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Sulforaphane, a naturally specialized metabolite, plays significant roles in human disease prevention and plant defense. Myrosinase (MY) is a key gene responsible for the catalysis of sulforaphane formation, but the molecular mechanisms through which MY regulates sulforaphane biosynthesis in plants remains largely unknown. Here, we discovered that the change of sulforaphane content in broccoli sprouts caused by exogenous selenite treatments is positively related to BoMY expression. BoMY overexpression in the Arabidopsis thaliana tgg1 mutants could dramatically increase myrosinase activity and sulforaphane content in the rosette leaves of 35S::BoMY/tgg1 and rescue its phenotypes. Moreover, an obvious increase of myrosinase activity and sulforaphane content was displayed in transgenic BoMY-overexpressed broccoli lines. In addition, a 2 033 bp promoter fragment of BoMY was isolated. Yeast one-hybrid (Y1H) library screening experiment uncovered that one bHLH transcription factor, BoFAMA, could directly bind to BoMY promoter to activate its expression, which was further evidenced by Y1H assay and dual-luciferase reporter assay. BoFAMA is a selenite-responsive transcription factor that is highly expressed in broccoli leaves; its protein is solely localized to nucleus. Additionally, genetic evidence suggested that the knockdown of FAMA gene in Arabidopsis thaliana could significantly decrease sulforaphane yield by inhibiting the expression of myrosinase genes. Interestingly, exogenous selenite supply could partially restore the low level of sulforaphane content in transgenic Arabidopsis FAMA-silencing plants. Our findings uncover a novel function of FAMA-MY module in the regulation of selenite-mediated sulforaphane synthesis and provide a new insights into the molecular mechanism by which selenite regulates the accumulation of sulforaphane in plants.

IntroductionThe quality of traditional Chinese medicine is based on the content of their secondary metabolites, which vary with habitat adaptation and ecological factors. This study focuses on Lonicera japonica Flos (LJF), a key traditional herbal medicine, and aims to evaluate how ecological factors impact its quality.MethodsWe developed a new evaluation method combining high-performance liquid chromatography (HPLC) fingerprinting technology and MaxEnt models to assess the effects of ecological factors on LJF quality. The MaxEnt model was used to predict suitable habitats for current and future scenarios, while HPLC was employed to analyze the contents of key compounds. We also used ArcGIS for spatial analysis to create a quality zoning map.ResultsThe analysis identified 21 common chromatographic peaks, with significant variations in the contents of Hyperoside, Rutin, Chlorogenic acid, Cynaroside, and Isochlorogenic acid A across different habitats. Key environmental variables influencing LJF distribution were identified, including temperature, precipitation, and elevation. The current suitable habitats primarily include regions south of the Yangtze River. Under future climate scenarios, suitable areas are expected to shift, with notable expansions in southern Gansu, southeastern Tibet, and southern Liaoning. The spatial distribution maps revealed that high-quality LJF is predominantly found in central and southern Hebei, northern Henan, central Shandong, central Sichuan, southern Guangdong, and Taiwan.DiscussionThe study indicates that suitable growth areas can promote the accumulation of certain secondary metabolites in plants, as the accumulation of these metabolites varies. The results underscore the necessity of optimizing quality based on cultivation practices. The integration of HPLC fingerprinting technology and the MaxEnt model provides valuable insights for the conservation and cultivation of herbal resources, offering a new perspective on evaluating the impact of ecological factors on the quality of traditional Chinese medicines.

IntroductionThe incorporation of Staphylococcus xylosus in sausage production is hypothesized to affect various physicochemical properties and flavor profiles of sausages. This study aimed to evaluate the simulation of these features in a sausage model and establish its applicability for in vitro studies.MethodsBoth a control and an experimental model, inclusive of Staphylococcus xylosus, were assessed for changes in physicochemical indexes (pH and water activity, Aw) and the concentration of flavoring components (esters and aldehydes). Thiobarbituric acid reactive substances (TBARS) values were also measured to evaluate lipid oxidation.ResultsThe introduction of Staphylococcus xylosus resulted in no significant changes in pH and Aw between the sausage and the model. However, there was a considerable increase in the content of volatile flavor compounds, specifically esters and aldehydes, in the experimental groups compared to the control. Additionally, the TBARS values in experimental groups were significantly lower than those in the control group at the end of the testing period.DiscussionThe findings indicate that Staphylococcus xylosus plays a critical role in enhancing the flavor profile of sausages through the increased synthesis of volatile compounds and inhibiting fat oxidation. The sausage model effectively simulated the physicochemical and flavor index responses, demonstrating its potential utility for further in vitro research on sausage fermentation and preservation techniques.

Bioaerosols are biologically originated particles in the atmosphere, which is mainly composed of bacteria, fungi, viruses, pollen, spores, and the fragmentation and disintegration of plants and animals. Bioaerosols are easy to be spread in the lower atmosphere and cause various epidemic diseases, which is harmful to human health. The forecasting and alert of bioaerosols have important scientific significance and reality needs. In this paper, a method is proposed for estimating and predicting the concentration profile of atmospheric bioaerosols using fluorescence lidar observational data. Using the powerful nonlinear prediction ability of artificial neural networks and through repeated training, a mathematical model can be established for the relationship among atmospheric environment, meteorological parameters, and bioaerosol concentration profiles. The input parameters are temperature and humidity, aerosol extinction coefficient, backscatter coefficient, PM2.5, PM10, SO2, NO2, CO, O3, and wind speed, and outputs the concentration profile of bioaerosols. The prediction results with the measurement relative deviation of genetic algorithm back propagation (GA-BP) neural network and adaptive genetic algorithm back propagation (AGA-BP) neural network were analyzed. The results indicate that the AGA-BP neural network can effectively predict the concentration distribution of bioaerosols, and the predicted concentrations of bioaerosols are 1793 particles × m−3, 3088 particles × m−3, 5261 particles × m−3, 7410 particles × m−3 and 9133 particles × m−3 for air quality with superior, fine, mild contamination, middle level pollution and heavy pollution at an altitude of 0.315 km, respectively. We found that the predicted concentration of pollution weather is much higher than that of good weather. Furthermore, the AGA-BP neural network was used to predict the concentration profiles of atmospheric bioaerosols under different weather conditions, which provided a new research method for forecasting and alert of atmospheric bioaerosols.

