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
.
Viral myocarditis in children (VMCC) is a severe condition that requires effective treatment options. Astragalus membranaceus Injection (AMI) has been widely used for the treatment of VMCC and has ...shown promising results. In light of this, we conducted an overview of systematic reviews (OoSRs) and meta-analyses of randomized controlled trials (RCTs) to provide a comprehensive summary of the available evidence regarding the efficacy and safety of AMI in treating VMCC.
We conducted a thorough search of 8 databases up until November 18th, 2022 to identify all systematic reviews (SRs) pertaining to the use of AMI for VMCC. We assessed the methodology quality, report quality, and evidence quality of the retrieved SRs using the AMSTAR-2, PRISMA, and GRADE frameworks. For meta-analysis, we used either a fixed-effects or a random-effects model to calculate effect sizes and 95% confidence intervals (CI) with Stata version 12.0, based on the number of original trials. We presented general results in evidence maps utilizing bubble plots.
A total of 4 SRs, comprising 115 RCTs and 9048 patients, were determined to be eligible for inclusion in OoSRs. Our findings revealed moderate-certainty evidence that combining AMI with western medicine (WM) improved the effective rate, cure rate and electrocardiogram results, while reducing creatine kinase, creatine kinase-MB, and lactate dehydrogenase levels for VMCC compared to the WM group. Furthermore, combination therapy did not increase adverse drug reactionsRR=0.79, 95%CI (0.44, 1.40), P>0.05 for VMCC. Evidence maps demonstrated that combining AMI with WM was more advantageous for treating VMCC.
AMI is a valuable therapeutic option for VMCC, demonstrating remarkable efficacy and a favorable safety profile. However, to confirm these findings and determine the optimal dosing and administration regimens, further prospective studies are necessary. Our work provides a foundation for future research on this topic. While our findings support the effectiveness and safety of combining AMI with WM for treating VMCC, caution should be exercised in interpreting these results due to the quality of the current literature. Larger-scale, well-designed studies are necessary to confirm the results and provide high-quality evidence.
To advance the management and outcomes of VMCC within the context of Chinese medicine, our study highlights the need for ongoing research efforts in this area. We believe that additional research will expand our understanding of the mechanisms underlying the effects of AMI and WM on VMCC, and ultimately benefit patients with this condition.
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This study investigated the effects of 12 weeks of specifically designed physical activity intervention on working memory and motor competence in preschool children and explored the correlation ...between working memory changes and motor competence changes by the intervention.
Four classes of preschool children were grouped into an intervention group and a control group. Children in the intervention group received a 12-week physical activity intervention, while children in the control group followed their daily routine as usual. Before and after the intervention period, children were assessed with the 1-back task and Movement Assessment Battery for Children, second edition (MABC-2) to measure their working memory and motor competence, respectively.
Regarding working memory, the accuracy on the 1-back task increased significantly in the intervention group relative to the control group. The intervention group demonstrated a greater decrease in response time from pre- to posttest than the control group, but the difference was not statistically significant. Regarding motor competence, children's manual dexterity, aiming and catching and total score increased significantly in the intervention group relative to the control group, while no significant difference in static and dynamic balance was observed between the two groups. Furthermore, the correlation results showed that changes in the efficacy and efficiency of working memory were positively related to changes in static and dynamic balance and the total score on the MABC-2.
These findings demonstrated that 12 weeks of specifically designed physical activity intervention could improve preschool children's efficacy of working memory as well as manual dexterity, aiming and catching and global motor competence. The improvement in the efficacy and efficiency of working memory was positively related to the improvement in static and dynamic balance and global motor competence.
Doping heterometal atoms into ligand-protected gold superatom nanoclusters (Aun NCs) is proposed to further diversify their geometrical and electronic structures and enhance their photoluminescent ...properties, which are attributed to the mixing and effects between atoms. However, the fundamental principles that govern the optoelectronic properties of the doped Aun NCs remain elusive. Herein, we systematically explored the two prototypical 8-electron Aun (n = 11, 13) NCs, both with and without Ir dopant atoms, using comprehensive ab initio calculations and real-time nonadiabatic molecular dynamics simulations. These doped Aun NCs maintain their parent geometrical structures and 8-electron superatomic configuration (1S21P6). The strong core-shell (Ir-Aun) electronic coupling significantly expands the energy gap, resulting in a weak nonadiabatic coupling matrix element, which in turn increases carrier lifetime. This increase is mainly governed by the low-frequency vibration mode. We uncovered the relationship between electronic structures, electron vibration, and carrier dynamics for these doped Aun NCs. These calculated results provide crucial insights for the atomically precise design of metal NCs with superior optoelectronic properties.
The electrochemical nitrogen reduction reaction (NRR) is a promising energy‐efficient and low‐emission alternative to the traditional Haber–Bosch process. Usually, the competing hydrogen evolution ...reaction (HER) and the reaction barrier of ambient electrochemical NRR are significant challenges, making a simultaneous high NH3 formation rate and high Faradic efficiency (FE) difficult. To give effective NRR electrocatalysis and suppressed HER, the surface atomic structure of W18O49, which has exposed active W sites and weak binding for H2, is doped with Fe. A high NH3 formation rate of 24.7 μg h−1 mgcat−1 and a high FE of 20.0 % are achieved at an overpotential of only −0.15 V versus the reversible hydrogen electrode. Ab initio calculations reveal an intercalation‐type doping of Fe atoms in the tunnels of the W18O49 crystal structure, which increases the oxygen vacancies and exposes more W active sites, optimizes the nitrogen adsorption energy, and facilitates the electrocatalytic NRR.
