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This review summarizes the latest advances in TfR1-targeted nanomedicine for brain tumor therapy.

Nucleic acid-based therapy emerges as a powerful weapon for the treatment of tumors thanks to its direct, effective, and lasting therapeutic effect. Encouragingly, continuous nucleic acid-based drugs have been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Despite the tremendous progress, there are few nucleic acid-based drugs for brain tumors in clinic. The most challenging problems lie on the instability of nucleic acids, difficulty in traversing the biological barriers, and the off-target effect. Herein, nucleic acid-based therapy for brain tumor is summarized considering three aspects: (i) the therapeutic nucleic acids and their applications in clinical trials; (ii) the various administration routes for nucleic acid delivery and the respective advantages and drawbacks. (iii) the strategies and carriers for improving stability and targeting ability of nucleic acid drugs. This review provides thorough knowledge for the rational design of nucleic acid-based drugs against brain tumor.

Extensive efforts are devoted to refining metal sites for optimizing the catalytic performance of single-atom nanozymes (SANzymes), while the contribution of the defect environment of neighboring metal sites lacks attention. Herein, an iron-based SANzyme (Fe-SANzyme) is rationally designed by edge-site engineering, which intensively exposes edge-hosted defective Fe-N

Some recent authors suggest that the extended view fails because it does not follow from functionalism. For although functionalism can tell us whether a system is cognitive, it does not show whether such a newly identified cognitive system can be attributed to the very same subject. I argue that Clark and Chalmers can dodge this attack by claiming that the Parity Principle is essentially an analogy. In their crucial thought experiment, it can be argued that Otto’s notebook is similar to Inga’s biological memory in that they are functionally equivalent, and it seems that the only relevant difference between them is concerned with their being located inside/outside the skull/skin. Provided that Inga’s biological memory is part of Inga’s cognition, analogously, Otto’s notebook should also be regarded as part of Otto’s cognition. However, I argue that this alleged analogy does not hold because the location is not the only difference that matters. Otto’s notebook and Inga’s biological memory are taken as part of a whole for different reasons, and because of this, they actually belong to different kinds of wholes. Otto’s notebook is part of a whole because such a whole functions as a cognitive system, but Inga’s biological memory is part of a whole because it is within a “proper whole” whose boundary is determined by reproduction. As a result, the analogy does not really work.

Idarubicin (IDA), an anthracycline antineoplastic drug, is commonly used in the treatment of acute myeloid leukemia (AML) with reasonable response rates and clinical benefits. However, some patients still relapse, or do not respond, and suffer high fatality rates. Recent studies have shown that overexpression of PARP-1 may represent an important risk factor in AML patients. The aim of the present study was to determine the underlying molecular mechanisms by which the PARP-1 inhibitor Olaparib enhances the chemosensitivity of the leukemia cell line K562 and THP1 to IDA. Our data demonstrated that PARP-1 is upregulated in AML patients as well as in K562 and THP1 cells, and that the suppression of PARP-1 activity by Olaparib enhances the inhibitory effect of IDA. A mechanistic study revealed that Olaparib decreases the expressions of p-ATM, p-IκBα, XIAP and p65, and upregulates Bax, cleaved-Caspase-3 and γ-H2AX. Olaparib can enhance the induction of DNA damage by IDA, probably mediated by the inhibition of the ATM-related DNA damage response. Moreover, we also found that the nuclear translocation of p65 and the nuclear export of NEMO are inhibited when IDA and Olaparib are combined. Our results suggest that Olaparib attenuates the activity of the NF-κB pathway and decreases the DNA damage response induced by IDA. Therefore, we conclude that Olaparib is a potentially valuable chemosensitizer for leukemia patients.

