The Change of Teleost Skin Commensal Microbiota Is Associated With Skin Mucosal Transcriptomic Responses During Parasitic Infection by Ichthyophthirius multifillis

Teleost skin serves as the first line of defense against invading pathogens, and contain a skin-associated lymphoid tissue (SALT) that elicit gut-like immune responses against antigen stimulation. Moreover, exposed to the water environment and the pathogens therein, teleost skin is also known to be colonized by diverse microbial communities. However, little is known about the interactions between microbiota and the teleost skin mucosal immune system, especially dynamic changes about the interactions under pathogen infection. We hypothesized that dramatic changes of microbial communities and strong mucosal immune response would be present in the skin of aquatic vertebrate under parasite infection. To confirm this hypothesis, we construct an infected model with rainbow trout (Oncorhynchus mykiss), which was experimentally challenged by Ichthyophthirius multifiliis (Ich). H & E staining of trout skin indicates the successful invasion of Ich and shows the morphological changes caused by Ich infection. Critically, increased mRNA expression levels of immune-related genes were detected in trout skin from experimental groups using qRT-PCR, which were further studied by RNA-Seq analysis. Here, through transcriptomics, we detected that complement factors, pro-inflammatory cytokines, and antimicrobial genes were strikingly induced in the skin of infected fish. Moreover, high alpha diversity values of microbiota in trout skin from the experimental groups were discovered. Interestingly, we found that Ich infection led to a decreased abundance of skin commensals and increased colonization of opportunistic bacteria through 16S rRNA pyrosequencing, which were mainly characterized by lose of Proteobacteria and increased intensity of Flavobacteriaceae. To our knowledge, our results suggest for the first time that parasitic infection could inhibit symbionts and offer opportunities for other pathogens' secondary infection in teleost skin

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Semantic Activation in Badminton Action Processing and Its Modulation by Action Duration: An ERP Study

Action processing is crucial for sports activities. Using event-related potentials (ERPs), the present study investigated whether semantics were activated in action processing and, if so, whether semantic activation was modulated by action duration. Badminton athletes were recruited to finish a lexical decision task following an action-semantic priming paradigm, in which short (400 ms) or long (1000 ms) action videos served as primes, and semantically congruent or incongruent action words served as targets. The ERP results showed a P300 effect, that is, larger P300 amplitudes were observed for targets primed by semantically incongruent action videos than for targets primed by semantically congruent action videos, only when the action videos were long and not when the action videos were short. Moreover, a late positive component (LPC) was only sensitive to action duration, showing that the targets primed by long action videos elicited larger LPC amplitudes compared to the targets primed by short action videos. These results suggested that semantics could be activated in action processing and that semantic activation was modulated by action duration, supporting a link between the language system and action processing

Ecosystem service research in protected areas: A systematic review of the literature on current practices and future prospects

Protected areas (PAs) are globally important environmental management tools against the effects of human activities, as they support the conservation of marine biodiversity, habitats, ecosystems and the processes within them, as well as resources in a broad sense. However, the application of Ecosystem Services (ESs) research in the environmental management of PAs has not been elucidated and it still has obvious shortcomings. Here, we present the first systematic review of studies that have assessed the application of ES research in PAs, evaluated the beneficial evidence of using ES for PA management, and identified research gaps to be addressed for future work. The majority of the 84 studies examined were conducted in Europe (44.44%) and Asia (30.77%), and they primarily examined cultural and provisioning ESs. Most case studies focused on methodological design and lacked an understanding of the spatial and temporal evolution patterns of ESs and of the interaction between ESs and management decisions in PAs. Future studies of PAs should (1) identify the main ESs provided, (2) improve ESs assessment methods and data acquisition capabilities, and (3) assess how pressures from outside the boundaries of PAs affect their ability to maintain biodiversity and ESs in the long term

Dual-amplification system based on CRISPR-Cas12a and horseradish peroxidase-tethered magnetic microspheres for colorimetric detection of microcystin-LR

