittarius Arm tangent by using the 65-m Shanghai Tian Ma Radio Telescope（TMRT） equipped with broadband feeds and a digital backend. Six hydrogen RRLs（H96α-H101α）at C band（6289 MHz-7319 MHz） were observed simultaneously toward a sky area of 2°× 1.2° by using on-the-fly mapping mode. These transitions were then stacked together for detection of ionized gas. Star forming complexes G48.6＋0.1 and G49.5-0.3 were detected in the integrated intensity map.We found agreements between our measured centroid velocities and previous results for the 21 known HII regions in the mapped area. For more than 80 cataloged HII region candidates without previous RRL measurements, we obtained new RRL spectra at 30 targeted positions. In addition, we detected 25 new discrete RRL sources with spectral S/N 〉 5σ, and they were not listed in the catalogs of previously known HII regions. The distances for 44 out of these 55 new RRL sources were estimated.
基金supported by NIH grants U54CA268084,U54CA261694,and R01CA228272National Science Foundation grants EFMA-1830961 and CBET-2430743+1 种基金philanthropic support from Rob and Kristin Goldman,Mr.David Sachsthe Christina Carinato Charitable Foundation.
文摘Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin.Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales,from nanometers to micrometers.Single molecule localization microscopy(SMLM)methods,such as STORM,are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization.Multi-label imaging of chromatin is necessary to unpack its structural complexity.However,these efforts are challenged by the high-density nuclear environment,which can affect antibody binding affinities,diffusivity and non-specific interactions.Optimizing buffer conditions,fluorophore stability,and antibody specificity is crucial for achieving effective antibody conjugates.Here,we demonstrate a sequential immunolabeling protocol that reliably enables three-color studies within the dense nuclear environment.This protocol couples multiplexed localization datasets with a robust analysis algorithm,which utilizes localizations from one target as seed points for distance,density and multi-label joint affinity measurements to explore complex organization of all three targets.Applying this multiplexed algorithm to analyze distance and joint density reveals that heterochromatin and euchromatin are not-distinct territories,but that localization of transcription and euchromatin couple with the periphery of heterochromatic clusters.This work is a crucial step in molecular imaging of the dense nuclear environment as multi-label capacity enables for investigation of complex multi-component systems like chromatin with enhanced accuracy.
基金supported by Natural Science Foundation of Sichuan Province(Grants 2023NSFSC1154).
文摘In a recent study published in Science,Chen and colleagues unveiled the mechanism by which hepatic alkylation repair homolog protein 5(ALKBH5)regulates the glucagon receptor(GCGR)and mechanistic target of rapamycin complex 1(mTORC1)signaling pathways via two independent mechanisms,thereby integrating the modulation of glucose and lipid metabolism homeostasis.1 This research explores the regulation of metabolic homeostasis and the pathogenesis of metabolic diseases from the perspective of RNAbinding proteins,offering new drug targets for alleviating metabolicassociated fatty liver disease(MAFLD)and metabolic disorders.
文摘With the support by the National Natural Science Foundation of China and the Chinese Academy of Sciences,the research team led by Prof.Li Junbai(李峻柏)at the CAS Key Lab of Colloid,Interface and Thermodynamics,Institute of Chemistry,Chinese Academy of Sciences,revealed the distribution of proteins in the transformation of inorganic/protein hybrid crystals by super-resolution microscopy,which
基金supported by the National Natural Science Foundation of China(NO.82171829)the Key Project of the Science and Technology Department of Sichuan Province(NO.2025YFHZ0205)+2 种基金the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(NO.ZYYC25010)supported by the Intramural Research Program of the U.S.National Institutes of Health(NIH)National Institute of Dental and Craniofacial Research(NIDCR).
文摘The intake of sugars,especially glucose and fructose,has significantly increased with the change of lifestyle.Excessive intake of sugar has been proven to be associated with tumors and inflammatory diseases.Fructose directly mediates innate immune responses;however,whether it can directly regulate T-cell immunity remains unknown.We show that high fructose consumption accelerates the development of inflammatory bowel disease(IBD)by promoting the generation of T helper 1(Th1)and T helper 17(Th17)cells.It was demonstrated that fructose promotes the differentiation of Th1 and Th17 cells directly by enhancing mechanistic target of rapamycin complex 1(mTORC1)activation through the glutamine metabolism-dependent pathway.Reactive oxygen species(ROS)-induced activation of transforming growth factor-β(TGF-β)is also involved in fructose-induced Th17 cell generation.Moreover,metformin can reverse Th1 and Th17 cell generation induced by fructose by suppressing mTORC1 activation and reducing ROS-mediated TGF-βactivation.Finally,we identified metformin as an in vivo therapeutic drug for relieving high fructose consumption-induced T-cell inflammation and colitis aggravation.Our study revealed a previously unknown adverse effect of high fructose consumption in disrupting immune homeostasis and exacerbating IBD by directly promoting T-cell immunity,and showed metformin is a potential therapeutic for reversing the T cell immune imbalance caused by long-term high fructose consumption.
