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Circulating tumor cells (CTCs), as important liquid biopsy target, can provide valuable information for cancer progress monitoring and individualized treatment. However, current isolation platforms incapable of balancing capture efficiency, specificity, cell viability, and gentle release have restricted the clinical applications of CTCs. Herein, inspired by the structure and functional merits of natural membrane interfaces, we established an antibody-engineered red blood cell (RBC-Ab) affinity interface on microfluidic chip for high-performance isolation and release of CTCs. The lateral fluidity, pliability, and anti-adhesion property of the RBC microfluidic interface enabled efficient CTCs capture (96.5%), high CTCs viability (96.1%), and high CTCs purity (average 4.2-log depletion of leukocytes). More importantly, selective lysis of RBCs by simply changing the salt concentration was utilized to destroy the affinity interface for efficient and gentle release of CTCs without nucleic acid contamination. Using this chip, CTCs were successfully detected in colon cancer samples with 90% sensitivity and 100% specificity (20 patients and 10 healthy individuals). After the release process, KRAS gene mutations of CTCs were identified from all the 5 cancer samples, which was consistent with the results of tissue biopsy. We expect this RBC interface strategy will inspire further biomimetic interface construction for rare cell analysis.

Immune checkpoint therapy has provided a weapon against cancer, but its response rate has been extremely low due to the lack of effective predictors. Herein, we developed a F RET strategy based on l ectin for glycan labeling and an a ptamer for PD-L1 antigen recognition for visualization of PD-L1-specific g lycosylation (FLAG). The FLAG strategy combines the PD-L1 aptamer, which efficiently labels the PD-L1 polyantigen with smaller steric hindrance than the PD-L1 antibody, and metabolism-free lectin labeling for glycosylation. As a result, the FLAG strategy enables in situ visualization of PD-L1-specific glycosylation on the tissue section while maintaining the spatial context and tissue architecture. Due to nonmetabolic labeling, the FLAG strategy revealed that the tissue level of PD-L1-specific glycosylation is correlated with the efficacy of PD-1/PD-L1 therapy. Overall, the FLAG strategy provides a powerful tool for revealing the significance of PD-L1 glycosylation, offering the unprecedented potential for immunophenotypic differential analysis to predict the immunotherapy response.

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. It has been shown that microRNAs (miRNAs) exert a significant influence in the pathogenesis of PCOS; however, the relationship between miRNA, PCOS, and GC apoptosis is not entirely understood.MethodsTo clarify the effect of miR-194 in PCOS, CCK-8, Ki67 staining, AO/EB, and flow cytometry assays were used to assess cell growth, proliferation, and apoptosis in KGN cells, which were artificially stimulated to overexpress miR-194. Luciferase reporter assays and rescue experiments were used to elucidate the mechanism underlying miR-194 in PCOS.ResultsmiR-194 expression was significantly up-regulated in rat models of PCOS and the ovarian GCs of PCOS patients. miR-194 suppression promoted KGN cell growth and proliferation. miR-194 overexpression also induced cell apoptosis, while miR-194 downregulation had an opposite effect. Furthermore, up-regulating heparin-binding EGF-like growth factor (HB-EGF) expression rescued the pro-apoptotic effects of miR-194 upregulation on KGN cells.ConclusionsmiR-194 is increased in PCOS granulosa cell and may function as a novel biomarker and therapeutic target for KGN cells via HB-EGF regulation.

The on-farm deployment of genetically modified crops may negatively affect nontarget arthropods, potentially disrupting food web structure and ecosystem functions. Aphid-parasitoid interactions are well-suited to study these potential impacts in agro-ecosystems. Over the span of 8 years, we systematically compared infestation levels of the aphid Aphis gossypii, its associated parasitoid community and overall parasitism rate between transgenic Cry1Ac + CpTI cotton and nontransgenic cotton. Furthermore, we measured the impact of transgenic Cry1Ac + CpTI cotton on structural traits and interspecies interactions within quantitative aphid-parasitoid food webs.Transgenic Cry1Ac + CpTI cotton did not affect the abundance of aphids and parasitoids, or in-field parasitism rates. Despite weak interannual variability, transgenic Cry1Ac + CpTI cotton also did not alter food web architecture or biological control services.Our work not only elucidates the impact of transgenic Cry1Ac + CpTI cotton on different nontarget arthropods (i.e. aphids, parasitoids, hyperparasitoids) and their associated ecosystem services or disservices, but also diversifies the ecological risk assessment toolbox for transgenic insecticidal crops. © 2021 Society of Chemical Industry.

We aim to identify a panel of differentially methylated regions (DMRs) for predicting survival outcomes for patients with CRC from the TCGA (n = 393). Four DMRs (MUC12, TBX20, CHN2, and B3GNT7) were selected as candidate prognostic markers for CRC. The prediction potential of selected DMRs was validated by the targeted bisulfite sequencing method in an independent cohort with 251 Chinese CRC patients. DMR methylation scores (DMSs) were constructed to evaluate the prognosis of CRC. Results of the validation cohort confirmed that higher DMSs were associated with poor overall survival (OS) of CRC, with hazard ratio (HR) value ranged from 1.445 to 2.698 in multivariable Cox models. Patients in the high prognostic index (high-PI) group showed a markedly unfavorable prognosis compared to the low-PI group in both TCGA discovery cohort (HR = 3.508, 95%CI: 2.196-5.604, P < 0.001) and independent validation cohort (HR = 1.912, 95%CI: 1.258-2.907, P = 0.002).

The first corona-pandemic, coronavirus disease 2019 (COVID-19) caused a huge health crisis and incalculable damage worldwide. Knowledge of how to cure the disease is urgently needed. Emerging immune escaping mutants of the virus suggested that it may be potentially persistent in human society as a regular health threat as the flu virus. Therefore, it is imperative to identify appropriate biomarkers to indicate pathological and physiological states, and more importantly, clinic outcomes. Proteins are the performers of life functions, and their abundance and modification status can directly reflect the immune status. Protein glycosylation serves a great impact in modulating protein function. The use of both unmodified and glycosylated proteins as biomarkers has also been proved feasible in the studies of SARS, Zika virus, influenza, etc. In recent years, mass spectrometry-based glycoproteomics, as well as proteomics approaches, advanced significantly due to the evolution of mass spectrometry. We focus on the current development of the mass spectrometry-based strategy for COVID-19 biomarkers' investigation. Potential application of glycoproteomics approaches and challenges in biomarkers identification are also discussed.

Spartina alterniflora has become one of the top exotic invasive plants in coastal China. Accurate and timely mapping of coastal wetlands is critical to understand the spatiotemporal dynamics of S. ...

