Miracle-dz/UniFAR-FTUs huggingface dataset:
APOBECs and Herpesviruses

The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of DNA cytosine deaminases provides a broad and overlapping defense against viral infections. Successful viral pathogens, by definition, have evolved strategies to escape restriction by the APOBEC enzymes of their hosts. HIV-1 and related retroviruses are thought to be the predominant natural substrates of APOBEC enzymes due to obligate single-stranded (ss)DNA replication intermediates, abundant evidence for cDNA strand C-to-U editing (genomic strand G-to-A hypermutation), and a potent APOBEC degradation mechanism. In contrast, much lower mutation rates are observed in double-stranded DNA herpesviruses and the evidence for APOBEC mutation has been less compelling. However, recent work has revealed that Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), and herpes simplex virus-1 (HSV-1) are potential substrates for cellular APOBEC enzymes. To prevent APOBEC-mediated restriction these viruses have repurposed their ribonucleotide reductase (RNR) large subunits to directly bind, inhibit, and relocalize at least two distinct APOBEC enzymes—APOBEC3B and APOBEC3A. The importance of this interaction is evidenced by genetic inactivation of the EBV RNR (BORF2), which results in lower viral infectivity and higher levels of C/G-to-T/A hypermutation. This RNR-mediated mechanism therefore likely functions to protect lytic phase viral DNA replication intermediates from APOBEC-catalyzed DNA C-to-U deamination. The RNR-APOBEC interaction defines a new pathogen-host conflict that the virus must win in real-time for transmission and pathogenesis. However, partial losses over evolutionary time may also benefit the virus by providing mutational fuel for adaptation.
Downstream Changes in Odonate (Insecta: Odonata) Communities along a Suburban to Urban Gradient: Untangling Natural and Anthropogenic Effects

Simple Summary Dragonflies are sensitive to natural and human-caused variation in the aquatic and terrestrial habitats where their larvae and adults live. For example, a reduction in shady vegetation, as a consequence of increasing stream size or streamside deforestation, often causes a reduction in specialized forest species and an increase in generalist species. We surveyed larvae and adults at 15 sites along the Reedy River in Greenville Co, SC, USA, from headwater sites in forested suburban landscapes through the urban core of the city of Greenville. We described the sediment characteristics and shoreline vegetation in two 4 m × 20 m plots at each site, and measured the percentage of developed land, forested land, grasslands, and wetlands within 500 m of each plot center. At a small scale, within plots, larval abundance and diversity increased with increasing amounts of dead debris that may provide a refuge from predators. Adult abundance and diversity correlated with the amount of aquatic and shoreline vegetation used as perches. At a large scale, diversity responded more to natural changes in habitat than urbanization: damselfly diversity increased downstream and dragonfly diversity was greatest in sunny, open habitats with fields, wetlands, and open water. Abstract The community structure of lotic odonates (Insecta: Odonata) changes downstream, but it is difficult to untangle natural and anthropogenic causes. We surveyed larvae and adults at 15 sites along the Reedy River in Greenville Co., SC, USA, from sites in forested suburban landscapes through the urban core of the city of Greenville. We used principal component analyses and Akaike information criteria models to describe the relationships between larval and adult community descriptors (abundance, richness, and diversity) and habitat characteristics at several spatial scales, including water chemistry, sediment and detritus, aquatic and streamside vegetation, and the percent cover of landforms in the surrounding landscape. At all scales, larval abundance, richness, and diversity correlated with the amount of detritus. At a small scale, adult indices correlated with the amount of sunlight and streamside vegetation. Zygopteran community composition was nested at a large scale; richness and diversity did not correlate with changes in the landscape but increased downstream. Anisopteran composition was also nested, but richness correlated with the percent cover of field, wetland, and open water in the habitat and was unrelated to downstream site position. Landscape transformation affected anisopterans more than zygopterans by opening habitats that facilitate these generalist heliotherms.
Recent Advances in Lipid-Based Nanosystems for Gemcitabine and Gemcitabine–Combination Therapy

