Characteristics and risks of microplastic contamination in aquaculture ponds near the Yangtze Estuary, China.

Microplastic pollution has been frequently reported in natural water environments, but studies on the occurrence and characteristics of microplastic in aquaculture environments especially in pond production system are relatively scarce. Herein, we investigated the abundance and characteristics of microplastic pollution in aquaculture ponds that farm different species (fish, prawn and crab) near the Yangtze Estuary, China. The average abundance of microplastic in pond water and sediment was 36.25 ± 6.79 items/L and 271.65 ± 164.83 items/kg, respectively. Compared to fish ponds (208.43 ± 57.82 items/kg), microplastic abundance was significantly higher in sediment of crab and prawn ponds (312.02 ± 38.76 and 248.87 ± 36.51 items/kg respectively). Across all ponds, transparent, white and black microplastic were the common colors. Fiber was the most common type, accounting for 40.9% and 58.6% in pond water and sediment, respectively. The size of microplastic was mainly distributed between 300 and 1000 µm. For microplastic polymer composition, polyethylene (PE) was predominant in pond water, accounting for 55%, followed by polyamide with 15%. The predominant polymer in sediment was PE with 34%, followed by polypropylene with 18%. As for the ecological risk assessment of microplastic, the pollution load index was 7.6 (risk level I) and 8.9 (risk level I) for pond water and sediment, respectively. The polymer hazard index was 85.3 (risk level II) and 12.1 (risk level II) for pond water and sediment, respectively. Taken together, the pollution risk index was rated as high and very high for pond sediment and water, respectively. These results provide a basis for the comprehensive evaluation and developing practical approaches to deal with microplastic in aquaculture pond, which is of great significance to the healthy development of pond aquaculture.

Genome-wide identification and expression analysis of C-type lectins in discus fish (Symphysodon aequifasciatus) during parental care.

Discus fish (Symphysodon aequifasciatus) exhibit a unique parental care behavior: adult discus produces secretion through their skin, on which the larvae live after birth. The immune components in the skin mucus of parental discus would change during different parental care. C-type lectins (CTLs) could identify and eliminate pathogenic microorganisms and play important roles in innate immunity. Studies on CTLs of discus fish especially during parental care, however, are scarce. Here, we identified 186 CTL genes that distributed in 27 linkage groups based on discus genome. Phylogenetic analysis showed that S. aequifasciatus CTL (SaCTL) members were grouped into 14 subfamilies. A total of 80 gene replication events occurred, of which 15 pairs were subjected to segmental duplication and 65 pairs underwent tandem duplication. Ka/Ks ranged from 0.11 (SaCTL25/SaCTL158) to 0.68 (SaCTL36/SaCTL69), all undergoing purifying selection. RNA-seq analysis revealed that SaCTL members, including duplicated genes, in the skin of parental discus show distinct expression patterns in different care stages and between male and female parents. The SaCTL11 was differentially expressed in most care stages and reached the maximum after eggs spawned, but the expression of its paired SaCTL14 was low in each stage. The SaCTL39 increased first and then decreased, reaching a peak in eggs spawned, while paired SaCTL48 first decreased and then increased, reaching a peak in hatched eggs. The SaCTL50 was differentially expressed only in female fish during care, but not in male fish. These results provide new insights into the evolution and potential functional differentiation of CTLs in discus fish during parental care.

Reshaping the plastisphere upon deposition: Promote N2O production through affecting sediment microbial communities in aquaculture pond.

