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To assess the role of dietary creatine on myofiber characteristics and protein synthesis in muscle, we fed grass carp (Ctenopharyngodon idellus, initial body weight: 88.47 ± 1.44 g) creatine-supplemented diets (1.84, 5.91, 8.48, and 15.44 g/kg diet) for 8 weeks. Creatine supplementation did not affect growth performance, but significantly increased creatine contents in muscle and liver. At 8.48 g/kg, creatine decreased the activities of alanine transaminase and aspartate aminotransferase in serum, and improved hardness and chewiness of muscle due to shorter myofiber mean diameter, higher myofiber density and the frequencies of the diameters of class I and III and collagen content, longer sarcomere length, and upregulated mRNA levels of slow myosin heavy chains. Creatine supplementation upregulated the mRNA expressions of myogenic regulatory factors. The 8.48 g/kg creatine-supplemented diet significantly increased the contents of protein, total amino acids (AAs), essential AAs, and free flavor AAs in muscle, the protein levels of insulin-like growth factor I, myogenic differentiation antigen, and peroxisome proliferator-activated receptor-γ coactlvator-1α in muscle, and stimulated the phosphorylation of target of rapamycin (TOR) pathway in muscle. In summary, 8.48 mg/kg creatine improved fish health and skeletal muscle growth, and increased hardness and protein synthesis in muscle of grass carp by affecting myofiber characteristics and the TOR signaling pathway. A second-order regression model revealed that the optimal dietary creatine supplementation of grass carp ranges between 8.48 and 12.04 g/kg.

The present study was conducted to investigate the effects of supplementing the practical diet with yeast autolysate (YA) on the growth performance, immunity, and disease resistance of Pacific white shrimp Litopenaeus vannamei. Four isonitrogenous and isolipidic practical diets were formulated. The relatively high-fish-meal control diet contained 25% fish meal without YA supplementation (E1). The other control diet contained 20% fish meal without YA (E2). With the E2 diet as the basis, two additional experimental diets were created by further supplementation with 1% YA (E3) and 2% YA (E4). The shrimp (initial weight: 0.30 ± 0.02 g) were fed with the four experimental diets for 8 weeks and then challenged with Vibrio parahaemolyticus. The results indicated that there were no significant differences in survival rate (SR) or feed intake (FI) among these groups. The weight gain rate (WGR) of group E1 was not significantly different from that of groups E3 and E4. The feed conversion ratio (FCR) in group E4 was lower than that of group E2, and group E4 had the highest protein efficiency ratio (PER). The total hemocyte counts (THC) and lysozyme activities in group E3 and group E4 were significantly higher than those of the other groups. Group E3 had the highest respiratory burst (RB). After V. parahaemolyticus administration, group E3 and group E4 had significantly lower cumulative mortalities than group E1 did. In conclusion, the 20% fish meal diet without YA supplementation (E2) yielded a significantly lower growth rate than the 25% fish meal diet without YA supplementation (E1) did. Furthermore, the Pacific white shrimp that received dietary supplementation with 1% YA demonstrated improved growth rate, immune response, and resistance to the V. parahaemolyticus challenge compared with those that were fed the 20% fish meal diet without YA supplementation (E2).

Fish meal is increasingly being replaced by plant protein raw materials, meanwhile, it brings phytic acid, which combines with phosphorus to form phytate phosphorus and leads to a low utilization rate of phosphorus in shrimp. To solve this problem, this study investigated the effects of phytase supplementation on growth performance, phosphorus utilization, antioxidants, and digestion in red swamp crayfish (Procambarus clarkii). Crayfish (initial mean weight: 8.69 ± 0.15 g, N = 324) were randomly divided into six groups each with three replicates of 18 individuals each, and hand-fed for 8 weeks with one of six experimental diets (50 and 490 g kg

Background: Few validated instruments exist for use in hidradenitis suppurativa (HS) trials. Objectives: To develop a novel HS Investigator Global Assessment (HS-IGA) and to validate its psychometric properties. Methods: Development of HS-IGA involved discussion among stakeholders, including patients, within HISTORIC. Data from replicate phase III randomized controlled trials evaluating HS treatment were utilized. Multivariate models identified lesion type and body region as variables of importance. Classification and regression trees for ordinal responses were built. Validation included assessment of test–retest reliability, predictive validity, responsiveness and clinical meaningfulness. Results: There were 3024 unique measurements available in PIONEER I. Mean and median lesion counts by region were largely

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is mainly characterized by chronic and progressive inflammation that damages the gastrointestinal mucosa. Increasing studies have enlightened that dysregulated cell death occurs in the inflamed sites, leading to the disruption of the intestinal barrier and aggravating inflammatory response. Ferroptosis, a newly characterized form of regulated cell death, is driven by the lethal accumulation of lipid peroxides catalyzed by cellular free iron. It has been widely documented that the fundamental features of ferroptosis, including iron deposition, GSH exhaustion, GPX4 inactivation, and lipid peroxidation, are manifested in the injured gastrointestinal tract in IBD patients. Furthermore, manipulation of the critical ferroptotic genes could alter the progression, severity, or even morbidity of the experimental colitis. Herein, we critically summarize the recent advances in the field of ferroptosis, focusing on interpreting the potential engagement of ferroptosis in the pathogenesis of IBD. Moreover, we are attempting to shed light on a perspective insight into the possibility of targeting ferroptosis as novel therapeutic designs for the clinical intervention of these gastrointestinal diseases.

Lysine crotonylation as a protein post-translational modification regulates diverse cellular processes and functions. However, the role of crotonylation in nutrient signaling pathways remains unclear. Here, we find a positive correlation between global crotonylation levels and leucine-deprivation-induced autophagy. Crotonylome profiling identifies many crotonylated proteins regulated by leucine deprivation. Bioinformatics analysis dominates 14-3-3 proteins in leucine-mediated crotonylome. Expression of 14-3-3ε crotonylation-deficient mutant significantly inhibits leucine-deprivation-induced autophagy. Molecular dynamics analysis shows that crotonylation increases molecular instability and disrupts the 14-3-3ε amphipathic pocket through which 14-3-3ε interacts with binding partners. Leucine-deprivation-induced 14-3-3ε crotonylation leads to the release of protein phosphatase 1B (PPM1B) from 14-3-3ε interaction. Active PPM1B dephosphorylates ULK1 and subsequently initiates autophagy. We further find that 14-3-3ε crotonylation is regulated by HDAC7. Taken together, our findings demonstrate that the 14-3-3ε-PPM1B axis regulated by crotonylation may play a vital role in leucine-deprivation-induced autophagy.

