Miracle-dz/UniFAR-FTUs huggingface dataset:
Programmed Death-Ligand 1 Expression Potentiates the Immune Modulatory Function Of Myeloid-Derived Suppressor Cells in Systemic Lupus Erythematosus

Multiple studies have explored the potential role of programmed death-ligand 1 (PD-L1) as a mediator of Myeloid-derived suppressor cells (MDSCs) effects in various cancers. However, the role PD-L1 expression in MDSCs on autoimmune disease is still largely unknown.This study was undertaken to whether MDSC expressing PD-L1 have more potent immunoregulatory activity and control autoimmunity more effectively in two murine models of lupus (MRL/lpr mice and Roquinsan/san mice). The populations of MDSC were increased in peripheral blood of lupus patients. The mRNA levels of immunosuppressive molecules were profoundly decreased in MDSCs from lupus patients and mice. Co-culture with splenocytes showed that PD-L1 expressing MDSCs from control mice expand both Treg cells and regulatory B cells more potently. Infusion of PD-L1 expressing MDSCs reduced autoantibody levels and degree of proteinuria and improved renal pathology of two animal models of lupus. Moreover, PD-L1 expressing MDSCs therapy can suppress double negative (CD4-CD8-CD3+) T cells, the major pathogenic immune cells and follicular helper T cells in MRL/lpr mice, and podocyte damage. Our results indicate PD-L1 expressing MDSCs have more potent immunoregualtory activity and ameliorate autoimmunity more profoundly. These findings suggest PD-L1 expressing MDSCs be a promising therapeutic strategy targeting systemic autoimmune diseases.
SH-1028, An Irreversible Third-Generation EGFR TKI, Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer

SH-1028 is an irreversible third-generation EGFR TKI. Both SH-1028 and osimertinib have a pyrimidine structure (a typical mutant-selective EGFR TKI structure). Compared with osimertinib, SH-1028 is modified on the indole ring, thus resulting in a more stable 6,7,8,9-tetrahydro-pyrrolo [1, 2-a] indol structure. In this study, we explored the anti-tumor effect of SH-1028 in vitro and in vivo, the inhibition of cell signal, such as EGFR and ERK phosphorylation, and verified the relationship between the pharmacokinetics and pharmacodynamic responses. Firstly, SH-1028 selectively inhibited EGFR sensitive and resistant mutations, with up to 198-fold more effective compared with wild-type EGFR cells. Then, in mouse xenograft models, oral administration of SH-1028 at a daily dose of 5 mg/kg significantly inhibited proliferation of tumor cells with EGFR sensitive mutation (exon 19 del) and resistant mutation (T790 M) for consecutive 14 days, with no TKI-induced weight loss. Moreover, SH-1028 exhibited good bioavailability, and was distributed extensively from the plasma to the tissues. The main metabolite of SH-1028, Imp3, was tested and showed no wild-type EGFR inhibition or off-target effects. In conclusion, SH-1028 is a new third-generation EGFR inhibitor that exhibits potent activity against EGFR sensitive and resistant (T790 M) mutations.
Regulation of Inflammatory Response by Transmembrane Adaptor Protein LST1

LST1 is a small adaptor protein expressed in leukocytes of myeloid lineage. Due to the binding to protein tyrosine phosphatases SHP1 and SHP2 it was thought to have negative regulatory function in leukocyte signaling. It was also shown to be involved in cytoskeleton regulation and generation of tunneling nanotubes. LST1 gene is located in MHCIII locus close to many immunologically relevant genes. In addition, its expression increases under inflammatory conditions such as viral infection, rheumatoid arthritis and inflammatory bowel disease and its deficiency was shown to result in slightly increased sensitivity to influenza infection in mice. However, little else is known about its role in the immune system homeostasis and immune response. Here we show that similar to humans, LST1 is expressed in mice in the cells of the myeloid lineage. In vivo, its deficiency results in alterations in multiple leukocyte subset abundance in steady state and under inflammatory conditions. Moreover, LST1-deficient mice show significant level of resistance to dextran sodium sulphate (DSS) induced acute colitis, a model of inflammatory bowel disease. These data demonstrate that LST1 regulates leukocyte abundance in lymphoid organs and inflammatory response in the gut.
The structure of lithium silicate melts revealed by high-temperature Raman spectroscopy

