Advancing Natural Product Discovery: A Structure-Oriented Fractions Screening Platform for Compound Annotation and Isolation.

Natural product discovery is hindered by the lack of tools that integrate untargeted nuclear magnetic resonance and mass spectrometry data on a library scale. This article describes the first application of the innovative NMR/MS-based machine learning tool, the "Structure-Oriented Fractions Screening Platform (SFSP)", enabling functional-group-guided fractionation and accelerating the discovery and characterization of undescribed natural products. The concept was applied to the extract of a marine fungus known to be a prolific producer of diverse natural products. With the assistance of SFSP, we isolated 24 flavipidin derivatives and five phenalenone analogues from Aspergillus sp. GE2-6, revealing 27 undescribed compounds. Compounds 7-22 were proposed as isomeric derivatives featuring a 5/6-ring fusion, formed by the dimerization of flavipidin E (5). Compounds 23 and 24 were envisaged as isomeric derivatives with a 6/5/6-ring fusion, generated through the degradation of two flavipidin E molecules. Furthermore, flavipidin A (1) and asperphenalenone E (28) exhibited potent anti-influenza (PR8) activities, with IC50 values of 21.9 ± 0.2 and 12.9 ± 0.1 µM, respectively. Meanwhile, asperphenalenone (26) and asperphenalenone P (27) treatments exhibited significant inhibition of HIV pseudovirus infection in 293FT cells, boasting IC50 values of 6.1 ± 0.9 and 4.6 ± 1.1 µM, respectively. Overall, SFSP streamlines natural product isolation through NMR and MS data integration, as showcased by the discovery of numerous undescribed flavipidins and phenalenones based on NMR olefinic signals and low-field hydroxy signals.

Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study.

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

Lumen-apposing metal stents versus traditional self-expanding metal stents for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Endoscopic drainage has become the preferred treatment for pancreatic fluid collections (PFCs). There is still a lack of reliable evidence to prove which metal stent is the best choice for endoscopic ultrasound (EUS)-guided drainage of PFCs. In this study, we aimed to evaluate the efficacy and safety of lumen-apposing metal stents (LAMS) compared to traditional self-expanding metal stents (SEMS) in meta-analysis. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to July 15, 2023. Relevant publications that compared LAMS with traditional SEMS for drainage of patients' PFCs under EUS-guidance were included. This meta-analysis assessed endpoints using Review Manager 5.3 and Stata 14.0 statistical software. RESULT: Nine citations comprising 707 patients with PFCs were included. The clinical success rate of LAMS tended to be higher than that of SEMS (RR = 1.07, 95%CI [1.00, 1.15], P = 0.05). LAMS had a lower technical success rate (RR = 0.97, 95%CI [0.94, 0.99], P = 0.02) and faster procedure time (minutes) (MD = - 24.29, 95%CI [- 25.59, - 22.99], P < 0.00001) compared to SEMS. In addition, LAMS had fewer overall adverse events (RR = 0.64, 95%CI [0.48, 0.87], P = 0.004). For specific adverse events, LAMS had fewer migration (RR = 0.37, 95%CI [0.19, 0.72], P = 0.003), occlusion (RR = 0.43, 95%CI [0.22, 0.82], P = 0.01) and infection (RR = 0.38, 95%CI [0.20, 0.70], P = 0.002). There was no significant difference in bleeding and perforation between the two stents. For hospital stay (days), LAMS group was similar to SEMS group (MD = - 3.34, 95%CI [- 7.71, - 1.03], P = 0.13). Regarding recurrence, LAMS group was fewer than SEMS group (RR = 0.41, 95%CI [0.21, 0.78], P = 0.007). CONCLUSION: Compared to traditional SEMS, LAMS has a higher clinical success rate, faster procedure time, fewer adverse events, similar hospital stay and lower recurrence rate in EUS-guided drainage of PFCs. LAMS is a good choice with a high technical success rate over 95%, and using a shorter length or "one-step" operation can further improve it. Richer placement experience is required for LAMS placement under EUS-guidance.

Transcriptomic insights into the immune response of the intestine to Aeromonas veronii infection in northern snakehead (Channa argus).