Owing to the dominant functions of mitochondria in multiple cellular metabolisms and distinct types of regulated cell death, maintaining a functional mitochondrial network is fundamental for the cellular homeostasis and body fitness in response to physiological adaptations and stressed conditions. The process of mitophagy, in which the dysfunctional or superfluous mitochondria are selectively engulfed by autophagosome and subsequently degraded in lysosome, has been well formulated as one of the major mechanisms for mitochondrial quality control. To date, the PINK1-PRKN-dependent and receptors (including proteins and lipids)-dependent pathways have been characterized to determine the mitophagy in mammalian cells. The mitophagy is highly responsive to the dynamics of endogenous metabolites, including iron-, calcium-, glycolysis-TCA-, NAD(+)-, amino acids-, fatty acids-, and cAMP-associated metabolites. Herein, we summarize the recent advances toward the molecular details of mitophagy regulation in mammalian cells. We also highlight the key regulations of mammalian mitophagy by endogenous metabolites, shed new light on the bidirectional interplay between mitophagy and cellular metabolisms, with attempting to provide a perspective insight into the nutritional intervention of metabolic disorders with mitophagy deficit. Abbreviations: acetyl-CoA: acetyl-coenzyme A; ACO1: aconitase 1; ADCYs: adenylate cyclases; AMPK: AMP-activated protein kinase; ATM: ATM serine/threonine kinase; BCL2L1: BCL2 like 1; BCL2L13: BCL2 like 13; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ca(2+): calcium ion; CALCOCO2: calcium binding and coiled-coil domain 2; CANX: calnexin; CO: carbon monoxide; CYCS: cytochrome c, somatic; DFP: deferiprone; DNM1L: dynamin 1 like; ER: endoplasmic reticulum; FKBP8: FKBP prolyl isomerase 8; FOXO3: forkhead box O3; FTMT: ferritin mitochondrial; FUNDC1: FUN14 domain containing 1; GABA: γ-aminobutyric acid; GSH: glutathione; HIF1A: hypoxia inducible factor 1 subunit alpha; IMMT: inner membrane mitochondrial protein; IRP1: iron regulatory protein 1; ISC: iron-sulfur cluster; ITPR2: inositol 1,4,5-trisphosphate type 2 receptor; KMO: kynurenine 3-monooxygenase; LIR: LC3 interacting region; MAM: mitochondria-associated membrane; MAP1LC3: microtubule associated protein 1 light chain 3; MFNs: mitofusins; mitophagy: mitochondrial autophagy; mPTP: mitochondrial permeability transition pore; MTOR: mechanistic target of rapamycin kinase; NAD(+): nicotinamide adenine dinucleotide; NAM: nicotinamide; NMN: nicotinamide mononucleotide; NO: nitric oxide; NPA: Niemann-Pick type A; NR: nicotinamide riboside; NR4A1: nuclear receptor subfamily 4 group A member 1; NRF1: nuclear respiratory factor 1; OPA1: OPA1 mitochondrial dynamin like GTPase; OPTN: optineurin; PARL: presenilin associated rhomboid like; PARPs: poly(ADP-ribose) polymerases; PC: phosphatidylcholine; PHB2: prohibitin 2; PINK1: PTEN induced kinase 1; PPARG: peroxisome proliferator activated receptor gamma; PPARGC1A: PPARG coactivator 1 alpha; PRKA: protein kinase AMP-activated; PRKDC: protein kinase, DNA-activated, catalytic subunit; PRKN: parkin RBR E3 ubiquitin protein ligase; RHOT: ras homolog family member T; ROS: reactive oxygen species; SIRTs: sirtuins; STK11: serine/threonine kinase 11; TCA: tricarboxylic acid; TP53: tumor protein p53; ULK1: unc-51 like autophagy activating kinase 1; VDAC1: voltage dependent anion channel 1

With more and more attention paid to the study of ocean exploration, the long-term monitoring and detection of underwater environment have become a demand. In some researches, the dense sensor deployment is used to monitor the underwater environment. Because of the strong maneuverability of target, the detection performance of the intensive sensor deployment is not high. Therefore, the autonomous underwater vehicle (AUV) is used to monitor the underwater environment. In this paper, we use a group of AUVs which consist of two AUVs with a certain distance to monitor and detect the underwater environment. Firstly, we point out the optimal detection mode of the group of AUVs is along a straight line. Then, based on the linear detection mode, the coverage degree of underwater environment is quantitatively analyzed. Besides that, we give the theoretical formula of target detection probability for stationary and moving targets. Finally, we give some simulation results to further verify the correctness of the theoretical results.

In mammals, forkhead box O3 (foxo3) plays important roles in liver immune system. The foxo3 can regulate cell cycle, DNA repair, hypoxia, apoptosis and so on. However, as such an important transcription factor, few studies on foxo3 in fish have been reported. The present study characterized the foxo3 in turbot (Scophthalmus maximus L.). Lipopolysaccharide (LPS) incubated in vitro (hepatocytes) and injected in vivo (turbot liver) were used to construct inflammatory models. The foxo3 was interfered and overexpressed to investigate its functions in liver inflammation. The open reading frame (ORF) of foxo3 was 1998 bp (base pair), encoding 665 amino acids. Sequence analysis showed that foxo3 of turbot was highly homologous to other fishes. Tissue distribution analysis revealed that the highest expression of foxo3 was in muscle. Immunofluorescence result showed that foxo3 was expressed in cytoplasm and nucleus. Knockdown of foxo3 significantly increased mRNA levels of tumor necrosis factor-α (tnf-α), interleukin-1β (il-1β), interleukin-6 (il-6), myeloid-differentiation factor 88 (myd88), cd83, toll-like receptor 2 (tlr-2) and protein level of c-Jun N-terminal kinase (JNK) in sifoxo3 + LPS (siRNA of foxo3+ LPS) group compared with NC + LPS (negative control + LPS) group in turbot hepatocytes. Overexpressed foxo3 significantly decreased mRNA levels of tnf-α, il-6, nuclear transcription factor-kappa B (nf-κb), cd83, tlr-2 and the protein level of JNK in vitro. In vivo analysis, foxo3 knockdown significantly increased levels of GOT in serum after LPS injection compared with NC+LPS group. Overexpressed foxo3 significantly decreased levels of GPT and GOT in pcDNA3.1-foxo3+LPS group compared with pcDNA3.1+LPS group in vivo. Foxo3 knockdown significantly increased mRNA levels of tnf-α, il-1β, il-6, nf-κb, myd88 and protein level of JNK in vivo in sifoxo3+LPS group compared with NC+LPS group in turbot liver. Overexpressed foxo3 significantly decreased mRNA levels of il-1β, il-6, myd88, cd83, jnk and protein level of JNK in pcDNA3.1-foxo3+LPS group compared with pcDNA3.1+LPS group in turbot liver. The results indicated that foxo3 might modulate LPS-activated hepatic inflammation in turbot by decreasing the proinflammatory cytokines, the levels of GOT and GPT as well as activating JNK/caspase-3 and tlr-2/myd88/nf-κb pathways. Taken together, these findings indicated that FoxO3 may play important roles in liver immune responses to LPS in turbot and the research of FoxO3 in liver immunity enriches the studies on immune regulation, and provides theoretical basis and molecular targets for solving liver inflammation and liver injury in fish.

