•A unified fire-induced concrete spalling theory is proposed.•Fire-induced spalling is categorised into three types according to their distinct governing mechanisms, viz., thermo-hygral, ...thermo-mechanical and thermo-chemical spalling.•The spalling temperature range, influencing factors and the protective measures for each type of spalling are discussed.•A design concept of ‘multiple defense line against fire-induced concrete spalling’ is introduced based on the unified fire-induced concrete spalling theory.
Spalling of concrete is a great potential threat to fire resistance of concrete structures. Understanding the underlying mechanism is important to predict and mitigate this unfavorable phenomenon. Currently, there are two main mechanisms to explain the fire-induced concrete spalling: viz. spalling due to (a) pore pressure buildup or (b) thermal stress. The relative importance of these two mechanisms has been a subject of intense debate in the research community over the past few decades. This paper presents a critical review of conflicting and concordant points on concrete spalling at high temperature and proposes a unified and coherent fire-induced concrete spalling theory. Therein, the authors propose three types of thermal spalling depending on the governing mechanisms: thermo-hygral spalling, thermo-mechanical spalling and thermo-chemical spalling. The criteria to forecast each type of spalling are established and the spalling temperature range for each of them is analysed. The spalling pattern, influencing factors and preventive measures for each type of spalling are also discussed in this paper.
Background:
Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture ...(EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD).
Methods:
The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2—signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB).
Results:
EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1β, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells.
Conclusion:
We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.
Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the ...perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.
Traditional microwaves absorption materials (MAMs) are applied in the form of coatings, generally inflexible, with high production costs and poor adaptability to applications in different locations. ...The diversification of application scenarios requires materials with multifunctionalities, but it is extremely challenging to integrate multifunctionalities within single material at present. Herein, a multifunctional CoNC@GN/PCL/TPU MAMs is synthesized. The CoNC@GN nano‐micro absorber has high‐efficiency microwave absorption ability. The electromagnetic microwave absorption performance is ultra‐light (4 wt.%), ultra‐thin (2.3 mm), and broadband (6.21 GHz), which is better than similar MAMs. Additionally, the samples have highly efficient electro‐thermal conversion properties, enabling controlled electrical heating performance and excellent self‐healing properties. More remarkably, the sample has an electrically driven shape memory effect that allows the material to target the absorption of multi‐angle incident electromagnetic waves. Therefore, CoNC@GN/PCL/TPU absorbers are the key to truly opening up opportunities for flexible, shape memory, and multifunctional absorbers in frontier applications such as wearables, deformable robots, and chip protection.
Flexible composites with multifunctional CoNC@GN/PCL/TPU are synthesized with outstanding Joule thermal properties, self‐healing properties, electrically driven shape memory effect, and efficient microwave absorption properties. The absorbing properties and radar cross section of the material under different electromagnetic wave incidence are also investigated. Interestingly, the maximum absorption of electromagnetic waves by adjusting the angle of the material can be achieved. With a thickness of 2.3 mm, the effective absorption bandwidth of the material reaches 6.21 GHz.
Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene ...expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC.
circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization.
The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression.
We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.
Background and Purpose
Non‐alcoholic steatohepatitis (NASH) is the more severe form of metabolic associated fatty liver disease (MAFLD) and no pharmacological treatment as yet been approved. ...Identification of novel therapeutic targets and their agents is critical to overcome the current inadequacy of drug treatment for NASH.
Experimental Approach
The correlation between heat shock factor 1 (HSF1) levels and the development of NASH and the target genes of HSF1 in hepatocyte were investigated by chromatin‐immunoprecipitation sequencing. The effects and mechanisms of SYSU‐3d in alleviating NASH were examined in relevant cell models and mouse models (the Ob/Ob mice, high‐fat and high‐cholesterol diet and the methionine‐choline deficient diet‐fed mice). The actions of SYSU‐3d in vivo were evaluated.
Key Results
HSF1 is progressively reduced with mitochondrial dysfunction in NASH pathogenesis and activation of this transcription factor by its newly identified activator SYSU‐3d effectively inhibited all manifestations of NASH in mice. When activated, the phosphorylated HSF1 (Ser326) translocated to nucleus and bound to the promoter of PPARγ coactivator‐1α (PGC‐1α) to induce mitochondrial biogenesis. Thus, increasing mitochondrial adaptive oxidation and inhibiting oxidative stress. The deletion of HSF1 and PGC‐1α or recovery of HSF1 in HSF1‐deficiency cells showed the HSF1/PGC‐1α pathway was mainly responsible for the anti‐NASH effects of SYSU‐3d independent of AMP‐activated protein kinase (AMPK).
Conclusion and Implications
Activation of HSF1 is a practical therapeutic approach for NASH treatment via the HSF1/PGC‐1α/mitochondrial pathway and SYSU‐3d can be considered as a potential candidate for the treatment of NASH.
The molecular mode of SYSU‐3d action against NASH is dependent on the HSF1/PGC‐1α/mitochondrial pathway, which initially increases lipid oxidation followed by decreases oxidative stress, preventing injury, inflammation, and fibrosis. Our combined findings indicate that correction of the HSF1 suppression can be utilised as a practicable therapeutic approach for the treatment of NASH.
