Lymphatic Uptake of a Highly Lipophilic Protease Inhibitor Prodrug from a Lipid-Based Formulation is Limited by Instability in the Intestine.

Dabigatran etexilate (DABE) is a lipophilic double alkyl ester prodrug of dabigatran (DAB) which is a serine protease inhibitor used clinically as an anticoagulant. Recently, translocation of serine protease enzymes, including trypsin, from the gut into the mesenteric lymph and then blood has been associated with organ failure in acute and critical illnesses (ACIs). Delivery of DABE into mesenteric lymph may thus be an effective strategy to prevent organ failure in ACIs. Most drugs access the mesenteric lymph in low quantities following oral administration, as they are rapidly transported away from the intestine via the blood. Here, we examine the potential to deliver DABE into the mesenteric lymph by promoting association with lymph lipid transport pathways via co-administration with a lipid-based formulation (LBF). A series of self-emulsifying LBFs were designed and tested in vitro for their potential to form stable DABE loaded emulsions and keep DABE solubilised and stable over time in simulated gastrointestinal conditions. The LBFs were found to form fine emulsions with a droplet size of 214 ± 30 nm and DABE was stable in the formulation. The stability of DABE in vitro in simulated intestinal conditions, plasma and lymph samples was also evaluated to ensure stability in collected samples and to evaluate whether the prodrug is likely to release active DAB. Ultimately, a highly uniform and stable self-emulsifying Type III A LBF of DABE was chosen for progression into in vivo studies in male Sprague Dawley rats to confirm the lymphatic uptake and plasma pharmacokinetics. Both in vitro and in vivo in plasma and lymph, DABE was rapidly converted to an intermediate and DAB. The main species present in vivo in both plasma and lymph was DAB and mass transport of DABE and DAB in lymph was minimal (∼0.5 % of dose). Importantly, the concentration of DABE in lymph was substantially (20-176 fold) higher than in plasma, supporting that if the prodrug were stable and did not convert to DAB in the intestine, it would be lymphatically transported. Future studies will therefore focus on optimizing the design of the prodrug and formulation to improve stability during absorption and further promote lymphatic uptake.

OsRH52A, a DEAD-Box protein, is required for embryo sac development by regulating functional megaspore specification in rice.

The development of the embryo sac is an important factor affecting seed setting in rice. Numerous genes associated with embryo sac (ES) development have been identified in plants. However, the function of the DEAD-box RNA helicase family genes on ES is poorly known in rice. Here, we characterized a rice DEAD-box protein, OsRH52A, which was localized in the nucleus and cytoplasm and highly expressed in the floral organs in rice. The knockout mutant, rh52a, displayed partial ES sterility, including degenerated ES (21.0%) and the presence of double-female-gametophyte (DFG) structure (11.8%). The DFG developed from two functional megaspores (FM) near the chalazal end in one ovule, and 3.4% of DFG could fertilize via the sac near the micropylar pole in rh52a. OsRH52A was found to interact with OsMFS1 and ZIP4, both of which play a role in homologous recombination in rice meiosis. RNA-seq identified 234 down-regulated differentially expressed genes (DEGs) associated with reproductive development, including the two genes, OsMSP1 and HSA1b, required for female germline cell specification. Taken together, our study demonstrated that OsRH52A is essential for the development of the embryo sac and provided cytological evidence regarding the formation of DFG.

Genome-wide and pan-genomic analysis reveals rich variants of NBS-LRR genes in a newly developed wild rice line from Oryza alta Swallen.

Introduction: Oryza alta Swallen is an allotetraploid perennial wild rice and contains CCDD genome, which may harbor favorable genes for the enrichment of genetic resource. Methods: A new wild rice line, Huaye 5, was developed from Oryza alta Swallen in our lab. Whole genome re-sequencing and pan-genomic analysis were employed to analyze its genomic variations and novel genes. Results and Discussion: More than ten million genomic variations were detected when compared with Asian cultivar. Among the variational genes, 724, 197 and 710 genes coded protein kinase, synthetase and transcription factor, respectively. A total of 353, 131 and 135 variational genes were associated with morphological trait, physiological trait, resistance or tolerance, respectively. A total of 62 were NBS-LRR genes were detected, in which 11 NBS-LRR genes expressed in sheath and mature stem, and 26 expressed in young and mature roots expressed. The pan-genome sequences of wild rice species with CCDD genome were constructed by integrating 8 Oryza alta (OA), 2 Oryza grandiglumis (OG) and 18 Oryza latifolia (OL) accessions. A total of 28 non-reference NBS-LRR genes were revealed, and 7 of which were mainly expressed in mature roots. This research demonstrated rich DNA variation in the Oryza alta Swallen that may provide a new germplasm for rice resistance breeding.