This study investigated the effects of dietary lysolecithin on growth performance, feed utilization and metabolic responses of channel catfish (Ictalurus punctatus). Fish (initial weight: 14.77 ± 0.45 g) were randomly fed one of five practical diets supplemented with graded levels of lysolecithin (0, 125, 250, 375 and 500 mg/kg) in quadruplicate groups for 10 weeks. Results showed that no significant differences in weight gain, condition factor and viscerosomatic index among all the treatments. Fish fed diet supplemented with 250 mg/kg lysolecithin had significantly decreased feed conversion ratio and significantly increased protein efficiency ratio compared to that fed the control diet. The group with 250 mg/kg of dietary lysolecithin had higher protein and lower lipid contents in the whole body, and lower lipid content in the liver than those in the control group. Groups supplemented with 250–500 mg/kg of dietary lysolecithin had significantly higher gastric and intestinal lipase activities than the control group. Dietary lysolecithin at the level of 250 mg/kg significantly increased the activities of Na⁺, K⁺‐ATPase, alkaline phosphatase, total antioxidative capacity, total superoxide dismutase, glutathione peroxidase and catalase and significantly decreased the content of malondialdehyde compared to the control diet. In conclusion, dietary supplementation of lysolecithin could confer benefits of feed utilization, body composition and antioxidative capacity of channel catfish.

Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-β induction than that of its predecessor PB2-292I. IFN-β attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-β. In the mouse in vivo model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.

Two control diets based on the commercial formula were designed to contain high (27%, D1) and low (22%, D2) levels of fish meal, respectively. Into D2, 500, 1000 and 1500 mg kg−1 of yeast extract were added, respectively, yielding three experimental diets (YE1 through YE3). Shrimp (initial body weight 0.30 g ± 0.02 g) were fed with the experimental diets, five tanks each diet and 30 shrimp individuals each tank, for 8 weeks, and then challenged with Vibrio parahaemolyticus. The results showed that the specific growth rate (SGR) of shrimp in D2 was significantly lower than that of shrimp in D1 (P 0.05). YE significantly improved the activity of glutathione S-transferase. The concentration of glutathione (GSH) and the total serum anti-oxidative capacity (T-AOC) of D1 were significantly higher than those of shrimp feeding other diets (P 0.05). In conclusion, 1000–1500 mg kg−1 of YE was suggested to be supplemented into the practical diets to improve the growth, anti-oxidative capacity and intestinal morphology of shrimp L. vannamei.

Objective To compare labor patterns in pregnancies affected by fetal anomalies to low-risk singletons. Study Design Labor data from the Consortium on Safe Labor, a multicenter retrospective study from 19 U.S. hospitals, including 98,674 low-risk singletons compared with 6,343 pregnancies with fetal anomalies were analyzed. Repeated-measures analysis constructed mean labor curves by parity, gestational age, and presence of fetal anomaly in women who reached full dilation. Interval-censored regression analysis adjusted for covariables was used to determine the median traverse times for labor progression. Results Labor curves for all groups indicated slower labor progress for patients with fetal anomalies. The most significant trends in median traverse times were observed in the preterm nulliparous and term multiparous groups. The median traverse times from 4 cm to complete dilation in the preterm nulliparous control versus anomaly groups were 5.0 and 5.4 hours (p Conclusion Labor proceeds at a slower rate in pregnancies affected by anomalies.

Interleukin-17 (IL-17) is an important cytokine that plays a critical role in the inflammatory response and host defense against extracellular pathogens. In the present study, six novel IL-17 family genes (MaIL-17) were identified by analyzing Asian swamp eel (Monopterus albus) genome. Sequence analysis revealed that the MaIL-17 family genes shared similar features, comprising a signal peptide, an IL-17 superfamily region, and four conserved cysteines. Phylogenetic analysis showed that the MaIL-17 genes were clustered together with their corresponding IL-17 genes from other species. The similarity and identity of all IL-17 family genes indicated that the MaIL-17 genes are conserved among teleosts, while Ma-IL-17D is more conserved than the other Ma-IL-17s. Except for MaIL-17A/F3 and MaIL-17D, all MaIL-17s shared the same genomic structure as the genes from other fish, namely three exons and two introns. The MaIL-17s showed conserved synteny among fish, and we found that the MaIL-17D locus has a more conserved syntenic relationship with the loci from other fish and humans. These results demonstrated that MaIL-17D and human IL-17D might have evolved from a common ancestral gene and subsequently diverged. The analysis of swamp eel reference genes revealed that EEF1A1 (encoding eukaryotic translation elongation factor 1 alpha 1) was an ideal reference gene for accurate real-time qRT-PCR normalization in the swamp eel. The MaIL-17 genes are widely distributed throughout tissues, suggesting that MaIL-17s carry out their biological functions in immune and non-immune tissues compartments. The transcript of Ma-IL17s exhibited different fold changes in head kidney cells in response to Aeromonas veronii phorbol 12-myristate 13-acetate (PMA) and polyinosinic:polycytidylic acid (poly I:C) challenge, showing that MaIL-17A/F1 has stronger antiviral activities compared with other MaIL-17 family genes, and that MaIL-17A/F3 and MaIL-17A/F2 possess stronger effects against extracellular pathogens compared with the others; however, MaIL-17C2 and MaIL-17D may play vital roles during pathogen infection. The differential immune responses of these genes to Aeromonas veronii, PMA and poly I:C implied distinct mechanisms of host defense against extracellular pathogens.

