LSR targets YAP to modulate intestinal Paneth cell differentiation.

Lipolysis-stimulated lipoprotein receptor (LSR) is a multi-functional protein that is best known for its roles in assembly of epithelial tricellular tight junctions and hepatic clearance of lipoproteins. Here, we investigated whether LSR contributes to intestinal epithelium homeostasis and pathogenesis of intestinal disease. By using multiple conditional deletion mouse models and ex vivo cultured organoids, we find that LSR elimination in intestinal stem cells results in the disappearance of Paneth cells without affecting the differentiation of other cell lineages. Mechanistic studies reveal that LSR deficiency increases abundance of YAP by modulating its phosphorylation and proteasomal degradation. Using gain- and loss-of-function studies, we show that LSR protects against necrotizing enterocolitis through enhancement of Paneth cell differentiation in small-intestinal epithelium. Thus, this study identifies LSR as an upstream negative regulator of YAP activity, an essential factor for Paneth cell differentiation, and a potential therapeutic target for necrotizing enterocolitis.

Effects of wildfire disturbance on forest soil microbes and colonization of ericoid mycorrhizal fungi in northern China.

Wildfires affect forest succession and restoration by changing the community structure of soil microorganisms. Mycorrhizal formation is essential for plant growth and development. However, the driving mechanism of their natural succession after wildfire is still unclear. In this study, we examined the community structure of soil bacteria and fungi along a time series of natural recovery after wildfires in the Greater Khingan Range of China (2020 fires, 2017 fires, 2012 fires, 2004 fires, 1991 fires, and unburned). By exploring the effects of wildfire on plant traits, fruit nutrition, colonization of mycorrhizal fungi and its influencing mechanism. The results show that natural succession after wildfires significantly changed the community composition of bacteria and fungi, with ß diversity having a greater impact but less impact on the α diversity of microorganisms. Wildfires significantly changed plant traits and fruit nutrient content. The changes in colonization rate and customization intensity of mycorrhizal fungi were caused by increased MDA content and soluble sugar content and increased MADS-box gene and DREB1 gene expression in lingonberry (Vaccinium vitis-idaea L.). Our results showed that the soil bacterial and fungal communities in the boreal forest ecosystem changed significantly during wildfire recovery and changed the colonization rate of lingonberry mycorrhizal fungi. This study provides a theoretical basis for the restoration of forest ecosystems after wildfires.

Biodegradation of polyethylene by Meyerozyma guilliermondii and Serratia marcescens isolated from the gut of waxworms (larvae of Plodia interpunctella).

The widespread use of polyethylene (PE) causes a large amount of indigestible plastic waste. Waxworms (the larvae of Plodia interpunctella) can eat PE, but the degradation principle of PE under the action of intestinal microorganisms is still unclear, especially the insufficient research on key degradable PE strains. In this study, we fed waxworms with PE. Two strains with high PE degradation efficiency were isolated and purified, and the effects of single and microbial consortia on PE degradation were evaluated by water contact angle (WCA), FTIR, GC-MS, SEM and RT-qPCR. The results showed that Meyerozyma guilliermondii ZJC1 (MgZJC1) and Serratia marcescens ZJC2 (SmZJC2) could degrade PE. However, the degradation efficiency of the microbial consortium was higher, and the weight loss rate of PE was 15.87 %. In addition, the PE degradation products of MgZJC1 were C9H10O, C20H15NO, C28H44O3 and C16H32O2, and the PE degradation products of SmZJC2 were C16H18O, C14H18N2O7 and C31H48O6. The PE degradation products of the microbial consortium were C11H24, C19H10O, C15H32, C14H30, C16H34, C25H52 and C27H56. RT-qPCR results showed that SmZJC2 promoted PE degradation by upregulating the expression of multiple genes, such as multicopper oxidase genes (PiSm-CueO). MgZJC1 responded to carbon deficiency by upregulating the expression of multiple genes, such as key enzyme genes in the tricarboxylic acid (TCA) cycle. This study can be used to develop an efficient microbial consortium for PE degradation and provide a basis for the reuse of PE waste. It can also provide a research basis for the joint degradation of PE by microbial consortia composed of bacteria and fungi.

Lingonberry (Vaccinium vitis-idaea L.) Interact With Lachnum pygmaeum to Mitigate Drought and Promote Growth.

