The size-dependent in vivo toxicity of amorphous silica nanoparticles: A systematic review.

The extensive application of amorphous silica nanoparticles (aSiNPs) in recent years has resulted in unavoidable human exposure in daily life, thus raising widespread concerns regarding the safety of aSiNPs on human health. The particle size is one of the important characteristics of nanomaterials that could influence their toxicity. For the reason that particles with smaller sizes possess larger surface area, which may lead to higher surface activity and biological reactivity. However, due to the complexity of experimental conditions and biological systems, the relationship between the particle size and the toxic effect of aSiNPs remains unclear. Therefore, this systematic review aims to investigate how particle size influences the toxic effect of aSiNPs in vivo and to analyze the relevant experimental factors affecting the size-dependent toxicity of aSiNPs in vivo. We found that 83.8% of 35 papers included in the present review came to the conclusion that smaller-sized aSiNPs exhibited stronger toxicity, though a few papers (6 papers) put forward different opinions. The reasons for smaller aSiNPs manifested greater toxicity were summarized. In addition, certain important experimental factors could influence the size-dependent effects and in vivo toxicity of aSiNPs, such as the synthesis method of aSiNPs, disperse medium of aSiNPs, administration route of aSiNPs, species or strain of experimental animals, sex of experimental animals, aggregation/agglomeration and protein corona of aSiNPs.

Amorphous silica nanoparticles cause abnormal cytokinesis and multinucleation through dysfunction of the centralspindlin complex and microfilaments.

BACKGROUND: With the large-scale production and application of amorphous silica nanoparticles (aSiNPs), its adverse health effects are more worthy of our attention. Our previous research has demonstrated for the first time that aSiNPs induced cytokinesis failure, which resulted in abnormally high incidences of multinucleation in vitro, but the underlying mechanisms remain unclear. Therefore, the purpose of this study was firstly to explore whether aSiNPs induced multinucleation in vivo, and secondly to investigate the underlying mechanism of how aSiNPs caused abnormal cytokinesis and multinucleation. METHODS: Male ICR mice with intratracheal instillation of aSiNPs were used as an experimental model in vivo. Human hepatic cell line (L-02) was introduced for further mechanism study in vitro. RESULTS: In vivo, histopathological results showed that the rate of multinucleation was significantly increased in the liver and lung tissue after aSiNPs treatment. In vitro, immunofluorescence results manifested that aSiNPs directly caused microfilaments aggregation. Following mechanism studies indicated that aSiNPs increased ROS levels. The accumulation of ROS further inhibited the PI3k 110ß/Aurora B pathway, leading to a decrease in the expression of centralspindlin subunits MKLP1 and CYK4 as well as downstream cytokines regulation related proteins Ect2, Cep55, CHMP2A and RhoA. Meanwhile, the particles caused abnormal co-localization of the key mitotic regulatory kinase Aurora B and the centralspindlin complex by inhibiting the PI3k 110ß/Aurora B pathway. PI3K activator IGF increased the phosphorylation level of Aurora B and improved the relative ratio of the centralspindlin cluster. And ROS inhibitors NAC reduced the ratio of multinucleation, alleviated the PI3k 110ß/Aurora B pathway inhibition, and then increased the expression of MKLP1, CYK4 and cytokinesis-related proteins, whilst NAC restored the clustering of the centralspindlin. CONCLUSION: This study demonstrated that aSiNPs led to multinucleation formation both in vivo and in vitro. ASiNPs exposure caused microfilaments aggregation and inhibited the PI3k 110ß/Aurora B pathway through excessive ROS, which then hindered the centralspindlin cluster as well as restrained the expression of centralspindlin subunits and cytokinesis-related proteins, which ultimately resulted in cytokinesis failure and the formation of multinucleation.

An ESIPT-based ratiometric fluorescent probe for detecting H2O2 in water environment and biosystems.

