Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. ...However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.
Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Mutations in MFN2 cause the neurodegenerative disease Charcot-Marie-Tooth ...type 2A (CMT2A). The molecular basis underlying the physiological and pathological relevance of MFN2 is unclear. Here, we present crystal structures of truncated human MFN2 in different nucleotide-loading states. Unlike other dynamin superfamily members including MFN1, MFN2 forms sustained dimers even after GTP hydrolysis via the GTPase domain (G) interface, which accounts for its high membrane-tethering efficiency. The biochemical discrepancy between human MFN2 and MFN1 largely derives from a primate-only single amino acid variance. MFN2 and MFN1 can form heterodimers via the G interface in a nucleotide-dependent manner. CMT2A-related mutations, mapping to different functional zones of MFN2, lead to changes in GTP hydrolysis and homo/hetero-association ability. Our study provides fundamental insight into how mitofusins mediate mitochondrial fusion and the ways their disruptions cause disease.
Triple negative breast cancer (TNBC) is a complex and malignant breast cancer subtype that lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor ...receptor 2 (HER2), thereby making therapeutic targeting difficult. TNBC is generally considered to have high malignancy and poor prognosis. However, patients diagnosed with certain rare histomorphologic subtypes of TNBC have better prognosis than those diagnosed with typical triple negative breast cancer. In addition, with the discovery and development of novel treatment targets such as the androgen receptor (AR), PI3K/AKT/mTOR and AMPK signaling pathways, as well as emerging immunotherapies, the therapeutic options for TNBC are increasing. In this paper, we review the literature on various histological types of TNBC and focus on newly developed therapeutic strategies that target and potentially affect molecular pathways or emerging oncogenes, thus providing a basis for future tailored therapies focused on the mutational aspects of TNBC.
Urbanization is taking place at an unprecedented rate around the world, particularly in China in the past few decades. One of the key impacts of rapid urbanization on the environment is the effect of ...urban heat island (UHI). Understanding the effects of landscape pattern on UHI is crucial for improving the ecology and sustainability of cities. This study investigated how landscape composition and configuration would affect UHI in the Shanghai metropolitan region of China, based on the analysis of land surface temperature (LST) in relation to normalized difference vegetation index (NDVI), vegetation fraction (Fv), and percent impervious surface area (ISA). Two Landsat ETM+ images acquired on March 13 and July 2, 2001 were used to estimate LST, Fv, and percent ISA. Landscape metrics were calculated from a high spatial resolution (2.5
×
2.5
m) land-cover/land-use map. Our results have showed that, although there are significant variations in LST at a given fraction of vegetation or impervious surface on a per-pixel basis, NDVI, Fv, and percent ISA are all good predictors of LST on the regional scale. There is a strong negative linear relationship between LST and positive NDVI over the region. Similar but stronger negative linear relationship exists between LST and Fv. Urban vegetation could mitigate the surface UHI better in summer than in early spring. A strong positive relationship exists between mean LST and percent ISA. The residential land is the biggest contributor to UHI, followed by industrial land. Although industrial land has the highest LST, it has limited contribution to the overall surface UHI due to its small spatial extend in Shanghai. Among the residential land-uses, areas with low- to-middle-rise buildings and low vegetation cover have much high temperatures than areas with high-rise buildings or areas with high vegetation cover. A strong correlation between the mean LST and landscape metrics indicates that urban landscape configuration also influences the surface UHI. These findings are helpful for understanding urban ecology as well as land use planning to minimize the potential environmental impacts of urbanization.
► Strong relationship between LST and vegetation and impervious surface. ► Stronger vegetation mitigation effect on UHI in summer than in early spring. ► Largest residential contribution to UHI. ► Strong influence of Urban landscape configuration on UHI.
Abstract
Iron-chalcogenide superconductors have emerged as a promising Majorana platform for topological quantum computation. By combining topological band and superconductivity in a single material, ...they provide significant advantage to realize isolated Majorana zero modes. However, iron-chalcogenide superconductors, especially Fe(Te,Se), suffer from strong inhomogeneity which may hamper their practical application. In addition, some iron-pnictide superconductors have been demonstrated to have topological surface states, yet no Majorana zero mode has been observed inside their vortices, raising a question of universality about this new Majorana platform. In this work, through angle-resolved photoemission spectroscopy and scanning tunneling microscopy/spectroscopy measurement, we identify Dirac surface states and Majorana zero modes, respectively, for the first time in an iron-pnictide superconductor, CaKFe
4
As
4
. More strikingly, the multiple vortex bound states with integer-quantization sequences can be accurately reproduced by our model calculation, firmly establishing Majorana nature of the zero mode.
