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Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons. Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium (Kv) channel subunit gene in a rat model of central post-stroke pain, thereby increasing Kcna2 expression and relieving central pain. However, in the absence of nerve injury, increasing histone deacetylase 2 expression decreased Kcna2 expression, decreased Kv current, increased the excitability of neurons in the ventral posterolateral nucleus area, and led to neuropathic pain symptoms. Moreover, treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage, reversed histone deacetylase 2 upregulation and Kv1.2 downregulation, and alleviated mechanical hypersensitivity in central post-stroke pain rats. These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation, mediated by iron overload, are important factors in central post-stroke pain pathogenesis and could serve as new targets for central post-stroke pain treatment.

Abstract Background As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gliomas (LGGs). Methods The present study included 413 LGG samples from TCGA RNA-seq dataset (training cohort) and 172 LGG samples from CGGA RNA-seq dataset (validation cohort). The cholesterol metabolism-related signature was identified by the LASSO regression model. Bioinformatics analyses were performed to explore the functional roles of this signature in LGGs. Kaplan-Meier and Cox regression analyses were enrolled to estimate prognostic value of the risk signature. Results Our findings suggested that cholesterol metabolism was tightly associated clinicopathologic features and genomic alterations of LGGs. Bioinformatics analyses revealed that cholesterol metabolism played a key role in immunosuppression of LGGs, mainly by promoting macrophages polarization and T cell exhaustion. Kaplan-Meier curve and Cox regression analysis showed that cholesterol metabolism was an independent prognostic indicator for LGG patients. To improve the clinical application value of the risk signature, we also constructed a nomogram model to predict the 1-, 3- and 5-year survival of LGG patients. Conclusion The cholesterol metabolism was powerful prognostic indicator and could serve as a promising target to enhance personalized treatment of LGGs.

The design concept of a Small High-flux Multipurpose LBE(Lead Bismuth Eutectic) cooled Fast Reactor (SHMLFR) was proposed in the paper. The primary cooling system of the reactor is forced circulation, and the fuel element form is arc-plate loaded high enrichment MOX fuel. The core is cylindrical with a flux trap set in the center of the core, which can be used as an irradiation channel. According to the requirements of the core physical design, a series of physical design criteria and constraints were given, and the steady and transient parameters of the reactor were calculated and analyzed. Regarding the thermal and hydraulic phenomena of the reactor, a simplified model was used to conduct a preliminary analysis of the fuel plates at special positions, and the temperature field distribution of the fuel plate with the highest power density under different coolant flow rates was simulated. The results show that the various parameters of SHMLFR meet the requirements and design criteria of the physical design of the core and the thermal design of the reactor. This implies that the conceptual design of SHMLFR is feasible.

Abstract We report the amorphous Si passivation of Ge pMOSFETs fabricated on (001)-, (011)-, and (111)-orientated surfaces for advanced CMOS and thin film transistor applications. Amorphous Si passivation of Ge is carried out by magnetron sputtering at room temperature. With the fixed thickness of Si t Si, (001)-oriented Ge pMOSFETs achieve the higher on-state current I ON and effective hole mobility μ eff compared to the devices on other orientations. At an inversion charge density Q inv of 3.5 × 1012 cm−2, Ge(001) transistors with 0.9 nm t Si demonstrate a peak μ eff of 278 cm2/V × s, which is 2.97 times higher than the Si universal mobility. With the decreasing of t Si, I ON of Ge transistors increases due to the reduction of capacitive effective thickness, but subthreshold swing and leakage floor characteristics are degraded attributed to the increasing of midgap D it.