Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, we report an endovascular approach for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization was confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS) and histological analysis. The safety of the embolization therapy was assessed through biocompatibility evaluation and histopathology assays. Our strategy, seamlessly integrating secure drug packaging, agile magnetic actuation and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson’s disease: a randomized controlled trial

BackgroundFreezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson’s disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD.MethodsThis study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes.ResultsTwo patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1.ConclusionHigh-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD

A Welding Fatigue Analysis of a Quick-Replacement Battery Box for Electric Vehicles

In order to counter the problems of cracks and large area fractures in the welding points of quick-replacement battery boxes for electric vehicles (which may lead to the concentration of stress), in this study, a fatigue analysis of the welding points, based on a load spectrum, was used to predict welding points’ fatigue and improve the structural life of quick-replacement battery boxes. Firstly, a model of the quick-replacement battery box was established in SolidWorks software; secondly, the welding points’ fatigue was analyzed using the Optistruct module of HyperMesh software, and the topology of the quick-replacement battery box was optimized according to the results of the analysis; finally, for testing purposes and to achieve a lighter weight and an improved structural life, the fatigue of the welding points of the optimized battery box was analyzed. The results of the analysis showed that the force of the quick-replacement battery box was primarily concentrated at the connection between the middle bottom plate and the partition. Additionally, retaining the number of welding points at the hanging ear was shown to be beneficial for maintaining stiffness during electric vehicle operation; however, the number of welding points at the partition connection could be appropriately reduced. Before optimization, the maximum fatigue damage values of the welding points were 2.763 × 10−6, 3.833 × 10−6, and 6.728 × 10−6, respectively, satisfying the criteria of fatigue damage to the welding points. After optimization, the fatigue damage values of the welding points in the quick-replacement battery box were significantly reduced to 4.431 × 10−8, 4.562 × 10−8, and 8.885 × 10−8, respectively, compared with their pre-optimized levels. Consequently, the stress concentration was alleviated effectively, thereby meeting the conditions for fatigue damage. These results have important theoretical and engineering significance for the design and optimization of quick-replacement battery boxes for electric vehicles

Dynamic Service Migration with Partially Observable Information in Mobile Edge Computing

Service migration, determining when, where and how to migrate the ongoing service, is of paramount importance in mobile edge computing (MEC) for provisioning high quality of service to mobile users. With respect to high network dynamics and stringent delay requirements, service migration is a rather challenging issue in MEC. In this paper, we formulate service migration as a partially observable Markov decision process (POMDP) based on the fact that an edge server can only obtain partial users' information, or the information of its own serving users. A learning-based intelligent service migration algorithm, named iSMA, is proposed to minimize the long-term service delay of all users. iSMA consists of two function modules, a latent space model and a cross-entropy planning algorithm, where the latent space model is used to infer the full state of the environment based on the partial information observed, and the cross-entropy planning algorithm is used to search the best service migration strategy. Numerical results show that our proposed iSMA reduces the service delay by about 58% when compared with a well-known deep learning-based solution

Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury

Myocardial ischemia/reperfusion (I/R) injury is the main cause of increasing postischemic heart failure and currently there is no definite treatment for myocardial I/R injury. It has been suggested that oxidative stress-induced mitochondrial dysfunction plays an important role in the pathological development of myocardial I/R. In this study, Yiqi Huoxue (YQHX) prescription, as a kind of Chinese herbal formula, was developed and shown to alleviate I/R injury. Network analysis combined with ultrahigh-performance liquid chromatography-high resolution mass spectrometry expounded the active components of YQHX and revealed the mitophagy-regulation mechanism of YQHX treating I/R injury. In vivo experiments confirmed YQHX significantly alleviated I/R myocardial injury and relieved oxidative stress. In vitro experiments validated that YQHX could relieve hypoxia/reoxygenation injury and attenuate oxidative stress via improving the structure and function of mitochondria, which was strongly related to regulating mitophagy. In summary, this study demonstrated that YQHX, which could alleviate I/R injury via targeting mitophagy, might be a potential therapeutic strategy for myocardial I/R injury

An imported human case with the SARS-CoV-2 Omicron subvariant BA.2.75 in Yunnan Province, China

The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021. It showed increased transmissibility and immune evasion with far more amino acid mutations in the spike (S) protein than the previously circulating variants of concern (VOCs). Notably, on 15 July 2022, we monitored the first VOC / Omicron subvariant BA.2.75 in China from an imported case. Moreover, nowadays, this subvariant still is predominant in India. It has nine additional mutations in the S protein compared to BA.2, three of which (W152R, G446S, and R493Q reversion) might contribute to higher transmissibility and immune escape. This subvariant could cause wider spread and pose a threat to the global situation. Our timely reporting and continuous genomic analysis are essential to fully elucidate the characteristics of the subvariant BA.2.75 in the future

