BACKGROUND RPF2 is a crucial factor in ribosome synthesis,which has been linked to the development of several cancers.However,the mechanism of RPF2 in gastric carcinogenesis is unclear.AIM To explore the role and mech...BACKGROUND RPF2 is a crucial factor in ribosome synthesis,which has been linked to the development of several cancers.However,the mechanism of RPF2 in gastric carcinogenesis is unclear.AIM To explore the role and mechanism of RPF2 in the pathogenesis of Helicobacter pylori(H.pylori)infection.METHODS GES-1 was co-cultured with H.pylori in vitro to detect changes in the expression of RPF2.Overexpression and silencing of RPF2 were performed.Quantitative realtime polymerase chain reaction(q-PCR)and Western blot(WB)were used to determine mRNA and protein expression of RPF2,protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and epithelial-mesenchymal transitionrelated factors MMP2 and MMP9;cell counting kit 8 and wound healing assays were utilized to evaluate cell viability and migratory capacity;q-PCR,WB,and immunohistochemistry were employed to establish RPF2 expression in cancer tissues.RESULTS H.pylori facilitated RPF2 expression and triggered AKT/mTOR signaling pathway.Functional experiments showed that RPF2 overexpression could promote a series of malignant transformations such as cell proliferation,cell migration and invasion,and further enhance AKT/mTOR signaling pathway activation.RPF2 knockdown had the opposite effect.In addition,RPF2 expression was higher in gastric cancer tissues than in adjacent tissues.CONCLUSION RPF2 plays a significant role in the pathogenic mechanism of H.pylori infection and may be useful in the detection and management of gastric cancer caused by H.pylori infection.展开更多
BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of canc...BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.展开更多
Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechan...Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.Th...The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.展开更多
Mammaliaforms are extinct and extant organisms that are closely related to mammals.Studying mammaliaforms helps scientists understand the evolutionary processes that led to various mammalian features.In two consecutiv...Mammaliaforms are extinct and extant organisms that are closely related to mammals.Studying mammaliaforms helps scientists understand the evolutionary processes that led to various mammalian features.In two consecutive studies in Nature,Dr.MAO Fangyuan and Dr.ZHANG Chi from the Institute of Vertebrate Paleontology and Paleoanthropology(IVPP)of the Chinese Academy of Sciences(CAS),together with colleagues from Australia and the United States.展开更多
The retroviral vector （RCAS） has been widely used in avian system to study development and diseases, but is not suitable for mammals which do not produce the retrovirus receptor TVA. In this review, we trace the cur...The retroviral vector （RCAS） has been widely used in avian system to study development and diseases, but is not suitable for mammals which do not produce the retrovirus receptor TVA. In this review, we trace the current uses of RCAS-TVA approach in mammalian system with improved strategies, including generation of tv-a transgenic mice, use of soluble TVA receptor and retroviral receptor-ligand fusion proteins, improvement of RCAS vectors, and compare a series of mammalian models in variant studies of gene function, development, oncogenesis and gene therapy. All those studies demonstrate that the RCAS-TVA based mammalian models are powerful tools for understanding the mechanisms and target treating of human diseases.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
Inflammatory bowel diseases(IBDs),with blurred etiology,show a rising trend and are of global concern.Of various factors involved in IBD pathogenesis and development,inflammation has been shown to play a major role.Re...Inflammatory bowel diseases(IBDs),with blurred etiology,show a rising trend and are of global concern.Of various factors involved in IBD pathogenesis and development,inflammation has been shown to play a major role.Recognition of the molecular and cellular pathways that induce IBD is an emerging subject to develop targeted therapies.Mammalian target of rapamycin(mTOR)is one the most common receptors of many inflammatory pathways,including that of IBD.To this end,we intend to overview the mTOR inhibitors for their possible efficacy in present and future approaches to treatment of IBD.展开更多
