Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequ...Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequent repression of gene transcription.Abnormal EZH2 expression or mutation is associated with various cancers,particularly lymphoma,and breast and prostate cancer.EZH2 has been investigated as an important target in cancer therapy and potential EZH2-targeted drugs have been developed.This article reviews the research progress on the mechanism of transcriptional regulation of EZH2 and the development and clinical use of some inhibitors targeting EZH2.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
Two Gd_(2)complexes,namely[Gd_(2)(dbm)_(2)(HL_(1))_(2)(CH_(3)OH)_(2)]·4CH_(3)OH(1)and[Gd_(2)(dbm)_(2)(L_(2))_(2)(CH_(3)OH)_(2)]·2CH_(3)OH(2),where H_(3)L_(1)=(Z)-N'-[4-(diethylamino)-2-hydroxybenzylidene...Two Gd_(2)complexes,namely[Gd_(2)(dbm)_(2)(HL_(1))_(2)(CH_(3)OH)_(2)]·4CH_(3)OH(1)and[Gd_(2)(dbm)_(2)(L_(2))_(2)(CH_(3)OH)_(2)]·2CH_(3)OH(2),where H_(3)L_(1)=(Z)-N'-[4-(diethylamino)-2-hydroxybenzylidene]-2-hydroxyacetohydrazide,H_(2)L_(2)=(E)-N'-(5-bromo-2-hydroxy-3-methoxybenzylidene)nicotinohydrazide,Hdbm=dibenzoylmethane,have been constructed by adopting the solvothermal method.Structural characterization unveils that both complexes 1 and 2 are constituted by two Gd^(3+)ions,two dbm-ions,two CH_(3)OH molecules,and two polydentate Schiff-base ligands(HL_(1)^(2-)or L_(2)^(2-)).In addition,complex 1 contains four free methanol molecules,whereas complex 2 harbors two free methanol molecules.By investigating the interactions between complexes 1 and 2 and four types of bacteria(Bacillus subtilis,Escherichia coli,Staphylococcus aureus,Candida albicans),it was found that both complexes 1 and 2 exhibited potent antibacte-rial activities.The interaction mechanisms between the ligands H_(3)L_(1),H_(2)L_(2),complexes 1 and 2,and calf thymus DNA(CT-DNA)were studied using ultraviolet-visible spectroscopy,fluorescence titration,and cyclic voltammetry.The results demonstrated that both complexes 1 and 2 can intercalate into CT-DNA molecules,thereby inhibiting bacterial proliferation to achieve the antibacterial effects.CCDC:2401116,1;2401117,2.展开更多
Binary sequences constructed by Legendre symbols are widely used in communication and cryptography since they have many good pseudo-random properties.In this paper,we determine the 2-adic complexity of the sum sequenc...Binary sequences constructed by Legendre symbols are widely used in communication and cryptography since they have many good pseudo-random properties.In this paper,we determine the 2-adic complexity of the sum sequence of any k many Legendre sequences and show that the 2-adic complexity of the sum sequences of any k many Legendre sequences reaches the maximum by proving the case of k=2 and 3,which implies that the sum sequences can resist the attack of rational approximation algorithm.展开更多
This study explores the development of an organic-inorganic hybrid coating to enhance the corrosion resistance and photocatalytic properties of AZ31 Mg alloy modified by plasma electrolytic oxidation(PEO).The PEO proc...This study explores the development of an organic-inorganic hybrid coating to enhance the corrosion resistance and photocatalytic properties of AZ31 Mg alloy modified by plasma electrolytic oxidation(PEO).The PEO process typically generates a porous oxide layer,which can reduce corrosion protection by allowing corrosive agents to penetrate the substrate.To address this limitation,phenopyridine(PHEN)and 2-methylimidazole(2-IMD)were incorporated into the PEO surface to form a robust organic layer on the Mg alloy.Potassium hydroxide(KOH)was used to adjust the pH,improving the interaction and solubility between the organic molecules and the PEO coating.The hybrid coating exhibited unique twig-like surface structures that contributed to forming a multifunctional coating with high corrosion resistance and superior photocatalytic activity.The PEO-PHEN-2IMD sample on the Mg alloy demonstrated exceptional corrosion