Miracle-dz/UniFAR-FTUs huggingface dataset:
Single Cell Transcriptome Sequencing Reveals the Potential Mechanism of Heterogeneity in Immunoregulatory Function Between Mesenchymal Stromal Cells

Background: Mesenchymal stromal cells (MSCs) could be applied for the treatment of immune-related diseases. However, some studies have found there is enormous heterogeneity in immunomodulatory function of MSCs isolated from different tissue. At present, the underlying mechanism of heterogeneity in immunoregulatory function is still unclear. Methods: In this study, the foreskin mesenchymal stromal cells (FSMSCs) and human umbilical cord mesenchymal stromal cells (HuMSCs) were isolated and cultured to the 3rd passage. Cell types were confirmed according to the standard of International Association for Cell Therapy. Then, FSMSCs and HuMSCs were co-cultured with human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharides (LPS) in viro respectively. And the supernatant was sampled for enzyme-linked immunosorbent assay to investigate the secretion of IL-1β, IL-6, IL-10, TNF-α and TGF-β. Finally, single cell transcriptome sequencing was performed in order to elucidate the mechanism for the difference of immunomodulatory function.Results: FSMSCs and HuMSCs are successfully identified as MSCs. When co-cultured with LPS pre-treated PBMC, FSMSCs and HuMSCs could effectively reduce the secretion of IL-1β and TNF-α. But FSMSCs were able to stimulate the PBMC to secrete more IL-10, TGF-β and IL-6. Furthermore, 4 MSCs subsets in integrated data were identified, including Proliferative MSCs , Pericyte, Immune MSCs and Progenitor Proliferative MSCs. Among them, the proportions of Immune MSCs in FSMSCs and HUMSCs were 56% and 10% respectively. Varieties of immune-related genes, gene sets and regulons were enriched in Immune MSCs. And Immune MSCs with powful transcriptional activity were found to be near to Pericyte at the degree of differentiation and closed to other cell subsets. Finally, the foreskin tissue might be an ideal source of isolating Immune MSCs when comparing the subset composition of MSCs derived from adipose tissue and bone marrow from public database. Conclusions: Immune MSCs may play a key role in the heterogeneity of immunoregulatory function. It is a new insight that Immune MSCs could be isolated and better applied for the treatment of immune-related diseases without being limited by the heterogeneity of immunomodulatory function derived from different tissues.
Biophysical and biochemical attributes of hybrid epithelial/mesenchymal phenotypes

The epithelial–mesenchymal transition (EMT) is a biological phenomenon associated with explicit phenotypic and molecular changes in cellular traits. Unlike the earlier-held popular belief of it being a binary process, EMT is now thought of as a landscape including diverse hybrid E/M phenotypes manifested by varying degrees of the transition. These hybrid cells can co-express both epithelial and mesenchymal markers and/or functional traits, and can possess the property of collective cell migration, enhanced tumor-initiating ability, and immune/targeted therapy-evasive features, all of which are often associated with worse patient outcomes. These characteristics of the hybrid E/M cells have led to a surge in studies that map their biophysical and biochemical hallmarks that can be helpful in exploiting their therapeutic vulnerabilities. This review discusses recent advances made in investigating hybrid E/M phenotype(s) from diverse biophysical and biochemical aspects by integrating live cell-imaging, cellular morphology quantification and mathematical modeling, and highlights a set of questions that remain unanswered about the dynamics of hybrid E/M states.
Fruit and Vegetable Wholesale Market Waste: Safety and Nutritional Characterisation for Their Potential Re-Use in Livestock Nutrition

Compared to other food categories, fruits and vegetables are the most wasted. This leads to the squandering of economic, social, and environmental resources. The reallocation of fruit and vegetable waste (FVW) into animal feed contributes to the sustainability of livestock production, reducing the impact of feed production for land use. In this study, the fruit and vegetable waste from the General Wholesale Market of Milan was considered. FVW samples were collected for one year and were analysed for safety parameters and nutritional, vitamin, and mineral composition. Data showed that dry matter (DM) was on average 10.82 ± 1.21% and neutral detergent fibre (NDF) was on average 22.43 ± 4.52% DM. The presence of soluble sugars (30.51 ± 7.61% DM, on average) was also detected. However, the high moisture content of this waste makes it easily perishable, with detrimental effects on quality, storage, and transportation. A strategy was therefore proposed to reduce the water content of FVW by pressing. Overall, the results highlighted the significant nutritional value of FVW from the wholesale market and the need to develop appropriate technologies to maintain the food chain line safe.
A knowledge-based model for context-aware smart service systems