The current study aimed to explore the combined and individual effects of vitamin D (VitD) status in three trimesters during pregnancy and cord blood (CB) on child growth trajectories from birth to 4 years of age. Pregnant women (n = 1100) were recruited between 2013 and 2016 in the Shanghai Birth Cohort (SBC) Study. A total of 959 mother–child dyads were included. VitD status was measured by LC-MS/MS at three trimesters (T1, T2, T3) and CB. Children’s weight, length/height, and head circumference were assessed at birth, 42 days, 6, 12, 24 months, and 4 years of age, and standardized into z-scores [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HCZ) and weight-for-length z-score (WLZ)]. Using the group-based trajectory model (GBTM), the trajectories of the four growth parameters were categorized into discrete groups. The generalized estimating equation (GEE) was employed to analyze the mixed effect of 25(OH)D throughout pregnancy on growth trajectories. The association between 25(OH)D status and each growth trajectory group was examined by multivariable logistic regression. Each 10 ng/mL increase in 25(OH) throughout three trimesters was not associated with four anthropometric parameters. Each 10 ng/mL increase in VitD in T3 was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.75; 95% CI: 0.62, 0.91; p < 0.01). Each 10 ng/mL increase in VitD in CB was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.57; 95% CI: 0.43, 0.76; p < 0.01). No significant association was found between maternal or CB VitD and LAZ or HCZ. Three trimesters’ VitD throughout pregnancy had no persistent effect on the offspring’s growth trajectory. However, higher VitD status in the third trimester and CB related to a lower risk of high-increasing WAZ from birth to 4 years of age. Elevated VitD levels in late pregnancy and cord blood may protect against continuous early-life weight growth at high levels.

The variation of tropospheric nitrogen dioxide (NO2) vertical column densities (VCDs) indirectly reflects the difference in pollution emissions from industrial production and transportation. Accurately analyzing its pollution sources and driving factors plays an important role in energy conservation, emission reduction, and air pollution reduction. NO2 concentration products of Sentinel-5P (Sentinel-5 Precursor) TROPOMI (TROPOspheric Monitoring Instrument) from 2019 to 2021 and Aura OMI (Ozone Monitoring Instrument) from 2009 to 2021, combined with China’s main energy consumption, the growth value of the industry, Gross Domestic Product (GDP), and other data were used to analyze the influencing factors of NO2 variations. Firstly, NO2 tropospheric vertical column densities (NO2 TVCDs) of China increased by 14.72% and 3.26% in 2021 and 2020 compared with the 2019. The secondary and tertiary industry and the national energy consumption increased synchronously, which was highly related to the increase in NO2 TVCDs. Secondly, the impact of COVID-19 (coronavirus disease 2019) on China’s industrial production and residents was mainly concentrated in the first quarter of 2020, which leading to a decline in the annual average NO2 concentration in densely populated areas in 2020 compared to the same period in 2019. The industrial production scale and production capacity has gradually recovered since April 2020, and the NO2 concentration has gradually reached or exceeded the level of the same period of 2019. Finally, atmospheric pollution prevention and control measures played a positive role in the decline of NO2 of China.

Utilizing a sausage model and principal component analysis (PCA), a strain of Lactobacillus plantarum that significantly improved the flavor substance of sausage was selected. It was added to the sausage, and the pH, Aw, color, peroxide value (POV), thiobarbituric acid (TBARS), and volatile flavor substances of Sichuan sausage production were measured at 0, 1, 3, 7 and 14 d, using the uninoculated group as control. A partial least squares discriminant analysis model (PLS-DA) was applied to evaluate the characteristic flavor substances in sausages with VIP (variable important in projection) > 1 and P < 0.05 as screening conditions. Results showed that, the pH of control and Lactobacillus plantarum-fermented sausages declined and then gradually rose with fermentation time. The Aw reduced dramatically, the POV and TBARS increased significantly, while there was no significant change in color (P>0.05). And the pH, Aw, POV and TBARS values were significantly lower in Lactobacillus plantarum inoculated sausages compared to the control group. In comparison to the control group, the sausages inoculated with Lactobacillus plantarum had significantly higher concentrations of alcohols, ketones, and esters, as well as significantly enhanced the concentrations of characteristic flavor substances (isovaleric acid, 3-hydroxy-2-butanone, phenylethylaldehyde and phenylethanol). In summary, Lactobacillus plantarum M-25 selected by the sausage model was effective in enhancing the quality and flavor characteristics of sausages.

Abstract Two lactic acid bacteria (LAB) strains were screened in traditional Sichuan sausage, and their nitrite‐reducing performance in different production processes was determined in this study. LAB were isolated from traditional Sichuan sausages and identified by 16S rDNA sequencing. The effects of the isolated bacteria on the bacterial community, physicochemical properties, and nitrite‐decreasing capacity during sausage fermentation were investigated by comparing nonactivated treatment and activated treatment at 30°C. The results showed that the screened two LAB strains were identified as Pediococcus pentosaceus and Leuconostoc mesenteroides, which adapted well to the new habitat of fermented sausage, reaching a maximum of 7.00 and 7.32 lg CFU g−1 in the nonactivated treatment, 7.65 and 7.52 lg CFU g−1 in the activated treatment, and the two strains had strong acidizing potential, which could inhibit the growth of saprophytic bacteria. Otherwise, the activated treatment was better than the traditional process for nitrite degradation and fermentation time, except for color. Both strains contribute to nitrite consumption while reducing fermentation time and sausage production cycles. In conclusion, these two strains are expected to be the starting point for the improvement of biological safety and nitrite residue control in traditional Sichuan sausage production.

Saccharomyces cerevisiae (S. cerevisiae) and Kluyveromyces marxianus (K. marxianus) are often used as fermenters in yogurt and alcohol, and have been less studied within meat products. The yeasts were added to sauce meat, and the uninoculated group served as a control in this study to examine and compare the changing patterns of physicochemical and flavor characteristics of S. cerevisiae and K. marxianus on sauce meat during storage. The changes in moisture content, aw, pH, thiobarbituric acid reactive substances (TBARS), and other flavor characteristics were measured in sauce meat during the first, second, fourth, and sixth months after production. The following factors were examined: moisture content, aw, pH, TBARS, peroxide value (POV), acid value (AV), soluble protein (SP), free amino acid (FAA), and volatile flavoring compounds. With VIP > 1 and p < 0.05 as the screening conditions, the partial least squares model (PLS-DA) was used to assess the distinctive flavor components in the sausages. The findings demonstrated that the three groups’ changes in sauce meat were comparable during the first two months of storage but differed significantly between the 4th and 6th months. The moisture content, water activity, and pH of the sauce meat decreased gradually with the storage time; TBARS, AV, and FAA increased significantly; SP decreased significantly from 2.61 to 1.72, while POV increased to 0.03 and then decreased to 0.02. The POV and TBARS values of the yeast-infected meat were substantially lower than those of the control group, and the POV and TBARS values of the meat inoculated with S. cerevisiae were particularly decreased (p < 0.05). The POV and TBARS values of SC (S. cerevisiae group) decreased by 49.09% and 40.15%, respectively, compared to CK (the control group) at the time of storage until June. The experimental group (KM: K. marxianus group) significantly increased the SP and FAA values of the sauce meat (p < 0.05) by 32.4% and 29.84% compared to the CK group, respectively. Esters and olefins as well as alcohols and esters were much greater in meat that had been supplemented with S. cerevisiae and K. marxianus than in meat from the control group. In conclusion, inoculating sauce meat with S. cerevisiae can significantly enhance the quality and flavor of sauce meat while it is being stored.