MORE FLORET1 controls anther development by negatively regulating key tapetal genes in both diploid and tetraploid rice.

Polyploid hybrid rice (Oryza sativa) has great potential for increasing yields. However, hybrid rice depends on male fertility and its regulation, which is less well studied in polyploid rice than in diploid rice. We previously identified a MYB transcription factor, MORE FLORET1 (MOF1), whose mutation causes male sterility in neo-tetraploid rice. MOF1 expression in anthers peaks at anther Stage 7 (S7) and progressively decreases to low levels at S10. However, it remains unclear how the dynamics of MOF1 expression contribute to male fertility. Here, we carefully examined anther development in both diploid and tetraploid mof1 rice mutants, as well as lines ectopically expressing MOF1 in a temporal manner. MOF1 mutations caused delayed degeneration of the tapetum and middle layer of anthers and aberrant pollen wall organization. Ectopic MOF1 expression at later stages of anther development led to retarded cytoplasmic reorganization of tapetal cells. In both cases, pollen grains were aborted and seed production was abolished, indicating that precise control of MOF1 expression is essential for male reproduction. We demonstrated that five key tapetal genes, CYP703A3 (CYTOCHROME P450 HYDROXYLASE 703A3), OsABCG26 (Oryza sativa ATP BINDING CASSETTE G26), PTC1 (PERSISTENT TAPETAL CELL1), PKS2 (POLYKETIDE SYNTHASE 2), and OsABCG15 (Oryza sativa ATP BINDING CASSETTE G15), exhibit expression patterns opposite to those of MOF1 and are negatively regulated by MOF1. Moreover, DNA affinity purification sequencing (DAP-seq), luciferase activity assays, and electrophoretic mobility shift assays indicated that MOF1 binds directly to the PKS2 promoter for transcriptional repression. Our results provide a mechanistic basis for the regulation of male reproduction by MOF1 in both diploid and tetraploid rice. This study will facilitate the development of polyploid male sterile lines, which are useful for breeding of polyploid hybrid rice.

The impact of backpack load on adolescent's stair descent gait.

This study investigates the impact of increasing backpack load on the gait of adolescents during stair descent. Sixteen healthy male students (age = 12.9 ± 0.6 years) were required to descend the stairs in 4 loaded conditions. The kinematic, kinetic, and EMG data were collected synchronously and gait parameters, especially indicators of balance control, were analyzed. The posterior tilt angles (COM-COP IA in the sagittal plane) (0 %-42 %, 48 %-53 %, 58 %-91 %, p < 0.01), trunk anterior tilt angles (9-33 %, 51-65 %, p < 0.01), and CV of stride length (p < 0.01) increased with the backpack load. The COM-Step edge separation decreased with the increased backload (p < 0.01). In addition, the hip flexion torque (25-40 %, 45-51 %, p < 0.01), the rectus femoris activation, and the hip stiffness increased significantly as the load up to 15 % Body Weight (BW)and 20 % BW. The increasing backpack load may affect adolescent's stair descent gait. Especially as the load was up to 15 % BW, the adolescents' bodies tended to tilt backwards relative to the support foot during the single stance phase. They may activate the hip flexors and tilt forward the trunk to recover from the balance perturbation, which was associated with increased hip flexion torques. This adjustment was more pronounced with the increasing backpack load. However, excessive forward flexion may increase the risk of forward falls. The boundaries of adjustment need further research in the future. Findings from this study provide baseline information on the intrinsic mechanisms of balance control during stair descent.

Genomic evidence of genetic diversity and functional evolution in Flavobacterium columnare.