ABSTRACT The structure of lithium silicate glasses and melts was studied by in situ Raman spectroscopy at temperatures from 293 to 1423 K. The composition range of the studied melts varied from 33 to 60 mol. % of lithium oxide. A curve-fitting procedure was applied for data analysis taking into account the second coordination sphere of silica atoms. To obtain a correct interpretation of all bands in the Raman spectra, additional types of structural unit, carrying the information about the neighbors, were introduced into a description of glasses and melts structure. It was shown that structural units possessing two non-bridging oxygen atoms are typical of almost all the melts of the lithium silicate system, with their content in the system being higher than that in the melts of the sodium silicate system of the same composition. Such an unusual behavior of these melts under increased temperature as well as the elevated concentration of species with two non-bridging oxygen atoms may significantly affect the viscosity value of lithium silicate melts.
A Palmitoylethanolamide Producing Lactobacillus paracasei Improves Clostridium difficile Toxin A-Induced Colitis

Genetically engineered probiotics, able to in situ deliver therapeutically active compounds while restoring gut eubiosis, could represent an attractive therapeutic alternative in Clostridium difficile infection (CDI). Palmitoylethanolamide is an endogenous lipid able to exert immunomodulatory activities and restore epithelial barrier integrity in human models of colitis, by binding the peroxisome proliferator–activated receptor-α (PPARα). The aim of this study was to explore the efficacy of a newly designed PEA-producing probiotic (pNAPE-LP) in a mice model of C. difficile toxin A (TcdA)-induced colitis. The human N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), a key enzyme involved in the synthesis of PEA, was cloned and expressed in a Lactobacillus paracasei that was intragastrically administered to mice 7 days prior the induction of the colitis. Bacteria carrying the empty vector served as negative controls (pLP). In the presence of palmitate, pNAPE-LP was able to significantly increase PEA production by 27,900%, in a time- and concentration-dependent fashion. Mice treated with pNAPE-LP showed a significant improvement of colitis in terms of histological damage score, macrophage count, and myeloperoxidase levels (−53, −82, and −70.4%, respectively). This was paralleled by a significant decrease both in the expression of toll-like receptor-4 (−71%), phospho-p38 mitogen-activated protein kinase (−72%), hypoxia-inducible factor-1-alpha (−53%), p50 (−74%), and p65 (−60%) and in the plasmatic levels of interleukin-6 (−86%), nitric oxide (−59%), and vascular endothelial growth factor (−71%). Finally, tight junction protein expression was significantly improved by pNAPE-LP treatment as witnessed by the rescue of zonula occludens-1 (+304%), Ras homolog family member A-GTP (+649%), and occludin expression (+160%). These protective effects were mediated by the specific release of PEA by the engineered probiotic as they were abolished in PPARα knockout mice and in wild-type mice treated with pLP. Herein, we demonstrated that pNAPE-LP has therapeutic potential in CDI by inhibiting colonic inflammation and restoring tight junction protein expression in mice, paving the way to next generation probiotics as a promising strategy in CDI prevention.
Satisfaction and Quality of Life of Families Participating in Two Different Early Intervention Models in the Same Context: A Mixed Methods Study