Recent developments in organic plastic scintillators capable of pulse shape discrimination (PSD) enable a breakthrough in discrimination between neutrons and gammas. Plastic scintillator detectors coupled with silicon photomultipliers (SiPMs) offer many advantages, such as lower power consumption, smaller volume, and especially insensitivity to magnetic fields , compared with conventional photomultiplier tubes (PMTs). A SensL SiPM has two outputs: a standard output and a fast output. It is known that the charge injected into the fast output electrode is typically approximately 2% of the total charge generated during the avalanche, whereas the charge injected into the standard output electrode is nearly 98% of the total. Fast signals from SiPMs exhibit better performance in terms of timing and time-correlated measurements compared with standard signals. The pulse duration of a standard signal is on the order of hundreds of nanoseconds, whereas the pulse duration of the main monopole waveform of a fast signal is a few tens of nanoseconds. Fast signals are traditionally thought to be suitable for photon counting at very high speeds but unsuitable for PSD due to the partial charge collection. Meanwhile, the standard outputs of SiPMs coupled with discriminating scintillators have yielded nice PSD performances, but there have been no reports on PSD using fast signals. Our analysis shows that fast signals can also provide discrimination if the rate of charge injection into the fast output electrode is fixed for each event, even though only a portion of the charge is collected. In this work, we achieved successful PSD using fast signals; meanwhile, using a coincidence timing window of less 3 nanoseconds between the readouts from both ends of the detector reduced the influence of the high SiPM dark current. We experimentally achieved good timing performance and PSD capability simultaneously.

The structural, elastic, anisotropy, and thermodynamic properties of R3-B2C were investigated using first-principles density functional calculations. The calculated equilibrium parameters are in good agreement with the available theoretical results. The elastic constants, elastic modulus, and elastic anisotropies of R3-B2C were also determined in the pressure range of 0–100 GPa. The calculated elastic modulus indicates that R3-B2C is a potential superhard material. The calculated elastic anisotropic factors suggest that R3-B2C is elastically anisotropic. A band structure study shows that R3-B2C is a direct semiconductor with band gap of 0.170 eV. Moreover, we predict the thermodynamic properties and obtain the relationships among the thermal expansion, temperature, and pressure, as well as the  

The mechanical and electronic properties of P3m1-BCN have been studied by using first principles calculations. The anisotropy studies of Young's modulus, shear modulus and Poisson's ratio show that P3m1-BCN exhibits a large anisotropy. Electronic structure study shows that P3m1-BCN is an indirect semiconductor with band gap of 4.10 eV. Unusually, the band gap of P3m1-BCN increase with increasing pressure.

Based on density function theory with the ultrasoft pseudopotential scheme in the frame of the local density approximation and the generalized gradient approximation, we have systematically studied the structural stability, elastic properties, and mechanical properties of BCN compound with Imm2 and I 4 ¯ m2 phases. It was found that Imm2 and I 4 ¯ m2 phases are both mechanically stable. Imm2 phase is a direct semiconductor with bandgap of 2.54 eV, whereas I 4 ¯ m2 phase is an indirect semiconductor with bandgap of 0.45 eV. The bulk modulus, shear modulus, Young’s modulus, Poisson’s ratio and Debye temperature have been calculated. For Imm2 (I 4 ¯ m2) phase, the bulk modulus, shear modulus, Young’s modulus and Debye temperature are 365 GPa (345 GPa), 394 GPa (358 GPa), 839 GPa (798 GPa) and 1925 K (1841 K).

A fully tetrahedrally bonded boron nitride (BN) allotrope with an orthorhombic structure (Pbca-BN, space group: Pbca) was investigated by first-principles calculations. In this work, we have investigated the structural, elastic, electronic properties and elastic anisotropy of Pbca-BN by density functional theory method with the ultrasoft pseudopotential scheme in the frame of the local density approximation (LDA) and the generalized gradient approximation (GGA). From our calculations, we found that Pbca-BN has a bulk modulus of 344 GPa, a shear modulus of 316 GPa, a large Debye temperature 1734 K, a small Possion’s ratio 0.14, and the hardness of 60.1 GPa, thereby making it a superhard material with potential technological and industrial applications. Our calculations predict that Pbca-BN is mechanically stable and it is an insulator with wide band gap of 5.399 eV.

