Determination of mycobiota and aflatoxin contamination in commercial bee pollen from eight provinces and one autonomous region of China.

The co-occurrence of fungi and mycotoxins in various foods has been frequently reported in many countries, posing a serious threat to the health and safety of consumers. In this study, the mycobiota in five types of commercial bee pollen samples from China were first revealed by DNA metabarcoding. Meanwhile, the content of total aflatoxins in each sample was investigated by high-performance liquid chromatography with fluorescence detection. The results demonstrated that Cladosporium (0.16 %-89.29 %) was the most prevalent genus in bee pollen, followed by Metschnikowia (0-81.12 %), unclassified genus in the phylum Ascomycota (0-81.13 %), Kodamaea (0-73.57 %), and Penicillium (0-36.13 %). Meanwhile, none of the assayed aflatoxins were determined in the 18 batches of bee pollen samples. In addition, the fungal diversity, community composition, and trophic mode varied significantly among five groups. This study provides comprehensive information for better understanding the fungal communities and aflatoxin residues in bee pollen from different floral origins in China.

Insights into the intestinal toxicity of foodborne mycotoxins through gut microbiota: A comprehensive review.

Mycotoxins, which are fungal metabolites, pose a significant global food safety concern by extensively contaminating food and feed, thereby seriously threatening public health and economic development. Many foodborne mycotoxins exhibit potent intestinal toxicity. However, the mechanisms underlying mycotoxin-induced intestinal toxicity are diverse and complex, and effective prevention or treatment methods for this condition have not yet been established in clinical and animal husbandry practices. In recent years, there has been increasing attention to the role of gut microbiota in the occurrence and development of intestinal diseases. Hence, this review aims to provide a comprehensive summary of the intestinal toxicity mechanisms of six common foodborne mycotoxins. It also explores novel toxicity mechanisms through the "key gut microbiota-key metabolites-key targets" axis, utilizing multiomics and precision toxicology studies with a specific focus on gut microbiota. Additionally, we examine the potential beneficial effects of probiotic supplementation on mycotoxin-induced toxicity based on initial gut microbiota-mediated mycotoxicity. This review offers a systematic description of how mycotoxins impact gut microbiota, metabolites, and genes or proteins, providing valuable insights for subsequent toxicity studies of mycotoxins. Furthermore, it lays a theoretical foundation for preventing and treating intestinal toxicity caused by mycotoxins and advancing food safety practices.

Rapid and stable hydrogen detection based on Pd-modified WO3 nanosheets.

Materials with accurate and durable gas detection are essential for gas sensors. We developed a facile and effective method to deposit Pd onto WO3 nanosheets and used the samples for hydrogen gas sensing. The combination of the 2D ultrathin nanostructure of WO3 and the spillover effect of Pd enables a detection concentration down to 20 ppm of hydrogen and high selectivity against other gases including methane, butane, acetone, isopropanol, etc. Moreover, the durability of the sensing materials was testified through 50 cycles of exposure to 200 ppm of hydrogen. These outstanding performances are mainly attributed to a homogeneous and tenacious decoration of Pd on the surface of WO3 nanosheets, providing an attractive choice for practical applications.

Pretreating mesenchymal stem cells with IL-6 regulates the inflammatory response of DSS-induced ulcerative colitis in rats.