Background Evidence suggests a potential relationship between gut microbiota and chronic postoperative pain (CPP). This study aimed to explore the predictive and preventive potential of preoperative gut microbiota in CPP in breast cancer survivors. Methods In the clinical experiments, we designed a nested case-control study to compared preoperative gut microbiota of breast cancer survivors with and without CPP using 16s rRNA sequencing. The primary outcome was clinically meaningful pain in or around the operative area 3 months after surgery. Logistic prediction models based on previously identified risk factors for CPP in breast cancer survivors were tested with and without differential bacteria to evaluate the model's potential for improvement with the addition of gut microbiota information. In the animal experiments, preoperative fecal microbiota was transplanted from patients with and without CPP to mice, and a spared nerve injury (SNI) model was used to mimic neuropathic pain in CPP. Mechanical hyperalgesia and the expression of markers of spinal microglia and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed. Results Sixty-six CPP patients and 66 matched controls were analyzed. Preoperative gut microbiota composition was significantly different in the 2 groups at phylus, family, and genera levels. The discrimination of the clinical prediction model (determined by area under the receiver operating characteristic curve) improved by 0.039 and 0.099 after the involvement of differential gut microbiota at the family and genus levels, respectively. After fecal microbiota transplantation (FMT), "CPP microbiota" recipient mice exhibited significantly increased mechanical hyperalgesia and decreased expression of Ppar-γ and arginase-1 (Arg-1) in the spinal cord. Conclusions Preoperative gut microbiota has the potential to predict and prevent the development of CPP and plays a causal role in its development via the PPAR-γ-microglia pathway in the spinal cord. Thus, it could be targeted to develop a prevention strategy for CPP in breast cancer survivors.

Medicago ruthenica (L.) Ledeb. has received considerable attention due to its value for forage production and ecological restoration in northern China. Gene expression profiles of interesting genes may provide accurate and reliable results for biological function research, in addition to mRNA, including microRNA (miRNA) as a key element that participates in various biological functions. Quantitative real-time polymerase chain reaction (RT-qPCR) is a useful method that has been widely used in gene expression analysis of mRNA and miRNA, and the selection of consistently stable reference genes is essential to normalize RT-qPCR data under different experimental conditions. In this study, the expression stability of nine candidate reference genes was evaluated with DeltaCt, Bestkeeper, NormFinder, geNorm and RefFinder methods. The expression stability of reference genes varied under different experimental conditions. Overall, EF-1α as much more stably reference gene in different subsets recommended for normalization. The relative expression levels of GN4 and miR156f were analyzed to test the reliability of the optimal reference genes. The results suggested that the best stable reference genes can be simultaneously utilized in the normalization of both mRNA and miRNA expression by RT-qPCR analysis, which may facilitate genetic studies of this leguminous plant.

Non-bovine milk is an underappreciated type of milk with geographical characteristics of production, consumption and nutrition. Although the structure similarity of microbial community from the different types of non-bovine milk are very different, the composition of microbial community, especially those belonging to pathogenic bacteria or lactic acid bacteria in non-bovine milk, may be more diverse than that of cow milk. Microbial community analysis based on high-throughput sequencing coupled with microbial annotation on species level, environmental factors of milk producing areas, and milk nutritional composition is considered to be very necessary strategy in future research of non-bovine milk. This review provides a reference for evaluating food safety and nutrition of non-bovine milk and dairy products.

Background aims Mesenchymal stromal cells and immunosuppressive factor IL-37 can both suppress concanavalin A (Con A)-induced hepatitis in mice. Endometrial regenerative cells (ERCs), novel types of mesenchymal-like stromal cells, possess powerful immunomodulatory effects and are effective in treating various diseases. The aim of this study was to explore the effects of ERCs in suppressing Con A-induced hepatitis and determine whether IL-37 overexpression could enhance the therapeutic effect of ERCs in this process. Methods ERCs were extracted from the menstrual blood of healthy female volunteer donors. The IL-37 gene was transferred into ERCs, and the expression of IL-37 in cells was detected by western blot and enzyme-linked immunosorbent assay. Hepatitis was induced by Con A in C57BL/6 mice that were randomly divided into groups treated with phosphate-buffered saline, ERCs, IL-37 or ERCs transfected with the IL-37 gene (IL-37-ERCs). Cell tracking, liver function, histopathological and immunohistological changes, immune cell proportions and levels of cytokines were measured 24 h after Con A administration. Results Compared with ERC or IL-37 treatment, IL-37-ERCs further reduced levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and improved histopathological changes in the liver. In addition, IL-37-ERC treatment further reduced the proportions of M1 macrophages and CD4+ T cells and increased the proportion of regulatory T cells. Moreover, IL-37-ERC treatment resulted in lower levels of IL-12 and interferon gamma, and higher level of transforming growth factor beta. Conclusions The results of this study suggest that ERCs can effectively alleviate Con A-induced hepatitis. Furthermore, IL-37 overexpression can significantly enhance the therapeutic efficacy of ERCs by augmenting the immunomodulatory and anti-inflammatory properties of ERCs. This study may provide a promising strategy for treatment of T-cell-dependent hepatitis.

Inflammation is a defense mechanism associated with a wide range of diseases. Celastrol is a small molecule isolated from traditional Chinese medicine with potent anti-inflammation activity. In this study, we established an integrated quantitative proteomics strategy to investigate the acute response to celastrol treatment in a rat macrophage cell line challenged with lipopolysaccharide (LPS). Both stable-isotopic based non-targeted quantitative profiling and PRM-based targeted quantitation methods were employed. Dimethyl-labeling based non-targeted profiling revealed 28 and 52 proteins that significantly up- and down-regulated by celastrol. Bioinformatics analysis pinpoint key signaling pathways affected. Seven proteins were selected for examining their time-dependent regulatory pattern in response to celastrol using targeted PRM quantitation. The abundance of mRNA at multiple time-points of selected proteins was also examined. Celastrol induced an acute response of selected key transcriptional factors in terms of mRNA or protein abundance within one hour. Interestingly, regulatory trend of mRNA and protein abundance suggested a novel dual mechanism of celastrol in the terms of acute anti-inflammation. The integrated quantitative proteomic strategy established in this study constitutes an efficient workflow to characterize key components and their time-dependent regulatory pattern for monitoring drug response.