Flavobacterium columnare is the causative agent of columnaris disease in freshwater fish. Columnaris disease can cause heavy economic losses in aquaculture. In this study, whole-genome sequencing was used to characterize this pathogen. F. columnare isolate AH-01 had a circular chromosome and plasmid that encoded a total of 3,022 genes. Isolate GX-01 only had a circular chromosome and encoded 2,965 genes. Genomic islands, prophage regions, and CRISPR/Cas systems were identified in both genomes. Both genomes presented evidence of gene variation and horizontal transfer, both of which are the essential components of genetic diversity, genome plasticity, and functional evolution. Single-gene phylogeny and comparative genome analyses were performed to investigate the variation and evolution of this pathogen. Genetic analysis of 16S rRNA and housekeeping gene sequences significantly clustered 55 F. columnare isolates into four clades. The intragroup identity of the 16S rRNA gene exceeded 99%, while the intergroup identity was below the species delineation threshold. We discovered significant translocation, inversion, and rearrangement events that influenced local synteny within each group. Notably, the observed alignments varied considerably among all the studied groups. The core genomes of all strains with available sequences comprised 747 genes, corresponding to approximately 25% of the genome. Core genome multilocus sequence typing, genome-wide orthology and phylogenetic analyses, and average nucleotide identity suggested that the currently existing F. columnare was an assemblage of several distinct species, with levels of divergence at least equivalent to those between recognized bacterial species. The present investigation provided genomic evidence of gene variation and horizontal transfer, which were the basis of genetic diversity, genome plasticity, and functional evolution. The findings supported a proposed new taxonomic perspective on F. columnare.

Autotetraploid rice: challenges and opportunities.

Autotetraploid rice is a type of germplasm developed from the whole genome duplication of diploid rice, leading to large grains, high nutrient content, and resistance. However, its low fertility has reduced yield and hampered commercialization. To address this issue, a new type of high fertility tetraploid rice was developed, which may serve as a useful germplasm for polyploid rice breeding. In this review, we summarize the progress made in understanding the cellular and molecular genetic mechanisms underlying the low fertility of autotetraploid rice and its F1 hybrid, as well as the main types of new tetraploid rice with high fertility. Lastly, the idea of utilizing the multi-generation heterosis of neo-tetraploid rice in the future is proposed as a reference for polyploid rice breeding.

The protective effect of inactivated Flavobacterium columnare vaccine in grass carp (Ctenopharyngodon idellus).

Flavobacterium columnare, which causes columnaris disease, is responsible for significant mortality in grass carp. Vaccination is a safe and effective measure to combat this disease, and this study aimed to investigate the immune protective effects of different treatments using an inactivated F. columnare vaccine. The vaccine was prepared by inactivating the bacteria with 0.05% formaldehyde at 4°C for 24 hours. The experiments involving grass carp were divided into two parts. In Experiment 1, the immune effects of two isolates, JX-01 (genomovar I) and MU-04 (genomovar II), were compared, along with the impact of white oil adjuvant and the number of immunizations. The results showed that when the white oil adjuvant was used as a booster, the relative percent survival (RPS) of the JW2 group and MW2 group after 8 weeks of the first immunization was 34% and 61%, respectively. In Experiment 2, only the MU-04 (genomovar II) isolate was used as an antigen, with the white oil adjuvant as a booster. The effects of different doses (CFU=108, 107, and 106 bacteria/mL) on immune responses were compared, and the RPS values in the MW6, MW7, and MW8 groups after 4 weeks of the first immunization were found to be 38%, 57%, and 71%, respectively. Furthermore, in the cross-antigen protection experiment, the MW2 group exhibited an RPS of 55% against the JX-01 isolate, which was significantly higher than the control group (33%). These findings suggest that an inactivated vaccine comprising an appropriate antigen isolate when administered with a white oil adjuvant as a booster, can provide effective protection in grass carp.

Effects of Mobile Phone Use on Gait and Balance Control in Young Adults: A Hip-Ankle Strategy.