Microplastics (MPs) could provide vector for microorganisms to form biofilm (plastisphere), but the shaping process of MPs biofilm and its effects on the structure and function of sedimentary microbial communities especially in aquaculture environments are not reported. For this, we incubated MPs biofilm in situ in an aquaculture pond and established a sediment microcosm with plastisphere. We found that the formation of MPs biofilm in surface water was basically stable after 30 d incubation, but the biofilm communities were reshaped after deposition for another 30 d, because they were more similar to plastisphere communities incubated directly within sediment but not surface water. Moreover, microbial communities of MPs-contaminated sediment were altered, which was mainly driven by the biofilm communities present on MPs, because they but not sediment communities in proximity to MPs had a more pronounced separation from the control sediment communities. In the presence of MPs, increased sediment nitrification, denitrification and N2O production rates were observed. The K00371 (NO2-⇋NO3-) pathway and elevated abundance of nxrB and narH genes were screened by metagenomic analysis. Based on structural equation model, two key bacteria (Alphaproteobacteria bacterium and Rhodobacteraceae bacterium) associated with N2O production were further identified. Overall, the settling of MPs could reshape the original biofilm and promote N2O production by selectively elevating sedimental microorganisms and functional genes in aquaculture pond.

Astaxanthin mitigates oxidative stress caused by microplastics at the expense of reduced skin pigmentation in discus fish.

Microplastics (MPs) exposure generally triggers oxidative stress in fish species and vertebrate pigmentation is commonly influenced by oxidative stress, but MPs-induced oxidative stress on fish pigmentation and body color phenotype has not been reported. The aim of this study is to determine whether astaxanthin could mitigate the oxidative stress caused by MPs but at the expense of reduced skin pigmentation in fish. Here, we induced oxidative stress in discus fish (red skin color) by 40 or 400 items/L MPs under both astaxanthin (ASX) deprivation and supplementation. We found that lightness (L*) and redness (a*) values of fish skin were significantly inhibited by MPs under ASX deprivation. Moreover, MPs exposure significantly reduced ASX deposition in fish skin. The total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity in fish liver and skin were both significantly increased with the increase of MPs concentration, but content of glutathione (GSH) in fish skin showed a significant decrease. For ASX supplementation, the L*, a* values and ASX deposition were significantly improved by ASX, including the skin of MPs-exposed fish. The T-AOC and SOD levels changed non-significantly in fish liver and skin under the interaction of MPs and ASX, but ASX significantly reduced GSH content in fish liver. Biomarker response index indicated that ASX could improve the moderately altered antioxidant defense status of MPs-exposed fish. This study suggests that the oxidative stress caused by MPs was mitigated by ASX but at expense of reduced fish skin pigmentation.

Bispecific GPC3/PD­1 CAR­T cells for the treatment of HCC.

Constantly stimulated by the tumor microenvironment (TME), programmed death 1 (PD­1) is elevated, and it interacts with PD ligand 1 (PD­L1), rendering chimeric antigen receptor (CAR)­T cells dysfunctional. Hence, CAR­T cells immune to PD­1­induced immunosuppression were constructed to improve the function of CAR­T cells in hepatocellular carcinoma (HCC). Double­target CAR­T cells, targeting glypican­3 (GPC3) [a tumour-associated antigen (TAA)] and hindering PD­1­PD­L1 binding, were established. The expression of GPC3, PD­L1, and inhibitory receptors was measured using flow cytometry. The cytotoxicity, cytokine release, and differentiation level of CAR­T cells were determined using lactate dehydrogenase release assay, enzyme­linked immunosorbent assay, and flow cytometry, respectively. HCC cells were targeted and eliminated by double­target CAR­T cells. These double­target CAR­T cells limit PD­1­PD­L1 binding and sustain cytotoxicity to PD­L1+ HCC cells. The relatively low IR expression and differentiation level in double­target CAR­T cells in tumour tissues induced tumour­suppression and extended survival in PD­L1+ HCC TX models, as opposed to their single­target counterparts. The results of the present study suggested that the newly constructed double­target CAR­T cells exhibit stronger tumour­suppressing effects in HCC than their single­target counterparts, which are common, suggesting the potential of strengthening CAR­T cell activity in HCC treatment.

Genome-wide identification and skin expression of immunoglobulin superfamily in discus fish (Symphysodon aequifasciatus) reveal common genes associated with vertebrate lactation.