The outbreak of the COVID-19 has resulted in a great increase in the use of H2O2 disinfectant, which is listed as one of the commonly used disinfectants for COVID-19 by the U.S. Environmental Protection Agency. However, excessive use of H2O2 disinfectant can threaten human health and damage the water environment. Therefore, it's of great importance to detect H2O2 in aquatic environments and biological systems. Herein, we proposed a novel ESIPT ratio fluorescent probe (named probe 1) for detecting H2O2 in water environment and biosystems. Probe 1 emits blue fluorescence as the introduction of the phenylboronic acid disrupts the ESIPT process. After reacting with H2O2, the phenylboronic acid is oxidatively removed, and the ESIPT process is restored, which makes the fluorescence emission wavelength red-shifted. Probe 1 exhibited a short response time, high sensitivity, and a large Stokes shift to H2O2. Importantly, it has been successfully used to detect H2O2 not only in actual water samples, but also endogenous and exogenous H2O2 in living cells. The characteristics of probe 1 have a wide range of applications in environmental and biological systems.

Evaluation of reliability and validity regarding the Chinese version of Critical Cultural Competence Scale for clinical nurses. / 临床护士评判性文化能力量表的汉化及信效度评价.

OBJECTIVES: Patients from different social environments and cultural backgrounds have different nursing needs. If nurses ignore the cultural differences of patients, it is easy to lead to the strained nurse-patient relationship, affect the nursing effect and cause harm to patients. Critical cultural competence (CCC) can help nurses to meet the nursing needs of patients from different cultural backgrounds, which is beneficial to building a harmonious nurse-patient relationship and improving the quality of nursing. Almutairi, et al designed the Critical Cultural Competence Scale (CCCS) which can be used to evaluate accurately nurses' CCC. No studies have reported the development of a critical cultural competence measurement tool for nurses or the introduction of foreign scales in China. This study aims to conduct Chinese and cross-cultural debugging and test the reliability of the English version of the CCCS in order to form CCCS suitable for Chinese cultural background and provide an effective evaluation tool for investigating the current situation of clinical nurses' CCC. METHODS: This study used Brislin's back-translation model to translate and back-translation the English version of CCCS. The Chinese version of CCCS was then created through cross-cultural debugging by expert consultation and a pre-survey with a sample size of 30 clinical nurses. From August to October 2019, 580 clinical nurses were surveyed using a whole group sampling method. The participants were randomly divided into 2 groups with a 7꞉3 ratio. One group (n=406) was used for exploratory factor analysis and reliability analysis, while the other group (n=174) was used for confirmatory factor analysis. Six experts used the scale-level content validity index (S-CVI) and the item-level content validity index (I-CVI) to assess content validity. In the exploratory factor analysis, items were screened using the critical ratio method, and were tested using the KMO (Kalser-Meyer-Olkin) index, Bartlett's sphericity test, and principal component analysis. In the confirmatory factor analysis, average variance extracted (AVE), goodness of fit index (GFI), adjusted goodness of fit index (AGFI), and root mean square error of approximation (RMSEA) were used to assess the degree of fit of the constructed model. For the total scale and the 4 subscales, the Cronbach's α coefficient, split-half reliability, and retest reliability were used to assess the scale's reliability. RESULTS: The S-CVI was 0.930, while the I-CVI ranged from 0.833 to 0.944. For all items, the critical ratio exceeded 3, and the difference between the high and low subgroups was statistically significant (P<0.05). Exploratory factor analysis revealed critical knowledge subscale had a KMO value of 0.676, with the total scale and other 3 subscales all having a KMO value >0.8 and a chi-square value of 814.32 to 12 442.45 for the Bartlett's spherical test, with degree of freedom ranging from 21 to 136 (P<0.001), indicating that all items were suitable for factor analysis. The principal component analysis showed that 17, 12, 7, and 7 items were extracted from the 4 subscales, with 4, 3, 2, and 2 components whose eigenvalues were more than 1, and the cumulative variance contribution was 66.0%, 54.3%, 56.6%, and 70.2%, respectively. The confirmatory factor analysis showed that the AVE of the 4 subscales were 0.637, 0.499, 0.560, and 0.565, GFI was 0.904, AGFI was 0.863, and RMSEA was 0.076. The Cronbach's α coefficient for the total scale and subscales ranged from 0.811 to 0.878, the split-half reliability ranged from 0.707 to 0.842, and the retest reliability was 0.827. CONCLUSIONS: The Chinese version of the CCCS has good reliability and validity, and it can be used as a valid assessment tool for clinical nurses' critical cultural competence in China.