BACKGROUND: This study aimed to derive the effects of walking while using a mobile phone on balance perturbation and joint movement among young adults. METHODS: Sixteen healthy college students with no history of brain injury were tested. The participants were asked to walk under four different conditions: (1) walking, (2) browsing, (3) dialing, and (4) texting. Indicators related to balance control and lower limb kinematic/kinetic parameters were analyzed using the continuous relative phase and statistical nonparametric mapping methods. RESULTS: Walking while using a mobile phone slowed participants' gait speed and reduced the cadence, stride length, and step length. The posterior tilt angle (0-14%, 57-99%), torque of the hip flexion (0-15%, 30-35%, 75-100%), and angle of the hip flexion (0-28%, 44-100%) decreased significantly. The activation of biceps femoris and gastrocnemius, hip stiffness, and ankle stiffness increased significantly. This impact on gait significantly differed among three dual tasks: texting > browsing > dialing. CONCLUSION: Che overlap of walking and mobile phone use affects the gait significantly. The "hip-ankle strategy" may result in a "smooth" but slower gait, while this strategy was deliberate and tense. In addition, this adjustment also increases the stiffness of the hip and ankle, increasing the risk of fatigue. Findings regarding this effect may prove that even for young healthy adults, walking with mobile phone use induces measurable adjustment of the motor pattern. These results suggest the importance of simplifying the control of the movement.

An uncharacterized protein NY1 targets EAT1 to regulate anther tapetum development in polyploid rice.

BACKGROUND: Autotetraploid rice is a useful germplasm for the breeding of polyploid rice; however, low fertility is a major hindrance for its utilization. Neo-tetraploid rice with high fertility was developed from the crossing of different autotetraploid rice lines. Our previous research showed that the mutant (ny1) of LOC_Os07g32406 (NY1), which was generated by CRISPR/Cas9 knock-out in neo-tetraploid rice, showed low pollen fertility, low seed set, and defective chromosome behavior during meiosis. However, the molecular genetic mechanism underlying the fertility remains largely unknown. RESULTS: Here, cytological observations of the NY1 mutant (ny1) indicated that ny1 exhibited abnormal tapetum and middle layer development. RNA-seq analysis displayed a total of 5606 differentially expressed genes (DEGs) in ny1 compared to wild type (H1) during meiosis, of which 2977 were up-regulated and 2629 were down-regulated. Among the down-regulated genes, 16 important genes associated with tapetal development were detected, including EAT1, CYP703A3, CYP704B2, DPW, PTC1, OsABCG26, OsAGO2, SAW1, OsPKS1, OsPKS2, and OsTKPR1. The mutant of EAT1 was generated by CRISPR/Cas9 that showed abnormal tapetum and pollen wall formation, which was similar to ny1. Moreover, 478 meiosis-related genes displayed down-regulation at same stage, including 9 important meiosis-related genes, such as OsREC8, OsSHOC1, SMC1, SMC6a and DCM1, and their expression levels were validated by qRT-PCR. CONCLUSIONS: Taken together, these results will aid in identifying the key genes associated with pollen fertility, which offered insights into the molecular mechanism underlying pollen development in tetraploid rice.

YAP1 silencing attenuated lung injury/fibrosis but worsened diaphragmatic function by regulating oxidative stress and inflammation response in mice.

Oxidative stress is a crucial mechanism in the pathophysiology of lung injury/fibrosis and diaphragmatic dysfunction. Yes-associated protein 1 (YAP1) is a key oxidative stress response regulator. However, how lung injury/fibrosis and the subsequent YAP1 silencing treatment affect diaphragmatic function remains largely uncharacterized. In this study, mice models of acute lipopolysaccharide (LPS) and paraquat exposure were used to establish acute lung injury and chronic pulmonary fibrosis. AT2 and C2C12 cells were co-cultured under LPS and paraquat challenge. YAP1 was interfered with shRNA given in vivo and verteporfin administration in vitro. Pulmonary histology, contractile properties, and cross-sectional areas (CSAs) of the diaphragm and gastrocnemius were evaluated. Histological and biochemical analyses were performed for targeted biomarker determination. We found that LPS and paraquat caused significant lung injury/fibrosis and significantly reduced the diaphragmatic-specific force and CSAs compared with the control. YAP1 silencing alleviated inflammatory cell infiltration or collagen deposition in the lungs yet worsened the already impaired diaphragmatic function by increasing inflammatory cytokines (IL-6 and TNF-α), mitochondrial reactive oxidative species (ROS) emission, protein degradation (Murf-1, atrogin-1, and calpain), and decreasing antioxidant capabilities (superoxide dismutase 2 and glutathione peroxidase). No significant improvements were observed in diaphragmatic function by transient YAP1 knockdown in the gastrocnemius. In vitro, LPS- or paraquat-caused cytotoxicity in AT2 cells was mostly alleviated by verteporfin in a concentration that was 20-fold higher than that in C2C12 cells (20 and 1 µg/mL, respectively). Finally, 0.5 µg/mL of verteporfin significantly ameliorated hydrogen peroxide-induced proteolytic activity and antioxidant enzyme suppression in C2C12 cells, whereas 2 µg/mL of verteporfin deteriorated the same. Collectively, lung injury/fibrosis adversely affects the diaphragm. YAP1 inhibition alleviates lung injury/fibrosis but worsens diaphragmatic function potentially by enhancing inflammatory cytokines and ROS-mediated protein degradation. This disparity might be attributed to differences in susceptibility to YAP1 inhibition between muscles and the lungs.

