56 research outputs found

    Human Amniotic Fluid Stem Cell-Derived Exosomes as a Novel Cell-Free Therapy for Cutaneous Regeneration

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    Adult wound healing often results in fibrotic scarring that is caused by myofibroblast aggregation. Human amniotic fluid stem cells (hAFSCs) exhibit significantly anti-fibrotic scarring properties during wound healing. However, it is little known whether hAFSCs directly or indirectly (paracrine) contribute to this process. Using the full-thickness skin-wounded rats, we investigated the therapeutic potential of hAFSC-derived exosomes (hAFSC-exo). Our results showed that hAFSC-exo accelerated the wound healing rate and improved the regeneration of hair follicles, nerves, and vessels, as well as increased proliferation of cutaneous cells and the natural distribution of collagen during wound healing. Additionally, hAFSC-exo suppressed the excessive aggregation of myofibroblasts and the extracellular matrix. We identified several miRNAs, including let-7-5p, miR-22-3p, miR-27a-3p, miR-21-5p, and miR-23a-3p, that were presented in hAFSC-exo. The functional analysis demonstrated that these hAFSC-exo-miRNAs contribute to the inhibition of the transforming growth factor-β (TGF-β) signaling pathway by targeting the TGF-β receptor type I (TGF-βR1) and TGF-β receptor type II (TGF-βR2). The reduction of TGF-βR1 and TGF-βR2 expression induced by hAFSC-exo was also confirmed in the healing tissue. Finally, using mimics of miRNAs, we found that hAFSC-exo-miRNAs were essential for myofibroblast suppression during the TGF-β1-induced human dermal fibroblast-to-myofibroblast transition in vitro. In summary, this study is the first to show that exosomal miRNAs used in hAFSC-based therapy inhibit myofibroblast differentiation. Our study suggests that hAFSC-exo may represent a strategic tool for suppressing fibrotic scarring during wound healing

    What you don't know... can't hurt you? A natural field experiment on relative performance feedback in higher education

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    This paper studies the effect of providing feedback to college students on their position in the grade distribution by using a natural field experiment. This information was updated every six months during a three-year period. We find that greater grades transparency decreases educational performance, as measured by the number of examinations passed and grade point average (GPA). However, self-reported satisfaction, as measured by surveys conducted after feedback is provided but before students take their examinations, increases. We provide a theoretical framework to understand these results, focusing on the role of prior beliefs and using out-of-trial surveys to test the model. In the absence of treatment, a majority of students underestimate their position in the grade distribution, suggesting that the updated information is “good news” for many students. Moreover, the negative effect on performance is driven by those students who underestimate their position in the absence of feedback. Students who overestimate initially their position, if anything, respond positively. The performance effects are short lived—by the time students graduate, they have similar accumulated GPA and graduation rates

    GDPR-oriented intelligent checking method of privacy policies compliance

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    The implementation of the EU’s General Data Protection Regulation (GDPR) has resulted in the imposition of over 300 fines since its inception in 2018.These fines include significant penalties for prominent companies like Google, which were penalized for their failure to provide transparent and comprehensible privacy policies.The GDPR, known as the strictest data protection laws in history, has made companies worldwide more cautious when offering cross-border services, particularly to the European Union.The regulation's territorial scope stipulates that it applies to any company providing services to EU citizens, irrespective of their location.This implies that companies worldwide, including domestic enterprises, are required to ensure compliance with GDPR in their privacy policies, especially those involved in international operations.To meet this requirement, an intelligent detection method was introduced.Machine learning and automation technologies were utilized to automatically extract privacy policies from online service companies.The policies were converted into a standardized format with a hierarchical structure.Through natural language processing, the privacy policies were classified, allowing for the identification of relevant GDPR concepts.In addition, a constructed GDPR taxonomy was used in the detection mechanism to identify any missing concepts as required by GDPR.This approach facilitated intelligent detection of GDPR-oriented privacy policy compliance, providing support to domestic enterprises while they provided cross-border services to EU users.Analysis of the corpus samples reveals the current situation that mainstream online service companies generally fail to meet GDPR compliance requirements

    Chemical Composition and Strontium Isotope Characteristics of Scheelite from the Doranasai Gold Deposit, NW China: Implications for Ore Genesis