In real-time optimization, plant-model mismatch can be handled by adding bias and gradient correction terms to the model-based optimization problem in order to meet the first-order necessary conditions of optimality. However, since these correction terms do not ensure the satisfaction of the second-order condition of optimality upon convergence, the model that is used in the optimization can be inadequate. In the framework of iterative modifier-adaptation, this paper proposes to only use effective model parameter updates to ensure and to speed up the convergence to the process optimum. Additionally, this paper shows that model adequacy can and should be enforced explicitly in model parameter adaptation. By means of a simulation study of maximizing the product yield in a fed-batch reactor, we demonstrate that the proposed model adaptation procedure computes model parameters which make the iterative real-time optimization with modifier-adaptation converge faster and more reliably to the plant optimum.

The CXC chemokine receptors (CXCRs) play critical roles in innate and adaptive immune systems. In this study, six Asian swamp eel (Monopterus albus) CXCRs (MaCXCR1-4) were identified and their molecular characterization and expression patterns were analyzed. The open reading frames (ORFs) of MaCXCR1a, MaCXCR1b, MaCXCR2, MaCXCR3a, MaCXCR3b, and MaCXCR4 were 1074 bp (base pairs), 1080 bp, 1125 bp, 1146 bp, 1083 bp, and 1140 bp, and encoded proteins of 357 aa (amino acids), 359 aa, 374 aa, 381 aa, 360 aa, and 379 aa, respectively. All these CXCRs have seven conserved transmembrane domains and four cysteines (with the exception of MaCXCR3b). Multiple sequence alignment revealed that the MaCXCRs possess a typical G-protein receptor family 1 signature and a DRY motif. There are also one to four potential N-glycosylation sites in the extracellular regions of the MaCXCRs, mainly distributed in the N-terminus and extracellular hydrophilic loop (ECL) 2 region. Phylogenetic analysis demonstrated that the MaCXCRs were clustered together with homologous proteins from other fish. Taken together with the amino acid identity and similarity analysis, these results suggested that the MaCXCRs are conserved with other homologous genes, in which CXCR4 is more conserved than CXCR1-3. The MaCXCRs loci showed conserved synteny among teleost fish, and we found that human CXCR1 shares a common ancestor with fish CXCR1a. MaCXCRs were constitutively expressed in a wide range of tissues (especially in immune-related tissues) with different expression levels, suggesting that the MaCXCRs have different roles in un-stimulated tissues, and may play vital roles under normal conditions. MaCXCRs showed different fold changes in the spleen after Aeromonas veronii and polyinosinic-polycytidylic acid (poly I:C) challenge, which suggested that MaCXCR1a and MaCXCR3a have longer antiviral activities compared with their antibacterial functions, and that MaCXCR1b possesses stronger antiviral than antibacterial activity. MaCXCR4 may play vital roles during bacterial and viral infection; however, MaCXCR2 has relatively small effect in antibacterial and antiviral responses. The differential responses of these genes to bacteria and poly I:C implied the differences in the mechanisms of defense against viruses and bacteria.

Objectives Trichinella spiralis is a zoonotic parasite with a complex parasitic life cycle and exposed to animals or humans by infectious meat. To control transmissions of T. spiralis through the food chain to humans, sensitive and selective multihost sera-diagnosis is urgent needed for monitoring T. spiralis exposure. Methods A competition enzyme-linked immunosorbent assay (cELISA) for T. spiralis infection diagnosis in multihost sera was developed based on recombinant cystatin-like protein (rCLP-cELISA) as well as monoclonal antibodies. The sensitivity and accuracy of the rCLP-cELISA were quantified using swine (n = 1316), mice (n = 189) and human (n = 157) serum samples. T. spiralis-antibody targeting test ability of the rCLP-cELISA in swine (n = 22) and human (n = 36), instead of other parasites or viruses antibodies, was evaluated. Results The rCLP-cELISA showed high agreement with commercial ELISA kits in field swine sera assessed by Cohen’s kappa value (κ = 0.7963). And it showed 100% specificity in human trichinellosis detection with sensitivity of 96.49%, no cross-reaction with other parasite or virus infections, and high positive detection rate of 87.5% in low-dose infected swine. Besides, the rCLP-cELISA exhibited potential in the detection of T. spiralis, T. nelsoni and Trichinella T8 infections. Conclusions The rCLP-cELISA can be used for T. spiralis-associated antibody test in multihost sera., Author summary Infections with T. spiralis that lives in host muscles for long periods of time are commonly difficult to diagnosis without causing a strong immune response or symptoms. The habit of eating raw/undercooked pork meat accidentally introduces humans into the exposure of T. spiralis that circulates between herds and rodents. There is an urgent need for serological antibody test of T. spiralis to monitor the infection of humans as well as hosts in the food chain, which is restricted by the mixture type of current used antigens and species-specific secondary antibodies for different hosts. We developed a novel recombinant cystatin-like protein-based competition enzyme-linked immunosorbent assay (rCLP-cELISA) employing monoclonal antibody. The proposed method showed considerable sensitivity and specificity in filed swine sera and human serum samples with good versatility in mice. Taking advantage of its controllable quality stability, the rCLP-cELISA had potential applications for screening of T. spiralis infections for multihost sera in one test. With the development of monoclonal antibody modification strategies and the discovery of antigenic proteins from parasitic pathogens, the proposed competition ELISA also provides useful reference for the improvement of serological assay for monitoring the exposure of zoonotic parasites.

H9N2 avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to cocirculating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain a sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016 to 2017 was by far the largest, but the mechanistic explanation behind the scale of infection is not clear. Here, we found that just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new subclades, changed antigenicity, and increased their prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus subclades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into cocirculating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C and increased viral replication in the upper and lower respiratory tracts of infected mice, which could account for the sharp increase in human cases of H7N9 virus infection in the 2016–2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential. IMPORTANCE Avian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to cocirculating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role as a donor of new subclade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (genotype 72 [G72]) with enhanced infectivity in humans during the 2016–2017 H7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of the prevalence and variants of H9N2 virus in chicken flocks is necessary for the detection of zoonotic mutations.

Ferroptosis is characterized as a novel form of regulated cell death, which is initiated by the lethal accumulation of lipid peroxidation catalyzed by cellular labile free iron. This iron driven cell death sharply differs from other well characterized forms of regulated cell death at morphological, genetic and biochemical levels. Increasing research has elaborated a high relevance between dysregulated ferroptosis and the pathogenesis of degenerative diseases and organs injury in human patients. Additionally, targeted induction of ferroptosis is considered as a potentially therapeutic design for the clinical intervention of other therapy-resistant cancers. It is well understood that mitochondria, the cellular powerhouse, determine several types of regulated cell death. Recently, compromised mitochondrial morphology and functionalities have been primarily formulated in ferroptosis. Several mitochondria associated proteins and metabolic processes have been elaborated to fine-tune ferroptotic program. Herein, we critically review the recent advances in this booming field, with focus on summarizing the multifaceted mitochondrial regulation of ferroptosis and providing a perspective on the potential biochemical basis. Finally, we are attempting to shed light on an integrative view on the possibility of mitochondria- and ferroptosis-targeting therapeutics as novel treatment designs for the intervention of ferroptosis related diseases.

