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المغامرون الصغار : ملحمة عالمية : استكشاف الطاقة النفط
ليث ولين وزياد. المغامرون الصغار بانتظار المغامرات دوما لكن سرعان ما يجدون أنفسهم أمام قضية غامضة وشائقة بسبب اختفاء البروفيسور أديب. المتهم الرئيسي في قضية انفجار مصنع شركة إنيرجيز وسيسعون معا إلى كشف الحقيقة بالبحث عنه وإثبات براءته.
Book
Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox
Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called “calcification paradox”. Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.
This study uncovers the role of extracellular vesicles from bone matrix as a messenger in the development of osteoporosis and vascular calcification (calcification paradox) during skeletal aging and menopause by transferring miR-483-5p and miR-2861.
Journal Article
The Protective Effects of Osteocyte‐Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging
Both Alzheimer's disease (AD) and osteoporosis (OP) are common age‐associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCYYoung‐EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCYYoung‐EVs are diminished in aged osteocyte‐derived EVs (OCYAged‐EVs). Based on the self‐constructed OCY‐EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY‐EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a‐shRNA adenovirus inhibits OCYYoung‐EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCYYoung‐EVs, compared to OCYAged‐EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY‐EV as a regulator of brain health, suggesting a novel mechanism in bone‐brain communication. It is found that the osteocyte‐derived extracellular vesicles (OCY‐EVs) isolated from young osteocytes can ameliorate cognitive impairment and pathogenies of AD, but not OCY‐EVs isolated from aged osteocytes. OCY‐EV can transfer to the brain under physiological and pathological conditions. The study uncovers the role of OCY‐EVs as a regulator of brain, suggesting a novel mechanism in bone‐brain communication.
Journal Article
A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules
Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (
C
RISPR-Cas12a- and
aT
F-mediated
s
mall
m
ol
e
cu
l
e detect
or
). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and
p
-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.
Bacterial allosteric transcription factors can sense and respond to a variety of small molecules. Here the authors present CaT-SMelor which uses Cas12a and allosteric transcription factors to detect small molecules in the nanomolar range.
Journal Article
The Vehicle Routing Problem: State-of-the-Art Classification and Review
Transportation planning has been established as a key topic in the literature and social production practices. An increasing number of researchers are studying vehicle routing problems (VRPs) and their variants considering real-life applications and scenarios. Furthermore, with the rapid growth in the processing speed and memory capacity of computers, various algorithms can be used to solve increasingly complex instances of VRPs. In this study, we analyzed recent literature published between 2019 and August of 2021 using a taxonomic framework. We reviewed recent research according to models and solutions, and divided models into three categories of customer-related, vehicle-related, and depot-related models. We classified solution algorithms into exact, heuristic, and meta-heuristic algorithms. The main contribution of our study is a classification table that is available online as Appendix A. This classification table should enable future researchers to find relevant literature easily and provide readers with recent trends and solution methodologies in the field of VRPs and some well-known variants.
Journal Article
Augmented and Virtual Reality (AR/VR) for Education and Training in the AEC Industry: A Systematic Review of Research and Applications
With updated equipment and maturing technology, the applications of augmented and virtual reality (AR/VR) technologies in the architecture, engineering, and construction (AEC) industry are receiving increasing attention rapidly. Especially in education and training, an increasing number of researchers have started to implement AR/VR technologies to provide students or trainees with a visual, immersive, and interactive environment. In this article, a systematic review of AR/VR technologies for education and training in the AEC industry is conducted. First of all, through comprehensive analysis, 82 related studies are identified from two databases, namely Scopus and Web of Science. Secondly, the VOSviewer is used to analyze the current status of AR/VR for education and training in the AEC industry. Thirdly, the identified studies are classified into different categories according to their application domains by qualitative analysis. Fourthly, after a further filtering, 17 out of the 82 studies are included in the meta-analysis to quantify the actual impact of AR/VR. The results indicate that there are some limitations in the applications of AR/VR for education and training in the AEC industry. Finally, to further explore the reasons for the existence of limitations, the 82 studies are summarized to analyze the current challenges of AR/VR for education and training in the AEC industry. This study also provides insights into future trends in AR/VR for education and training in the AEC industry.