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    Scheelite, as a common accessory mineral found in hydrothermal deposits, is an indicator that allows the study of the ore-forming hydrothermal process and the tracing of fluid sources. The Doranasai gold deposit is a large-sized orogenic gold deposit in the South Altai, and orebodies occur as veins in the Devonian Tuokesalei Formation and Permian albite granite dykes. The ores are quartz veins and altered tectonites (rocks). Here, scheelite can be observed in the early-stage milky quartz veins, the middle-stage smoky quartz-polymetallic sulfide veins, and the altered albite granite dykes. In this study, the scheelites of these three types were carefully investigated in terms of texture, element, and isotope geochemistry to understand their ore-forming processes and fluid sources. The results showed that all types of scheelite were rich in Sr and poor in Mo, indicating that their ore-forming fluids had no genetic relation to magmatic–hydrothermal activities. The scheelites were characterized by the enrichment of medium rare earth element (MREE) and positive Eu anomaly in the chondrite-standardized REE patterns. This indicated the REE differentiation between scheelite and fluid, i.e., REE3+ and Na+ were in the form of valence compensation, preferentially replacing Ca2+ and selectively entering the scheelite lattice. The trace element composition of scheelite showed that the ore-forming fluid system was relatively closed, mesothermal, Na-rich, and reductive. The Sr isotope ratio of the scheelite (0.704819–0.70860, average 0.706372) was higher than that of the ore-bearing albite granite dyke (0.704654–0.704735), indicating that the Tuokesalei Formation is the main source for the fluids forming the Doranasai deposit

    DataSheet1_Super enhancer-driven core transcriptional regulatory circuitry crosstalk with cancer plasticity and patient mortality in triple-negative breast cancer.docx

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    Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer. Core transcriptional regulatory circuitry (CRC) consists of autoregulated transcription factors (TFs) and their enhancers, which dominate gene expression programs and control cell fate. However, there is limited knowledge of CRC in TNBC. Herein, we systemically characterized the activated super-enhancers (SEs) and interrogated 14 CRCs in breast cancer. We found that CRCs could be broadly involved in DNA conformation change, metabolism process, and signaling response affecting the gene expression reprogramming. Furthermore, these CRC TFs are capable of coordinating with partner TFs bridging the enhancer-promoter loops. Notably, the CRC TF and partner pairs show remarkable specificity for molecular subtypes of breast cancer, especially in TNBC. USF1, SOX4, and MYBL2 were identified as the TNBC-specific CRC TFs. We further demonstrated that USF1 was a TNBC immunophenotype-related TF. Our findings that the rewiring of enhancer-driven CRCs was related to cancer immune and mortality, will facilitate the development of epigenetic anti-cancer treatment strategies.</p

    Improved hybrid reactive power compensation system based on FC and STATCOM and its control method

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    The purpose of this study is to solve the main problems in distribution networks, including increased line loss and reduced power supply quality caused by insufficient capacitive reactive power. To reduce the capacity, voltage, and current stress of an active module of a compensation device and improve the cost performance of the device, an improved hybrid reactive power compensation system based on a fixed capacitor (FC) and a static synchronous compensator (STATCOM) is proposed. The topological structure and basic operating principle of the proposed reactive power compensation system are introduced. In addition, from the perspectives of output voltage, current, power, loss of the active part, and system compensation cost, the performances of the proposed reactive compensator and the inductively coupled STATCOM (L-STATCOM) are compared and analyzed. Furthermore, the key parameters of the proposed system are designed, and the joint optimization control strategy of the FC and STATCOM is studied. The correctness and effectiveness of the proposed topology structure and control method are verified by simulations.Supported by the General Project of Hunan Natural Science Foundation (2021JJ30715), the Scientific Research Fund of Hunan Provincial Education Department (20B029) and the Graduate Research Innovation Project of Changsha University of Science & Technology (CX2021SS52)

    Image3_Super enhancer-driven core transcriptional regulatory circuitry crosstalk with cancer plasticity and patient mortality in triple-negative breast cancer.TIF

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    Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer. Core transcriptional regulatory circuitry (CRC) consists of autoregulated transcription factors (TFs) and their enhancers, which dominate gene expression programs and control cell fate. However, there is limited knowledge of CRC in TNBC. Herein, we systemically characterized the activated super-enhancers (SEs) and interrogated 14 CRCs in breast cancer. We found that CRCs could be broadly involved in DNA conformation change, metabolism process, and signaling response affecting the gene expression reprogramming. Furthermore, these CRC TFs are capable of coordinating with partner TFs bridging the enhancer-promoter loops. Notably, the CRC TF and partner pairs show remarkable specificity for molecular subtypes of breast cancer, especially in TNBC. USF1, SOX4, and MYBL2 were identified as the TNBC-specific CRC TFs. We further demonstrated that USF1 was a TNBC immunophenotype-related TF. Our findings that the rewiring of enhancer-driven CRCs was related to cancer immune and mortality, will facilitate the development of epigenetic anti-cancer treatment strategies.</p
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