Root development relies on the establishment of meristematic tissues that give rise to distinct cell types that differentiate across defined temporal and spatial gradients. Dissection of the ...developmental trajectories and the transcriptional networks that underlie them could aid understanding of the function of the root apical meristem in both dicots and monocots. Here, we present a single-cell RNA (scRNA) sequencing and chromatin accessibility survey of rice radicles. By temporal profiling of individual root tip cells we reconstruct continuous developmental trajectories of epidermal cells and ground tissues, and elucidate regulatory networks underlying cell fate determination in these cell lineages. We further identify characteristic processes, transcriptome profiles, and marker genes for these cell types and reveal conserved and divergent root developmental pathways between dicots and monocots. Finally, we demonstrate the potential of the platform for functional genetic studies by using spatiotemporal modeling to identify a rice root meristematic mutant from a cell-specific gene cohort.
Douchi is a type of Chinese traditional fermented food that is an important source of protein and is used in flavouring ingredients. The end product is affected by the microbial community present ...during fermentation, but exactly how microbes influence the fermentation process remains poorly understood. We used an Illumina MiSeq approach to investigate bacterial and fungal community diversity during both douchi-koji making and fermentation. A total of 181,443 high quality bacterial 16S rRNA sequences and 221,059 high quality fungal internal transcribed spacer reads were used for taxonomic classification, revealing eight bacterial and three fungal phyla. Firmicutes, Actinobacteria and Proteobacteria were the dominant bacterial phyla, while Ascomycota and Zygomycota were the dominant fungal phyla. At the genus level, Staphylococcus and Weissella were the dominant bacteria, while Aspergillus and Lichtheimia were the dominant fungi. Principal coordinate analysis showed structural separation between the composition of bacteria in koji making and fermentation. However, multivariate analysis of variance based on unweighted UniFrac distances did identify distinct differences (p <0.05), and redundancy analysis identified two key genera that are largely responsible for the differences in bacterial composition between the two steps. Staphylococcus was enriched in koji making, while Corynebacterium was enriched in fermentation. This is the first investigation to integrate douchi fermentation and koji making and fermentation processes through this technological approach. The results provide insight into the microbiome of the douchi fermentation process, and reveal a structural separation that may be stratified by the environment during the production of this traditional fermented food.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This article deals with the stability of neural networks (NNs) with time-varying delay. First, a generalized reciprocally convex inequality (RCI) is presented, providing a tight bound for ...reciprocally convex combinations. This inequality includes some existing ones as special case. Second, in order to cater for the use of the generalized RCI, a novel Lyapunov-Krasovskii functional (LKF) is constructed, which includes a generalized delay-product term. Third, based on the generalized RCI and the novel LKF, several stability criteria for the delayed NNs under study are put forward. Finally, two numerical examples are given to illustrate the effectiveness and advantages of the proposed stability criteria.
Sunitinib resistance is a major challenge for advanced renal cell carcinoma (RCC). Understanding the underlying mechanisms and developing effective strategies against sunitinib resistance are highly ...desired in the clinic. Here we identified an lncRNA, named lncARSR (lncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response. Therefore, lncARSR may serve as a predictor and a potential therapeutic target for sunitinib resistance.
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•lncARSR promotes sunitinib resistance and predicts poor response of RCC patients•Intercellular transfer of lncARSR by exosomes disseminates sunitinib resistance•lncARSR acts as a ceRNA for miR-34 and miR-449 to promote AXL and c-MET expression•Targeting lncARSR or AXL/c-MET in sunitinib-resistant RCC restores drug sensitivity
Qu et al. identify lncARSR as a mediator of sunitinib resistance in renal cell carcinoma by acting as a competing endogenous RNA for miR-34 and miR-449, thereby increasing expression of their targets AXL and c-MET, and show that exosome-mediated transmission of lncARSR can confer resistance to sensitive cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Wilms tumor gene on the X chromosome (WTX) is a putative tumor suppressor gene in Wilms tumor, but its expression and functions in other tumors are unclear. Colorectal cancer (CRC) is the third ...leading cause of cancer-related deaths in women and the second leading cause in men in the United States. We demonstrated that WTX frequently lost in CRC which was highly correlated with cell proliferation, tumor invasion and metastasis. Mechanistically, WTX loss disrupts the interaction between RhoGDIα and CDC42 by losing of the binding with RhoGDIα and triggers the activation of CDC42 and its downstream cascades, which promotes CRC development and liver metastasis. The aberrant upregulation of miR-20a/miR-106a were identified as the reason of WTX loss in CRC both in vivo and in vitro. These study defined the mechanism how miR-20a/miR-106a-mediated WTX loss regulates CRC progression and metastasis, and provided a potential therapeutic target for preventing CRC progression.
Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around ...the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC5) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals.
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•First comprehensive review of antibiotics and ARGs in lakes is shown.•Species sensitivity distribution was used to analyse the risk of antibiotics.•Quinolones in water of lakes from China are higher than other lakes worldwide.•There is limited research on the role of aquatic biota on the propagation of ARGs.•Lakes are an important environment to investigate the spread and transport of ARGs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Recent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause ...of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown.
lncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs.
The microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway.
MRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential ...regulator for Akt activation by various stresses. Surprisingly, AMPK is also activated by growth factor EGF through Ca2+/Calmodulin-dependent kinase and is essential for EGF-mediated Akt activation and biological functions. AMPK phosphorylates Skp2 at S256 and promotes the integrity and E3 ligase activity of Skp2 SCF complex leading to K63-linked ubiquitination and activation of Akt and subsequent oncogenic processes. Importantly, AMPK-mediated Skp2 S256 phosphorylation promotes breast cancer progression in mouse tumor models, correlates with Akt and AMPK activation in breast cancer patients, and predicts poor survival outcomes. Finally, targeting AMPK-mediated Skp2 S256 phosphorylation sensitizes cells to anti-EGF receptor targeted therapy. Our study sheds light on how stress and EGF induce Akt activation and new mechanisms for AMPK-mediated oncogenesis and drug resistance.
Antibiotic resistance genes (ARGs) and microplastics in the environment are of great public concern due to their potential risk to human health. Microplastics can form distinct bacterial communities ...and absorb pollutants from the surrounding environment, which provide potential hosts and exert possible selection pressure of ARGs. We provide a practical evaluation of the scientific literature regarding this issue. The occurrence and transport of ARGs on microplastics in wastewater treatment plants, aquatic, terrestrial, and air environments were summarized. Selective enrichment of ARGs and antibiotic resistance bacteria on microplastics have been confirmed in different environments. Aggregates may be crucial to understand the behavior and transport of ARGs on microplastics, especially in the aquatic and terrestrial environment. Microplastics could be a carrier of ARGs between the environment and animals. Accumulation of pollutants and dense bacterial communities on microplastics provide favorable conditions for higher transfer rate and evolution of ARGs. More studies are still needed to understand the enrichment, transport, and transfer of ARGs on microplastics and provide a fundamental basis for evaluating their exposure health risk to humans.
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•ARGs on microplastics in WWTPs, water, soil, and air were summarized.•Distinct ARG composition on microplastics was due to selective enrichment.•Aggregates are crucial to study the transport and transfer of ARGs on microplastic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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