The immunomodulatory properties of mesenchymal stem cells (MSCs) have been broadly investigated in research on inflammatory diseases including ulcerative colitis. Treating MSCs with an inflammatory stimulus before transplantation is an adaptive strategy that helps MSCs survive in areas of inflammation and promotes the regulation of local immune responses. This study aimed to examine the effects of pretreating bone marrow MSCs (BMSCs) with Interleukin-6 (IL-6) on attenuation of dextran sulfate sodium (DSS)-induced ulcerative colitis in rats. Experimental ulcerative colitis was induced in Wistar rats by administering 2% DSS in their water for 7 days and normal water for the next 3 days. The experimental group received 1 × 106/0.4 ml of BMSCs that were treated with IL-6 for 24 h. Histological changes, colon length, and disease activity index were compared among groups, and the levels of TNF-α, IL-6, and IL-1ß in homogenate supernatants were evaluated using ELISA. IL-6-pretreated BMSCs significantly reduced the colonic damage score. The colon length shortened by 6.1 ± 0.14 cm for the rats that received IL-6-pretreated BMSCs, whereas the control group rats' value was 3.8 ± 0.14 cm on the 14th day. The levels of pro-inflammatory cytokines were significantly decreased in the colons of the IL-6-pretreated BMSCs group compared with those of the control group (p < 0.05). This study revealed that IL-6-pretreated BMSCs ameliorated DSS-induced colitis via local anti-inflammatory action and suggested that IL-6-pretreated BMSCs are a promising therapeutic agent for ulcerative colitis treatment.

Performance investigation of the probability-aided maximum likelihood sequence detector for a probabilistic shaped 16-QAM system.

In this paper, for the first time, a probability-aided maximum-likelihood sequence detector (PMLSD) is experimentally investigated through a 64-GBaud probabilistic shaped 16-ary quadrature amplitude modulation (PS-16QAM) transmission experiment. In order to relax the impacts of PS technology on the decision module, a PMLSD decision scheme is investigated by modifying the decision criterion of maximum-likelihood sequence detector (MLSD) correctly. Meanwhile, a symbol-wise probability-aided maximum a posteriori probability (PMAP) scheme is also demonstrated for comparison. The results show that the PMLSD scheme outperforms the direct decision scheme about 1.0-dB optical signal to noise ratio (OSNR) sensitivity. Compared with symbol-wise PMAP scheme, PMLSD scheme can effectively relax the impacts of PS technology on the decision module and a more than 0.8-dB improvement in terms of OSNR sensitivity in back-to-back (B2B) case is obtained. Finally, we successfully transmit the PS-16QAM signals over a 2400-km fiber link with a bit error ratio (BER) lower than 1.00×10-3 by adopting the PMLSD scheme.

OSI-027 inhibits the tumorigenesis of colon cancer through mediation of c-Myc/FOXO3a/PUMA axis.

Colon cancer is a gastrointestinal malignancy that is one of the leading causes of tumor-associated deaths. It has been reported that the mammalian target of rapamycin (mTOR) can lead to the progression of colon cancer. However, the mechanism by which mTOR inhibitor (OSI-027) mediates the tumorigenesis of colon cancer remains largely unknown. Cell function of colon cancer was investigated by cell counting kit-8 flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In addition, quantitative real-time polymerase chain reaction and Western blot were used to investigate the mechanism underlying the function of OSI-027 in colon cancer. OSI-027 dose-dependently reduced colon cancer cell viability by inducing cell apoptosis. In addition, OSI-027 induced the apoptosis of colon cancer cells via upregulation of PUMA. OSI-027 promoted the expression of PUMA by activation of forkhead box protein O3a (FOXO3a), and c-Myc knockdown partially increased FOXO3a and PUMA levels. Moreover, OSI-027 attenuated the tumor growth of colon cancer through the mediation of the mTOR/c-Myc/FOXO3a axis. OSI-027 attenuates colon cancer progression through the mediation of the c-Myc/FOXO3a/PUMA axis. Thereby, this study might shed new insights on exploring the strategies against colon cancer.

Investigation of the low-complexity Hilbert FIR filter enhanced 112-Gbit/s SSB 16-QAM transmission with parallelized Kramers-Kronig reception over 1440-km SSMF.

