Exosomes are generated within the multivesicular endosomes (MVEs) as intraluminal vesicles (ILVs) and secreted during the fusion of MVEs with the cell membrane. The mechanisms of exosome biogenesis ...remain poorly explored. Here we identify that RAB31 marks and controls an ESCRT-independent exosome pathway. Active RAB31, phosphorylated by epidermal growth factor receptor (EGFR), engages flotillin proteins in lipid raft microdomains to drive EGFR entry into MVEs to form ILVs, which is independent of the ESCRT (endosomal sorting complex required for transport) machinery. Active RAB31 interacts with the SPFH domain and drives ILV formation via the Flotillin domain of flotillin proteins. Meanwhile, RAB31 recruits GTPase-activating protein TBC1D2B to inactivate RAB7, thereby preventing the fusion of MVEs with lysosomes and enabling the secretion of ILVs as exosomes. These findings establish that RAB31 has dual functions in the biogenesis of exosomes: driving ILVs formation and suppressing MVEs degradation, providing an exquisite framework to better understand exosome biogenesis.
Hydrogels as metal ions adsorbents are commonly applied in wastewater treatment field. However, low swelling ratio (SR) of ever reported hydrogel adsorbents prevents adsorptive sites from effectively ...exposing to metal ions, leading to unpleasant removal efficiency for trace metal ions. Designing high SR for hydrogel adsorbents can increase contact area between adsorbents and metal ions, being favorable for the internal adsorption sites exposure to metal ions. Thus, improved adsorption performance for removing trace metal ions can be achieved by endowing high SR for hydrogel adsorbents. In the present work, poly(acrylic acid) hydrogel adsorbent achieves high SR up to 8130 g/g by employing calcium hydroxide (Ca(OH)2) nano-spherulites as cross-linkers, which can effectively adsorb various trace metal ions including Cu2+, Cd2+, Cr6+, Fe3+, Mn2+, Ni2+, Zn2+, Ce3+ and Ag+. The removal ratios reach 46.8% for Cu2+ (initial concentration C0 = 0.16 mg/L), 57.1% for Cd2+ (C0 = 0.56 mg/L), 26.9% for Cr6+ (C0 = 0.52 mg/L), 5.3% for Fe3+ (C0 = 0.56 mg/L), 52.7% for Mn2+ (C0 = 0.55 mg/L), 52.5% for Ni2+ (C0 = 0.59 mg/L), 58.4% for Zn2+ (C0 = 0.65 mg/L), 70% for Ce3+ (C0 = 0.7 mg/L) and 45.3% for Ag+ (C0 = 1.08 mg/L) by using such adsorbent, respectively. This work develops a potential hydrogel adsorbent for the efficient removal of trace metal ions.
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•Hydrogel adsorbent for removing trace metal ions (<1 mg/L) has been innovatively designed.•Nanoparticles (diameter < 5 nm) are used to cross-link polymer hydrogel.•The swelling ratio of such hydrogel adsorbent is high up to 8130 g/g.•High adsorption efficiency for trace metal ions can be achieved by using such adsorbent.
Formative assessment (FA) has been used to facilitate EFL learning and teaching. However, due to factors such as task complexity and time constraints, FA implementation faces a variety of challenges, ...especially in countries with an exam-oriented education system. Drawing on the case of EFL teachers from Chinese public secondary schools, this study examines the features of FA practice and explains their underlying aspects in an EFL exam-oriented context from a social psychology perspective. It adopts a mixed-methods research approach. Guided by the theory of planned behavior, 10 English teachers from Guangdong province in China were interviewed to establish an item pool for a structured questionnaire. A total of 161 English teachers from four cities in Guangdong province took part in the subsequent survey. The results revealed that the participating teachers have an implicit understanding of FA, based primarily on its literal meaning and their own teaching experience. They know and follow FA methods but lack confidence about their own practice. Regional differences were significant. Possible reasons for the perceptions and practices of Chinese EFL teachers from public secondary schools are the teachers' own attitudes, the influence of other stakeholders, and the limitations of the FA methods. The study elucidates the features of FA practice and its mechanism in an EFL exam-oriented context.