The anti-metabolite drug gemcitabine is widely used for the treatment of a variety of cancers. At present, gemcitabine is administered as a hydrochloride salt that is delivered by slow intravenous injection in cycles of three or four weeks. Although regarded as a ‘front-line’ chemotherapeutic agent, its efficacy is hampered by poor target cell specificity, sub-optimal cellular uptake, rapid clearance from circulation, the development of chemoresistance, and undesirable side-effects. The use of organic, inorganic, and metal-based nanoparticles as delivery agents presents an opportunity to overcome these limitations and safely harness optimal drug efficacy and enhance their therapeutic indices. Among the many and varied nano delivery agents explored, the greatest body of knowledge has been generated in the field of lipid-mediated delivery. We review here the liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, exosomes, lipid-polymer hybrids, and other novel lipid-based agents that have been developed within the past six years for the delivery of gemcitabine and its co-drugs.
Effect of Different Surface Treatment Methods on Bond Strength of Dental Ceramics to Dental Hard Tissues: A Systematic Review

For long-term successful use of ceramic materials in dental procedures, it is necessary to ensure reliable bonding of restorations to dental substrates. This can be achieved by the application of a proper luting cement and through additional surface conditioning. The present systematic review summarizes the most up-to-date evidence on the use of different surface modification methods to enhance the bond strength of dental ceramics to the hard tissues of the teeth. The authors of the review searched the Web of Science, Scopus, and MEDLINE databases to identify relevant articles published between 1 January 2010 and 1 January 2020. A total of 4892 records were identified, and after screening, the full text of 159 articles was evaluated, which finally resulted in the inclusion of 19 studies. The available reports were found to be heterogeneous in terms of materials and methodology, and therefore, only within-studies comparison was performed instead of comparison between studies. A statistically significant difference in the bond strength between the samples treated with different methods of surface conditioning, or between conditioned and nonconditioned samples, was revealed by most of the studies. Predominantly, the studies showed that a combination of mechanical and chemical methods was the most effective way of enhancing bond strength. Artificial aging and luting cement were also identified as the factors significantly influencing bond strength.
Lutein Exerts Antioxidant and Anti-Inflammatory Effects and Influences Iron Utilization of BV-2 Microglia

Lutein is a tetraterpene carotenoid, which has been reported as an important antioxidant and it is widely used as a supplement. Oxidative stress participates in many human diseases, including different types of neurodegenerative disorders. Microglia, the primary immune effector cells in the central nervous system, are implicated in these disorders by producing harmful substances such as reactive oxygen species (ROS). The protective mechanisms which scavenge ROS include enzymes and antioxidant substances. The protective effects of different carotenoids against oxidative stress have been described previously. Our study focuses on the effects of lutein on antioxidant enzymes, cytokines and iron metabolism under stress conditions in BV-2 microglia. We performed cell culture experiments: BV-2 cells were treated with lutein and/or with H2O2; the latter was used for inducing oxidative stress in microglial cells. Real-time PCR was performed for gene expression analyses of antioxidant enzymes, and ELISA was used for the detection of pro- and anti-inflammatory cytokines. Our results show that the application of lutein suppressed the H2O2-induced ROS (10′: 7.5 ng + 10 µM H2O2, p = 0.0002; 10 ng/µL + 10 µM H2O2, p = 0.0007), influenced iron utilization and changed the anti-inflammatory and pro-inflammatory cytokine secretions in BV-2 cells. Lutein increased the IL-10 secretions compared to control (24 h: 7.5 ng/µL p = 0.0274; 10 ng/µL p = 0.0008) and to 10 µM H2O2-treated cells (24 h: 7.5 ng/µL + H2O2, p = 0.0003; 10 ng/µL + H2O2, p = 0.0003), while it decreased the TNFα secretions compared to H2O2 treated cells (24 h: 7.5 ng/µL + H2O2, p < 0.0001; 10 ng/µL + H2O2, p < 0.0001). These results contribute to understanding the effects of lutein, which may help in preventing or suppressing ROS-mediated microglia activation, which is related to neuronal degeneration in oxidative stress scenario.
Towards Detecting Red Palm Weevil Using Machine Learning and Fiber Optic Distributed Acoustic Sensing

