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As bone marrow transplant (BMT) is gradually applied to the study of central nervous system (CNS) disease, it is needed to investigate the proper dose of chemotherapy to eradicate bone marrow cells while bringing little damage to brain. In the present study, we established a BMT model with varied busulfan and cyclophosphamide (Bu-Cy) dosages. The recipient mice's chimera rate, neuronal death, neuroinflammation, and behavioral functions were all investigated. Chimerism of peripheral blood cells was shown to rise with Bu-Cy treatment doses, with 60.7% in the Bu(20 mg/kg)/Cy(100 mg/kg) group and 93.0% in the Bu(35 mg/kg)/Cy(100 mg/kg) group. Recipients with Bu(35 mg/kg)/Cy(100 mg/kg) therapy had brain injury, increased neuroinflammation, diminished neurogenesis and cognitive abnormalities, whereas animals given a lesser dosage had no such brain damages. Conclusively, considering the chimerism and the possibility to damage brain, we recommend Bu(20 mg/kg)/Cy(100 mg/kg) is the ideal dose in BMT for studying CNS diseases in the C57/BL6 mouse strain.

The synthesis of ionic olefin linked three-dimensional covalent organic frameworks (3D COFs) is greatly challenging given the hardness of the formation of stable carbon-carbon double bonds (–C = C–). Herein, we report a general strategy for designing porous positively charged sp2 carbon-linked 3D COFs through the Aldol condensation promoted by quaternization. The obtained 3D COFs, namely TFPM-PZI and TAPM-PZI, showed impressive chemical stability. Furthermore, the positively charged frameworks with regular porosity endow 3D ionic COFs with selective capture radioactive ReO4−/TcO4− and great removal efficiency in simulated Hanford waste. This research not only broadens the category of 3D COFs but also promotes the application of COFs as efficient functional materials.

With the increasing thermal challenges of electronic equipment, topology optimization of heat sinks has aroused great research interest in recent years. However, most related researches deal with heat transfer problems of the laminar flow. Only several papers deal with heat transfer problems of the turbulent flow which exhibits better heat dissipation capacity. This paper intends to demonstrate the topology optimization of turbulent forced convective heat sinks with a computational-cheap multi-layer thermofluid model. Based on the assumption of a hydrodynamically fully developed turbulent flow, a single-layer flow model is derived from the 3D turbulent flow model. Viscous effects in the out-of-plane direction are modeled as the additional terms in the derived momentum and transportation equations. Similarly, based on the assumption of adaptive temperature profiles in the out-of-plane direction, heat fluxes between adjacent layers are modeled and a multi-layer heat transfer model is constructed. Further, the porosity field is introduced to describe the channel’s topology and the corresponding topology optimization scheme is presented. Topology optimizations of a heat sink for coil-cooling are carried out to reduce the average temperature rise of the heat source under a maximum volume fraction constraint. The accuracy of the multi-layer model is evaluated via 3D thermofluid simulation of optimized and reference designs. Topology-optimized heat sinks exhibit better thermal performance and provide up to a 32.39% reduction of the average temperature rise, compared with the reference designs. Additionally, a comparative study is also provided between designs optimized in heat transfer problems under laminar and turbulent flows.

Amyloid-β (Aβ) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aβ produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aβ clearance remain largely unknown. The kidney is thought to be responsible for Aβ clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aβ in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aβ clearance via the kidney were assessed. We detected Aβ in the kidneys and urine of both humans and animals and found that the Aβ level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aβ deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aβ levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aβ from the blood, suggesting that facilitation of Aβ clearance via the kidney represents a novel potential therapeutic approach for AD.