The Hilbert transform links the log-magnitude and the phase of the field modulated signals as long as the minimum phase condition is satisfied in the Kramer-Kronig (KK) receiver. In discrete-time signal processing, the Hilbert transform is generally replaced by a finite impulse response (FIR) filter to reduce the computational complexity, that is the so-called Hilbert transform FIR (HT-FIR) filter. The performance of the HT-FIR filter is extremely important, as the in-band flatness, the ripple, the group delay, the Gibbs phenomenon, and the edge effect, which indeed impair the phase retrieval. Hence, we investigate four different HT-FIR filter schemes that are in the form of type III and type IV based on the frequency-domain (FD) sampling approach and the time-domain (TD) windowing function approach. Also, we analyze the performance for each filter under different digital upsampling scenarios and conclude that a trade-off between the reduced inter-symbol-interference (ISI) and the Gibbs phenomenon is essential to obtain an optimal sampling rate and an improved KK performance when the HT-FIR filter with a short length is adopted. The results show that the FD-based HT-FIR filter can relax the upsampling requirement while having a better in-band flatness and a lower edge effect. The experiment is conducted in the parallelized block-wise KK reception-based 112-Gbit/s SSB 16-QAM optical transmission system over a 1920-km cascaded Raman fiber amplifier (RFA) link to investigate the limit transmission performance of the practical KK receiver. The experimental results show that when the transmission distance is up to 1440-km, the BER of the FD-based HT-FIR filter can be lower than the soft decision-forward error correction (SD-FEC) threshold of 2 × 10-2 with only 3 samples per symbol (3-SPS) upsampling rate and 8 non-integer tap coefficients are used, while other TD-based HT-FIR filter schemes with a BER lower than the SD-FEC threshold require at least 4-SPS upsampling rate.

Palladium hydride with high-index facets for enhanced methanol oxidation.

Nobel metal catalysts with high-index facets feature a high density of steps and kink sites, which bring about high activity but could be unstable during the electrocatalytic process. Doping with interstitial hydrogen atoms is a unique and effective way to regulate the electronic structure of the host materials. The formation of hydride also helps to stabilize the active sites on the surface of catalysts. Herein, we demonstrate the conformal doping of H atoms into the Pd nanostructure with preferential exposure of {730} facets, forming concave nanocubes of palladium hydride. Compared to the palladium counterparts, the palladium hydride catalysts show enhanced activity and stability in electrocatalytic methanol oxidation, and the structural differences between the Pd and PdH catalysts are revealed by XRD and X-ray photoelectron spectroscopy. Our work presents a powerful strategy for designing durable catalysts with high performance by combining high-index facet with interstitial atom doping.

LNK promotes the growth and metastasis of triple negative breast cancer via activating JAK/STAT3 and ERK1/2 pathway.

BACKGROUND: LNK adaptor protein is a crucial regulator of normal hematopoiesis, which down-regulates activated tyrosine kinases at the cell surface resulting in an antitumor effect. To date, little studies have examined activities of LNK in solid tumors except ovarian cancer. METHODS: Clinical tissue chips were obtained from 16 clinical patients after surgery. Western blotting assay and quantitative real time PCR was performed to measure the expression of LNK. We investigate the in vivo and vitro effect of LNK in Triple Negative Breast Cancer by using cell proliferation、migration assays and an in vivo murine xenograft model. Western blotting assay was performed to investigate the mechanism of LNK in triple negative breast cancer. RESULTS: We found that the levels of LNK expression were elevated in high grade triple-negative breast cancer through Clinical tissue chips. Remarkably, overexpression of LNK can promote breast cancer cell proliferation and migration in vivo and vitro, while silencing of LNK show the opposite phenomenon. We also found that LNK can promote breast cancer cell to proliferate and migrate via activating JAK/STAT3 and ERK1/2 pathway. CONCLUSIONS: Our results suggest that the adaptor protein LNK acts as a positive signal transduction modulator in TNBC.