In the Linxia Basin on the northeast margin of the Tibetan Plateau, the Cenozoic strata are very thick and well exposed. Abundant mammalian fossils are discovered in the deposits from the Late Oligocene to the Early P...In the Linxia Basin on the northeast margin of the Tibetan Plateau, the Cenozoic strata are very thick and well exposed. Abundant mammalian fossils are discovered in the deposits from the Late Oligocene to the Early Pleistocene. The Dzungariotherium fauna comes from the sandstones of the Jiaozigou Formation, including many representative Late Oligocene taxa. The Platybelodon fauna comes from the sandstones of the Dongxiang Formation and the conglomerates of the Laogou Formation, and its fossils are typical Middle Miocene forms, such as Hemicyon, Amphicyon, Platybelodon, Choerolophodon, Anchitherium, and Hispanotherium. The Hipparion fauna comes from the red clay of the Liushu and Hewangjia Formations, and its fossils can be distinctly divided into four levels, including three Late Miocene levels and one Early Pliocene level. In the Linxia Basin, the Hipparion fauna has the richest mammalian fossils. The Equus fauna comes from the Wucheng Loess, and it is slightly older than that of the classical Early Pleistocene Nihewan Fauna. The mammalian faunas from the Linxia Basin provide the reliable evidence to divide the Cenozoic strata of this basin and correlate them with European mammalian sequence.展开更多
Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear loc...Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence(NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza viruses.However, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.展开更多
AIM：To elucidate the effect of rapamycin on regulating the production of interleukin（IL）-1β in Aspergillus fumigatus（A.fumigatus）-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus k...AIM：To elucidate the effect of rapamycin on regulating the production of interleukin（IL）-1β in Aspergillus fumigatus（A.fumigatus）-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus keratitis is associated with the mammalian target of rapamycin（mT OR）/Toll-like receptor 4（TLR4） signaling pathway.METHODS：Fungal keratitis mouse models of susceptible C57 BL/6 mice were established using A.fumigatus.The mice were subsequently treated with rapamycin.The protein levels of p-mT OR,TLR4,and IL-1β in normal and infected corneal tissue were measured by Western blot.The TLR4 and IL-1β m RNA levels were determined by real-time polymerase chain reaction（PCR）.RESULTS：In C57 BL/6 mice,rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine,IL-1β.The expression of TLR4,stimulated by A.fumigatus,was reduced as well when the mT OR signaling pathway was suppressed by rapamycin.CONCLUSION：Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β.The inhibitory effect on IL-1β expression can be associated with the mT OR/TLR4 signaling pathway in A.fumigatus infection in mice.展开更多
Baculovirus can transduce a wide range of mammalian cells and is considered a promising gene therapy vector. However,the low transduction efficiency of baculovirus into many mammalian cells limits its practical applic...Baculovirus can transduce a wide range of mammalian cells and is considered a promising gene therapy vector. However,the low transduction efficiency of baculovirus into many mammalian cells limits its practical application. Co-expressing heterologous viral glycoproteins(GPs), such as vesicular stomatitis virus G protein(VSV G), with baculovirus native envelope protein GP64 is one of the feasible strategies for improving virus transduction. Tick-borne thogotoviruses infect mammals and their GPs share sequence/structure homology and common evolutionary origins with baculovirus GP64.Herein, we tested whether thogotovirus GPs could facilitate the entry of the prototype baculovirus Autographa californica multiple multiple nucleopolyhedrovirus(AcMNPV) into mammalian cells. The gp genes of two thogotoviruses, Thogoto virus and Dhori virus, were inserted into the AcMNPV genome. Both GPs were properly expressed and incorporated into the envelope of the recombinant AcMNPVs. The transduction rates of recombinant AcMNPVs expressing the two thogotovirus GPs increased for approximately 4–12 fold compared to the wild type AcMNPV in six of the 12 tested mammalian cell lines. It seemed that thogotovirus GPs provide the recombinant AcMNPVs with different cell tropisms and showed better performance in several mammalian cells compared to VSV G incorporated AcMNPV. Further studies showed that the improved transduction was a result of augmented virus-endosome fusion and endosome escaping, rather than increased cell binding or internalization. We found the AcMNPV envelope protein GP64-mediated fusion was enhanced by the thogotovirus GPs at relatively higher p H conditions. Therefore, the thogotovirus GPs represent novel candidates to improve baculovirus-based gene delivery vectors.展开更多
Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is ...Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.展开更多
From 1985 to 1987, four new localities with abundant fossil mammals were dis-covered by Cao, Tian and others in the Zhoukoudian (Choukoutien) area, Beijing. They are theEast, West, Shangdian and Donglingzi caves. The ...From 1985 to 1987, four new localities with abundant fossil mammals were dis-covered by Cao, Tian and others in the Zhoukoudian (Choukoutien) area, Beijing. They are theEast, West, Shangdian and Donglingzi caves. The East Cave fauna consists of 28 speices ofmammals and its age is middle Early Pleistocene. The East Cave assemblage shows that a tem-perature-falling event took place at around 1.20 Ma B.P. at Zhoukoudian. Sixteen species ofmammals were collected from the West Cave, which are mainly forms of late Early Pleistoceneage. The West Cave fauna represents a transitional fauna from the East Cave fauna (dry-cold)to the fauna (warm) at locality 9. The Shangdian Cave fauna is composed of four forms, beingMiddle Pleistocene in age. The Donglingzi Cave fauna contains 21 Late Pleistocene forms. Inthe cave two fossil horizons may be distinguished. The age of the lower horizon is early LatePleistocene, which is equivalent to that of the New Cave fauna; while the fauna of the upper ho-rizon may be correlated with the Upper Cave fauna.展开更多
This paper describes Mammalian fossils of 18 species discovered at Donghuangzhuang,about 15 km from NE of Qufu county,Shandong Province.The materials were collected bya farmer in 1984 and were sent to The Shandong Pro...This paper describes Mammalian fossils of 18 species discovered at Donghuangzhuang,about 15 km from NE of Qufu county,Shandong Province.The materials were collected bya farmer in 1984 and were sent to The Shandong Provincial Museum for studing.A short fieldinvestigation was made by Wang Jinwen,Sha Yesue(BGMRSD),Han Qingwen(SDM)andthe present author in same year.The age of the fauna is tentatively considered as the late Late Eocene,probably correlatedas the Heti Fauna(Yuanqu Basin).It represents the first occurrence of Late Eocene fossils inthis province.展开更多
The mammalian target of rapamycin （mTOR） pathway plays an important role in neuronal growth, proliferation and differentiation. To better understand the role of mTOR pathway involved in the induction of spinal cord ...The mammalian target of rapamycin （mTOR） pathway plays an important role in neuronal growth, proliferation and differentiation. To better understand the role of mTOR pathway involved in the induction of spinal cord injury, rat models of spinal cord injury were established by modified Allen＇s stall method and interfered for 7 days by intraperitoneal administration of mTOR activator adenosine triphosphate and mTOR kinase inhibitor rapamycin. At 1-4 weeks after spinal cord injury induction, the Basso, Beattie and Bresnahan locomotor rating scale was used to evaluate rat locomotor function, and immunohistochemical staining and western blot analysis were used to detect the expression of nestin （neural stem cell marker）, neuronal nuclei （neuronal marker）, neuron specific enolase, neurofilament protein 200 （axonal marker）, glial fibrillary acidic protein （astrocyte marker）, Akt, mTOR and signal transduction and activator of transcription 3 （STAT3）. Results showed that adenosine triphosphate-mediated Akt/mTOR/STAT3 pathway increased endogenous neural stem cells, induced neurogenesis and axonal growth, inhibited excessive astrogliosis and improved the locomotor function of rats with spinal cord injury.展开更多
Deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reporte...Deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reported as altered in neuroendocrine tumors(NETs). m TOR inhibitors used in clinical practice are derived from rapamycin,an anti-cancer agent also used as an immunosuppressor after organ transplantation. Everolimus and temsirolimus are the two rapamycin-derived m TOR inhibitors used in NETs. Notably everolimus has been approved in advanced progressive well/moderatelydifferentiated pancreatic NETs(p NETs). It inhibits specifically the m TORC1 subunit of m TOR,not interacting with m TORC2. Although everolimus produced a significant prolongation of progression-free survival a number of patients with p NETs do not benefit from the drug due