Discus Symphysodon spp. employs an unusual parental care behavior where fry feed on parental skin mucus after hatching. Studies on discus immunoglobulin superfamily (IgSF) especially during parental care are scarce. Here, a total of 518 IgSF members were identified based on discus genome and clustered into 12 groups, unevenly distributing on 30 linkage groups. A total of 92 pairs of tandem duplication and 40 pairs of segmental duplication that underwent purifying selection were identified. IgSF genes expressed differentially in discus skin during different care stages and between male and female parents. Specifically, the transcription of btn1a1, similar with mammalian lactation, increased after spawning, reached a peak when fry started biting on parents' skin mucus, and then decreased. The expression of btn2a1 and other immune members, e.g., nect4, fcl5 and cd22, were up-regulated when fry stopped biting on mucus. These results suggest the expression differentiation of IgSF genes in skin of discus fish during parental care.

Microplastics inhibit biofloc formation and alter microbial community composition and nitrogen transformation function in aquaculture.

Biofloc technology, extensively used in intensive aquaculture systems, can prompt the formation of microbial aggregates. Microplastics (MPs) are detected abundantly in aquaculture waters. This study explored the effects of MPs on biofloc formation, microbial community composition and nitrogen transformation function in simulated biofloc aquaculture production systems. The formation process and settling performance of bioflocs were examined. High-throughput sequencing of 16S and 18S rRNA genes was used to investigate the microbial community compositions of bioflocs. Nitrogen dynamics were monitored and further explained from functional genes and microorganisms related to nitrogen transformation by metagenome sequencing. We found that the aggregates consisting of bioflocs and MPs were formed and the systems with MPs had relatively weak settling performance. No significant differences in bacterial diversity (p > 0.05) but significant differences in eukaryotic diversity (p < 0.05) were found between systems without and with MPs. Significant separations in the microbial communities of prokaryotes (p = 0.01) and eukaryotes (p = 0.01) between systems without and with MPs were observed. The peak concentration of nitrite nitrogen (NO2--N) in systems with MPs was lower than that in systems without MPs (pControl/MPs Low = 0.02 and pControl/MPs High = 0.03), probably due to the low abundance of hao and affiliated Alphaproteobacteria_bacterium_HGW-Alphaproteobacteria-1 and Alphaproteobacteria_bacterium, but the high abundance of nxrA and affiliated Alphaproteobacteria_bacterium_SYSU_XM001 and Hydrogenophaga_pseudoflava that related to nitrification. The low concentration of NO2--N in systems with MPs suggested that the presence of MPs might inhibit ammonia oxidation but promote nitrite oxidation by altering the microbial community structure and function. These results indicated that aggregates consisting of bioflocs and MPs could be formed in aquaculture water, and thus, inhibiting their settlement and altering nitrogen transformation function by affecting the microbial community composition.

Occurrence and Characteristics of Microplastics Contamination in Different Intensive Aquaculture Systems Nearby the Yangtze Estuary, China.

Microplastics (MPs) pollution has been extensively investigated in natural fishery waters, but studies on intensive aquaculture systems are scarce. Here, the occurrence and properties of MPs were investigated and compared between four different aquaculture systems nearby the Yangtze Estuary. The average MPs concentration was in order of recirculating aquaculture system (RAS, 1.67 particles/L) < aquarium (2.47 particles/L) < cement pond (10.09 particles/L) < earthen pond (13.81 particles/L). Compared to fragment MPs, fiber was the more abundant shape in aquarium (85.88%), RAS (77.61%) and earthen pond (68.13%). A total of six colors were found in four systems. The black MPs accounted for 56.86% and 47.45% in aquarium and RAS system, respectively. The high proportion of blue MPs was found in cement pond (37.65%) and earthen pond (40%). The most MPs sizes observed in the four systems were 43% of 50-300 µm MPs in aquarium; 44% and 30.19% of 300-1000 µm MPs in RAS and cement pond, respectively; and 30.19% of 3000-5000 µm MPs in earthen pond. For polymers, polypropylene occupied 47.83% in aquarium and RAS, 41.46% in cement pond and 27.79% in earthen pond. Proportion of rayon was highest in RAS (60.87%) and 34.04% of nylon was found in earthen pond. These results could provide scientific reference for further traceability and removal of MPs in different aquaculture systems.

