Highlights • Epigenetic mechanisms include DNA methylation, histone modifications and non-coding RNAs. • Epigenetic mechanisms translate environmental stimuli into modifications in gene expression. • ...Epigenetic mechanisms play a pivotal role in aging and the pathogenesis of AD. • Epigenetic therapies have promising potentials for AD treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
With the development and progress of nanotechnology, the prospect of using nanorobots to achieve targeted drug delivery is becoming possible. Although nanorobots can potentially improve ...nano-drug delivery systems, there remains a significant challenge to fabricating magnetically controllable nanorobots with a size suitable for drug delivery in complex in vivo environments. Most of the current research focused on the preparation and functionalization of microscale and milliscale robots due to the relative difficulties in fabricating nanoscale robots. To address this problem and move towards in vivo applications, this study uses electron beam lithography to fabricate achiral planar L-shaped nanorobots that are biocompatible with immune cells. Their minimal planar geometry enabled nanolithography to fabricate nanorobots with a minimum feature size down to 400 nm. Using an integrated imaging and control system, the locomotive behavior of the L-shaped nanorobots in a fluidic environment was studied by examining their velocity profiles and trajectories. Furthermore, the nanorobots exhibit excellent cell compatibility with various types of cells, including macrophage cells. Finally, the long-term cell culture medium immersion test demonstrated that the L-shaped nanorobots have robust stability. This work will demonstrate the potential to use these nanorobots to operate in vivo without triggering immune cell responses.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PARP inhibitors have achieved great success in cancers with BRCA mutations, but only a small portion of patients carry BRCA mutations, which results in their narrow indication spectrum. Recently, ...emerging evidence has demonstrated that combinations of PARP and PI3K inhibitors could evoke unanticipated synergistic effects in various cancers, even including BRCA-proficient ones. In this work, a series of PARP/PI3K dual inhibitors were designed, synthesized, and evaluated for their biological activities. It was found that compounds 9a and 23a exhibited excellent inhibitory activities against PARP-1 (9a: IC50 = 1.57 nM, 23a: IC50 = 0.91 nM) and PI3Kα (9a: IC50 = 2.0 nM, 23a: IC50 = 1.5 nM), and showed promising antiproliferative activities against both BRCA-deficient (HCT-116, HCC-1937) and BRCA-proficient (SW620, MDA-MB-231/468) tumor cells. 9a and 23a also exhibited considerable in vivo antitumor efficacy in an MDA-MB-468 xenograft mouse model, with TGI values of 56.39% and 48.77%, respectively. Additionally, 23a possessed promising profiles including high kinase selectivity and low cardiotoxicity. Overall, this work indicates 9a and 23a might be potential PARP/PI3K dual inhibitors for cancer therapy and deserve further research.
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•A series of PARP/PI3K dual inhibitors were designed, synthesized, and evaluated for their biological activities.•Compounds 9a and 23a exhibited strong PARP/PI3K inhibitory activities.•9a and 23a showed considerablei antitumor efficacy in vitro and in vivo.•23a possessed promising kinase selectivity and low cardiotoxicity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have grown horizontal oriented, high growth rate, well-aligned polar (0001) single crystalline GaN nanowires and high-density and highly aligned GaN nonpolar (11–20) nanowires on r-plane ...substrates by metal organic chemical vapor deposition. It can be found that the polar nanowires showed a strong yellow luminescence (YL) intensity compared with the nonpolar nanowires. The different trends of the incorporation of carbon in the polar, nonpolar, and semipolar GaN associated with the atom bonding structure were discussed and proved by energy-dispersive X-ray spectroscopy, suggesting that C-involved defects are the origin responsible for the YL in GaN nanowires.
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IJS, KILJ, NUK, PNG, UL, UM
The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome ...sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.
The recycling of construction and demolition waste (CDW) remains an urgent problem to be solved. In the industry, raw CDW needs to be manually sorted. To achieve high efficiency and avoid the risks ...of manual sorting, a sorting robot can be designed to grasp and sort CDW on a conveyor belt. But dynamic grasping on the conveyor belt is a challenge. We collected location information with a three-dimensional camera and then evaluated the method of dynamic robotic grasping. This paper discusses the grasping strategy of rough processed CDW on the conveyor belt, and implements the function of grasping and sorting on the recycling line. Furthermore, two new mathematical models for a robotic locating system are established, the accuracy of the model is tested with Matlab, and the selected model is applied to actual working conditions to verify the sorting accuracy. Finally, the robot kinematics parameters are optimized to improve the sorting efficiency through experiments in a real system, and it was concluded that when the conveyor speed was kept at around 0.25 m·s
−1
, better sorting results could be achieved. Increasing the speed and shortening the acceleration/deceleration time would reach the maximum efficiency when the load would allow it. Currently, the sorting efficiency reached approximately 2000 pieces per hour, showing a high accuracy.
