Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Pseudomonas aeruginosa biofilm membrane vesicles supports multiple mechanisms of biogenesis

Outer Membrane Vesicles (OMVs) are ubiquitous in bacterial environments and enable interactions within and between species. OMVs are observed in lab-grown and environmental biofilms, but our understanding of their function comes primarily from planktonic studies. Planktonic OMVs assist in toxin delivery, cell-cell communication, horizontal gene transfer, small RNA trafficking, and immune system evasion. Previous studies reported differences in size and proteomic cargo between planktonic and agar plate biofilm OMVs, suggesting possible differences in function between OMV types. In Pseudomonas aeruginosa interstitial biofilms, extracellular vesicles were reported to arise through cell lysis, in contrast to planktonic OMV biogenesis that involves the Pseudomonas Quinolone Signal (PQS) without appreciable autolysis. Differences in biogenesis mechanism could provide a rationale for observed differences in OMV characteristics between systems. Using nanoparticle tracking, we found that P. aeruginosa PAO1 planktonic and biofilm OMVs had similar characteristics. However, P. aeruginosa PA14 OMVs were smaller, with planktonic OMVs also being smaller than their biofilm counterparts. Large differences in Staphylococcus killing ability were measured between OMVs from different strains, and a smaller within-strain difference was recorded between PA14 planktonic and biofilm OMVs. Across all conditions, the predatory ability of OMVs negatively correlated with their size. To address biogenesis mechanism, we analyzed vesicles from wild type and pqsA mutant biofilms. This showed that PQS is required for physiological-scale production of biofilm OMVs, and time-course analysis confirmed that PQS production precedes OMV production as it does in planktonic cultures. However, a small sub-population of vesicles was detected in pqsA mutant biofilms whose size distribution more resembled sonicated cell debris than wild type OMVs. These results support the idea that, while a small and unique population of vesicles in P. aeruginosa biofilms may result from cell lysis, the PQS-induced mechanism is required to generate the majority of OMVs produced by wild type communities.
Overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues predicts poor survival in pancreatic ductal adenocarcinoma

Overexpressed genes in tumors usually contributed to aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Using Gene Expression Omnibus (GEO) profiles including GSE46234, GSE71989, and GSE107610, we detected overexpressed genes in tumors with R program, which were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and Reactome pathway databases. Then, we performed a survival analysis of enriched genes based on TCGA profile. Our results revealed that high BUB1B, CCNA2, CDC20, and CDK1 expression in tumors was significantly associated with worse overall survival (OS) (Log rank P=0.00338, P=0.0447, P=0.00965, and P=0.00479, respectively), which was validated using a Kaplan–Meier plotter with a median cutoff (Log rank P=0.028, P=0.0035, P=0.039, and P=0.0033, respectively). Moreover, overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues was significantly associated with disease-free survival (DFS) in PDAC patients (Log rank P=0.00565, P=0.0357, P=0.00104, and P=0.00121, respectively). BUB1B, CCNA2, CDC20, and CDK1 were significantly overexpressed in deceased PDAC patients (all P<0.01) and in patients with recurrence/disease progression (all P<0.05). In addition, PDAC patients with neoplasms of histologic grade G3-4 had significantly higher BUB1B, CCNA2 and CDC20 levels (all P<0.05). In conclusion, the up-regulation of BUB1B, CCNA2, CDC20, CDK1, and WEE1 in tumor tissues are associated with worse OS and DFS in PDAC and is correlated with advanced tumor stage and tumor development.
Design–functionality relationships for adhesion/growth-regulatory galectins

Significance Glycan-lectin recognition is vital to embryogenesis, and progression in common diseases such as cancer and osteoarthritis. However, the rules governing specificity for the functional pairing and postbinding events are not yet understood, even though human lectins have been thoroughly characterized structurally. Herein, we employ protein engineering to produce new types of variants via redesign of modular lectin architecture. Comparative assays with cells (for growth regulation) and surface-programmable nanovesicles (for bridging) revealed qualitative effector/antagonist changes caused by topological switching, using human galectins-1 and -3 as a test case. In addition to identifying galectin-3’s unique chimera-type design as a means to enable functional antagonism between galectins, this approach generates new promising tools for imaging studies on lattices and for innovative therapeutic approaches. Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N′-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.
Impact of Mechanical Load on the Expression Profile of Synovial Fibroblasts from Patients with and without Osteoarthritis