Convenient and ultrasensitive detection of pesticides is demanded for healthcare and environmental monitoring, which can be realized with a dual-modal strategy. In this paper, based on a biotin-labeled IgG-modified gold nanoparticle (AuNP@IgG-bio) probe, a dual-modal immunosensor was proposed for detecting chloroacetamide herbicides. This platform is relied on the dephosphorylation of ascorbic acid 2-phosphate (AA2P) by alkaline phosphatase (ALP). In addition to this process, ascorbic acid (AA)-triggered deposition of silver on gold nanostars (AuNSs) and the fluorogenic reaction of dehydrogenated AA and o-phenylenediamine (OPD) occur sequentially. Thus, the dual readout of the color change of red-green-blue (RGB) and fluorescence generation in situ induced by crystal growth can be used. The limits of detection (LODs) were as low as 1.20 ng/mL of acetochlor (ATC), 0.89 ng/mL of metolachlor, 1.22 ng/mL of propisochlor, and 0.99 ng/mL of their mixture by a smartphone and 0.44 ng/mL of ATC, 1.59 ng/mL of metolachlor, 2.80 ng/mL of propisochlor, and 0.72 ng/mL of their mixture by a spectrofluorometer. The recoveries from corn were 91.4-105.1% of the colorimetric mode and 92.4-106.2% of the fluorescent mode. Due to its simple observation mode and good performance, this dual-modal immunosensor possesses considerable application prospects.

Creatine improves flesh quality on mammalian but studies on crustaceans are scarce. In the present study, diets with six levels of creatine (1.23, 2.58, 5.12, 8.28, 14.12, 24.49 g kg−1 diet) were hand-fed to juvenile Litopenaeus vannamei (IBW: 1.50 ± 0.02 g) reared in freshwater for 46 days. Results showed creatine supplementation did not affect the growth performance (FBW: 17.04 ± 1.28 g) or the content of guanidinoacetic acid in muscle and hepatopancreas whereas significantly increased muscular creatine content. Diet with 8.28 g kg−1 creatine significantly increased muscular hardness and chewiness by decreasing myofiber diameter and increasing myofiber density. Additionally, creatine downregulated the mRNA expression of fast sMyHC1, sMyHC2, sMyHC6a and upregulated slow sMyHC5 and sMyHC15 mRNA expression. Muscular protein, collagen, total amino acid and flavor amino acid contents increased with creatine supplementation. In conclusion, the diet with 8.28 g kg−1 creatine improved the flesh quality of L. vannamei.

Avian influenza virus (AIV) can cross species barriers to infect humans and other mammals. However, these species-cross transmissions are most often dead-end infections due to host restriction. Current research about host restriction focuses mainly on the barriers of cell membrane, nuclear envelope, and host proteins; whether microRNAs (miRNAs) play a role in host restriction is largely unknown. In this study, we used porcine alveolar macrophage (PAM) cells as a model to elucidate the role of miRNAs in host range restriction. During AIV infection, 40 dysregulation expressed miRNAs were selected in PAM cells. Among them, two Sus scrofa (ssc; swine) miRNAs, ssc-miR-221-3p and ssc-miR-222, could inhibit the infection and replication of AIV in PAM cells by directly targeting viral genome and inducing cell apoptosis via inhibiting the expression of anti-apoptotic protein HMBOX1. Avian but not swine influenza virus caused upregulated expressions of ssc-miR-221-3p and ssc-miR-222 in PAM cells. We further found that NF-κB P65 was more effectively phosphorylated upon AIV infection and that P65 functioned as a transcription activator to regulate the AIV-induced expression of miR-221-3p/222. Importantly, we found that ssc-miR-221-3p and ssc-miR-222 could also be specifically upregulated upon AIV infection in newborn pig tracheal epithelial (NPTr) cells and also exerted anti-AIV function. In summary, our study indicated that miRNAs act as a host barrier during cross-species infection of influenza A virus. IMPORTANCE The host range of an influenza A virus is determined by species-specific interactions between virus and host cell factors. Host miRNAs can regulate influenza A virus replication; however, the role of miRNAs in host species specificity is unclear. Here, we show that the induced expression of ssc-miR-221-3p and ssc-miR-222 in swine cells is modulated by NF-κB P65 phosphorylation in response to AIV infection but not swine influenza virus infection. ssc-miR-221-3p and ssc-miR-222 exerted antiviral function via targeting viral RNAs and causing apoptosis by inhibiting the expression of HMBOX1 in host cells. These findings uncover miRNAs as a host range restriction factor that limits cross-species infection of influenza A virus.

Background To better understand the profile of individuals with severe coronavirus disease 2019 (COVID-19), we characterised individuals hospitalised with COVID-19 and compared them to individuals previously hospitalised with influenza. Methods We report the characteristics (demographics, prior conditions and medication use) of patients hospitalised with COVID-19 between December 2019 and April 2020 in the US (Columbia University Irving Medical Center [CUIMC], STAnford Medicine Research data Repository [STARR-OMOP], and the Department of Veterans Affairs [VA OMOP]) and Health Insurance Review & Assessment [HIRA] of South Korea. Patients hospitalised with COVID-19 were compared with patients previously hospitalised with influenza in 2014–19. Results 6,806 (US: 1,634, South Korea: 5,172) individuals hospitalised with COVID-19 were included. Patients in the US were majority male (VA OMOP: 94%, STARR-OMOP: 57%, CUIMC: 52%), but were majority female in HIRA (56%). Age profiles varied across data sources. Prevalence of asthma ranged from 7% to 14%, diabetes from 18% to 43%, and hypertensive disorder from 22% to 70% across data sources, while between 9% and 39% were taking drugs acting on the renin-angiotensin system in the 30 days prior to their hospitalisation. Compared to 52,422 individuals hospitalised with influenza, patients admitted with COVID-19 were more likely male, younger, and, in the US, had fewer comorbidities and lower medication use. Conclusions Rates of comorbidities and medication use are high among individuals hospitalised with COVID-19. However, COVID-19 patients are more likely to be male and appear to be younger and, in the US, generally healthier than those typically admitted with influenza.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19., Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. IFI16 positively upregulates RIG-I transcription through direct binding to and recruitment of RNA polymerase II to the RIG-I promoter. IFI16 also binds to influenza viral RNA via its HINa domain and to RIG-I protein with its PYRIN domain, thus promoting IAV-induced K63-linked polyubiquitination and RIG-I activation. Our work demonstrates that IFI16 is a positive regulator of RIG-I signalling during influenza virus infection, highlighting its role in the RIG-I-like-receptor-mediated innate immune response to IAV and other RNA viruses, and suggesting its possible exploitation to modulate the antiviral response.