Correlation between procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 and breast cancer.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), which affects collagen synthesis, is associated with breast cancer. The purpose of the study is to detect the expression of PLOD2 in breast cancer and to evaluate the correlation between PLOD2 and clinicopathologic characteristics and prognosis of patients with breast cancer. 50 paired samples including breast cancer tissues and adjacent non-tumor tissues were formalin-fixed and evaluated by immunohistochemistry. The results revealed that PLOD2 expression in breast cancer tissues was much higher than that in tissues adjacent to breast cancer. High expression of PLOD2 was positively associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.001). However, high expression of PLOD2 was negatively related to Ki-67 (P < 0.001) while positively related to progesterone receptor (PR) (P = 0.001). PLOD2 expression was positively related to the metastasis of breast cancer. Therefore, high expression of PLOD2 was identified as a poor prognostic biomarker for patients with breast cancer. These results suggest a novel molecular mechanism in breast cancer tumorigenesis, thus providing a potential therapeutic target of breast cancer.

A Novel Naphthyridine Derivative, 3u, Induces Necroptosis at Low Concentrations and Apoptosis at High Concentrations in Human Melanoma A375 Cells.

Naphthyridine derivatives are a widely-used class of heterocycles due to their pharmacological activities. A novel compound (10-Methoxy-1,2,3,4-tetrahydrobenzo(g)(1,3) diazepino(1,2-a)-(1,8)naphthyridin-6-yl)(phenyl) methanone (named 3u), showed good anticancer activity in the human malignant melanoma cell line A375 via Thiazolyl Blue Tetrazolium Bromide (MTT) assay. After Western blotting confirmed, we found that 3u induces necroptosis at low concentrations and apoptosis at high concentrations via the upregulation of death receptors and scaffold protein in A375 cells. Furthermore, by combining 3u with the caspase inhibitor zVAD-fmk or Receptor Interacting Serine/Threonine Kinase 1 (RIP1) kinase inhibitor Necrostatin-1 (Nec-1), we found that the activity of caspase-8 was the crucial factor that determined whether either apoptosis or necroptosis occurred. The results indicate that 3u should be considered as a potential chemical substance for melanoma treatment.

A microfluidic device for studying chemotaxis mechanism of bacterial cancer targeting.

Bacterial cancer targeting may become an efficacious cancer therapy, but the mechanisms underlying bacterial specificity for cancer cells need to be explored prior to adopting it as a new clinical application. To characterize the mechanism of bacterial chemotactic preference towards cancer cells, we developed a microfluidic device for in vitro study. The device consists of a cell culture chamber on both sides of a central bacteria channel, with micro-channels used as barriers between them. The device, when used as model for lung cancer, was able to provide simultaneous three-dimensional co-culture of multiple cell lines in separate culture chambers, and when used as model for bacterial chemotaxis, established constant concentration gradients of biochemical compounds in a central channel by diffusion through micro-channels. Fluorescence intensity of green fluorescence protein (GFP)-encoding bacteria was used to measure bacterial taxis behavior due to established chemotactic gradients. Using this platform, we found that Escherichia coli (E. coli) clearly illustrated the preference for lung cancer cells (NCI-H460) which was attributed to biochemical factors secreted by carcinoma cells. Furthermore, by secretome analysis and validation experiments, clusterin (CLU) was found as a key regulator for the chemotaxis of E. coli in targeting lung cancer.

Erratum to: The clinical and genetic characteristics in children with mitochondrial disease in China.

1. The post code for the fourth address in the affiliation should be 050031. 2. Three items are missing in the first row of Table 1. The correct form of the first row is as follows: 3. The second "55%" in the fourth paragraph of DISCUSSION should be 50%. 4. "MLEAS" in the sixth paragraph of DISCUSSION should be MELAS.

The clinical and genetic characteristics in children with mitochondrial disease in China.

Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing (NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases (62.5%) with mitochondrial DNA (mtDNA) mutation, and 15 cases (37.5%) with nuclear DNA (nDNA) mutation. M.3243A>G (n=7) accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1 (n=7), PDHA1 (n=2), and NDUFV1, NDUFAF6, SUCLA2, SUCLG1, RRM2B, and C12orf65, respectively.