Bohai Sea (BHS) is a semi-enclosed shallow continental sea in China that has suffered from the deteriorative hydrodynamic environment due to large-scale reclamation. Single-factor simulations of tidal dynamic and material transport under the influence of the coastline changes from 1999 to 2019 in BHS were carried out. The model results showed that the amplitude of M2 tide increased slightly in Liaodong Bay and Bohai Bay, but decreased obviously in Laizhou Bay along with larger reclamation. The amplitude variation of the semi-diurnal constituents (M2, S2) was greater than the diurnal ones (K1, O1). The basin residence time in Liaodong Bay and Laizhou Bay increased by 5.44% and 49.44% from 1999 to 2019, respectively. Runoff of the Huanghe River can shorten the residence time of Laizhou bay while only having little effect on Bohai Bay and Liaodong Bay. The study of the Bohai Sea evolution can provide recommendations for subsequent marine ecological restoration efforts and serve as a reference for the study of other large semi-enclosed bays.

Background: There is increasing evidence that long non-coding RNAs (lncRNAs) can be used as potential prognostic factors for cancer. This study aimed to develop a prognostic model for lung adenocarcinoma (LUAD) using angiogenesis-related long non-coding RNAs (lncRNAs) as potential prognostic factors.Methods: Transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify aberrantly expressed angiogenesis-related lncRNAs in LUAD. A prognostic signature was constructed using differential expression analysis, overlap analysis, Pearson correlation analysis, and Cox regression analysis. The model’s validity was assessed using K-M and ROC curves, and independent external validation was performed in the GSE30219 dataset. Prognostic lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks were identified. Immune cell infiltration and mutational characteristics were also analyzed. The expression of four human angiogenesis-associated lncRNAs was quantified using quantitative real-time PCR (qRT-PCR) gene arrays.Results: A total of 26 aberrantly expressed angiogenesis-related lncRNAs in LUAD were identified, and a Cox risk model based on LINC00857, RBPMS-AS1, SYNPR-AS1, and LINC00460 was constructed, which may be an independent prognostic predictor for LUAD. The low-risk group had a significant better prognosis and was associated with a higher abundance of resting immune cells and a lower expression of immune checkpoint molecules. Moreover, 105 ceRNA mechanisms were predicted based on the four prognostic lncRNAs. qRT-PCR results showed that LINC00857, SYNPR-AS1, and LINC00460 were significantly highly expressed in tumor tissues, while RBPMS-AS1 was highly expressed in paracancerous tissues.Conclusion: The four angiogenesis-related lncRNAs identified in this study could serve as a promising prognostic biomarker for LUAD patients.

BackgroundExtensive malignant-appearing calcifications have traditionally been considered a contraindication for breast-conserving surgery. The evaluation of calcifications largely depends on mammography, which is limited by tissue superimposition and is unable to reveal spatial information about extensive calcifications. Three-dimensional imaging modality is needed to reveal the architecture of extensive calcifications. In the present study, a novel cone-beam breast CT-guided surface location technique was investigated to facilitate breast-conserving surgery in breast cancer patients with extensive malignant breast calcifications.MethodsBiopsy-proved early breast cancer patients with extensive malignant-appearing breast calcifications were included. A patient will be considered suitable for breast-conserving surgery if the spatial segmental distribution of calcifications is found by 3D images of cone-beam breast CT. Then, the margins of the calcifications were located in contrast-enhanced cone-beam breast CT images. Next, skin markers were located using radiopaque materials, and cone-beam breast CT was reperformed to confirm the accuracy of surface location. During breast-conserving surgery, lumpectomy was performed according to the previous surface location, and an intraoperative specimen x-ray was applied to double-check that the entire lesion was removed. Margin assessment was made for both intraoperative frozen section and postoperative pathology examination.ResultsFrom May 2019 to Jun 2022, 11 eligible breast cancer patients in our institution were included. Breast-conserving surgery was performed successfully in all patients using the surface location approach mentioned before. All patients achieved negative margins and satisfied cosmetic results.ConclusionThis study proved the feasibility of cone-beam breast CT-guided surface location for facilitating breast-conserving surgery in breast cancer patients with extensive malignant breast calcifications.

Summary: The SARS-CoV-2 variants B.1.617.1 (Kappa) contain multiple mutations in the spike protein. However, the effect of B.1.617.1 lineage-related mutants on viral infectivity and inactivated-virus vaccine efficacy remains to be defined. We therefore constructed 12 B.1.617.1-related pseudoviruses and systematically studied the effects of mutations on virus infectivity and neutralization resistance to convalescent and inactivated virus vaccine sera. Our results show that the B.1.617.1 variant exhibited both higher infectivity and neutralization resistance in sera at 1 or 3 months after vaccination of 28 individuals and at 14 and 200 days after discharge of 15 convalescents. Notably, 89% of vaccines and 100% of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against one single mutation: E484Q. Besides, we found a significant decrease in neutralizing activity in convalescent patients and BBIBP-CorV vaccines for B.1.1.529. These findings demonstrate that inactivated-virus vaccination or convalescent sera showed reduced, but still significant, neutralization against the B.1.617.1 variant.

Abstract Background Previous studies have indicated that quantitative MRI (qMR) is beneficial for diagnosis of breast cancer. As a novel qMR technology, synthetic MRI (syMRI) may be advantageous by offering simultaneous generation of T1 and T2 mapping in one scan within a few minutes and without concern to the deposition of the gadolinium contrast agent in cell nucleus. In this study, the potential of quantitative mapping derived from Synthetic MRI (SyMRI) to diagnose breast cancer was investigated. Methods From April 2018 to May 2019, a total of 87 patients with suspicious breast lesions underwent both conventional and SyMRI before treatment. The quantitative metrics derived from SyMRI, including T1 and T2 values, were measured in breast lesions. The diagnostic performance of SyMRI was evaluated with unpaired Student’s t-tests, receiver operating characteristic curve analysis and multivariate logistic regression analysis. The AUCs of quantitative values were compared using Delong test. Results Among 77 patients who met the inclusion criteria, 48 were diagnosed with histopathological confirmed breast cancers, and the rest had benign lesions. The breast cancers showed significantly higher T1 (1611.61 ± 215.88 ms) values and lower T2 (80.93 ± 7.51 ms) values than benign lesions. The area under the ROC curve (AUC) values were 0.931 (95% CI: 0.874–0.989) and 0.883 (95% CI: 0.810–0.956) for T1 and T2 maps, respectively, in diagnostic discrimination between breast cancers and benign lesions. A slightly increased AUC of 0.978 (95% CI: 0.915–0.993) was achieved by combining those two relaxation-based quantitative metrics. Conclusion In conclusion, our preliminary study showed that the quantitative T1 and T2 values obtained by SyMRI could distinguish effectively between benign and malignant breast lesions, and T1 relaxation time showed the highest diagnostic efficiency. Furthermore, combining the two quantitative relaxation metrics further improved their diagnostic performance.