Microplastics drive nitrification by enriching functional microorganisms in aquaculture pond waters.

The plastisphere refers to biofilm formation on the microplastic (MP) surface, but its subsequent functions, especially driving the nitrogen biogeochemical cycle, are rarely studied. Here, MPs were incubated in the pelagic water and benthic water-sediment interface of an aquaculture pond, and the two corresponding microcosms amended with incubated plastisphere were simulated. The results showed decreased ammonia concentrations and increased nitrification rates in microcosms with either pelagic or benthic plastispheres. To uncover the possible mechanisms, the community structure and function of the plastisphere were investigated. As clarified by 16S rRNA, the community diversity of the pelagic plastisphere was significantly higher than that of the corresponding hydrosphere. Plastisphere communities, especially those incubated in pelagic water, were separated from the hydrosphere. Moreover, the abundance of Proteobacteria increased while the abundance of Cyanobacteria decreased in both plastispheres. Metagenome further revealed that the abundance of amoA and annotated Nitrososphaeraceae_archaeon and hao and affiliated Nitrosomonas_europaea, which contributed to ammonia oxidation to nitrite, was higher in the benthic plastisphere. Comparing the pelagic plastisphere with the corresponding hydrosphere, however, the abundance of nxrA and annotated Nitrobacter hamburgensis and nxrB and the affiliated Nitrospira moscoviensis, which are involved in nitrite oxidation, was more abundant in the plastisphere. These findings suggest that the plastisphere might selectively enrich functional microorganisms and genes in a habitat-dependent manner to promote nitrification in aquaculture ponds.

Anti-aging effect of ß-carotene through regulating the KAT7-P15 signaling axis, inflammation and oxidative stress process.

BACKGROUND: Research on aging is growing as the elderly make up a greater share of the population, focusing on reversing and inhibiting the aging process. The exhaustion and senescence of stem cells are the fundamental drivers behind aging. ß-Carotene has been depicted to have many biological functions, and we speculate that it may have an anti-aging effect. METHODS: Firstly, the anti-aging property of ß-carotene was investigated in vitro using mesenchymal stem cells (MSCs) induced by H2O2. The anti-aging effect was characterized using Western-bloting, confocal laser scanning microscopy, indirect immunofluorescence, and immunohistochemistry. The anti-aging property was also tested in vivo using aged mice. RESULTS: The in vitro experiment revealed that ß-carotene could relieve the aging of MSCs, as evidenced by a series of aging marker molecules such as p16 and p21. ß-Carotene appeared to inhibit aging by regulating the KAT7-P15 signaling axis. The in vivo experiment revealed that ß-carotene treatment has significantly down-regulated the aging level of tissues and organs. CONCLUSIONS: In this work, we explored the anti-aging effect of ß-carotene in vivo and in vitro. The experimental results indicate that ß-carotene may be an important potential anti-aging molecule, which can be used as a drug or in functional food to treat aging in the future.

Lenvatinib with or without Concurrent Drug-Eluting Beads Transarterial Chemoembolization in Patients with Unresectable, Advanced Hepatocellular Carcinoma: A Real-World, Multicenter, Retrospective Study.

