Pittmanbyskov3198
Fully inkjet-printed device fabrication is a crucial goal to enable large-area printed electronics. The limited number of two-dimensional (2D) material inks, the bottom-gated structures, and the low current on/off ratio of thin-film transistors (TFTs) has impeded the practical applications of the printed 2D material TFTs. In the search for TFTs with high current ratios, we introduce a stable and efficient method of nitrogen-doped graphene (NDG) ink preparation for inkjet printing by liquid-phase exfoliation. The NDG thin film is print-stacked with molybdenum disulfide (MoS2) by multiple printing passes to construct a MoS2-NDG stack. We demonstrate top-gated fully inkjet-printed MoS2-NDG transistors with silver drain, source, and gate electrodes, and a barium titanate (BaTiO3) dielectric. A 100% inkjet-printed MoS2-NDG vertical 2D active heterostructure layer transistor with a current on/off ratio of 1200 is exhibited. The results may lead towards the development of all-printed 2D material-based transistor switches.Here, we examined the pathogenicity and genetic differences between classical swine fever viruses (CSFV) isolated on pig farms in North Vietnam from 2014-2018. Twenty CSFV strains from 16 pig farms were classified as genotype 2 (sub-genotypes 2.1b, 2.1c, and 2.2). The main sub-genotype, 2.1c, was classified phylogenetically as belonging to the same cluster as viruses isolated from the Guangdong region in South China. Strain HY58 (sub-genotype 2.1c), isolated from pigs in Vietnam, caused higher mortality (60%) than the Vietnamese ND20 strain (sub-genotype 2.2). The Vietnamese strain of sub-genotype 2.1b was estimated to have moderate virulence; indeed, genetic analysis revealed that it belongs to the same cluster as Korean CSFV sub-genotype 2.1b. Most CSFVs circulating in North Vietnam belong to sub-genotype 2.1c. Geographical proximity means that this genotype might continue to circulate in both North Vietnam and Southern China (Guangdong, Guangxi, and Hunan).Ornithodoros soft ticks are the only known vector and reservoir of the African swine fever virus, a major lethal infectious disease of Suidae. The co-feeding event for virus transmission and maintenance among soft tick populations has been poorly documented. We infected Ornithodoros moubata, a known tick vector in Africa, with an African swine fever virus strain originated in Africa, to test its ability to infect O. moubata through co-feeding on domestic pigs. In our experimental conditions, tick-to-tick virus transmission through co-feeding failed, although pigs became infected through the infectious tick bite.Bioisosteric replacement is a powerful tool for modulating the drug-like properties, toxicity, and chemical space of experimental therapeutics. In this review, we focus on selected cases where bioisosteric replacement and scaffold hopping have been used in the development of new anti-HIV-1 therapeutics. Moreover, we cover field-based, computational methodologies for bioisosteric replacement, using studies from our group as an example. It is our hope that this review will serve to highlight the utility and potential of bioisosteric replacement in the continuing search for new and improved anti-HIV drugs.Midazolam is a rapidly effective benzodiazepine drug that is widely used as a sedative worldwide. Due to its poor solubility in a neutral aqueous solution, the clinical use of midazolam is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have drawn worldwide attention. We prepared a stable nanosuspension system that causes little muscle irritation. The particle size of the midazolam nanocrystals (MDZ/NCs) was 286.6 ± 2.19 nm, and the crystalline state of midazolam did not change in the size reduction process. The dissolution velocity of midazolam was accelerated by the nanocrystals. The pharmacokinetics study showed that the AUC0-t of the MDZ/NCs was 2.72-fold (p less then 0.05) higher than that of the midazolam solution (MDZ/S), demonstrating that the bioavailability of the MDZ/NC injection was greater than that of MDZ/S. When midazolam was given immediately after the onset of convulsions, the ED50 for MDZ/NCs was significantly more potent than that for MDZ/S and DZP/S. The MDZ/NCs significantly reduced the malondialdehyde content in the hippocampus of the seizures model rats and significantly increased the glutathione and superoxide dismutase levels. These results suggest that nanocrystals significantly influenced the dissolution behavior, pharmacokinetic properties, anticonvulsant effects, and neuroprotective effects of midazolam and ultimately enhanced their efficacy in vitro and in vivo.We studied the association between food intake, based on the extent of processing, and prostate cancer risk in a population-based case-control study conducted in Montreal, Canada in 2005-2012. Incident prostate cancer cases (n = 1919) aged ≤75 years were histologically confirmed. Population controls (n = 1991) were randomly selected from the electoral list and frequency-matched to cases by age (±5 years). A 63-item food frequency questionnaire focusing on the two years prior to diagnosis/interview was administered by interviewers. The NOVA classification was used to categorize foods based on processing level. Unconditional logistic regression estimated the association between food intake and prostate cancer risk, adjusting for age, education, ethnicity, family history, and timing of last prostate cancer screening. Consumption of unprocessed or minimally processed foods showed a slight, inverse association (Odd ratio [OR] 0.86, 95% confidence interval [CI] 0.70-1.07; highest vs. lowest quartile) with prostate cancer. An increased risk was observed with higher intake of processed foods (OR 1.29, 95%CI 1.05-1.59; highest vs. lowest quartile), but not with consumption of ultra-processed food and drinks. The associations with unprocessed/minimally processed foods and processed foods were slightly more pronounced for high-grade cancers (ORs 0.80 and 1.33, respectively). Findings suggest that food processing may influence prostate cancer risk.The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms underlying the use of various types of stem cells in cancer treatment. In addition, we summarize recent progress in the clinical applications of stem cells, as well as common risks of this therapy. We finally give general directions for future studies, aiming to improve overall outcomes in the fight against cancer.Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.The existence of a prolonged, subclinical phase of foot-and-mouth disease virus (FMDV) infection in cattle was first recognized in the 1950s. Since then, the FMDV carrier state has been a subject of controversy amongst scientists and policymakers. A fundamental conundrum remains in the discordance between the detection of infectious FMDV in carriers and the apparent lack of contagiousness to in-contact animals. Although substantial progress has been made in elucidating the causal mechanisms of persistent FMDV infection, there are still critical knowledge gaps that need to be addressed in order to elucidate, predict, prevent, and model the risks associated with the carrier state. This is further complicated by the occurrence of a distinct form of neoteric subclinical infection, which is indistinguishable from the carrier state in field scenarios, but may have substantially different epidemiological properties. This review summarizes the current state of knowledge of the FMDV carrier state and identifies specific areas of research in need of further attention. Findings from experimental investigations of FMDV pathogenesis are discussed in relation to experience gained from field studies of foot-and-mouth disease.The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies following the remarkable patient responses observed with novel checkpoint blockade therapies, due to the potential for synergistic treatment. Cross-presenting DCs are recognized for their ability to prime CD8+ T cell responses to directly induce tumor death. Consequently, they are an attractive target for next-generation DC-based strategies. check details In this review, we define the universal classification system for cross-presenting DCs, and the vital role of this subset in mediating anti-tumor immunity. Furthermore, we will detail methods of targeting these DCs both ex vivo and in vivo to boost their function and drive effective anti-tumor responses.Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays.