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Nephronophthisis (NPHP) is a kind of ciliopathy. Interstitial fibrosis occurs at the early stage of the disease. TGF-β/Smad is a key signaling pathway in regulating interstitial fibrosis and epithelial-mesenchymal transition (EMT). In this study, we explored the activation of the TGF-β/Smad signaling pathway and EMT in NPHP1-defective MDCK cells to further understand the pathogenesis of NPHP.

NPHP1-knockdown (NPHP1

) MDCK cells were constructed by recombinant lentiviral short hairpin RNA, and NPHP1-knockout (NPHP1

) MDCK cells were constructed by using the CRISPR/Cas9 technique. The morphology and migration ability were observed under a microscope. Western blotting was used to detect the expression of E-cadherin, β-catenin, α-smooth muscle actin (α-SMA), fibroblast-specific protein-1(FSP1), TGF-β1, Smad2, Smad3, p-Smad3, Smad4 and Smad7. The localization of Smad3 was determined by immunofluorescence assay.

NPHP1

and NPHP1

MDCK cells were spindle-shaped and presented EMT-like changes. E-cadherin and β-catenin expression decreased, while α-SMA and FSP1 expression increased; the TGF-β/Smad signaling pathway was activated, Smad2, Smad3, p-Smad3 and Smad4 expression increased, Smad3 translocated to nuclear and Smad7 expression decreased compared with those in wild type MDCK cells. Overexpression of Smad7 reversed these changes to different degrees.

Our results indicate that NPHP1 defects induce the activation of the TGF-β/Smad signaling pathway and EMT in MDCK cells. These factors may be implicated in the pathogenesis of interstitial fibrosis in NPHP.