Objective The high resolution mass spectra database of common alkaloids were established and applied to the automatic screening of poisoning samples. Methods The accurate molecular mass and appropriate collision energy of each alkaloid was obtained by injecting alkaloid standard solutions into the Q exactive mass spectrometry directly or separated by high performance liquid chromatography and mass spectrometry analysis. The chromatographic analysis was performed on a HSS T3 column (2.1 mm×100 mm, 1.8 μm) by gradient elution using methanol and 5 mmol/L ammonium acetate containing 0.1% formic acid solution as mobile phase. The secondary mass information of alkaloid was collected in positive electrospray ionization and targeted-selected ion monitor-ddMS2 mode. The mass spectrometry data were applied to the automatic screening of actual samples. Results The mass spectrometry database of 72 alkaloids were established containing the theoretical accurate molecular mass, retention time collision energy and fragment ions. The multiple alkaloids in actual samples were locked rapidly by automatic screening with the mass spectra database. Conclusion This method is simple, fast, accurate and suitable for the rapid automatic screening of alkaloids in poisoned food sample.

Background The aim of this study was to determine the function of long non‐coding RNA small nucleolar RNA host gene 6 (SNHG6) in non‐small cell lung cancer (NSCLC) and its underlying mechanisms. Methods The association of SNHG6 or miR‐101‐3p with clinicopathological characteristics and prognosis in patents with NSCLC was assessed by TCGA dataset. Cell proliferation and invasion were evaluated by MTT and Transwell assays and SNHG6‐specific binding with miR‐101‐3p was verified by bioinformatic analysis, luciferase gene report and RNA immunoprecipitation assays. qRT‐PCR and Western blot was used to assess the effects of SNHG6 on the expression of miR‐101‐3p and chromodomain Y like (CDYL) in NSCLC cells. A xenograft tumor model in vivo was established to observe the effects of SNHG6 knockdown on tumor growth. Results We found that increased expression of SNHG6 was associated with pathological stage and lymph node infiltration, and acted as an independent prognostic factor of tumor recurrence in patients with NSCLC. Silencing SNHG6 expression repressed cell growth and invasion in vitro and in vivo, but overexpression of SNHG6 reversed these effects. Furthermore, SNHG6 was identified to act as a sponge of miR‐101‐3p, which could reduce cell proliferation and attenuate SNHG6‐induced CDYL expression. Low expression of miR‐101‐3p or high expression of CDYL was related to poor survival in patients with NSCLC. Conclusions Our findings demonstrated that lncRNA SNHG6 contributed to the proliferation and invasion of NSCLC by downregulating miR‐101‐3p.

Jiaozhou Bay (JZB), located at Qingdao City, north China, is a semi-enclosed shallow bay that has undergone large-scale land reclamation and is suffering from a deteriorated water environment. Long-term evolution of JZB with respect of coastline, tidal prism, tidal dynamics, water-exchange capacity, and pollutant transport from 1863 to 2020 was investigated in this paper, using remote sensing images, historical charts, and a numerical model. The JZB was predominated by natural evolution from 1863 to 1935, during which the coastline barely changed. Thereafter, human intervention became intense and more and more natural tidal flats were replaced by salt ponds, aquaculture area, and reclamation very quickly. As a result, tidal prism, area of tidal flats, and area of JZB decreased sharply by 0.290 km3, 182 km2, and 223 km2, respectively, from 1935 to 2020, corresponding to annual decreasing rates being of 123 times, 10 times, 12 times, respectively, as that of before 1935. A numerical model showed that the residual current in JZB tended to be weaker due to the change of coastline and bathymetry, which is not favoring the water-exchange and pollutant transport, especially in the northeast of JZB. The basin residence time increased from 15.5 days in 1935 to 17.6 days in 2020, because of weaker residual tidal current and smaller tidal prism. Local residence time increased significantly near the area with large land reclamation, especially in the northeast and west of JZB. Distribution of dissolved inorganic nitrogen (DIN), in each year, which is the dominant pollutant in JZB, indicated higher DIN concentration and weaker transport along with reclamation. The research on JZB evolution over the last 150 years can provide useful suggestions for the decision-makers of the local government to improve the marine ecosystem. The systematic method to investigate long-term water environment evolution of JZB can be used to study other semi-closed bays.

Target detection in synthetic aperture radar (SAR) images has a wide range of applications in military and civilian fields. However, for engineering applications involving edge deployment, it is difficult to find a suitable balance of accuracy and speed for anchor-based SAR image target detection algorithms. Thus, an anchor-free detection algorithm for SAR ship targets with deep saliency representation, called SRDet, is proposed in this paper to improve SAR ship detection performance against complex backgrounds. First, we design a data enhancement method considering semantic relationships. Second, the state-of-the-art anchor-free target detection framework CenterNet2 is used as a benchmark, and a new feature-enhancing lightweight backbone, called LWBackbone, is designed to reduce the number of model parameters while effectively extracting the salient features of SAR targets. Additionally, a new mixed-domain attention mechanism, called CNAM, is proposed to effectively suppress interference from complex land backgrounds and highlight the target area. Finally, we construct a receptive-field-enhanced detection head module, called RFEHead, to improve the multiscale perception performance of the detection head. Experimental results based on three large-scale SAR target detection datasets, SSDD, HRSID and SAR-ship-dataset, show that our algorithm achieves a better balance between ship target detection accuracy and speed and exhibits excellent generalization performance.

Reliable estimates of the prevalence of food allergy (FA) among the general Chinese population have remained unclear. This meta-analysis aims to provide an accurate estimate of FA prevalence in China with comprehensive data. A systematic literature search was conducted in eight electronic databases, i.e., China National Knowledge Infrastructure, Wanfang, Weipu, China Biology Medicine, Web of Science, PubMed, Cochrane, and Embase. A random-effects model was used to analyze the pooled prevalence of FA for four different assessment methods. A total of 46 eligible articles were included in the narrative synthesis, and 41 articles were ultimately included in the meta-analysis. Overall, the pooled prevalence of self-reported FA, self-reported physician-diagnosed FA, SPT (specific skin prick test)-positive FA, and OFC (open food challenge)-positive FA were 11.5% (95% CI: 9.8–13.5%), 5.3% (95% CI: 4.2–6.5%), 11.6% (95% CI: 9.6–14.1%), and 6.2% (95% CI: 4.4–8.7%), respectively. Subgroup analyses suggested that the prevalence of FA was affected by age, year of data collection, region, and sample size, but not by gender. This meta-analysis indicated that FA is common among Chinese people, with an increasing trend in prevalence during the past two decades. Given the high heterogenicity between these studies, a national survey with a large sample size based on standardized diagnosis is urgently needed to gain a more scientific understanding of the actual situation of food allergy in China.