A 12-week feeding trial was conducted to evaluate the effects of replacement of dietary fish oil by rapeseed oil on the growth, anti-oxidative capacity and inflammatory responses of large yellow croaker Larimichthys crocea (initial body weight: 36.02 ± 0.58 g). The control diet was designed to contain 6.5% of fish oil, and named as FO. Based on it, the fish oil was 50% and 100% replaced by rapeseed oil to make the other two diets (FR and RO, respectively). Results showed that the specific growth rate was significantly reduced, and the crude lipid contents in muscle and liver were significantly increased in the RO group. The total anti-oxidative capacity and expressions of superoxide dismutase 1 and 2, glutathion peroxidase and nuclear factor erythroid 2-related factor 2 in liver of fish fed RO were significantly lower. Dietary rapeseed oil significantly decreased expressions of arginase I and interleukin 10, and increased expressions of TNFα, interleukin 1β, toll-like receptor 22 and myeloid differentiation factor 88 in liver. In conclusion, high dietary rapeseed oil could suppress growth performance and liver anti-oxidative capacity, and induce inflammation of large yellow croaker. Keywords: Large yellow croaker, Fish oil, Rapeseed oil, Lipid deposition, Anti-oxidation, Inflammation

Photothermal therapy (PTT) can take advantage of the photothermal effects of photothermal agents to acquire the energy from laser irradiation and convert it into heat. This can intensively elevate the temperature of the surrounding environment to directly destroy the cancer cells. It is expected that PAs with strong absorption in near infrared (NIR) range might possess the ideal tissue-transparent feature and minimal damage to surrounding healthy tissues, beneficial to the practical application. Herein, well-dispersed L-cysteine modified MoS

The present study was conducted to investigate the effect of fish meal replacement with Clostridium autoethanogenum protein (CAP) on growth performance, haemato-biochemistry, digestive capacity, antioxidant index, and histopathological examination of liver and intestine in largemouth bass (Micropterus salmoides). Seven experimental diets were formulated with CAP replacement of 0% (CAP0), 15% (CAP15), 27% (CAP27), 39% (CAP39), 51% (CAP51), 63% (CAP63) and 75% (CAP75) fish meal, respectively. Results showed that replacement of fish meal by CAP did not affect SR, FBW, WGR, SGR and CF. While the fish fed diets containing CAP displayed a higher PER and a lower FCR than the control group (P 0.05). Additionally, The ADC of dry matter and protein were improved by addition of CAP (P 0.05). The lipase and amylase activities were not dramatically altered in stomach (P > 0.05), but were significantly increased in intestine with dietary substitution level up to 39% (P

Mammalian hyperpolarization-activated cyclic-nucleotide–modulated (HCN) channels bind cAMP preferably in the open state. Using sea urchin HCN channels, Idikuda et al. reveal less cAMP binding to the closed state and further reduced binding to the inactivated state and thus demonstrate intricate communication between the gate and ligand-binding domain., Hyperpolarization-activated cyclic-nucleotide–modulated (HCN) channels are nonselective cation channels that regulate electrical activity in the heart and brain. Previous studies of mouse HCN2 (mHCN2) channels have shown that cAMP binds preferentially to and stabilizes these channels in the open state—a simple but elegant implementation of ligand-dependent gating. Distinct from mammalian isoforms, the sea urchin (spHCN) channel exhibits strong voltage-dependent inactivation in the absence of cAMP. Here, using fluorescently labeled cAMP molecules as a marker for cAMP binding, we report that the inactivated spHCN channel displays reduced cAMP binding compared with the closed channel. The reduction in cAMP binding is a voltage-dependent process but proceeds at a much slower rate than the movement of the voltage sensor. A single point mutation in the last transmembrane domain near the channel’s gate, F459L, abolishes inactivation and concurrently reverses the response to hyperpolarizing voltage steps from a decrease to an increase in cAMP binding. ZD7288, an open channel blocker that interacts with a region close to the activation/inactivation gate, dampens the reduction of cAMP binding to inactivated spHCN channels. In addition, compared with closed and “locked” closed channels, increased cAMP binding is observed in channels purposely locked in the open state upon hyperpolarization. Thus, the order of cAMP-binding affinity, measured by the fluorescence signal from labeled cAMP, ranges from high in the open state to intermediate in the closed state to low in the inactivated state. Our work on spHCN channels demonstrates intricate state-dependent communications between the gate and ligand-binding domain and provides new mechanistic insight into channel inactivation/desensitization.

Singlet oxygen modifies several different proteins within cells. Idikuda et al. show that, in the case of the sea urchin hyperpolarization-activated cyclic nucleotide–gated channel, a histidine residue in S6 is essential for the abolition of voltage-dependent inactivation by singlet oxygen., Photochemically or metabolically generated singlet oxygen (1O2) reacts broadly with macromolecules in the cell. Because of its short lifetime and working distance, 1O2 holds potential as an effective and precise nanoscale tool for basic research and clinical practice. Here we investigate the modification of the spHCN channel that results from photochemically and chemically generated 1O2. The spHCN channel shows strong voltage-dependent inactivation in the absence of cAMP. In the presence of photosensitizers, short laser pulses transform the gating properties of spHCN by abolishing inactivation and increasing the macroscopic current amplitude. Alanine replacement of a histidine residue near the activation gate within the channel’s pore abolishes key modification effects. Application of a variety of chemicals including 1O2 scavengers and 1O2 generators supports the involvement of 1O2 and excludes other reactive oxygen species. This study provides new understanding about the photodynamic modification of ion channels by 1O2 at the molecular level.

