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Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that participates in various energy metabolism pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Besides, it is a required cofactor for post-translational modifications such as ADP-ribosylation and deacetylation by poly (ADP-ribose) polymerases (PARPs) and sirtuins, respectively. Thus, NAD regulates energy metabolism, DNA damage repair, gene expression, and stress response through these enzymes. Numerous studies have shown that NAD levels decrease with aging and under disturbed nutrient conditions, such as obesity. Additionally, a decline in NAD levels is closely related to the development of various metabolic disorders, including diabetes and fatty liver disease. In addition, many studies have revealed that administration of NAD precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), efficiently increase NAD levels in various tissues and prevent such metabolic diseases. These NAD precursors are contained in natural foods, such as cow milk, vegetables, and meats. Therefore, altered NAD metabolism can be a practical target for nutritional intervention. Recently, several human clinical trials using NAD precursors have been conducted to investigate the safety, pharmacokinetics, and efficacy against metabolic disorders such as glucose intolerance. In this review, we summarize current knowledge on the implications of NAD metabolism in metabolic diseases and discuss the outcomes of recent human clinical trials.

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The hydrogenated black TiO2 is receiving ever-increasing atten-tion, primarily due to the ability of capturing low energy photons in the solar spectrum and the highly efficient redox reactivity for solar-driven water splitting. However, an in-depth understanding of the physical insight into the redox reactivity is still missing. In this work, we conducted the density functional theory (DFT) study based on the model obtained from spectroscopic and aber-ration-corrected scanning transmission electron microscopy (AC-STEM) characterizations to reveal the synergy of H heteroatoms located at different surface sites where six-coordinated Ti (Ti6C) atom is converted from an inert trapping site to an interchange site of the photoexcited electrons. This in-depth understanding may be applicable to the rational design of highly efficient solar-harvesting catalysts.

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Inflammation and insomnia are two types of symptoms very likely occur in life, seriously perplexing people’s work and life. How to alleviate these symptoms is an urgent medical problem. Lucidone D (LUC) is a terpene from the ethanol extract of Ganoderma lucidum fruiting body. Triterpenoids are also the main pharmacological components of Ganoderma lucidum. In recent years, people pay more and more attention to its anti-inflammatory effect. In this study, LPS induced RAW264.7 macrophage inflammatory response model was used to evaluate the anti-inflammatory activity of LUC. The results showed that LUC could significantly inhibit the production of inflammatory mediators NO, which may play a role by down-regulating the expression level of iNOS and COX-2 proteins. Meanwhile, the production of TNF-α and IL-6 was significantly inhibited. These results indicate that LUC has obvious anti-inflammatory activity. Writhing and sedation tests in ICR male mice showed that LUC showed significant analgesic and sedative effects. In conclusion, these results suggest the anti-inflammatory, analgesic and sedative effects of LUC in vitro and in vivo.

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Objective of this study was to investigate the sedative and hypnotic effects of palmatine and to observe whether its mechanism is related to 5-hydroxytryptamine (5-HT) and GABA. The sedative and hypnotic effects of palmatine on mice were observed with mouse autonomic activity test, direct sleep test, pentobarbital sodium in suprathreshold and subthreshold dose sleep test. The content of GABA and 5-HT in brain homogenate was determined by ELISA  method. Mouse brain specimens were observed by immunohistochemistry for 5-HT expression in the nucleus of mouse brain. Palmatine could reduce spontaneous activities of mice, prolong the sleep time of mice induced by pentobarbital sodium in suprathreshold dose and shorten the sleep latency.  And it could increase the number of mice falling asleep induced by pentobarbital sodium in subthreshold dose and the incidence of falling asleep, but with no direct sleep effect. In addition, it enhanced the 5-HT content in brain, but had no effect on GABA content, and had no toxicity to PC12 cells. Palmatine plays a significant role in sedation and hypnosis, which may be associated with the increase of intra-cerebral 5-HT.

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Infections are estimated to cause approximately 15% of the world’s cancers with large geographic variations. Yet, Canadian estimates for specific cancer-causing infections are not available. To estimate the number of infection-associated cancers diagnosed among Canadian adults in 2015, we calculated population attributable risks (PARs) and the number of attributable cases for seven carcinogenic infections and their 20 associated cancers. A systematic literature search was performed for each infection to obtain data on infection prevalence in the population and the relative risk or odds ratio associated with the cancer it causes. When mechanistic evidence suggested that detection of a given infection within cancer tissue was sufficient to attribute the cancer to the infection, prevalence among cancer cases was used to approximate the PAR. Data from 61 studies formed the basis of our analyses. The estimated number of infection-attributable cancer cases for 2015 was: 3828 for human papillomavirus (HPV), 2052 for Helicobacter pylori, 578 for Epstein-Barr virus, 509 for hepatitis B and C viruses (HBV, HCV), 100 for human herpesvirus type 8, and 30 cases for human T-cell lymphotropic virus type 1. These seven infections were responsible for 3.7% of cancers diagnosed among Canadian adults in 2015; 3.5% among men and 4.0% among women. The infections with the highest number of attributable cases are largely preventable or treatable through vaccination (HBV and HPV), antibiotic therapy (H. pylori), or a combination of interventions (HCV), thereby representing an important target for reducing the infection-caused cancer burden among Canadians.