to early or late progression. Two supposed mechanisms of resistance to m TOR inhibitors are Akt and PI3 K activation,by means of m TORC2 and insulin growth factor(IGF)- IGF receptor signaling,respectively. BEZ235 is a multi-targeted inhibitor binding to PI3 K,m TORC1 and m TORC2,therefore potentially turning off all the supposed molecular targets of resistance to everolimus. The two clinical trials designed in p NETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was also halted. Tolerability of this drug was challenging and conditioned the feasibility of therapy. The BEZ experience is an example of the huge difference between the preclinical and clinical setting and prompts us to pay more attention to the phase Ⅰ step of clinical development and the design of phase Ⅱ clinical trials.展开更多
The obesity epidemic imposes a significant health burden on human beings.Current understanding of the mechanisms underlying the development of obesity is incomplete and contemporary treatment is often ineffective.Gast...The obesity epidemic imposes a significant health burden on human beings.Current understanding of the mechanisms underlying the development of obesity is incomplete and contemporary treatment is often ineffective.Gastrointestinal hormones are important regulators of food intake and energy metabolism.Previous studies indicate that the mammalian target of rapamycin signaling pathway in the gastric mucosa is crucially involved in fuel sensing in the gastrointestinal tract and plays a critical role in the coordination of nutrient availability and ingestive behavior via the production of gastric hormones.As an important component of the brain-gut axis regulating food intake and energy homeostasis,energy sensing in the gastrointestinal tract may provide a novel insight into our understanding of the precise coordination between the organism and cel-lular energy state.展开更多
BACKGROUND Mammalian target of rapamycin(mTOR)inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma(HCC).However,their role in established post-tra...BACKGROUND Mammalian target of rapamycin(mTOR)inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma(HCC).However,their role in established post-transplant HCC recurrence is uncertain.AIM To investigate whether mTOR inhibitor offers a survival benefit in posttransplant HCC recurrence.METHODS A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed.They were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression.The primary endpoint was post-recurrence survival.RESULTS Seventy-nine(55%)patients received an mTOR inhibitor-based immunosuppressive regime,while 64(45%)patients did not.The mTOR inhibitor group had a lower number of recurrent tumours(2 vs 5,P=0.02)and received more active treatments including radiotherapy(39 vs 22%,P=0.03)and targeted therapy(59 vs 23%,P<0.001).The median post-recurrence survival was 21.0±4.1 mo in the mTOR inhibitor group and 11.2±2.5 mo in the control group.Multivariate Cox regression analysis confirmed that mTOR inhibitor therapy was independently associated with improved post-recurrence survival(P=0.04,OR=0.482,95%CI:0.241-0.966).The number of recurrent tumours and use of other treatment modalities did not affect survival.No survival difference was observed between mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor.CONCLUSION mTOR inhibitors prolonged survival after post-transplant HCC recurrence.展开更多
Spermatogenesis is a complex differentiating developmental process in which undifferentiated spermatogonial germ cells differentiate into spermatocytes,spermatids,and finally,to mature spermatozoa.This multistage deve...Spermatogenesis is a complex differentiating developmental process in which undifferentiated spermatogonial germ cells differentiate into spermatocytes,spermatids,and finally,to mature spermatozoa.This multistage developmental process of spermatogenesis involves the expression of many male germ cell-specific long noncoding RNAs(lncRNAs)and highly regulated and specific gene expression.LncRNAs are a recently discovered large class of noncoding cellular transcripts that are still relatively unexplored.Only a few of them have postmeiotic;however,lncRNAs are involved in many cellular biological processes.The expression of lncRNAs is biologically relevant in the highly dynamic and complex program of spermatogenesis and has become a research focus in recent genome studies.This review considers the important roles and novel regulatory functions whereby lncRNAs modulate mammalian spermatogenesis.展开更多
基金Supported by the National Natural Science Foundation of China,No.82160634.