Objective The objective of this study is to describe the development of the Outpatient Experience Questionnaire (OPEQ) and to assess the validity and reliability of the scale. Design Literature review, patient interviews, Delphi method and Cross-sectional validation survey. Setting Six comprehensive public hospitals in China. Participants The survey was carried out on a sample of 600 outpatients. Main Outcome Measure(s) Acceptability of the questionnaire was assessed according to the overall response rate, item non-response rate and the average completion time. Correlation coefficients and confirmatory factor analysis were used to test construct validity. Delphi method was used to assess the content validity of the questionnaire. Cronbach's coefficient alpha and split-half reliability coefficient were used to estimate the internal reliability of the questionnaire. Results The overall response rate was 97.2% and the item non-response rate ranged from 0% to 0.3%. The mean completion time was 6 min. The Spearman correlations of item-total score ranged from 0.466 to 0.765. The results of confirmatory factor analysis showed that all items had factor loadings above 0.40 and the dimension intercorrelation ranged from 0.449 to 0.773, the goodness of fit of the questionnaire was reasonable. The overall authority grade of expert consultation was 0.80 and Kendall's coefficient of concordance W was 0.186. The Cronbach's coefficients alpha of six dimensions ranged from 0.708 to 0.895, the split-half reliability coefficient (Spearman–Brown coefficient) was 0.969. Conclusions The OPEQ is a promising instrument covering the most important aspects which influence outpatient experiences of comprehensive public hospital in China. It has good evidence for acceptability, validity and reliability.

Poor patient experience may trigger serious doctor-patient conflicts in China. Health system challenges related to access and financing may cause frustration in patients, but inadequate health literacy is an additional factor. This letter argues from two aspects that patient education is an effective and feasible pathway to improve patient experience, but its effects are influenced by underlying systemic problems and contextual factors in China.

A dosimeter for space ionization radiation field is developed, energy deposited in the sensitivity volume of ionization chamber induces an output current signal as weak as 10- 14 A, and the dynamic range of the signal is very high. Now, an ionization chamber is designed and a variable gain current feedback preamp module is designed for the weak output current amplification is connected to output of the ionization chamber anode. The amplifier module includes I-V converter with T shaped resistance net, zero correct circuit, low pass filter, voltage linear amplifier circuit, gain control circuit and voltage output circuit. A complete analysis of this current preamp with respect to its circuit structure, dynamic properties, its equivalent input noise and the temperature effect is given. The effects of stray impedances on the behavior of the current feedback preamp are taken into account and the techniques necessary to achieve an optimum stable electrometer, with respect to noise, Dc drift, leakage currents, are applied. Experiments show that the energy of dosimeter deposited in the sensitivity volume of ionization chamber induces an output current signal as weak as 10 -14 A, the current preamp can detect weak current effectively with the range from 100fA to 10μA through switchable gain.

When space vehicles reentry atmosphere at hypersonic speed, a plasma sheath enveloping the spacecraft forms. The plasma sheath is a medium which is frequency dependent and lossy, so reflection and attenuation will happen when radio signals transport through the plasma sheath. In this paper, Finite Difference Time Domain using Z-transform method(ZT-FDTD) is used to analyze the problem. At first, Maxwell equations are transformed to make the expression independent of the medium properties, thus, the same equations can be used in different frequency dependent mediums, this technology achieves the feature of code portability. Then the ZT-FDTD method is extended to the three-dimensional space, by comparing the sectional drawing of the result in 3D with that in 1D to make sure of the correctness of the simulation in 3D, and then the method is used to study the scattering characteristics of objects in different situations in 3D. Finally we compare and give the analysis of different situations.

To analyze the micro-track structure of heavy ions in a polymer material, parameters including bulk etch rate, track etch rate, etch rate ratio, and track core size were measured. The pieces of CR-39 were exposed to 100 MeV Si ions with normal incidence and were etched in 6.25N NaOH solution at 70 ?C. Bulk etch rate was read out by a profilemeter after several hours of etching. The other parameters were obtained by using an atomic force microscope (AFM) after a short time of etching. We have measured the second etch pits and minute etch pits to obtain the track growth curve and three dimension track structures to track the core size and etch rate measurements. The local dose of the track core was calculated by the ?-ray theory. In our study, we figure out that the bulk etch rate Vb = (1.58 ? 0.022) ?m/h, the track etch rate Vt = (2.90 ? 0.529) ?.m/h, the etch rate ratio V = 1.84 ? 0.031, and the track core radii r 4.65 nm. In the meantime, we find that the micro-track development violates the traditional track-growth model. For this reason, a scenario is carried out to provide an explanation.