resistance,with the lowest corrosion current density(I_(corr))of 1.92×10^(-10) A/cm^(2),a high corrosion potential(E_(corr)),and the highest top layer resistance(R_(top))of 2.57×10^(6)Ω·cm^(2),indicating excellent barrier properties.Additionally,the coating achieved complete(100%)degradation of methylene blue(MB)within 30 min under visible light.Density Functional Theory(DFT)calculations provide deeper insights into the bonding mechanisms and interaction stability between PHEN,2-IMD,and the PEO layer on the Mg alloy and MB dye.These findings confirmed the enhanced performance of the hybrid coating in both corrosion resistance and photocatalytic applications.展开更多
In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)pro...In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.展开更多
Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarge...Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.展开更多
Objectives:Although Yes-associated protein 1(YAP1)is an important oncogene in hepatocellular carcinoma(HCC)progression,its nuclear localization prevents it from being considered a potential therapeutic target.Recently...Objectives:Although Yes-associated protein 1(YAP1)is an important oncogene in hepatocellular carcinoma(HCC)progression,its nuclear localization prevents it from being considered a potential therapeutic target.Recently,studies have reported that coatomer protein complex subunit beta 2(COPB2)also plays a critical role in HCC development;however its mechanism of action is unclear.This study aimed to investigate the role of COPB2 and YAP1 in the progression of HCC and to elucidate the underlying mechanisms.Methods:COPB2 and YAP1 expression in HCC tissues were first analyzed by database searches and immunohistochemistry.Nomogram and artificial neural network models were established based on COPB2 and YAP1 expression.Cell proliferation was detected by cell counting kit-8 and clone formation assay,while cell migration and invasion were assessed using Transwell assays.Finally,the potential mechanisms underlying COPB2 regulation of YAP1 nuclear translocation were explored by immunofluorescence assay and Western blot.Results:COPB2 combined with YAP1 expression was associated with overall postoperative survival in HCC patients and was an independent prognostic factor.High expression of both COPB2 and YAP1 in patients may reduce the efficacy of postoperative transarterial chemoembolization therapy.In vitro experiments revealed that COPB2 affected the sensitivity of HCC cells to Cisplatin(DDP)by regulating YAP1 nuclear translocation.Conclusions:Our findings suggest that COPB2/YAP1 affects the drug sensitivity of HCC cells to DDP and that targeting COPB2/YAP1 may be a promising strategy for the precision treatment of HCC.展开更多
Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protei...Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.展开更多
An array of pyridine-ester enolate based organoboron complexes has been designed and synthesized via a one-pot cascade of Pd-catalyzedα-arylation and BF2complexation.The rapid structure-activity relationship(SAR)stud...An array of pyridine-ester enolate based organoboron complexes has been designed and synthesized via a one-pot cascade of Pd-catalyzedα-arylation and BF2complexation.The rapid structure-activity relationship(SAR)studies indicated that unsymmetrical N,O-chelated BF2complexes were highly fluorescent in solid state,and exhibited large Stokes shifts,excellent photostability,along with insensitivity to p H.Theα-aryl group could not only modulate the electronic effect but also inhibit the intermolecularπ-πstacking to promote the aggregation-induced emission(AIE)effect.DFT calculations and experiments identified that the intramolecular charge transfer properties of these N,O-chelates could be switched by the modification of substituents,resulting tunable fluorescence wavelengths.Furthermore,post-complexation modification was accomplished,including Suzuki-Miyaura cross-coupling,Buchwald-Hartwig amination,oxidative cleavage,along with a unique triple substitution reaction involving propargyl Grignard reagents.The exemplificative application of dimethylamine substituted boron complex as a reversible acidic vapor sensor was also demonstrated.展开更多