Early intervention is developed following different types of service organization, which in turn require different professional and family roles. The aim of this study was to compare the perceived satisfaction and family quality of life amongst families receiving early intervention developed at centers in comparison to those receiving the routines-based early intervention in families’ homes, that is a family centered intervention in ecological environments. Under a transformative paradigm, a mixed methods design was used, using the Consumer Report Effectiveness Scale (CRES-4) and the Beach Center Family Quality of Life Scale (FQOLS) and two focus groups as data collection instruments. The sample comprised 166 parents in the quantitative phase and 16 parents in the qualitative phase. Results showed that families receiving routines-based early intervention had greater satisfaction with the service although both groups showed similar scores for family quality of life in most of the analyzed domains. Three dimensions were identified throughout the qualitative phase: problem solving, professional team and service organization. Both the models analyzed have an impact on family quality of life and parents are in general satisfied. Strengths and weaknesses were found related to the problem-solving process, the role of the professional team, family empowerment and the service’s organization. The areas requiring further development are the effective training of professionals focused on family practices, the exchange of information with the family and a more participatory organization that takes parent’s perspectives into consideration. The value given to a combined model is another aspect highlighted in this study, as well as the need for a more agile assessment period to avoid unnecessary delays.
Localization of Epileptic Foci Based on Simultaneous EEG–fMRI Data

Combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) enables a non-invasive investigation of the human brain function and evaluation of the correlation of these two important modalities of brain activity. This paper explores recent reports on using advanced simultaneous EEG–fMRI methods proposed to map the regions and networks involved in focal epileptic seizure generation. One of the applications of EEG and fMRI combination as a valuable clinical approach is the pre-surgical evaluation of patients with epilepsy to map and localize the precise brain regions associated with epileptiform activity. In the process of conventional analysis using EEG–fMRI data, the interictal epileptiform discharges (IEDs) are visually extracted from the EEG data to be convolved as binary events with a predefined hemodynamic response function (HRF) to provide a model of epileptiform BOLD activity and use as a regressor for general linear model (GLM) analysis of the fMRI data. This review examines the methodologies involved in performing such studies, including techniques used for the recording of EEG inside the scanner, artifact removal, and statistical analysis of the fMRI signal. It then discusses the results reported for patients with primary generalized epilepsy and patients with different types of focal epileptic disorders. An important matter that these results have brought to light is that the brain regions affected by interictal epileptic discharges might not be limited to the ones where they have been generated. The developed methods can help reveal the regions involved in or affected by a seizure onset zone (SOZ). As confirmed by the reviewed literature, EEG–fMRI provides information that comes particularly useful when evaluating patients with refractory epilepsy for surgery.
Engineering Method for Tailoring Electrical Characteristics in TiN/TiO x /HfO x /Au Bi-Layer Oxide Memristive Devices

Memristive devices have led to an increased interest in neuromorphic systems. However, different device requirements are needed for the multitude of computation schemes used there. While linear and time-independent conductance modulation is required for machine learning, non-linear and time-dependent properties are necessary for neurobiologically realistic learning schemes. In this context, an adaptation of the resistance switching characteristic is necessary with regard to the desired application. Recently, bi-layer oxide memristive systems have proven to be a suitable device structure for this purpose, as they combine the possibility of a tailored memristive characteristic with low power consumption and uniformity of the device performance. However, this requires technological solutions that allow for precise adjustment of layer thicknesses, defect densities in the oxide layers, and suitable area sizes of the active part of the devices. For this purpose, we have investigated the bi-layer oxide system TiN/TiO x /HfO x /Au with respect to tailored I-V non-linearity, the number of resistance states, electroforming, and operating voltages. Therefore, a 4-inch full device wafer process was used. This process allows a systematic investigation, i.e., the variation of physical device parameters across the wafer as well as a statistical evaluation of the electrical properties with regard to the variability from device to device and from cycle to cycle. For the investigation, the thickness of the HfO x layer was varied between 2 and 8 nm, and the size of the active area of devices was changed between 100 and 2,500 µm2. Furthermore, the influence of the HfO x deposition condition was investigated, which influences the conduction mechanisms from a volume-based, filamentary to an interface-based resistive switching mechanism. Our experimental results are supported by numerical simulations that show the contribution of the HfO x film in the bi-layer memristive system and guide the development of a targeting device.
The Effect of Technology Innovation on Corporate Sustainability in Chinese Renewable Energy Companies