Intestinal inflammation is a protective response that is implicated in bacterial enteritis triggered by gastrointestinal infection. The immune mechanisms elicited in teleost against the infection of Aeromonas veronii are largely unknown. In this study, we performed a de novo northern snakehead (Channa argus) transcriptome assembly using Illumina sequencing platform. On this basis we performed a comparative transcriptomic analysis of northern snakehead intestine from A. veronii-challenge and phosphate buffer solution (PBS)-challenge fish, and 2076 genes were up-regulated and 1598 genes were down-regulated in the intestines infected with A. veronii. The Gene Ontology (GO) enrichment analysis indicated that the differentially expressed genes (DEGs) were enriched to 27, 21 and 20 GO terms in biological process, cellular component, and molecular function, respectively. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 420 DEGs were involved in 194 pathways. Moreover, 33 DEGs were selected for quantitative real-time PCR analysis to validate the RNA-seq data. The results reflected the consistency of the expression levels between qRT-PCR and RNA-seq data. In addition, a time-course analysis of the mRNA expression of 33 immune-related genes further indicated that the intestinal inflammation to A. veronii infection simultaneously regulated gene expression alterations. The present study provides transcriptome data of the teleost intestine, allowing us to understand the mechanisms of intestinal inflammation triggered by bacterial pathogens. DATA AVAILABILITY STATEMENT: All data supporting the findings of this study are available within the article and Supplementary files. The RNA-seq raw sequence data are available in NCBI short read archive (SRA) database under accession number PRJNA615958.

Kueishanamides A and B from the Hydrothermal Vent Sediment Derived Streptomyces sp. WU20.

Marine actinomycetes are known for their production of remarkable organic molecules, particularly those featuring polyoxygenated long-chain backbones. Determining the absolute configurations of these compounds remains a challenging task even today. In this study, we successfully established the planar structures and absolute configurations of two highly flexible amide alkaloids from Streptomyces sp. WU20: kueishanamides A (1) and B (2). These compounds possess a C13 linear backbone and each contains five stereogenic carbon centers. Our approach involved a combination of spectroscopic and computational methods, including J-based configurational analysis and VCD calculations, ensuring the unambiguous determination of their configurations. Kueishanamide A (1) and kueishanamide B (2) showed moderate antifungal activity against pathogenic fungus Crytococcus neoformans, with MIC values of 25 µg/mL each.

Active Learning Optimisation of Binary Coded Metasurface Consisting of Wideband Meta-Atoms.

The design of a metasurface array consisting of different unit cells with the objective of minimizing its radar cross-section is a popular research topic. Currently, this is achieved by conventional optimisation algorithms such as genetic algorithm (GA) and particle swarm optimisation (PSO). One major concern of such algorithms is the extreme time complexity, which makes them computationally forbidden, particularly at large metasurface array size. Here, we apply a machine learning optimisation technique called active learning to significantly speed up the optimisation process while producing very similar results compared to GA. For a metasurface array of size 10 × 10 at a population size of 106, active learning took 65 min to find the optimal design compared to genetic algorithm, which took 13,260 min to return an almost similar optimal result. The active learning optimisation strategy produced an optimal design for a 60 × 60 metasurface array 24× faster than the approximately similar result generated by GA technique. Thus, this study concludes that active learning drastically reduces computational time for optimisation compared to genetic algorithm, particularly for a larger metasurface array. Active learning using an accurately trained surrogate model also contributes to further lowering of the computational time of the optimisation procedure.

Dietary supplementation of probiotics fermented Chinese herbal medicine Sanguisorba officinalis cultures enhanced immune response and disease resistance of crucian carp (Carassius auratus) against Aeromonas hydrophila.

Aeromonas hydrophila, a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila, regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection.

Talaropeptins A and B, Tripeptides with an N-trans-Cinnamoyl Moiety from the Marine-Derived Fungus Talaromyces purpureogenus CX11.