The article describes ethylene polymerization reactions with transition metal catalysts based on complexes of CoCl_(2) and FeCl_(2) with an N,N,N-tridentate ligand 2,6-bis[1-(2,6-dimethylphenylimino)ethyl]pyridine. Th...The article describes ethylene polymerization reactions with transition metal catalysts based on complexes of CoCl_(2) and FeCl_(2) with an N,N,N-tridentate ligand 2,6-bis[1-(2,6-dimethylphenylimino)ethyl]pyridine. The complexes are converted into polymerization catalysts by reacting them either with polymethylalumoxane (MAO) or with a combination of Al(C2H5)2Cl and Mg(C4H9)2 at an [Al]:[Mg] ratio of ~3. Both MAO-activated complexes readily polymerize ethylene at 35 ℃ with the formation of linear, low molecular weight polymers with a narrow molecular weight distribution. The same complexes, when activated with the Al(C2H5)2Cl-Mg(C4H9)2 combination, form multi-center catalysts and generate polyethylenes with a broad molecular weight distribution.展开更多
BACKGROUND Gastric cancer(GC)is a common type of digestive cancer with high morbidity and mortality rates worldwide.Considerable effort has been expended in understanding the mechanism of GC development and metastasis...BACKGROUND Gastric cancer(GC)is a common type of digestive cancer with high morbidity and mortality rates worldwide.Considerable effort has been expended in understanding the mechanism of GC development and metastasis.The current study therefore explores the involvement of microRNAs in the regulation of GC progression.AIM To explore the expression and function of miR-30e-3p in GC development.METHODS MiR-30e-3p was found to be downregulated in GC,with low levels thereof predicting poor outcomes among patients with GC.Functionally,we revealed that miR-30e-3p suppressed cell growth and metastatic behaviors of GC cells.Bioinformatics analysis predicted that THO complex 2(THOC2)was a direct target of miR-30e-3p,and the interaction between miR-30e-3p and THOC2 was further validated by a luciferase reporter assay.RESULTS Our findings revealed that knockdown of THOC2 inhibited the growth and metastatic behaviors of GC cells.After investigating signaling pathways involved in miR-30e-3p regulation,we found that the miR-30e-3p/THOC2 axis regulated the PI3K/AKT/mTOR pathway in GC.CONCLUSION Our findings suggest the novel functional axis miR-30e-3p/THOC2 is involved in GC development and progression.The miR-30e-3p/THOC2 axis could be utilized to develop new therapies against GC.展开更多
Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcri...Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.展开更多
The first three-dimensional interaction potential energy surface （PES） of the Ar2-Ne complex is developed using the single and double excitation coupled cluster theory with noniterative treatment of triple excitatio...The first three-dimensional interaction potential energy surface （PES） of the Ar2-Ne complex is developed using the single and double excitation coupled cluster theory with noniterative treatment of triple excitations CCSD（T）. The aug-cc-pVQZ basis sets are employed for all atoms, including an additional （3s3p2d2flg） set of midpoint bond functions. The calculated single point energies are fitted to an analytic two-dimensional potential model at each of seven fixed rAr~ values. The seven model potentials are then used to construct the three- dimensional PES by interpolating along （r-re） using a sixth-order polynomial. The PES is used in the following rovibrational energy levels calculations. The comparisons of theoretical transition frequencies and spectroscopic constants with the experimental results are given.展开更多
