Philadelphia chromosome (Ph)/BCR‐ABL‐positive (ph+) ALL is the most common genetic abnormality associated with ALL and has been shown to confer the worst prognosis to both children and adults. ...Increasing evidence has revealed that the dysregulation of prolyl isomerase Pin 1 contributes to multicancer development and progression, including ALL, although the underlying molecular mechanisms remain unclear. Here, we report that the expression of Pin 1 was enhanced in ph+ ALL patient samples and was associated positively with the expression of BCR‐ABL. Genetically or pharmacologically inhibiting Pin 1 expression or activity produces potent therapeutic efficacy against ph+ ALL. We further demonstrated that BCR‐ABL enhances the prolyl isomerase activity of Pin 1 by decreasing the phosphorylated level of Pin 1 at Ser 71 and interacting with DAPK1. The inhibition of BCR‐ABL activity by imatinib in human ph+ ALL cells reduces the prolyl isomerase activity of Pin 1, further suggesting a key role of the newly identified BCR‐ABL‐Pin 1 axis in ph+ ALL progression. Thus, the combined suppression of Pin 1 and BCR‐ABL proteins may be exploited as an additional target therapy for ph+ ALL.
The expression of Pin 1 was enhanced in ph+ ALL patient samples and was associated positively with the expression of BCR‐ABL. Genetically or pharmacologically inhibiting Pin 1 expression or activity produces potent therapeutic efficacy against ph+ ALL. BCR‐ABL enhances the prolyl isomerase activity of Pin 1 by decreasing the phosphorylated level of Pin1 at Ser 71 and interacting with DAPK1. The inhibition of BCR‐ABL activity by imatinib in human ph+ ALL cells reduces the prolyl isomerase activity of Pin 1, further suggesting a key role of the newly identified BCR‐ABL‐Pin 1 axis in ph+ ALL progression.
Abstract
Philadelphia chromosome (Ph)/
BCR
‐
ABL
‐positive (ph
+
)
ALL
is the most common genetic abnormality associated with
ALL
and has been shown to confer the worst prognosis to both children and ...adults. Increasing evidence has revealed that the dysregulation of prolyl isomerase Pin 1 contributes to multicancer development and progression, including
ALL
, although the underlying molecular mechanisms remain unclear. Here, we report that the expression of Pin 1 was enhanced in ph
+
ALL
patient samples and was associated positively with the expression of
BCR
‐
ABL
. Genetically or pharmacologically inhibiting Pin 1 expression or activity produces potent therapeutic efficacy against ph
+
ALL
. We further demonstrated that
BCR
‐
ABL
enhances the prolyl isomerase activity of Pin 1 by decreasing the phosphorylated level of Pin 1 at Ser 71 and interacting with
DAPK
1. The inhibition of
BCR
‐
ABL
activity by imatinib in human ph
+
ALL
cells reduces the prolyl isomerase activity of Pin 1, further suggesting a key role of the newly identified
BCR
‐
ABL
‐Pin 1 axis in ph
+
ALL
progression. Thus, the combined suppression of Pin 1 and
BCR
‐
ABL
proteins may be exploited as an additional target therapy for ph
+
ALL
.
To evaluate the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donor (MSD allo-HSCT) for severe aplastic anemia (SAA).
The clinical data of 41 SAA ...patients received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively. 24 patients were male, 17 were female. Median age was 23 (5 - 43) years old. 28 patients had SAA-I, 9 had SAA-II, and 4 had post-hepatitis aplastic anemia. 17 patients received allogeneic bone marrow (BM) transplantation (allo-BMT), and 24 received allogeneic peripheral blood stem cell (PBSC) transplantation (allo-PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY) + anti-thymocyte globulin (ATG) + fludarabine (Flu), 21 received CY + ATG + Flu+ cytarabine (Ara-C) ± busulfan (Bu)/melphalan (Mel). Prophylaxis for graft-versus-host disease (GVHD): 25 patients received cyclosporine (CSA) plus short-term methotrexate (MTX), 16 received tacrolimus (FK506) plus short-term MTX. The median number of infused
Objective：To exam the effect and safety of conventional acupuncture（CA） on cardiac arrhythmia.Methods：Nine medical databases were searched until February 2016 for randomized controlled ...trials.Heterogeneity was measured by Cochran Q test.Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar.Results：Nine qualified studies involving 638 patients were included.Only 1 study had definitely low risk of bias,while 7 trials were rated as unclear and 1 as high.Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation（Af） and atrial flutter（AF） relative risk（RR）：1.09;95% confidence interval（CI）：0.79–1.49;P=0.61;I2=61%,P=0.11.However,1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment,and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study,as well as the response rate in CA plus deslanoside group by another study.Meta-analysis of CA plus anti-arrhythmia drug（AAD） was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat（VPB） patients（RR,1.19,95% CI：1.05–1.34;P=0.005;I2=13%,P=0.32）,and an improvement in quality-of-life score（QOLS） of VPB also showed in 1 individual study.Besides,a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients（MD –21.84 –27.21,–16.47） and lower adverse events of CA alone were reported than amiodarone.Conclusions：CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia,especially in VPB and Af patients,which mainly based on a pooled estimate and result from 1 study with higher methodological quality.However,we could not reach a robust conclusion due to low quality of overall evidence.