We report the discovery of talaropeptins A (1) and B (2), tripeptides with an unusual 5/6/5 heterocyclic scaffold and an N-trans-cinnamoyl moiety, which were identified from the marine-derived fungus Talaromyces purpureogenus CX11. A bioinformatic analysis of the genome of T. purpureogenus CX11 and gene inactivation revealed that the biosynthesis of talaropeptins involves a nonribosomal peptide synthase gene cluster. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 1 and 2 were established by electronic circular dichroism calculations and Marfey's method. The plausible biosynthesis of 1 and 2 is also proposed on the basis of gene deletion, substrate feeding, and heterologous expression. Compounds 1 and 2 showed moderate antifungal activity against phytopathogenic fungus Fusarium oxysporum with MIC values of 12.5 and 25 µg/mL, respectively.

Risk factors of in-home unintentional injuries among 0-6-year-old children in Changsha city of China: a cross-sectional survey based on Bronfenbrenner's ecological system theory.

BACKGROUND: In-home unintentional injuries (IUIs) seriously threatened children's safety. Three factors, including risky behaviors, parental supervision, and home environmental risks, have been identified as major causes for IUIs. Studies considering the interrelations between the three were limited and no relative studies has been carried out among Chinese children. The purpose of this study is to fully explore the influences of behavioral, supervisory and environmental risk factors on IUIs and their associations among Chinese children on the bases of our self-developed scales. METHODS: Through stratified cluster sampling, a cross-sectional survey was conducted with 798 parents of children aged 0 ~ 6 years in Changsha, China. Social demographics and IUIs history in the past year were collected by self-administered questionnaires. Three IUI-related scales, which had been developed and validated by our team, aimed to measure risks from children behavior, parental supervision and in-home environment. Structural equation models were constructed to analyze the relationship of these factors and their influences on IUIs using SPSS 26.0 and AMOS 22.0. RESULTS: Seven hundred ninety-eight parents were surveyed in total, and 33.58% of them reported with IUIs history of their children. X2/df, goodness-of-fit index (GFI), adjusted goodness-of-fit index (AGFI) and the root-mean-square error of approximation (RMSEA) for the model of the whole children were 4.832, 0.879, 0.856 and 0.069 respectively, indicating an acceptable level of model fit. Direct influences were discovered between risky behaviors and children's IUIs. Home environmental risks indirectly exerted impacts on IUIs by the mediating effect of risky behaviors, while the significant effect of parental supervision only existed in children aged 4-6 and girls. CONCLUSIONS: Risky behaviors played a mediating role in IUIs among children. Supervision and environmental risks affected IUIs indirectly by the exposure to risky behaviors. Parental supervision may not be able to offset the risks posed by the environmental and behavioral factors, so effective IUIs prevention strategies should focus on behavioral and environmental interventions, with appropriate supervision strategies based on the age and sex characteristics of the child.

Characterization of New Gambierones Produced by Gambierdiscus balechii 1123M1M10.

The benthic dinoflagellate genus Gambierdiscus is the primary producer of toxins responsible for ciguatera poisoning (CP), a food intoxication endemic in tropical and subtropical areas of the world. We used high-performance liquid chromatography tandem high-resolution mass spectrometry (HPLC-HRMS) to investigate the toxin profile of Gambierdiscus balechii 1123M1M10, which was obtained from Marakei Island (2°01'N, 173°15'E), Republic of Kiribati, located in the central Pacific Ocean. Four new gambierone analogues including 12,13-dihydro-44-methylgambierone, 38-dehydroxy-12,13-dihydro-44-methylgambierone, 38-dehydroxy-44-methylgambierone, and desulfo-hydroxyl gambierone, and two known compounds, gambierone and 44-methylgambierone, were proposed by analyzing their fragmentation behaviors and pathways. Our findings provide new insights into the toxin profile of Gambierdiscus balechii 1123M1M10, which can be used as a biomarker for species identification, and lay the foundation for further toxin isolation and bioactivity studies of gambierones.

Two New Alkaloids from the Marine-Derived Fungus Penicillium sp. LSH-3-1.

Two new alkaloids, peniokaramine (1) and penipyranopyridine (6), along with seven known compounds, were isolated from the marine-derived fungus Penicillium sp. LSH-3-1. Their structures were elucidated from UV, IR, MS, 1D and 2D NMR spectroscopic data. The anti-inflammatory potential of compounds 1-8 in LPS-induced RAW264.7 cells was detected, revealing that compounds 3 and 5 significantly decreased LPS-induced production of pro-inflammatory mediators, including NO, IL-6 and TNF-α. Compounds 1-8 were also screened for their cytotoxic activity against A549 cells and compound 1 showed moderate activity.