Polycomb repressive complex 2(PRC2)contributes to catalyze the methylation of histone H3 at lysine 27 and plays vital roles in transcriptional silencing and growth development in various organisms.In Magnaporthe oryza...Polycomb repressive complex 2(PRC2)contributes to catalyze the methylation of histone H3 at lysine 27 and plays vital roles in transcriptional silencing and growth development in various organisms.In Magnaporthe oryzae,histone H3K27 is found to associate with altered transcription of in planta induced genes.However,it is still unknown whether and how H3K27me3 modification is involved in pathogenicity to rice and stress response.In this study,we found that core subunits of PRC2,Kmt6-Suz12-Eed,were required for fungal pathogenicity to rice in M.oryzae.Kmt6-Suz12-Eed localized in the nuclei and was necessary for the establishment of H3K27me3 modification.With ChIP-seq analysis,9.0%of genome regions enriched with H3K27me3 occupancy,which corresponded to 1033 genes in M.oryzae.Furthermore,deletion of Kmt6,Suz12 or Eed altered genome-wide transcriptional expression,while the de-repression genes in theΔkmt6 strain were highly associated with H3K27me3 occupancy.Notably,plenty of genes which encode effectors and secreted enzymes,secondary metabolite synthesis genes,and cell wall stress-responsive genes were directly occupied with H3K27me3 modification and de-repression in theΔkmt6 strain.These results elaborately explained how PRC2 was required for pathogenicity,which is closely related to effector modulated host immunity and host environment adaption.展开更多
A series of Ce1-xFexO2 （x=0, 0.2, 0.4, 0.6, 0.8, 1） complex oxide catalysts were prepared using the coprecipitation method. The catalysts were characterized by means of XRD and H2-TPR. The reactions between methane ...A series of Ce1-xFexO2 （x=0, 0.2, 0.4, 0.6, 0.8, 1） complex oxide catalysts were prepared using the coprecipitation method. The catalysts were characterized by means of XRD and H2-TPR. The reactions between methane and lattice oxygen from the complex oxides were investigated. The characteristic results revealed that the combination of Ce and Fe oxide in the catalysts could lower the temperature necessary to reduce the cerium oxide. The catalytic activity for selective CH4 oxidation was strongly influenced by dropped Fe species. Adding the appropriate amount of Fe2O3 to CeO2 could promote the action between CH4 and CeO2. Dispersed Fe2O3 first returned to the original state and would then virtually form the Fe species on the catalyst, which could be considered as the active site for selective CH4 oxidation. The appearance of carbon formation was significant and the oxidation of carbon appeared to be the rate-determining step; the amounts of surface reducible oxygen species in CeO2 were also relevant to the activity. Among all the catalysts, Ce0.6Fe0.402 exhibited the best activity, which converted 94.52% of CH4 at 900 ℃.展开更多
A new metal-organic coordination polymer [Zn（pzdc）（mbix）]n·nH2O（H2pzdc = pyrazine-2,3- dicarboxylic acid, mbix = 1,3-bis（imidazol-1-ylmethyl）-benzene） 1 has been hydrothermally synthesized and structurall...A new metal-organic coordination polymer [Zn（pzdc）（mbix）]n·nH2O（H2pzdc = pyrazine-2,3- dicarboxylic acid, mbix = 1,3-bis（imidazol-1-ylmethyl）-benzene） 1 has been hydrothermally synthesized and structurally characterized by elemental analysis, IR, TG, fluorescence spectrum and single-crystal X-ray diffraction. Yellow crystals crystallize in monoclinic system, space group P21/n with a = 8.5519（6）, b = 14.8764（10）, c = 16.4108（11） A, β = 103.4520（10）o, V = 2030.5（2）A^3, C（20）H（18）N6O5Zn, Mr = 487.77, Dc = 1.596 g/cm^3, F（000） = 1000, Z = 4, μ（MoK α） = 1.257 mm^-1, the final R = 0.0260 and w R = 0.0706 for 3445 observed reflections（I 〉 2σ（I））. The structure of 1 exhibits a one-dimensional chain-like structure. In addition, natural bond orbital（NBO） analysis was performed by the PBE0/LANL2DZ method in Gaussian 03 Program. The calculation results show obvious covalent interaction between the coordinated atoms and Zn（Ⅱ） ion.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
基金supported by the National Natural Science Foundation of China(32360166,31760321).