Background: Despite the better prognosis given by surgical resection and chemotherapy in low-grade glioma (LGG), progressive transformation is still a huge concern. In this case, the S100A gene family, being capable of regulating inflammatory responses, can promote tumor development. Methods: The analysis was carried out via ONCOMINE, GEPIA, cBioPortal, String, GeneMANIA, WebGestalt, LinkedOmics, TIMER, CGGA, R 4.0.2 and immunohistochemistry. Results: S100A2, S100A6, S100A10, S100A11, and S100A16 were up-regulated and S100A1 and S100A13 were down-regulated in LGG compared to normal tissues. S100A3, S100A4, S100A8, and S100A9 expression was up-regulated during the progression of glioma grade. In addition, genetic variation of the S100A family was high in LGG, and the S100A family genes mostly function through IL-17 signaling pathway, S100 binding protein, and inflammatory responses. The TIMER database also revealed a relationship between gene expression and immune cell infiltration. High expression of S100A2, S100A3, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, S100A13, and S100A16 was significantly associated with poor prognosis in LGG patients. S100A family genes S100A2, S100A3, S100A6, S100A10, and S100A11 may be prognosis-related genes in LGG, and were significantly associated with IDH mutation and 1p19q codeletion. The immunohistochemical staining results also confirmed that S100A2, S100A3, S100A6, S100A10, and S100A11 expression was upregulated in LGG. Conclusion: The S100A family plays a vital role in LGG pathogenesis, presumably facilitating LGG progression via modulating inflammatory state and immune cell infiltration.

Coexisting species may experience population and range changes alone or jointly in response to environmental change. Here, we used six climate variables and ten modeling algorithms to predict the distribution of two Takydromus species (T. septentrionalis and T. sexlineatus) in China. We identified the sympatric and allopatric areas by comparing projections between the two species based on habitat suitability under present and future climate scenarios. We constructed the hypervolumes of six climate variables for the two species and then evaluated overlaps between hypervolumes. From this study, we know the following. First, minimum temperature of coldest month contributes the most to the prediction of habitat suitability. Second, habitats suitable for the two species will shift northward in response to climate warming. Third, the range of T. sexlineatus will expand across the four future time intervals before 2,100, namely the 2021–2040, 2041–2060, 2061–2080, and 2081–2100 intervals, under both Shared socioeconomic pathway (SSP) 245 and SSP585 scenarios, and the range of T. septentrionalis will also expand in the future except at the 2081–2100 interval under the SSP585 scenario. Fourth, the sympatric areas will contract or expand under the SSP245 scenario and expand across the four future time intervals before 2,100 under the SSP585 scenario. Fifth, the niche hypervolumes of the two species partially overlapped, and the differences in niche centroid show some degree of niche differentiation between the two species. These results allow to conclude that climate warming will not only drive the northward drift of sympatric areas but also increase the size of these areas if nothing is done to limit the emission of greenhouse gases. Given the existence of hybridization and introgression between T. septentrionalis and T. sexlineatus in the field where they coexist, we also conclude that climate warming will increase chances of hybridization and introgression between the two species.

Antibiotic resistance genes (ARGs) as emergence contaminations have spread widely in the water environment. Wild fish may be recipients and communicators of ARGs in the water environment, however, the distribution and transmission of ARGs in the wild fish and relevant water environment were rarely reported. Here, we have profiled ARGs and bacterial communities in wild freshwater fish and relevant water in a peri-urban river using high-throughput qPCR and 16S rRNA gene sequence. A total of 80 and 220 unique ARG subtypes were identified in fish and water samples. Fish and water both showed significant ARG seasonal variations (P0.05). The highest absolute abundance of ARGs in fish and water occurred in summer (1.32 × 10

Cerebroprotein hydrolysate‐I (CH‐I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH‐I on brain senescence via JAK2/STAT3 pathway. The results showed that CH‐I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence‐positive cells induced by D‐galactose. In vivo, CH‐I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH‐I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH‐I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH‐I in delaying aging., Cerebroprotein hydrolysate‐I prevent D‐gal induced senescence of PC12 cells Cerebroprotein hydrolysate‐I prevent hippocampal senescence in mice induced by D‐gal Cerebroprotein hydrolysate‐I regulate telomerase by JAK2/STAT3 pathway to delay senescence ​

To explore genetic diversity and estimate the genetic differences among populations of Lutraria maxima in the coastal waters off south to southeast China, the morphology of the species of five different geographical populations (Beihai, Weizhou Island, Zhanjiang, Xiamen, and Fuzhou) in Guangxi, Guangdong, and Fujian provinces was studied statistically in combination with the microsatellite markers. As revealed by morphological principal component analysis (PCA), the cumulative contribution rate of the first three principal components was 72.596%. The discrimination accuracy ranged from 47.5% to 80.0%, and the scatter plots of principal component and discriminant analysis were consistent in overall, showing that the Xiamen and Fuzhou populations were overlapped obviously. For microsatellite markers, 10 pairs of polymorphic primers were obtained by high-throughput transcriptome sequencing, and used for genetic diversity analysis. It was showed that the average number of alleles and effective alleles observed in each population ranged from 8.100 to 10.900, and from 3.497 to 4.228, respectively. The average observed heterozygosity (Ho) and expected heterozygosity (He) in the five populations ranged from 0.541 to 0.615, and from 0.642 to 0.733, respectively. The genetic distance (DA) ranged from 0.078 to 0.523, and the population genetic differentiation index (FST) ranged from 0.027 to 0.139. The unweighted pair-population method with arithmetic means (UPGMA) and structure analysis showed that the five populations could be divided into two main clusters, the Beibu Gulf group (Beihai and Weizhou Island) and the Southeast China Sea group (Zhanjiang, Xiamen, and Fuzhou), suggesting that L. maxima has been separated geographically by the barrier of the Leizhou Peninsula into two groups in evolution, which provided us with a scientific clue to better protect the bioresource and establish an appropriate fishery management stocks for L. maxima populations in south China.

