The Shc adaptor protein, particularly its p52 isoform, has been identified as a primary signaling partner for the tyrosine(s)-phosphorylated cytoplasmic tails of activated β3 integrins. Inspired by our recent structu...The Shc adaptor protein, particularly its p52 isoform, has been identified as a primary signaling partner for the tyrosine(s)-phosphorylated cytoplasmic tails of activated β3 integrins. Inspired by our recent structure of the Shc PTB domain in complex with a bi-phosphorylated peptide derived from β3 cytoplasmic tail, we have initiated the investigation of Shc interaction with phospholipids of the membrane. We are particularly focused on PtdIns and their effects on Shc mediated integrin signaling in vitro. Here we present thermodynamic profiles and molecular details of the interactions between Shc, integrin, and PtdIns, all of which have been studied by ITC and solution NMR methods. A model of p52 Shc interaction with phosphorylated β3 integrin cytoplasmic tail at the cytosolic face of the plasma membrane is proposed based on these data.展开更多
Gain based predistorter (PD) is a highly effective and simple digital baseband predistorter which compensates for the nonlinear distortion of PAs. Lookup table (LUT) is the core of the gain based PD. This paper presen...Gain based predistorter (PD) is a highly effective and simple digital baseband predistorter which compensates for the nonlinear distortion of PAs. Lookup table (LUT) is the core of the gain based PD. This paper presents a discrete Newton’s method based adaptive technique to modify LUT. We simplify and convert the hardship of adaptive updating LUT to the roots finding problem for a system of two element real equations on athematics. And we deduce discrete Newton’s method based adaptive iterative formula used for updating LUT. The iterative formula of the proposed method is in real number field, but secant method previously published is in complex number field. So the proposed method reduces the number of real multiplications and is implemented with ease by hardware. Furthermore, computer simulation results verify gain based PD using discrete Newton’s method could rectify nonlinear distortion and improve system performance. Also, the simulation results reveal the proposed method reaches to the stable statement in fewer iteration times and less runtime than secant method.展开更多
Background:Rhodiola rosea L.(R.rosea),a traditional Chinese medicinal herb,has gained global attention for its diverse pharmacological activities,especially its anti-tumor effect.While studies have confirmed that R.ro...Background:Rhodiola rosea L.(R.rosea),a traditional Chinese medicinal herb,has gained global attention for its diverse pharmacological activities,especially its anti-tumor effect.While studies have confirmed that R.rosea can hinder the growth of multiple cancer cells,the underlying mechanisms of R.rosea in breast cancer remain elusive.Objective:To investigate the anti-breast cancer efficacy and potential mechanism of R.rosea.Methods:UPLC-Q/TOF MS was utilized to examine the components of R.rosea.Eight-week-old MMTV-PyMT mice were used to assess the potential impact of R.rosea in breast cancer development.Flow cytometry was performed to evaluate the effectiveness of immune cells in mediating the anti-tumor effects of R.rosea.Additionally,the xCELLigence system aided in examining the proliferation of breast cancer cells after treatment with R.rosea.Furthermore,RNA-seq,RT-qPCR and Western blot were employed to elucidate the underlying mechanism of R.rosea in breast cancer.Lastly,network pharmacology was applied to delve deeper into the primary chemically active components responsible for the pharmacological effects of R.rosea.Results:R.rosea exhibits a substantial effect in curtailing the progression of breast cancer,accomplished by repressing the proliferation of tumor cells and reconfiguring the tumor microenvironment(TME).Mechanistically,R.rosea exerts its anti-tumor effects by downregulating the expression of HIF-1α,TGF-β,and Smad3 in tumor cells,thereby alleviating the hypoxic TME and enhancing immune surveillance.Conclusion:Our study revealed that R.rosea suppressed the development of breast cancer by inhibiting the hy-poxic immune microenvironment mediated by the activation of HIF-1α/TGF-β/Smad signaling pathway in tumor cells.These findings,which underscore R.rosea potential as a potent antineoplastic agent,offer a compelling basis for its use as an adjuvant therapy in the treatment of breast cancer.展开更多
Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys...Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys Macaca mulatta(M.mulatta)and Macaca fascicularis(M.fascicularis)and New World monkey Callithrix jacchus(C.jacchus).Infected M.mulatta and M.fascicularis showed abnormal chest radiographs,an increased body temperature and a decreased body weight.Viral genomes were detected in swab and blood samples from all animals.Viral load was detected in the pulmonary tissues of M.mulatta and M.fascicularis but not C.jacchus.Furthermore,among the three animal species,M.mulatta showed the strongest response to SARS-CoV-2,including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues.Collectively,these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M.mulatta as the most suitable for modeling COVID-19.展开更多
文摘The Shc adaptor protein, particularly its p52 isoform, has been identified as a primary signaling partner for the tyrosine(s)-phosphorylated cytoplasmic tails of activated β3 integrins. Inspired by our recent structure of the Shc PTB domain in complex with a bi-phosphorylated peptide derived from β3 cytoplasmic tail, we have initiated the investigation of Shc interaction with phospholipids of the membrane. We are particularly focused on PtdIns and their effects on Shc mediated integrin signaling in vitro. Here we present thermodynamic profiles and molecular details of the interactions between Shc, integrin, and PtdIns, all of which have been studied by ITC and solution NMR methods. A model of p52 Shc interaction with phosphorylated β3 integrin cytoplasmic tail at the cytosolic face of the plasma membrane is proposed based on these data.