Introduction: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma (HCC). We aimed to compare the clinical outcomes of lenvatinib plus drug-eluting beads transarterial chemoembolization (DEB-TACE) versus lenvatinib alone in real-world practice. Methods: This retrospective analysis included 142 consecutive patients who received lenvatinib plus DEB-TACE and 69 patients who received lenvatinib alone as first-line treatment from 15 Chinese academic centers from November 2018 to November 2019. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) were evaluated by modified Response Evaluation Criteria in Solid Tumors criteria, and safety profiles were compared between the two groups. Results: The median OS and PFS were significantly longer in the combined therapy group than in the monotherapy group in whole cohort (median OS, 15.9 vs. 8.6 months, p = 0.0022; median PFS, 8.6 vs. 4.4 months, p < 0.001) and after propensity score matching analysis (median OS, 13.8 vs. 7.8 months, p = 0.03; median PFS, 7.8 vs. 4.5 months, p = 0.009). Moreover, the treatment option was an independent prognostic factor for OS and PFS with adjustment based upon baseline characteristics (adjusted hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.36-0.78, p = 0.001, and adjusted HR: 0.42, 95% CI: 0.30-0.60, p < 0.001, respectively) and propensity score (adjusted HR: 0.52, 95% CI: 0.36-0.76, p = 0.001, and adjusted HR: 0.46, 95% CI: 0.33-0.64, p < 0.001, respectively). Moreover, a greater ORR was observed in the combined group (ORR: 46.48% vs. 13.05%, p < 0.001). Furthermore, the most common adverse events (AEs) were elevated aspartate aminotransferase (54.9%) and fatigue (46.4%) in the lenvatinib plus DEB-TACE group and lenvatinib group, respectively. Most AEs were mild-to-moderate and manageable. Conclusions: With well-tolerated safety, lenvatinib plus DEB-TACE was more effective than lenvatinib monotherapy in improving OS, PFS, and ORR. Thus, it may be a promising treatment for advanced HCC. Future prospective studies confirming these findings are warranted.

Gut microbiota communities of reciprocal hybrids from koi (Cyprinus carpio) and goldfish (Carassius auratus) are more similar to koi than goldfish.

AIMS: To investigate the gut microbiota communities of reciprocal hybrids and inbred lines of koi (Cyprinus carpio) and goldfish (Carassius auratus), as well as the genetic effect of intestinal microbiota between hybrids and parents. METHODS AND RESULTS: The reciprocal hybrids and inbred lines derived from the parents, koi and goldfish, were established. Then, the bacterial 16S rRNA gene of intestinal contents was sequenced using Illumina Miseq PE300. Alpha diversity in the two types of hybrids was lower than inbred lines of koi or goldfish and was highest in goldfish, followed by koi. For beta diversity, microbial samples presented clear clusters and the two types of hybrids were more similar to koi than goldfish, indicating the gut microbiota of the reciprocal hybrids was more affected by koi. The dominant phyla were Proteobacteria, Actinobacteria and Firmicutes in koi, and Proteobacteria, Fusobacteria and Actinobacteria in goldfish, and Proteobacteria, Fusobacteria and Firmicutes in the reciprocal hybrids. In the case of Proteobacteria, the dominant classes were Alphaproteobacteria and Gammaproteobacteria in four fish. The dominant genera were norank_f_Rhizobiales_Incertae_Sedis and Plesiomonas in koi, Cetobacterium in goldfish, and Cetobacterium and ZOR0006 in the reciprocal hybrids. PICRUSt1 predictive function analysis showed that the reciprocal hybrids had lower abundance in the most functional categories than koi and goldfish. CONCLUSIONS: The gut microbiota of reciprocal hybrids was more affected by koi. Two types of hybrids possessed the same dominated phyla and were different from the inbred lines of koi and goldfish. SIGNIFICANCE AND IMPACT OF THE STUDY: It enhanced our understanding of gut microbiota of hybrid lines of goldfish and koi and provided a new perspective for the selective breeding of gut microbiota traits.

Different isoforms of growth hormone (20 kD-GH and 22 kD-GH) shows different biological activities in mesenchymal stem cell (MSC).