文摘BACKGROUND RPF2 is a crucial factor in ribosome synthesis,which has been linked to the development of several cancers.However,the mechanism of RPF2 in gastric carcinogenesis is unclear.AIM To explore the role and mechanism of RPF2 in the pathogenesis of Helicobacter pylori(H.pylori)infection.METHODS GES-1 was co-cultured with H.pylori in vitro to detect changes in the expression of RPF2.Overexpression and silencing of RPF2 were performed.Quantitative realtime polymerase chain reaction(q-PCR)and Western blot(WB)were used to determine mRNA and protein expression of RPF2,protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and epithelial-mesenchymal transitionrelated factors MMP2 and MMP9;cell counting kit 8 and wound healing assays were utilized to evaluate cell viability and migratory capacity;q-PCR,WB,and immunohistochemistry were employed to establish RPF2 expression in cancer tissues.RESULTS H.pylori facilitated RPF2 expression and triggered AKT/mTOR signaling pathway.Functional experiments showed that RPF2 overexpression could promote a series of malignant transformations such as cell proliferation,cell migration and invasion,and further enhance AKT/mTOR signaling pathway activation.RPF2 knockdown had the opposite effect.In addition,RPF2 expression was higher in gastric cancer tissues than in adjacent tissues.CONCLUSION RPF2 plays a significant role in the pathogenic mechanism of H.pylori infection and may be useful in the detection and management of gastric cancer caused by H.pylori infection.
基金Supported by National Natural Science Foundation of China,No.82360329Inner Mongolia Medical University General Project,No.YKD2023MS047Inner Mongolia Health Commission Science and Technology Plan Project,No.202201275.
文摘BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.
基金supported by the tenth batch of"3221"industrial innovation and scientific research projects in Bengbu City(beng talent[2020]No.8)the 2021 Bengbu Medical College Science and Technology Project[Natural Science,Project Number:2021byzd217].
文摘Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.
基金supported by the National Key R&D Program of China (2021YFC2300900,2021YFC2301300)Academic Promotion Programme of Shandong First Medical University (2019QL006)+2 种基金Natural Science Foundation of Shandong Province (ZR2020QH274)Yunnan Key Research and Development Program (202103AQ100001,202102AA310055)Key Program of Chinese Academy of Sciences (KJZD-SW-L11)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.
文摘Mammaliaforms are extinct and extant organisms that are closely related to mammals.Studying mammaliaforms helps scientists understand the evolutionary processes that led to various mammalian features.In two consecutive studies in Nature,Dr.MAO Fangyuan and Dr.ZHANG Chi from the Institute of Vertebrate Paleontology and Paleoanthropology(IVPP)of the Chinese Academy of Sciences(CAS),together with colleagues from Australia and the United States.
文摘The retroviral vector （RCAS） has been widely used in avian system to study development and diseases, but is not suitable for mammals which do not produce the retrovirus receptor TVA. In this review, we trace the current uses of RCAS-TVA approach in mammalian system with improved strategies, including generation of tv-a transgenic mice, use of soluble TVA receptor and retroviral receptor-ligand fusion proteins, improvement of RCAS vectors, and compare a series of mammalian models in variant studies of gene function, development, oncogenesis and gene therapy. All those studies demonstrate that the RCAS-TVA based mammalian models are powerful tools for understanding the mechanisms and target treating of human diseases.
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Inflammatory bowel diseases(IBDs),with blurred etiology,show a rising trend and are of global concern.Of various factors involved in IBD pathogenesis and development,inflammation has been shown to play a major role.Recognition of the molecular and cellular pathways that induce IBD is an emerging subject to develop targeted therapies.Mammalian target of rapamycin(mTOR)is one the most common receptors of many inflammatory pathways,including that of IBD.To this end,we intend to overview the mTOR inhibitors for their possible efficacy in present and future approaches to treatment of IBD.