文摘Enhancer of zeste homolog 2(EZH2)is a key epigenetic regulatory protein and enzyme catalytic subunit of the polycomb repressor complex 2(PRC2),responsible for catalyzing the trimethylation of histone H3K27 and subsequent repression of gene transcription.Abnormal EZH2 expression or mutation is associated with various cancers,particularly lymphoma,and breast and prostate cancer.EZH2 has been investigated as an important target in cancer therapy and potential EZH2-targeted drugs have been developed.This article reviews the research progress on the mechanism of transcriptional regulation of EZH2 and the development and clinical use of some inhibitors targeting EZH2.
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Two Gd_(2)complexes,namely[Gd_(2)(dbm)_(2)(HL_(1))_(2)(CH_(3)OH)_(2)]·4CH_(3)OH(1)and[Gd_(2)(dbm)_(2)(L_(2))_(2)(CH_(3)OH)_(2)]·2CH_(3)OH(2),where H_(3)L_(1)=(Z)-N'-[4-(diethylamino)-2-hydroxybenzylidene]-2-hydroxyacetohydrazide,H_(2)L_(2)=(E)-N'-(5-bromo-2-hydroxy-3-methoxybenzylidene)nicotinohydrazide,Hdbm=dibenzoylmethane,have been constructed by adopting the solvothermal method.Structural characterization unveils that both complexes 1 and 2 are constituted by two Gd^(3+)ions,two dbm-ions,two CH_(3)OH molecules,and two polydentate Schiff-base ligands(HL_(1)^(2-)or L_(2)^(2-)).In addition,complex 1 contains four free methanol molecules,whereas complex 2 harbors two free methanol molecules.By investigating the interactions between complexes 1 and 2 and four types of bacteria(Bacillus subtilis,Escherichia coli,Staphylococcus aureus,Candida albicans),it was found that both complexes 1 and 2 exhibited potent antibacte-rial activities.The interaction mechanisms between the ligands H_(3)L_(1),H_(2)L_(2),complexes 1 and 2,and calf thymus DNA(CT-DNA)were studied using ultraviolet-visible spectroscopy,fluorescence titration,and cyclic voltammetry.The results demonstrated that both complexes 1 and 2 can intercalate into CT-DNA molecules,thereby inhibiting bacterial proliferation to achieve the antibacterial effects.CCDC:2401116,1;2401117,2.
文摘Binary sequences constructed by Legendre symbols are widely used in communication and cryptography since they have many good pseudo-random properties.In this paper,we determine the 2-adic complexity of the sum sequence of any k many Legendre sequences and show that the 2-adic complexity of the sum sequences of any k many Legendre sequences reaches the maximum by proving the case of k=2 and 3,which implies that the sum sequences can resist the attack of rational approximation algorithm.
基金supported by the National Research Foundation of Korea(NRF)funded by the Korean government(MSIT)(No.2022R1A2C1006743).
文摘This study explores the development of an organic-inorganic hybrid coating to enhance the corrosion resistance and photocatalytic properties of AZ31 Mg alloy modified by plasma electrolytic oxidation(PEO).The PEO process typically generates a porous oxide layer,which can reduce corrosion protection by allowing corrosive agents to penetrate the substrate.To address this limitation,phenopyridine(PHEN)and 2-methylimidazole(2-IMD)were incorporated into the PEO surface to form a robust organic layer on the Mg alloy.Potassium hydroxide(KOH)was used to adjust the pH,improving the interaction and solubility between the organic molecules and the PEO coating.The hybrid coating exhibited unique twig-like surface structures that contributed to forming a multifunctional coating with high corrosion resistance and superior photocatalytic activity.The PEO-PHEN-2IMD sample on the Mg alloy demonstrated exceptional corrosion resistance,with the lowest corrosion current density(I_(corr))of 1.92×10^(-10) A/cm^(2),a high corrosion potential(E_(corr)),and the highest top layer resistance(R_(top))of 2.57×10^(6)Ω·cm^(2),indicating excellent barrier properties.Additionally,the coating achieved complete(100%)degradation of methylene blue(MB)within 30 min under visible light.Density Functional Theory(DFT)calculations provide deeper insights into the bonding mechanisms and interaction stability between PHEN,2-IMD,and the PEO layer on the Mg alloy and MB dye.These findings confirmed the enhanced performance of the hybrid coating in both corrosion resistance and photocatalytic applications.