Brain-computer interface (BCI) can be used as a real-time bidirectional information gateway between the brain and machines. In particular, rapid progress in invasive BCI, propelled by recent ...developments in electrode materials, miniature and power-efficient electronics, and neural signal decoding technologies has attracted wide attention. In this review, we first introduce the concepts of neuronal signal decoding and encoding that are fundamental for information exchanges in BCI. Then, we review the history and recent advances in invasive BCI, particularly through studies using neural signals for controlling external devices on one hand, and modulating brain activity on the other hand. Specifically, regarding modulating brain activity, we focus on two types of techniques, applying electrical stimulation to cortical and deep brain tissues, respectively. Finally, we discuss the related ethical issues concerning the clinical application of this emerging technology.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background The trajectory of ischemic stroke patients attributable to large vessel occlusion is fundamentally altered by endovascular thrombectomy. This study aimed to develop a nomogram for ...predicting 3-month mortality risk in patients with ischemic stroke attributed to artery occlusion in anterior circulation who received successful endovascular thrombectomy treatment. Methods and Results Patients with successful endovascular thrombectomy (modified Thrombolysis in Cerebral Infarction IIb or III) were enrolled from a multicenter registry as the training cohort. Step-wise logistic regression with Akaike information criterion was utilized to establish the best-fit nomogram. The discriminative value of the nomogram was tested by concordance index. An additional 224 patients from 2 comprehensive stroke centers were prospectively recruited as the test cohort for validating the new nomogram. Altogether, 417 patients were enrolled in the training cohort. Age (odds ratio OR, 1.07; 95% CI, 1.03-1.10), poor pretreatment collateral status (OR, 2.13; 95% CI, 1.18-3.85), baseline blood glucose level (OR, 1.12; 95% CI, 1.04-1.21), symptomatic intracranial hemorrhage (OR, 9.51; 95% CI, 4.54-19.92), and baseline National Institutes of Health Stroke Scale score (OR, 1.08; 95% CI, 1.03-1.12) were associated with mortality and were incorporated in the nomogram. The c-index of the nomogram was 0.835 (95% CI, 0.785-0.885) in the training cohort and 0.758 (95% CI, 0.667-0.849) in the test cohort. Conclusions The nomogram, composed of age, pretreatment collateral status, baseline blood glucose level, symptomatic intracranial hemorrhage, and baseline National Institutes of Health Stroke Scale score, may predict risk of mortality in patients with ischemic stroke and treated successfully with endovascular thrombectomy.
Over the past two decades, there has been a growing body of work on wireless devices that can operate on the length scales of biological cells and even smaller. A class of these devices receiving ...increasing attention are referred to as bio-hybrid actuators: tools that integrate biological cells or subcellular parts with synthetic or inorganic components. These devices are commonly controlled through magnetic manipulation as magnetic fields and gradients can be generated with a high level of control. Recent work has demonstrated that magnetic bio-hybrid actuators can address common challenges in small scale fabrication, control, and localization. Additionally, it is becoming apparent that these magnetically driven bio-hybrid devices can display high efficiency and, in many cases, have the potential for self-repair and even self-replication. Combining these properties with magnetically driven forces and torques, which can be transmitted over significant distances, can be highly controlled, and are biologically safe, gives magnetic bio-hybrid actuators significant advantages over other classes of small scale actuators. In this review, we describe the theory and mechanisms required for magnetic actuation, classify bio-hybrid actuators by their diverse organic components, and discuss their current limitations. Insights into the future of coupling cells and cell-derived components with magnetic materials to fabricate multi-functional actuators are also provided.
This review focuses on magnetically driven bio-hybrid micro actuators, categorized by major biological component, for environmental and biomedical applications.
Magnetic micro/nanorobots attracted much attention in biomedical fields because of their precise movement, manipulation, and targeting abilities. However, there is a lack of research on intelligent ...micro/nanorobots with stimuli-responsive drug delivery mechanisms for cancer therapy. To address this issue, we developed a type of strong covalently bound tri-bead drug delivery microrobots with NIR photothermal response azobenzene molecules attached to their carboxylic surface groups. The tri-bead microrobots are magnetic and showed good cytocompatibility even when their concentration is up to 200 µg/mL. In vitro photothermal experiments demonstrated fast NIR-responsive photothermal property; the microrobots were heated to 50 °C in 4 min, which triggered a significant increase in drug release. Motion control of the microrobots inside a microchannel demonstrated the feasibility of targeted therapy on tumor cells. Finally, experiments with lung cancer cells demonstrated the effectiveness of targeted chemo-photothermal therapy and were validated by cell viability assays. These results indicated that tri-bead microrobots have excellent potential for targeted chemo-photothermal therapy for lung cancer cell treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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