基金the National Natural Science Foundation of China(No.40232023)Chinese Academy of Sciences(No.KZCX2-103,RJZ2001-105)Ministry of Science and Technology of China(No.G2000077700).
文摘In the Linxia Basin on the northeast margin of the Tibetan Plateau, the Cenozoic strata are very thick and well exposed. Abundant mammalian fossils are discovered in the deposits from the Late Oligocene to the Early Pleistocene. The Dzungariotherium fauna comes from the sandstones of the Jiaozigou Formation, including many representative Late Oligocene taxa. The Platybelodon fauna comes from the sandstones of the Dongxiang Formation and the conglomerates of the Laogou Formation, and its fossils are typical Middle Miocene forms, such as Hemicyon, Amphicyon, Platybelodon, Choerolophodon, Anchitherium, and Hispanotherium. The Hipparion fauna comes from the red clay of the Liushu and Hewangjia Formations, and its fossils can be distinctly divided into four levels, including three Late Miocene levels and one Early Pliocene level. In the Linxia Basin, the Hipparion fauna has the richest mammalian fossils. The Equus fauna comes from the Wucheng Loess, and it is slightly older than that of the classical Early Pleistocene Nihewan Fauna. The mammalian faunas from the Linxia Basin provide the reliable evidence to divide the Cenozoic strata of this basin and correlate them with European mammalian sequence.
基金supported by the Science Research Project of the Guangdong Province (Grant no. 2016A050503047)Health and Medical Research Fund (Grant No. 12111832)+1 种基金Guangzhou Medical University High Level University Construction Project FundingResearch Grants Council of the Hong Kong Special Administrative Region, China, through the Theme Based Research Scheme (Ref: T11-705/14N)
文摘Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence(NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza viruses.However, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.
基金Supported by the National Natural Science Foundation of China(No.81470609No.81500695)
文摘AIM：To elucidate the effect of rapamycin on regulating the production of interleukin（IL）-1β in Aspergillus fumigatus（A.fumigatus）-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus keratitis is associated with the mammalian target of rapamycin（mT OR）/Toll-like receptor 4（TLR4） signaling pathway.METHODS：Fungal keratitis mouse models of susceptible C57 BL/6 mice were established using A.fumigatus.The mice were subsequently treated with rapamycin.The protein levels of p-mT OR,TLR4,and IL-1β in normal and infected corneal tissue were measured by Western blot.The TLR4 and IL-1β m RNA levels were determined by real-time polymerase chain reaction（PCR）.RESULTS：In C57 BL/6 mice,rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine,IL-1β.The expression of TLR4,stimulated by A.fumigatus,was reduced as well when the mT OR signaling pathway was suppressed by rapamycin.CONCLUSION：Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β.The inhibitory effect on IL-1β expression can be associated with the mT OR/TLR4 signaling pathway in A.fumigatus infection in mice.
基金supported by the grants from the National Natural Science Foundation of China (Grant Nos. 31370191 and 31621061)Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB11030400)the National Key R&D Program of China (Grant No. 2018YFA0507200)
文摘Baculovirus can transduce a wide range of mammalian cells and is considered a promising gene therapy vector. However,the low transduction efficiency of baculovirus into many mammalian cells limits its practical application. Co-expressing heterologous viral glycoproteins(GPs), such as vesicular stomatitis virus G protein(VSV G), with baculovirus native envelope protein GP64 is one of the feasible strategies for improving virus transduction. Tick-borne thogotoviruses infect mammals and their GPs share sequence/structure homology and common evolutionary origins with baculovirus GP64.Herein, we tested whether thogotovirus GPs could facilitate the entry of the prototype baculovirus Autographa californica multiple multiple nucleopolyhedrovirus(AcMNPV) into mammalian cells. The gp genes of two thogotoviruses, Thogoto virus and Dhori virus, were inserted into the AcMNPV genome. Both GPs were properly expressed and incorporated into the envelope of the recombinant AcMNPVs. The transduction rates of recombinant AcMNPVs expressing the two thogotovirus GPs increased for approximately 4–12 fold compared to the wild type AcMNPV in six of the 12 tested mammalian cell lines. It seemed that thogotovirus GPs provide the recombinant AcMNPVs with different cell tropisms and showed better performance in several mammalian cells compared to VSV G incorporated AcMNPV. Further studies showed that the improved transduction was a result of augmented virus-endosome fusion and endosome escaping, rather than increased cell binding or internalization. We found the AcMNPV envelope protein GP64-mediated fusion was enhanced by the thogotovirus GPs at relatively higher p H conditions. Therefore, the thogotovirus GPs represent novel candidates to improve baculovirus-based gene delivery vectors.