Abnormal DNA methylation is considered a vital hallmark to regulate gene expression and influence the development and progression of colorectal cancer (CRC). Although CRC-related methylation prognostic models have been developed, their clinical application is limited due to the lack of external validation and extension to other survival evaluation indicators. Therefore, this study aimed to develop and validate novel methylation prognostic models correlated with different survival indicators for individualized prognosis prediction for CRC patients. The prognostic-related CpG sites of methylation-driven genes screened by the MethylMix algorithm were identified and validated in The Cancer Genome Atlas (TCGA) CRC methylation data and our methylation data. The prognostic models correlated with different survival evaluation indicators (overall survival [OS] and disease-free survival [DFS]) were developed and validated in the TCGA CRC dataset (N = 376) and our independent CRC dataset (N = 227). We utilized the combination of selected 3-CpG methylation sites in three genes (DAPP1, FAM3D, and PIGR) to construct a prognostic risk-score model. In the training dataset, Kaplan-Meier survival analysis demonstrated that high-risk patients had significantly poorer survival than low-risk patients (pOS = .0014; pDFS

In this study, we aimed to develop B. subtilis spore coat protein A (CotA) for the enzymatic determination of bilirubin. Firstly, molecular docking and oxidation kinetic analysis confirmed the feasibility of CotA for oxidizing bilirubin. Secondly, CotA showed pH-preferable oxidization performance to direct bilirubin (DB) in acidic conditions and an alkaline-catalytic oxidation capacity to total bilirubin (TB). Mechanism analysis results confirm that the conformational changes of CotA, DB and UB caused by pH changes are responsible for the selective oxidation of DB and TB by CotA. Then, CotA exhibits better structural characteristics and enzymatic performance than M. verrucaria-derived bilirubin oxidase (Mv-BOD). Besides, the strong anti-interference ability helps CotA adapt to complex catalytic environment in the detection of DB and TB. Our results prove that CotA can be used as a promising candidate bio-enzymatic detection reagent for DB and TB.

Abuse of antibiotics in aquaculture have been alarming and might aggravate spread of resistance genes in the environment. Holistic ARGs proliferation checks require deeper analyses of coupled absolute abundances in 16S rRNA bacteria communities at the phylum level to detect biomarkers. Sulfanilamide (sul) and copper II sulfate (CuSO4 II) were, therefore, designed and added as separate or combined treatments in 9 replicate engineered goldfish tanks comprising 3 individual sul, 3 CuSO4 II, 3 (sul + CuSO4 II) combinations, and 3 controls within 180 days. The DNA from water and fish guts was sequenced under qPCR to determine 16S rRNA bacteria biomarkers co-occurring with the correspondent ARGs. Combined chemical addition at 0.8–1.5 mg sul + 0.5–1.0 mg CuSO4 II/3 L of tank waters reduced sequenced 16S rRNA bacteria absolute abundances in fish gut and water samples while portraying the biomarkers. Absolute abundances of the entire 16S rRNA bacteria was higher in fish guts (3.4 × 1014–4.9 × 108 copies/g) than water samples (1.5 × 109–2.6 × 1015 copies/L), respectively. Much as sul 1(log) were dominant over intl 1(log) genes, and their fundamental profiles were also higher in the fish guts than water samples; the Spearman’s correlation analyses revealed positive relationship (p Proteobacteria (10–50:15–65%) > Planktomycetes (10–52:8–25%) featured prominently based on LEfSe use as the hot-spotted biomarkers, hence justifying its higher prospects towards innovative environmental microbiological and biotechnological studies.

Background Short Tandem repeats (STRs) existed as popular elements in both eukaryotic and prokaryotic genomes. Results In this study, we analyzed the characteristics, distributions, and motif features of STRs within whole-genomes of 140 plant species. The results showed that STR density was negatively correlated with the genome size. Hexanucleotide repeat was the most abundant type of STRs. The distribution of algae shows a preference different from that of other plants. By analyzing GC contents of STRs and genome, it was concluded that STR motif was influenced by GC contents. Analysis of the long STRs in genome (length ≥ 1000 bp) found that dicots have the more long STRs. For STR types, di- and tri-nucleotide accounted for the highest proportion. Analyzing and designing long STRs in CDS (length ≥ 500 bp) was to verify the role of long STRs in Gossypium hirsutum TM-1 and Solanum tuberosum. By comparing the long STRs found in Fragaria x ananassa with other species, some evolutionary characteristics of the long STRs were obtained. Conclusions We got the characteristics, distribution, and motif features of STRs in the whole genome of 140 plants and obtained some evolutionary characteristics of long STRs. The study provides useful insights into STR preference, characteristics, and distribution in plants. How to cite: Zhu L, Wu H, Li H, et al., Short Tandem Repeats in plants: genomic distribution and function prediction. Electron J Biotechnol 2021;50. https://doi.org/10.1016/j.ejbt.2020.12.003

The complete chloroplast genome sequence of rare and endangered Camellia pubipetala Y. Wan & S. Z. Huang (Theaceae) was mentioned in this research. By studying comparatively, we found that the C. pubipetala Y. Wan & S. Z. Huang chloroplast genome was 156,993 bp in length and composed of 86,590 bp LSC, 18,211 bp SSC, and two reverse repeating regions with 26,090 bp. The whole GC content was 37.33%. The genome encoded 116 functional genes, including 80 protein-coding genes, 32 tRNA genes, and 4 rRNA genes. In order to find the phylogenetic relationship of C. pubipetala Y. Wan & S. Z. Huang within Camellia genus, we reconstructed phylogenetic tree. The results indicate that C. pubipetala Y. Wan & S. Z. Huang was closely related to Camellia huana voucher and Camellia ptilosperma.

Triclosan (TCS) is a ubiquitous antimicrobial used in many daily consumer products. It has been reported to induce endocrine disrupting effects at low doses in mammals, disturbing sex hormone function and thyroid function. The hypothalamus plays a crucial role in the maintenance of neuroendocrine function and energy homeostasis. We speculated that the adverse effects of TCS might be related to the disturbance of metabolic processes in hypothalamus. The present study aimed at investigating the effects of TCS exposure on the protein and metabolite profiles in hypothalamus of mice. Male C57BL/6 mice were orally exposed to TCS at the dosage of 10 mg/kg/d for 13 weeks. The hypothalamus was isolated and processed for mass spectrometry (MS)-based proteomics and metabolomics analyses. The results showed that a 10.6% decrease (P = 0.066) in body weight gain was observed in the TCS exposure group compared with vehicle control group. Differential analysis defined 52 proteins and 57 metabolites that delineated TCS exposed mice from vehicle controls. Among the differential features, multiple proteins and metabolites were found to play vital roles in neuronal signaling and function. Bioinformatics analysis revealed that these differentially expressed proteins and metabolites were involved in four major biological processes, including glucose metabolism, purine metabolism, neurotransmitter release, and neural plasticity, suggesting the disturbance of homeostasis in energy metabolism, mitochondria function, neurotransmitter system, and neuronal function. Our results may provide insights into the neurotoxicity of TCS and extend our understanding of the biological effects induced by TCS exposure.