This paper investigates the topology optimization of planar cooling channels using a low-cost multilayer thermofluid model. A novel three-layer model including the upper/lower cover-plate layers and the central solid-fluid mixing layer is proposed. The flow boundary layer effect and the heat transfer effect in the thickness direction are modeled as the flow coupling and thermal coupling effects between adjacent layers, respectively. Particularly, in order to estimate more accurate temperature fields, the constructed three-layer heat transfer model in the solid-fluid mixing channel is derived based on the assumption of adaptive temperature profiles in the thickness direction. Further, based on the three-layer thermofluid model, the porosity field is introduced to describe the channel’s topology, and the corresponding topology optimization scheme is presented. Several optimized channels under different constraints and boundary conditions are shown and discussed in comparison. Optimized channels show streamlined boundaries and reasonable layouts and exhibit competitive heat dissipation performance. Parametric studies are conducted to analyze the effectiveness and reliability of the topology optimization scheme. Further, to evaluate the accuracy and efficiency of the proposed three-layer model, optimized channels are simulated with the full 3D model and previous low-cost models. The proposed three-layer model exhibits good consistency with the full 3D model while achieves great improvement in efficiency.

With the increasing development of topology optimization theory in thermal-fluid problems, it has been widely applied in design problems of cooling structures. However, little researches have concurrently considered the design-dependent mechanical problems of optimized structures. This paper deals with porosity-based topology optimization of forced convection planar heat sinks considering out-of-plane design-dependent deformation problems. The optimization is performed on the middle cross-section and the mechanical behaviors of the upper cover plate are considered. Governing equations of fluid flow, heat transfer, and structural mechanic fields are constructed. Particularly, to concurrently model design-dependent loads and boundary conditions, a spring term with design-dependent stiffnesses and a design-dependent pressure term are introduced into the out-of-plane mechanical model. Numerical examples in fluid-mechanical decoupled and weakly-coupled cases are given to demonstrate the validity and potential of the present approach. Additionally, the presented scheme is also evaluated in cases considering the global mechanical behavior and cases considering the local mechanical behavior. Comparisons and verifications show that the proposed approach is effective in yielding planar heat sinks with optimized heat transfer capabilities and well-controlled out-of-plane mechanical behaviors.

The decline of fossil fuels is fostering research on carbon–neutral fuels such as nuclear energy, yet uranium supply is limited by actual techniques of uranium extraction from seawater. In particular, biofouling by marine bacteria and adsorbent instability are major drawbacks. Here we synthesized a novel amidoxime-functionalized antibacterial covalent organic framework that displays high stability and inhibits more than 90% the growth of marine bacteria, thus resulting in an enhanced uranium recovery capacity of 6.64 mg/g. Meanwhile, due to its exceptional fluorescence properties, the adsorbent can also be applied to highly sensitive on-site and real-time monitoring of UO22+.

Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of Alzheimer’s disease (AD). However, whether there are pathological changes in angiostatin levels in individuals with AD dementia is unclear, and whether plasma angiostatin has a relationship with major AD pathological processes and cognitive impairment remains unknown. To examine plasma angiostatin levels in patients with AD dementia and investigate the associations of angiostatin with blood and cerebrospinal fluid (CSF) AD biomarkers, we conducted a cross-sectional study including 35 cognitively normal control (CN) subjects and 59 PiB-PET-positive AD dementia patients. We found that plasma angiostatin levels were decreased in AD dementia patients compared to CN subjects. Plasma angiostatin levels were negatively correlated with plasma Aβ42 and Aβ40 levels in AD dementia patients and positively correlated with CSF total tau (t-tau) levels and t-tau/Aβ42 in AD dementia patients with APOE-ε4. In addition, plasma angiostatin levels had the potential to distinguish AD from CN. These findings suggest a link between angiostatin and AD pathogenesis and imply that angiostatin might be a potential diagnostic biomarker for AD.

It is traditionally believed that cerebral amyloid-beta (Aβ) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aβ. The role of peripherally produced Aβ in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aβ to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aβ in the blood, and caused AD phenotypes including Aβ plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aβ levels, and alleviated brain Aβ burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aβ plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aβ can decrease brain Aβ deposition and represents a novel therapeutic approach for AD.

