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Short-chain fatty acids are potential goalkeepers of atherosclerosis
Short-chain fatty acids (SCFAs) are metabolites produced by gut bacteria and play a crucial role in various inflammatory diseases. Increasing evidence suggests that SCFAs can improve the occurrence and progression of atherosclerosis. However, the molecular mechanisms through which SCFAs regulate the development of atherosclerosis have not been fully elucidated. This review provides an overview of the research progress on SCFAs regarding their impact on the risk factors and pathogenesis associated with atherosclerosis, with a specific focus on their interactions with the endothelium and immune cells. These interactions encompass the inflammation and oxidative stress of endothelial cells, the migration of monocytes/macrophages, the lipid metabolism of macrophages, the proliferation and migration of smooth muscle cells, and the proliferation and differentiation of Treg cells. Nevertheless, the current body of research is insufficient to comprehensively understand the full spectrum of SCFAs’ mechanisms of action. Therefore, further in-depth investigations are imperative to establish a solid theoretical foundation for the development of clinical therapeutics in this context.
Journal Article
صلوات تبتية : (رواية) /
تلقي الرواية الضوء على منطقة مجهولة جغرافيا وتاريخيا من الصين، وهي منطقة غير مألوفة للقارئ العربي، وتثير داخله شعورا مبهما بالسحر والغموض، ويتوازى بالرواية مساران سرديان، يروي المسار الرئيسي التغيرات التاريخية للتبت على مدار الخمسين عاما الماضية، وتحول بطل الرواية (جين مي وانغ تشا) من شخصية الراهب إلى العلماني، ويصف التمرد المسلح للمتشددين، والإصلاح الديمقراطي، ونشوب الحرب بين الصين والهند، وغيرها من الأحداث التاريخية الكبرى لتاريخ التبت، ومع الصعود والهبوط في مصير العديد من الشخصيات الصغيرة، تعرض الرواية النظرة التبتية حول مفهوم الموت والحياة وفهم وتجاوز المعاناة المتعلقة بحياة المعلم البوذي.
BOOK
A CRISPR–Cas9-triggered strand displacement amplification method for ultrasensitive DNA detection
Although polymerase chain reaction (PCR) is the most widely used method for DNA amplification, the requirement of thermocycling limits its non-laboratory applications. Isothermal DNA amplification techniques are hence valuable for on-site diagnostic applications in place of traditional PCR. Here we describe a true isothermal approach for amplifying and detecting double-stranded DNA based on a CRISPR–Cas9-triggered nicking endonuclease-mediated Strand Displacement Amplification method (namely CRISDA). CRISDA takes advantage of the high sensitivity/specificity and unique conformational rearrangements of CRISPR effectors in recognizing the target DNA. In combination with a peptide nucleic acid (PNA) invasion-mediated endpoint measurement, the method exhibits attomolar sensitivity and single-nucleotide specificity in detection of various DNA targets under a complex sample background. Additionally, by integrating the technique with a Cas9-mediated target enrichment approach, CRISDA exhibits sub-attomolar sensitivity. In summary, CRISDA is a powerful isothermal tool for ultrasensitive and specific detection of nucleic acids in point-of-care diagnostics and field analyses.
Isothermal DNA amplification techniques are useful for diagnostic applications in place of traditional PCR. Here the authors describe CRISDA, which combines CRISPR–Cas9 with strand displacement amplification and exhibits attomolar sensitivity and single-nucleotide specificity in DNA detection.
Journal Article
Construction Planning and Operation of Battery Swapping Stations for Electric Vehicles: A Literature Review
The popularity of electric vehicles has been limited by factors such as range, long charging times and fast power failure in winter. In order to overcome these challenges, battery swapping stations (BSS) have been constructed and greatly promoted in recent years. In this paper, the related literature on electric vehicle service is reviewed and the co-occurrence of keywords is analyzed using CiteSpace. The literature is classified according to clustering results and recurring themes, such as the location of BSS, inventory decisions, charging strategies and BSS assignment. In each topic, typical optimization models and algorithms proposed in previous studies are summarized. Then, this paper gives a case about the business model and revenue capacity calculation of BSS. Finally, it points out the future research direction of battery swapping stations for electric vehicles.
Journal Article
Quality of life in Parkinson's disease: A systematic review and meta‐analysis of comparative studies
Background Studies regarding the impact of Parkinson's disease (PD) on quality of life (QOL) have reported conflicting results, and the underlying QOL domains require further study. In order to understand the association between PD and QOL, we conducted this meta‐analysis to systematically compare QOL between PD patients and healthy controls. Method The PubMed, PsycINFO, EMBASE, and Web of Science databases were systematically searched. Data were analyzed using the random‐effects model. Results Twenty studies covering 2707 PD patients and 150,661 healthy controls were included in the study. Compared with healthy controls, PD patients had significantly poorer QOL overall and in most domains with moderate to large effects sizes. Different QOL measures varied in their association with quality of life, with the Parkinson's Disease Questionnaire‐39 (PDQ‐39) having the largest effect size (standard mean difference, SMD = −1.384, 95% CI: −1.607, −1.162, Z = 12.189, P < 0.001), followed by the Europe Quality of Life Questionnaire‐visual analogue scale (EQ‐VAS) (SMD = −1.081, 95% CI: −1.578, −0.584, Z = −4.265, P < 0.001), Europe Quality of Life Questionnaire‐5D (EQ‐5D) (SMD = −0.889, 95% CI: −1.181, −0.596, Z = −5.962, P < 0.001), and the Short‐form Health Survey (SF) scales (physical dimension: SMD = −0.826, 95% CI: −1.529, −0.123, Z = −2.303, P = 0.021; mental dimension: SMD = −0.376, 95% CI: −0.732, −0.019, Z = −2.064, P = 0.039). Conclusion PD patients had lower QOL compared with healthy controls in most domains, especially in physical function and mental health. Considering the negative impact of poor QOL on daily life and functional outcomes, effective measures should be developed to improve QOL in this population. Improving the QOL in patients with PD is an important concern, which can provide reference for decisions of policymakers and clinicians. PD patients had significantly poorer QOL, with moderate to large effect sizes in most domains. Moreover, different QOL measures had moderating effects on the results.