Identification and verification of a 4-gene signature predicting the overall survival of cervical cancer.

Cervical cancer (CC) is one of the most common gynecological malignancies, ranking fourth in both incidence and mortality in women worldwide. Early screening and treatment are of great significance in reducing the incidence and mortality of CC. Due to the complex molecular mechanisms of tumor progression, the predictive power of traditional clinical information is limited. In this study, an effective molecular model is established to assess prognosis of patients with CC and guide clinical treatment so as to improve their survival rate. Three high quality datasets (GSE138080, GSE52904, GSE67522) of expression profiling were obtained from gene expression omnibus (GEO) database. Another mRNA expression and clinicopathological data of CC were obtained from The Cancer Genome Atlas (TCGA) dataset. The bioinformatic analyses such as univariate analysis, multivariate Cox proportional-hazards model (Cox) analysis and lasso regression analysis were conducted to select survival-related differentially expressed genes (DEGs) and further establish a prognostic gene signature. Moreover, the performance of prognostic gene signature was evaluated based on Kaplan-Meier curve and receiver operating characteristic (ROC) curve. Gene set enrichment analysis (GSEA) and tumor immunity analysis were carried out to elucidate the molecular mechanisms and immune relevance. A 4-gene signature comprising procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), spondin1 (SPON1), secreted phosphoprotein 1 (SPP1), ribonuclease H2 subunit A (RNASEH2A) was established to predict overall survival (OS) of CC. The ROC curve indicated good performance of the 4-gene signature in predicting OS of CC based on the TCGA dataset. The 4-gene signature classified the patients into high-risk and low-risk groups with distinct OS rates of CC. Univariate analysis and multivariate Cox regression analysis revealed that the 4-gene signature was an independent factor affecting the prognosis of patients with CC. Our study developed a 4-gene signature capable of predicting the OS of CC. The findings may be beneficial to individualized clinical treatment and timely follow-up for patients with CC.

Association between Dietary Patterns and Physical Fitness among Chinese Children and Adolescents in Shaanxi Province.

BACKGROUND: This study aims to investigate the associations between dietary patterns (breakfast, egg, dairy products, and sugared beverage intake frequencies) and physical fitness among Chinese children and adolescents in Shaanxi Province. METHODS: Data were extracted from the Chinese National Survey on Students' Constitution and Health (CNSSCH). The study ultimately included 7305 participants (48.4% male, 51.6% female) aged 6-22 in Shaanxi Province, China. Multiple linear regression was used to examine the association of the frequency of breakfast, egg, dairy product, and sugared beverage intakes with physical fitness. RESULTS: The frequency of breakfast, egg, and dairy product intakes were all independently and positively associated with the level of physical fitness. The frequency of sugared beverage intake was negatively associated with the level of physical fitness. CONCLUSION: Healthier dietary patterns (i.e., higher breakfast, egg, and dairy product intakes and lower sugared beverage intake) were associated with greater physical fitness. Specifically, maintaining a healthy dietary pattern of breakfast, egg, and dairy product intakes can positively affect the strength and endurance performance of children and adolescents. Increased dairy product intake plays a crucial part in boosting the physical fitness total scores of children and adolescents.

Trends in Physical Fitness and Nutritional Status among School-Aged Children and Adolescents during the COVID-19 Pandemic in Shaanxi, China-A Cross-Sectional Study.