Journal Article
In vitro allosteric transcription factor-based biosensing
Bacterial allosteric transcription factors (aTFs) are a new class of recognition elements for in vitro biosensing.In vitro aTF-based biosensing approaches address issues of whole-cell biosensors and open a novel route to develop tailored aTF-based biosensors.Harnessing of aTF recognition coupled with proximity effect-driven output, DNA signal output, cell-free systems, and CRISPR-Cas outputs has been developed to configure biosensors in vitro.Unique traits of aTFs endow biosensing strategies with the characteristics of high accessibility, modularity, easy fine-tuning, and low cost.Concerted efforts are required to develop a modular, systematic, and predictable workflow for aTF discovery, aTF-based biosensor configuration, and fine-tuning to readily fulfill user-defined applications.
A biosensor is an analytical device that converts a biological response into a measurable output signal. Bacterial allosteric transcription factors (aTFs) have been utilized as a novel class of recognition elements for in vitro biosensing, which circumvents the limitations of aTF-based whole-cell biosensors (WCBs) and helps to meet the increasing requirement of small-molecule biosensors for diverse applications. In this review, we summarize the recent advances related to the configuration of aTF-based biosensors in vitro. Particularly, we evaluate the advantages of aTFs for in vitro biosensing and highlight their great potential for the establishment of robust and easy-to-implement biosensing strategies. We argue that key technical innovations and generalizable workflows will enhance the pipeline for facile construction of diverse aTF-based small-molecule biosensors.
Journal Article
Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence
The pathogenesis and clinical features of diabetic cardiomyopathy have been well-studied in the past decade, but effective approaches to prevent and treat this disease are limited. Diabetic cardiomyopathy occurs as a result of the dysregulated glucose and lipid metabolism associated with diabetes mellitus, which leads to increased oxidative stress and the activation of multiple inflammatory pathways that mediate cellular and extracellular injury, pathological cardiac remodelling, and diastolic and systolic dysfunction. Preclinical studies in animal models of diabetes have identified multiple intracellular pathways involved in the pathogenesis of diabetic cardiomyopathy and potential cardioprotective strategies to prevent and treat the disease, including antifibrotic agents, anti-inflammatory agents and antioxidants. Some of these interventions have been tested in clinical trials and have shown favourable initial results. In this Review, we discuss the mechanisms underlying the development of diabetic cardiomyopathy and heart failure in type 1 and type 2 diabetes mellitus, and we summarize the evidence from preclinical and clinical studies that might provide guidance for the development of targeted strategies. We also highlight some of the novel pharmacological therapeutic strategies for the treatment and prevention of diabetic cardiomyopathy.Diabetic cardiomyopathy occurs as a result of the dysregulated glucose and lipid metabolism, increased oxidative stress and activation of pro-inflammatory pathways associated with diabetes mellitus, which can induce cardiac remodelling and dysfunction. In this Review, Tan and colleagues discuss the pathogenesis of diabetic cardiomyopathy and describe signalling pathways that might be potential therapeutic targets.
Journal Article
Comprehensive Insights into Medicinal Research on Imidazole-Based Supramolecular Complexes
The electron-rich five-membered aromatic aza-heterocyclic imidazole, which contains two nitrogen atoms, is an important functional fragment widely present in a large number of biomolecules and medicinal drugs; its unique structure is beneficial to easily bind with various inorganic or organic ions and molecules through noncovalent interactions to form a variety of supramolecular complexes with broad medicinal potential, which is being paid an increasing amount of attention regarding more and more contributions to imidazole-based supramolecular complexes for possible medicinal application. This work gives systematical and comprehensive insights into medicinal research on imidazole-based supramolecular complexes, including anticancer, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and anti-inflammatory aspects as well as ion receptors, imaging agents, and pathologic probes. The new trend of the foreseeable research in the near future toward imidazole-based supramolecular medicinal chemistry is also prospected. It is hoped that this work provides beneficial help for the rational design of imidazole-based drug molecules and supramolecular medicinal agents and more effective diagnostic agents and pathological probes.
Journal Article