基金Supported by Italian Association for Cancer Research(AIRC),No.21956Italian Ministry of Health-5×1000 funds 2023.
文摘In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.
文摘Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.
文摘Objectives:Although Yes-associated protein 1(YAP1)is an important oncogene in hepatocellular carcinoma(HCC)progression,its nuclear localization prevents it from being considered a potential therapeutic target.Recently,studies have reported that coatomer protein complex subunit beta 2(COPB2)also plays a critical role in HCC development;however its mechanism of action is unclear.This study aimed to investigate the role of COPB2 and YAP1 in the progression of HCC and to elucidate the underlying mechanisms.Methods:COPB2 and YAP1 expression in HCC tissues were first analyzed by database searches and immunohistochemistry.Nomogram and artificial neural network models were established based on COPB2 and YAP1 expression.Cell proliferation was detected by cell counting kit-8 and clone formation assay,while cell migration and invasion were assessed using Transwell assays.Finally,the potential mechanisms underlying COPB2 regulation of YAP1 nuclear translocation were explored by immunofluorescence assay and Western blot.Results:COPB2 combined with YAP1 expression was associated with overall postoperative survival in HCC patients and was an independent prognostic factor.High expression of both COPB2 and YAP1 in patients may reduce the efficacy of postoperative transarterial chemoembolization therapy.In vitro experiments revealed that COPB2 affected the sensitivity of HCC cells to Cisplatin(DDP)by regulating YAP1 nuclear translocation.Conclusions:Our findings suggest that COPB2/YAP1 affects the drug sensitivity of HCC cells to DDP and that targeting COPB2/YAP1 may be a promising strategy for the precision treatment of HCC.
文摘Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.
基金grateful for the support by the National Natural Science Foundation of China(Nos.21702013,22271010)。
文摘An array of pyridine-ester enolate based organoboron complexes has been designed and synthesized via a one-pot cascade of Pd-catalyzedα-arylation and BF2complexation.The rapid structure-activity relationship(SAR)studies indicated that unsymmetrical N,O-chelated BF2complexes were highly fluorescent in solid state,and exhibited large Stokes shifts,excellent photostability,along with insensitivity to p H.Theα-aryl group could not only modulate the electronic effect but also inhibit the intermolecularπ-πstacking to promote the aggregation-induced emission(AIE)effect.DFT calculations and experiments identified that the intramolecular charge transfer properties of these N,O-chelates could be switched by the modification of substituents,resulting tunable fluorescence wavelengths.Furthermore,post-complexation modification was accomplished,including Suzuki-Miyaura cross-coupling,Buchwald-Hartwig amination,oxidative cleavage,along with a unique triple substitution reaction involving propargyl Grignard reagents.The exemplificative application of dimethylamine substituted boron complex as a reversible acidic vapor sensor was also demonstrated.
基金carried out according to the program of Fundamental Scientific Research of the Russian Federation
文摘The article describes ethylene polymerization reactions with transition metal catalysts based on complexes of CoCl_(2) and FeCl_(2) with an N,N,N-tridentate ligand 2,6-bis[1-(2,6-dimethylphenylimino)ethyl]pyridine. The complexes are converted into polymerization catalysts by reacting them either with polymethylalumoxane (MAO) or with a combination of Al(C2H5)2Cl and Mg(C4H9)2 at an [Al]:[Mg] ratio of ~3. Both MAO-activated complexes readily polymerize ethylene at 35 ℃ with the formation of linear, low molecular weight polymers with a narrow molecular weight distribution. The same complexes, when activated with the Al(C2H5)2Cl-Mg(C4H9)2 combination, form multi-center catalysts and generate polyethylenes with a broad molecular weight distribution.