With the increasing dissipated power levels of electronic equipment, heat sink design problems are significant aspects of some industrial design fields. Topology optimization theory has attracted much research interest in thermal-fluid problems to design high-performance heat sinks. These researches focus on optimizing the internal flow channel of heat sinks under predefined inlet and outlet schemes. However, inlet/outlet schemes also exhibit great influence on the performance of optimized heat sinks. This paper intends to demonstrate a concurrent optimization method of the internal flow channel, inlets, and outlets in forced convection heat sinks. The porosity field and moving morphable components (MMCs) are adopted to describe structural topologies of the internal channel design domain and the inlet/outlet design domains, respectively. The internal porosity field and the shape/position parameters of MMCs are applied as design variables. A conventional inlet/outlet component is presented and the corresponding topology description transformation function is constructed to convert the inlet/outlet topology into corresponding porosity fields. Further, the thermal-fluid coupling problems are solved through porosity-interpolated fluid flow and heat transfer governing equations. To ensure accurate inlet flow and temperature conditions during the topology iteration, continuous design-dependent inlet governing equations are established under inlet pressure, velocity, and flow flux boundary conditions. Design variables are concurrently optimized based on the sensitivity information. The proposed method is shown in detail by taking design problems of water-cooled heat sinks as examples. Various numerical examples are presented to validate the applicability and efficiency of this method.

To explore the value of combining apparent diffusion coefficients (ADC) and texture parameters from diffusion-weighted imaging (DWI) in predicting the pathological subtypes and stages of thymic epithelial tumors (TETs). Fifty-seven patients with TETs confirmed by pathological analysis were retrospectively enrolled. ADC values and optimal texture feature parameters were compared for differences among low-risk thymoma (LRT), high-risk thymoma (HRT), and thymic carcinoma (TC) by one-way ANOVA, and between early and advanced stages of TETs were tested using the independent samples t test. Receiver operating characteristic (ROC) curve analysis was performed to determine the differentiating efficacy. The ADC values in LRT and HRT were significantly higher than the values in TC (p = 0.004 and 0.001, respectively), also in early stage, values were significantly higher than ones in advanced stage of TETs (p

Uranium is a key element in the nuclear industry, but its unintended leakage has caused health and environmental concerns. Here we report a sp2 carbon-conjugated fluorescent covalent organic framework (COF) named TFPT-BTAN-AO with excellent chemical, thermal and radiation stability is synthesized by integrating triazine-based building blocks with amidoxime-substituted linkers. TFPT-BTAN-AO shows an exceptional UO22+ adsorption capacity of 427 mg g−1 attributable to the abundant selective uranium-binding groups on the highly accessible pore walls of open 1D channels. In addition, it has an ultra-fast response time (2 s) and an ultra-low detection limit of 6.7 nM UO22+ suitable for on-site and real-time monitoring of UO22+, allowing not only extraction but also monitoring the quality of the extracted water. This study demonstrates great potential of fluorescent COFs for radionuclide detection and extraction. By rational designing target ligands, this strategy can be extended to the detection and extraction of other contaminants., Porous materials for uranium capture have been developed in the past, but materials for simultaneous uranium capture and detection are scarce. Here the authors develop a stable covalent organic framework capable of adsorbing and detecting uranyl ions.

In this research, the adsorptive removal of diclofenac sodium, one of the representative pharmaceuticals and personal care products, from aqueous solution using Fe3O4@MOF-100(Fe) magnetic microspheres was studied for the first time. The Fe3O4@MOF-100(Fe) microspheres exhibit strong magnetism and stability, which were observed as a core-shell structure. The maximum adsorption capacity of Fe3O4@MOF-100(Fe) for diclofenac sodium can reach 377.36 mg L−1, which was higher than most of the adsorbents reported. The adsorption kinetics follows the pseudo-second-order kinetic equation. And the adsorption equilibrium of DCF can be described with Langmuir isotherm. In the cycle experiment, Fe3O4@MOF-100(Fe) material performed high adsorption efficiency for low-concentration diclofenac sodium solution, and the removal rate can still reach 80% after 5 cycles of adsorption without desorption. The mechanisms including electrostatic interaction, H-bond interaction, and π-π interaction that coexisted in the adsorption processes would be of benefit to enhance the adsorption capacity. The Fe3O4@MOF-100(Fe) magnetic microspheres offer exciting opportunities for further application.