Deciphering the effects of genotype and climatic factors on the performance, active ingredients and rhizosphere soil properties of Salvia miltiorrhiza

IntroductionSalvia miltiorrhiza Bunge is an important medicinal herb, which is widely cultivated in most parts of China. It has attracted considerable attention because of its pharmacological properties and potential health benefits.MethodsWe used a field experiment to determine the effects of different genotypes and climatic factors on the performance (plant biomass, morphological parameters), active ingredients, rhizosphere soil physicochemical properties and microbial composition of S. miltiorrhiza at five cultivation locations.ResultsThe results showed that these parameters were significantly different in the six different genotypes of S. miltiorrhiza from five producing areas. Genotype and soil physicochemical properties were the main factors affecting the growth traits of S. miltiorrhiza, while genotype, climate and soil physicochemical properties were the main factors affecting the content of active components of S. miltiorrhiza. Microbial phospholipid fatty acid analysis showed that the biomass of Gram-positive and Gram-negative bacteria was affected by the genotypes of S. miltiorrhiza plants, while the biomass of arbuscular mycorrhizal fungi, fungi, Gram-positive and Gram-negative bacteria was affected by climate factors.DiscussionBased on the main results, DS993 was the most suitable genotype for S. miltiorrhiza in the five producing areas from the perspective of comprehensive growth traits and medicinal components, while DS993 and DS2000 were suitable for planting in Shandong province from the perspective of origin. DS996 is not suitable for all of the above production areas. These results are helpful to understand the ecological adaptability of different genotypes of S. miltiorrhiza resources, and to select appropriate S. miltiorrhiza genotypes for specific planting areas, so as to maximize yield and quality

A single transcription factor is sufficient to induce and maintain secretory cell architecture

We hypothesized that basic helix–loop–helix (bHLH) MIST1 (BHLHA15) is a “scaling factor” that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PCs), whose function is to pump acid into the stomach, normally lack MIST1 and do not perform regulated secretion. Forced expression of MIST1 in PCs caused them to expand their apical cytoplasm, rearrange mitochondrial/lysosome trafficking, and generate large secretory granules. Mist1 induced a cohort of genes regulated by MIST1 in multiple organs but did not affect PC function. MIST1 bound CATATG/CAGCTG E boxes in the first intron of genes that regulate autophagosome/lysosomal degradation, mitochondrial trafficking, and amino acid metabolism. Similar alterations in cell architecture and gene expression were also caused by ectopically inducing MIST1 in vivo in hepatocytes. Thus, MIST1 is a scaling factor necessary and sufficient by itself to induce and maintain secretory cell architecture. Our results indicate that, whereas mature cell types in each organ may have unique developmental origins, cells performing similar physiological functions throughout the body share similar transcription factor-mediated architectural “blueprints.

Comprehensive treatment of recurrent and metastatic nasopharyngeal carcinoma: advances and future directions

Abstract The standard of care for patients with recurrent and metastatic nasopharyngeal carcinoma remains unclear. There is an urgent need to identify effective and low‐toxicity treatment methods for such patients. The integration of current evidence to form an optimal treatment modality for recurrent and/or metastatic nasopharyngeal is worth exploring. In recent years, several outstanding clinical trials have emerged for the comprehensive treatment of recurrent and/or metastatic nasopharyngeal carcinoma . New evidence has been added for the local treatment of patients with metastasis. Endoscopic surgery, radiomics, and other technologies help achieve precise local treatment. Novel immunotherapeutic drugs have been approved for the treatment of patients with metastasis in China. The combination of immunotherapy, chemotherapy, and targeted therapy is promising and requires confirmation. Future studies will continue to focus on individualization and precision medicine

Bone Marrow Derivation of Interstitial Cells of Cajal in Small Intestine Following Intestinal Injury