基金Supported by National Natural Science Foundation of China,No.81860442Ningxia Natural Science Foundation Project,No.2022AAC03525.
文摘BACKGROUND Gastric cancer(GC)is a common type of digestive cancer with high morbidity and mortality rates worldwide.Considerable effort has been expended in understanding the mechanism of GC development and metastasis.The current study therefore explores the involvement of microRNAs in the regulation of GC progression.AIM To explore the expression and function of miR-30e-3p in GC development.METHODS MiR-30e-3p was found to be downregulated in GC,with low levels thereof predicting poor outcomes among patients with GC.Functionally,we revealed that miR-30e-3p suppressed cell growth and metastatic behaviors of GC cells.Bioinformatics analysis predicted that THO complex 2(THOC2)was a direct target of miR-30e-3p,and the interaction between miR-30e-3p and THOC2 was further validated by a luciferase reporter assay.RESULTS Our findings revealed that knockdown of THOC2 inhibited the growth and metastatic behaviors of GC cells.After investigating signaling pathways involved in miR-30e-3p regulation,we found that the miR-30e-3p/THOC2 axis regulated the PI3K/AKT/mTOR pathway in GC.CONCLUSION Our findings suggest the novel functional axis miR-30e-3p/THOC2 is involved in GC development and progression.The miR-30e-3p/THOC2 axis could be utilized to develop new therapies against GC.
文摘Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.
文摘The first three-dimensional interaction potential energy surface （PES） of the Ar2-Ne complex is developed using the single and double excitation coupled cluster theory with noniterative treatment of triple excitations CCSD（T）. The aug-cc-pVQZ basis sets are employed for all atoms, including an additional （3s3p2d2flg） set of midpoint bond functions. The calculated single point energies are fitted to an analytic two-dimensional potential model at each of seven fixed rAr~ values. The seven model potentials are then used to construct the three- dimensional PES by interpolating along （r-re） using a sixth-order polynomial. The PES is used in the following rovibrational energy levels calculations. The comparisons of theoretical transition frequencies and spectroscopic constants with the experimental results are given.
基金the National Natural Science Foundation of China(Grant Nos.32170192 and 32000103)Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding(Grant No.2021C02064)+1 种基金Key Research and Development Project of China National Rice Research Institute(Grant No.CNRRI-2020-04)the Chinese Academy of Agricultural Sciences under the‘Elite Youth’Program and the Agricultural Sciences and Technologies Innovation Program.
文摘Polycomb repressive complex 2(PRC2)contributes to catalyze the methylation of histone H3 at lysine 27 and plays vital roles in transcriptional silencing and growth development in various organisms.In Magnaporthe oryzae,histone H3K27 is found to associate with altered transcription of in planta induced genes.However,it is still unknown whether and how H3K27me3 modification is involved in pathogenicity to rice and stress response.In this study,we found that core subunits of PRC2,Kmt6-Suz12-Eed,were required for fungal pathogenicity to rice in M.oryzae.Kmt6-Suz12-Eed localized in the nuclei and was necessary for the establishment of H3K27me3 modification.With ChIP-seq analysis,9.0%of genome regions enriched with H3K27me3 occupancy,which corresponded to 1033 genes in M.oryzae.Furthermore,deletion of Kmt6,Suz12 or Eed altered genome-wide transcriptional expression,while the de-repression genes in theΔkmt6 strain were highly associated with H3K27me3 occupancy.Notably,plenty of genes which encode effectors and secreted enzymes,secondary metabolite synthesis genes,and cell wall stress-responsive genes were directly occupied with H3K27me3 modification and de-repression in theΔkmt6 strain.These results elaborately explained how PRC2 was required for pathogenicity,which is closely related to effector modulated host immunity and host environment adaption.