New Cytotoxic Secondary Metabolites from Two Deep-Sea-Derived Fungi and the Co-Culture Impact on the Secondary Metabolic Patterns.

In this study, chemical profiles for two co-existing deep-sea-derived Penicillium fungal strains were thoroughly investigated. Two new compounds and 11 known compounds were identified from Penicillium sp. LXY140-R, while one new compound and 12 known compounds were isolated from Penicillium sp. LXY140-3. Their structures were elucidated by extensive 1D and 2D NMR experiments, which were supported by HR-ESI-MS data. The antiproliferative activities of all isolates against HCT-116, A549 and Bel-7402 cell lines were also evaluated. Compounds 2, 5, 6, 10 and 13 showed potent antiproliferative activity. To reveal the metabolic relationship of the two strains, we conducted co-culture experiments to discover cross-talk molecules by a device that allows only small molecule to communicate. Extensive HPLC/MS2 experiments were applied to identify the disturbance of the chemical profiles within the synthetic Penicillium-Penicillium community. The fungal strain LXY140-R was found to accumulate mono or multiple-acetylation derivatives of deoxynivalenol (DON) sesquiterpenes as responsible molecules by the disturbance of the metabolites produced by the LXY140-3 strain.

Design and synthesis of highly fluorescent and stable fullerene nanoparticles as probes for folic acid detection and targeted cancer cell imaging.

Rational design and construction of fullerene derivatives play significant roles in the development of applications for sensing, marking and imaging in biomedical fields. In the present work, a novel type of C60 fluorescent nanoparticle (C60 FNP) was synthesized by a combination of thiol-ene chemistry and modification with folic acid (FA). The as-prepared C60 FNPs exhibited intense blue luminescence with a relatively high quantum yield of 26%, which is higher than that of any other reported fluorescent fullerene-based nanomaterial. Moreover, they revealed superior photobleaching resistance under constant UV lamp illumination for 5 h and excellent photostablity after 9 months of storage in water. Due to the mutual hydrogen bond interaction, the obtained C60 FNPs were capable of acting as a sensitive and specific probe for FA detection and quantification, with a liner range of 0 to 80 µM and a detection limit of 0.24 µM. Satisfactory recoveries (95.4%-105.2%) were obtained from a series of actual samples, further confirming the feasibility of this nanoprobe. Additionally, taking advantage of the FA moiety, the C60 FNPs had easy access to penetrate into cancer cells with higher expression levels of folate receptors, thereby achieving the function of targeted cellular imaging.

Longitudinal Study of Brachial-Ankle Pulse Wave Velocity and Change in Estimated Glomerular Filtration Rate among Chinese Adults.

BACKGROUND AND OBJECTIVES: Studies on the association between arterial stiffness and kidney function have generated inconsistent results. Whether arterial stiffness is linked to decline in renal function warrants further study. This study aimed to investigate the association between brachial-ankle pulse wave velocity (baPWV) and longitudinal change in estimated glomerular filtration rate (eGFR) among Chinese adults. METHODS: In this longitudinal study, 8,264 participants in a community-based cohort had baPWV measured in 2010-2011 and were followed in subsequent surveys through to 2016. During each survey visit, fasting blood samples were collected for serum creatinine and eGFR was calculated. Participants were divided into 5 groups (Q1-Q5) by baPWV quintile. The association between baPWV and longitudinal changes in eGFR was assessed using generalized estimating equation models. RESULTS: A total of 8,045 participants were included in the final analysis. The average age was 54 ± 12 years (age range 24-97 years), and mean eGFR was 93.0 ± 18.6 mL/min/1.73 m2. There was an inverse linear association between baseline baPWV and eGFR change rate (p < 0.001). Compared with Q1 (lowest) group, the mean differences and 95% CI in eGFR decrease rate among Q2-Q5 groups were -0.23 (-0.62, 0.16), -0.67 (-1.06, -0.28), -1.11 (-1.50, -0.72), and -1.30 (-1.69, -0.92) mL/min/1.73 m2 per year, respectively, after adjustment for age, gender, and other potential confounders (p trend < 0.0001). For each 100 cm/s increase in baPWV at baseline, the fully adjusted mean difference in eGFR decrease rate was -0.14 mL/min/1.73 m2 per year (95% CI -0.18, -0.10; p < 0.0001). Compared with participants with baPWV < 1,400 cm/s, the fully adjusted mean difference in eGFR decrease rate was -0.92 mL/min/1.73 m2 per year (95% CI -1.18, -0.66) for those with baPWV ≥ 1,400 cm/s (p < 0.0001). CONCLUSIONS: Participants with a higher baPWV at baseline had a greater decrease in eGFR over time. Future studies could examine the relationship between baPWV and decline in renal function in higher risk cohorts, and its potential role in targeting reno-protective interventions to those who may benefit from them most.