The majority of tissue-specific environmental quality standards (EQSs) considering metal tolerance are prior to the chemical-specific EQSs in aquatic organisms. However, metal baseline levels in marine organisms were very scarce. We explored the correlation between Hg, Cd, Pb, Cu, and Zn concentrations in water or sediments and those metal concentrations in marine organisms (crustacean, mollusc, and fish) by generalized additive models (GAMs) and executed a meta-analysis of Hg, Cd, Pb, Cu, and Zn contents in those three organisms by implementing cumulative frequency distribution analysis of individual metal distribution in a heavy metal-contaminated semi-enclosed Bay, China. Results showed that the average contents of Hg, Cd, Pb, Cu, and Zn were 0.042±0.01, 0.38±0.22, 1.72±0.65, 3.61±1.01, and 16.08±6.33 μg/L in water; 0.064±0.02, 0.42±0.04, 20.54±7.76, 28.97±3.90, and 96.74±35.11 μg/g dw in sediment; and 0.0049±0.0028, 0.52±0.28, 0.24±0.15, 11.05±6.95, and 21.12±4.47 μg/g dw in crustacean, 0.015±0.0087, 0.24±0.17, 0.08±0.02, 0.37±0.35, and 10.62±6.79 μg/g dw in mollusc; and 0.0038±0.0028, 0.065±0.05, 0.32±0.19, 2.01±0.59, and 16.04±4.97 μg/g dw in fish. The mercury content in mollusc presented a negative correlation with mercury content in sediment, while the content of other metals (Cd, Pb, Cu, and Zn) in organisms showed positive correlations with the content of those metals in water or sediment. We further obtained tissue-baseline-C5% in crustacean, mollusc, and fish which were 1.191, 3.341, and 0.014 μg/g dw for Cu; 0.013, 0.072, and 0.033 μg/g dw for Cd, 0.015, 0.027, and 0.052 μg/g dw for Pb; 9.515, 14.422, and 0.056 μg/g dw for Zn; and 0.0009, 0.004, and 0.0035 μg/g dw for Hg, respectively. However, there were no obvious relationships of the 4d-NOEC in laboratory toxicity tests with C5%, as well as C50% and 4d-LC50 or tolerance index a for Cu, Cd, Pb, Zn, and Hg in organisms. Our results pointed out the controversy of laboratory sensitive species toxicity results for deriving chemical-specific EQSs with field studies. We advocated to set up the metal concentration baselines in aquatic organisms and further served the tissue-specific EQSs, which are essential basis for geochemical recordings, bio-monitoring, and semi-enclosed bay management in the world.

HOX transcript antisense intergenic RNA (HOTAIR) is a lncRNA with a length of 2,158 nucleotides and its two terminal domains could combine with different complexes to function at the level of transcription and translation. It overexpresses in many cancers including gastric cancer. HOTAIR could play an oncogenic role in the initiation and progression of gastric cancer through interaction with microRNAs, such as miR-330/618/126 in the PI3K/Akt signaling pathways. HOTAIR single nucleotide polymorphisms (SNPs) may have genotype-function and allele-specific effect on gastric cancer by a mechanism that specific SNP could give rise to a variation of HOTAIR and alter the binding site of microRNAs. Both rs920778 T allele and rs4759314 G allele will enhance the susceptibility to gastric cancer in the Chinese populations. In a word, the suppression of HOTAIR and overexpression of downstream microRNAs may be potential therapeutic strategies of gastric cancer related to HOTAIR.

Gastric cancer (GC) is a common malignant tumor, which has a high incidence and fatality. Therefore, it is important to clarify the molecular mechanism of the occurrence and development for GC and to find more effective treatments and targeted drugs. In this study, we found that the kinase suppressor of Ras1 (KSR1) was increased in GC tissues and cell lines. Silencing of KSR1 inhibited the proliferation, migration and invasion of MKN-45 cells. E3 ligase Praja2 was downregulated in GC tissues and cell lines. In addition, praja2 promoted ubiquitylation of KSR1, but inhibited MEK-ERK signal pathways. Functional analysis indicated overexpression of praja2 inhibited the proliferation, migration and invasion of MKN-45 cells, while MG132 or FGF2 treatment removed the inhibitory effects of praja2 on GC progression. In vivo tumorigenesis experiments indicated praja2 inhibited tumor growth via KSR1-MEK-ERK axis. In conclusion, praja2 promoted the ubiquitylation and degradation of KSR1, which disturbed MEK- ERK signaling and inhibited GC progression. Our study might provide a novel target for GC clinical treatment.

As a highly dynamic organelle, mitochondria undergo constant fission and fusion to change their morphology and function, coping with various stress conditions. Loss of the balance between fission and fusion leads to impaired mitochondria function, which plays a critical role in the pathogenesis of Parkinson disease (PD). Yet the mechanisms behind mitochondria dynamics regulation remain to be fully illustrated. Chaperone-mediated autophagy (CMA) is a lysosome-dependent process that selectively degrades proteins to maintain cellular proteostasis. In this study, we demonstrated that MARCHF5, an E3 ubiquitin ligase required for mitochondria fission, is a CMA substrate. MARCHF5 interacted with key CMA regulators and was degraded by lysosomes. Severe oxidative stress compromised CMA activity and stabilized MARCHF5, which facilitated DNM1L translocation and led to excessive fission. Increase of CMA activity promoted MARCHF5 turnover, attenuated DNM1L translocation, and reduced mitochondria fragmentation, which alleviated mitochondrial dysfunction under oxidative stress. Furthermore, we showed that conditional expression of LAMP2A, the key CMA regulator, in dopaminergic (DA) neurons helped maintain mitochondria morphology and protected DA neuronal viability in a rodent PD model. Our work uncovers a critical role of CMA in maintaining proper mitochondria dynamics, and loss of this regulatory control may occur in PD and underlie its pathogenic process. Abbreviations: CMA: chaperone-mediated autophagy; DA: dopaminergic; DNM1L: dynamin 1 like; FCCP: carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; HSPA8: heat shock protein family A (Hsp70) member 8; LAMP2A: lysosomal associated membrane protein 2A; MARCHF5: membrane-associated ring-CH-type finger 5; MMP: mitochondria membrane potential; OCR: oxygen consumption rate; 6-OHDA: 6-hydroxydopamine; PD: Parkinson disease; SNc: substantia nigra pars compacta; TEM: transmission electron microscopy; TH: tyrosine hydroxylase; TMRE: tetramethylrhodamine ethyl ester perchlorate; WT: wild type.