Red palm weevil (RPW) is a detrimental pest, which has wiped out many palm tree farms worldwide. Early detection of RPW is challenging, especially in large-scale farms. Here, we introduce the combination of machine learning and fiber optic distributed acoustic sensing (DAS) techniques as a solution for the early detection of RPW in vast farms. Within the laboratory environment, we reconstructed the conditions of a farm that includes an infested tree with ∼12 day old weevil larvae and another healthy tree. Meanwhile, some noise sources are introduced, including wind and bird sounds around the trees. After training with the experimental time- and frequency-domain data provided by the fiber optic DAS system, a fully-connected artificial neural network (ANN) and a convolutional neural network (CNN) can efficiently recognize the healthy and infested trees with high classification accuracy values (99.9% by ANN with temporal data and 99.7% by CNN with spectral data, in reasonable noise conditions). This work paves the way for deploying the high efficiency and cost-effective fiber optic DAS to monitor RPW in open-air and large-scale farms containing thousands of trees.
Upregulation of the Renin–Angiotensin System Pathways and SARS-CoV-2 Infection: The Rationale for the Administration of Zinc-Chelating Agents in COVID-19 Patients

The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 shedding by activating the zinc-metalloprotease ADAM17, which ultimately leads to systemic upregulation of ACE2 activity. Moreover, based on experimental models, it was also shown the detrimental effect of the excessive systemic activity of ACE2 through its downstream pathways, which leads to “clinical” manifestations resembling COVID-19. In this regard, strong upregulation of circulating ACE2 activity was recently reported in COVID-19 patients, thus supporting the previous hypothesis that COVID-19 may derive from upregulation of ACE2 activity. Based on this, a reasonable hypothesis of using inhibitors that curb the upregulation of both ACE2 and ADAM17 zinc-metalloprotease activities and consequent positive feedback-loops (initially triggered by SARS-CoV-2 and subsequently sustained independently on viral trigger) is proposed as therapy for COVID-19. In particular, zinc-chelating agents such as citrate and ethylenediaminetetraacetic acid (EDTA) alone or in combination are expected to act in protecting from COVID-19 at different levels thanks to their both anticoagulant properties and inhibitory activity on zinc-metalloproteases. Several arguments are presented in support of this hypothesis and based on the current knowledge of both beneficial/harmful effects and cost/effectiveness, the use of chelating agents in the prevention and therapy of COVID-19 is proposed. In this regard, clinical trials (currently absent) employing citrate/EDTA in COVID-19 are urgently needed in order to shed more light on the efficacy of zinc chelators against SARS-CoV-2 infection in vivo.
Obesity Affects HDL Metabolism, Composition and Subclass Distribution

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin–cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.
Phospholipid-Gold Nanorods Induce Energy Crisis in MCF-7 Cells: Cytotoxicity Evaluation Using LC-MS-Based Metabolomics Approach

Phospholipid-modified gold nanorods (phospholipid-GNRs) have demonstrated drastic cytotoxicity towards MCF-7 breast cancer cells compared to polyethylene glycol-coated GNRs (PEG-GNRs). In this study, the mechanism of cytotoxicity of phospholipid-GNRs towards MCF-7 cells was investigated using mass spectrometry-based global metabolic profiling and compared to PEGylated counterparts. The results showed that when compared to PEG-GNRs, phospholipid-GNRs induced significant and more pronounced impact on the metabolic profile of MCF-7 cells. Phospholipid-GNRs significantly decreased the levels of metabolic intermediates and end-products associated with cellular energy metabolisms resulting in dysfunction in TCA cycle, a reduction in glycolytic activity, and imbalance of the redox state. Additionally, phospholipid-GNRs disrupted several metabolism pathways essential for the normal growth and proliferation of cancer cells including impairment in purine, pyrimidine, and glutathione metabolisms accompanied by lower amino acid pools. On the other hand, the effects of PEG-GNRs were limited to alteration of glycolysis and pyrimidine metabolism. The current work shed light on the importance of metabolomics as a valuable analytical approach to explore the molecular effects of GNRs with different surface chemistry on cancer cell and highlights metabolic targets that might serve as promising treatment strategy in cancer.
p62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)–Curcumin Complex

The hyperactivation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), frequently found in many tumor types, can be responsible for cancer resistance to therapies and poor patient prognosis. Curcumin has been shown to activate NRF2 that has cytotprotective or protumorigenic roles according to tumor stage. The present study aimed at investigating whether the zinc–curcumin Zn(II)–curc compound, which we previously showed to display anticancer effects through multiple mechanisms, could induce NRF2 activation and to explore the underlying molecular mechanisms. Biochemical studies showed that Zn(II)–curc treatment increased the NRF2 protein levels along with its targets, heme oxygenase-1 (HO-1) and p62/SQSTM1, while markedly reduced the levels of Keap1 (Kelch-like ECH-associated protein 1), the NRF2 inhibitor, in the cancer cell lines analyzed. The silencing of either NRF2 or p62/SQSTM1 with specific siRNA demonstrated the crosstalk between the two molecules and that the knockdown of either molecule increased the cancer cell sensitivity to Zn(II)–curc-induced cell death. This suggests that the crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to increase cancer patient response to therapies.
Unravelling the Dermatological Potential of the Brown Seaweed Carpomitra costata