There are two main types of growth hormone (GH) in the circulatory system. One is 22 kD-GH, which is the predominant isoform in the circulating system, 90% GH is present as a 22 kD protein, and 10% of GH is present as a 20 kD protein. Amino acid sequences are identical between 20 kD-GH and 22 kD-GH protein, except that 20 kD-GH lacks 15 amino acid residues 32 to 46. Studies have shown that GH has many important biological effects on mesenchymal stem cells (MSCs). However, so far, the cellular characteristics of the two types of GH have not been studied in BM-MSCs. Furthermore, the biological activity of 20 kD-GH has not been explored in BM-MSCs. For this, in the current work, BM-MSCs were used as in vitro cell model. We have carried out the current research using a series of experimental techniques (such as Western-blot and indirect immunofluorescence). Firstly, we explored the cell behavior of two types of GH in the Bm-MSC model and found that they showed different biological characteristics; Secondly, we investigated the biological characteristics of 20 kD-GH and 22 kD-GH, and results showed that 22 kD-GH and 20 kD-GH exhibited different signaling profiles; Thirdly, we found that the 20 kD-GH and 22 kD-GH Gexhibited different regulatory effects on the osteogenic differentiation of BM-MSCs. The current research lays a solid foundation for further studies on the regulatory effects of GH on MSCs.

22-kD growth hormone-induced nuclear GHR/STAT5/CyclinD1 signaling pathway plays an important role in promoting mesenchymal stem cell proliferation.

Growth hormone (GH) exhibited the important biological activities in the mesenchymal stem cell (MSCs). However, the cellular behavior and properties of GH/GHR in MSCs remain unclear. A series of experiments (such as confocal laser scanning microscope [CLSM] and Western-blot) were performed to systematically investigate the cellular behavior of GH/GHR in MSCs, and the results showed that GH/GHR not only internalized into the cytoplasm, but also transported into the cell nuclei of MSCs. Furthermore, we studied the molecular mechanism by which GH/GHR internalized into cell, and the results indicated that clathrin plays more important role in the process of GHR internalization. More importantly, it can be found that nuclear-targeted GHR has the important biological functions in MSCs, which could promote MSCs proliferation. We further revealed the molecular mechanism by which nuclear-localized GHR regulates MSCs proliferation, and found that nuclear-targeted GHR enhanced the phosphorylation of STAT5, and the activated STAT5 initiates the transcription of CyclinD1, after which, the complex of CyclinD1 and CDK4 further phosphorylates Rb, and the activated Rb releases E2F1, the released E2F1 ultimately realizes the biological function of GH promoting cell proliferation. In short, in the current study，we used MSCs as a model to study the cellular behavior and properties of GH/GHR, and found that GH/GHR can internalize into cell cytoplasm and transport into the cell nuclei. Further work showed that nuclear GHR could drive cell proliferation via GHR/STAT5/CyclinD1 signaling pathway. The current research has laid an important foundation for further study on the regulatory effect of GH on MSCs.

Micro/nano-plastics cause neurobehavioral toxicity in discus fish (Symphysodon aequifasciatus): Insight from brain-gut-microbiota axis.

Numerous studies have investigated neurobehavioral toxicity of microplastics, but no studies have illustrated mechanism via brain-gut axis. Here, juvenile discus fish (Symphysodon aequifasciatus) were exposed for 96 h to microfibers (900 µm, fiber, MFs) or nanoplastics (~88 nm, bead, NPs) with three concentrations (0, 20 and 200 µg/L). Accumulation in fish gut was independent of plastics type and concentration. MFs reduced growth performance while NPs weakened swimming and predatory performance of post-exposed discus. For brain cholinesterase activity, acetylcholinesterase was activated by NPs while NPs/MFs exposure inhibited butyrylcholinesterase. Concentrations of neurotransmitters (acetylcholine, dopamine and γ-aminobutyric acid) increased in brain but decreased in gut after NPs or MFs exposure. For gut microbiota, increased richness under MFs exposure was observed. At phylum level, Proteobacteria proportion was lower in NPs but higher in MFs. Abundance of Clostridia and Fusobacteriia (Bacillus), potentially secreting neurotransmitters, increased in NPs but decreased in MFs. Brain transcriptomics revealed seven upregulated and four downregulated genes concerning neural-activities. Pathways of neuroactive ligand-receptor interaction and serotonergic synapse were enriched in both MFs and NPs, but dopaminergic synapse pathway was enriched only in MFs. These results established a novel mechanism by which microplastics might cause behavioral toxicities via brain-gut-microbiota axis.

Microplastics: A tissue-specific threat to microbial community and biomarkers of discus fish (Symphysodon aequifasciatus).

As detriments in aquatic environments, microplastics (MPs) have been commonly studied on organisms, but tissue-scale effects of MPs were poorly understood. Discus fish (Symphysodon aequifasciatus), herewith, were exposed to polystyrene MPs (0/20/200 µg/L) for 28 d. We found that MPs significantly inhibited growth performance. MPs were observed in skin, gill and intestine after 14/28-d exposure. MPs bioaccumulation was independent of exposure time, but increased with MPs concentrations. Microbial community diversity of fish gill, but not skin and intestine, in MPs treatments was significantly increased. Bacterial community of MP-treated skin and gill were obviously separated from control. Skin dominant phyla changed from Actinobacteriota to Proteobacteria and Firmicutes. Proteobacteria gradually occupied dominance in gill after exposure. Furthermore, MPs-induced skin oxidative stress was demonstrated by the activation of superoxide dismutase and catalase. Skin malondialdehyde also increased and showed significant correlations with four bacterial phyla, e.g., Proteobacteria. Gill Na+/K+-ATPase activity decreased, strongly correlating to microbial community changes caused by MPs. Intestinal digestive enzymes activity (pepsin, lipase and α-amylase) reduced, revealing correlation with bacterial community especially Fibrobacterota. These results suggest a tissue-specific effect of MPs to microbial community and biomarkers in aquatic organism.

Uridine alleviates carbon tetrachloride-induced liver fibrosis by regulating the activity of liver-related cells.

At present, liver fibrosis is a major challenge of global health. When hepatocyte regeneration cannot compensate for hepatocyte death, it will develop into liver fibrosis in chronic liver disease. Initially, collagen produced by myofibroblasts plays a role in maintaining liver integrity, but excessive collagen accumulation can inhibit the residual liver function, leading to liver failure. At present, many scientists are actively looking for drugs to alleviate liver fibrosis. In the current study, we investigated the potential role of uridine in the treatment of liver fibrosis (uridine is a plant/animal-derived pyrimidine nucleoside, therefore uridine can also be ingested and absorbed by the body, accompanied by the process of food intake). For this, we systematically studied the effect of uridine on CCl4-induced liver fibrosis in vitro and in vivo through a series of technologies, such as Western blot, laser confocal scanning microscope, ELISA and immunohistochemistry. The experimental results showed that uridine can effectively reduce the accumulation of collagen in liver. Furthermore, uridine can improve the activity of liver cells and alleviate CCl4-induced liver injury. Furthermore, uridine can significantly alleviate the risk factors caused by hepatic stellate cell activation, uridine treatment significantly down-regulated the expression of α-SMA, collagen type-I and fibronectin. In conclusion, the current research shows that uridine can alleviate CCl4-induced liver fibrosis, suggesting that uridine can be used as a potential drug to alleviate liver fibrosis.

Distinct skin morphological and transcriptomic profiles between wild and albino Oscar Astronotus ocellatus.

Oscar Astronotus ocellatus is an important ornamental fish, including albino and wild varieties. Albino individuals attract aquarium hobbyists due to their unique body color, but studies on the species' albinism mechanism are currently scarce. Here, we investigated the morphological and transcriptomic profiles of the skin of albino and wild Oscar. The results showed that the albino type had fewer oval-shaped melanophores and immature melanosomes but that the wild type contained more stellate-shaped melanophores and mature melanosomes. Albino Oscar had a degenerative pigment layer without obvious melanin deposition and content, while the wild type contained more concentrated melanin within the pigment layer. A total of 272,392 unigenes were detected, 109 of which were identified as differentially expressed genes (DEGs) between albino and wild Oscar. Pathways of DEGs, including those involved in complement and coagulation cascades, novobiocin biosynthesis, Th1 and Th2 cell differentiation, and tropane, piperidine and pyridine alkaloid biosynthesis, were significantly enriched. DEGs, including upregulated Sfrp5 and Tat, and downregulated Wnt-10a, Ppp3c, Notch1 and Trim27 involved in the Wnt signaling pathway, Notch signaling pathway, tyrosine metabolism, MAPK signaling pathway and melanogenesis, might be associated with the albinism of Oscar. This study characterized the difference in melanophore morphology between wild and albino Oscar and identified some albinism-related candidate genes and signaling pathways, helping to understand the genetic mechanism of fish albinism.

Tenacissoside H Induces Autophagy and Radiosensitivity of Hepatocellular Carcinoma Cells by PI3K/Akt/mTOR Signaling Pathway.

Tenacissoside H (TEH), which has anti-inflammatory and anti-tumor effects, is a major active ingredient extracted from the stem of Marsdenia tenacissima. However, the effect of TEH on hepatocellular carcinoma (HCC) as well as the underlying mechanisms are still indistinct. Presently, HCC cells (including Huh-7 and HepG2) were dealt with different concentrations of TEH. The proliferation and apoptosis of HCC cells were determined via Cell Counting Kit-8 (CCK8) assay and flow cytometry. In addition, Western blot was conducted to evaluate the expressions of autophagy-and apoptosis-related proteins. Tissue immunofluorescence was carried out to evaluate LC3B expression in the tumor tissues. The data showed that TEH suppressed the growth of HCC cells in a concentration-dependent manner. Besides, TEH enhanced radiosensitivity and promoted the apoptosis of HCC cells. Moreover, the mRNA and protein levels of autophagy-related genes (LC3-II/LC2-I, ATG5, Beclin-1) were significantly promoted by TEH. Mechanistically, TEH attenuated the activation of PI3K/Akt/mTOR signaling pathway. However, inhibition of PI3 K pathway abolished the anti-tumor effects of TEH in HCC cells. Collectively, this study suggested that TEH increases the radiosensitivity of HCC cells via inducing autophagy and apoptosis through downregulating PI3K/Akt/mTOR signaling pathway.

Brain transcriptome analysis reveals genes involved in parental care behaviour in discus fish (Symphysodon haraldi).

Parental care is common in mammals and allows offspring to obtain milk, a substance rich in a range of nutritional and non-nutritional factors crucial to the survival of newborns. The discus fish Symphysodon spp., an Amazonian cichlid, shows an unusual behaviour: Free-swimming fry bite on their parents' skin mucus for growth and development during the first month after hatching. This is similar to the breastfeeding behaviour of mammals, but little is known about the regulatory mechanism by which discus secrete 'milk' and the related genes involved in parental care. Here, transcriptome sequencing was performed by using the brain tissues of female discus fish in parental and non-parental care. The results showed that a total of 86 differentially expressed genes (71 up-regulated genes and 15 down-regulated genes) were obtained by comparing parental with non-parental discus fish, including up-regulated LAPTM, FOXB, SOX1S, OTX2 and NR1F2, and down-regulated EDNRB, PRKCD, H1-5 and HBE. Through functional enrichment analysis, a total of 20 pathways were identified, e.g., estrogen signaling pathway, inflammatory mediator regulation of TRP channels, vascular smooth muscle contraction, GnRH signaling pathway, neurotrophin signaling pathway, NOD-like receptor signaling pathway, Jak-STAT signaling pathway, Fc gamma R-mediated phagocytosis, serotonergic synapse, autophagy-animal and cytokine-cytokine receptor interaction. These pathways and related genes might play important roles in the regulation of discus 'milk' secretion.