Osteoarthritis (OA) affects the integrity of the entire joint including the synovium. The most abundant cells in the synovium are fibroblasts (SF). Excessive mechanical loading might contribute to OA pathogenesis. Here, we investigate the effects of mechanical loading on SF derived from non-OA (N-SF) and OA patients (OA-SF). We treated N-SF and OA-SF with or without mechanical loading for 48h after 24h of preincubation. Then we assessed gene and protein expression of proinflammatory factors (TNFα, COX-2, PG-E2, IL-6), extracellular matrix (ECM) components (COL1, FN1) and glycosaminoglycans (GAGs) via RT-qPCR, ELISA, DMMB assay and HPLC. Mechanical loading significantly increased TNFα and PG-E2 secretion by N-SF and OA-SF, whereas in OA-SF IL-6 secretion was reduced. COL1 and FN1 secretion were downregulated in N-SF during loading. OA-SF secreted less COL1 compared to N-SF under control conditions. In contrast, OA-SF in general expressed more FN1. GAG synthesis was upregulated in N-SF, but not in OA-SF during loading with OA-SF displaying a higher charge density than N-SF. Mechanical loading enhanced proinflammatory factor expression and GAG synthesis and decreased secretion of ECM components in N-SFs, indicating a contributing role of SF to OA development.
Polysaccharides from the Edible Mushroom Agaricus bitorquis (Quél.) Sacc. Chaidam Show Anti-hypoxia Activities in Pulmonary Artery Smooth Muscle Cells

Three kinds of new water-soluble polysaccharides (FA, FB and FC) were isolated from wild mushroom Agaricus bitorquis (Quél.) Sacc. Chaidam by the classical method “water extraction and alcohol precipitation” and purified by column chromatography. The Mw of FA, FB and FC ranged from 5690 Da to 38,340 Da. The three polysaccharide fractions in the fruiting body were mainly composed of 4 kinds of monosaccharides, including glucose, galactose, mannose, and arabinose, among which glucose and galactose were the major monosaccharides. The FTIR and NMR spectroscopy indicated that the skeleton of three fractions composed of a (1→4)-α-D-glycosidic backbone containing α-D-mannopyranose. In vitro anti-hypoxia activity data showed that three polysaccharide fractions possessed a significant effect on inhibiting PASM cells apoptosis under hypoxia. Among them, FC at the concentration of 200 µg/mL revealed a significant anti-hypoxia effect. These results revealed that the intracellular polysaccharides possessed potent anti-hypoxic activity, which might be related to inhibiting LDH and NADPH oxidase expression and promoting the formation of 5-hydroxytryptamine, dopamine, endothelins, acetylcholine. More importantly, FC showed good performance inducing KV1.5 expression and prohibiting KIR6.2 formation at protein level.
Studying the Effect of Different Gas-Phase Chemical Kinetic Mechanisms on the Formation of Oxidants, Nitrogen Compounds and Ozone in Arid Regions

CMAQ was implemented in the central region of Saudi Arabia and the effect of simulating models using various chemical mechanisms on selected oxidants, nitrogen species, and O3 was investigated. CB05TUCL predicted OH, MEPX, and NOz about 7%, 7.7%, and 8% more than CB05E51 respectively; however, there was no observable difference in the O3 predictions. The differences in variations of SAPRC07 mechanism (SAPRC07TB, SAPRC07TC, and SAPRC07TIC) for all parameters were less than 1%. RACM2 produced the highest OH and H2O2 concentrations. RACM2 enhanced OH production in the range of 24% - 32% and H2O2 by 9% over other mechanisms; these are comparatively less than the findings of other studies. Similarly, CB05 produced over 40% more PAN concentration than CB05. Moreover, PAN concentrations produced by all mechanisms were very high compared to other studies. SAPRC07 produced approximately 3% more mean surface O3 concentration than RACM2 and approximately 10% more than CB05. RACM2 O3 predictions were higher than CB05 by 7%. The predicted O3 concentrations by CB05, RACM2, and SAPRC07 were 6%, 11%, and 15% more than the average observed concentrations, which indicate that closest predictions to the observed values were by CB05. This study concludes that there is a wide variation of mechanisms with respect to the predictions of oxidants and nitrogen compounds; however, less variation is noticed in predictions of O3. For any air pollution control strategies and photochemical modeling studies in the current region or in any other arid regions, the CB05 mechanism is recommended.
Magnocellular and parvocellular pathway contributions to facial threat cue processing

