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Proteinuria, an indication of kidney disease, is caused by the malfunction of podocytes, which play a key role in maintaining glomerular filtration. Angiopoietin-like 3 (ANGPTL3) has been documented to have a cell-autonomous involvement in podocytes, and deletion of Angptl3 in podocytes reduced proteinuria in adriamycin-induced nephropathy. Here, we developed a monoclonal antibody (mAb) against ANGPTL3 to investigate its effects on podocyte injury in an ADR nephropathy mouse model and puromycin (PAN) induced podocyte damage in vitro. The mAb against the human ANGPTL3-FLD sequence (5E5F6) inhibited the binding of ANGPTL3-FLD to integrin β3. Treatment with the 5E5F6 mAb in ADR nephropathy mice mitigated proteinuria and led to a significant decline in podocyte apoptosis, reactive oxygen species (ROS) generation and mitochondrial fragmentation. In PAN-induced podocyte damage in vitro, the 5E5F6 mAb blocked the ANPGPLT3-mediated activation of integrin αvβ3 and Rac1, which regulated the mitochondrial homeostasis. Altogether, anti-ANGPLT3-FLD mAb attenuates proteinuria and podocyte lesions in ADR mice models, as well as PAN-induced podocyte damage, in part through regulating mitochondrial functions. Our study provides a therapeutic approach for targeting ANGPTL3 in proteinuric kidney disease.

Grass carp (Ctenopharyngodon idella) is the most widely produced freshwater aquaculture product worldwide. However, its susceptibility to microbial infections during its cultivation restricts its development. The complement system plays an important role in immune defence. To investigate the transcription of the complement factor C5 and production of its cleavage product C5a in grass carp infected with grass carp reovirus (GCRV), the full-length C5 gene sequence was cloned and sequenced using the rapid amplification of cDNA ends method, and C5 transcription and C5a production in different grass carp tissues at different GCRV infection stages were determined by RT-qPCR and western blotting, respectively. Our results showed that the full-length cDNA of the C5 gene was 5365-bp long, encoding 1687 amino acids. Signal peptide prediction showed that C5 had a secretory signal peptide. After artificial infection with GCRV, C5 transcription in grass carp liver increased significantly before the appearance of symptoms. C5a generation in the liver increased significantly from the onset of disease symptoms, and continued to increase until recovery. GCRV induced C5 cleavage in grass carp, with C5a production.

Background The non-local module has been primarily used in literature to capturing long-range dependencies. However, it suffers from prohibitive computational complexity and lacks the interactions among positions across the channels. Methods We present a deformed non-local neural network (DNL-Net) for medical image segmentation, which has two prominent components; deformed non-local module (DNL) and multi-scale feature fusion. The former optimizes the structure of the non-local block (NL), hence, reduces the problem of excessive computation and memory usage, significantly. The latter is derived from the attention mechanisms to fuse the features of different levels and improve the ability to exchange information across channels. In addition, we introduce a residual squeeze and excitation pyramid pooling (RSEP) module that is like spatial pyramid pooling to effectively resample the features at different scales and improve the network receptive field. Results The proposed method achieved 96.63% and 92.93% for Dice coefficient and mean intersection over union, respectively, on the intracranial blood vessel dataset. Also, DNL-Net attained 86.64%, 96.10%, and 98.37% for sensitivity, accuracy and area under receiver operation characteristic curve, respectively, on the DRIVE dataset. Conclusions The overall performance of DNL-Net outperforms other current state-of-the-art vessel segmentation methods, which indicates that the proposed network is more suitable for blood vessel segmentation, and is of great clinical significance.

Both bacterioplankton and eukaryoplankton communities play important roles in the geochemical cycles and energy flows of river ecosystems. However, whether a seasonal change in bacterioplankton and eukaryoplankton communities is synchronous remains unclear. To test the synchronicity and analyze how physical and chemical environmental factors affect these communities, we compared bacterioplankton and eukaryoplankton communities in surface water samples between March (dry season) and June (rainfall season) considering water environmental factors. Our results showed that there was no significant difference in operational taxonomic unit number, Shannon index, and Chao1 index in bacterioplankton and eukaryoplankton communities between March and June. However, principal component analysis showed that the communities were significantly different between the sampling times and sampling sites. Water temperature (WT), oxidation-reduction potential (ORP), water transparency (SD), NO

To understand how a bacteria-free fish gut ecosystem develops microbiota as the fish ages, we performed a 1-year study on the gut microbiota of hatchling gibel carp (Carassius auratus gibelio). Our results indicate that the gut microbial diversity increases significantly as the fish develop. The gut microbial community composition showed significant shifts corresponding to host age and appeared to shift at two time points despite consistent diet and environmental conditions, suggesting that some features of the gut microbial community may be determined by the host's development. Dietary and environmental changes also seem to cause significant shifts in the fish gut microbial community. This study revealed that the gut microbiota of gibel carp assemble into distinct communities at different times during the host's development and that this process is less affected by the surrounding environment than by the host diet and development. Community phylogenetic analyses based on the net relatedness index further showed that environmental filtering (host selection) deterministically governs the gut microbial community composition. More importantly, the influence of host-associated deterministic filtering tends to weaken significantly over the course of the host's development. However, further studies are needed to assess whether this host development-dependent shift in gut microbiota will still exist under different rearing strategies.

The spatial distribution pattern of organisms is a basic issue in understanding the mechanisms of community assembly. Although the spatial distributions of animals and plants have been well studied, those of microorganisms are still being debated. In this study, we used a fish gut microecosystem to detect the spatial pattern of microbes, because it can provide a relatively unified and stable environment. Results suggest that the turnover of intestinal bacterial assemblages showed a weak but highly significant negative correlation between similarity and distances in the microbial community, in respect of both grass carp intestinal loci distances and the geographical distance between fish sampling sites. Our results also suggest that intestinal bacterial assemblages responded to differences within the external environment and within different parts of the fish themselves. These results show that some, or possibly all, microbes are restricted in their distribution and that environmental factors are also important influences on the structure of intestinal bacterial assemblages. The fish gut microecosystem is useful in promoting study of the spatial distribution patterns of microorganisms.

The intestinal bacteria of vertebrates form a close relationship with their host. External and internal conditions of the host, including its habitat, affect the intestinal bacterial community. Similarly, the intestinal bacterial community can, in turn, influence the host, particularly with respect to disease resistance. We compared the intestinal bacterial communities of grass carp that were collected from farm-ponds or a lake. We conducted denaturing gradient gel electrophoresis of amplified 16S rRNA genes, from which 66 different operational taxonomic units were identified. Using both the unweighted pair-group method with arithmetic means clustering and principal component analysis ordination, we found that the intestinal bacterial communities from the two groups of pond fish were clustered together and inset into the clusters of wild fish, except for DF-7, and there was no significant correlation between genetic diversity of grass carp and their intestinal bacterial communities (Mantel one-tailed test, R=0.157, P=0.175). Cetobacterium appeared more frequently in the intestine of grass carp collected from pond. A more thorough understanding of the role played by intestinal microbiota on fish health would be of considerable benefit to the aquaculture industry.