Abstract
The ground surface temperature (GST) serves as a crucial indicator for understanding land-atmosphere mass and energy exchange. The shift from manual measurement to automated station for GST ...in China after 2002 introduced inconsistencies at certain stations, potentially distorting research findings. Here, daily automatedly observed GST from 2003 to 2017 at 615 selected meteorological stations were updated by constructing linear regression model based on manually observed air temperature (AT) and GST from 1960 to 2002. Then, the spatiotemporal variations of GST from 1960 to 2017 and its driving factors were investigated. Results indicated that: (1) the AT-GST linear regression model could effectively mitigate the inconsistency caused by the change of GST observation methods, enhancing data reliability. (2) GST in China showed little change from 1960–1980, but increased significantly across all regions from 1980 to 2000, with the increase rate slowed down except in the Qinghai–Tibet plateau (QTP) and southwest China after 2000. Notable GST increase is concentrated in colder regions, including the QTP, northeast (NEC), and northwest China (NWC). (3) Evapotranspiration (ET) and vapor pressure deficit were the primary drivers of annual GST variations at the regional scale, while their contributions to GST variations exhibited notable seasonal variability. Our findings could offer valuable scientific insights for addressing climate change, enhancing surface environmental models, and safeguarding ecological environments.
Chemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles ...(EVs) mediate MDR, but the underlying mechanism remains unclear, especially the effects of chemotherapeutic agents on this process.
Extracellular vesicles isolation was performed by differential centrifugation. The recipient cells that acquired ATP-binding cassette sub-family B member 1 (ABCB1) proteins were sorted out from co-cultures according to a stringent multi-parameter gating strategy by fluorescence-activated cell sorting (FACS). The transfer rate of ABCB1 was measured by flow cytometry. The xenograft tumor models in mice were established to evaluate the transfer of ABCB1 in vivo. Gene expression was detected by real-time PCR and Western blotting.
Herein, we show that a transient exposure to chemotherapeutic agents can strikingly increase Rab8B-mediated release of extracellular vesicles (EVs) containing ABCB1 from drug-resistant cells, and accelerate these EVs to circulate back onto plasma membrane of sensitive tumor cells via the down-regulation of Rab5. Therefore, intercellular ABCB1 transfer is significantly enhanced; sensitive recipient cells acquire a rapid but unsustainable resistance to evade the cytotoxicity of chemotherapeutic agents. More fascinatingly, in the xenograft tumor models, chemotherapeutical drugs also locally or distantly increase the transfer of ABCB1 molecules. Furthermore, some Non-small-cell lung carcinoma (NSCLC) patients who are undergoing primary chemotherapy have a rapid increase of ABCB1 protein in their monocytes, and this is obviously associated with poor chemotherapeutic efficacy.
Chemotherapeutic agents stimulate the secretion and recycling of ABCB1-enriched EVs through the dysregulation of Rab8B and Rab5, leading to a significant increase of ABCB1 intercellular transfer, thus assisting sensitive cancer cells to develop an urgent resistant phenotype. Our findings provide a new molecular mechanism of how chemotherapeutic drugs assist sensitive cancer cells in acquiring an urgent resistance.
Abstract
Background
Embryonal rhabdomyosarcoma (ERMS) of the uterine cervix is rare, but the population affected is mostly underage females. The scope of surgery has now evolved from extensive to ...limited, and organ-preserving surgery combined with chemotherapy is recommended to preserve the patient’s fertility. However, reports of birth outcomes are rare.
Case
A minor woman with cervical ERMS who underwent only an outpatient biopsy of the lesion had no residual lesion on subsequent multipoint cervical biopsy and refused radical surgery or cervical conization, after which the patient received a nonclassical regimen of chemotherapy. The patient stopped the chemotherapy on her own, but the patient conceived spontaneously 16 years later with a good pregnancy outcome and no recurrence.
Conclusions
This case suggests that preservation of reproductive function is often feasible in immature women with cervical ERMS, and the prognosis is usually good as long as the primary tumour can be surgically removed and the lesion is free of residual disease. We also look forward to reports of subsequent growth and pregnancy outcomes in other children with reproductive tract RMS. In cervical ERMS, accurate evaluation of the disease and development of an individualized treatment plan are crucial, and the protection of reproductive function and psychological well-being deserves special attention.
Image hashing is an emerging technology in multimedia security for applications such as image authentication, digital watermarking, and image copy detection. In this paper, we propose a robust image ...hashing based on the observations that image pixels of each ring are almost unchanged after rotation and ring-based image entropies are approximately linearly changed by content-preserving operations. This hashing is achieved by converting the input image into a normalized image, dividing the normalized image into different rings and extracting the ring-based entropies to produce hash. Hash similarity is measured by correlation coefficient. Experiments show that our hashing is robust against content-preserving manipulations such as JPEG compression, watermark embedding, scaling, rotation, brightness and contrast adjustment, gamma correction and Gaussian low-pass filtering. Receiver operating characteristics (ROC) curve comparisons with notable algorithms indicate that our hashing has better classification performances than the compared algorithms.