文摘Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.
基金This study was a contribution to the 30th IGC Project 96-30-16 supported by the State Planning Commission and the Beijing Bureau of Geology and Mineral Resources.Yuan Lingsheng,Li Chang'an,Li Longyin,Chen Lianfang,Chi Zhenqing and Zhang Xujiao also took
文摘From 1985 to 1987, four new localities with abundant fossil mammals were dis-covered by Cao, Tian and others in the Zhoukoudian (Choukoutien) area, Beijing. They are theEast, West, Shangdian and Donglingzi caves. The East Cave fauna consists of 28 speices ofmammals and its age is middle Early Pleistocene. The East Cave assemblage shows that a tem-perature-falling event took place at around 1.20 Ma B.P. at Zhoukoudian. Sixteen species ofmammals were collected from the West Cave, which are mainly forms of late Early Pleistoceneage. The West Cave fauna represents a transitional fauna from the East Cave fauna (dry-cold)to the fauna (warm) at locality 9. The Shangdian Cave fauna is composed of four forms, beingMiddle Pleistocene in age. The Donglingzi Cave fauna contains 21 Late Pleistocene forms. Inthe cave two fossil horizons may be distinguished. The age of the lower horizon is early LatePleistocene, which is equivalent to that of the New Cave fauna; while the fauna of the upper ho-rizon may be correlated with the Upper Cave fauna.
文摘This paper describes Mammalian fossils of 18 species discovered at Donghuangzhuang,about 15 km from NE of Qufu county,Shandong Province.The materials were collected bya farmer in 1984 and were sent to The Shandong Provincial Museum for studing.A short fieldinvestigation was made by Wang Jinwen,Sha Yesue(BGMRSD),Han Qingwen(SDM)andthe present author in same year.The age of the fauna is tentatively considered as the late Late Eocene,probably correlatedas the Heti Fauna(Yuanqu Basin).It represents the first occurrence of Late Eocene fossils inthis province.
文摘The mammalian target of rapamycin （mTOR） pathway plays an important role in neuronal growth, proliferation and differentiation. To better understand the role of mTOR pathway involved in the induction of spinal cord injury, rat models of spinal cord injury were established by modified Allen＇s stall method and interfered for 7 days by intraperitoneal administration of mTOR activator adenosine triphosphate and mTOR kinase inhibitor rapamycin. At 1-4 weeks after spinal cord injury induction, the Basso, Beattie and Bresnahan locomotor rating scale was used to evaluate rat locomotor function, and immunohistochemical staining and western blot analysis were used to detect the expression of nestin （neural stem cell marker）, neuronal nuclei （neuronal marker）, neuron specific enolase, neurofilament protein 200 （axonal marker）, glial fibrillary acidic protein （astrocyte marker）, Akt, mTOR and signal transduction and activator of transcription 3 （STAT3）. Results showed that adenosine triphosphate-mediated Akt/mTOR/STAT3 pathway increased endogenous neural stem cells, induced neurogenesis and axonal growth, inhibited excessive astrogliosis and improved the locomotor function of rats with spinal cord injury.
