Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.
Impact of Endocytosis and Lysosomal Acidification on the Toxicity of Copper Oxide Nano- and Microsized Particles: Uptake and Gene Expression Related to Oxidative Stress and the DNA Damage Response

The toxicity of the copper oxide nanoparticles (CuO NP) has been attributed to the so-called “Trojan horse”-type mechanism, relying on the particle uptake and extensive intracellular release of copper ions, due to acidic pH in the lysosomes. Nevertheless, a clear distinction between extra- and intracellular-mediated effects is still missing. Therefore, the impact of the endocytosis inhibitor hydroxy-dynasore (OH-dyn), as well as bafilomycin A1 (bafA1), inhibiting the vacuolar type H+-ATPase (V-ATPase), on the cellular toxicity of nano- and microsized CuO particles, was investigated in BEAS 2 B cells. Selected endpoints were cytotoxicity, copper uptake, glutathione (GSH) levels, and the transcriptional DNA damage and (oxidative) stress response using the high-throughput reverse transcription quantitative polymerase chain reaction (RT-qPCR). OH-dyn markedly reduced intracellular copper accumulation in the cases of CuO NP and CuO MP; the modulation of gene expression, induced by both particle types affecting especially HMOX1, HSPA1A, MT1X, SCL30A1, IL8 and GADD45A, were completely abolished. BafA1 lowered the intracellular copper concentration in case of CuO NP and strongly reduced transcriptional changes, while any CuO MP-mediated effects were not affected by bafA1. In conclusion, the toxicity of CuO NP depended almost exclusively upon dynamin-dependent endocytosis and the intracellular release of redox-active copper ions due to lysosomal acidification, while particle interactions with cellular membranes appeared to be not relevant.
In Situ Study on Ni–Mo Stability in a Water‐Splitting Device: Effect of Catalyst Substrate and Electric Potential

Abstract Nickel–molybdenum (Ni–Mo) alloys are well studied as highly effective electrocatalyst cathodes for water splitting. Understanding deactivation pathways is a key to improving the performance of these catalysts. In this study, in situ characterization by UV/Vis spectroscopy and AFM of the morphology and Mo leaching of an Ni–Mo electrocatalyst was performed with the goal of understanding the stability and related Mo leaching mechanism. Switching the potential towards higher overpotentials results in a nonlinear change in Mo leaching. Multiple processes are proposed to take place, such as a decrease in the extent of Mo oxidation at the cathode induced by more strongly reducing potentials, while simultaneously the increase in the local pH at the cathode due to the hydrogen evolution reaction causes more Mo leaching. The change in capacitance of these materials depends strongly on the change in surface composition and not only on the surface area. In situ UV/Vis spectroscopy showed that Mo leaching is a continuous process over the course of 4 h of operation. Finally, the material was deposited on different substrates and the effect on Ni–Mo stability was studied. The substrate has a significant, albeit complex, influence on the stability and activity of Ni–Mo cathodes. In terms of stability in 1 m KOH, Ni–Mo was found to be best deposited on stainless steel substrates operated at low overpotentials, on which it showed nearly no change in capacitance and exhibited low Mo leaching.
Exploring the impact of sleep and stress on daily physical activity of cardiac patients: a preliminary study.