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Chronic infection with hepatitis B virus (HBV) is a major public health problem. Recently, RNA interfering-based strategy has shown great potential to eradicate HBV infection. In current study, we report the experimental observation of plant-derived artificial microRNAs (amiRNAs) acting as therapeutics in HBsAg-/+ transgenic mice. Two pieces of small silencing RNA sequences, siR471 and siR519, against HBV surface antigen gene (HBsAg) were designed and expressed in lettuce using plant endogenous microRNA biogenesis machinery. Administration of amiRNAs-containing lettuce decoction specifically inhibited the HBsAg gene expression. In long term treatments, the liver injury in HBsAg-/+ transgenic mice were alleviated and no toxicological effects were observed. Compared with synthetic siRNA, feeding amiRNAs at a lower level achieved a similar inhibitory effect on HBsAg expression in mice. These results strongly suggest that employing plant endogenous miRNA biogenesis machinery to generate medicinal siRNAs is a novel way to solve the problems of siRNA stability and reduce the potential side effects of RNAi therapy.

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Blood culture (BC) remains gold standard for the evaluation and diagnosis of neonatal sepsis. Time when BC becomes positive and the type of microorganism isolated are crucial in deciding the antimicrobial management. Likely pathogenicity of organisms growing in BC could potentially be predicted based on the “time to positivity” (TTP). We aimed to estimate the predictive value of isolating a likely pathogenic organism depending on TTP; evaluate the aetiological trend and neonatal mortality rate due to culture proven neonatal sepsis for over a decade and verify whether the application of a “36 hour rule” to discontinue empiric antibiotics in newborn infants with negative BC would be safe.

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We conducted a field experiment during three field seasons using age 0+ year Atlantic salmon Salmo salar to investigate if enrichment during rearing, in the form of structural complexity (shelters), reduced immediate (within 2 days after release) predation mortality by piscine predators (brown trout Salmo trutta) and if such rearing environments improved long-term (2-3 months after release) post-release survival. In addition, we investigated if predation mortality of released fry was size-selective. Salmo salar fry were reared in a structurally enriched environment or in a conventional rearing environment and given otolith marks using alizarin during the egg stage to distinguish between enriched and conventionally-reared fry. The outcome from the field experiments showed that structural enrichment did not consistently reduce immediate predation mortality and it did not improve, or had a negative effect on, the recapture rate of fry from the river 2-3 months after release. The data also showed that enriched rearing tended to reduce growth. Additionally, we found that S. trutta predators fed on small individuals of the released fry. Overall, the data suggest that structural enrichment alone is not sufficient to improve long-term survival of hatchery-reared fish after release and that other factors might affect post-release survival. This article is protected by copyright. All rights reserved.

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Although lithium metal is an ideal anode with high theoretical capacity, the Li dendrite formation and volume change have limited its application. We report a vertical polyaniline nanowire-coated carbon nanotube (CNT/PANI) composite flexible electrode on which Li could be homogeneously deposited to obtain CNT/PANI@Li anode. In the composite, CNT/PANI acted as a host matrix with well-distributed Li ion flux attributed to high electroactive surface area, thereby effectively suppressing Li dendrite. Compared with pure CNT electrode, the CNT/PANI electrode presented low overpotential and stable long-term cycle with much less fluctuant stripping/plating profiles. The potential application of CNT/PANI@Li in all-flexible full cells was demonstrated by combing flexible organic poly (2, 5-dihydroxyl-1, 4-benzoquinonyl sulfide)/carbon nanotube (PDHBQS/CNT) composite film, in which the cathode achieves an eminent performance of 120 mA h g-1 at 50 mA g-1. Furthermore, the pouch batteries with good flexibility were tested successfully and demonstrated a promising future for all-flexible and high-performance Li metal batteries.

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Bacterial genomics has revolutionized our understanding of the microbial tree of life; however, mapping and visualizing the distribution of functional traits across bacteria remains a challenge. Here, we introduce AnnoTree-an interactive, functionally annotated bacterial tree of life that integrates taxonomic, phylogenetic and functional annotation data from over 27 000 bacterial and 1500 archaeal genomes. AnnoTree enables visualization of millions of precomputed genome annotations across the bacterial and archaeal phylogenies, thereby allowing users to explore gene distributions as well as patterns of gene gain and loss in prokaryotes. Using AnnoTree, we examined the phylogenomic distributions of 28 311 gene/protein families, and measured their phylogenetic conservation, patchiness, and lineage-specificity within bacteria. Our analyses revealed widespread phylogenetic patchiness among bacterial gene families, reflecting the dynamic evolution of prokaryotic genomes. Genes involved in phage infection/defense, mobile elements, and antibiotic resistance dominated the list of most patchy traits, as well as numerous intriguing metabolic enzymes that appear to have undergone frequent horizontal transfer. We anticipate that AnnoTree will be a valuable resource for exploring prokaryotic gene histories, and will act as a catalyst for biological and evolutionary hypothesis generation. AnnoTree is freely available at http://annotree.uwaterloo.ca.