Rational design of a reversible fluorescent probe for sensing GSH in mitochondria.

Glutathione (GSH) is the most abundant biological thiol in cells. It can participate in metabolic processes, regulate the body's oxidation level and is essential for various cell functions. An abnormal concentration of glutathione in the cell is directly related to some diseases. Therefore, it is very important to develop fast, sensitive and reversible detection methods for GSH. Herein, we designed a reversible fluorescent probe (named GeP) for sensing GSH based on the nucleophilic addition and dissociation of intracellular GSH to GeP. The probe GeP showed a fast response time and a 20-fold fluorescence change toward GSH. It exhibited excellent mitochondrial-targeted performance and could be used to monitor GSH in mitochondria. Importantly, GeP could also enable superresolution fluorescence imaging of mitochondria through stochastic optical reconstruction microscopy.

FoxO1 Silencing Facilitates Neurological Function Recovery in Intracerebral Hemorrhage Mice via the lncRNA GAS5/miR-378a-5p/Hspa5 Axis.

OBJECTIVE: Intracerebral hemorrhage (ICH) is the most devastating stroke subtype. Transcription factor Forkhead box O1 (FoxO1) is extensively implicated in cerebral injury. This study investigated the mechanism of FoxO1 in neurological function recovery in ICH mice. METHODS: A murine model of ICH was established. The modified neurological severity score (mNSS), forelimb placement test, and corner turn test were adopted to evaluate the neurological function of mice. The brain water content was measured and the pathological changes of cerebral tissues were observed. The levels of IL-1ß, IL-6, and TNF-α were determined. The expressions of FoxO1, lncRNA GAS5, miR-378a-5p, and heat shock 70 kDa protein 5 (Hspa5) in mouse cerebral tissues were examined. The binding relationships among FoxO1, lncRNA GAS5, miR-378a-5p, and Hspa5 were validated. Functional rescue experiments were designed to verify the role of lncRNA GAS5/miR-378a-5p/Hspa5 axis in neurological function recovery in ICH mice. RESULTS: FoxO1 was highly expressed in cerebral tissues of ICH mice. FoxO1 silencing facilitated neurological function recovery in ICH mice, evidenced by decreased mNSS, improved forelimb placement rate, reduced turning defects, declined brain water content, relieved edema, intracellular vacuoles, and inflammatory cell infiltration, and reduced IL-1ß, IL-6, and TNF-α levels. FoxO1 enhanced lncRNA GAS5 expression by binding to its promoter. LncRNA GAS5 facilitated Hspa5 transcription by sponging miR-378a-5p. Intervention of lncRNA GAS5/miR-378a-5p/Hspa5 axis reversed the promoting effect of FoxO1 silencing on the neurological function recovery in ICH mice. CONCLUSION: FoxO1 silencing facilitated neurological function recovery in ICH mice via the lncRNA GAS5/miR-378a-5p/Hspa5 axis.

The Size-dependent Cytotoxicity of Amorphous Silica Nanoparticles: A Systematic Review of in vitro Studies.

With the increasing production and application of engineered amorphous silica nanoparticles (aSiNPs), people have more opportunities to be exposed to aSiNPs. However, the knowledge of its adverse health effects and related mechanisms is still limited, compared with the well-studied crystalline micron-sized silica. Since small differences in the physical-chemical properties of nanoparticles could cause significant differences in the toxic effect, it is important to distinguish how these variations influence the outcoming toxicity. Notably, particle size, as one of the essential characterizations of aSiNPs, is relevant to its biological activities. Thus, the aim of this systematic review was to summarize the relationship between the particle size of aSiNPs and its adverse biological effects. In order to avoid the influence of complicated in vivo experimental conditions on the toxic outcome, only in vitro toxicity studies which reported on the cytotoxic effect of different sizes aSiNPs were included. After the systematic literature retrieval, selection, and quality assessment process, 76 eligible scientific papers were finally included in this review. There were 76% of the studies that concluded a size-dependent cytotoxicity of aSiNPs, in which smaller-sized aSiNPs possessed greater toxicity. However, this trend could be modified by certain influence factors, such as the synthetic method of aSiNPs, particle aggregation state in cell culture medium, toxicity endpoint detection method, and some other experimental conditions. The effects of these influence factors on the size-dependent cytotoxicity of aSiNPs were also discussed in detail in the present review.