Abstract Human faces evolved to signal emotions, with their meaning contextualized by eye gaze. For instance, a fearful expression paired with averted gaze clearly signals both presence of threat and its probable location. Conversely, direct gaze paired with facial fear leaves the source of the fear‐evoking threat ambiguous. Given that visual perception occurs in parallel streams with different processing emphases, our goal was to test a recently developed hypothesis that clear and ambiguous threat cues would differentially engage the magnocellular (M) and parvocellular (P) pathways, respectively. We employed two‐tone face images to characterize the neurodynamics evoked by stimuli that were biased toward M or P pathways. Human observers (N = 57) had to identify the expression of fearful or neutral faces with direct or averted gaze while their magnetoencephalogram was recorded. Phase locking between the amygdaloid complex, orbitofrontal cortex (OFC) and fusiform gyrus increased early (0‐300 ms) for M‐biased clear threat cues (averted‐gaze fear) in the &bgr;‐band (13‐30 Hz) while P‐biased ambiguous threat cues (direct‐gaze fear) evoked increased &thgr; (4‐8 Hz) phase locking in connections with OFC of the right hemisphere. We show that M and P pathways are relatively more sensitive toward clear and ambiguous threat processing, respectively, and characterize the neurodynamics underlying emotional face processing in the M and P pathways.
Protective Effect of Koumine, an Alkaloid from Gelsemium Sempervirens, on Injury Induced by H2O2 in IPEC-J2 Cells

Medicinal herbal plants have been commonly used for intervention in different diseases and improvement of health worldwide. Koumine, an alkaloid monomer found abundantly in Gelsemium plants, can be effectively used as an antioxidant. The purpose of this study was to evaluate the potential protective effect of koumine against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in porcine intestinal epithelial cell line (IPEC-J2 cells). MTT assays showed that koumine significantly increased cell viability in H2O2-mediated IPEC-J2 cells. Preincubation with koumine ameliorated H2O2-medicated apoptosis by decreasing reactive oxygen species (ROS) production, and efficiently suppressed the lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production. Moreover, a loss of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) activities was restored to normal level in H2O2-induced IPEC-J2 cells upon koumine exposure. Furthermore, pretreatment with koumine suppressed H2O2-mediated loss of mitochondrial membrane potential, caspase-9 and caspase-3 activation, decrease of Bcl-2 expression and elevation of Bax expressions. Collectively, the results of this study indicated that koumine possesses the cytoprotective effects in IPEC-J2 cells during exposure to H2O2 by suppressing production of ROS, inhibiting the caspase-3 activity and influencing the expression of Bax and Bcl-2. Koumine could potentially serve as a protective effect against H2O2-induced apoptosis.
Monolithic Integrated Device of GaN Micro-LED with Graphene Transparent Electrode and Graphene Active-Matrix Driving Transistor

Micro-light-emitting diodes (micro-LEDs) are the key to next-generation display technology. However, since the driving circuits are typically composed of Si devices, numerous micro-LED pixels must be transferred from their GaN substrate to bond with the Si field-effect transistors (FETs). This process is called massive transfer, which is arguably the largest obstacle preventing the commercialization of micro-LEDs. We combined GaN devices with emerging graphene transistors and for the first-time designed, fabricated, and measured a monolithic integrated device composed of a GaN micro-LED and a graphene FET connected in series. The p-electrode of the micro-LED was connected to the source of the driving transistor. The FET was used to tune the work current in the micro-LED. Meanwhile, the transparent electrode of the micro-LED was also made of graphene. The operation of the device was demonstrated in room temperature conditions. This research opens the gateway to a new field where other two-dimensional (2D) materials can be used as FET channel materials to further improve transfer properties. The 2D materials can in principle be grown directly onto GaN, which is reproducible and scalable. Also, considering the outstanding properties and versatility of 2D materials, it is possible to envision fully transparent micro-LED displays with transfer-free active matrices (AM), alongside an efficient thermal management solution.
Investigation of Permeation of Theophylline through Skin Using Selected Piperazine-2,5-Diones

Transdermal administration of drugs that penetrate, in this case directly into the blood circulation, has many advantages and is promising for many drugs thanks to its easy application and good patient compliance. (S)-8-Methyl-6,9-diazaspiro[4.5]decan-7,10-dione (alaptide), has been studied as a potential chemical permeation enhancer. Based on its structure, four selected piperazine-2,5-diones were synthesized by means of multi-step synthetic pathways. All the compounds were investigated on their ability to enhance the permeation of the model drug theophylline from the hydrophilic medium propylene glycol:water (1:1). In vitro experiments were performed using vertical Franz diffusion cells at constant temperature 34 ± 0.5 °C and using full-thickness pig (Sus scrofa f. domestica) ear skin. Withdrawn samples were analyzed by RP-HPLC for determination of the permeated amount of theophylline. All the compounds were applied in ratio 1:10 (w/w) relative to the amount of theophylline. One hour after application, the permeated amount of theophylline from formulations with alaptide and (3S,6S)-3,6-dimethylpiperazine-2,5-dione, was ca. 15- and 12-fold higher, respectively, than from the formulation without the tested compounds. Despite the enhancement ratio of both enhancers in a steady state was ca. 2.3, the pseudo-enhancement ratio in the time range from 1 to 3 h was 4.4. These enhancement ratios indicate that the compounds are able to enhance the permeation of agents through the skin; however, the short-term application of both compound formulations seems to be more advantageous. In addition, the screening of the cytotoxicity of all the prepared compounds was performed using three cell lines, and the compounds did not show any significant toxic effect.
Comparative genome analysis of Korean field strains of infectious laryngotracheitis virus