In the current work, a series of black polyimide (PI) films with excellent thermal and dimensional stability at elevated temperatures were successfully developed. For this purpose, two aromatic ...diamines including 4,4'-iminodianline (NDA) and 2-(4-aminophenyl)-5- aminobenzimidazole (APBI) were copolymerized with pyromellitic dianhydride (PMDA) to afford PIs containing imino groups (-NH-) in the molecular structures. The referenced PI film, PI-ref, was simultaneously prepared from PMDA and 4,4'-oxydianiline (ODA). The introduction of imino groups endowed the PI films with excellent blackness and opaqueness with the optical transmittance lower than 2% at the wavelength of 600 nm at a thickness of 25 μm and lightness (
) below 10 for the CIE (Commission International Eclairage) Lab optical parameters. Meanwhile, the introduction of rigid benzimidazole units apparently improved the thermal and dimensional stability of the PI films. The PI-d film based on PMDA and mixed diamines (NDA:APBI = 70:30, molar ratio) showed a glass transition temperature (
) of 445.5 °C and a coefficient of thermal expansion (CTE) of 8.9 × 10
/K in the temperature range of 50 to 250 °C, respectively. It is obviously superior to those of the PI-a (PMDA-NDA,
= 431.6 °C; CTE = 18.8 × 10
/K) and PI-ref (PMDA-ODA,
= 418.8 °C; CTE: 29.5 × 10
/K) films.
Electrolyte engineering via fluorinated additives is promising to improve cycling stability and safety of high‐energy Li‐metal batteries. Here, an electrolyte is reported in a porous lithium fluoride ...(LiF) strategy to enable efficient carbonate electrolyte engineering for stable and safe Li‐metal batteries. Unlike traditionally engineered electrolytes, the prepared electrolyte in the porous LiF nanobox exhibits nonflammability and high electrochemical performance owing to strong interactions between the electrolyte solvent molecules and numerous exposed active LiF (111) crystal planes. Via cryogenic transmission electron microscopy and X‐ray photoelectron spectroscopy depth analysis, it is revealed that the electrolyte in active porous LiF nanobox involves the formation of a high‐fluorine‐content (>30%) solid electrolyte interphase layer, which enables very stable Li‐metal anode cycling over one thousand cycles under high current density (4 mA cm−2). More importantly, employing the porous LiF nanobox engineered electrolyte, a Li || LiNi0.8Co0.1Mn0.1O2 pouch cell is achieved with a specific energy of 380 Wh kg−1 for stable cycling over 80 cycles, representing the excellent performance of the Li‐metal pouch cell using practical carbonate electrolyte. This study provides a new electrolyte engineering strategy for stable and safe Li‐metal batteries.
Electrolyte engineering via fluorinated additives is promising to improve the cycling stability and safety of high‐energy Li‐metal batteries. The electrolyte in an active porous LiF nanobox involves the formation of a high‐fluorine‐content (>30%) solid electrolyte interphase layer to achieve a ≈3.5 Ah Li || LiNi0.8Co0.1Mn0.1O2 pouch cell with a specific energy of 380 Wh kg−1 under a practical carbonate electrolyte.
Organic dye based NIR‐II fluorescent probes, owing to their high signal‐to‐background ratio and deeper penetration, are highly useful for deep‐tissue high‐contrast imaging in vivo. However, it is ...still a challenge to design activatable NIR‐II fluorescent probes. Here, a novel class of polymethine dyes (NIRII‐RTs), with bright (quantum yield up to 2.03 %), stable, and anti‐solvent quenching NIR‐II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR‐II dyes NIRII‐RT3 and NIRII‐RT4, equipped with a carboxylic acid group, can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target‐activatable NIRII‐RT probes (NIRII‐RT‐pH, NIRII‐RT‐ATP and NIRII‐RT‐Hg) for pH, adenosine triphosphate (ATP), and metal‐ion detection, were synthesized. By applying the NIRII‐RT probe, the real‐time monitoring of drug‐induced hepatotoxicity was realized.
The presented work reports a new class of polymethine dyes (NIRII‐RTs) with bright, stable, and anti‐quenching NIR‐II emissions together with large Stokes shifts. Importantly, by introducing the carboxylic acid functional group, the novel dyes NIRII‐RT3 and NIRII‐RT4 can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast.
Background
Professional identity formation (PIF) in medical students is a multifactorial phenomenon, shaped by ways that clinical and non-clinical experiences, expectations and environmental factors ...merge with individual values, beliefs and obligations. The relationship between students’ evolving professional identity and self-identity or personhood remains ill-defined, making it challenging for medical schools to support PIF systematically and strategically. Primarily, to capture prevailing literature on PIF in medical school education, and secondarily, to ascertain how PIF influences on medical students may be viewed through the lens of the ring theory of personhood (RToP) and to identify ways that medical schools support PIF.
Methods
A systematic scoping review was conducted using the systematic evidence-based approach. Articles published between 1 January 2000 and 1 July 2020 related to PIF in medical students were searched using PubMed, Embase, PsycINFO, ERIC and Scopus. Articles of all study designs (quantitative and qualitative), published or translated into English, were included. Concurrent thematic and directed content analyses were used to evaluate the data.
Results
A total of 10443 abstracts were identified, 272 full-text articles evaluated, and 76 articles included. Thematic and directed content analyses revealed similar themes and categories as follows: characteristics of PIF in relation to professionalism, role of socialization in PIF, PIF enablers and barriers, and medical school approaches to supporting PIF.
Discussion
PIF involves iterative construction, deconstruction and inculcation of professional beliefs, values and behaviours into a pre-existent identity. Through the lens of RToP, factors were elucidated that promote or hinder students’ identity development on individual, relational or societal levels. If inadequately or inappropriately supported, enabling factors become barriers to PIF. Medical schools employ an all-encompassing approach to support PIF, illuminating the need for distinct and deliberate longitudinal monitoring and mentoring to foster students’ balanced integration of personal and professional identities over time.
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