Teleost fish have more complex interferon receptor systems than mammals. In the present study, genes encoding four cytokine receptor family B (CRFBs) and two interferon gamma receptors (IFNGRs) in Dabry's sturgeon (Acipenser dabryanus) were identified by RNA-sequencing. Sequence analysis revealed that the Dabry's sturgeon CRFBs and IFNGRs contained several conserved characteristics features, including signal peptides and a transmembrane domain. Phylogenetic analysis suggested that they belong to the CRFB3, CRFB5, and IFNGR protein families, and were named CRFB3a, CRFB3b, CRFB5a, CRFB5b, IFNGR1, and IFNGR2. The expression patterns of the CRFB and IFNGR genes were investigated in Dabry's sturgeon. The expression levels of CRFB5a, CRFB5b, and IFNGR1 showed no significant changes, suggesting that those genes do not mediate embryonic development. By contrast, the high expression levels of CRFB3a, CRFB3b, and IFNGR2 in the fertilized egg, 16-cell phase, and initial blastula stage implied the existence of maternally expression in the oocyte and association with embryonic development. Tissue distribution analysis revealed that the CRFB and IFNGR proteins have potential functions in immune and non-immune tissue compartments. Comprehensive analysis in Dabry's sturgeon revealed that the expression fold changes of CRFB3a, CRFB3b, CRFB5a, and CRFB5b in Dabry's sturgeon stimulated with poly I:C were higher than those in fish administrated with lipopolysaccharide (LPS). Conversely, the fold changes IFNGRs mRNA levels stimulated with LPS were higher than those in fish administrated with poly I: C. CRFB5a and IFNGR2 genes showed the earliest responses to the poly I: C, and the CRFB5a and IFNGR1 genes showed the earliest responses to LPS. These results implied that CRFB5a has important role in the IFN immune response. Our findings indicated that the Dabry's sturgeon CRFB and IFNGR genes have important functions in antiviral and antibacterial immune responses. The differential responses of these genes to poly I: C and LPS implied differences in the defense mechanisms against viruses and bacteria.

In mammals, type I interferons (IFNs) are primarily regulated by transcription factors of the IFN regulatory (IRF) family. Interferon regulatory factor 5 (IRF-5) plays pivotal roles in antiviral and inflammatory responses. In the present study, we found that zebrafish (Danio rerio) IRF5 is a key player in the regulation of the expression of type I IFN and its antiviral immune response. IRF5 was upregulated in zebrafish embryonic fibroblast cells (ZF4) when challenged with grass carp reovirus (GCRV). Moreover, the expression profiles of Mx, IFN, Viperin, and IRF7, but not IRF3, were upregulated by overexpression of IRF5 in Epithelioma papulosum cyprinid cells (EPCs). Luciferase assays revealed that the activation of the IFNϕ1 promoter was stimulated by overexpression of IRF5 and IRF5-△IAD (IRF5 lacking the IRF-associated domain), respectively. However, overexpression of IRF5 or IRF5-△IAD inhibited the activity of the IFNϕ3 promoter. IRF5-△DBD (lacking the DNA-binding domain) had no influence in the activation of the IFNϕ1 and IFNϕ3 promoters. Furthermore, the determination of the cytopathic effect (CPE) numbers and viral titers revealed that the viral concentration was reduced by ectopic expression of IRF5 in EPC cells. Ectopic expression of IRF5 in EPC cells could protect cells from GCRV and significantly inhibited GCRV virus replication. These data indicated that IRF5 could limit viral replication through an IFN-dependent pathway.

Humbert’s mumbling in prison shows the readers his true inner world and his tragic fate. Throughout Lolita, it is evidently clear that Humbert’s ethical choice is inextricably linked with his depressed heart and tragic fate. Based on ethical literary criticism proposed by Professor Nie Zhenzhao, this paper analyzes Humbert’s life, which is a life full of ethical choices. This article, based on Humbert’s ethical choice of Charlotte Haze, Lolita and Quilty, and his ultimate ethical redemption, reveals his ethical dilemma in ethical choice, his Sphinx Factors, the interweaving of his free will and rational will, and his ultimate ethical choice. Humbert’s ethical choices eventually led to his tragic fate.

Dabry’s sturgeon (Acipenser dabryanus), mainly distributed in the upper Yangtze River, is considered as a rare and endangered species in China. To date, its innate immune system remains largely undetermined. In the present study, we identified an interleukin 1 beta (IL-1β) gene with a 6-exon/5-intron structure from Dabry’s sturgeon. The predicted protein sequence has a typical IL-1 family signature, containing 12 β-strands and no signal peptide. Although the predicted amino acid sequence encoded by the IL-1β gene had low sequence identity and similarity to other fish IL-1βs, the Dabry's sturgeon IL-1 β protein clustered together with proteins from other fish IL-1β type II group homologous proteins. The different expression levels of the IL-1β gene in various embryonic developmental stages implied that IL-1β might be subject to maternal transmission and mediate embryonic development. Tissue distribution analysis revealed that the IL-1β was ubiquitously expressed (especially in the skin and gill), suggesting that the IL-1β could play a vital role in the first immune barrier under normal conditions. Transcriptional analysis indicated that the IL-1β gene transcription levels in spleen leukocytes following polyinosinic-polycytidylic acid (Poly I:C) and lipopolysaccharide (LPS) stimulation were 3-fold and 12-fold higher than those in the control, respectively. The different IL-1β gene responses to poly I:C and LPS suggested differences in defense mechanisms against viruses and bacteria in Dabry’s sturgeon.

A 10-week feeding trial was conducted to explore the effects of dietary biotin and carbohydrate and their interactions on the growth performance and glucose metabolism in juvenile turbot (Scophthalmus maximus L.). Six isonitrogenous and isolipidic diets from a 2 × 3 factorial design was formulated with two levels of carbohydrate (16% and 25%) and three levels of biotin (0 mg/kg, 0.25 mg/kg and 1.5 mg/kg) respectively. The results showed that juvenile turbots fed with 16% of dietary carbohydrate and 1.5 mg/kg of biotin had the highest specific growth rate (SGR) and higher activities of intestinal amylase and stomach pepsin. Dietary biotin lowered the postprandial plasma glucose at 9 h and 24 h, regardless of dietary carbohydrate levels. However, postprandial plasma glucose at 24 h in groups with 25% of dietary carbohydrate was consistently higher than those in groups with 16% of dietary carbohydrate, regardless of dietary biotin levels. In conclusion, dietary biotin significantly decreased plasma glucose by increasing insulin level in plasma, activating PI3K (phosphoinositide 3-kinase)/AKT (protein kinase b) signaling pathway, promoting glucose transportation, glycolysis, pentose phosphate pathway and glycogen synthesis but inhibiting gluconeogenic pathway. Compared with the increased plasma glucose and growth inhibition in juvenile turbot caused by excessive dietary carbohydrate level (25%), however, the hypoglycemic effect of biotin is limited.

