The milling stability of thin-walled components is an important issue in the aviation manufacturing industry, which greatly limits the removal rate of a workpiece. However, for a thin-walled workpiece, the dynamic cha...The milling stability of thin-walled components is an important issue in the aviation manufacturing industry, which greatly limits the removal rate of a workpiece. However, for a thin-walled workpiece, the dynamic characteristics vary at different positions. In addition, the removed part also has influence on determining the modal parameters of the workpiece. Thus,the milling stability is also time-variant. In this work, in order to investigate the time variation of a workpiece＇s dynamic characteristics, a new computational model is firstly derived by dividing the workpiece into a removed part and a remaining part with the Ritz method. Then, an updated frequency response function is obtained by Lagrange＇s equation and the corresponding modal parameters are extracted. Finally, multi-mode stability lobes are plotted by the different quadrature method and its accuracy is verified by experiments. The proposed method improves the computational efficiency to predict the time-varying characteristics of a thin-walled workpiece.展开更多
The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB str...The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB strip for GAPDH to demonstrate that this was an unintentional error in image selection.Additionally,we noticed that the Transwell images in the two upper panels of the right column in Figure 4J are misleading due to errors in image selection.We have attached the original data to show that this was also an unintentional error.We assure you that these two corrections do not alter the scientificconclusionof thearticle.展开更多
Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to treatment.Fibroblast growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,incl...Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to treatment.Fibroblast growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,including proliferation,survival,migration,and dif-ferentiation.FGFR1 was predominantly expressed in GBM tissues,and FGFR1 expression was negatively correlated with overall survival.We rationally designed a novel small molecule CYY292,which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro.CYY292 also exerted an effect on the conserved Ser777 residue of FGFR1.CYY292 dose-depen-dently inhibited cell proliferation,epithelial-mesenchymal transition,stemness,invasion,and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells,and this effect was prevented by pharmacological inhibitors and critical gene knockdown.In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547.CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models.This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292,which targets FGFR1,on downstream signaling pathways directly reducing GBM cell growth,invasion,and metastasis and thus impairing the recruitment,activation,and function of immune cells.展开更多
Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely o...Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs.Here,we hypothesize that the cholinergic antiinflammatory pathway(CAP),which is recognized as a neuroimmunological pathway,may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS.Using lipopolysaccharide(LPS)and bacterial lung inflammation models,we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase(ChAT)and vesicular acetylcholine transporter(VAChT)in lung tissue were significantly increased 6 hours after MSC infusion.When the vagus nerve was blocked orα7 nicotinic acetylcholine(ACh)receptor(α7nAChR)-knockout mice were used,the therapeutic effects of MSCs were significantly reduced,suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment.Our results further showed that MSC-derived prostaglandin E2(PGE2)likely promoted ACh synthesis and release.Additionally,based on the efficacy of nAChR andα7nAChR agonists,we found that lobeline,the nicotinic cholinergic receptor excitation stimulant,may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study(ChiCTR2100047403).In summary,we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome,providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.展开更多
Brine shrimp(Artemia)has existed on Earth for 400 million years and has major ecological importance in hypersaline ecosystems.As a crucial live food in aquaculture,brine shrimp cysts have become one of the most import...Brine shrimp(Artemia)has existed on Earth for 400 million years and has major ecological importance in hypersaline ecosystems.As a crucial live food in aquaculture,brine shrimp cysts have become one of the most important aquatic products traded worldwide.However,our understanding of the biodiversity,prevalence and global connectedness of viruses in brine shrimp is still very limited.A total of 143 batches of brine shrimp(belonging to seven species)cysts were collected from six continents including 21 countries and more than 100 geographic locations worldwide during 1977–2019.In total,55 novel RNA viruses were identified,which could be assigned to 18 different viral families and related clades.Eleven viruses were dsRNA viruses,16 were+ssRNA viruses,and 28 were−ssRNA viruses.Phylogenetic analyses of the RNA-directed RNA polymerase(RdRp)showed that brine shrimp viruses were often grouped with viruses isolated from other invertebrates and fungi.Remarkably,most brine shrimp viruses were related to those from different hosts that might feed on brine shrimp or share the same ecological niche.A notable case was the novel brine shrimp noda-like virus 3,which shared 79.25%(RdRp)and 63.88%(capsid proteins)amino acid identity with covert mortality nodavirus(CMNV)that may cause losses in aquaculture.In addition,both virome composition and phylogenetic analyses revealed global connectedness in certain brine shrimp viruses,particularly among Asia and Northern America.This highlights the incredible species diversity of viruses in these ancient species and provides essential data for the prevalence of RNA viruses in the global aquaculture industry.More broadly,these findings provide novel insights into the previously unrecognized RNA virosphere in hypersaline ecosystems worldwide and demonstrate that human activity might have driven the global connectedness of brine shrimp viruses.展开更多
基金co-supported by the National Natural Science Foundation of China (No.51575319)the Young Scholars Program of Shandong University (No. 2015WLJH31)+1 种基金the Major National Science and Technology Project (No. 2014ZX04012-014)the Tai Shan Scholar Foundation (No. TS20130922)
文摘The milling stability of thin-walled components is an important issue in the aviation manufacturing industry, which greatly limits the removal rate of a workpiece. However, for a thin-walled workpiece, the dynamic characteristics vary at different positions. In addition, the removed part also has influence on determining the modal parameters of the workpiece. Thus,the milling stability is also time-variant. In this work, in order to investigate the time variation of a workpiece＇s dynamic characteristics, a new computational model is firstly derived by dividing the workpiece into a removed part and a remaining part with the Ritz method. Then, an updated frequency response function is obtained by Lagrange＇s equation and the corresponding modal parameters are extracted. Finally, multi-mode stability lobes are plotted by the different quadrature method and its accuracy is verified by experiments. The proposed method improves the computational efficiency to predict the time-varying characteristics of a thin-walled workpiece.