Arenaviruses are a large family of enveloped negative-strand RNA viruses that include several causative agents of severe hemorrhagic fevers. Currently, there are no FDA-licensed drugs to treat arenavirus infection except for the off-labeled use of ribavirin. Here, we performed antiviral drug screening against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) using an FDA-approved drug library. Five drug candidates were identified, including mycophenolic acid, benidipine hydrochloride, clofazimine, dabrafenib, and apatinib, for having strong anti-LCMV effects. Further analysis indicated that benidipine hydrochloride inhibited LCMV membrane fusion, and an adaptive mutation on the LCMV glycoprotein D414 site was found to antagonize the anti-LCMV activity of benidipine hydrochloride. Mycophenolic acid inhibited LCMV replication by depleting GTP production. We also found mycophenolic acid, clofazimine, dabrafenib, and apatinib can inhibit the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Owing to their FDA-approved status, these drug candidates can potentially be used rapidly in the clinical treatment of arenavirus and SARS-CoV-2 infection.

BACKGROUND: Due to adipose-derived stem cells (ASCs) being easy to obtain, their rapid proliferation rate, and their multidirectional differentiation capabilities, they have been widely used in the field of regenerative medicine. With the progress of decellularized adipose tissue (DAT) and adipose tissue engineering research, the role of DAT in promoting angiogenesis has gradually been emphasized. METHODS: We examined the biological characteristics and biosafety of DAT and evaluated the stem cell maintenance ability and promotion of growth factor secretion through conducting in vitro and in vivo studies. RESULTS: The tested ASCs showed high rat:es of proliferation and adhered well to DAT. The expression levels of essential genes for cell stem maintenance, including OCT4, SOX2, and Nanog were low at 2–24 h and much higher at 48 and 96 h. The Adipogenic expression level of markers for ASCs proliferation including PPARγ, C/EPBα, and LPL increased from 2 to 96 h. Co-culture of ASCs and DAT increased the secretion of local growth factors, such as VEGF, PDGF-bb, bFGF, HGF, EGF, and FDGF-bb, and secretion gradually increased from 0 to 48 h. A model of full-thickness skin defects on the back of nude mice was established, and the co-culture of ASCs and DAT showed the best in vivo treatment effect. CONCLUSION: The application of DAT promotes wound healing, and DAT combined with ASCs may be a promising material in adipose tissue engineering and regenerative medicine.

Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu-San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu-San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.

The conservation and management of rain and water in a city environment are a crucial aspect of sustainability. Sponge cities are a solution for the remediation of excessive water consumption, high pollution, and rainstorm waterlogging in urban areas. Perennial ryegrass (Lolium perenne L.) is a common species and promising bioremediation plant for the construction of sponge cities. It could be useful to purify high nitrogen and phosphorus content in wastewater runoff, but its response to high total nitrogen (TN) and total phosphorus (TP) levels has not been studied. The present study aimed to evaluate the effects of high TN + TP level on seed germination, plant growth, antioxidant response, and assimilation rate of N and P in perennial ryegrass. Compared with the control, treatments with 20 mg/L N + 4 mg/L P (20N4P) significantly decreased germination potential at day 3, but the germination rate at day 10 was similar between all treatments and the control, suggesting that a high TN + TP concentration might delay germination, but not prevent it. Treatment with 20N4P also induced significant withering and decreased shoot length, root length, and dry shoot weight of ryegrass seedlings, compared with the control. Treatments with 80N16P significantly decreased levels of chlorophyll a (Chl-a) and chlorophyll b (Chl-b), demonstrating inhibition of photosynthesis. Compared with the control, treatment with 40N8P increased the carotenoid (Car), malondialdehyde (MDA), and glutathione (GSH) content, which might alleviate oxidative stress induced by high TN + TP concentration. Moreover, high levels of TN + TP (160N32P and 320N64P) significantly reduced the removal capacity of N and P by plants. Overall, the present results provide a theoretical foundation for the development of ryegrass for bioremediation of wastewater during construction of sponge cities.

The Cadmium (Cd)-polluted soils are is an increasing concern worldwide. Phytoextraction of Cd pollutants by high biomass plants, such as sweet sorghum, is considered an environmentally-friendly, cost-effective and sustainable strategy for remediating this problem. Nitrogen (N) is a macronutrient essential for plant growth, development and stress resistance. Nevertheless, how nitrate, as an important form of N, affects Cd uptake, translocation and accumulation in sweet sorghum is still unclear. In the present study, a series of nitrate levels (N1, 0.5 mm; N2, 2 mm; N3, 4 mm; N4, 8 mm and N5, 16 mm) with or without added 5 μm CdCl2 treatment in sweet sorghum was investigated hydroponically. The results indicate that Cd accumulation in the aboveground parts of sweet sorghum was enhanced by optimum nitrate supply, resulting from both increased dry weight and Cd concentration. Although root-to-shoot Cd translocation was not enhanced by increased nitrate, some Cd was transferred from cell walls to vacuoles in leaves. Intriguingly, expression levels of Cd uptake and transport genes, SbNramp1, SbNramp5 and SbHMA3, were not closely related to increased Cd as affected by nitrate supply. The expression of SbNRT1.1B in relation to nitrate transport showed an inverted 'U' shape with increasing nitrate levels under Cd stress, which was in agreement with trends in Cd concentration changes in aboveground tissues. Based on the aforementioned results, nitrate might regulate Cd uptake and accumulation through expression of SbNRT1.1B rather than SbNramp1, SbNramp5 or SbHMA3, the well-documented genes related to Cd uptake and transport in sweet sorghum.

Two halophilic archaeal strains, C90T and YPL13T, were isolated from a salt lake and a salt mine in PR China. The two strains were found to form two clusters (97.5 and 89.5 % similarity between them, respectively) separating them from the three current members of the genus Natronomonas (95.4–97.0 % and 86.6–89.3 % similarity, respectively) on the basis of the 16S rRNA and rpoB′ gene sequence similarities and phylogenetic analysis. Diverse phenotypic characteristics differentiate strains C90T and YPL13T from current Natronomonas members. The polar lipids of strain C90T were phosphatidic acid, phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), phosphatidylglycerol sulphate, two unidentified glycolipids, a major glycolipid and a minor glycolipid, while those of strain YPL13T were PG, PGP-Me, two unidentified phospholipids and a glycolipid. The average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH) values between the two strains were 79.8 and 27.1 %, respectively, which were much lower than the threshold values proposed as a species boundaries (ANI 95–96 % and isDDH 70 %), which revealed that the two strains represent two novel species; these values (ANI 76.6–80.0 % and isDDH 21.6–27.0 %) of the strains examined in this study and the current members of Natronomonas are much lower than the recommended threshold values, suggesting that strains C90T and YPL13T represent two genomically different species of Natronomonas . These results showed that strains C90T (=CGMCC 1.13738T=JCM 32961T) and YPL13T (=CGMCC 1.13884T=JCM 31111T) represent two novel species of Natronomonas , for which the names Natronomonas halophila sp. nov. and Natronomonas salina sp. nov. are proposed.