Tripartite motif (TRIM) proteins are receiving increased research interest because of their roles in a wide range of cellular biological processes in innate immunity. In zebrafish (Danio rerio), the functions of the finTRIM (ftr) family are unclear. In the present study, we investigated the expression pattern of ftr12, ftr51, ftr67, ftr82, ftr83, and ftr84 in zebrafish for the first time. The results showed that ftr12, ftr67, and ftr84 are maternally expressed in the oocyte and highly expressed at the early stage (0–4 hpf) of embryo (P

Fatty acid translocase/cluster of differentiation 36 (FAT/CD36) functions as a membrane long-chain fatty acid transporter in various tissues in land animals. Not much is known about the CD36 molecule in teleost fish. Therefore, we studied CD36 in grass carp (Ctenopharyngodon idella, ciCD36). The full-length complementary DNA sequence of ciCD36 was 1976 bp, with an ORF of 468 amino acids, which had high sequence similarity to the CD36 of common carp. The messenger RNA (mRNA) expression of ciCD36 was high in the intestine, heart, liver, visceral tissue, and brain, but absent in the kidney. The protein expression of ciCD36 was high in the brain, intestine, liver, heart, muscle, eye, visceral tissue, gonad, and gill, but not in the kidney. Four groups of grass carp (16 tanks) were fed three times daily to satiation with 17.2 kJ gross energy/g diet (control, CON), 19.4 kJ gross energy/g diet (more energy supplied by proteins, HP), 19.9 kJ gross energy/g diet (more energy supplied by fat, HF), and 19.1 kJ gross energy/g diet (more energy supplied by carbohydrate, HC) for 11 weeks, respectively. At the end of the feeding experiment, the fish were fasted for 48 h, and the brain, heart, intestine, and liver were sampled and designated as the 0-h samples. The fish were then fed a single meal of the above four diets, and these tissues were collected at 8- and 24-h intervals after refeeding to analyze ciCD36 mRNA and protein expression levels. The results showed that at the transcriptional and translational levels, ciCD36 expression was significantly affected by refeeding time and the different diets (P

Background: Gemcitabine and cisplatin combined with conventional radiotherapy in treating patients with cervical cancer, resulted in a favourable conclusion but accompanied with high toxicity. The objective of our research was to assess the tolerability, efficacy and feasibility of dual chemotherapy in addition to image-guided adaptive brachytherapy and highly conformal external beam radiation therapy. Methods & Materials: From June 2011 to November 2013, 81 cervical cancer patients with FIGO stage IB2-IIIB medical records were retrospectively reviewed. All patients received whole pelvic radiotherapy (WPRT) to a total dose of 50.4 Gy/ 1.8 Gy Chemoradiotherapy prescription objectives were: concurrent gemcitabine (125 mg/m2) and cisplatin (30 mg/m2) during the 6 weeks of external beam radiation therapy (EBRT) followed by two cycles of gemcitabine (1 g/m2, d1, d8) and cisplatin (25 mg/m2 d1-d3) on the tenth week. External beam radiotherapy was followed by image-guided brachytherapy of 24 Gy/ 4 fractions. Version 4 of the common terminology criteria for adverse events (CTCAE v 4.0) was used in grading the toxicities. Results: Sixty-nine patients obtained complete response (CR), six had a partial response (PR), and five patients had stable disease (SD). The disease control rate (DCR= SD and ORR) and overall response rate (ORR= PR, CR or PR) were 92.6% and 85.2% respectively. The 3-year and 5-year estimated overall survival (OS) was 75.4% and 66.3%, and the 3-year and 5-year estimated progression-free survival (PFS) were 78.2% and 65.4%. The median PFS time and OS time were 36.8 months and 45.5 months, respectively. Distance metastasis was evident in the lung (3 patients), pelvic wall (2 patients), liver (3 patients) and bone (2 patients). Six (6) had a local relapse, and two (2) patients had local relapse plus simultaneous systemic metastatic tumour. Conclusions: Unlike past results, gemcitabine and cisplatin appear to be tolerable, efficient and feasible when combined with conformal radiotherapy.

Antimicrobial peptides (AMPs) are a conserved component of the innate immune response in many species. In the present study, the cDNA sequences encoding two AMPs (cathelicidin and NK‐lysin, comprising 1,576 and 606 bp, respectively) were cloned from Dabry's sturgeon (Acipenser dabryanus). Phylogenetic analysis demonstrated that the two AMPs were clustered together with homologous protein sequences from other fish. NK‐lysin was highly expressed during early embryonic development, suggesting maternal transmission. Tissue distribution analysis showed that cathelicidin had the highest expression in the liver and NK‐lysin was most abundantly expressed in the spleen. In response to Poly I:C treatment, the expression of cathelicidin was upregulated at 12 and 24 hr post induction (hpi), but downregulated at 72 hpi. NK‐lysin mRNA expression increased after treatment with Poly I:C, reaching a peak at 24 hpi. Lipopolysaccharide treatment also induced the expression of two antimicrobial peptide genes. Lipopolysaccharide treatment significantly upregulated the expression of cathelicidin at 6, 24, and 48 hpi, and upregulated NK‐lysin expression at 6 and 12 hpi. These results suggested that two AMPs could participate in the immune response induced by poly I:C or LPS stimulation.

At present, the research of object detection in automatic driving is mainly based on the actual automatic driving vehicle. This method is expensive, less feasible, and difficult to test. Based on CARLA, we proposed an efficient and low-cost object detection method, which can overcome the shortcomings of the actual vehicle research. In this paper, firstly, we obtained images from CARLA, and then the data set is obtained by cleaning and labeling the image. Finally, based on the data set established in this paper, we train the models of YOLOv4, CenterNet and Faster-RCNN respectively, and make a comparative study on the test set. The results show that YOLOv4 has the best detection effect without special optimization method.

An 8-week feeding trial was conducted to study the effect of long-term low-salinity stress on the growth performance, and expression of osmolarity and metabolism-related genes (Na+-K+-ATPase α-subunit and in gills, trypsin and chymotypsin in hepatopancreas) in white shrimp (L. vannamei). Four groups of the white shrimp (mean initial weight, 0.31 ± 0.02 g) were cultivated at salinity of 2, 10, 20 and 30 psu for 8-week. All treatments were conducted in triplicate of 40 each. The results indicated that shrimps reared at salinity 20 psu and 30 psu were significantly higher in final weight, weight gain and specific growth ratio than the other treatments (p