Technology innovation has become the main driving force of China’s economic growth. Sustainable development highlights the harmonious symbiosis of the economy and the ecological environment. Renewable energy companies characterized by technology-intensive and environmental friendliness are playing an increasingly important role in achieving economic development while alleviating environmental pressure. Therefore, this paper selects the A-share renewable energy listed companies in China between 2014 and 2019 as samples, using the fixed-effect model and the logit model to explore the effect of technology innovation on corporate sustainability. We find that technology innovation has a positive effect on both financial sustainability (FS) and social and environmental sustainability (SES). Due to the imbalance of regional social and environmental development and different degrees of emphasis placed on environmental and social responsibility, the positive impact of technology innovation on SES is heterogeneous between the east and the central and west regions. Moreover, as the strategic emerging industry, although the renewable energy industry is granted lots of subsidies from the government, the results show that when government subsidies exceed the threshold, the effect of technology innovation on FS is weakened. Government subsidies have a negative moderating effect on the relationship between innovation and SES. Furthermore, we subdivide government subsidies into government subsidies beforehand (GSB) and government subsidies afterwards (GSA). We reveal that the threshold effect of government subsidies mainly comes from GSA, while the moderating effect of government subsidies is caused by GSA and GSB. This paper is an expansion and enrichment of current studies on sustainable development and also puts forward feasible suggestions for the government to formulate precise and effective subsidy policies to stimulate technology innovation.
Biomembrane Structure and Material Properties Studied With Neutron Scattering

Cell membranes and their associated structures are dynamical supramolecular structures where different physiological processes take place. Detailed knowledge of their static and dynamic structures is therefore needed, to better understand membrane biology. The structure–function relationship is a basic tenet in biology and has been pursued using a range of different experimental approaches. In this review, we will discuss one approach, namely the use of neutron scattering techniques as applied, primarily, to model membrane systems composed of lipid bilayers. An advantage of neutron scattering, compared to other scattering techniques, is the differential sensitivity of neutrons to isotopes of hydrogen and, as a result, the relative ease of altering sample contrast by substituting protium for deuterium. This property makes neutrons an ideal probe for the study of hydrogen-rich materials, such as biomembranes. In this review article, we describe isotopic labeling studies of model and viable membranes, and discuss novel applications of neutron contrast variation in order to gain unique insights into the structure, dynamics, and molecular interactions of biological membranes. We specifically focus on how small-angle neutron scattering data is modeled using different contrast data and molecular dynamics simulations. We also briefly discuss neutron reflectometry and present a few recent advances that have taken place in neutron spin echo spectroscopy studies and the unique membrane mechanical data that can be derived from them, primarily due to new models used to fit the data.
Effects of Heterogeneous Environment After Deforestation on Plant Phenotypic Plasticity of Three Shrubs Based on Leaf Traits and Biomass Allocation

Phenotypic plasticity among natural plant populations is a species-specific ecological phenomenon of paramount importance that depends on their life forms, development stages, as well as environmental factors. While this phenomenon is broadly understood, it has hardly been observed in nature. This study aimed at understanding phenotypic plasticity and ecological adaptability in three shrubs (Salix etosia, Rubus setchuenensis, and Hydrangea aspera) affected by potential environmental variables after deforesting in sparse Larix spp. forest and tall shrub mixed secondary forests. Soil organic carbon content, total nitrogen content, and available nitrogen content were greater outside the forests, contrary to other measured factors whose availability was higher in the forest interiors. In case of leaf traits and stoichiometric indicators, there were significant interactions of leaf area (LA), leaf dry matter (DW), specific leaf area (SLA), and leaf phosphorus content (LPC) between shrub species and heterogeneous environments (P < 0.05) but not for leaf C/N, N/P, and C/P. Principal components analysis (PCA) indicated that soil temperature, pH value, soil carbon content, soil nitrogen content, and MBC and MBN mainly constituted the first component. Summarized results indicated that TB and leaf C/P of S. etosia were significantly correlated with three principal components, but only marginal significant correlations existed between R/S and relevant components. SLA and R/S of R. setchuenensis had marginal significant relationships with independent variables. Both SLA and TB of H. aspera were significantly correlated with three principal components. Based on the pooled values of leaf functional traits and leaf stoichiometric indicators, R. setchuenensis (vining type) had better leaf traits plasticity to adapt to a heterogeneous environment. In descending order, the ranks of biomass allocation plasticity index of three shrubs were H. aspera (bunch type), R. setchuenensis (vining type), and S. etosia (erect type). The highest integrated plasticity values of leaf traits and biomass allocation was observed in H. aspera (bunch type), followed by R. setchuenensis, and by S. etosia with less adaptive plasticity in heterogeneous environments.
Characterization of FtsH Essentiality in Streptococcus mutans via Genetic Suppression