The application of Ericoid mycorrhizal (ErM) fungi is considered to be an important strategy for increasing plant yield and drought resistance. In this study, we isolated and identified two ErM fungi that can promote the growth of lingonberry. We tried to understand the potential of these two ErM fungi to promote the growth of lingonberry and the strategies to help plants cope with water shortage. The use value of ErM fungi was evaluated by inoculating Oidiodendron maius FC (OmFC) or Lachnum pygmaeum ZL6 (LpZL6), well-watered (WW) and severe drought stress (SDS). The results showed that the mycelium of LpZL6 was denser than that of OmFC, and both ErM fungi significantly increased the biomass of lingonberry stems and roots. They also significantly increased the chlorophyll content by 65.6 and 97.8%, respectively. In addition, inoculation with LpZL6 fungi can improve drought resistance, promote root growth and increase root wet weight by 1157.6%. Drought reduced the chlorophyll content and soluble sugar content of lingonberry but increased significantly after inoculation with LpZL6. Inoculation with LpZL6 decreased lingonberry's malondialdehyde (MDA) content but increased the superoxide dismutase (SOD) activity. Overall, these results indicated that the successful coexistence of ErM fungi and lingonberry alleviated the adverse effects of drought stress through higher secondary metabolites and photosynthetic pigment synthesis.

Loss of CLDN5 in podocytes deregulates WIF1 to activate WNT signaling and contributes to kidney disease.

Although mature podocytes lack tight junctions, tight junction integral membrane protein claudin-5 (CLDN5) is predominantly expressed on plasma membranes of podocytes under normal conditions. Using podocyte-specific Cldn5 knockout mice, we identify CLDN5 as a crucial regulator of podocyte function and reveal that Cldn5 deletion exacerbates podocyte injury and proteinuria in a diabetic nephropathy mouse model. Mechanistically, CLDN5 deletion reduces ZO1 expression and induces nuclear translocation of ZONAB, followed by transcriptional downregulation of WNT inhibitory factor-1 (WIF1) expression, which leads to activation of WNT signaling pathway. Podocyte-derived WIF1 also plays paracrine roles in tubular epithelial cells, as evidenced by the finding that animals with podocyte-specific deletion of Cldn5 or Wif1 have worse kidney fibrosis after unilateral ureteral obstruction than littermate controls. Systemic delivery of WIF1 suppresses the progression of diabetic nephropathy and ureteral obstruction-induced renal fibrosis. These findings establish a function for podocyte CLDN5 in restricting WNT signaling in kidney.

MicroRNA-126-5p Inhibits the Migration of Breast Cancer Cells by Directly Targeting CNOT7.

BACKGROUND: To assess the effect of microRNA-126-5p (miR-126-5p) on the migration of the breast cancer MCF7 cell line. METHODS: GSE143564 was downloaded from the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo) to identify the differentially expressed miRNAs between breast cancer and adjacent tissues. Quantitative reverse transcription PCR (RT-qPCR) was used to assess miR-126-5p levels in the normal 184A1 breast cell line and the breast cancer MCF7 cell line. The MCF7 cell line was then transfected with miR-126-5p mimics or corresponding negative control (NC-mimic). The proliferation and migration abilities of the MCF7 cell line were measured by methyl thiazolyl tetrazolium (MTT), Transwell and scratch healing assays. CCR4-NOT transcription complex and subunit 7 (CNOT7) expression levels in the NC-mimic and miR-126-5p mimic groups were measured by Western blot analysis. Bioinformatic analysis and a dual-luciferase reporter assay were performed to identify the miR-126-5p target gene. RESULTS: One hundred forty-eight differentially expressed miRNAs (downregulated = 55, upregulated = 93) were identified. MiR-126-5p expression in the MCF7 cell line was significantly downregulated relative to that of 184A1 cell line (P < 0.05). Compared with that observed in the control and NC-mimic groups, cell proliferation in the miR-126-5p mimic group was significantly decreased at 48 and 72 h posttransfection (P < 0.05). In addition, the scratch healing rate and number of membrane-piercing cells in the miR-126-5p overexpression group were lower than those detected in the control and NC groups (P < 0.05). Furthermore, miR-126-5p could reduce the luciferase activity for the wild-type CNOT7 gene 3'-untranslated region (UTR) reporter (P < 0.05) but had no effect on the mutant 3'UTR reporter (P > 0.05). Compared with that observed in the NC and control groups, the levels of CNOT7 in the miR-126-5p overexpression group decreased (P < 0.05). CONCLUSION: Upregulation of miR-126-5p can inhibit the migration of the breast cancer MCF7 cell line, which may involve its direct targeting of the 3'UTR of CNOT7.