Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of SOX18/CLAUDIN5 disrupts the pulmonary endothelial barrier in ventilator-induced lung injury

Mechanical strain contributes to ventilator-induced lung injury (VILI) through multi-factorial and complex mechanisms that remain unresolved. Prevailing evidence suggests that the loss of pulmonary endothelial tight junctions (TJs) plays a critical role. TJs are dynamically regulated by physiologic and hemodynamic forces to stabilize the endothelial barrier. The transcription factor sex-determining region Y-box (SOX)-18 is important in regulating blood vessel development and vascular permeability through its ability to regulate the transcription of Claudin-5, an endothelial TJ protein. Previously, we demonstrated that SOX18 expression is increased by shear stress in the pulmonary endothelium. Therefore, in this study, we investigated how mechanical strain mediated through cyclic stretch affects the SOX18/Claudin-5 regulatory axis. Our data demonstrate that SOX18 and Claudin-5 are downregulated in human lung microvascular endothelial cells (HLMVEC) exposed to cyclic stretch and the mouse lung exposed to high tidal mechanical ventilation. Overexpression of SOX18 reduced the loss of Claudin-5 expression in HLMVEC with cyclic stretch and preserved endothelial barrier function. Additionally, overexpression of Claudin-5 in HLMVEC ameliorated barrier dysfunction in HLMVEC exposed to cyclic stretch, although SOX18 expression was not enhanced. Finally, we found that the targeted overexpression of SOX18 in the pulmonary vasculature preserved Claudin-5 expression in the lungs of mice exposed to HTV. This, in turn reduced lung vascular leak, attenuated inflammatory lung injury, and preserved lung function. Together, these data suggest that enhancing SOX18 expression may prove a useful therapy to treat patients with ventilator-induced lung injury.
Harnessing the genomic diversity of Pseudomonas strains against lettuce bacterial pathogens

Lettuce is a major vegetable crop worldwide that is affected by numerous bacterial pathogens, including Xanthomonas hortorum pv. vitians, Pseudomonas cichorii, and Pectobacterium carotovorum. Control methods are scarce and not always effective. To develop new and sustainable approaches to contain these pathogens, we screened more than 1,200 plant-associated Pseudomonas strains retrieved from agricultural soils for their in vitro antagonistic capabilities against the three bacterial pathogens under study. Thirty-five Pseudomonas strains significantly inhibited some or all three pathogens. Their genomes were fully sequenced and annotated. These strains belong to the P. fluorescens and P. putida phylogenomic groups and are distributed in at least 27 species, including 15 validly described species. They harbor numerous genes and clusters of genes known to be involved in plant-bacteria interactions, microbial competition, and biocontrol. Strains in the P. putida group displayed on average better inhibition abilities than strains in the P. fluorescens group. They carry genes and biosynthetic clusters mostly absent in the latter strains that are involved in the production of secondary metabolites such as 7-hydroxytropolone, putisolvins, pyochelin, and xantholysin-like and pseudomonine-like compounds. The presence of genes involved in the biosynthesis of type VI secretion systems, tailocins, and hydrogen cyanide also positively correlated with the strains’ overall inhibition abilities observed against the three pathogens. These results show promise for the development of biocontrol products against lettuce bacterial pathogens, provide insights on some of the potential biocontrol mechanisms involved, and contribute to public Pseudomonas genome databases, including quality genome sequences on some poorly represented species.
A bibliometric analysis of 100 top-cited journal articles related to acupuncture regulation of the autonomic nervous system

Purpose Research on the effects of acupuncture on autonomic function has been conducted for several decades, and a few notable studies have emerged in recent years. This study used bibliometric analysis to assess 100 top-cited articles to characterize the current status and research trends over the last three decades. Methods The 100 top-cited publications were identified from the Web of Science Core Collection database. The bibliometrix package in R was used for quantitative and qualitative analyses of the publication patterns and the country/region, institution, and author contributions. VOSviewer was used to construct networks based on co-citation analysis of the journals and the keyword co-occurrence. Results The 100 top-cited articles were identified with a total of 8,123 citations (range: 37–345). The majority of the articles came from the USA (n = 42), followed by Japan (n = 14) and mainland China (n = 13). Articles from the USA exhibited the largest number of citations (3,582 citations), followed by articles from Japan (1,189 citations), then articles from mainland China (755 citations). Neurosciences/Neurology was the most studied research area (n = 41). The Autonomic Neuroscience: Basic and Clinical published the largest number of papers (n = 14), while Brain Research received the largest number of citations (205 citations). Longhurst JC was the most productive author (10 publications), and Sato A was first among the cited authors (87 citations). The most frequently cited articles that focused on gastrointestinal, cardiovascular, or gynecologic responses to acupuncture regulation of the autonomic nervous system first appeared in the 1990s, peaked in the 2000s, then decreased after 2010. Publication of articles focused on the anti-inflammatory effects of acupuncture associated with autonomic function demonstrated an increasing trend over the last three decades. Conclusion From the initial studies focusing on the autonomic mechanism of visceral responses to acupuncture, researchers concentrated on exploring the autonomic mechanism of acupuncture in the control of systemic inflammation. Non-invasive electrical methods that activate somato-autonomic reflexes are current translational directions in clinical practice. Additional investigation of the underlying neuroanatomical basis of somato-autonomic reflexes also is needed.
Optimal Designs for Random Coefficient Regression Models with Heteroscedastic Errors