► We find that image pixels in each ring are almost unchanged after image rotation. ► We also find that ring-based image entropies are approximately linearly changed. ► We propose a robust image hashing based on the above observations. ► Our hashing is robust against content-preserving manipulations such as rotation. ► Our hashing has better classification performances than some notable algorithms.
Cervical cancer has long been a common malignance troubling women. However, there are few studies developing nomogram with comprehensive factors for the prognosis of cervical cancer. Hence, we aimed ...to build a nomogram to calculate the overall survival (OS) probability in patients with cervical cancer.
Data of 9876 female patients in SEER database and diagnosed as cervical cancer during 2010-2015, was retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression model were applied to select predicted factors and a nomogram was developed to visualize the prediction model. The nomogram was compared with the FIGO stage prediction model. Harrell's C-index, receiver operating curve, calibration plot and decision curve analysis were used to assess the discrimination, accuracy, calibration and clinical utility of the prediction models.
Eleven independent prognostic variables, including age at diagnosis, race, marital status at diagnosis, grade, histology, tumor size, FIGO stage, primary site surgery, regional lymph node surgery, radiotherapy and chemotherapy, were used to build the nomogram. The C-index of the nomogram was 0.826 (95% CI: 0.818 to 0.834), which was better than that of the FIGO stage prediction model (C-index: 0.785, 95% CI: 0.776 to 0.793). Calibration plot of the nomogram was well fitted in 3-year overall OS prediction, but overfitting in 5-year OS prediction. The net benefit of the nomogram was higher than the FIGO prediction model.
A clinical useful nomogram for calculating the overall survival probability in cervical cancer patients was developed. It performed better than the FIGO stage prediction model and could help clinicians to choose optimal treatments and precisely predict prognosis in clinical care and research.
Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Coronavirus disease 2019 (COVID-19) has a significant impact on the health and quality of life of MG patients and may even ...trigger the onset of MG in some cases. With the worldwide development of the COVID-19 vaccination, several new-onset MG cases and exacerbations following the COVID-19 vaccines have been acknowledged. The potential link between myasthenia gravis (MG) and COVID-19 has prompted the need for further investigation into the underlying molecular mechanism.
The differential expression analysis identified six differentially expressed genes (DEGs) shared by myasthenia gravis (MG) and COVID-19, namely SAMD9, PLEK, GZMB, JUNB, NR4A1, and NR1D1. The relationship between the six common genes and immune cells was investigated in the COVID-19 dataset. The predictive value of the shared genes was assessed and a nomogram was constructed using machine learning algorithms. The regulatory miRNAs, transcription factors and small molecular drugs were predicted, and the molecular docking was carried out by AutoDock.
We have identified six common DEGs of MG and COVID-19 and explored their immunological effects and regulatory mechanisms. The result may provide new insights for further mechanism research.
Cancer cells are characterized by aberrant activation of lipid biosynthesis, producing saturated fatty acids and monounsaturated fatty acids via stearoyl-CoA desaturases (SCD) for regulating ...metabolic and signaling platforms. SCD1 overexpression functions as an oncogene in lung cancer and predicts a poor clinical outcome. This study aimed to investigate the role of SCD1 inhibition by EGFR inhibitor (Gefitinib)-based anti-tumor therapy of lung cancer both in vitro and in vivo.
CCK-8 assay was performed to determine cell viability. The SCD1 mRNA level was detected by qPCR. The protein levels were assessed by Western blotting. E-cadherin and N-cadherin levels were determined by immunofluorescence. Apoptosis detection was conducted by flow cytometry. Cell migration or invasion was evaluated by transwell assay. The tumor sizes and tumor volumes were calculated in nude mice by subcutaneous injection of A549 cells transfected with vector of pcDNA3.1-SCD1 or negative control. Expression of Ki-67 was detected by immunohistochemistry.
SCD1 up-regulated expression was observed in lung cancer cell lines. Cells with overexpressed SCD1 had high IC50 values for Gefitinib in A549 and H1573 cell lines. Overexpression of SCD1 inhibited Gefitinib-induced apoptosis, decreased cell vitality and impaired ability of migration and invasion, while these effects were counteracted by A939572. Mechanistically, SCD1 promoted the activation of proliferation and metastasis-related EGFR/PI3K/AKT signaling, and up-regulated epithelial to mesenchymal transition (EMT) phenotype in the two cell lines, which was restored by SCD1 inhibition. Furthermore, in spite of EGFR inhibition, overexpression of SCD1 in vivo significantly promoted tumor growth by activating EGFR/PI3K/AKT signaling in tumor tissues, but A939572 treatment restricted SCD1-induced tumor progression and inhibited EMT phenotype of cancer cells in vivo.
These findings indicated that inhibition of oncogene SCD1 is required for targeting EGFR therapy in lung cancer.
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