This study aimed to investigate whether 25-hydroxyvitamin D (25(OH)D) concentrations are correlated to overweight/obesity in infants and to explore a threshold of 25(OH)D. A total of 1205 six-month-old infants from two community hospitals in Shanghai were randomly recruited, and 925 of them were followed up at 12 months. Concentration of 25(OH)D, weight, and length were measured at two time points. Overweight/obesity was defined as a weight-for-length Z-score >97th percentile. The prevalence of overweight/obesity at 6 and 12 months was 6.88% and 5.26%, respectively. The occurrence of vitamin D (VitD) deficiency (p = 0.02) and 12 months (adjusted β: −0.22; 95% CI: −0.41, −0.02; p = 0.03), while the relationship between 25(OH)D at 6 months and WLP at 12 months was nonlinear, where 35 ng/mL was identified as an inflection point. Those with a concentration of 25(OH)D p = 0.02) compared to the group with a concentration of 25(OH)D ≥35 ng/mL. Moreover, a concentration of 25(OH)D p = 0.03). A suboptimal 25(OH)D concentration

The large-scale production and frequent use of endocrine-disrupting chemicals (EDCs) have led to the continuous release and wide distribution of these pollutions in the natural environment. At low levels, EDC exposure may cause metabolic disorders, sexual development, and reproductive disorders in aquatic animals and humans. Adsorption treatment, particularly using nanocomposites, may represent a promising and sustainable method for EDC removal from wastewater. EDCs could be effectively removed from wastewater using various carbon-based nanomaterials, such as carbon nanofiber, carbon nanotubes, graphene, magnetic carbon nanomaterials, carbon membranes, carbon dots, carbon sponges, etc. Important applications of carbon nanocomposites for the removal of different kinds of EDCs and the theory of adsorption are discussed, as well as recent advances in carbon nanocomposite synthesis technology and characterization technology. Furthermore, the factors affecting the use of carbon nanocomposites and comparisons with other adsorbents for EDC removal are reviewed. This review is significant because it helps to promote the development of nanocomposites for the decontamination of wastewater.

Background: The aim of this study was to investigate the predictive value of a prognostic model based on the lymphocyte-to-monocyte ratio (LMR) before radioiodine treatment for the recurrence of papillary thyroid carcinoma (PTC). Methods: Clinicopathological data of 441 patients with papillary thyroid cancer were collected retrospectively. The Receiver operating characteristic (ROC) was used to determine the optimal cut-off value for predicting PTC recurrence by LMR before radioiodine treatment. Recurrence was the endpoint of the study, and survival was estimated by the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank test. Univariate and multifactorial analyses were performed using Cox proportional-hazards models to identify risk factors associated with PTC recurrence. Results: The ROC curve showed that the best cut-off value of LMR before radioiodine treatment to predict recurrence in patients with PTC was 6.61, with a sensitivity of 54.1%, a specificity of 73%, and an area under the curve of 0.628. The recurrence rate was significantly higher in the low LMR group (16%) than in the high LMR group (5%) ( P = 0.001, χ 2 = 12.005). Multifactorial analysis showed that LMR < 6.61 ( P = 0.006; HR = 2.508) and risk stratification (high risk) ( P = 0.000; HR = 5.076) before radioiodine treatment were independent risk factors predicting recurrence in patients with PTC. Patients with preoperative LMR < 6.61 and high risk stratification had the lowest recurrence-free survival rate and the shortest recurrence-free survival time. Conclusions: The LMR-based prognostic model before radioactive iodine treatment is valuable for early prediction of PTC recurrence and it can be used in clinical practice as a supplement to risk stratification and applied in combination to help screen out patients with poorer prognosis early.

The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds 1–3, were isolated from Ajuga ovalifolia var. calantha. Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound 2 selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound 2 targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound 2 passed the majority of the parameters of common drug discovery rules. Compound 2 restrained A549 proliferation (IC50 = 8.68 ± 0.96 μM), invasion and caused A549 cell apoptosis by inhibiting the SHP2–ERK/AKT signaling pathway. Finally, compound 2 (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment.

This paper presents an algorithm for the retrieval of nitrous oxide profiles from the Atmospheric InfraRed Sounder (AIRS) on the Earth Observing System (EOS)/Aqua using a nonlinear optimal estimation method. First, an improved Optimal Sensitivity Profile (OSP) algorithm for channel selection is proposed based on the weighting functions and the transmissions of the target gas and interfering gases, with 13 channels selected for inversion in this algorithm. Next, the data of the High-Performance Instrumented Airborne Platform for Environmental Research (HIAPER) Pole-to-Pole Observations (HIPPO) aircraft and the Earth System Research Laboratory (ESRL) are used to verify the retrieval results, including the atmospheric nitrous oxide profile and the column concentration. The results show that using AIRS satellite data, the atmospheric nitrous oxide profile between 300–900 hPa can be well retrieved with an accuracy of ~0.1%, which agrees with the corresponding Jacobian peak interval of selected channels. Analysis of the AIRS retrievals demonstrates that the AIRS measurements provide useful information to capture the spatial and temporal variations in nitrous oxide between 300–900 hPa.

Based on the residual turbulent scintillation theory, the Mie-scattering lidar can measure the intensity of atmospheric turbulence by detecting the light intensity scintillation index of the laser return signal. In order to evaluate and optimize the reliability of the Mie-scattering lidar system for detecting atmospheric turbulence, the appropriate parameters of the Mie-scattering lidar system are selected and optimized using the residual turbulent scintillation theory. Then, the Fourier transform method is employed to perform the numerical simulation of the phase screen of the laser light intensity transformation on the vertical transmission path of atmospheric turbulence. The phase screen simulation, low-frequency optimization, and scintillation index calculation methods are provided in detail, respectively. Based on the phase distribution of the laser beam, the scintillation index is obtained. Through the relationship between the scintillation index and the atmospheric turbulent refractive index structure constant, the atmospheric turbulence profile is inverted. The simulation results show that the atmospheric refractive index structure constant profile obtained by the iterative method is consistent with the input HV5/7 model below 6500 m, which has great guiding significance to carry out actual experiments to measure atmospheric turbulence using the Mie lidar.