The diamond anvil cell experiments have revealed that the calcium ferrite（CF）-type aluminous phase is probably an important component of subducted mid-oceanic ridge basalt（MORB） in the lower mantle. ...In this study, we have performed first principles lattice dynamics calculations for the Mg Al2O4 end-member of the aluminous phase based on density functional perturbation theory using two functionals within the local density approximation（LDA） and generalized gradient approximation（GGA） for bracketing the calculated properties at their lower and upper limits, respectively. A simple empirical pressure correction at zero temperature has been applied to both LDA and GGA. The results of room-temperature equation of state（EOS） and zero-pressure thermal expansion calculated by GGA with pressure correction have shown the best agreement with available experimental data. The high-pressure and temperature thermodynamic properties have been obtained using the GGA with correction method. The pressure-volume relations are fitted with a third-order high-temperature Birch-Murnaghan EOS. The isobaric heat capacity, the coefficient of thermal expansion and isothermal bulk modulus are fitted with polynomials and their coefficients are reported in the range of 0–40 GPa and 300–2000 K. The density profile of MORB estimated using the computational thermo-elastic constants supports the hypothesis that the subducted oceanic slabs could gain enough downwelling forces into the lower mantle.
S3; Sixteen widespread elite indica parents including seven CMS lines and nine restorer lines, and their 63 F1 hybrids were chosen to compare the eleven traits of grain quality. Overall results ...showed that the frequency of negative over-dominance, dominance and partial dominance was much higher than that of positive ones and heterosis, indicating that the values of F1 hybrids were generally lower than the means of their parents in quality characteristics. There existed apparent disparity in grain quality performance among F1 hybrids varied with the traits. The characteristics of chalky area percentage, chalky grain percentage, gel consistency and head rice recovery had a great variation in all kinds of tested heterosis indices including the mid-parent heterosis index, over high-value parent heterosis index and over low-value parent heterosis index, which suggested that special attention should be paid to the selection of F1 hybrids in these traits in breeding. The mean values of F1hybrids were significantly lower than those of their higher parents in all the traits but close to or significantly lower than those of their mid-parent values except for kernel length and amylose content; and significantly higher than those of their lower parents except for brown rice recovery, milled rice recovery and gel consistency.
Characteristic spectra in the 0.5-2.5 terahertz （THz） range of three commercial derv fuel oils have been obtained using THz time-domain spectroscopy and calculated using density functional theory. ...The simulated results and experimental absorption curves suggest that the skeleton vibration is predominant in the THz region, and the absorption bumps of diesels are a superpo- sition of various components. The investigation demonstrates that different diesels can be distinguished using THz time-domain spectroscopy and THz technology is a promising method to detect the composition and properties of diesels via chemical analysis.
To characterize the antigenicity of nucleocapsid proteins (NP) derived from canine coronavirus (CCoV) and canine respiratory coronavirus (CRCoV) in China, the N genes of CCoV (CCoV-BJ70) and CRCoV ...(CRCoV-BJ202) were cloned from swabs obtained from diseased pet dogs in Beijing and then sequenced. The recombinant NPs (rNPs) were expressed in
Escherichia coli
and purified by nickel-affinity column and size exclusion chromatography. Sequencing data indicated that the N genes of CCoV-BJ70 and CRCoV-BJ202 belonging to two distinctly different groups were relatively conserved within each subgroup. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that rNPs of CCoV and CRCoV were expressed efficiently and isolated with a final purity of over 95%. Western blot analysis revealed the rNP from CRCoV could cross-react with mice antisera against human coronavirus (HCoV-229E, NL63, OC43, HKU1), while rNP of CCoV had cross-reactivity with only anti-sera against viruses belonging to the same group (HCoV-229E and NL63). In summary, CCoV and CRCoV rNPs were successfully expressed in
E. coli
and showed antigenic cross-reactivity with antisera raised against human coronaviruses. These findings indicate that further serologic studies on coronavirus infections at the animal-human interface are needed.
The high efficiency all-small-molecule organic solar cells (OSCs) normally require optimized morphology in their bulk heterojunction active layers. Herein, a small-molecule donor is designed and ...synthesized, and single-crystal structural analyses reveal its explicit molecular planarity and compact intermolecular packing. A promising narrow bandgap small-molecule with absorption edge of more than 930 nm along with our home-designed small molecule is selected as electron acceptors. To the best of our knowledge, the binary all-small-molecule OSCs achieve the highest efficiency of 14.34% by optimizing their hierarchical morphologies, in which the donor or acceptor rich domains with size up to ca. 70 nm, and the donor crystals of tens of nanometers, together with the donor-acceptor blending, are proved coexisting in the hierarchical large domain. All-small-molecule photovoltaic system shows its promising for high performance OSCs, and our study is likely to lead to insights in relations between bulk heterojunction structure and photovoltaic performance.
Variations in the high-frequency oscillations of tropical cyclones （TCs） over the western North Pacific （WNP） are studied in numerical model simulations. Power spectrum analysis of maximum wind ...speeds at 10 m （MWS10） from an ensemble of 15 simulated TCs shows that oscillations are significant for all TCs. The magnitudes of oscillations in MWS10 are similar in the WNP and South China Sea （SCS）; however, the mean of the averaged significant periods in the SCS （1.93 h） is shorter than that in the open water of the WNP （2.83 h）. The shorter period in the SCS is examined through an ensemble of simulations, and a case simulation as well as a sensitivity experiment in which the continent is replaced by ocean for Typhoon Hagupit （2008）. The analysis of the convergence efficiency within the boundary layer suggests that the shorter periods in the SCS are possibly due to the stronger terrain effect, which intensifies convergence through greater friction. The enhanced convergence strengthens the disturbance of the gradient and thermal wind balances, and then contributes to the shorter oscillation periods in the SCS.
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