文摘The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB strip for GAPDH to demonstrate that this was an unintentional error in image selection.Additionally,we noticed that the Transwell images in the two upper panels of the right column in Figure 4J are misleading due to errors in image selection.We have attached the original data to show that this was also an unintentional error.We assure you that these two corrections do not alter the scientificconclusionof thearticle.
基金supported by the National Natural Science Foundation of China(No.81971180,81973168 and 82003793)CAMS Innovation Fund for Medical Sciences(No.2019-12M-5-028)+1 种基金the Scientific Research Project of Wenzhou,Zhejiang,China(No.ZY2019001)the National Natural Science Foundation of Zhejiang Province,China(No.LZ22H300002).
文摘Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to treatment.Fibroblast growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,including proliferation,survival,migration,and dif-ferentiation.FGFR1 was predominantly expressed in GBM tissues,and FGFR1 expression was negatively correlated with overall survival.We rationally designed a novel small molecule CYY292,which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro.CYY292 also exerted an effect on the conserved Ser777 residue of FGFR1.CYY292 dose-depen-dently inhibited cell proliferation,epithelial-mesenchymal transition,stemness,invasion,and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells,and this effect was prevented by pharmacological inhibitors and critical gene knockdown.In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547.CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models.This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292,which targets FGFR1,on downstream signaling pathways directly reducing GBM cell growth,invasion,and metastasis and thus impairing the recruitment,activation,and function of immune cells.
基金supported by the National Key Research and Development Program of China,Stem Cell and Translational Research(2018YFA0107200,2019YFA0110303,2021YFA1100600)National Natural Science Foundation of China(81730005,32130046,81900075,81970109,82170540,81721003)+2 种基金Natural Science Foundation of Guangdong Province(2018A0303130305,2021A1515011759,2022A1515012452,2022A1515011919)Key Research and Development Program of Guangdong Province(2019B020236002)Key Scientific and Technological Program of Guangzhou City(201803040011),and Pearl River S&T Nova Program of Guangzhou(201906010095).
文摘Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs.Here,we hypothesize that the cholinergic antiinflammatory pathway(CAP),which is recognized as a neuroimmunological pathway,may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS.Using lipopolysaccharide(LPS)and bacterial lung inflammation models,we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase(ChAT)and vesicular acetylcholine transporter(VAChT)in lung tissue were significantly increased 6 hours after MSC infusion.When the vagus nerve was blocked orα7 nicotinic acetylcholine(ACh)receptor(α7nAChR)-knockout mice were used,the therapeutic effects of MSCs were significantly reduced,suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment.Our results further showed that MSC-derived prostaglandin E2(PGE2)likely promoted ACh synthesis and release.Additionally,based on the efficacy of nAChR andα7nAChR agonists,we found that lobeline,the nicotinic cholinergic receptor excitation stimulant,may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study(ChiCTR2100047403).In summary,we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome,providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.
基金This work was supported by the National Key Research and Development Program of China(2018YFD0900501)Central Public-interest Scientific Institution Basal Research Fund,YSFRI,CAFS(20603022022005)+6 种基金Shinan District Science and Technology Foundation(Qingdao)(2022-2-027-ZH)Central Public-interest Scientific Institution Basal Research Fund,CAFS(2020TD39)China Agriculture Research System(CARS-48)C.L.was supported by the Youth Innovation Team of Shandong Higher Education Institution(2021KJ064)the National Natural Science Foundation of China(32200004)W.S.was supported by the Academic Promotion Programme of Shandong First Medical University(2019QL006)E.C.H.was funded by a National Medical Health and Research Council(Australia)Investigator Grant(GNT2017197).
文摘Brine shrimp(Artemia)has existed on Earth for 400 million years and has major ecological importance in hypersaline ecosystems.As a crucial live food in aquaculture,brine shrimp cysts have become one of the most important aquatic products traded worldwide.However,our understanding of the biodiversity,prevalence and global connectedness of viruses in brine shrimp is still very limited.A total of 143 batches of brine shrimp(belonging to seven species)cysts were collected from six continents including 21 countries and more than 100 geographic locations worldwide during 1977–2019.In total,55 novel RNA viruses were identified,which could be assigned to 18 different viral families and related clades.Eleven viruses were dsRNA viruses,16 were+ssRNA viruses,and 28 were−ssRNA viruses.Phylogenetic analyses of the RNA-directed RNA polymerase(RdRp)showed that brine shrimp viruses were often grouped with viruses isolated from other invertebrates and fungi.Remarkably,most brine shrimp viruses were related to those from different hosts that might feed on brine shrimp or share the same ecological niche.A notable case was the novel brine shrimp noda-like virus 3,which shared 79.25%(RdRp)and 63.88%(capsid proteins)amino acid identity with covert mortality nodavirus(CMNV)that may cause losses in aquaculture.In addition,both virome composition and phylogenetic analyses revealed global connectedness in certain brine shrimp viruses,particularly among Asia and Northern America.This highlights the incredible species diversity of viruses in these ancient species and provides essential data for the prevalence of RNA viruses in the global aquaculture industry.More broadly,these findings provide novel insights into the previously unrecognized RNA virosphere in hypersaline ecosystems worldwide and demonstrate that human activity might have driven the global connectedness of brine shrimp viruses.