The glyoxalase system is a ubiquitous enzymatic network which plays important roles in biological life. It consists of glyoxalase 1 (GLO1), glyoxalase 2 (GLO2), and reduced glutathione (GSH), which perform an essential metabolic function in cells by detoxifying methylglyoxal (MG) and other endogenous harmful metabolites into non-toxic d-lactate. MG and MG-derived advanced glycation endproducts (AGEs) are associated with various diseases, such as diabetes, cardiovascular disease, neurodegenerative disorders and cancer, and GLO1 is a key rate-limiting enzyme in the anti-glycation defense. The abnormal activity and expression of GLO1 in various diseases make this enzyme a promising target for drug design and development. This review focuses on the regulatory mechanism of GLO1 in diverse pathogenic conditions with a thorough discussion of GLO1 regulators since their discovery, including GLO1 activators and inhibitors. The different classes, chemical structure and structure-activity relationship are embraced. Moreover, assays for the discovery of small molecule regulators of the glyoxalase system are also introduced in this article. Compared with spectrophotometer-based assay, microplate-based assay is a more simple, rapid and quantitative high-throughput method. This review will be useful to design novel and potent GLO1 regulators and hopefully provide a convenient reference for researchers.

Objectives: The diagnostic performance of intravoxel incoherent motion diffusion–weighted imaging (IVIM-DWI) in the differential diagnosis of breast tumors remains debatable among published studies. Therefore, this meta-analysis aimed to pool relevant evidence regarding the diagnostic performance of IVIM-DWI in the differential diagnosis of breast tumors.Methods: Studies on the differential diagnosis of breast lesions using IVIM-DWI were systemically searched in the PubMed, Embase and Web of Science databases in recent 10 years. The standardized mean difference (SMD) and 95% confidence intervals of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f) were calculated using Review Manager 5.3, and Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as assess publication bias and heterogeneity. Fagan's nomogram was used to predict the posttest probabilities.Results: Sixteen studies comprising 1,355 malignant and 362 benign breast lesions were included. Most of these studies showed a low to unclear risk of bias and low concerns regarding applicability. Breast cancer had significant lower ADC (SMD = −1.38, P < 0.001) and D values (SMD = −1.50, P < 0.001), and higher f value (SMD = 0.89, P = 0.001) than benign lesions, except D* value (SMD = −0.30, P = 0.20). Invasive ductal carcinoma showed lower ADC (SMD = 1.34, P = 0.01) and D values (SMD = 1.04, P = 0.001) than ductal carcinoma in situ. D value demonstrated the best diagnostic performance (sensitivity = 86%, specificity = 86%, AUC = 0.91) and highest post-test probability (61, 48, 46, and 34% for D, ADC, f, and D* values) in the differential diagnosis of breast tumors, followed by ADC (sensitivity = 76%, specificity = 79%, AUC = 0.85), f (sensitivity = 80%, specificity = 76%, AUC = 0.85) and D* values (sensitivity = 84%, specificity = 59%, AUC = 0.71).Conclusion: IVIM-DWI parameters are adequate and superior to the ADC in the differentiation of breast tumors. ADC and D values can further differentiate invasive ductal carcinoma from ductal carcinoma in situ. IVIM-DWI is also superior in identifying lymph node metastasis, histologic grade, and hormone receptors, and HER2 and Ki-67 status.

Aerosol plays a very important role in affecting the earth-atmosphere radiation budget, and particle size distribution is an important aerosol property parameter. Therefore, it is necessary to determine the particle size distribution. However, the particle size distribution determined by the particle extinction efficiency factor according to the Mie scattering theory is an ill-conditioned integral equation, namely, the Fredholm integral equation of the first kind, which is very difficult to solve. To avoid solving such an integral equation, the BP neural network prediction model was established. In the model, the aerosol optical depth obtained by sun photometer CE-318 and kernel functions obtained by Mie scattering theory were used as the inputs of the neural network, particle size distributions collected by the aerodynamic particle sizer APS 3321 were used as the output, and the Levenberg–Marquardt algorithm with the fastest descending speed was adopted to train the model. For verifying the feasibility of the prediction model, some experiments were carried out. The results show that BP neural network has a better prediction effect than that of the RBF neural network and is an effective method to obtain the aerosol particle size distribution of the whole atmosphere column using the data of CE-318 and APS 3321.

Oil tank inventory is significant for the economy and the military, as it can be used to estimate oil reserves. Traditional oil tank detection methods mainly focus on the geometrical characteristics and spectral features of remotely sensed images based on feature engineering. The methods have a limited application capability when the distribution pattern of ground objects in the image changes and the imaging condition varies largely. Therefore, we propose an end-to-end deep convolution network Res2-Unet+, to detect oil tanks in a large-scale area. The Res2-Unet+ method replaces the typical convolution block in the encoder of the original Unet method using hierarchical residual learning branches. A hierarchical branch is used to decompose the feature map into a few sub-channel features. To evaluate the generalization and transferability of the proposed model, we use high spatial resolution images from three different sensors in different areas to train the oil tank detection model. Images from yet another sensor in another area are used to evaluate the trained model. Three more widely used methods, Unet, Segnet, and PSPNet, are trained and evaluated for the same dataset. The experiments prove the effectiveness, strong generalization, and transferability of the proposed Res2-Unet+ method.

Porcine reproductive and respiratory syndrome virus (PRRSV) can cause respiratory disease and reproductive failure in pregnant pigs. Previous transcriptome analyses in susceptive cells have mainly concentrated on pulmonary alveolar macrophages (PAM) and Marc-145 cells, and on the respiratory system. Some studies reported that apoptosis of placental cells and pig endometrial epithelial cells (PECs) is an obvious sign linked to reproductive failure in pregnant sows, but the mechanism is still unknown. In this study, Sn-positive PECs were isolated and apoptosis rates were assessed by flow cytometry. PRRSV-infected PECs exhibited apoptosis, indicative of their susceptibility to PRRSV. Subsequently, the whole transcriptome was compared between mock- and PRRSV-infected PECs and 54 differentially expressed microRNAs (DEmiRNAs), 104 differentially expressed genes (DEGs), 22 differentially expressed lncRNAs (DElncRNAs), and 109 isoforms were obtained, which were mainly enriched in apoptosis, necroptosis, and p53 signal pathways. Integration analysis of DEmiRNA and DEG profiles revealed two microRNAs (ssc-miR-339-5p and ssc-miR-181d-5p) and five genes (SLA-DQB1, THBS1, SLC3A1, ZFP37, and LOC100517161) participating in the apoptosis signal, of which THBS1 and SLC3A1 were mainly linked to the p53 pathway. Integration analysis of DEGs with DElncRNA profiles identified genes involved in apoptosis signal pathway are regulated by LTCONS_00010766 and LTCONS_00045988. Pathway enrichment revealed that the phagosome and p53 pathways are the two main signals causing apoptosis of PECs, and functional analysis revealed a role of miR-339-5p in regulating apoptosis of PECs after PRRSV inoculation.

