SciCombinator

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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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To find more effective test and intervention measures, and to achieve the first 90 of the 90-90-90 target, this study was conducted for the first time to develop and assess an innovative HIV anonymous urine test service-based vending machine and Internet at universities of China. From June to December 2016, 11 vending machines were placed in 7 pilot universities in Beijing, Sichuan, Yunnan and Heilongjiang provinces. A total of 957 HIV urine collection kits were dispensed free and also through vending machines and 378 (39.5%) urine samples were returned and 376 (99.5%) of them were qualified to be tested for HIV antibody in professional laboratories. Participants searched for confidential test results using an ID code online. Only seven (1.86%) urine samples were positive. Monitoring data showed 67.8% (255/376) participants searched for test results online, 72.2% of kits were purchased in dormitory buildings and 27.8% were purchased in teaching buildings and 88.9% were purchased between 21:00 and 24:00. In conclusion, this study analyzes the acceptability, feasibility and effectiveness of HIV testing and intervention service.

21

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.

21

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.

0

The number and type of ion channels present in the membrane determines the electrophysiological function of every neuron. In many species, stereotyped output of neurons often persists for years [1], and ion channel dysregulation can change these properties to cause severe neurological disorders [2-4]. Thus, a fundamental question is how do neurons coordinate channel expression to uphold their firing patterns over long timescales [1, 5]? One major hypothesis purports that neurons homeostatically regulate their ongoing activity through mechanisms that link membrane voltage to expression relationships among ion channels [6-10]. However, experimentally establishing this feedback loop for the control of expression relationships has been a challenge: manipulations that aim to test for voltage feedback invariably disrupt trophic signaling from synaptic transmission and neuromodulation in addition to activity [9, 11, 12]. Further, neuronal activity often relies critically on these chemical mediators, obscuring the contribution of voltage activity of the membrane per se in forming the channel relationships that determine neuronal output [6, 13]. To resolve this, we isolated an identifiable neuron in crustaceans and then either kept this neuron silent or used a long-term voltage clamp protocol to artificially maintain activity. We found that physiological voltage activity-independent of all known forms of synaptic and neuromodulatory feedback-maintains most channel mRNA relationships, while metabotropic influences may play a relatively smaller role. Thus, ion channel relationships likely needed to maintain neuronal identity are actively and continually regulated at least in part at the level of channel mRNAs through feedback by membrane voltage.

0

Arsenic is a carcinogenic contaminant of water and food and a growing threat to human health in many regions of the world. This study focuses on the fern Pteris vittata (Pteridaceae), which is extraordinary in its ability to tolerate and hyperaccumulate very high levels of arsenic that would kill any other plant or animal outside the Pteridaceae. Here, we use RNA-seq to identify three genes (GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE (PvGAPC1), ORGANIC CATION TRANSPORTER 4 (PvOCT4), and GLUTATHIONE S-TRANSFERASE (PvGSTF1) that are highly upregulated by arsenic and are necessary for arsenic tolerance, as demonstrated by RNAi. The proteins encoded by these genes have unexpected properties: PvGAPC1 has an unusual active site and a much greater affinity for arsenate than phosphate; PvGSTF1 has arsenate reductase activity; and PvOCT4 localizes as puncta in the cytoplasm. Surprisingly, PvGAPC1, PvGSTF1, and arsenate localize in a similar pattern. These results are consistent with a model that describes the fate of arsenate once it enters the cell. It involves the conversion of arsenate into 1-arseno-3-phosphoglycerate by PvGAPC1. This “chemically trapped” arsenate is pumped into specific arsenic metabolizing vesicles by the PvOCT4 protein. Once inside these vesicles, 1-arseno-3-phosphoglycerate hydrolyses to release arsenate, which is then reduced by PvGSTF1 to arsenite, the form of arsenic stored in the vacuoles of this fern. This mechanism is strikingly similar to one recently described Pseudomonas aeruginosa, whose tolerance to arsenic also involves the biosynthesis and transport of 1-arseno-3-phosphoglycerate, indicating that P. vittata has evolved a simple, bacterial-like mechanism for arsenic tolerance.

0

Sleep is fundamental to animal survival but is a vulnerable state that also limits how much time can be devoted to critical wake-dependent activities [1]. Although many animals are day-active and sleep at night, they exhibit a midday nap, or “siesta,” that can vary in intensity and is usually more prominent on warm days. In humans, the balance between maintaining the wake state or sleeping during the day has important health implications [2], but the mechanisms underlying this dynamic regulation are poorly understood. Using the well-established Drosophila melanogaster animal model to study sleep [3], we identify a new wake-sleep regulator that we term daywake (dyw). dyw encodes a juvenile hormone-binding protein [4] that functions in neurons as a day-specific anti-siesta gene, with little effect on sleep levels during the nighttime or in the absence of light. Remarkably, dyw expression is stimulated in trans via cold-enhanced splicing of the dmpi8 intron [5] from the reverse-oriented but slightly overlapping period (per) clock gene [6]. The functionally integrated dmpi8-dyw genetic unit operates as a “behavioral temperate acclimator” by increasingly counterbalancing siesta-promoting pathways as daily temperatures become cooler and carry reduced risks from daytime heat exposure. While daily patterns of when animals are awake and when they sleep are largely scheduled by the circadian timing system, dyw implicates a less recognized class of modulatory wake-sleep regulators that primarily function to enhance flexibility in wake-sleep preference, a behavioral plasticity that is commonly observed in animals during the midday, raising the possibility of shared mechanisms.