ABSTRACT The advancement of the Internet of Things, big data, and mobile computing leads to the need for smart services that enable the context awareness and the adaptability to their changing contexts. Today, designing a smart service system is a complex task due to the lack of an adequate model support in awareness and pervasive environment. In this paper, we present the concept of a context-aware smart service system and propose a knowledge model for context-aware smart service systems. The proposed model organizes the domain and context-aware knowledge into knowledge components based on the three levels of services: Services, Service system, and Network of service systems. The knowledge model for context-aware smart service systems integrates all the information and knowledge related to smart services, knowledge components, and context awareness that can play a key role for any framework, infrastructure, or applications deploying smart services. In order to demonstrate the approach, two case studies about chatbot as context-aware smart services for customer support are presented.
Aggregate Flexibility of Virtual Power Plants With Temporal Coupling Constraints

The virtual power plant (VPP) provides an efficient way to manage a bunch of distributed energy resources (DERs). In order to participate in the system operation and power market as a whole, the estimation of VPP power flexibility is indispensable. However, the temporal coupling constraints make it intractable to aggregate the power flexibility directly. In this paper, we formulate the flexibility evaluation problem as a chance constrained optimization model incorporated the randomness of renewables. To make it tractable, the evaluated flexibility is represented by the combination of a virtual generator and a virtual battery which is decomposed by a robust optimization algorithm. Then, a novel high-dimensional polytope based bound shrinking method is proposed to estimate the parameters of the virtual generator and virtual battery. The numerical test results show the proposed method obtain much more precise results with lower conservativeness than those of existing methods. The disaggregation feasibility of the evaluation results is also verified.
Sentiment Beta and Asset Prices: Evidence from China

ABSTRACT This article examines the relationship between sentiment beta and stock returns in Chinese stock market. Stocks with low (negative) sentiment beta significantly outperform those with high (positive) sentiment beta. When arbitrage is highly restricted or the stocks are difficult to value, the negative relationship between sentiment beta and stock returns is more pronounced. Further investigation shows that the results are mainly driven by periods of crisis and low economic policy uncertainty (EPU). In general, there exists an against minus catering sentiment (AMC) pricing factor in China.
The social welfare of marketplace lending: Evidence from natural disasters

Using natural disasters as exogenous shocks to the peer-to-peer (P2P) loan market, we document a local increase in loan demand post-disaster. Interest rates and delinquencies from loans approved during this demand shock are similar to pre-event levels. Loans allocated prior to a disaster are more likely to suffer delinquency over the life of the loan, but loans granted a hardship accommodation delay of payment reduce the likelihood of future delinquency providing relief to borrowers and reduced delinquency costs to investors. Contrary to regulatory concerns that P2P lending is predatory, our results suggest they provide positive social welfare benefits.
Study on the Preparation and Properties of Impervious and Breathable Sand Based on Hydrophobic Theory

Land desertification, a severe global ecological and environmental problem, brings challenges to the sustainable utilization of land resources in the world. The purpose of this research is to use hydrophobic theory to prepare impervious and breathable sand, and to solve the problems of sandy soil that seeps easily and makes it difficult for vegetation to survive in desertified areas. The influences of coating material content, first-level and second-level rough structure on the impermeability and air permeability of impervious and breathable sand were studied. The research showed that, with the increase in coating material content, the impervious performance of the sample increased firstly and then decreased, and the air permeability rose continuously. The hydrostatic pressure resistance of the sample can reach an extreme value of 53 mm. The first-level rough structure of micron structure can greatly improve the hydrophobic performance, thus improving the impervious performance. The addition of micron calcium carbonate would improve the hydrostatic pressure resistance height of the sample to 190 mm. The sample would reach a superhydrophobic state in the condition of a first-level rough structure of a nano structure built by nano silica, and the contact angle was up to 152.0°, so that the hydrostatic pressure resistance height can rise to 205 mm. The best performance would be achieved under the condition of relatively less raw material with a second-level rough structure of micro–nano. At this point, the contact angle of the sample reached 152.8° and the hydrostatic pressure resistance height was up to 205 mm. At the same time, the air permeability index of the above four kinds of impervious and breathable sand met all planting requirements. The sample prepared can satisfy the demands of different degrees of impermeability and air permeability, and can be widely used in desertification control.
Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy

The advent of T-cell-based immunotherapy has remarkably transformed cancer patient treatment. Despite their success, the currently approved immunotherapeutic protocols still encounter limitations, cause toxicity, and give disparate patient outcomes. Thus, a deeper understanding of the molecular mechanisms of T-cell activation and inhibition is much needed to rationally expand targets and possibilities to improve immunotherapies. Protein ubiquitination downstream of immune signaling pathways is essential to fine-tune virtually all immune responses, in particular, the positive and negative regulation of T-cell activation. Numerous studies have demonstrated that deregulation of ubiquitin-dependent pathways can significantly alter T-cell activation and enhance antitumor responses. Consequently, researchers in academia and industry are actively developing technologies to selectively exploit ubiquitin-related enzymes for cancer therapeutics. In this review, we discuss the molecular and functional roles of ubiquitination in key T-cell activation and checkpoint inhibitory pathways to highlight the vast possibilities that targeting ubiquitination offers for advancing T-cell-based immunotherapies.
Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance

Low-grade chronic inflammation plays a pivotal role in the pathogenesis of insulin resistance (IR), and skeletal muscle has a central role in this condition. NLRP3 inflammasome activation pathways promote low-grade chronic inflammation in several tissues. However, a direct link between IR and NLRP3 inflammasome activation in skeletal muscle has not been reported. Here, we evaluated the NLRP3 inflammasome components and their role in GLUT4 translocation impairment in skeletal muscle during IR. Male C57BL/6J mice were fed with a normal control diet (NCD) or high-fat diet (HFD) for 8 weeks. The protein levels of NLRP3, ASC, caspase-1, gasdermin-D (GSDMD), and interleukin (IL)-1β were measured in both homogenized and isolated fibers from the flexor digitorum brevis (FDB) or soleus muscle. GLUT4 translocation was determined through GLUT4myc-eGFP electroporation of the FBD muscle. Our results, obtained using immunofluorescence, showed that adult skeletal muscle expresses the inflammasome components. In the FDB and soleus muscles, homogenates from HFD-fed mice, we found increased protein levels of NLRP3 and ASC, higher activation of caspase-1, and elevated IL-1β in its mature form, compared to NCD-fed mice. Moreover, GSDMD, a protein that mediates IL-1β secretion, was found to be increased in HFD-fed-mice muscles. Interestingly, MCC950, a specific pharmacological NLRP3 inflammasome inhibitor, promoted GLUT4 translocation in fibers isolated from the FDB muscle of NCD- and HFD-fed mice. In conclusion, we found increased NLRP3 inflammasome components in adult skeletal muscle of obese insulin-resistant animals, which might contribute to the low-grade chronic metabolic inflammation of skeletal muscle and IR development.
RNAseq and RNA molecular barcoding reveal differential gene expression in cortical bone following hindlimb unloading in female mice

Disuse-induced bone loss is seen following spinal cord injury, prolonged bed rest, and exposure to microgravity. We performed whole transcriptomic profiling of cortical bone using RNA sequencing (RNAseq) and RNA molecular barcoding (NanoString) on a hindlimb unloading (HLU) mouse model to identify genes whose mRNA transcript abundances change in response to disuse. Eleven-week old female C57BL/6 mice were exposed to ambulatory loading or HLU for 7 days (n = 8/group). Total RNA from marrow-flushed femoral cortical bone was analyzed on HiSeq and NanoString platforms. The expression of several previously reported genes associated with Wnt signaling and metabolism was altered by HLU. Furthermore, the increased abundance of transcripts, such as Pfkfb3 and Mss51, after HLU imply these genes also have roles in the cortical bone’s response to altered mechanical loading. Our study demonstrates that an unbiased approach to assess the whole transcriptomic profile of cortical bone can reveal previously unidentified mechanosensitive genes and may eventually lead to novel targets to prevent disuse-induced osteoporosis.
Temperature-Sensing Inks Using Electrohydrodynamic Inkjet Printing Technology