FtsH belongs to the AAA+ ATP-dependent family of proteases, which participate in diverse cellular processes and are ubiquitous among bacteria, chloroplasts, and mitochondria. FtsH is poorly characterized in most organisms, especially compared to other major housekeeping proteases. In the current study, we examined the source of FtsH essentiality in the human oral microbiome species Streptococcus mutans, one of the primary etiological agents of dental caries. By creating a conditionally lethal ftsH mutant, we were able to identify a secondary suppressor missense mutation in the vicR gene, encoding the response regulator of the essential VicRK two-component system (TCS). Transcriptomic analysis of the vicR (G195R) mutant revealed significantly reduced expression of 46 genes, many of which were located within the genomic island Tnsmu2, which harbors the mutanobactin biosynthetic gene cluster. In agreement with the transcriptomic data, deletion of the mutanobactin biosynthetic gene cluster suppressed ftsH essentiality in S. mutans. We also explored the role of FtsH in S. mutans physiology and demonstrated its critical role in stress tolerance, especially acid stress. The presented results reveal the first insights within S. mutans for the pleiotropic regulatory function of this poorly understood global regulator.
Static Context Header Compression and Fragmentation (SCHC) over LoRaWAN

The Static Context Header Compression and fragmentation (SCHC) specification (RFC 8724) describes generic header compression and fragmentation techniques for Low-Power Wide Area Network (LPWAN) technologies. SCHC is a generic mechanism designed for great flexibility so that it can be adapted for any of the LPWAN technologies. This document defines a profile of SCHC (RFC 8724) for use in LoRaWAN networks and provides elements such as efficient parameterization and modes of operation. Stream: Internet Engineering Task Force (IETF) RFC: 9011 Category: Standards Track Published: April 2021 ISSN: 2070-1721 Authors: O. Gimenez, Ed. Semtech I. Petrov, Ed. Acklio Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Further information on Internet Standards is available in Section 2 of RFC 7841. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at . https://www.rfc-editor.org/info/rfc9011 Copyright Notice Copyright (c) 2021 IETF Trust and the persons identified as the document authors. All rights reserved. This document is subject to BCP 78 and the IETF Trust's Legal Provisions Relating to IETF Documents ( ) in effect on the date of publication of this document. Please review these documents carefully, as they describe your rights and restrictions https://trustee.ietf. org/license-info Gimenez & Petrov Standards Track Page 1 with respect to this document. Code Components extracted from this document must include Simplified BSD License text as described in Section 4.e of the Trust Legal Provisions and are provided without warranty as described in the Simplified BSD License. Table of
Responsible tourism towards sustainable development: literature review and research agenda

ABSTRACT Responsible tourism has been researched by scholars focusing on various avenues of responsiveness over the years, however, our understanding of the antecedents and implications of this phenomenon is still limited. This article presents a systematic review by synthesizing the extant research works published since 2002 and creates a road map for future studies. Through this review, we intend to impart better assimilation of theories, methodologies, and emergent constructs explored in responsible tourism literature focusing on various stakeholders. Additionally, we emphasized the advancement of research in this area in the Asia-Pacific region.