An accurate target source position is sometimes useful for the pointing observation with the collimated telescopes of the Hard X-ray Modulation Telescope(Insight-HXMT),which is determined by the reliability of the ins...An accurate target source position is sometimes useful for the pointing observation with the collimated telescopes of the Hard X-ray Modulation Telescope(Insight-HXMT),which is determined by the reliability of the instrumental response.Insight-HXMT has the unique design that all three main payloads(LE,ME and HE)consist of detector groups with three fields of views(FOVs)whose orientations differ by 60°.As the point-spread functions are different at different positions in the FOV coordinates,the count rate ratios between the detector groups depend on the position of an X-ray source in the FOVs.Based on the multi-FOV design,we develop a localization method for an X-ray source in the pointing observation of Insight-HXMT.The accuracy of the method is investigated with the pointing observations of the Crab with different exposures.We find that the statistical error decreases with the exposure,and the systematic error is dominant for the exposure>128 s.With the exposure of1024 s,the total error is 0°.015 for the Crab.This method can effectively distinguish the Rapid Burster H 1730–333and Slow Burster GX 354–0,which are only 0°.5 apart and can both contribute to bursts in the light curve obtained by Insight-HXMT.We also apply the pointing observation localization method to locate the X-ray counterpart of FRB 200428 with high precision.The located position is consistent with SGR J1935+2154 within 1σuncertainty of 10′,which provides important evidence that fast radio bursts can originate from magnetars.展开更多
O6-methylguanine DNA methyltransferase(MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cell...O6-methylguanine DNA methyltransferase(MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells(GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide(TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line(SF-767) and 7 MGMT-negative cell lines(U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB(NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines(P < 0.05). However, there was no significant difference in the 50% inhibition concentration(IC50) of TMZ between MGMT-positive and MGMT-negative GSCs(P > 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132(an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone(P < 0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.展开更多
Angioimmunoblastic T-cell lymphoma(AITL) is a rare,distinct subtype of peripheral T-cell lymphoma,possessing an aggressive course and poor prognosis with no standard therapy.Twelve patients who have failed at least tw...Angioimmunoblastic T-cell lymphoma(AITL) is a rare,distinct subtype of peripheral T-cell lymphoma,possessing an aggressive course and poor prognosis with no standard therapy.Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine(CsA),prednisone(PDN),and monthly,high-dose intravenous immunoglobulin(HDIVIG).The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function.All patients were examined for response,toxicity and survival.The most significant toxicities(≥ grade 2) were infection(16.7%),renal insufficiency(8.3%),hypertension(8.3%),diabetes(8.3%) and insomnia(16.7%).Discontinuation of treatment occurred in one patient(8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection.Treatment-related death was not observed.The overall response rate was 75.0%(complete response,33.3%;partial response,41.7%).With a median follow-up of 25.5 months,the median duration of response was 20 months(range,12 to 49 months) and the median progression-free survival(PFS) was 25.5 months(range,10 to 56 months).The 2-year PFS rate was 81.5%.Our findings indicate the combination of CsA,PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.展开更多
We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be class...We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be classified roughly into four different states.Type-C quasi-periodic oscillations(QPOs)observed by NICER(about 0.1-6 Hz)and Insight-HXMT(about 0.7-8 Hz)are also reported in this work.Meanwhile,we study various physical quantities related to QPO frequency.The QPO rms-frequency relationship in the energy band 1-10 keV indicates that there is a turning pointing in frequency around2 Hz,which is similar to that of GRS 1915+105.A possible hypothesis for the relationship above may be related to the inclination of the source,which may require a high inclination to explain it.The relationships between QPO frequency and QPO rms,hardness,total fractional rms and count rate have also been found in other transient sources,which can indicate that the origin of type-C QPOs is non-thermal.展开更多
基金a project funded by China National Space Administration(CNSA)the Chinese Academy of Sciences(CAS)+3 种基金supports from the National Key R&D Program of China(2021YFA0718500)the National Natural Science Foundation of China under Grant Nos.U1838202,U1838201,U2038102,and U1838113the Youth Innovation Promotion Association of the CAS(Grant No.2018014)partially supported by International Partnership Program of Chinese Academy of Sciences(Grant No.113111KYSB20190020)。