Fingolimod (FTY720) is used as an immunosuppressant for multiple sclerosis. Numerous studies indicated its neuroprotective effects in stroke. However, the mechanism remains to be elucidated. This ...study was intended to investigate the mechanisms of phosphorylated FTY720 (pFTY720), which was the principle active molecule in regulating astrocyte‐mediated inflammatory responses induced by oxygen‐glucose deprivation (OGD). Results demonstrated that pFTY720 could protect astrocytes against OGD‐induced injury and inflammatory responses. It significantly decreased pro‐inflammatory cytokines, including high mobility group box 1 (HMGB1) and tumour necrosis factor‐α (TNF‐α). Further, studies displayed that pFTY720 could prevent up‐regulation of Toll‐like receptor 2 (TLR2), phosphorylation of phosphoinositide 3‐kinase (PI3K) and nuclear translocation of nuclear factor kappa B (NFκB) p65 subunit caused by OGD. Sphingosine‐1‐phosphate receptor 3 (S1PR3) knockdown could reverse the above change. Moreover, administration of TLR2/4 blocker abolished the protective effects of pFTY720. Taken together, this study reveals that pFTY720 depends on S1PR3 to protect astrocytes against OGD‐induced neuroinflammation, due to inhibiting TLR2/4‐PI3K‐NFκB signalling pathway.
Introduction Self-concordant goals are those that align closely with an individual’s intrinsic interests and values, driving autonomous motivation, and resulting in higher satisfaction and goal ...achievement. The relevance of studying the link between ego identity and goal self-concordance lies in understanding how a well-defined ego identity can foster the pursuit of authentic and fulfilling goals. Objectives This study investigates the relationship between ego identity and goal self-concordance, focusing on how individuals’ sense of identity influences their alignment with personal goals. Methods Data were gathered through a cross-sectional analysis of 292 students and a longitudinal follow-up with 98 participants over two intervals. Results Results confirmed significant correlations between ego identity status and various dimensions of goal self-concordance. Notably, different ego identity statuses exhibited distinct levels of goal self-concordance, ranked from highest to lowest as follows: identity achievement, achievement-foreclosure intermediate, moratorium, foreclosure, moratorium-diffusion intermediate, and diffusion. Cross-lagged analysis revealed a causal relationship where ego identity influences goal self-concordance, providing insights into the cognitive and behavioral processes involved in goal setting. Discussion This study extends the implications of the goal self-concordance model and reveals a causal relationship between ego identity status and goal self-concordance. From a practical perspective, our findings suggest that educational and developmental interventions aimed at supporting identity development and commitment could lead to more self-concordant goal setting. Such programs could ultimately promote greater well-being and personal growth among students.
Infection is a major cause of death in children, and it is particularly important to identify biological indicators of early infection. Previous studies showed that the neutrophil CD64 (nCD64) index ...may be a useful biomarker for infection. The purpose of this study was to investigate use of the nCD64 index to identify infection in children from a pediatric ICU (PICU) in China.
This prospective observational study enrolled 201 children who were admitted to our PICU and were divided into an infection group and a non-infection group. In each patient, C-reactive protein (CRP), nCD64 index, procalcitonin (PCT), and white blood cell count were measured during the first 24 h after admission. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity, specificity, and diagnostic value of the nCD64 index for infection.
Among all 201 children, the infection group had greater levels of CRP, nCD64 index, and PCT (all p < 0.05). ROC analysis indicated the nCD64 index had a sensitivity of 68.8%, specificity of 90.7%, accuracy of 80.5%, and an optimal cut-off value of 0.14, which had better diagnostic value than CRP or PCT. For children with postoperative fever, the nCD64 index also distinguished systemic inflammatory response syndrome (SIRS) from infection with accuracy of 79%.
The nCD64 index is a useful biomarker for the diagnosis of early infection in children admitted to the PICU.
Angiosarcoma is a mesenchymal soft tissue sarcoma with a tendency for vascular endothelial differentiation. It is highly malignant with a poor prognosis but has a low incidence. Epithelioid ...angiosarcoma of the gastrointestinal tract is rare, and simultaneous multiple lesions of the stomach and small intestine are even rarer. It is easy to be misdiagnosed clinically. We report on a case of preoperative misdiagnosis of gastric cancer and postoperative diagnosis of epithelioid angiosarcoma with multiple lymph node metastases.
A 75-year-old patient who was admitted to the hospital because of fatigue, melena and dysuria for >1 month.
Gastroscopy revealed gastric fundus ulcer and the biopsy revealed poorly differentiated adenocarcinoma of the fundus. We performed a radical gastrectomy for gastric cancer during which multiple ulcers were found in the jejunum and resected. Postoperative pathology showed multiple epithelioid angiosarcoma in the stomach and small intestine with lymph node metastases. The patient did not receive further treatment and died 2 month after the surgery.
Gastrointestinal epithelioid angiosarcoma is one of the differential diagnoses of gastrointestinal adenocarcinoma and surgery is the main treatment. The lymph nodes are one of the main sites of metastasis.
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