Evaluation of a New IFN-γ Release Assay for Rapid Diagnosis of Active Tuberculosis in a High-Incidence Setting.

Blood-based interferon-gamma (IFN-γ) release assays (IGRAs) have been proven to be useful in the diagnosis of Mycobacterium tuberculosis (Mtb) infection. However, IGRAs have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. The established T-SPOT. TB assay containing Mtb-specific antigens ESAT-6 and CFP10 are widely used for immunodiagonsis of Mtb infection, but the high cost is one of the restricting factors against its clinical application in the developing countries. More recently, a cost-saving IGRA assay, TS-SPOT, was approved in China. This new assay contains an additional antigen Rv3615c. Rv3615c contains broadly recognized CD4+ and CD8+ epitopes, and T-cell responses to Rv3615c are as specific for Mtb infection as the responses to ESAT-6 and CFP10 in both Mtb-infected humans and M. bovis-infected cattle. Therefore, we assessed the likely effect of inclusion of Rv3615c as stimulus besides ESAT-6 and CFP10 in an IGRA assay and evaluated the performance of TS-SPOT for diagnosis of Mtb infection and active TB compared with T-SPOT.TB. We tested 155 active TB patients, 90 non-TB lung disease patients, and 55 healthy individuals. The results presented an improved positive rate for diagnosis of active TB and Mtb infection, that could be attributable to inclusion of Rv3615c in the mixture of stimulatory antigens. The diagnostic efficiency of TS-SPOT assay for active TB was as follows: sensitivity 80.00%, specificity 83.45%, positive predictive value (PPV) 83.78%, negative predictive value (NPV) 83.45%, positive likelihood ratio (LR+) 4.83, and negative likelihood ratio (LR-) 0.24. The results were similar to those of T-SPOT.TB, with an excellent agreement (κ = 0.91, 95% CI: 0.85-0.95) being observed between these two assays. The sensitivities of the TS-SPOT assay varied for patients with different forms of active TB, with the highest sensitivity for patients with culture-positive pulmonary TB (92.16%) and the lowest for those with tuberculosis meningitis (50.00%). Taken together, the current evidence indicates that this new TS-SPOT assay is a useful adjunct to the current tests for rapid diagnosis of active TB and Mtb infection in low-income and high-incidence settings due to its characteristics of cost-effectiveness and high-quality.

Highly sensitive detection of cancer-related genes based on complete fluorescence restoration of a molecular beacon with a functional overhang.

The accurate detection of cancer-related genes is of great significance for early diagnosis and targeted therapy of cancer. In this contribution, an automatically cycling operation of a functional overhang-containing molecular beacon (OMB)-based sensing system was proposed to perform amplification detection of the p53 gene. Contrary to the common molecular beacon (MB), a target DNA is designated to hybridize with a label-free recognition probe (RP) with a hairpin structure rather than OMB. In the presence of a target DNA of interest, the locked primer in RP opens and triggers the subsequent amplification procedures. The newly-developed OMB is not only capable of accomplishing cyclical nucleic acid strand-displacement polymerization (CNDP) with the help of polymerase and nicking endonuclease, but is also cleaved by restriction endonucleases, removing the quencher away from the fluorophore. Thus, the target DNA at an extremely low concentration is expected to generate a considerable amount of double-stranded and cleaved OMBs, and the quenched fluorescence is completely restored, leading to a dramatic increase in fluorescence intensity. Utilizing this sensing platform, the target gene can be detected down to 8.2 pM in a homogeneous way, and a linear response range of 0.01 to 150 nM could be obtained. More strikingly, the mutant genes can be easily distinguished from the wild-type ones. The proof-of-concept demonstrations reported herein are expected to promote the development of DNA biosensing systems, showing great potential in basic research and clinical diagnosis.

[Construction of an Escherichia coli strain for sensitive detection of arsenite ion in water].