文摘An accurate target source position is sometimes useful for the pointing observation with the collimated telescopes of the Hard X-ray Modulation Telescope(Insight-HXMT),which is determined by the reliability of the instrumental response.Insight-HXMT has the unique design that all three main payloads(LE,ME and HE)consist of detector groups with three fields of views(FOVs)whose orientations differ by 60°.As the point-spread functions are different at different positions in the FOV coordinates,the count rate ratios between the detector groups depend on the position of an X-ray source in the FOVs.Based on the multi-FOV design,we develop a localization method for an X-ray source in the pointing observation of Insight-HXMT.The accuracy of the method is investigated with the pointing observations of the Crab with different exposures.We find that the statistical error decreases with the exposure,and the systematic error is dominant for the exposure>128 s.With the exposure of1024 s,the total error is 0°.015 for the Crab.This method can effectively distinguish the Rapid Burster H 1730–333and Slow Burster GX 354–0,which are only 0°.5 apart and can both contribute to bursts in the light curve obtained by Insight-HXMT.We also apply the pointing observation localization method to locate the X-ray counterpart of FRB 200428 with high precision.The located position is consistent with SGR J1935+2154 within 1σuncertainty of 10′,which provides important evidence that fast radio bursts can originate from magnetars.
基金supported by the National Natural Science Foundation of China(No.30772551)the Science &Technology Program of Guangdong Province(No.2011B031800178)+1 种基金National High-technology Research and Development Program of China(No.2012AA02A508)Specialized Research Fund for the Doctoral Program of Higher Education(No.20110171110076)
文摘O6-methylguanine DNA methyltransferase(MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells(GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide(TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line(SF-767) and 7 MGMT-negative cell lines(U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB(NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines(P < 0.05). However, there was no significant difference in the 50% inhibition concentration(IC50) of TMZ between MGMT-positive and MGMT-negative GSCs(P > 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132(an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone(P < 0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.
文摘Angioimmunoblastic T-cell lymphoma(AITL) is a rare,distinct subtype of peripheral T-cell lymphoma,possessing an aggressive course and poor prognosis with no standard therapy.Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine(CsA),prednisone(PDN),and monthly,high-dose intravenous immunoglobulin(HDIVIG).The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function.All patients were examined for response,toxicity and survival.The most significant toxicities(≥ grade 2) were infection(16.7%),renal insufficiency(8.3%),hypertension(8.3%),diabetes(8.3%) and insomnia(16.7%).Discontinuation of treatment occurred in one patient(8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection.Treatment-related death was not observed.The overall response rate was 75.0%(complete response,33.3%;partial response,41.7%).With a median follow-up of 25.5 months,the median duration of response was 20 months(range,12 to 49 months) and the median progression-free survival(PFS) was 25.5 months(range,10 to 56 months).The 2-year PFS rate was 81.5%.Our findings indicate the combination of CsA,PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.
基金the HXMT mission,a project funded by China National Space Administration(CNSA)and the Chinese Academy of Sciences(CAS)supported by the National Key R&D Program of China(2016YFA0400800)the National Natural Science Foundation of China(Grant Nos.11673023,U1838201,U1838115,U1838111,U1838202,11733009 and U1838108)。
文摘We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be classified roughly into four different states.Type-C quasi-periodic oscillations(QPOs)observed by NICER(about 0.1-6 Hz)and Insight-HXMT(about 0.7-8 Hz)are also reported in this work.Meanwhile,we study various physical quantities related to QPO frequency.The QPO rms-frequency relationship in the energy band 1-10 keV indicates that there is a turning pointing in frequency around2 Hz,which is similar to that of GRS 1915+105.A possible hypothesis for the relationship above may be related to the inclination of the source,which may require a high inclination to explain it.The relationships between QPO frequency and QPO rms,hardness,total fractional rms and count rate have also been found in other transient sources,which can indicate that the origin of type-C QPOs is non-thermal.