Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles

Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.International Society for Advancement of Cytometry Marylou Ingram Scholar 2019-2023H2020 EXPERTSwedish foundation of Strategic Research (SSF-IRC; FormulaEx)ERC CoG (DELIVER)Swedish Medical Research CouncilAccepte

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study

IntroductionThe efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear.Methods3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer’s tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment.ResultsBased on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs.DiscussionThe use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019)

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Wireless Data Acquisition System Development and Application on HVAC Equipment

AbstractAn appropriate monitoring and control system of the HVAC system is necessary to reduce its energy consumption on the premise of ensure the users’ comfort. A suite of wireless data acquisition system for HVAC system have been developed in this paper to resolve the cabling difficulties existing in the installation process of the sensors distributed at the end of the HVAC system. The acquisition system utilized a low-power and high-performance stm32f103RBT6 microcontroller as the MCU and a wireless transceiver module nRF24L01 and an Ethernet transceiver module W5100 to transfer data. Then the data will be stored in the SQL database and can be observed online. The working process and the practical applications of the acquisition system have been introduced. Finally an acquisition experiment based on the water system of an actual air conditioning system is conducted and the result shows that the wireless data acquisition system works stably and can overcome the difficulties in cabling and signal attenuation

Women on board: is it a boon or bane?

This study examines how investors react to the appointment of women as directors in Singapore-listed companies, as well as highlights the determinants of their reaction

Complicated microstructure transformation mechanism of the greenly grinding coating layer

The grinding surface mechanical property is important for its working life span, which is determined by the microstructure distribution. To improve the machining mechanical performance, the greenly grinding generated heat is utilized to generate the coating layer without extra liquid. However, the coating layer microstructure composite is difficult to predict due to the non-steady grinding temperature. A digital complicated microstructure transformation (DCM) model is established and coupled with the transient grinding heat based on the validated improved finite difference method. The austenization, the ferrite reverted transformation, the cementite precipitation, the bainite transformation and the martensite transformation are all considered and automatically distinguished according to the grinding coating CCT. The analytic results indicate that the larger grinding depth mainly increases the bainite content, which can be restricted by improving the feeding rate, and the quicker feeding rate can increase the martensite content by three times. Combined with the measurement of corresponding representative mechanical performances (hardness and the residual stress), the achieved model is verified as an effective tool to realize the microstructure prediction. The research brings about a novelty macro mechanical property control of the grinding coating layer and is significant for achieving higher mechanical performance in surface strengthening manufacturing components