BACKGROUND Current approaches to cardiac rehabilitation services tailoring are often based on patient demographics or readiness for behavior change. However, the success of interventions acceptance and improved adherence to recommendations could be much higher when considering and adapting to a patient's lifestyle, such as sleep and stress. AIMS We aimed to analyze the potential associations between patient sleep and stress and daily moderate-intensity activity in patients with cardiovascular disease and to gain experience on the methods to collect and analyze a combination of qualitative and quantitative data. METHODS Patients with cardiovascular disease enrolled for an outpatient cardiac rehabilitation program were assessed at the study baseline regarding sociodemographic, clinical profile, and perceived level of stress. To collect daily physical activity and sleep data, all participants had two-week long diaries. Collected data was analyzed through correlation analysis, linear regression, and one-way ANOVA analysis. RESULTS The mean age of the participants (n =11) was 67.3 ± 9.6 years old. The patients were mainly male (82 %), married (91 %), and having at least one comorbid disease (64 %). The results of the analysis revealed that the night sleep duration is associated with moderate-intensity physical activity [F(1,6) =7.417, p =0.034]. Stress was not associated with patients' moderate-intensity daily physical activity. CONCLUSION The outcomes of the study can support the development of e-health and home-based interventions design and strategies to promote adherence to physical activity. Tailoring an intervention to a daily behavioral pattern of a patient, such as sleep, can support the planning of the physical activity in a form to be easier accepted by the patient. This finding emphasizes the need for further investigation of the association with a larger population sample and the use of objective physical activity and sleep-related measure instruments. HIPPOKRATIA 2019, 23(1): 15-20.
Scheduling of a Parcel Delivery System Consisting of an Aerial Drone Interacting with Public Transportation Vehicles

This paper proposes a novel parcel delivery system which consists of a drone and public transportation vehicles such as trains, trams, etc. This system involves two delivery schemes: drone-direct scheme referring to delivering to a customer by a drone directly and drone–vehicle collaborating scheme referring to delivering a customer based on the collaboration of a drone and public transportation vehicles. The fundamental characteristics including the delivery time, energy consumption and battery recharging are modelled, based on which a time-dependent scheduling problem for a single drone is formulated. It is shown to be NP-complete and a dynamic programming-based exact algorithm is presented. Since its computational complexity is exponential with respect to the number of customers, a sub-optimal algorithm is further developed. This algorithm accounts the time for delivery and recharging, and it first schedules the customer which leads to the earliest return. Its computational complexity is also discussed. Moreover, extensive computer simulations are conducted to demonstrate the scheduling performance of the proposed algorithms and the impacts of several key system parameters are investigated.
Host stimuli and operator binding sites controlling protein interactions between virulence master regulator ToxR and ToxS in Vibrio cholerae

Abstract Protein–protein interactions (PPIs) are key mechanisms in the maintenance of biological regulatory networks. Herein, we characterize PPIs within ToxR and its co‐activator, ToxS, to understand the mechanisms of ToxR transcription factor activation. ToxR is a key transcription activator that is supported by ToxS for virulence gene regulation in Vibrio cholerae. ToxR comprises a cytoplasmic DNA‐binding domain that is linked by a transmembrane domain to a periplasmic signal receiver domain containing two cysteine residues. ToxR‐ToxR and ToxR‐ToxS PPIs were detected using an adenylate‐cyclase‐based bacterial two‐hybrid system approach in Escherichia coli. We found that the ToxR‐ToxR PPIs are significantly increased in response to ToxR operators, the co‐activator ToxS and bile salts. We suggest that ToxS and bile salts promote the interaction between ToxR molecules that ultimately results in dimerization. Upon binding of operators, ToxR‐ToxR PPIs are found at the highest frequency. Moreover, disulfide‐bond‐dependent interaction in the periplasm results in homodimer formation that is promoted by DNA binding. The formation of these homodimers and the associated transcriptional activity of ToxR were strongly dependent on the oxidoreductases DsbA/DsbC. These findings show that protein and non‐protein partners, that either transiently or stably interact with ToxR, fine‐tune ToxR PPIs, and its associated transcriptional activity in changing environments.
The Anti-Inflammatory and Cytoprotective Efficiency of Curvularin, a Fungal Macrolactone against Lipopolysaccharide-Induced Inflammatory Response in Nucleus Pulposus Cells: An In Vitro Study

