NETs are chromatin-derived webs extruded from neutrophils as a result of either infection or sterile stimulation using chemicals, cytokines, or microbes. In addition to the classical role that NETs ...play in innate immunity against infection and injuries, NETs have been implicated extensively in cancer progression, metastatic dissemination, and therapy resistance. The purpose of this review is to describe recent investigations into NETs and the roles they play in tumor biology and to explore their potential as therapeutic targets in cancer treatment.
Bullosis diabeticorum is a distinct, spontaneous, noninflammatory, blistering condition of acral skin that is unique to patients with diabetes mellitus, resulting in the infection, ulcer, gangrene ...and even amputation. This paper summarized the nursing practice of patient with bullosis diabeticorum combined with diabetic foot ulcer. Based on the comprehensive nursing evolution, an effective nursing plan consisting of wound care, pain control, psychological care and health education was established to improve the wound healing and patient’s quality of life during treatment. (糖尿病性大疱病是一种发生在糖尿病患者四肢远端的特异性皮肤损害。本文总结1例糖尿病性大疱合并足溃疡的护理经验。根据患者的评估情况, 在稳定血糖的基础上, 加强伤口护理、疼痛管理、心理护理、健康教育等护理措施, 促进水疱吸收, 加快足溃疡愈合, 改善患者生活质量。)
While silica nanoparticles (SiNPs) have wide applications, they inevitably increase atmospheric particulate matter and human exposure to this nanomaterial. Numerous studies have focused on how to ...disclose SiNP toxicity and on understanding its toxic mechanisms. However, there are few studies in the literature reporting the interaction between endoplasmic reticulum (ER) stress and SiNP exposure, and the corresponding detailed mechanisms have not been clearly determined. In this study, CCK-8 and flow cytometry assays demonstrated that SiNPs gradually decreased cell viability and increased cell apoptosis in RAW 264.7 macrophage cells in dose- and time-dependent manners. Western blot analysis showed that SiNPs significantly activated ER stress by upregulating GRP78, CHOP, and ERO1α expression. Meanwhile, western blot analysis also showed that SiNPs activated the mitochondrial-mediated apoptotic signaling pathway by upregulating BAD and Caspase-3, and downregulating the BCL-2/BAX ratio. Moreover, 4-phenylbutyrate (4-PBA), an ER stress inhibitor, significantly decreased GRP78, CHOP, and ERO1α expression, and inhibited cell apoptosis in RAW 264.7 macrophage cells. Furthermore, overexpression of CHOP significantly enhanced cell apoptosis, while knockdown of CHOP significantly protected RAW 264.7 macrophage cells from apoptosis induced by SiNPs. We found that the CHOP-ERO1α-caspase-dependent apoptotic signaling pathway was activated by upregulating the downstream target protein ERO1α and caspase-dependent mitochondrial-mediated apoptotic signaling pathway by upregulating Caspase-3 and downregulating the ratio of BCL-2/BAX. In summary, ER stress participated in cell apoptosis induced by SiNPs and CHOP regulated SiNP-induced cell apoptosis, at least partly, via activation of the CHOP-ERO1α-caspase apoptotic signaling pathway in RAW 264.7 macrophage cells.
The CO2 reduction reaction (CO2RR) is an essential step in natural photosynthesis and artificial photosynthesis to provide carbohydrate foods and hydrocarbon energy in the carbon-neutral cycle. ...However, the current solar conversion efficiencies and/or product selectivity of the CO2RR are very sluggish due to its complicated multiple-step charge transfer reactions. Here, we systematically investigate the charge transfer reaction rate during CO2 reduction on CuBi2O4 photocathodes, where the surface is modified with 3-aminopropyltriethoxysilane (APTES). We discover that the surface amine group increases the charge separation rate, significantly enhancing the surface charge transfer reaction rate. However, the surface acidity has less influence on the first-order reaction, indicating that a rate-determining step (RDS) exists in the early stage of the photoelectrochemical cell (PEC) processes. Moreover, the intensity-modulated photocurrent spectroscopy (IMPS) confirms that both surface charge transfer and the recombination rate on APTES-coated CuBi2O4 are larger than bare CuBi2O4 while possessing comparable charge transfer efficiencies. Overall, the surface charge transfer reactions under the PEC condition require designing more effective nanostructured photoelectrodes and powerful characterization methods to intrinsically increase the charge separation and transfer rate while reducing the recombination rate.
The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) in stroke patients caused by thromboembolic occlusion of the internal carotid artery (ICA) remains unclear. Our ...objectives were to evaluate the critical role of NETs in the induction of hypercoagulability in stroke and to identify the functional significance of NETs during atherothrombosis.
The levels of NETs, activated platelets (PLTs), and PLT-derived microparticles (PMPs) were detected in the plasma of 55 stroke patients and 35 healthy controls. NET formation and thrombi were analysed using immunofluorescence. Exposed phosphatidylserine (PS) was evaluated with flow cytometry and confocal microscopy. PCA was analysed using purified coagulation complex, thrombin, and fibrin formation assays.
The plasma levels of NETs, activated PLTs, and PMP markers in the carotid lesion site (CLS) were significantly higher than those in the aortic blood. NETs were decorated with PS in thrombi and the CLS plasma of ICA occlusion patients. Notably, the complementary roles of CLS plasma and thrombin-activated PLTs were required for NET formation and subsequent PS exposure. PS-bearing NETs provided functional platforms for PMPs and coagulation factor deposition and thus increased thrombin and fibrin formation. DNase I and lactadherin markedly inhibited these effects. In addition, NETs were cytotoxic to endothelial cells, converting these cells to a procoagulant phenotype. Sivelestat, anti-MMP9 antibody, and activated protein C (APC) blocked this cytotoxicity by 25%, 39%, or 52%, respectively.