文摘Gain based predistorter (PD) is a highly effective and simple digital baseband predistorter which compensates for the nonlinear distortion of PAs. Lookup table (LUT) is the core of the gain based PD. This paper presents a discrete Newton’s method based adaptive technique to modify LUT. We simplify and convert the hardship of adaptive updating LUT to the roots finding problem for a system of two element real equations on athematics. And we deduce discrete Newton’s method based adaptive iterative formula used for updating LUT. The iterative formula of the proposed method is in real number field, but secant method previously published is in complex number field. So the proposed method reduces the number of real multiplications and is implemented with ease by hardware. Furthermore, computer simulation results verify gain based PD using discrete Newton’s method could rectify nonlinear distortion and improve system performance. Also, the simulation results reveal the proposed method reaches to the stable statement in fewer iteration times and less runtime than secant method.
基金sponsored by the National Natural Science Foun-dation of China(Grant 82274175 and 82474168 to Q.Y.S.,Grant 82174026 to H.Y.F.,Grant 82404915 to L.J.)the Natural Science Foun-dation of Zhejiang Province(Grant LY22H280012 to H.Y.F..,Grant Y23H280029 to X.L.)+1 种基金Zhejiang Provincial Administration of Traditional Chinese Medicine Co-construction Key Project(Grant GZY-ZJ-KJ-23069 to Q.Y.S.)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents.
文摘Background:Rhodiola rosea L.(R.rosea),a traditional Chinese medicinal herb,has gained global attention for its diverse pharmacological activities,especially its anti-tumor effect.While studies have confirmed that R.rosea can hinder the growth of multiple cancer cells,the underlying mechanisms of R.rosea in breast cancer remain elusive.Objective:To investigate the anti-breast cancer efficacy and potential mechanism of R.rosea.Methods:UPLC-Q/TOF MS was utilized to examine the components of R.rosea.Eight-week-old MMTV-PyMT mice were used to assess the potential impact of R.rosea in breast cancer development.Flow cytometry was performed to evaluate the effectiveness of immune cells in mediating the anti-tumor effects of R.rosea.Additionally,the xCELLigence system aided in examining the proliferation of breast cancer cells after treatment with R.rosea.Furthermore,RNA-seq,RT-qPCR and Western blot were employed to elucidate the underlying mechanism of R.rosea in breast cancer.Lastly,network pharmacology was applied to delve deeper into the primary chemically active components responsible for the pharmacological effects of R.rosea.Results:R.rosea exhibits a substantial effect in curtailing the progression of breast cancer,accomplished by repressing the proliferation of tumor cells and reconfiguring the tumor microenvironment(TME).Mechanistically,R.rosea exerts its anti-tumor effects by downregulating the expression of HIF-1α,TGF-β,and Smad3 in tumor cells,thereby alleviating the hypoxic TME and enhancing immune surveillance.Conclusion:Our study revealed that R.rosea suppressed the development of breast cancer by inhibiting the hy-poxic immune microenvironment mediated by the activation of HIF-1α/TGF-β/Smad signaling pathway in tumor cells.These findings,which underscore R.rosea potential as a potent antineoplastic agent,offer a compelling basis for its use as an adjuvant therapy in the treatment of breast cancer.
基金supported by the National Research and Development Project of China(2020YFC0841100,2020YFC0846400,and 2020YFA0707600)CAMS Innovation Fund for Medical Sciences(2016-I2M-2-006 and 2020-I2M-CoV19-012)+1 种基金the Talents Project of Yunnan Province(2017HB068)the Special Funds for High-level Health and Family Planning Technical Personnel training of Yunnan Province(D-201653).
文摘Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys Macaca mulatta(M.mulatta)and Macaca fascicularis(M.fascicularis)and New World monkey Callithrix jacchus(C.jacchus).Infected M.mulatta and M.fascicularis showed abnormal chest radiographs,an increased body temperature and a decreased body weight.Viral genomes were detected in swab and blood samples from all animals.Viral load was detected in the pulmonary tissues of M.mulatta and M.fascicularis but not C.jacchus.Furthermore,among the three animal species,M.mulatta showed the strongest response to SARS-CoV-2,including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues.Collectively,these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M.mulatta as the most suitable for modeling COVID-19.