Study Design Developing an in vitro model for assessing the anti-inflammatory properties of curvularin. Purpose To evaluate the efficacy of natural fungal macrolactone as a therapeutic drug against lipopolysaccharide (LPS)-induced inflammation in primary human nucleus pulposus cells (NPCs) in vitro. Overview of Literature Lumbar disk disease is a common cause of lower back pain (LBP) and sciatica. It is an established fact that inflammation, rather than mechanical compression on the nerve root, plays a role in the cause of LBP and sciatica. Current treatment options for reducing inflammation are either nonsteroidal anti-inflammatory drugs or steroids, prolonged use of which can potentially lead to adverse effects such as gastrointestinal disturbances and renal and cardiac issues. Hence, there is a need for better antiinflammatory drugs with no or minimal complications for treating inflammation-induced LBP and sciatica. Curvularin (Cur), a fungal macrolactone, is known for its anti-inflammatory activity, but nothing is known about its impact on inflammation due to disk pathologies. Methods Primary NPCs were cultured and characterized by flow cytometry and immunocytochemistry using the CD24 antibody and treated with 10 μg/mL LPS for 36 hours and then treated with Cur, betamethasone, and dexamethasone (10 μg/mL) for 48 hours, after which cell cycle analysis, cell viability assay, and gene expression studies (quantitative polymerase chain reaction [PCR] and quantitative real-time-PCR) were conducted. The NPCs treated with Cur downregulated the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6); matrix metalloproteinases (MMPs; MMP-2 and MMP-3), ADAMTS; and apoptotic marker (cytochrome c). Results In our study, Cur-treated cells showed enhanced expression of collagen 9A1 and insulin-like growth factor receptor 1, indicating the recovery of NPCs from inflammatory assault. Conclusions Based on observations, the anti-inflammatory properties of Cur render it an excellent drug molecule for treating disk degeneration nonsurgically, by direct injection into spinal disks when treating LBP and sciatica.
Components of human breast milk: from macronutrient to microbiome and microRNA

Human breast milk (HBM) is essential for the infant’s growth and development right after birth and is an irreplaceable source of nutrition for early human survival. Various infant formulas have many similarities to HBM in many components, but there is no perfect substitute for HBM. Recently, various breast milk components and their roles have been studied according to the development of various analysis techniques. As is already well known, HBM contains about 87%–88% water, and 124- g/L solid components as macronutrients, including about 7% (60–70 g/L) carbohydrates, 1% (8–10 g/L) protein, and 3.8% (35–40 g/L) fat. The composition may vary depending on the environmental factors, including maternal diet. Colostrum is low in fat but high in protein and relatively rich in immune-protective components. Although HBM contains enough vitamins to ensure normal growth of the infant, vitamins D and K may be insufficient, and the infant may require their supplementation. Growth factors in HBM also serve as various bioactive proteins and peptides on the intestinal tract, vasculature, nervous system, and endocrine system. In the past, HBM of a healthy mother was thought to be sterile. However, several subsequent studies have confirmed the presence of rich and diverse microbial communities in HBM. Some studies suggested that the genera Staphylococcus and Streptococcus may be universally predominant in HBM, but the origin of microbiota still remains controversial. Lastly, milk is the one of most abundant body fluid of microRNAs, which are known to play a role in various functions, such as immunoprotection and developmental programming, through delivering from HBM and absorption by intestinal epithelial cells. In conclusion, HBM is the most important source of nutrition for infants and includes microbiomes and miRNAs for growth, development, and immunity.
Water Treatment: Are Membranes the Panacea?

Alongside the rising global water demand, continued stress on current water supplies has sparked interest in using nontraditional source waters for energy, agriculture, industry, and domestic needs. Membrane technologies have emerged as one of the most promising approaches to achieve water security, but implementation of membrane processes for increasingly complex waters remains a challenge. The technical feasibility of membrane processes replacing conventional treatment of alternative water supplies (e.g., wastewater, seawater, and produced water) is considered in the context of typical and emerging water quality goals. This review considers the effectiveness of current technologies (both conventional and membrane based), as well as the potential for recent advancements in membrane research to achieve these water quality goals. We envision the future of water treatment to integrate advanced membranes (e.g., mixed-matrix membranes, block copolymers) into smart treatment trains that achieve several goals, including fit-for-purpose water generation, resource recovery, and energy conservation. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 11 is June 8, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Time dependence of myocardial cell necrosis during photodynamic therapy with various photosensitizer contact time