The purpose of this article is to present the optimal designs based on D-, G-, A-, I-, and D β-optimality criteria for random coefficient regression (RCR) models with heteroscedastic errors. A sufficient condition for the heteroscedastic structure is given to make sure that the search of optimal designs can be confined at extreme settings of the design region when the criteria satisfy the assumption of the real valued monotone design criteria. Analytical solutions of D-, G-, A-, I-, and D β-optimal designs for the RCR models are derived. Two examples are presented for random slope models with specific heteroscedastic errors.
Genetic, epigenetic and enviromental influencing factors on the regulation of precocious and delayed puberty

The pubertal development onset is controlled by a network of genes that regulate the gonadotropin releasing hormone (GnRH) pulsatile release and the subsequent increase of the circulating levels of pituitary gonadotropins that activate the gonadal function. Although the transition from pre-pubertal condition to puberty occurs physiologically in a delimited age-range, the inception of pubertal development can be anticipated or delayed due to genetic and epigenetic changes or environmental conditions. Most of the genetic and epigenetic alterations concern genes which encode for kisspeptin, GnRH, LH, FSH and their receptor, which represent crucial factors of the hypothalamic-pituitary-gonadal (HPG) axis. Recent data indicate a central role of the epigenome in the regulation of genes in the hypothalamus and pituitary that could mediate the flexibility of pubertal timing. Identification of epigenetically regulated genes, such as Makorin ring finger 3 (MKRN3) and Delta-like 1 homologue (DLK1), respectively responsible for the repression and the activation of pubertal development, provides additional evidence of how epigenetic variations affect pubertal timing. This review aims to investigate genetic, epigenetic, and environmental factors responsible for the regulation of precocious and delayed puberty.
ML364 exerts the broad-spectrum antivirulence effect by interfering with the bacterial quorum sensing system

Antivirulence strategy has been developed as a nontraditional therapy which would engender a lower evolutionary pressure toward the development of antimicrobial resistance. However, the majority of the antivirulence agents currently in development could not meet clinical needs due to their narrow antibacterial spectrum and limited indications. Therefore, our main purpose is to develop broad-spectrum antivirulence agents that could target on both Gram-positive and Gram-negative pathogens. We discovered ML364, a novel scaffold compound, could inhibit the productions of both pyocyanin of Pseudomonas aeruginosa and staphyloxanthin of Staphylococcus aureus. Further transcriptome sequencing and enrichment analysis showed that the quorum sensing (QS) system of pathogens was mainly disrupted by ML364 treatment. To date, autoinducer-2 (AI-2) of the QS system is the only non-species-specific signaling molecule that responsible for the cross-talk between Gram-negative and Gram-positive species. And further investigation showed that ML364 treatment could significantly inhibit the sensing of AI-2 or its nonborated form DPD signaling in Vibrio campbellii MM32 and attenuate the biofilm formation across multi-species pathogens including Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The results of molecular docking and MM/GBSA free energy prediction showed that ML364 might have higher affinity with the receptors of DPD/AI-2, when compared with DPD molecule. Finally, the in vivo study showed that ML364 could significantly improve the survival rates of systemically infected mice and attenuate bacterial loads in the organs of mice. Overall, ML364 might interfere with AI-2 quorum sensing system to exert broad-spectrum antivirulence effect both in vitro and in vivo.
Tuberculosis: The success tale of less explored dormant Mycobacterium tuberculosis

Mycobacterium tuberculosis (M.tb) is an intracellular pathogen that predominantly affects the alveolar macrophages in the respiratory tract. Upon infection, the activation of TLR2 and TLR4- mediated signaling pathways leads to lysosomal degradation of the bacteria. However, bacterium counteracts the host immune cells and utilizes them as a cellular niche for its survival. One distinctive mechanism of M.tb to limit the host stress responses such as hypoxia and nutrient starvation is induction of dormancy. As the environmental conditions become favorable, the bacteria resuscitate, resulting in a relapse of clinical symptoms. Different bacterial proteins play a critical role in maintaining the state of dormancy and resuscitation, namely, DevR (DosS), Hrp1, DATIN and RpfA-D, RipA, etc., respectively. Existing knowledge regarding the key proteins associated with dormancy and resuscitation can be employed to develop novel therapies. In this review we aim to highlight the current knowledge of bacterial progression from dormancy to resuscitation and the gaps in understanding the transition from dormant to active state. We have also focused on elucidating a few therapeutic strategies employed to prevent M.tb resuscitation.
Airmass Classification and Analysis of Aerosol Types at El Arenosillo (Spain)