In order to construct an Escherichia coli strain with high sensitivity and specificity to detect arsenic ion using fluorescence as reporter, a sensitive strain to arsenic ion was obtained by knocking out the gene arsB that acts as an arsenic efflux pump. The pET28b vector containing arsenite detecting cassette Pars-arsR-egfp was constructed and then transformed into arsB deleted mutant. Measuring conditions of this constructed whole-cell biosensor were optimized and its linear concentration range, limit of detection and specificity were determined. This modified biosensor was much more sensitive than that using wild-type strain as host. The optimal detection range of As³âº concentration was 0.013 to 42.71 µmol/L, and the limit concentration of detection was as low as 5.13 nmol/L. Thus we successfully improved the sensitivity of arsenite detecting biosensor by modification of E. coli genome, which may provide useful strategies for development and optimization of microbial sensors to detect heavy metals.

High-capacity and low-cost long-reach OFDMA PON based on distance-adaptive bandwidth allocation.

We propose and experimentally demonstrate a distance-adaptive bandwidth allocation scheme to realize high-capacity long-reach orthogonal frequency division multiple access passive optical network (OFDMA PON) with cost-effective electro-absorption modulator (EAM). In our scheme, the subcarriers in downstream OFDM signal are properly allocated to the optical network units (ONUs) with different fiber transmission lengths. By this means, the detrimental influence of power fading induced by dispersion and chirp can be avoided, thus all OFDM subcarriers can be modulated with high-order quadrature amplitude modulation (QAM) format, leading to a high transmission capacity. A proof-of-concept experiment is performed, in which three ONUs with transmission distances of 25, 50, and 100 km are assigned with different subcarriers, respectively. By using distance-adaptive bandwidth allocation technique, an OFDM signal of 34.5 Gb/s is successfully delivered to the ONUs with a bit error ratio (BER) lower than 2 × 10(-3).

Systematic analysis of gene expression pattern in has-miR-760 overexpressed resistance of the MCF-7 human breast cancer cell to doxorubicin.

BACKGROUND/AIMS: Chemoresistance of breast cancer is a growing problem and still a major clinical obstacle to successful treatment in clinical patients. miR-760 was significantly downregulated in chemoresistance breast cancer tissues compared to chemo-sensitive tissues in our previous study. However, the role of miR-760 in modulating drug resistance remains largely unexplored. In this study, we sought to determine the expression pattern of miR-760 targeted mRNAs, and explore their potential functions and participated-pathways in breast cancer drug resistance cells. RESULTS: Compared to parental cell line MCF-7, miR-760 was downregulated by 6.15 folds in MCF-7/Adr cells. The qRT-PCR result showed that compared to miR-760 negative control cells group, miR-760 was up-regulated 15.817 folds after miR-760 lentiviral transfection in miR-760 mimics group. The microarray data showed that 270 genes were dysregulated over 2-fold change in MCF-7/Adr cells after miR-760 overexpressed, including 241 up-regulated and 29 downregulated genes. GO analysis result appeared that the predicted target genes of miR-760 mainly regulated DNA binding, protein binding, molecular function, nucleic acid binding, and so on; the pathway analysis data demonstrated that these target genes mainly involved in cell cycle, TGF-beta signaling pathway, mRNA processing reactome, G protein signaling, apoptosis, Wnt signaling pathway, and other signaling pathways. There were 3 predicted target genes (RHOB, ANGOTL4, ABCA1) of miR-760 were selected at a P value<0.05 and the fold enrichment was>40. CONCLUSION: Our study explored the genes expression pattern after miR-760 overexpresssed, and confirmed 3 dominantly dysregulated genes, which could expand the insights into the miR-760 function and molecular mechanisms in drug resistance of breast cancer. This study might afford a comprehensive understanding of miR-760 as prognostic biomarkers during clinical treatment, and we supposed that the miR-760 expression levels in drug resistance carcinoma tissues could be pursued to develop new strategies for targeted therapies in chemoresistant breast cancer patients.