We studied how the photosensitizer contact time affects the myocardial necrosis time during photodynamic therapy under a confocal microscopic system. Electrical conduction block by photodynamic reaction would be utilized as new catheter ablation for tachyarrhythmia to reduce complications. Photodynamic therapy with a short drug-light interval, which induces the oxidation mainly on the cell membrane is profitable to induce immediate myocardial cell necrosis. The necessary time to induce necrosis is important in the catheter ablation since the real-time electrocardiogram diagnosis is used to judge the treatment effect in clinical. The photosensitizer distribution changes from moment to moment during the therapy in vivo. It is necessary to investigate the time dependence of myocardial cell necrosis with various photosensitizer contact time in vitro. We measured the intracellular Ca2+ using fluo-4 AM during and after the photosensitization reaction. Talaporfin sodium was used as the photosensitizer, a CW red diode laser of 664 nm in wavelength was used for the photosensitizer excitation. Irradiance was 120 mW/cm2 . The necrosis occurrence time was analyzed as the sufficient intracellular Ca2+ decrease after the membrane rupture. The photosensitizer contact time was varied up to 60 min. The necessary time for the myocardial cell necrosis decreased with photosensitizer contact time increasing and the necessary time for the myocardial cell necrosis reached a minimum value of 150 s when photosensitizer contact time was 15 min. After 15 min of photosensitizer contact time, the necessary time for the myocardial cell necrosis increased as photosensitizer contact time increased.
Non-pharmacological Interventions in Residents with Behavioral and Psychological Symptoms of Dementia

Changes in behavior are common in dementia and can be challenging to address. The purpose of this pilot study was to look at how effective non-pharmacological interventions are in decreasing associated behaviors among residents in a skilled nursing facility. Pharmacological interventions have been the primary method to decreasing these behaviors; however, these interventions may lead to faster disease progression. There is an increased awareness of the potential uses of non-pharmacological treatment for residents with dementia; however, there are challenges that go along with this approach. A set of interview questions was asked to four staff members of a nursing home piloting a non-pharmacological approach. Three main categories emerged from the interviews. These categories include: decision to use the non-pharmacological interventions, alternative interventions used, and the responsiveness to using the interventions. Findings suggest that these non-pharmacological interventions were effective in decreasing problematic behaviors. Findings also suggest the need for continued education and ongoing research involving the topic of using non-pharmacological interventions to treat these behaviors residents with dementia sometimes exhibit. NONPHARMACOLOGICAL INTERVENTIONS 3
Immunization with the H5N1 Recombinant Vaccine Candidate Induces High Protection in Chickens against Vietnamese Highly Pathogenic Avian Influenza Virus Strains

Vietnam is one of the countries most affected worldwide by the highly pathogenic avian influenza (HPAI) virus, which caused enormous economic loss and posed threats to public health. Over nearly two decades, with the antigenic changes in the diversified H5Ny viruses, the limited protective efficacy of the available vaccines was encountered. Therefore, it is necessary to approach a technology platform for the country to accelerate vaccine production that enables quick response to new influenza subtypes. This study utilized a powerful reverse genetics technique to successfully generate a recombinant H5N1 vaccine strain (designated as IBT-RG02) containing two surface proteins (haemagglutinin (HA) and neuraminidase (NA)) from the HPAI H5N1 (A/duck/Vietnam/HT2/2014(H5N1)) of the dominant clade 2.3. 2.1c in Vietnam during 2012–2014. Importantly, the IBT-RG02 vaccine candidate has elicited high antibody titres in chickens (geometric mean titre (GMT) of 6.42 and 6.92, log2 on day 14 and day 28 p.i. , respectively). To test the efficacy, immunized chickens were challenged with the circulating virulent strains. As results, there was a high protection rate of 91.6% chickens against the virulent A/DK/VN/Bacninh/NCVD-17A384/2017 of the same clade and a cross-protection of 83.3% against A/duck/TG/NAVET(3)/2013 virus of clade 1.1. Our promising results showed that we can independently master the reverse genetics technology for generation of highly immunogenic vaccine candidates, and henceforth, it is a timely manner to reformulate avian influenza virus vaccines against variable H5 clade HPAI viruses in Vietnam.
Addition of Orange Peel in Orange Jam: Evaluation of Sensory, Physicochemical, and Nutritional Characteristics