A novel dual-amplification system based on CRISPR-Cas12a and horseradish peroxidase (HRP) was developed for colorimetric determination of MC-LR. This dual-amplification was accomplished by combining the nuclease activity of CRISPR-Cas12a with the redox activity of HRP. HRP linked to magnetic beads through an ssDNA (MB-ssDNA-HRP) was used to induce a color change of the 3,3′,5,5′-tetramethylbenzidine (TMB)-H2O2 chromogenic substrate solution. Specific binding of MC-LR with its aptamer initiated the release of a complementary DNA (cDNA), which was designed to activate the trans-cleavage activity of CRISPR-Cas12a. Upon activation, Cas12a cut the ssDNA linker in MB-ssDNA-HRP, causing a reduction of HRP on the magnetic beads. Consequently, the UV–Vis absorbance of the HRP-catalyzed reaction was decreased. The dual-signal amplification facilitated by CRISPR-Cas12a and HRP enabled the colorimetric detection of MC-LR in the range 0.01 to 50 ng·mL−1 with a limit of detection (LOD) of 4.53 pg·mL−1. The practicability of the developed colorimetric method was demonstrated by detecting different levels of MC-LR in spiked real water samples. The recoveries ranged from 86.2 to 118.5% and the relative standard deviation (RSD) was 8.4 to 17.6%. This work provides new inspiration for the construction of effective signal amplification platforms and demonstrates a simple and user-friendly colorimetric method for determination of trace MC-LR

Effects of metabolizable energy and crude protein levels on laying performance, egg quality and serum biochemical indices of Fengda-1 layers

This study was conducted to investigate the effects of dietary ME and CP levels on laying performance, egg quality and serum biochemical indices of Fengda-1 layers. In a 2 × 3 factorial arrangement, 2,400 Fengda-1 layers (32 wk of age) were randomly assigned to 6 experimental diets with 2,650 and 2,750 kcal of ME/kg of diet, each containing 14.50%, 15.00% and 15.50% CP, respectively. Each dietary treatment was replicated 5 times, and feed and water were provided ad libitum. The trial lasted for 10 wk, including a 2-week acclimation period and an 8-week experimental period. Our results showed that ADFI decreased as the ME level of diet increased from 2,650 to 2,750 kcal/kg (P  0.05). Based on the data under the experimental conditions, the optimal dietary ME and CP levels of Fengda-1 layers are 2,650 kcal/kg and 15.00% (33 to 41 wk of age)

Table_1_Major cardiovascular events under biologic psoriasis therapies: a 19-year real-world analysis of FAERS data.docx

ObjectiveOver the years when biologic psoriasis therapies (TNF inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, and IL-17 inhibitors) have been used in psoriasis patients, reports of major cardiovascular events (MACEs) have emerged. This study aims to investigate the association between MACEs and biologic psoriasis therapies by using information reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsFAERS data (January 2004 to December 2022) were reviewed. For each drug–event pair, the proportional reporting ratio (PRR) and the multi-item gamma Poisson shrinker (MGPS) algorithms were used to identify drug–adverse event associations.ResultsWe filtered the query for indication and identified 173,330 reports with psoriasis indication in FAERS throughout the analyzed time frame. MACEs occurred in 4,206 patients treated with biologics. All the four biological classes had an elevated and similar reporting rates for MACEs relative to other alternative psoriasis treatments (PRR from 2.10 to 4.26; EB05 from 1.15 to 2.45). The descending order of association was IL-12/23 inhibitors>IL-17 inhibitors>IL-23 inhibitors>TNF inhibitors. The signal strength for myocardial infarction (PRR, 2.86; χ2, 296.27; EBGM 05, 1.13) was stronger than that for stroke, cardiac fatality, and death. All the biological classes demonstrated a little higher EBGM 05 score≥1 for the MACEs in patients aged 45–64 years. The time-to-onset of MACEs was calculated with a median of 228 days.ConclusionsAnalysis of adverse event reports in the FAERS reflects the potential risk of MACEs associated with the real-world use of biological therapies in comparison to other alternative psoriasis treatments. Future long-term and well-designed studies are needed to further our knowledge regarding the cardiovascular safety profile of these agents.</p