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Colorectal cancer (CRC), classified as a lethal form of cancer, substantially threatens human well-being. Cancer stem cells (CSCs) reflect subsets for cancerous cells having basic stem-cell type properties, being significantly involved in the development of chemoresistance and tumor relapsing. The aberrant TRIM27 expression in various types of cancer indicates its potential involvement in cancer growth and progression. The current understanding of the TRIM27 involvement in CRC remains limited. In current study indicated that TRIM27 can potentially promote CSC-type phenotype of Cisplatin (DDP)-resistant CRC cells. YTHDF1 recruitment onto m6A-amended TRIM27 was crucial for facilitating the TRIM27 translating process in DDP-resistant CRC cells. The present research proposes that TRIM27 exhibits an oncogenic role by enhancing the CSC-type properties in DDP-resistant CRC via the m6A-modified pathway. The potential therapy for combating the relapse of CRC may include TRIM27 and YTHDF1, as they have been found to have significant roles in promoting CSC-type phenotypic characteristics.

Abstract Background Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease and has become a heavy economic and social burden due to its high prevalence and morbidity. The most effective strategy is that patients with DKD should be diagnosed and treated early. Preliminary studies showed that the Chinese herbal Tangshen Formula (TSF) may delay the progression of DKD, reducing microalbuminuria and macroalbuminuria and improving renal function. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of TSF in patients with DKD. Methods/design This trial is a 13-center, randomized, double-blind, placebo-controlled study. A total of 632 participants will be randomized in a 1:1 ratio to an experiment group (TSF plus losartan) and a control group (placebo plus losartan). The trial cycle will last 24 weeks. The primary outcome will be the change in the urine microalbumin–creatinine ratio from baseline to week 24. The secondary outcome will be the change in the rate of progression to the clinical proteinuria period after intervention, the rate of urine microalbumin negative conversion, the rate of normal urinary microalbumin, the doubling rate of the baseline creatinine value and the glomerular filtration rate between the two groups. Safety in medication will also be evaluated. Discussion We hypothesize that patients with type 2 diabetes in the early stage of DKD will benefit from TSF. If successful, this study will provide evidence-based recommendations for clinicians. Trial registration ClinicalTrials.gov, NCT03009864. Registered January 2017.

CoCrFeNiMn high-entropy alloy (HEA) has great potential for engineering application due to its good ductility and high fracture toughness at low temperature. It can be deposited on components as coatings to take advantage of its excellent properties and reduce the cost. In this study, CoCrFeNiMn HEA coatings were deposited on 316L stainless steel substrates by atmospheric plasma spraying (APS) technique, and a series of transient thermal shock tests were performed. It was found that the coatings contained two main phases: a face-centered cubic (FCC) solid solution phase and a flocculent oxides phase. The elemental contents of Co, Cr, Fe, and Ni were close to equal atomic percentage in the coating, while Mn was reduced significantly. The oxygen was mainly distributed in the dark flocculent oxides phase. After transient thermal shock tests, these two phases remained stable, but some tiny cracks appeared on the surface. Meanwhile, the microhardness of the coating after transient thermal shock tests also showed stable, ∼ 420 HV. Weibull statistics were used to analyze the reliability of the microhardness, and the Weibull modulus m was distributed from 9 to 15. The CoCrFeNiMn HEA coating exhibited high phase stability and excellent properties under transient thermal shock, making it have service advantages in extreme environments, especially in the fields of the development of future nuclear and aerospace structural materials.

Abstract Background Novel Muscovy duck reovirus (N-MDRV), emerged in southeast China in 2002, which can infect a wide range of waterfowl and induces clinical signs and cytopathic effects that are distinct from those of classical MDRV, and continues to cause high morbidity and 5–50% mortality in ducklings. The present study aimed to investigate the characteristics of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China. Results Two novel MDRV strains, designated as MDRV-SH12 and MDRV-DH13, were isolated from two diseased Muscovy ducklings in Guangdong province, China in June 2012 and September 2013, respectively. Sequencing of the complete genomes of these two viruses showed that they consisted of 23,418 bp and were divided into 10 segments, ranging from 1191 bp (S4) to 3959 bp (L1) in length, and all segments contained conserved sequences in the 5′ non-coding region (GCUUUU) and 3′ non-coding region (UCAUC). Pairwise sequence comparisons demonstrated that MDRV-SH12 and MDRV-DH13 showed the highest similarity with novel MDRVs. Phylogenetic analyses of the nucleotide sequences of all 10 segments revealed that MDRV-SH12 and MDRV-DH13 were clustered together with other novel waterfowl-origin reoviruses and were distinct from classical waterfowl-origin and chicken-origin reoviruses. The analyses also showed possible genetic re-assortment events in segment M2 between waterfowl-origin and chicken-origin reoviruses and the segments encoding λA, μA, μNS, σA, and σNS between classical and novel waterfowl-origin reoviruses. Potential recombination events detection in segment S2 suggests that MDRV-SH12 and MDRV-DH13 may be recombinants of classical and novel WRVs. Conclusions The results presented in this study, the full genomic data for two novel MDRV strains, will improve our understanding of the evolutionary relationships among the waterfowl-origin reoviruses circulating in China, and may aid in the development of more effective vaccines against various waterfowl-origin reoviruses.

Abstract Background Hepatitis E virus (HEV) is one of most important zoonotic viruses, and it can infect a wide range of host species. Avian HEV has been identified as the aetiological agent of big liver and spleen disease or hepatitis-splenomegaly syndrome in chickens. HEV infection is common among chicken flocks in China, and there are currently no practical measures for preventing the spread of the disease. The predominant avian HEV genotype circulating in China have been identified as genotype 3 strains, although some novel genotypes have also been identified from chicken flocks in China. Results In this study, we used a meta-transcriptomics approach to identify a new subtype of genotype 3 avian HEV in broiler chickens at a poultry farm located in Shenzhen, Guangdong Province, China. The complete genome sequence of the avian HEV, designated CaHEV-GDSZ01, is 6655-nt long, including a 5′ UTR of 24 nt and a 3′ UTR of 125 nt (excluding the poly(A) tail), and contains three open reading frames (ORFs). Sequence analysis indicated that the complete ORF1 (4599 nt/1532 aa), ORF2 (1821 nt/606 aa) and ORF3 (264 nt/87 aa) of CaHEV-GDSZ01 share the highest nucleotide sequence identity (85.8, 86.7 and 95.8%, respectively) with the corresponding ORFs of genotype 3 avian HEV. Phylogenetic analyses further demonstrated that the avian HEV identified in this study is a new subtype of genotype 3 avian HEV. Conclusions Our results demonstrate that a new subtype of genotype 3 avian HEV is endemic in Guangdong, China, and could cause high mortality in infected chickens. This study also provides full genomic data for better understanding the evolutionary relationships of avian HEV circulating in China. Altogether, the results presented in this study suggest that more attention should be paid to avian HEV and its potential disease manifestation.

Abstract Background The transcription factor PR domain containing 16 (PRDM16) is known to play a significant role in the determination and function of brown and beige fat. However, the role of PRDM16 in tumor biology has not been well addressed. Here we investigated the impact of PRDM16 on tumor growth and metastasis in lung cancer. Methods UALCAN database, immunoblotting and immunohistochemistry analysis were used to assess PRDM16 expression in lung cancer patients. Kaplan-Meier plotter database was used to analyze the overall survival of patients with lung cancer stratified by PRDM16 expression. PRDM16 overexpression and knockdown experiments were conducted to assess the effects of PRDM16 on growth and metastasis in vitro and in vivo, and its molecular mechanism was investigated in lung adenocarcinoma cells by chromatin immunoprecipitation-sequencing (ChIP-Seq), real time-quantitative PCR (RT-qPCR), luciferase assay, xenograft models and rescue experiments. Results PRDM16 was downregulated in lung adenocarcinomas, and its expression level correlated with key pathological characteristics and prognoses of lung adenocarcinoma patients. Overexpressing PRDM16 inhibited the epithelial-to-mesenchymal transition (EMT) of cancer cells both in vivo and in vitro by repressing the transcription of Mucin-4 (MUC4), one of the regulators of EMT in lung adenocarcinomas. Furthermore, deleting the PR domain from PRDM16 increased the transcriptional repression of MUC4 by exhibiting significant differences in histone modifications on its promoter. Conclusions Our findings demonstrate a critical interplay between transcriptional and epigenetic modifications during lung adenocarcinoma progression involving EMT of cancer cells and suggest that PRDM16 is a metastasis suppressor and potential therapeutic target for lung adenocarcinomas.

FAM83A (family with sequence similarity 83, member A) has been found to be highly expressed in cancers. The purpose of this study was to clarify the role and mechanism of FAM83A in lung cancers. The expression of FAM83A in lung cancer cells was enhanced by gene transfection or knocked down by small interfering RNA interference. The key proteins of the Wnt signaling pathway, the Hippo signaling pathway, and epithelial–mesenchymal transition (EMT) were examined using Western blot. The proliferation and invasion of lung cancer cells were examined using cell proliferation, colony formation, and invasion assays. The expression of FAM83A in lung cancer tissues was significantly increased and was correlated with advanced tumor–node–metastasis (TNM) stage and poor prognosis. Overexpression of FAM83A enhanced the proliferation, colony formation, and invasion of lung cancer cells. Meanwhile, FAM83A overexpression increased the expression of active β-catenin and Wnt target genes and the activity of EMT. Furthermore, in FAM83A-overexpressed cells, the activity of Hippo pathway was downregulated, whereas the expression of yes-associated protein (YAP) and its downstream targets cyclin E and CTGF were upregulated. The inhibitor of the Wnt signaling pathway, XAV-939, reversed the promoting effect of FAM83A on YAP, cyclin E, and CTGF. On knocking down the expression of FAM83A, we obtained the opposite results. However, the inhibitor of GSK3β, CHIR-99021, restored the expression of YAP, cyclin E, and CTGF after FAM83A was knocked down. FAM83A is highly expressed in lung cancers and correlated with advanced TNM stage and poor prognosis. FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process.