Journal Article
Mass production of bulk artificial nacre with excellent mechanical properties
Various methods have been exploited to replicate nacre features into artificial structural materials with impressive structural and mechanical similarity. However, it is still very challenging to produce nacre-mimetics in three-dimensional bulk form, especially for further scale-up. Herein, we demonstrate that large-sized, three-dimensional bulk artificial nacre with comprehensive mimicry of the hierarchical structures and the toughening mechanisms of natural nacre can be facilely fabricated via a bottom-up assembly process based on laminating pre-fabricated two-dimensional nacre-mimetic films. By optimizing the hierarchical architecture from molecular level to macroscopic level, the mechanical performance of the artificial nacre is superior to that of natural nacre and many engineering materials. This bottom-up strategy has no size restriction or fundamental barrier for further scale-up, and can be easily extended to other material systems, opening an avenue for mass production of high-performance bulk nacre-mimetic structural materials in an efficient and cost-effective way for practical applications.
Artificial materials that replicate the mechanical properties of nacre represent important structural materials, but are difficult to produce in bulk. Here, the authors exploit the bottom-up assembly of 2D nacre-mimetic films to fabricate 3D bulk artificial nacre with an optimized architecture and excellent mechanical properties.
Journal Article
Long non‐coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA‐223 down‐regulation in viral myocarditis
Viral myocarditis (VMC) commonly triggers heart failure, for which no specific treatments are available. This study aims to explore the specific role of long non‐coding RNA (lncRNA) maternally expressed 3 (MEG3) in VMC. A VMC mouse model was induced by Coxsackievirus B3 (CVB3). Then, MEG3 and TNF receptor‐associated factor 6 (TRAF6) were silenced and microRNA‐223 (miR‐223) was over‐expressed in the VMC mice, followed by determination of ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Dual‐luciferase reporter assay was introduced to test the interaction among MEG3, TRAF6 and miR‐223. Macrophages were isolated from cardiac tissues and bone marrow, and polarization of M1 or M2 macrophages was induced. Then, the expressions of components of NLRP3 inflammatory body (NLRP3, ASC, Caspase‐1), M1 markers (CD86, iNOS and TNF‐α) and M2 markers (CD206, Arginase‐1 and Fizz‐1) were measured following MEG3 silencing. In the VMC mouse model, MEG3 and TRAF6 levels were obviously increased, while miR‐223 expression was significantly reduced. Down‐regulation of MEG3 resulted in the inhibition of TRAF6 by promoting miR‐223. TRAF6 was negatively correlated with miR‐223, but positively correlated with MEG3 expression. Down‐regulations of MEG3 or TRAF6 or up‐regulation of miR‐223 was observed to increase mouse weight, survival rate, LVEF and LVFS, while inhibiting myocarditis and inflammation via the NF‐κB pathway inactivation in VMC mice. Down‐regulation of MEG3 decreased M1 macrophage polarization and elevated M2 macrophage polarization by up‐regulating miR‐223. Collectively, down‐regulation of MEG3 leads to the inhibition of inflammation and induces M2 macrophage polarization via miR‐223/TRAF6/NF‐κB axis, thus alleviating VMC.
Journal Article
Stromal induction of BRD4 phosphorylation Results in Chromatin Remodeling and BET inhibitor Resistance in Colorectal Cancer
BRD4, a Bromodomain and Extraterminal (BET) protein family member, is a promising anti-cancer drug target. However, resistance to BET inhibitors targeting BRD4 is common in solid tumors. Here, we show that cancer-associated fibroblast (CAF)-activated stromal signaling, interleukin-6/8-JAK2, induces BRD4 phosphorylation at tyrosine 97/98 in colorectal cancer, resulting in BRD4 stabilization due to interaction with the deubiquitinase UCHL3. BRD4 phosphorylation at tyrosine 97/98 also displays increased binding to chromatin but reduced binding to BET inhibitors, resulting in resistance to BET inhibitors. We further show that BRD4 phosphorylation promotes interaction with STAT3 to induce chromatin remodeling through concurrent binding to enhancers and super-enhancers, supporting a tumor-promoting transcriptional program. Inhibition of IL6/IL8-JAK2 signaling abolishes BRD4 phosphorylation and sensitizes BET inhibitors in vitro and in vivo. Our study reveals a stromal mechanism for BRD4 activation and BET inhibitor resistance, which provides a rationale for developing strategies to treat CRC more effectively.
BRD4 has a pro-tumorigenic role but non-cell-autonomous mechanisms of BRD4 activation need to be elucidated. Here the authors unravel a mechanism by which CAFs activate BRD4 and induce resistance to BET inhibitors in cancer cells through IL6/IL8 signaling.
Journal Article
Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1–SOX2 positive-feedback loop
CD133 and Notch1 double-positive GSCs were preferentially located along Jagged1-expressing white matter tracts, which exhibited a demyelinated phenotype. The NOTCH1–SOX9–SOX2 positive-feedback loop controls GSC invasion along white matter tracts.
Journal Article