Temperature measurement is very important for thermal control, which is required for the advancement of mechanical and electronic devices. However, current temperature sensors are limited by their inability to measure curved surfaces. To overcome this problem, several methods for printing flexible substrates were proposed. Among them, electrohydrodynamic (EHD) inkjet printing technology was adopted because it has the highest resolution. Since EHD inkjet printing technology is limited by the type of ink used, an ink with temperature-sensing properties was manufactured for use in this printer. To confirm the applicability of the prepared ink, its resistance characteristics were investigated, and the arrangement and characteristics of the particles were observed. Then, the ink was printed using the EHD inkjet approach. In addition, studies of the meniscus shapes and line widths of the printed results under various conditions confirmed the applicability of the ink to the EHD inkjet printing technology and the change in its resistance with temperature.
Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy

Simple Summary The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. Abstract The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.
What's Wrong with This Picture? A Critical Review of Current Centers for Medicare & Medicaid Services Coverage Criteria for Continuous Glucose Monitoring

Numerous studies have demonstrated the clinical value of continuous glucose monitoring (CGM) in type 1 diabetes and type 2 diabetes populations. However, the eligibility criteria for CGM coverage required by the Centers for Medicare & Medicaid Services (CMS) ignore conclusive evidence that supports CGM use in various diabetes populations that are currently deemed ineligible. This article discusses the limitations and inconsistencies of the CMS eligibility criteria relative to current scientific evidence and proposes workable solutions to address this issue and improve the safety and care of all individuals with diabetes.
Practical Report of Disaster-Related Mental Health Interventions Following the Great East Japan Earthquake during the COVID-19 Pandemic: Potential for Suicide Prevention

Background: This practical report aims to publicize the ongoing disaster-related mental health interventions following the Great East Japan Earthquake during the COVID-19 pandemic. Methods: Disaster-related mental health interventions consisted of: (1) screening high-risk evacuees with high psychological distress (Kessler 6 score ≥ 13) or binge drinking; and (2) visiting selected high-risk individuals and providing them counseling through outreach in evacuee housing. These activity records were compiled from existing material in the Sendai City Office; therefore, no new interviews or questionnaire surveys were conducted. Results: During the COVID-19 pandemic, we introduced telephone counseling and shortened the time of support as a result of the restrictions. Counselors addressed issues of “loneliness” or “isolation” among evacuees, who had little connection with society due to the pandemic. Moreover, the procedure for obtaining COVID-19 special financial aid was explained to evacuees in financial difficulty. During this period, the suicide rates in the affected area did not increase significantly as compared to the national average. Conclusions: Our report may be instructive in terms of preventing suicide during the pandemic using high-risk approaches and counselors trained in disaster-related mental health interventions.
An Insight into Sesamolin: Physicochemical Properties, Pharmacological Activities, and Future Research Prospects

Sesame seeds are rich in lignan content and have been well-known for their health benefits. Unlike the other sesame lignan compounds (i.e., sesamin and sesamol), the study of the pharmacological activity of sesamolin has not been explored widely. This review, therefore, summarizes the information related to sesamolin’s pharmacological activities, and the mechanism of action. Moreover, the influence of its physicochemical properties on pharmacological activity is also discussed. Sesamolin possessed neuroprotective activity against hypoxia-induced reactive oxygen species (ROS) and oxidative stress in neuron cells by reducing the ROS and inhibiting apoptosis. In skin cancer, sesamolin exhibited antimelanogenesis by affecting the expression of the melanogenic enzymes. The anticancer activity of sesamolin based on antiproliferation and inhibition of migration was demonstrated in human colon cancer cells. In addition, treatment with sesamolin could stimulate immune cells to enhance the cytolytic activity to kill Burkitt’s lymphoma cells. However, the toxicity and safety of sesamolin have not been reported. And there is also less information on the experimental study in vivo. The limited aqueous solubility of sesamolin becomes the main problem, which affects its pharmacological activity in the in vitro experiment and clinical efficacy. Therefore, solubility enhancement is needed for further investigation and determination of its pharmacological activity profiles. Since there are fewer reports studying this issue, it could become a future prospective research opportunity.