Abstract The Aerosol Robotic Network (AERONET) site “El Arenosillo,” equipped with a Cimel sun photometer, has been in operation since 2000. The data collected there are analyzed to establish an aerosol synoptic climatological description that is representative of the region. Different air masses and aerosol types are present over the site depending on the synoptic conditions. The frequent intrusion of dust from the Sahara Desert at El Arenosillo suggested the use of back trajectories to determine the airmass origins of other types of aerosol observed there. The focus of this study is to classify the air masses arriving at El Arenosillo by means of back-trajectory analyses and to characterize the aerosol within each type by means of the aerosol optical depth (AOD) and its spectral signature, given as the Angstrom exponent (AE). The goal is to determine how aerosols observed over the station (receptor site) differ depending on source region and transport pathways. Two classification methods are used, one b.
Endometrial small extracellular vesicles regulate human trophectodermal cell invasion by reprogramming the phosphoproteome landscape

A series of cyclical events within the uterus are crucial for pregnancy establishment. These include endometrial regeneration following menses, under the influence of estrogen (proliferative phase), then endometrial differentiation driven by estrogen/progesterone (secretory phase), to provide a microenvironment enabling attachment of embryo (as a hatched blastocyst) to the endometrial epithelium. This is followed by invasion of trophectodermal cells (the outer layer of the blastocyst) into the endometrium tissue to facilitate intrauterine development. Small extracellular vesicles (sEVs) released by endometrial epithelial cells during the secretory phase have been shown to facilitate trophoblast invasion; however, the molecular mechanisms that underline this process remain poorly understood. Here, we show that density gradient purified sEVs (1.06–1.11 g/ml, Alix+ and TSG101+, ∼180 nm) from human endometrial epithelial cells (hormonally primed with estrogen and progesterone vs. estrogen alone) are readily internalized by a human trophectodermal stem cell line and promote their invasion into Matrigel matrix. Mass spectrometry-based proteome analysis revealed that sEVs reprogrammed trophectoderm cell proteome and their cell surface proteome (surfaceome) to support this invasive phenotype through upregulation of pro-invasive regulators associated with focal adhesions (NRP1, PTPRK, ROCK2, TEK), embryo implantation (FBLN1, NIBAN2, BSG), and kinase receptors (EPHB4/B2, ERBB2, STRAP). Kinase substrate prediction highlighted a central role of MAPK3 as an upstream kinase regulating target cell proteome reprogramming. Phosphoproteome analysis pinpointed upregulation of MAPK3 T204/T202 phosphosites in hTSCs following sEV delivery, and that their pharmacological inhibition significantly abrogated invasion. This study provides novel molecular insights into endometrial sEVs orchestrating trophoblast invasion, highlighting the microenvironmental regulation of hTSCs during embryo implantation.
Comparative transcriptomic analysis-based identification of the regulation of foreign proteins with different stabilities expressed in Pichia pastoris

Introduction The industrial yeast Pichia pastoris is widely used as a cell factory to produce proteins, chemicals and advanced biofuels. We have previously constructed P. pastoris strains that overexpress protein disulfide isomerase (PDI), which is a kind of molecular chaperone that can improve the expression of an exogenous protein when they are co-expressed. Chicken cystatin (cC) is a highly thermostable cysteine protease inhibitor and a homologous protein of human cystatin C (HCC). Wild-type cC and the two mutants, I66Q and ΔW (a truncated cC lacking the á-helix 2) represent proteins with different degrees of stability. Methods Wild-type cC, I66Q and ΔW were each overexpressed in P. pastoris without and with the coexpression of PDI and their extracellular levels were determined and compared. Transcriptomic profiling was performed to compare the changes in the main signaling pathways and cell components (other than endoplasmic reticulum quality control system represented by molecular chaperones) in P. pastoris in response to intracellular folding stress caused by the expression of exogenous proteins with different stabilities. Finally, hub genes hunting was also performed. Results and discussion The coexpression of PDI was able to increase the extracellular levels of both wild-type cC and the two mutants, indicating that overexpression of PDI could prevent the misfolding of unstable proteins or promote the degradation of the misfolded proteins to some extent. For P. pastoris cells that expressed the I66Q or ΔW mutant, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses of the common DEGs in these cells revealed a significant upregulation of the genes involved in protein processing, but a significant downregulation of the genes enriched in the Ribosome, TCA and Glycolysis/Gluconeogenesis pathways. Hub genes hunting indicated that the most downregulated ribosome protein, C4QXU7 in this case, might be an important target protein that could be manipulated to increase the expression of foreign proteins, especially proteins with a certain degree of instability. Conclusion These findings should shed new light on our understanding of the regulatory mechanism in yeast cells that responds to intracellular folding stress, providing valuable information for the development of a convenient platform that could improve the efficiency of heterologous protein expression in P. pastoris.
The role of mind body interventions in the treatment of irritable bowel syndrome and fibromyalgia