Abstract Background Diabetic distal symmetric polyneuropathy (DSPN) is one of the most common microvascular complications of diabetes mellitus, and it has become a major public health problem worldwide because of its high and increasing prevalence, morbidity, and disability rate. The current medications for DSPN are not entirely satisfactory. Preliminary studies indicated that the Chinese herbal TangBi Formula may alleviate signs and symptoms and improve the velocity of nerve conduction in patients with DSPN. This study was designed to determine if Chinese herbal medicine used in combination with conventional treatment is more effective than conventional treatment alone. Methods/design We are conducting a multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial as a means of assessing the therapeutic effects of traditional Chinese medicine (TCM) treatment. A total of 188 patients will be randomized in a 1:1 ratio to a treatment group (TangBi Formula plus mecobalamin) and a control group (placebo plus mecobalamin). The test period lasts 6 months, during which all of the patients will be given standard medical care as recommended by established guidelines. The primary outcome will be development of differences in changes in clinical symptoms and signs in patients and changes in Michigan Diabetic Neuropathy Score (MDNS) between the two groups before and after treatment. The secondary outcome will be changes in nerve conduction velocity and in single clinical signs and symptoms. Safety assessments and adverse events will also be evaluated. Discussion We postulate that patients with DSPN will benefit from therapy that includes TCM. If successful, this work will provide an evidence-based complementary therapeutic approach for treatment of DSPN. Trial registration ClinicalTrials.gov, NCT03010241 . Registered on 2 January 2017

Backgroud: Acupuncture is common used for Bell's palsy in clinic, however, recent systematic reviews all shows that there is no sufficient evidence to support the effectiveness of acupuncture for Bell's palsy because ofthe poor quality and heterogeneity. It's urgently necessary to develop a guideline of acupuncture for Bell's palsy based on principles of evidence-based medicine to optimize acupuncture treating, standardize outcomes evaluating and to improve the quality of acupuncture for patients with Bell's palsy under general circumstances.

Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 μM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway.

In order to clarify the succession pattern and potential functions of the microbial communities in fermented grains for Nongxiangxing baijiu, high-throughput sequencing was used to investigate the dynamic change of microbial community structure, and the correlations between microbial community structure and physicochemical indicators were analyzed at different fermentation stages. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict the potential functions of microbial communities in fermented grains. The results showed that Firmicutes, Proteobacteria, Actinobacteriota, Ascomycota, and Basidiomycota were the dominant phyla in fermented grains. The dominant genera were Lactobacillus, Bacillus, Staphylococcus, Thermoactinomyces, Kazachstania, Wickerhamomyces, Penicillium, Candida, Aspergillus, Meyerozyma, Debaryomyces, with Lactobacillus, Kazachstania and Wickerhamomyces being the absolutely dominant ones. The contents of reducing sugar and starch showed a significantly positive correlation with 8 bacterial genera (P < 0.05). Acidity and moisture content showed a significantly negative correlation with 10 bacterial genera. Some fungi were significantly correlated with physicochemical indicators. PICRUSt analysis showed that the relative abundance of functional enzymes was significantly different at different fermentation stages, and the dominant microorganisms in fermented grains participated in glycolysis, acid metabolism and ethanol synthesis to form a complete metabolic chain, indicating that the microbial community succession of fermented grains could be the major reason for the differences in metabolism at different fermentation stages. The findings of this study would provide a theoretical basis for the study of the metabolic mechanisms of microorganisms used for baijiu brewing.

This study was performed in order to understand the differences in bacterial communities and physicochemical indicators between bottom and wall pit mud for nongxiangxing baijiu. Five physicochemical indicators of pit mud were analyzed. High-throughput sequencing technology was used to investigate the bacterial communities, and correlation analysis was carried out between bacterial communities and physicochemical indicators. The results showed that the pH and catalase activity in bottom pit mud were significantly higher than those in wall pit mud (P < 0.05), while the opposite was true for ammonium nitrogen content (P < 0.05). The dominant bacterial phyla in pit mud were Firmicutes, Bacteroidetes, and Synergistetes. The dominant genera in bottom pit mud were Hydrogenispora, Caproiciproduces, Aminobacterium, and Proteiniphilum, the relative abundance of Hydrogenispora being significantly higher than that in wall pit mud (P < 0.05). The dominant genera in wall pit mud were Capriocipiroducens, Lactobacillus, Syntrophaceticus, and Aminobacterium, the relative abundance of Capriocipiroducens, Lactobacillus and Syntrophaceticus being significantly higher than that in bottom pit mud (P < 0.05). The physicochemical indicators and bacterial communities in bottom and wall pit mud were different. Among the physicochemical indicators, pH had the greatest impact on the bacterial community in bottom pit mud, and Hydrogenispora was the iconic genus of bacteria in pit bottom mud. The relative abundance of enzymes involved in acid metabolism was higher in pit wall mud. In conclusion, there were spatial differences in the bacterial communities between bottom and wall pit mud, which could have an important impact on the fermentation of baijiu.