BACKGROUND: This study aimed to explore the characteristics of trends in physical fitness and nutritional status among school-aged students during the COVID-19 pandemic, which could help to develop targeted guidelines and policies for students (adolescents) to promote health during lockdowns resulting from public health emergencies. METHODS: The physical fitness and nutritional status were measured from 2019 to 2021; the correlation between years and grade were analyzed. RESULTS: a declining trend was found in aerobic fitness, strength fitness, speed fitness, and BMI during this lockdown. CONCLUSION: The changes in dietary behavior and the decrease in outdoor physical activities may be the reason for the decline. Furthermore, differences in subjects' growth and limited space at home must be considered in the formulation of exercise and nutritional plans. According to the results of our study, exercise for aerobic fitness should receive more attention when students are enduring a pandemic lockdown. In addition, saying "no" to high-calorie foods in the form of snacking and ultra-processed food was the key to improving subjects' nutritional status.

Correlation between Campus-Built Environment and Physical Fitness in College Students in Xi'an-A GIS Approach.

BACKGROUND: This research aimed to investigate the correlation between students' physical fitness and campus-built environment, which could put forward some suggestions for the construction of a campus environment. METHOD: Four colleges in Xi'an were regarded as special "semi-closed" spaces. Combined with ArcGIS and SPSS, the correlation between the built environment of colleges and the students' physical fitness test results in 2019 was analyzed (n = 1498). RESULTS: regarding the men questioned in this research, there was a significant correlation between street connectivity and vital capacity, grip strength, 50 m running, 1000 m running, a significant correlation between land use mix and vital capacity, sit-and-reach, pull-up, grip strength, a significant correlation between green space per capita and vital capacity, grip strength, 50 m running, and a significant correlation between walk score and vital capacity, pull-up, grip strength, and 50 m running. Regarding the women questioned in this research, there was a significant correlation between street connectivity and vital capacity, grip strength, 50 m running, 800 m running, curl-up, a significant correlation between land use mix and vital capacity, sit-and-reach, curl-up, grip strength, 800 m running, a significant correlation between green space per capita and vital capacity, grip strength, curl-up, sit-and-reach, and a significant correlation between walk score and vital capacity, curl-up, grip strength, and 800 m running. CONCLUSION: the built environment on campus can indirectly affect the physical fitness of college students. Increasing the number of intersections and short connections of campus streets, ensuring that the green space of the campus meets the standards, and reasonably arranging the site selection of buildings are conducive to improving the physical fitness of students.

Biomechanical Comparison between Down-the-Line and Cross-Court Topspin Backhand in Competitive Table Tennis.

The aim of this study was to compare the kinematic and kinetic differences of the racket arm when balls were hit cross-court (CC) and down the line (DL) by topspin backhand. Eight elite female players participated and were instructed to hit the ball down the line and cross-court using a topspin backhand. Kinematic and kinetic data were collected. The results show that at the impact, participants had a greater wrist flexion angle in DL than CC (p = 0.017). The angular velocity of shoulder flexion (p = 0.038), shoulder abduction (p = 0.006) and thorax-pelvis internal rotation (p = 0.017) was faster when participants impacted the ball DL than CC. As for the joint kinetics, the shoulder external rotation moment was greater in CC than DL (p = 0.043). For a high-quality DL technique, it is important to exhibit a greater wrist flexion and have faster adduction and flexion in the shoulder, as well as faster internal rotation in thorax-pelvis, while having a smaller wrist flexion and more external rotation power in the shoulder are important to perform a CC at the impact. If these key and different factors of hitting CC and DL are ignored, it may lead to failure to complete a high-quality shot.

Responses of lipid metabolism and lipidomics in the hepatopancreas of Pacific white shrimp Litopenaeus vannamei to microcystin-LR exposure.

Microcystin-LR (MC-LR) is a toxic substance that threatens the health of aquatic animals. Hepatopancreas is the target organ of MC-LR toxicity. In this study, we investigated the effects of MC-LR on hepatopancreas lipid metabolism and lipidomic responses in Litopenaeus vannamei. After MC-LR exposure for 72 h, the hepatopancreas showed obvious tissue damage, and the activities of several lipase isoenzymes were decreased. Furthermore, the relative gene expression levels of lipolysis (CPT1, AMPKα), lipogenesis (SREBP, FAS, ACC, 6PGD), and long-chain fatty acid ß-oxidation (ACDL, ACDVL, ACBP) were increased. MC-LR exposure also affected lipidomics homeostasis. Specifically, the levels of glycerophospholipids (phosphatidylcholine, phosphatidic acid, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, lyso-phosphatidylglycerol), sphingolipids (sphingomyelin and ceramides) and cholesteryl ester were increased, and those of phosphatidylinositol and triglyceride were decreased. The significantly altered lipid molecules were mainly associated with the pathways of lipid and fatty acid metabolism and autophagy. These results reveal that MC-LR exposure influences lipid metabolism and lipidomic homeostasis in the shrimp hepatopancreas.