The ever-increasing interest in keeping a young appearance and healthy skin has leveraged the skincare industry. This, coupled together with the increased concern regarding the safety of synthetic products, has boosted the demand for new and safer natural ingredients. Accordingly, the aim of this study was to evaluate the dermatological potential of the brown seaweed Carpomitra costata. The antioxidant, anti-enzymatic, antimicrobial, photoprotective and anti-inflammatory properties of five C. costata fractions (F1–F5) were evaluated. The ethyl acetate fraction (F3) demonstrated the most promising results, with the best ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC50 of 140.1 µg/mL) and the capacity to reduce reactive oxygen species (ROS) production promoted by UVA and UVB radiation in 3T3 cells, revealing its antioxidant and photoprotective potential. This fraction also exhibited the highest anti-enzymatic capacity, inhibiting the activities of collagenase, elastase and tyrosinase (IC50 of 7.2, 4.8 and 85.9 µg/mL, respectively). Moreover, F3 showed anti-inflammatory potential, reducing TNF-α and IL-6 release induced by LPS treatment in RAW 264.7 cells. These bioactivities may be related to the presence of phenolic compounds, such as phlorotannins, as demonstrated by NMR analysis. The results highlight the potential of C. costata as a source of bioactive ingredients for further dermatological applications.
Changes in Glutathione Content in Liver Diseases: An Update

Glutathione (GSH), a tripeptide particularly concentrated in the liver, is the most important thiol reducing agent involved in the modulation of redox processes. It has also been demonstrated that GSH cannot be considered only as a mere free radical scavenger but that it takes part in the network governing the choice between survival, necrosis and apoptosis as well as in altering the function of signal transduction and transcription factor molecules. The purpose of the present review is to provide an overview on the molecular biology of the GSH system; therefore, GSH synthesis, metabolism and regulation will be reviewed. The multiple GSH functions will be described, as well as the importance of GSH compartmentalization into distinct subcellular pools and inter-organ transfer. Furthermore, we will highlight the close relationship existing between GSH content and the pathogenesis of liver disease, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic cholestatic injury, ischemia/reperfusion damage, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatocellular carcinoma. Finally, the potential therapeutic benefits of GSH and GSH-related medications, will be described for each liver disorder taken into account.
Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum–etoposide (ICIs+EP) with platinum–irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum–etoposide (Pem+EP), durvalumab plus platinum–etoposide (Dur+EP), atezolizumab plus platinum–etoposide (Atz+EP), platinum–amrubicin (AP), IP, and platinum–etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.
Study of Radiation Characteristics of Intrinsic Josephson Junction Terahertz Emitters with Different Thickness of Bi2Sr2CaCu2O8+δ Crystals

The radiation intensity from the intrinsic Josephson junction high-Tc superconductor Bi2Sr2CaCu2O8+δ terahertz emitters (Bi2212-THz emitters) is one of the most important characteristics for application uses of the device. In principle, it would be expected to be improved with increasing the number of intrinsic Josephson junctions N in the emitters. In order to further improve the device characteristics, we have developed a stand alone type of mesa structures (SAMs) of Bi2212 crystals. Here, we understood the radiation characteristics of our SAMs more deeply, after we studied the radiation characteristics from three SAMs (S1, S2, and S3) with different thicknesses. Comparing radiation characteristics of the SAMs in which the number of intrinsic Josephson junctions are N∼ 1300 (S1), 2300 (S2), and 3100 (S3), respectively, the radiation intensity, frequency as well as the characteristics of the device working bath temperature are well understood. The strongest radiation of the order of few tens of microwatt was observed from the thickest SAM of S3. We discussed this feature through the N2-relationship and the radiation efficiency of a patch antenna. The thinner SAM of S1 can generate higher radiation frequencies than the thicker one of S3 due to the difference of the applied voltage per junctions limited by the heat-removal performance of the device structures. The observed features in this study are worthwhile designing Bi2212-THz emitters with better emission characteristics for many applications.