Interstitial cells of Cajal (ICCs) in gastrointestinal tract are specialized cells serving as pacemaker cells. The origin of ICCs is currently not fully characterized. In this work, we aimed to study whether bone marrow-derived cells (BMDCs) could contribute to the origin of ICCs in the muscular plexus of small intestine using GFP-C57BL/6 chimeric mice.Engraftment of BMDCs in the intestine was investigated for GFP expression. GFP positive bone marrow mononuclear cells reached a proportion of 95.65%±3.72% at different times in chimerism. Donor-derived cells distributed widely in all the layers of the gastrointestinal tract. There were GFP positive BMDCs in the myenteric plexus, which resembled characteristics of ICCs, including myenteric location, c-Kit positive staining, and ramified morphology. Donor-derived ICCs in the myenteric plexus contributed to a percentage ranging 9.25%±4.9% of all the ICCs in the myenteric plexus. In conclusion, here we described that donor-derived BMDCs might differentiate into gastrointestinal ICCs after radiation injury, which provided an alternative source for the origin of the ICCs in the muscular plexus of adult intestine. These results further identified the plasticity of BMDCs and indicated therapeutic implications of BMDCs for the gastrointestinal dysmotility caused by ICCs disorders

Table_1_Deciphering the effects of genotype and climatic factors on the performance, active ingredients and rhizosphere soil properties of Salvia miltiorrhiza.docx

IntroductionSalvia miltiorrhiza Bunge is an important medicinal herb, which is widely cultivated in most parts of China. It has attracted considerable attention because of its pharmacological properties and potential health benefits.MethodsWe used a field experiment to determine the effects of different genotypes and climatic factors on the performance (plant biomass, morphological parameters), active ingredients, rhizosphere soil physicochemical properties and microbial composition of S. miltiorrhiza at five cultivation locations.ResultsThe results showed that these parameters were significantly different in the six different genotypes of S. miltiorrhiza from five producing areas. Genotype and soil physicochemical properties were the main factors affecting the growth traits of S. miltiorrhiza, while genotype, climate and soil physicochemical properties were the main factors affecting the content of active components of S. miltiorrhiza. Microbial phospholipid fatty acid analysis showed that the biomass of Gram-positive and Gram-negative bacteria was affected by the genotypes of S. miltiorrhiza plants, while the biomass of arbuscular mycorrhizal fungi, fungi, Gram-positive and Gram-negative bacteria was affected by climate factors.DiscussionBased on the main results, DS993 was the most suitable genotype for S. miltiorrhiza in the five producing areas from the perspective of comprehensive growth traits and medicinal components, while DS993 and DS2000 were suitable for planting in Shandong province from the perspective of origin. DS996 is not suitable for all of the above production areas. These results are helpful to understand the ecological adaptability of different genotypes of S. miltiorrhiza resources, and to select appropriate S. miltiorrhiza genotypes for specific planting areas, so as to maximize yield and quality.</p

Additional file 1 of Paneth cell-derived iNOS is required to maintain homeostasis in the intestinal stem cell niche

Additional file 1: Figure S1. Phenotype characterization of iNOS−/− mice. A Genotyping of iNOS−/− mice was achieved by 1.5% agarose gel electrophoresis. Het = heterozygote, KO = knockout, NTC = no template control. B qPCR analysis of iNOS mRNA levels in wild-type mice and iNOS−/− mice. C Comparison of wild-type and iNOS−/− littermate body weights. *P < 0.05, n = 5. Figure S2. qPCR analysis of Nos2 in WT and iNOS−/− enteroids. Enteroids derived from the two groups were released and collected on day 4 after culturing, and then total RNA was extracted and used for qPCR testing. **P < 0.01. Figure S3. Loss of iNOS significantly decreased the protein level of p27 Kip1 in the intestinal crypts. Bar = 100 μm. Figure S4. Histogram of differentially expressed genes (DEGs) between the control group and iNOS−/− group. There were 168 upregulated genes (pink) and 155 downregulated genes (blue) in the iNOS−/− group compared with the control group. N = 3 for each group. Figure S5. qPCR validation for those genes implicated by RNA-Seq. A–D qPCR validation of the upregulated genes in RNA-Seq results. E–G qPCR validation of the genes that were downregulated in RNA-Seq. H qPCR results of the mRNA level of Dll4 gene, which was a component of Notch signaling pathway. I–L qPCR examination of adaptive immunity related genes. M–P qPCR validation of gluconeogenesis related genes. (*P < 0.05, ***P < 0.001). Figure S6. RNA-Seq data of inflammatory factors. The analysis of RNA-Seq data showed that mRNA levels of Tnf and Ifgn were significantly increased due to iNOS deficiency, but Il1b and Nfkb1 did not change significantly. (*P < 0.05). Figure S7. GSEA of genes downregulated in association with iNOS depletion. Differentially downregulated genes in the iNOS−/− group were also closely related to glycolytic processes in addition to gluconeogenesis (n = 3)