Attenuated live infectious laryngotracheitis (ILT) virus (ILTV) vaccines have been used to prevent and control the outbreak of ILT worldwide. Recent studies using high-throughput sequencing technology have increased the number of complete genome sequences of ILTVs, enabling comparative genome analysis. Although 37 complete genome sequences of ILTV, including vaccine strains, have been reported, the complete genome sequence of any field strain of ILTV in South Korea is yet to be published. In this study, we determined and analyzed the complete genome sequences of three virulent Korean field strains of ILTV (40798/10/Ko, 0206/14/Ko, and 30678/14/Ko). Two of the Korean field strains (40798/10/Ko and 0206/14/Ko) displayed fewer non-synonymous single nucleotide polymorphisms than those of the Serva vaccine strain, indicating that these Korean field strains of ILTV most likely originated from the vaccine strain. The third ILTV strain, 307678/14/Ko, had two regions in the genome showing recombination between the Serva vaccine-like strain and the Australian A20 vaccine-like strain. Comparative genome analysis of ILTV using the Korean field strains with variable virulence can shed light on the recent trend of the emergence of virulent ILTV strains in the field. A few amino acid changes in the genome of ILTV vaccines could enhance the virulence in the vaccine strain, and natural recombination should be considered one of the major risks for the generation of revertant strains of ILTV under field conditions.
Materials and structures used in meniscus repair and regeneration: a review

Meniscus is a vital functional unit in knee joint. It acts as a lubricating structure, a nutrient transporting structure, as well as shock absorber during jumping, twisting and running and offers stability within the knee joint. It helps in load distribution, in bearing the tensile hoop stresses and balancing by providing a cushion effect between hard surfaces of two bones. Meniscus may be injured in sports, dancing, accident or any over stressed condition. Any meniscal lesion can lead to a gradual development of osteoarthritis or erosion of bone contact surface due to disturbed load and contact stress distribution caused by injury/pain. Once injured, the possibilities of self-repair are rare in avascular region of meniscus, due to lack of blood supply in avascular region. Meniscus has vascular and avascular regions in structure. Majority of the meniscus parts turn avascular with increase in age. Purpose of this review is to highlight advances in meniscus repair with special focus on tissue engineering using textile/fiber based scaffolds, as well as the recent technical advances in scaffolds for meniscus recon- struction/ regeneration treatment.
New Iridoid Derivatives from the Fruits of Cornus officinalis and Their Neuroprotective Activities

Three previously undescribed iridoids, cornusfurals A–C, were isolated from the ethanolic extracts of fruits of Cornus officinalis. Their structures were elucidated by spectroscopic methods, including one-dimensional and two-dimensional nuclear magnetic resonance, ultraviolet spectroscopy, infrared spectroscopy, and mass spectrometry. The neuroprotective activity was evaluated by measuring corticosterone-induced damage in PC12 cells. The results showed that cornusfural B decreased corticosterone-induced PC12 cell damage compared with that in model cells.
JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress

The restoration of homeostasis after tissue damage relies on proper spatial-temporal control of damage-induced apoptosis and compensatory proliferation. In Drosophila imaginal discs these processes are coordinated by the stress response pathway JNK. We demonstrate that JNK signaling induces a dose-dependent extension of G2 in tissue damage and tumors, resulting in either transient stalling or a prolonged but reversible cell cycle arrest. G2-stalling is mediated by downregulation of the G2/M-specific phosphatase String(Stg)/Cdc25. Ectopic expression of stg is sufficient to suppress G2-stalling and reveals roles for stalling in survival, proliferation and paracrine signaling. G2-stalling protects cells from JNK-induced apoptosis, but under chronic conditions, reduces proliferative potential of JNK-signaling cells while promoting non-autonomous proliferation. Thus, transient cell cycle stalling in G2 has key roles in wound healing but becomes detrimental upon chronic JNK overstimulation, with important implications for chronic wound healing pathologies or tumorigenic transformation.