基金Supported by the National Natural Science Foundation of China(No.21576112)Natural Science Foundation Project of Jilin Province(No.20130521019JH and 20150623024TC-19)+1 种基金Natural Science Foundation Project of the Education Department of Jilin Province(No.[2014]152)the Science and Technology Development Plan of Siping City(2015049)
文摘Three lanthanide（III） complexes [Ln（4-NCP）（1,4-BDC）]n·xn H2O（Ln = Pr（1）, Sm（2）, Nd（3）. 4-HNCP = 2-（4-carboxyphenyl）imidazo（4,5-f）（1,10）phenanthroline, 1,4-H2 BDC = benzene-1,4-dicarboxylic acid） have been hydrothermally synthesized and characterized via elemental analysis, infrared spectrometry and single-crystal X-ray diffraction. Structural analyses revealed that complexes 1~3 possess similar porous three-dimensional frameworks with the point symbol {4^（12）·6~3}. Meanwhile, complexes 1~3 exhibit excellent thermal stabilities and complex 2 exhibits characteristic luminescent property.
基金the National Natural Science Foundation of China (50574046)National Natural Science Foundation of Major Research Projects (90610035)+1 种基金Natural Science Foundation of Yunnan Province (2004E0058Q)High School Doctoral Subject Special Science and Re- search Foundation of Ministry of Education (20040674005)
文摘A series of Ce1-xFexO2 （x=0, 0.2, 0.4, 0.6, 0.8, 1） complex oxide catalysts were prepared using the coprecipitation method. The catalysts were characterized by means of XRD and H2-TPR. The reactions between methane and lattice oxygen from the complex oxides were investigated. The characteristic results revealed that the combination of Ce and Fe oxide in the catalysts could lower the temperature necessary to reduce the cerium oxide. The catalytic activity for selective CH4 oxidation was strongly influenced by dropped Fe species. Adding the appropriate amount of Fe2O3 to CeO2 could promote the action between CH4 and CeO2. Dispersed Fe2O3 first returned to the original state and would then virtually form the Fe species on the catalyst, which could be considered as the active site for selective CH4 oxidation. The appearance of carbon formation was significant and the oxidation of carbon appeared to be the rate-determining step; the amounts of surface reducible oxygen species in CeO2 were also relevant to the activity. Among all the catalysts, Ce0.6Fe0.402 exhibited the best activity, which converted 94.52% of CH4 at 900 ℃.
基金supported by the Science and Technology Development Project of Jilin Provincial Science&Technology Department(201205080)the Science and Technology Research Projects of the Education Office of Jilin Province(No.2013.384)
文摘A new metal-organic coordination polymer [Zn（pzdc）（mbix）]n·nH2O（H2pzdc = pyrazine-2,3- dicarboxylic acid, mbix = 1,3-bis（imidazol-1-ylmethyl）-benzene） 1 has been hydrothermally synthesized and structurally characterized by elemental analysis, IR, TG, fluorescence spectrum and single-crystal X-ray diffraction. Yellow crystals crystallize in monoclinic system, space group P21/n with a = 8.5519（6）, b = 14.8764（10）, c = 16.4108（11） A, β = 103.4520（10）o, V = 2030.5（2）A^3, C（20）H（18）N6O5Zn, Mr = 487.77, Dc = 1.596 g/cm^3, F（000） = 1000, Z = 4, μ（MoK α） = 1.257 mm^-1, the final R = 0.0260 and w R = 0.0706 for 3445 observed reflections（I 〉 2σ（I））. The structure of 1 exhibits a one-dimensional chain-like structure. In addition, natural bond orbital（NBO） analysis was performed by the PBE0/LANL2DZ method in Gaussian 03 Program. The calculation results show obvious covalent interaction between the coordinated atoms and Zn（Ⅱ） ion.
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.