ObjectivesAlthough systematic evaluation has confirmed the efficacy of fresh fecal microbiota transplantation (FMT) for treatment of recurrent and/or refractory and/or relapse C. difficile infection (RCDI), it lacks the support of well-designed randomized controlled trials (RCTs), and the latest guidelines do not optimize the management of FMT. In this paper, we focus on an in-depth study of fresh FMT and fecal infusion times to guide clinical practice.MethodsWe reviewed studies in PubMed, Medline, Embase, the Cochrane library and Cochrane Central written in English. The retrieval period was from the establishment of the databases to September 20th, 2018. The retrieval objects were published RCTs of RCDI treated by fresh FMT. The intervention group was fresh FMT group, while the control group included antibiotic therapy or placebo or frozen FMT or capsule. The primary and secondary outcomes were the clinical remission of diarrhea without relapse after 8-17 weeks and the occurrence of severe adverse events, respectively. Subgroup analysis analyzed the effect of single and multiple fecal infusions. Two authors independently completed the information extraction and assessed risk of bias and overall quality of the evidence.Results8 randomized controlled trials met the inclusion criteria, involving 537 patients (273 in the fresh FMT group and 264 in the control group). The recurrence rate of clinical diarrhea in the fresh FMT group was 11.0% (30/273), which was significantly lower than the control group (24.6%, 65/264; P < 0.05); the pooled relative risk (RR) was 0.38 (95%CI:0.16-0.87; I2 = 67%; P = 0.02) in the fresh FMT group, and the clinical heterogeneity was significant and random effects model was used; However, there was no significant difference neither for the effect of antibiotic treatment/frozen feces transplanted by enema (RR = 1.07; 95%CI: 0.64-1.80; I2 = 0%; P = 0.79) or capsule/frozen feces transplanted by colonoscopy (RR = 0.42; 95%CI: 0.05-3.94; I2 = 43%; P = 0.45) compared with fresh FMT. The subgroup analysis showed that FMT by multiple infusions could effectively and significantly (RR = 0.24; 95%CI:0.10-0.58; I2 = 0%; P = 0.001) improve the clinical diarrhea remission rate. Most mild to moderate adverse events caused by FMT were self-limited and could be quickly alleviated; no severe adverse events happened because of FMT.ConclusionsOverall, the use of fresh feces for bacterial transplantation was the best efficiency for RCDI compared to antibiotic therapy or placebo. The fecal transmission method by enema was not ideal, but capsules or frozen feces transported by colonoscopy could be an alternative treatment compared to fresh FMT. For patients with severe RCDI, multiple fecal transplants can effectively improve their diarrhea remission rate. The focus of future research should be on how to standardize the production of capsules or frozen feces to better guide the clinical management of RCDI patients by FMT.

Adaptation of fine root plasticity to soil nutrients heterogeneity in natural forest ecosystems has not been well explored. The study aimed to determine seasonal variations of fine root traits in Pinus koraiensis natural forests and explore the relationship between fine root traits and soil properties. Root and soil samples were collected from the coniferous broad-leaved mixed forest (BP), monospecific P. koraiensis forest (MP), and coniferous mixed forest (CP). Soil available phosphorus (P) content for MP was 31.7% and 39.8% lower than for BP and CP. Soil cation exchange capacity (CEC) for MP was lower by 23.5% and 27.2% than for BP and CP, respectively. In July, specific root lengths and root surface areas for BP and CP (mixed forests) were significantly higher than for MP (monospecific forest). A structural equation model showed that CEC had a significant effect on fine root traits. Root diameter, root volume density, and root surface area density were negatively correlated with CEC. Fine root traits plasticity of P. koraiensis are closely related to soil available nutrient contents, CEC, and species composition at the ecosystem level.

Wolbachia naturally infects a wide variety of arthropods, where it plays important roles in host reproduction. It was previously reported that Wolbachia did not infect silkworm. By means of PCR and sequencing we found in this study that Wolbachia is indeed present in silkworm. Phylogenetic analysis indicates that Wolbachia infection in silkworm may have occurred via transfer from parasitic wasps. Furthermore, Southern blotting results suggest a lateral transfer of the wsp gene into the genomes of some wild silkworms. By antibiotic treatments, we found that tetracycline and ciprofloxacin can eliminate Wolbachia in the silkworm and Wolbachia is important to ovary development of silkworm. These results provide clues towards a more comprehensive understanding of the interaction between Wolbachia and silkworm and possibly other lepidopteran insects.

Mutation of distal-less homeobox 3 (DLX3) is responsible for human tricho-dento-osseous syndrome (TDO) with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP) genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO) inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

The Yinchuan area, which lies in the eastern part of Northwest China, is one of the main transportation paths and origins of sand dust in China. In order to investigate the aerosol number size distribution and its temporal-spatial evolution over this area, direct solar radiation data taken from September 2012 to October 2013 by a sun photometer CE-318 located at Beifang University of Nationalities (106°29′E, 38°13′N) were analyzed. The particle number size distributions were retrieved from the aerosol optical depth (AOD) by use of the extinction inversion method. The experiment results show that although the averaged size distribution satisfies basically the Junge function, there are two obvious peaks at the particle radius of 0.6 μm and 1.4 μm, respectively. Because sand-dust weather occurs frequently, the particle size distribution in Spring is obviously larger than that in other seasons, which coincides with AOD variation tendency. Moreover, in sand-dust weather the particles number concentration is larger than that of background weather with one order of magnitude, especially for the number of concentration of large particles and giant particles. The research results have very important reference value for quantitative study of the influence of aerosol on atmosphere physics and chemistry process and monitoring of sand-dust weather and air pollution of this area.

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder caused by mutations in the ABCD1 gene. Approximately 20% of X-ALD female carriers may develop neurological symptoms. Skewed X chromosome inactivation (XCI) has been proposed to influence the manifestation of symptoms in X-ALD carriers, but data remain conflicting so far. We identified a three generation kindred, with five heterozygous females, including two manifesting carriers. XCI pattern and the ABCD1 allele expression were assessed in order to determine if symptoms in X-ALD carriers could be related to skewed XCI and whether skewing within this family is more consistent with genetically influenced or completely random XCI.We found a high frequency of skewing in this family. Four of five females had skewed XCI, including two manifesting carriers favoring the mutant allele, one asymptomatic carrier favoring the normal allele, and one female who was not an X-ALD carrier. Known causes of skewing, such as chromosomal abnormalities, selection against deleterious alleles, XIST promoter mutations, were not consistent with our results.Our data support that skewed XCI in favor of the mutant ABCD1 allele would be associated with the manifestation of heterozygous symptoms. Furthermore, XCI skewing in this family is genetically influenced. However, the underlying mechanism remains to be substantiated by further experiments.