Characterization of the lncRNA-miRNA-mRNA regulatory network to reveal potential functional competing endogenous RNAs in traumatic brain injury.

Traumatic brain injury (TBI) is one of the most common acute central nervous system injury diseases. Given the medical and socio-economic burdens of TBI patients, the pathogenesis in TBI and the latent intervention targets needed to be further illuminated. Long non-coding RNAs (lncRNAs) had been revealed to play a vital role in the regulation of pathogenesis after TBI. However, the mutual communication and adjustment of lncRNA associated competing for endogenous RNA (ceRNA) networks in TBI have not been explored to date. In this study, we systematically sequenced the whole transcriptome of lncRNAs, miRNAs, and mRNAs between sham and TBI groups and a total of 939 differentially expressed (DE) lncRNAs, 46 DE miRNAs, and 1,951 DE mRNAs were obtained. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein interaction relationship analyses were conducted for DE mRNAs to identify hub DE genes in TBI. Based on the criteria of bioinformatics prediction, the lncRNA associated ceRNA network covering 201 lncRNAs, 22 miRNAs, and 79 mRNAs was constructed. This study provides a novel perspective on the molecular mechanism of lncRNA in TBI and identifies certain lncRNAs as potential therapeutic targets against TBI.

Transcriptomic analysis reveals innate immune mechanisms of an underlying parasite-resistant grouper hybrid (Epinephelus fuscogutatus × Epinephelus lanceolatus).

Hybridization is an artificial breeding strategy for generating potentially desirable offspring. Recently, a novel Hulong grouper hybrid (Epinephelus fuscogutatus × Epinephelus lanceolatus) yielded significant growth superiority over its parent. Improved innate immunity is considered as another desirable feature during hybridization. However, whether this Hulong grouper achieved disease resistance has not yet been revealed. In this study, we first examine the infection intensity of C. irritans in the Hulong grouper, and found that the Hulong grouper is less susceptible to C. irritans primary infection. A higher immobilization titer was found in the infected Hulong grouper at Day 2 when compared with the control grouper. Furthermore, severe hyperplasia was observed in the orange-spotted grouper, but not in the Hulong grouper's skin epidermis. To further understand the innate immune mechanism against C. irritans, we conducted a comparative transcriptome analysis of the Hulong grouper during the infection. There are 6464 differentially expressed genes (DEGs) identified in the skin between the control and infected Hulong grouper. This indicates that the innate immune components, such as the complement system, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Interleukin 17 (IL-17) signaling pathway, and Toll-like receptor (TLR) signaling pathway were up-regulated during the infection. These results show that the C. irritans infection can induce a remarkable inflammatory response in the Hulong grouper. Moreover, a total of 75 pairs of orthologs with the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions ＞1, considered rapidly evolving genes (REGs), was identified between the Hulong and orange-spotted grouper. More critically, most REGs were enriched in the immune system, suggesting that rapid evolution of the immune system might occur in the Hulong grouper. These results provide a more comprehensive understanding of the innate immunity mechanism of the hybrid Hulong grouper.

Study on the characterization of grouper (Epinephelus coioides) immunoglobulin T and its positive cells.

Immunoglobulins (Igs) play a vital role in the adaptive immunity of gnathostomes. IgT, a particular Ig class in teleost fishes, receives much attention concerning the mucosal immunity. While, the characteristic and function of Epinephelus coioides IgT is still unknown. In our study, a polyclonal antibody was first prepared with grouper IgT heavy chain recombinant protein. IgT was revealed to be polymeric in serum and mucus. In normal groupers, IgT had high expression level in head kidney and spleen, while little amount in gills, thymus, gut and liver. The number of IgT-positive cells in different tissues was in line with their IgT expression. Furthermore, IgT could coat fractional bacteria in the mucus. In conclusion, this research revealed the protein characteristic, basal expression and bacterial coverage of grouper IgT. This is the first study to identify the characteristic of grouper IgT and demonstrate the capacity of coating microbes.