文摘Deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reported as altered in neuroendocrine tumors(NETs). m TOR inhibitors used in clinical practice are derived from rapamycin,an anti-cancer agent also used as an immunosuppressor after organ transplantation. Everolimus and temsirolimus are the two rapamycin-derived m TOR inhibitors used in NETs. Notably everolimus has been approved in advanced progressive well/moderatelydifferentiated pancreatic NETs(p NETs). It inhibits specifically the m TORC1 subunit of m TOR,not interacting with m TORC2. Although everolimus produced a significant prolongation of progression-free survival a number of patients with p NETs do not benefit from the drug due to early or late progression. Two supposed mechanisms of resistance to m TOR inhibitors are Akt and PI3 K activation,by means of m TORC2 and insulin growth factor(IGF)- IGF receptor signaling,respectively. BEZ235 is a multi-targeted inhibitor binding to PI3 K,m TORC1 and m TORC2,therefore potentially turning off all the supposed molecular targets of resistance to everolimus. The two clinical trials designed in p NETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was also halted. Tolerability of this drug was challenging and conditioned the feasibility of therapy. The BEZ experience is an example of the huge difference between the preclinical and clinical setting and prompts us to pay more attention to the phase Ⅰ step of clinical development and the design of phase Ⅱ clinical trials.
基金Supported by Grants from the National Natural Science Foundation of China,No.30971434,30871194,30971085 and 81030012Program for New Century Excellent Talents in University,Beijing Natural Science Foundation,No.7112080
文摘The obesity epidemic imposes a significant health burden on human beings.Current understanding of the mechanisms underlying the development of obesity is incomplete and contemporary treatment is often ineffective.Gastrointestinal hormones are important regulators of food intake and energy metabolism.Previous studies indicate that the mammalian target of rapamycin signaling pathway in the gastric mucosa is crucially involved in fuel sensing in the gastrointestinal tract and plays a critical role in the coordination of nutrient availability and ingestive behavior via the production of gastric hormones.As an important component of the brain-gut axis regulating food intake and energy homeostasis,energy sensing in the gastrointestinal tract may provide a novel insight into our understanding of the precise coordination between the organism and cel-lular energy state.
文摘BACKGROUND Mammalian target of rapamycin(mTOR)inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma(HCC).However,their role in established post-transplant HCC recurrence is uncertain.AIM To investigate whether mTOR inhibitor offers a survival benefit in posttransplant HCC recurrence.METHODS A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed.They were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression.The primary endpoint was post-recurrence survival.RESULTS Seventy-nine(55%)patients received an mTOR inhibitor-based immunosuppressive regime,while 64(45%)patients did not.The mTOR inhibitor group had a lower number of recurrent tumours(2 vs 5,P=0.02)and received more active treatments including radiotherapy(39 vs 22%,P=0.03)and targeted therapy(59 vs 23%,P<0.001).The median post-recurrence survival was 21.0±4.1 mo in the mTOR inhibitor group and 11.2±2.5 mo in the control group.Multivariate Cox regression analysis confirmed that mTOR inhibitor therapy was independently associated with improved post-recurrence survival(P=0.04,OR=0.482,95%CI:0.241-0.966).The number of recurrent tumours and use of other treatment modalities did not affect survival.No survival difference was observed between mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor.CONCLUSION mTOR inhibitors prolonged survival after post-transplant HCC recurrence.
基金supported by the National Natural Science Foundation of China(3187131067)the Agricultural Science and Technology Innovation Program(ASTIP-2016-IAS-06 and CAAS-XTCX2016010)the China Agriculture Research System(CARS-36).
文摘Spermatogenesis is a complex differentiating developmental process in which undifferentiated spermatogonial germ cells differentiate into spermatocytes,spermatids,and finally,to mature spermatozoa.This multistage developmental process of spermatogenesis involves the expression of many male germ cell-specific long noncoding RNAs(lncRNAs)and highly regulated and specific gene expression.LncRNAs are a recently discovered large class of noncoding cellular transcripts that are still relatively unexplored.Only a few of them have postmeiotic;however,lncRNAs are involved in many cellular biological processes.The expression of lncRNAs is biologically relevant in the highly dynamic and complex program of spermatogenesis and has become a research focus in recent genome studies.This review considers the important roles and novel regulatory functions whereby lncRNAs modulate mammalian spermatogenesis.