Numerous studies have implicated changes in the Y chromosome in male cancers, yet few have investigated the biological importance of Y chromosome noncoding RNA. Here we identify a group of Y chromosome–expressed long noncoding RNA (lncRNA) that are involved in male non–small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive male NSCLC cell lines demonstrated a dose-dependent induction of linc-SPRY3-2/3/4 following irradiation, which was not observed in radioresistant male NSCLC cell lines. Cytogenetics revealed the loss of chromosome Y (LOY) in the radioresistant male NSCLC cell lines. Gain- and loss-of-function experiments indicated that linc-SPRY3-2/3/4 transcripts affect cell viability and apoptosis. Computational prediction of RNA binding proteins (RBP) motifs and UV-cross-linking and immunoprecipitation (CLIP) assays identified IGF2BP3, an RBP involved in mRNA stability, as a binding partner for linc-SPRY3-2/3/4 RNA. The presence of linc-SPRY3-2/3/4 reduced the half-life of known IGF2BP3 binding mRNA, such as the antiapoptotic HMGA2 mRNA, as well as the oncogenic c-MYC mRNA. Assessment of Y chromosome in NSCLC tissue microarrays and expression of linc-SPRY3-2/3/4 in NSCLC RNA-seq and microarray data revealed a negative correlation between the loss of the Y chromosome or linc-SPRY3-2/3/4 and overall survival. Thus, linc-SPRY3-2/3/4 expression and LOY could represent an important marker of radiotherapy in NSCLC.Significance:This study describes previously unknown Y chromosome–expressed lncRNA regulators of radiation response in male NSCLC and show a correlation between loss of chromosome Y and radioresistance.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus causing severe disease and mortality. MERS-CoV infection failed to elicit robust IFN response, suggesting that the virus might have evolved strategies to evade host innate immune surveillance. In this study, we identified and characterized type I IFN antagonism of MERS-CoV open reading frame (ORF) 8b accessory protein. ORF8b was abundantly expressed in MERS-CoV–infected Huh-7 cells. When ectopically expressed, ORF8b inhibited IRF3-mediated IFN-β expression induced by Sendai virus and poly(I:C). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKε and chaperone protein HSP70, which is required for the activation of IKKε and IRF3. An infection study using recombinant wild-type and ORF8b-deficient MERS-CoV further confirmed the suppressive role of ORF8b in type I IFN induction and its disruption of the colocalization of HSP70 with IKKε. Ectopic expression of HSP70 relieved suppression of IFN-β expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-β induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKε activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKε for interaction with HSP70.

Bromodomain (BRD)-containing proteins are a class of epigenetic readers with unique recognition for N-acetyl-lysine in histones and functions of gene transcription and chromatin modification, known to be critical in various cancers. However, little is known about the roles of distinct BRD-containing protein genes in hepatocellular carcinoma (HCC). Most recently, we investigated the transcriptional and survival data of BRD1, BRD2, BRD3, BRD4, BRD7, BRD8, BRD9 in HCC patients through ONCOMINE, UALCAN, Human Protein Atlas, GEPIA, cBioPortal, STRING, TIMER databases. BRD1/2/3/4/7/8/9 were over-expressed in HCC and were significantly associated with clinical cancer stages and pathological tumor grades. High mRNA expressions of BRD4/8/9 were promising candidate biomarkers in HCC patients. The rate of sequence alternations in BRD1/2/3/4/7/8/9 was relatively high (52%) in HCC patients, and the genetic alternations were correlated with shorter overall survival and disease-free survival in HCC patients. Additionally, the mRNA expression levels of individual BRD genes were significantly positively associated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. And the associations between BRD1/2/3/4/7/8/9 and diverse immune marker sets showed a significance. Overall, these results indicated that BRD4/8/9 could be potential prognostic markers and druggable epigenetic targets in HCC patients.

This study aimed to characterize the expression status and potentially mechanistic involvement of SNHG7 in pituitary adenoma. Relative expression of SNHG7 and miR-449a was analyzed by real-time PCR. Cell viability was measured with Cell Counting Kit-8 (CCK-8). Cell apoptosis was determined by PI/Annexin V double staining followed by flow cytometry analysis. Cell invasion and migration were analyzed by wound healing and transwell assays, respectively. The regulatory action of miR-449a on SNHG7 was interrogated by luciferase reporter assay. We also investigated the pro-tumor activity of SNHG7 with the MMQ xenograft tumor mouse model. We identified the aberrant up-regulation of SNHG7 in pituitary adenoma both in vivo and in vitro, which associated with poor survival outcome. siRNA-mediated SNHG7-knockdown decreased cell viability, increased apoptosis and compromised migration and invasion. We further predicted and validated that SNHG7 negatively regulated miR-449a via sponging. Concurrent inhibition of miR-449a restored cell viability, apoptosis, migration and invasion influenced by SNHG7-deficiency. Most importantly, we demonstrated that SNHG7-silencing delayed xenograft tumor progression, which was accompanied with increased miR-449a and decreased Ki67 intensity. Our study highlighted the essential oncogenic properties of the SNHG7/miR-449a axis in pituitary adenoma.

Elevated postprandial triacylglycerols (TAG) are an important risk factor for cardiovascular disease. Men have higher plasma TAG and impaired TAG clearance compared to women, which may contribute to sex differences in risk of cardiovascular disease. Understanding mechanisms of sex differences in TAG metabolism may yield novel therapeutic targets to prevent cardiovascular disease. Cholesteryl ester transfer protein (CETP) is a lipid shuttling protein known for its effects on high‐density lipoprotein (HDL) cholesterol levels. Although mice lack CETP, we previously demonstrated that transgenic CETP expression in female mice alters TAG metabolism. The impact of CETP on TAG metabolism in males, however, is not well understood. Here, we demonstrate that CETP expression increases plasma TAG in males, especially in very‐low density lipoprotein (VLDL), by impairing postprandial plasma TAG clearance compared to wild‐type (WT) males. Gonadal hormones were required for CETP to impair TAG clearance, suggesting a role for sex hormones for this effect. Testosterone replacement in the setting of gonadectomy was sufficient to restore the effect of CETP on TAG. Lastly, liver androgen receptor (AR) was required for CETP to increase plasma TAG. Thus, expression of CETP in males raises plasma TAG by impairing TAG clearance via testosterone signaling to AR. Further understanding of how CETP and androgen signaling impair TAG clearance may lead to novel approaches to reduce TAG and mitigate risk of cardiovascular disease.

Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8+ T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms., Tocilizumab has been used to treat the excessive inflammatory responses in COVID-19 patients. Here, the authors use single-cell RNA sequencing results from two severe COIVD-19 patients to provide high-dimensional immune profiling data, and to implicate potential cellular and molecular insights for the therapeutic effects of tocilizumab.

Medium- and long-chain triacylglycerols (MLCTs) were synthesized from rapeseed oil (RO), one kind of commonly used edible long-chain triacylglycerols (TGs), and then delivered to high-fat diet (HFD)-induced obese rats. Compared with RO, MLCT consumption exhibited more potent effects on reducing body and tissue weight gains, plasma TG, and total cholesterol (TC) levels and on improving hepatic TG, TC, fatty acid synthase, acetyl-CoA carboxylase, and lipoprteinlipase contents. Meanwhile, lower amounts of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1, and endotoxin in plasma, lower levels of interleukin-6 and TNF-α, and higher levels of interleukin-10 in both livers and white adipose tissues were detected in MLCT-fed rats. MLCT intake also remarkably suppressed the size of adipocytes and the number of macrophages. In conclusion, our study suggested that the interesterified MLCT was more efficacious in improving the lipid metabolism and inflammation in HFD-induced obese rats than RO.

The sensory impacts of two thiols, 2-methyl-3-furanthiol (MFT) and 2-furfurylthiol (FFT), in Chinese soy sauce aroma-type Baijiu (SSB), strong aroma-type Baijiu (STB), and light aroma-type Baijiu (LTB) (liquor) were evaluated and combined with partial least squares discriminant analysis (PLS-DA) to differentiate Chinese Baijiu. The flavor dilution factors of these two thiols ranged from 81 to 6561, and quantitative results showed that MFT and FFT were significantly more abundant (p 0.05) in SSB. Notably, hierarchical cluster analysis and PLS-DA results revealed that these compounds can be used to differentiate Chinese LTB, STB, and SSB. According to their prominent organoleptic and distinguishing roles, these two thiols can be regarded as flavor markers for SSB.

Background Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions. Case presentation In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.1522C > T (p.Arg508Trp) in exon 9 of the HLCS gene, which generates an increased Km value for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of the HLCS gene is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation, c.638_642delAACAC (p.His213Profs*4), in the BTD gene is also identified. Conclusions The Chinese proband carries the reported Arg508Trp variant, the novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15), which expands the mutational spectrum of the HLCS gene, and the novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4), which expands the mutational spectrum of the BTD gene. Furthermore, reversible hearing damage is rarely reported in patients with HLCS deficiency, which deserves further discussion.

Sanguisorba officinalis L. (family Rosaceae, subfamily Rosoideae) is a plant found throughout Southern Europe, Northern Africa, and Eastern Asia. This study demonstrated the antibacterial activity of a purified polyphenolic extract (PPE) from S. officinalis L. against Bacillus subtilis using growth inhibitory and apoptosis assays, and investigated the antibacterial mechanism responsible for changes in cell membrane properties. Fourier transform infrared spectroscopy suggested that PPE altered the cell wall and membrane properties of B. subtilis. Further determination of cell membrane integrity and permeability revealed that B. subtilis membrane integrity was more severely damaged by PPE at the minimum inhibitory concentration (MIC) than at the minimum bactericidal concentrati on (MBC). Instead, PPE at the MBC reduced cell membrane fluidity by significantly decreasing the proportion of anteiso- and iso-branched phospholipid fatty acids (PLFAs) from 64.17 ± 0.28% and 27.23 ± 0.03% in the control to 5.57 ± 1.06% and 6.00 ± 1.40%, respectively (P

Background The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages. Methods MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund’s Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis. Results MOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1β, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages. Conclusion MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.

Background Glutaric acidemia type II (GA II) or multiple acyl-CoA dehydrogenase deficiency (MADD, OMIM 231680) is an inherited autosomal recessive disease affecting fatty acid, amino acid and choline metabolism, due to mutations in one of three genes namely, electron transfer flavoprotein alpha-subunit, ETFA, electron transfer flavoprotein β-subunit, ETFB and electron transfer flavoprotein dehydrogenase, ETFDH. Currently, few studies have reported genetic profiling of neonatal-onset GA II. This study aimed to identify the genetic mutations in a Chinese family with GA II. Case presentation We reported a case of GA II with purulent meningitis and septicemia and identified a novel ETFDH gene mutation in a female infant. The patient developed an episode of hypoglycemia and hypotonicity on the postnatal first day. Laboratory investigations revealed elevations of multiple acylcarnitines indicating glutaric acidemia type II in newborn screening analysis. Urinary organic acids were evaluated for the confirmation and revealed a high glutaric acid excretion. Genetic analysis revealed two mutations in the ETFDH gene (c.623_626 del / c. 1399G > C), which were considered to be the etiology for the disease. The novel mutation c.623_626 del was identified in the proband infant and her father, her mother was carriers of the mutation c.1399G > C. Conclusions A novel variant (c.623_626 del) and a previously reported missense (c.1399G > C) in the ETFDH gene have been identified in the family. The two variants of ETFDH gene identified probably underlie the pathogenesis of Glutaric acidemia type II in this family, and also enlarge ETFDH genotype-phenotype correlations spectrum.

Aberrant DNA methylation could regulate the expression of tumor suppressor gene DLEC1 and oncogene PBX3 and was related to the occurrence and prognosis of gastric cancer (GC). In this study, the associations between DLEC1 and PBX3 promoter methylation in peripheral blood leukocytes (PBLs) and the risk and prognosis of GC were investigated. The methylation status of DLEC1 and PBX3 promoter in PBLs of 368 GC cases and 382 controls was detected by the methylation-sensitive high-resolution melting (MS-HRM) method. Logistic and Cox regression were adopted to analyze the associations of DLEC1 and PBX3 methylation with GC risk and prognosis, respectively. Confounding biases were controlled by propensity score (PS). Compared with negative methylation (Nm), DLEC1-positive methylation (Pm) was associated with increased GC risk in PS (OR 2.083, 95% CI 1.220–3.558, P = 0.007), but PBX3 Pm was not associated with GC risk. In the elderly group (≥ 60 years), DLEC1 Pm was associated with increased GC risk (OR 2.951, 95% CI 1.426–6.104, P = 0.004). The combined effects between DLEC1 methylation and consumption of dairy products, fried food intake and Helicobacter pylori (H. pylori) infection on GC risk were discovered (ORc 3.461, 95% CI 1.847–6.486, P