BACKGROUND: MiR-499 is a cardiac-abundant miRNA. However, the biological functions of miR-499 in differentiated cardiomyocytes or in the cardiomyocyte differentiation process is not very clear. Sox6 is believed to be one of its targets, and is also believed to play a role in cardiac differentiation. Therefore, our aim was to investigate the association between Sox6 and miR-499 during cardiac differentiation. METHODOLOGY/PRINCIPAL FINDINGS: Using a well-established in vitro cardiomyocyte differentiation system, mouse P19CL6 cells, we found that miR-499 was highly expressed in the late stage of cardiac differentiation. In cells stably transfected with miR-499 (P-499 cells), it was found that miR-499 could promote the differentiation into cardiomyocytes at the early stage of cardiac differentiation. Notably, cell viability assay, EdU incorporation assay, and cell cycle profile analysis all showed that the P-499 cells displayed the distinctive feature of hyperplastic growth. Further investigation confirmed that miR-499 could promote neonatal rat cardiomyocyte proliferation. MiR-499 knock-down enhanced apoptosis in the late differentiation stage in P19CL6 cells, but overexpression of miR-499 resulted in a decrease in the apoptosis rate. Sox6 was identified as a direct target of miR-499 and its expression was detected from day 8 or day 10 of cardiac differentiation of P19CL6 cells. Sox6 played a role in cell viability, inhibited cell proliferation and promoted cell apoptosis in P19CL6 cells and cardiomyocytes. The overexpression of Sox6 could reverse the proliferation and anti-apoptosis effects of miR-499. It was also found that miR-499 might exert its function by regulating cyclin D1 via its influence on Sox6. CONCLUSIONS/SIGNIFICANCE: miR-499 probably regulates the proliferation and apoptosis of P19CL6 cells in the late stage of cardiac differentiation via its effects on Sox6 and cyclin D1.

BACKGROUND: Islet 1 (ISL1), a LIM-homeodomain transcription factor is essential for promoting pancreatic islets proliferation and maintaining endocrine cells survival in embryonic and postnatal pancreatic islets. However, how ISL1 exerts the role in adult islets is, to date, not clear. METHODOLOGY/PRINCIPAL FINDINGS: Our results show that ISL1 expression was up-regulated at the mRNA level both in cultured pancreatic cells undergoing glucose oxidase stimulation as well in type 1 and type 2 diabetes mouse models. The knockdown of ISL1 expression increased the apoptosis level of HIT-T15 pancreatic islet cells. Using HIT-T15 and primary adult islet cells as cell models, we show that ISL1 promoted adult pancreatic islet cell proliferation with increased c-Myc and CyclinD1 transcription, while knockdown of ISL1 increased the proportion of cells in G(1) phase and decreased the proportion of cells in G(2)/M and S phases. Further investigation shows that ISL1 activated both c-Myc and CyclinD1 transcription through direct binding on their promoters. CONCLUSIONS/SIGNIFICANCE: ISL1 promoted adult pancreatic islet cell proliferation and probably by activating c-Myc and CyclinD1 transcription through direct binding on their promoters. Our findings extend the knowledge about the crucial role of ISL1 in maintaining mature islet cells homeostasis. Our results also provide insights into the new regulation relationships between ISL1 and other growth factors.

Recent findings suggest the feasibility of cardiac repair by transplantation of bone marrow mesenchymal stem cell (MSCs). However, it remains controversial regarding which cell type is the best source for transplanting into the ischemic heart because of lack of well-defined cell markers. In this study, we investigated the in vitro and in vivo effects of the novel multipotent marrow mesenchymal stem cells (MMSCs) from human bone marrow. Pluripotent markers (Oct4, Bmi1, and Abcg2) and vascular endothelial growth factor (VEGF) were detected by RT-PCR and immunofluorescence in MMSCs. Myocardial differentiation was induced in the expanded MMSC cultures by treatment with 5-azacyline. Expressions of VEGF in the animals transplanted with MMSCs were markedly increased in comparison with the animals injected with fibroblasts or saline at both mRNA and protein levels. VEGF expression was observed in both transplanted MMSCs and recipient cardiomyocytes by immunofluorescence. Confocal immunofluorescence microscopy revealed the specific markers for cardiomyocytes and endothelial cells in transplanted MMSCs 14 days after transplantation. Vessel count was increased and left ventricular function improved post-MMSC transplantation. These results indicate that transplantation of purified MMSCs from human bone marrow upregulated VEGF expression, enhanced angiogenesis, and improved the functional recovery following myocardial infarction in rats.

Selenocysteine methyltransferase (SMT) is a key enzyme involved in the Se metabolism pathway, and it is responsible for the catalysis of Se-methylselenocysteine (SeMSC) compound formation. Previous studies showed that selenium treatment activated SMT expression and promoted the accumulation of glucosinolates (GSLs) and sulforaphane, but the roles and functional mechanisms of SMT in mediating GSLs and sulforaphane synthesis remain unclear. In this study, we identified the BoSMT gene in broccoli and uncovered its roles in mediating GSLs biosynthesis. Transgenic assays revealed that BoSMT is involved in SeMSC biosynthesis in broccoli. More importantly, the contents of GSLs and sulforaphane were significantly increased in the BoSMT-overexpressing broccoli lines but decreased in the knockdown lines, suggesting that BoSMT played a positive role in regulating GSLs and sulforaphane synthesis. Further evidence indicated that BoSMT-mediated overaccumulation of GSLs and sulforaphane might be due to the increase in the endogenous SeMSC content. Compared with the mock (water) treatment, selenite-induced significantly increases of the SeMSC content in the BoSMT-knockdown plants partially compensated the phenotype of GSLs and sulforaphane loss. Compared with the mock treatment, exogenous SeMSC treatment significantly increased the contents of GSL and sulforaphane and activated GSL synthesis-related gene expression, suggesting that SeMSC acted as a positive regulator for GSL and sulforaphane production. Our findings provided novel insights into selenium-mediated GSLs and sulforaphane accumulation. The genetic manipulation of BoSMT might be a useful strategy for improving the dietary nutritional values of broccoli. [ABSTRACT FROM AUTHOR]

RESUMO A Hélice Tríplice tornou-se um modelo reconhecido internacionalmente, que está no âmago da disciplina emergente de estudos de inovação, e um guia de políticas e práticas nos âmbitos local, regional, nacional e multinacional. As interações universidade-indústria-governo, que formam uma “hélice tríplice” de inovação e empreendedorismo, são a chave para o crescimento econômico e o desenvolvimento social baseados no conhecimento. O artigo apresenta a origem do modelo, seu conceito, dinâmica, fontes e rotas alternativas.