Reformability evaluation of blasting-enhanced permeability in in situ leaching mining of low-permeability sandstone-type uranium deposits

It is essential to evaluate the blasting-enhanced permeability (BEP) feasibility of a low-permeability sandstone-type uranium deposit. In this work, the mineral composition, reservoir physical properties and rock mechanical properties of samples from sandstone-type uranium deposits were first measured. Then, the reformability evaluation method was established by the analytic hierarchy process-entropy weight method (AHP-EWM) and the fuzzy mathematics method. Finally, evaluation results were verified by the split Hopkinson Pressure Bar (SHPB) experiment and permeability test. Results show that medium sandstone, argillaceous sandstone and siltstone exhibit excellent reformability, followed by coarse sandstone and fine sandstone, while the reformability of sandy mudstone is poor and is not able to accept BEP reservoir stimulation. The permeability improvement and the distribution of damage fractures before and after the SHPB experiment confirm the correctness of evaluation results. This research provides a reformability evaluation method for the BEP of the low-permeability sandstone-type uranium deposit, which contributes to the selection of the appropriate regional and stratigraphic horizon of the BEP and the enhanced ISL of the low-permeability sandstone-type uranium deposit

DataSheet_1_Genetic basis of maize kernel protein content revealed by high-density bin mapping using recombinant inbred lines.docx

Maize with a high kernel protein content (PC) is desirable for human food and livestock fodder. However, improvements in its PC have been hampered by a lack of desirable molecular markers. To identify quantitative trait loci (QTL) and candidate genes for kernel PC, we employed a genotyping-by-sequencing strategy to construct a high-resolution linkage map with 6,433 bin markers for 275 recombinant inbred lines (RILs) derived from a high-PC female Ji846 and low-PC male Ye3189. The total genetic distance covered by the linkage map was 2180.93 cM, and the average distance between adjacent markers was 0.32 cM, with a physical distance of approximately 0.37 Mb. Using this linkage map, 11 QTLs affecting kernel PC were identified, including qPC7 and qPC2-2, which were identified in at least two environments. For the qPC2-2 locus, a marker named IndelPC2-2 was developed with closely linked polymorphisms in both parents, and when tested in 30 high and 30 low PC inbred lines, it showed significant differences (P = 1.9E-03). To identify the candidate genes for this locus, transcriptome sequencing data and PC best linear unbiased estimates (BLUE) for 348 inbred lines were combined, and the expression levels of the four genes were correlated with PC. Among the four genes, Zm00001d002625, which encodes an S-adenosyl-L-methionine-dependent methyltransferase superfamily protein, showed significantly different expression levels between two RIL parents in the endosperm and is speculated to be a potential candidate gene for qPC2-2. This study will contribute to further research on the mechanisms underlying the regulation of maize PC, while also providing a genetic basis for marker-assisted selection in the future.</p

DataSheet_2_Genetic basis of maize kernel protein content revealed by high-density bin mapping using recombinant inbred lines.xlsx

Maize with a high kernel protein content (PC) is desirable for human food and livestock fodder. However, improvements in its PC have been hampered by a lack of desirable molecular markers. To identify quantitative trait loci (QTL) and candidate genes for kernel PC, we employed a genotyping-by-sequencing strategy to construct a high-resolution linkage map with 6,433 bin markers for 275 recombinant inbred lines (RILs) derived from a high-PC female Ji846 and low-PC male Ye3189. The total genetic distance covered by the linkage map was 2180.93 cM, and the average distance between adjacent markers was 0.32 cM, with a physical distance of approximately 0.37 Mb. Using this linkage map, 11 QTLs affecting kernel PC were identified, including qPC7 and qPC2-2, which were identified in at least two environments. For the qPC2-2 locus, a marker named IndelPC2-2 was developed with closely linked polymorphisms in both parents, and when tested in 30 high and 30 low PC inbred lines, it showed significant differences (P = 1.9E-03). To identify the candidate genes for this locus, transcriptome sequencing data and PC best linear unbiased estimates (BLUE) for 348 inbred lines were combined, and the expression levels of the four genes were correlated with PC. Among the four genes, Zm00001d002625, which encodes an S-adenosyl-L-methionine-dependent methyltransferase superfamily protein, showed significantly different expression levels between two RIL parents in the endosperm and is speculated to be a potential candidate gene for qPC2-2. This study will contribute to further research on the mechanisms underlying the regulation of maize PC, while also providing a genetic basis for marker-assisted selection in the future.</p