Orange is highly nutritious and a source of phytochemical compounds. However, its by-products are usually discarded. In this study, we evaluated the effect of orange peel (OP) addition in orange jam on sensory, physicochemical, and nutritional characteristics. Four jam formulations were elaborated with different OP levels: OP0 (standard), OP4, OP8, and OP12 (Orange Peel 0, 4, 8 and 12%, respectively). All samples were evaluated for sensory acceptability, and physicochemical and nutritional composition. The addition of 12% orange peel in jam reduced (p < 0.05) the acceptability for all evaluated attributes, as well as overall acceptance and purchase intention. However, OP utilization increased (p < 0.05) the levels of water activity, soluble solids, titratable acidity, and sugars. Soluble solids/titratable acidity ratio, luminosity (L*), and yellow content (b*) decreased in all added OP jams, while red content (a*) increased. No change in the pH and moisture values of the product were observed after OP addition. Ash, protein, lipid, dietary fiber, ascorbic acid, carotenoids, phenolic compounds, and antioxidant capacity values increased after OP addition, while carbohydrate and energy content decreased. A texture test showed that adhesiveness decreased, while gumminess, chewiness, and elasticity increased after OP addition. We concluded that the addition of up to 8% orange peel in jam maintains sensory acceptability similar to that of the standard product. OP addition is a viable alternative to improve some of the product’s physicochemical and nutritional characteristics.
Morphological Transitions of Photoresponsive Vesicles from Amphiphilic Polypeptoid Copolymers for Controlled Release

Photoresponsive polymers have attracted increasing interest for a variety of applications. Here, we report a family of photoresponsive polypeptoid-based copolymer poly(ethylene glycol)-b-poly(N-(S-(o-nitrobenzyl)-thioethyl) glycine)-co-poly(N-(2-phenylethyl) glycine) (PEG-b-PNSN-co-PNPE) synthesized by the controlled ring-opening polymerization (ROP) technique. The key feature of the design is to incorporate both o-nitrobenzyl group moiety to offer the photoresponsive property and phenethyl residues to tune the structural and amphiphilic property of the system. We demonstrate that the cleavage degree of the o-nitrobenzyl group can reach to 100% upon UV-irradiation. With delicate design, a photoresponsive vesicle-to-sphere transition has been observed that facilitates the release of the encapsulants. This work provides a facile approach to prepare a type of photoresponsive polymers with tunable properties for drug delivery.
Arf6 Can Trigger Wave Regulatory Complex-Dependent Actin Assembly Independent of Arno

The small GTPase ADP-ribosylation factor 6 (Arf6) anchors at the plasma membrane to orchestrate key functions, such as membrane trafficking and regulating cortical actin cytoskeleton rearrangement. A number of studies have identified key players that interact with Arf6 to regulate actin dynamics in diverse cell processes, yet it is still unknown whether Arf6 can directly signal to the wave regulatory complex to mediate actin assembly. By reconstituting actin dynamics on supported lipid bilayers, we found that Arf6 in co-ordination with Rac1(Ras-related C3 botulinum toxin substrate 1) can directly trigger actin polymerization by recruiting wave regulatory complex components. Interestingly, we demonstrated that Arf6 triggers actin assembly at the membrane directly without recruiting the Arf guanine nucleotide exchange factor (GEF) ARNO (ARF nucleotide-binding site opener), which is able to activate Arf1 to enable WRC-dependent actin assembly. Furthermore, using labelled E. coli, we demonstrated that actin assembly by Arf6 also contributes towards efficient phagocytosis in THP-1 macrophages. Taken together, this study reveals a mechanism for Arf6-driven actin polymerization.