More vacancies: Both high NH3 formation rate (24.7 μg h−1 mgcat−1) and Faradic efficiency (20.0 %) are achieved on Fe‐doped W18O49 nanowires@carbon fiber papers at −0.15 V (vs. reversible hydrogen electrode). Fe atoms not only efficiently increase the number of oxygen vacancies of W18O49, but optimize the nitrogen adsorption energy, and facilitate the electrocatalytic nitrogen reduction reaction (NRR).
Rational control of the luminescent properties of ligand-protected coinage metal clusters has long been pursued but remains challenging. Here we explore the crucial structural and electronic factors ...governing the fluorescence of a diphosphine-protected Au13(dppe)5Cl23+ cluster by time-dependent density functional theory calculations. By substituting the central Au atom with group 5 to group 11 transition metal atoms, the emission wavelength is adjustable from red to blue, accompanied by enhanced fluorescence intensity compared with the undoped cluster. The evolution of light-emitting behavior upon doping and the corresponding roles of the dopant, Au cage, ligands, and their interplay are interpreted at the electronic structure level. In particular, strong dopant–Au cage interaction associated with large electron–hole overlap on the dopant are is a key factor to endow large emission energy and intensity. These theoretical results provide vital guidance for designing atomically precise nanoclusters with visible fluorescence and high quantum yield for practical uses.
The paper is to report the study of the effect of Shenfu injection on the enzyme activity of liver CYP450 and its mRNA level of rat liver. Microsome of rat liver was prepared after intravenous ...administration of Shenfu injection for 7 days. The enzyme activity was quantified by Cocktail method. Meanwhile, the mRNA expression of CYP1A2, CYP2B1/2, CYP2C11 and CYP3A1 in the liver was detected by RT-PCR. Shenfu injection obviously induced the enzyme activities of CYP2B and CYP2C. Meantime Shenfu injection decreased the enzyme activities of CYP1A2 and CYP3A. The mRNA levels of CYP2B and CYP2C were also induced in rats treated with Shenfu injection. But it obviously inhibited the mRNA level of CYP1A2 and CYP3A. Since the enzyme activity and mRNA level were obviously changed after administration, the potential effect of drug-drug interaction should be concerned.
Hydrogenation of carbon dioxide (CO2) is among the most promising approaches for reclaiming the major greenhouse gases to produce fuels and chemicals. Developing catalysts composed of natural ...abundant, economical and eco-friendly elements is critical for the industrialization of this technology. Silicon satisfies all these requirements but lacks activity. Using first-principles calculations, we show for the first time that the two-dimensional phase of silicon, i.e., mono- and few-layer silicene supported by a Ag(111) substrate, exhibits superior catalytic activity for CO2 hydrogenation, with selectivity being intrinsically controlled by the number of layers. The supported silicene monolayer as a catalyst leads to the formation of carbon monoxide, formic acid and formaldehyde, while the formation of methanol and methane is favored on bilayer silicene on the Ag substrate. The key parameters governing activity and selectivity are the densities and energy levels of surface dangling bond states, which in turn are mediated by the substrate coupling and covalent interaction between silicene layers. These theoretical results elucidate the fundamental principles for tailoring the catalytic properties of non-metal materials by controlling the number of layers and manipulating the surface states and will advance the development of silicon-based catalysts for renewable energy technologies.
Through the examples of explanatory and pragmatic trials on acupuncture for migraine and the comparison between research objectives, experiment environment and trial designs, the design of current ...clinical trial should focus on: (1) Making a point of continuum research on efficacy-effectiveness at trial design type; (2) Thinking highly of therapeutic effect criteria that could have a better show of trial purpose; (3) More use of qualitative research embedded in the randomized controlled trials. With these improvements, the effects of acupuncture could be evaluated more scientifically, objectively and comprehensively.
Relationships between large customers and suppliers expose lenders to additional risks. These risks may force lead agents to retain a larger share of syndicated loans, reducing loan-level ...diversification, and, in turn, increasing the required interest rate spread. Consistent with this view, we find that borrowers' dependence on a few larger customers or suppliers positively affects the cost of the loans indirectly through the loan structure. Instead, we do not observe a direct cost associated with large customer-supplier links, suggesting that lead agents do not increase the interest rate spread as compensation for the additional risks of dealing with borrowers with large customer-supplier links per se. Finally, we document an inverted U-shaped relationship between the length of the large customer-supplier link and the loan share held by the lead agent.
•Lead agent retains a larger share in loans to borrowers with large customer-supplier relationships.•Dependence on large customers or suppliers positively affects the cost of the loans through the loan structure.•The large customer-supplier link is not directly associated to any risk premium.•Inverted U-shaped relationship between the length of the large customer-supplier link and the lead agent's share of the loan.
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