Post-traumatic stress disorder (PTSD) is usually considered a psychiatric disorder upon emotional trauma. However, with the rising number of conflicts and traffic accidents around the world, the ...incidence of PTSD has skyrocketed along with traumatic brain injury (TBI), a complex neuropathological disease due to external physical force and is also the most common concurrent disease of PTSD. Recently, the overlap between PTSD and TBI is increasingly attracting attention, as it has the potential to stimulate the emergence of novel treatments for both conditions. Of note, treatments exploiting the microRNAs (miRNAs), a well-known class of small non-coding RNAs (ncRNAs), have rapidly gained momentum in many nervous system disorders, given the miRNAs' multitudinous and key regulatory role in various biological processes, including neural development and normal functioning of the nervous system. Currently, a wealth of studies has elucidated the similarities of PTSD and TBI in pathophysiology and symptoms; however, there is a dearth of discussion with respect to miRNAs in both PTSD and TBI. In this review, we summarize the recent available studies of miRNAs in PTSD and TBI and discuss and highlight promising miRNAs therapeutics for both conditions in the future.
Nanocrystalline (nc) materials can be defined as solids with grain sizes in the range of 1aAA"100nm. Contrary to coarse-grained metals, which become more difficult to twin with decreasing grain size, ...nanocrystalline face-centered-cubic (fcc) metals become easier to twin with decreasing grain size, reaching a maximum twinning probability, and then become more difficult to twin when the grain size decreases further, i.e. exhibiting an inverse grain-size effect on twinning. Molecular dynamics simulations and experimental observations have revealed that the mechanisms of deformation twinning in nanocrystalline metals are different from those in their coarse-grained counterparts. Consequently, there are several types of deformation twins that are observed in nanocrystalline materials, but not in coarse-grained metals. It has also been reported that deformation twinning can be utilized to enhance the strength and ductility of nanocrystalline materials. This paper reviews all aspects of deformation twinning in nanocrystalline metals, including deformation twins observed by molecular dynamics simulations and experiments, twinning mechanisms, factors affecting the twinning, analytical models on the nucleation and growth of deformation twins, interactions between twins and dislocations, and the effects of twins on mechanical and other properties. It is the authorsaAAtm intention for this review paper to serve not only as a valuable reference for researchers in the field of nanocrystalline metals and alloys, but also as a textbook for the education of graduate students.
Controlled in-plane rotation of the magnetic easy axis in manganite heterostructures by tailoring the interface oxygen network could allow the development of correlated oxide-based magnetic ...tunnelling junctions with non-collinear magnetization, with possible practical applications as miniaturized high-switching-speed magnetic random access memory (MRAM) devices. Here, we demonstrate how to manipulate magnetic and electronic anisotropic properties in manganite heterostructures by engineering the oxygen network on the unit-cell level. The strong oxygen octahedral coupling is found to transfer the octahedral rotation, present in the NdGaO3 (NGO) substrate, to the La2/3Sr1/3MnO3 (LSMO) film in the interface region. This causes an unexpected realignment of the magnetic easy axis along the short axis of the LSMO unit cell as well as the presence of a giant anisotropic transport in these ultrathin LSMO films. As a result we possess control of the lateral magnetic and electronic anisotropies by atomic-scale design of the oxygen octahedral rotation.
Traumatic brain injury (TBI) can lead to different neurological and psychiatric disorders. Circular RNAs (circRNAs) are highly expressed in the nervous system and enriched in synapses; yet, the ...underlying role and mechanisms of circRNAs in neurological impairment and dysfunction are still not fully understood. In this study, we investigated the expression of circRNAs and their relation with neurological dysfunction after TBI. RNA-Seq was used to detect differentially expressed circRNAs in injured brain tissue, revealing that circIgfbp2 was significantly increased. Up-regulated hsa_circ_0058195, which was highly homologous to circIgfbp2, was further confirmed in the cerebral cortex specimens and serum samples of patients after TBI. Moreover, correlation analysis showed a positive correlation between hsa_circ_0058195 levels and the Self-Rating Anxiety Scale scores in these subjects. Furthermore, knockdown of circIgfbp2 in mice relieved anxiety-like behaviors and sleep disturbances induced by TBI. Knockdown of circIgfbp2 in H
O
treated HT22 cells alleviated mitochondrial dysfunction, while its overexpression reversed the process. Mechanistically, we discovered that circIgfbp2 targets miR-370-3p to regulate BACH1, and down-regulating BACH1 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction. In conclusion, inhibition of circIgfbp2 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after TBI through the miR-370-3p/BACH1/HO-1 axis. Thus, circIgfbp2 might be a novel therapeutic target for anxiety and sleep disorders after TBI.
To establish a machine-learning model based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to differentiate combined hepatocellular–cholangiocarcinoma (cHCC-CC) from ...hepatocellular carcinoma (HCC) before surgery.