Our results indicate that NPHP1 defects induce the activation of the TGF-β/Smad signaling pathway and EMT in MDCK cells. These factors may be implicated in the pathogenesis of interstitial fibrosis in NPHP.The efficacy of n-3 polyunsaturated fatty acids (PUFAs) in improving outcomes in a renal ischemia-reperfusion injury (IRI) model has previously been reported. However, the underlying mechanisms remain poorly understood and few reports demonstrate how dietary n-3 PUFAs influence the composition of membrane phospholipids in the kidney. click here Additionally, it has not been elucidated whether perilla oil (PO), which is mainly composed of the n-3 alpha-linolenic acid, mitigates renal IRI. In this study, we investigated the effect of dietary n-3 PUFAs (PO), compared with an n-6 PUFA-rich soybean oil (SO) diet, on IRI-induced renal insufficiency in a rat model. Levels of membrane phospholipids containing n-3 PUFAs were higher in the kidney of PO-rich diet-fed rats than the SO-rich diet-fed rats. Levels of blood urea nitrogen and serum creatinine were significantly higher in the ischemia-reperfusion group than the sham group under both dietary conditions. However, no significant differences were observed in blood urea nitrogen, serum creatinine, or histological damage between PO-rich diet-fed rats and SO-rich diet-fed rats. In the kidney of PO-rich diet-fed rats, levels of arachidonic acid and arachidonic acid-derived pro-inflammatory lipid mediators were lower than SO-rich diet-fed rats. Eicosapentaenoic acid and eicosapentaenoic acid-derived lipid mediators were significantly higher in the kidney of PO-rich than SO-rich diet-fed rats. These results suggest that dietary n-3 PUFAs alter the fatty acid composition of membrane phospholipids and lipid mediators in the kidney; however, this does not attenuate renal insufficiency or histological damage in a renal IRI model.Yersinia outer protein M (YopM) is one of the effector proteins and essential for virulence. YopM is delivered by the Yersinia type III secretion system (T3SS) into the host cell, where it shows immunosuppressive effect through interaction with host proteins. Therefore, protein-protein interactions of YopM is significant to understand its molecular mechanism. In this study, we aimed to explore protein-protein interactions of YopM with the two components of T3SS, namely LcrV and LcrG. We used bimolecular fluorescence complementation (BiFC) assay and monitored the reassembly of green fluorescence protein in Escherichia coli. As an indicator of the protein-protein interaction, we monitored the in vivo reconstitution of fluorescence by measuring fluorescence intensity and imaging the cells under fluorescence microscope. We showed, for the first time, that YopM interacts with LcrG, but not with LcrV. Here, we propose BiFC assay as a simple method to screen novel interaction partners of YopM.Previous studies have shown the brain synchronization of all team members while completing a collaborative task. Moreover, this effect is influenced by a team's compositional elements, such as gender (opposite or same) or relationships (i.e., friends, lovers, or strangers) among team members. However, whether interpersonal brain synchronization (IBS) is affected by team members' experience, as well as the temporal dynamics of such brain synchronization, remains to be investigated. In the current study, we combined behavioral methods and functional near-infrared spectroscopy-based hyperscanning to examine the effect of member experience on team cooperation by an adopted continuous joint drawing task with 21 student-student dyads (S-S dyads) and 22 teacher-student dyads (T-S dyads). The results revealed that team members with differing experiences (T-S dyads) perform better than those with similar ones (S-S dyads). Moreover, we observed IBS in the left frontopolar region (channel 11). link2 However, we did not observe significant changes of the task-related IBS across time. Besides, IBS was negatively correlated with the participants' behavioral performance. Our findings demonstrate the importance of social experience in teamwork in the real world and suggest a possible mechanism for cooperation from a temporal and spatial perspective.Rheumatoid arthritis (RA) is a systemic autoimmune disease. Synovial hyperplasia and persistent inflammation serve as its typical pathological manifestations, which ultimately lead to joint destruction and function loss. Both clinical observations and metabolomics studies have revealed the prevalence of metabolic disorders in RA. In inflammatory immune microenvironments, energy metabolism is profoundly changed. Increasingly evidences suggest that this abnormality is involved in the occurrence and development of RA-related inflammation. Unsurprisingly, many energy metabolism sensors have been confirmed with immunoregulatory properties. As a representative, silent information regulator type 1 (Sirt1) controls many aspects of immune cells, such as cell lifespan, polarization, and secretion by functioning as a transcriptional regulator. Because of the profound clinical implication, researches on Sirt1 in the regulation of energy metabolism and immune functions under RA conditions have gradually gained momentum. This signaling balances glycolysis, lipid metabolism and insulin secretion orchestrating with other metabolism sensors, and consequently affects immune milieu through a so-called metabolism-immune feedback mechanism. This article reviews the involvement of Sirt1 in RA by discussing its impacts on energy metabolism and immune functions, and specially highlights the potential of Sirt1-targeting anti-rheumatic regimens. It also provides a theoretical basis for clarifying the mystery about the high incidence of metabolic complications in RA patients and identifying new anti-rheumatic reagents.Strains DS1-2T and AZ1-7, which were isolated from roots of plants, were taxonomically characterized based on polyphasic taxonomic and taxogenomic approaches. Both strains were Gram-stain-positive and filamentous bacteria which contained LL-diaminopimelic acid in cell-wall peptidoglycan and glucose and ribose in whole-cell hydrolysates. MK-9(H6), MK-10(H6), MK-9(H8), MK-10(H8) and MK-10(H4) were major menaquinones; iso-C160 and iso-C161G were predominant cellular fatty acids; diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol mannoside presented as major phospholipids; and the DNA G+C contents of 73.2 mol%. Strains DS1-2T and AZ1-7 showed 97.6-98.0 % 16S rRNA gene sequence similarity, 81.0-82.0 % ANIb, 84.8-85.3 % ANIm and 22.0-23.1 % digital DDH to their related type strains S. specialis GW41-1564T and S. hoynatensis S1412T. Comparative genomics results of these strains and their related type strains also revealed the differences and distributions of key genes associated with stress responses, environmental variables, plant interactions and bioactive metabolites. Based on the phenotypic, chemotaxonomic and genomic data, strains DS1-2T and AZ1-7 could be assigned to the novel species within the genus Streptomyces for which the name Streptomyces radicis sp. nov. link3 is proposed. The type strain is DS1-2T (=JCM 32152T =KCTC 39738T =TISTR 2403T).Tea (Camellia sinensis) is perhaps the most popular and economic beverage in the globe due to its distinctive fragrance and flavour generated by the leaves of commercially farmed tea plants. The tea microbiome has now become a prominent topic of attention for microbiologists in recent years as it can help the plant for soil nutrient acquisition as well as stress management. Tea roots are well known to be colonized by Arbuscular Mycorrhizal Fungi (AMF) and many other beneficial microorganisms that boost the growth of the tea which increases leaf amino acids, protein, caffeine, and polyphenols content. One of the primary goals of rhizosphere microbial biology is to aid in the establishment of agricultural systems that provide high quantities of the food supply while minimizing environmental effects and anthropogenic activities. The present review is aimed to highlight the importance of microbes (along with their phylogeny) derived from cultivated and natural tea rhizospheres to understand the role of AMF and rhizospheric bacterial population to improve plant growth, enhancement of tea quality, and protecting tea plants from pathogens. This review also summarizes recent advances in our understanding of the diversity and profile of tea-associated bacteria. The utilization of the tea microbiome as a "natural resource" could provide holistic development in tea cultivation to ensure sustainability, highlighting knowledge gaps and future microbiome research.Hypericum monogynum L. (Hypericaceae) has been used as a folk Chinese medicine for the treatment of inflammatory related diseases. Cyclooxygenase-2 (COX-2) is a crucial target for the development of agents to treat inflammation. To search for anti-inflammatory compounds from traditional Chinese medicines, a chemical constituent study along with COX-2 inhibitory activity analysis was performed for this plant. In this study, sixteen chemical monomers, including three undescribed oxidative degradation polycyclic polyprenylated acylphloroglucinols (PPAPs, hypemoins C-E), two undescribed PPAPs (hypemoins A and B), and 11 known compounds, were identified from the flowers of H. monogynum. Their structures were characterized by HRESIMS, NMR techniques, ECD, and single crystal X-ray diffraction. Four flavonoid derivatives showed remarkable COX-2 inhibitory activities, with IC50 values ranging from 0.220 ± 0.006 to 1.655 ± 0.098 μM. Among these compounds, the possible recognition mechanism between quercetin 3-(6″-O-caffeoyl)-β-3-D-galactoside and COX-2 was predicted by molecular docking analysis.