Caldecrin was originally isolated from the pancreas as afactor that reduced serum calcium levels. This secreted serine protease has chymotrypsin-like activity and is also known as chymotrypsin C; it belongs to the ela...Caldecrin was originally isolated from the pancreas as afactor that reduced serum calcium levels. This secreted serine protease has chymotrypsin-like activity and is also known as chymotrypsin C; it belongs to the elastase family. Although intravenous administration of caldecrin decreases the serum calcium concentration even when its protease activity is blocked,this effect does require cleavage of caldecrin's pro-peptide by trypsin,converting it to the mature enzyme. Ectopic intramuscular expression of caldecrin prevented bone resorption in ovariectomized mice. Caldecrin inhibited parathyroid hormone-stimulated calcium release from fetal mouse long bone organ cultures. Furthermore,caldecrin suppressed the formation of osteoclasts from bone marrow cells by inhibiting the receptor activator of nuclear factor-k B ligand(RANKL)-stimulated phospholipase Cγ-calcium oscillation-calcineurinnuclear factor of activated T-cells,cytoplasmic 1 pathway. Caldecrin also suppressed the bone resorption activity of mature osteoclasts by preventing RANKL-stimulated Src activation,calcium entry,and actin ring formation. In vivo and in vitro studies have indicated that caldecrin is a unique multifunctional protease with anti-osteoclastogenic activities that are distinct from its protease activity. Caldecrin might be a potential therapeutic target for the treatment of osteolytic diseases such as osteoporosis and osteoarthritis. This mini-review describes caldecrin's historical background and its mechanisms of action.展开更多
The resonant optical Kerr effect in the Langmuir-Blodegett film of 2,9,16,23-tetra heptadecylamido substituted vanadyl phthalocyanine was measured with femtosecond laser pulses to determine the relaxation time,and mea...The resonant optical Kerr effect in the Langmuir-Blodegett film of 2,9,16,23-tetra heptadecylamido substituted vanadyl phthalocyanine was measured with femtosecond laser pulses to determine the relaxation time,and meanwhile slow decay components were observed.The ultrafast nonlinearity of the molecule was also measured.展开更多
The mechanism of 2,9,16,23-tetra-heptadecylamido substituted vanadyl phthalocyanine Langmuir-Blodegett film was studied with femtosecond laser pulses.An ultrafast decay due to phonon-exciton coupling greatly affected ...The mechanism of 2,9,16,23-tetra-heptadecylamido substituted vanadyl phthalocyanine Langmuir-Blodegett film was studied with femtosecond laser pulses.An ultrafast decay due to phonon-exciton coupling greatly affected by temperature,and exciton-exciton annihilation leading to the recovery of the ground state(T~lops)and an even slower relaxation were observed.展开更多
The modal back-scattering matrix can be extracted from reverberation data. For high frequency cases the ’window smoothed’ processing has been proposed by E. C. Shang, T. F. Gao and D. J. Tang (2002) to extract the ...The modal back-scattering matrix can be extracted from reverberation data. For high frequency cases the ’window smoothed’ processing has been proposed by E. C. Shang, T. F. Gao and D. J. Tang (2002) to extract the ’window averaged’ back-scattering matrix. It is pointed out in this paper that in order to inverse the ’window averaged’ back-scattering matrix by changing the source depth data we have to assume that the matrix is not related to the source depth, and the numerical simulation on the question has been conducted.展开更多
A theoretical study of poly furfuryle alcohol (PFA), rhodamine B (Rh B) dye and their blends (PFA-Rh B) is carried out by using the density functional theory (DFT). Electronic states and opto-electronic properties are...A theoretical study of poly furfuryle alcohol (PFA), rhodamine B (Rh B) dye and their blends (PFA-Rh B) is carried out by using the density functional theory (DFT). Electronic states and opto-electronic properties are investigated. The electronic states indicate that the oligomers of FA are insulators and Rh B is a wide band gap semiconductor. Their blends have a narrow band gap of about 0.75 eV. The optoelectronic properties are studied using TDDFT, which indicates that the chain length of poly furfuryl alcohol is an effective parameter to control both energies and intensities of absorption in which longer chain causes absorption with high intensity within long wavelength. A single broad baned of electron excitations is more like 8-oligomer-RhB case, which centers at wavelengths about 599 nm and 625 nm. This band of absorption covers the whole visible region of spectrum.展开更多
Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied wi...Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.展开更多
文摘Caldecrin was originally isolated from the pancreas as afactor that reduced serum calcium levels. This secreted serine protease has chymotrypsin-like activity and is also known as chymotrypsin C; it belongs to the elastase family. Although intravenous administration of caldecrin decreases the serum calcium concentration even when its protease activity is blocked,this effect does require cleavage of caldecrin's pro-peptide by trypsin,converting it to the mature enzyme. Ectopic intramuscular expression of caldecrin prevented bone resorption in ovariectomized mice. Caldecrin inhibited parathyroid hormone-stimulated calcium release from fetal mouse long bone organ cultures. Furthermore,caldecrin suppressed the formation of osteoclasts from bone marrow cells by inhibiting the receptor activator of nuclear factor-k B ligand(RANKL)-stimulated phospholipase Cγ-calcium oscillation-calcineurinnuclear factor of activated T-cells,cytoplasmic 1 pathway. Caldecrin also suppressed the bone resorption activity of mature osteoclasts by preventing RANKL-stimulated Src activation,calcium entry,and actin ring formation. In vivo and in vitro studies have indicated that caldecrin is a unique multifunctional protease with anti-osteoclastogenic activities that are distinct from its protease activity. Caldecrin might be a potential therapeutic target for the treatment of osteolytic diseases such as osteoporosis and osteoarthritis. This mini-review describes caldecrin's historical background and its mechanisms of action.