Introduction Irritable bowel syndrome and fibromyalgia share similar pathophysiologic mechanisms including sensitization of peripheral and central pain pathways, autonomic dysfunction and are often co-diagnosed. Co-diagnosed patients experience increased symptom severity, mental health comorbidities, and decreased quality of life. The role of mind-body interventions, which have significant effects on central pain syndromes and autonomic dysregulation, have not been well-described in co-diagnosed patients. The aim of this state-of-the art narrative review is to explore the relationship between irritable bowel syndrome and fibromyalgia, and to evaluate the current evidence and mechanism of action of mind-body therapies in these two conditions. Methods The PubMed database was searched without date restrictions for articles published in English using the following keywords: fibromyalgia, irritable bowel syndrome, mind-body interventions, cognitive behavioral therapy, mindfulness based stress reduction, and yoga. Results Mind-body interventions resulted in improved patient-reported outcomes, and are effective for irritable bowel syndrome and fibromyalgia individually. Specifically, cognitive behavioral therapy and yoga trials showed decreased symptom severity, improved mental health, sleep and quality of life for both conditions individually, while yoga trials demonstrated similar benefits with improvements in both physical outcomes (gastrointestinal symptoms, pain/tenderness scores, insomnia, and physical functioning), mental health outcomes (anxiety, depression, gastrointestinal-specific anxiety, and catastrophizing), and quality of life, possibly due to alterations in autonomic activity. Conclusion Mind-body interventions especially CBT and yoga improve patient-reported outcomes in both irritable bowel syndrome and fibromyalgia individually. However, limited available data in co-diagnosed patients warrant high quality trials to better tailor programs to patient needs.
Distance Project-Based Learning During Lockdown and Learner’s Motivation

During the first lockdown due to Covid-19 pandemic, project-based learning (PBL) had to be implemented remotely. To gain knowledge on this learning context, we monitored motivation (in Self-Determination Theory framework), flow, social identification and self-rated performance during a 10-day project conducted with 281 engineering students. Final grades were also collected as objective performance indicators. Results show that intrinsic and identified motivation, flow, self-rated performance and group identification increased throughout the project, which suggests that remote PBL stimulated students’ needs for autonomy and competence without hindering their need for relatedness. Furthermore, the analysis of significant predictors of teams’ and individuals’ performance draw avenues for improving PBL and stimulating intrinsic and identified motivation, for the subject and for the project, at the right time along the program.
Silicon Photonics for Machine Learning: Training and Inference

Photonics neural networks employ optical device physics for neuron models, and optical interconnects for distributed, parallel, and analog processing for high-bandwidth, low-latency, and low-switching energy applications in AI and neuromorphic computing. We discuss silicon photonics for machine learning acceleration for inference and in situ training.
All-optical Switching using a Photonic Crystal Molecule with Asymmetric Fano Lineshape

We report 10 Gbps all-optical switching using a photonic molecule based on two lattice-shifted coupled photonic crystal nanocavities in Indium Phosphide. The process is enhanced by the asymmetric Fano resonance lineshape leading to 0.4 dB OSNR penalty at error rates smaller than 10−9 with switching energies as low as 19.5 fJ/bit or 39 fJ/pulse.
Over 2-Tb/s Net Bitrate Single-carrier Transmission Based on >130-GHz-Bandwidth InP-DHBT Baseband Amplifier Module

A record 2.11-Tb/s/wavelength net bitrate by optimizing entropy and code rate of 176-GBd PCS144QAM was generated with a >130-GHz-bandwidth InP-DHBT in-house amplifier and a 256-GSa/s ~80-GHz-bandwidth arbitrary waveform generator. We also demonstrated a 2.02-Tb/s net bitrate 240-km transmission with the ultra-broadband configuration.
Design of Dual-band Bandpass Filter With Novel Circuit Approach

This paper presents a novel method to design dual-band bandpass filters based on circuit values extraction approach. To employ the proposed technique, the examined circuit model's transfer function is first synthesized using specified transmission zeros (TZs) and reflection zeros (RZs). Based on the synthesized transfer function, the circuit elements are then removed one by one with the input admittance obtained. Furthermore, the coupling values of the suggested filters are derived using the standard filter synthesis approach. To demonstrate this novel approach, a third-order planar bandpass filter with a dual-band response is developed using microstrip technology. The theoretical study and simulation results were found to be in good agreement.