NETs played a pivotal role in the hypercoagulability of stroke patients. Strategies that prevent NET formation may offer a potential therapeutic strategy for thromboembolism interventions.
This study was supported by grants from the National Natural Science Foundation of China (61575058, 81873433 and 81670128) and Graduate Innovation Fund of Harbin Medical University (YJSKYCX2018-58HYD).
Along with the accelerated shift of coal mining to the ecologically fragile west, the contradiction between coal resource development and ecological protection in the western arid and semiarid coal ...mining areas is rapidly intensifying. Based on the above background, this thesis takes the coal mining area in the arid and semiarid regions as an example; applies the theories of ecology, coal mining subsidence, geodesy, and ecological restoration; uses remote sensing in synthetic aperture radar (SAR), geographic information system (GIS), and mathematical modelling to reveal the ecological evolution law of the mining area; measures the ecological damage of the mining area; and then proposes a reasonable ecological restoration strategy. The surface deformation monitoring study in the study area shows that on the whole, some areas in the study area have different degrees of surface subsidence disasters, and the maximum surface subsidence value exceeds 800 mm. From the distribution of surface subsidence in the study area, surface subsidence disasters mainly occur in the eastern and central mountainous areas rich in coal resources, as well as in the mining areas west of the Yellow River, and the subsidence basins are distributed in a series of irregular concentric ovals. In terms of the scale of surface subsidence in the study area, a total of 230.03 km2 of land in the study area showed surface subsidence hazards during the monitoring period, accounting for 13.78% of the total area of the study area, of which the area of severe subsidence was 44.98 km2 (2.69%). The area of more serious subsidence area is 101.33 km2 (6.07%), and the area affected by subsidence is 83.72 km2 (5.01%).
Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and ...H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems.
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•BCOR depletion induced endodermal and mesodermal differentiation of hESCs•BCOR, PRC1.1, and PRC2 components co-occupied promoters of differentiation genes•Deletions in the C terminus of BCOR abolished BCOR-PRC1.1 assembly at targets•The N terminus of BCOR repressed transcription independently of the C terminus
Molecular networks responsible for the maintenance of primed pluripotency in human embryonic stem cells (hESCs) remain poorly defined. Wang et al. identify BCOR as a critical hESC regulator that defines a subtype of the PRC1.1 complexes with distinct recruitment and repression mechanisms that are essential for silencing differentiation programs in hESCs.
Stroke is a prevalent global acute cerebrovascular condition, with ischaemic stroke being the most frequently occurring type. After a stroke, neutrophils accumulate in the brain and subsequently ...generate and release neutrophil extracellular traps (NETs). The accumulation of NETs exacerbates the impairment of the blood‒brain barrier (BBB), hampers neovascularization, induces notable neurological deficits, worsens the prognosis of stroke patients, and can facilitate the occurrence of t-PA-induced cerebral haemorrhage subsequent to ischaemic stroke. Alternative approaches to pharmacological thrombolysis or endovascular thrombectomy are being explored, and targeting NETs is a promising treatment that warrants further investigation.
Metastasis of breast cancer grows from the local invasion to the distant colonization. Blocking the local invasion step would be promising for breast cancer treatment. Our present study demonstrated ...AQP1 was a crucial target in breast cancer local invasion.
Mass spectrometry combined with bioinformatics analysis was used to identify AQP1 associated proteins ANXA2 and Rab1b. Co-immunoprecipitation, immunofluorescence assays and cell functional experiments were carried out to define the relationship among AQP1, ANXA2 and Rab1b and their re-localization in breast cancer cells. The Cox proportional hazards regression model was performed toward the identification of relevant prognostic factors. Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test.
Here, we show that the cytoplasmic water channel protein AQP1, a crucial target in breast cancer local invasion, recruited ANXA2 from the cellular membrane to the Golgi apparatus, promoted Golgi apparatus extension, and induced breast cancer cell migration and invasion. In addition, cytoplasmic AQP1 recruited cytosolic free Rab1b to the Golgi apparatus to form a ternary complex containing AQP1, ANXA2, and Rab1b, which induced cellular secretion of the pro-metastatic proteins ICAM1 and CTSS. Cellular secretion of ICAM1 and CTSS led to the migration and invasion of breast cancer cells. Both in vivo assay and clinical analysis data confirmed above results.
Our findings suggested a novel mechanism for AQP1-induced breast cancer local invasion. Therefore, targeting AQP1 offers promises in breast cancer treatment.
This paper deals with the power loss evaluation in gearshift assistant mechanism applied in automated manual transmission. The originalities include building the numerical models of gearshift ...assistant mechanism efficiency analysis for cost penalty evaluation and designing gear ratio matching algorithm to match the gear ratios of epicyclic mechanism with desired ones, which is expected to minimize the clutch friction losses by reducing the angular velocity differences between two clutch pads. In the numerical models, gear meshing losses and friction losses are considered the main power sink. By the kinematic relationships and power flow analysis, a set of generalized efficiency calculating formulas of simple epicyclic mechanism in six working modes with respect to teeth numbers are summarized, which are useful computer-aided tools in calculating multiple simple epicyclic mechanisms’ efficiency. The matched gear ratios and the efficiency models are tested on a powertrain simulation model and several simulation results are reported. Finally, this paper summarized the merits and further research targets of the proposed transmission, which is a promising structure to achieve swift and smooth gearshift with low power losses.
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