Double kissing mini-culotte versus mini-culotte stenting: insights from micro-computed tomographic imaging of bench testing.

AIMS: This study aimed to evaluate the morphologic characteristics of double kissing (DK) mini-culotte and mini-culotte stenting through imaging of bench testing. METHODS AND RESULTS: DK mini-culotte and mini-culotte stenting were performed in two silicone bifurcated phantoms with branch vessel diameter differences of 0.5 mm (Model 1) and 1.25 mm (Model 2), and their morphologic characteristics were evaluated by micro-computed tomography. In Model 1, metal carina length (0.25±0.13 mm vs 0.55±0.15 mm), area stenosis of the side branch ostium (SBO) (4.65±3.24% vs 12.5±3.93%), and maximum distance of malapposed struts for the wall facing the SBO (0.27±0.08 mm vs 0.49±0.15 mm) were lower in the DK mini-culotte group than in the mini-culotte group. In Model 2, metal carina length (0.21±0.47 mm vs 0.47±0.12 mm), SBO area stenosis (5.13±3.37% vs 15.00±6.18%), and maximum distance of malapposed struts (0.32±0.13 mm vs 0.68±0.10 mm) were also lower in the DK mini-culotte group. The results of factorial analysis showed that maximum distance of malapposed struts tended to be shorter in Model 1 (F=4.226, p=0.062). CONCLUSIONS: Compared with mini-culotte stenting, DK mini-culotte stenting was associated with shorter metal carina length, shorter maximum distance of malapposed struts, and smaller SBO area stenosis. Thus, DK mini-culotte stenting may obtain better morphologic characteristics.

Visualizing polymeric bioresorbable scaffolds with three-dimensional image reconstruction using contrast-enhanced micro-computed tomography.

There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). This study aimed to explore the feasibility of detecting polymeric BRS with 3-dimensional reconstruction of BRS images by contrast-enhanced mCT and to determine the optimal imaging settings. BRSs, made of poly-L-lactic acid (PLLA), were implanted in coronary bifurcation models. Five treatments were conducted to examine an optimal condition for imaging BRSs: Baseline treatment, samples were filled with normal saline and scanned with mCT immediately; Treatment-1, -2, -3 and -4, samples were filled with contrast medium and scanned with mCT immediately and 1, 2 and 3 h thereafter, corresponding to soaking time of contrast medium of 0, 1, 2 and 3 h. Compared to Baseline, mCT scanning completely discriminate the scaffold struts from the vascular lumen immediately after filling the samples with contrast agent but not from the vascular wall until the contrast agent soaking time was more than 2 h (Treatment-3 and -4). By setting 10-15 HU as a cut-point of CT values, the scaffold strut detectable rate at Baseline and Teatment-1, -2, -3 and -4 were 1.23 ± 0.31%, 1.65 ± 0.26%, 58.14 ± 12.84%, 97.97 ± 1.43% and 98.90 ± 0.38%, respectively (Treatment-3 vs. Treatment-2, p < 0.01); meanwhile, the success rate of 3D BRS reconstruction with high quality images at Baseline and Teatment-1, -2, -3 and -4 were 1.23%, 1.65%, 58.14%, 97.97% and 98.90%, respectively (Treatment-3 vs. Treatment-2, p < 0.01). In conclusions, reconstruction of 3D BRS images is technically feasible by contrast-enhanced mCT and soaking time of contrast agent for more than 2 h is necessary for complete separation of scaffold struts from the surrounding structures in the phantom samples.