Clinical and MRI data of 194 patients with histopathologically diagnosed cHCC-CC (n=52) or HCC (n=142) were analysed retrospectively. ITK-SNAP software was used to delineate three-dimensional (3D) lesions and extract high-throughput features. Feature selection was carried out based on Pearson's correlation coefficient and least absolute shrinkage and selection operator (LASSO) regression analysis. A radiomics model (radiomics features), a clinical model (i.e., clinical-image features), and a fusion model (i.e., radiomics features + clinical-image features) were established using six machine-learning classifiers. The performance of each model in distinguishing between cHCC-CC and HCC was evaluated with the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), sensitivity, and specificity.
Significant differences in liver cirrhosis, tumour number, shape, edge, peritumoural enhancement in the arterial phase, and lipid were identified between cHCC-CC and HCC patients (p<0.05). The AUC of the fusion model based on logistic regression was 0.878 (95% CI: 0.766–0.949) in the arterial phase in the test set, and the sensitivity/specificity was 0.844/0.714; however, the AUC of the clinical and radiomics models was 0.759 (95% CI: 0.663–0.861) and 0.838 (95% CI: 0.719–0.921) in the test set, respectively.
The fusion model based on DCE-MRI in the arterial phase can significantly improve the diagnostic rate of cHCC-CC and HCC as compared with conventional approaches.
•The radiomics based on DCE-MRI performs well differentiating cHCC-CC from HCC.•Logistic regression has important value in determining whether cHCC-CC from HCC.•The AUC of the fusion model is 0.878 in differentiating cHCC-CC from HCC.
This article systematically overviews the grain size effect on deformation twinning and detwinning in face-centered cubic (fcc) metals. With decreasing grain size, coarse-grained fcc metals become ...more difficult to deform by twinning, whereas nanocrystalline (nc) fcc metals first become easier to deform by twinning and then become more difficult, exhibiting an optimum grain size for twinning. The transition in twinning behavior from coarse-grained to nc fcc metals is caused by the change in deformation mechanisms. An analytical model based on observed deformation physics in nc metals, i.e., grain boundary emission of dislocations, provides an explanation of the observed optimum grain size for twinning in nc fcc metals. The detwinning process is caused by the interaction between dislocations and twin boundaries. Under a certain deformation condition, there exists a grain size range where the twinning process dominates over the detwinning process to produce the highest density of twins.
Microstructures and mechanical properties of equal-channel angular pressing (ECAP) processed and naturally aged ultrafine grained (UFG) and coarse grained (CG) 7075 Al alloys as well as their ...evolutions during annealing were investigated. After the same natural aging, the tensile yield strength, ultimate strength, and microhardness of the UFG samples were 103%, 35%, and 48% higher, respectively, than those of the CG samples, because of higher densities of Guinier–Preston (G–P) zones and dislocations in the UFG sample. Upon annealing, the microhardness of the UFG sample decreased gradually, while a hardening peak appeared for the CG sample. The peak was caused by the precipitation hardening of the metastable η
′ phase. For the UFG sample, the precipitation hardening was overcompensated by the significant decrease of microstrain (dislocation density) upon annealing, resulting in a lack of precipitation hardening peak. Differential scanning calorimetry indicates that the ECAP process only accelerated the phase precipitations, but did not change the sequence of phase precipitation. This study shows that severe plastic deformation has the potential to significantly improve the mechanical properties of age-hardening Al alloys.
Antibody–drug conjugates (ADCs) combine the specificity of an antibody with the cytotoxicity of a chemical agent. They represent a rapidly evolving area of oncology drug development and hold ...significant promise. There are currently nine ADCs on the market, more than half of which gained US Food and Drug Administration approval more recently, since 2019. Despite their enormous promise, the therapeutic window for these ADCs remains relatively narrow, especially when compared with other oncology drugs, such as targeted therapies or checkpoint inhibitors. In this review, we provide a detailed overview of the five dosing regimen optimization strategies that have been leveraged to broaden the therapeutic window by mitigating the safety risks while maintaining efficacy. These include body weight cap dosing; treatment duration capping; dose schedule (e.g., dosing frequency and dose fractionation); response‐guided dosing recommendations; and randomized dose‐finding. We then discuss how the lessons learned from these studies can inform ADC development going forward. Informed application of these dosing strategies should allow researchers to maximize the safety and efficacy for next‐generation ADCs.
With the usage of gas ferrocene Fe(C 5 H 5 ) 2 as a reactant, which is different from the traditional thin Fe film, to grow the high-quality carbon nanotubes (CNTs) in the high aspect ratio (AR) ...trench structure, it has many advantages to be the through-silicon vias (TSVs) material for the three-dimensional (3-D) stacking technology. In this work, we successfully demonstrate the full process flow, including CNT growing, chemical-mechanical planarization (CMP), and wafer temporary bonding for CNTs as TSVs in the 3-D stacking connection. The flexibility for this demonstrated process flow makes the integration of real high dense devices and CNTs as TSVs for the 3-D connection more easily.
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