基金Supported by the National Natural Science Foundation of China.
文摘The resonant optical Kerr effect in the Langmuir-Blodegett film of 2,9,16,23-tetra heptadecylamido substituted vanadyl phthalocyanine was measured with femtosecond laser pulses to determine the relaxation time,and meanwhile slow decay components were observed.The ultrafast nonlinearity of the molecule was also measured.
基金the National Natural Science Foundation of China.
文摘The mechanism of 2,9,16,23-tetra-heptadecylamido substituted vanadyl phthalocyanine Langmuir-Blodegett film was studied with femtosecond laser pulses.An ultrafast decay due to phonon-exciton coupling greatly affected by temperature,and exciton-exciton annihilation leading to the recovery of the ground state(T~lops)and an even slower relaxation were observed.
文摘The modal back-scattering matrix can be extracted from reverberation data. For high frequency cases the ’window smoothed’ processing has been proposed by E. C. Shang, T. F. Gao and D. J. Tang (2002) to extract the ’window averaged’ back-scattering matrix. It is pointed out in this paper that in order to inverse the ’window averaged’ back-scattering matrix by changing the source depth data we have to assume that the matrix is not related to the source depth, and the numerical simulation on the question has been conducted.
文摘A theoretical study of poly furfuryle alcohol (PFA), rhodamine B (Rh B) dye and their blends (PFA-Rh B) is carried out by using the density functional theory (DFT). Electronic states and opto-electronic properties are investigated. The electronic states indicate that the oligomers of FA are insulators and Rh B is a wide band gap semiconductor. Their blends have a narrow band gap of about 0.75 eV. The optoelectronic properties are studied using TDDFT, which indicates that the chain length of poly furfuryl alcohol is an effective parameter to control both energies and intensities of absorption in which longer chain causes absorption with high intensity within long wavelength. A single broad baned of electron excitations is more like 8-oligomer-RhB case, which centers at wavelengths about 599 nm and 625 nm. This band of absorption covers the whole visible region of spectrum.
基金supported by The Brain Tumour Charity(grant number GN-000707)supported by DKTK JF Upgrade Next Gen LOGGIC(B310-JF-LOGGIC-MDE)supported by the DFG through a Heisenberg professorship(BR 3662/5-1)and SFB-1479 Oncoescape-Project ID:441891347(P14)。
文摘Pilocytic astrocytomas(PA),the most common pediatric low-grade gliomas(pLGGs),are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence(OIS)accompanied with the senescence-associated secretory phenotype(SASP).This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach.We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib.Multi-omics factor analysis(MEFISTO)and single sample gene set enrichment analysis(ssGSEA)were employed to identify key OIS effectors and differentially regulated pathways upon MAPK inhibition.Trametinib treatment inhibited MAPK activity,OIS and SASP signatures across all omics levels,functionally underscored by reduced sensitivity towards senolytic drugs.We constructed a pathway network using a prior knowledge approach,mapping n=106 upregulated and n=84 downregulated direct downstream effectors of MAPK leading to OIS/SASP.These effectors are associated with better progression-free survival in pLGG patients,independent of tumor site,level of resection,and genetic aberration.Several compounds targeting signaling nodes(SOD-1,IRS1,CDK1/2,CK2)involved in OIS and under MAPK control were identified,of which n=4 were validated in an additional primary KIAA1549::BRAF fusion pLGG model as potential new therapeutic vulnerabilities for the treatment of pLGG.Our unbiased multiomics signaling pathway analysis identifies a specific and comprehensive network of MAPK-OIS-SASP interdependencies in pLGGs and suggests new therapeutic strategies for these tumors.