Changes in serum uric acid and the risk of cardiovascular disease and all-cause mortality in the general population.

BACKGROUND AND AIM: Longitudinal evidence on change in serum (SUA) with risk of cardiovascular disease (CVD) and all-cause mortality is limited, as many prior studies focused on baseline SUA. Further, the optimal threshold range of SUA change is unclear. METHODS AND RESULTS: A total of 63,127 participants without history of CVD were enrolled. Change in SUA was determined by the difference of SUA levels between 2006 and 2010, which divided by baseline SUA was percent change in SUA. Multivariable Cox proportional hazards models were used to calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). Our analysis also included restricted cubic spline model and three-piecewise Cox proportion hazards model to address the non-linearity between percent change in SUA and outcomes. During a median follow-up of 7.04 years, 3341 CVD and 3238 deaths occurred. We did not observed a significant association between changes in SUA and CVD. However, changes in SUA at extreme were associated with higher risk of all-cause mortality, the HRs (95% CIs) were 1.15 (1.02-1.29) and 1.20 (1.06-1.35) in the first and fifth quintile group, compared with the third quintile group. We further found a U-shaped association between percent change in SUA and all-cause mortality, and the optimal range was within 20%. CONCLUSIONS: Changes in SUA at extreme were risk factors for all-cause mortality, but not for CVD in the general population. The findings are relevant for role of SUA in the management of CVD risk and may contribute to improve identification of patients at higher risk.

New Drimane Sesquiterpenes and Polyketides from Marine-Derived Fungus Penicillium sp. TW58-16 and Their Anti-Inflammatory and α-Glucosidase Inhibitory Effects.

Marine fungi-derived natural products represent an excellent reservoir for the discovery of novel lead compounds with biological activities. Here, we report the identification of two new drimane sesquiterpenes (1 and 2) and six new polyketides (3-8), together with 10 known compounds (9-18), from a marine-derived fungus Penicillium sp. TW58-16. The planar structures of these compounds were elucidated by extensive 1D and 2D NMR, which was supported by HR-ESI-MS data. The absolute configurations of these compounds were determined by experimental and calculated electronic circular dichroism (ECD), and their optical rotations compared with those reported. Evaluation of the anti-inflammatory activity of compounds 1-18 revealed that compound 5 significantly inhibited the release of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells, correlating with the inhibition of expression of inducible nitric oxide synthase (iNOS). In addition, we revealed that compounds 1, 3-6, 14, 16, and 18 showed strong α-glucosidase inhibitory effects with inhibition rates of 35.4%, 73.2%, 55.6%, 74.4%, 32.0%, 36.9%, 88.0%, and 91.1%, respectively, which were comparable with or even better than that of the positive control, acarbose. Together, our results illustrate the potential of discovering new marine-based therapeutic agents against inflammation and diabetes mellitus.

Comparative Metabolomics Reveals Fungal Conversion of Co-Existing Bacterial Metabolites within a Synthetic Aspergillus-Streptomyces Community.

In nature, secondary metabolites have been proven to be the essential communication media between co-occurring microorganisms and to influence their relationship with each other. In this study, we conducted a metabolomics survey of the secondary metabolites of an artificial co-culture related to a hydrothermal vent fungal-bacterial community comprising Aspergillus sclerotiorum and Streptomyces and their reciprocal relationship. The fungal strain was found to increase the secretion of notoamides and the compound cyclo(Pro-Trp) produced by the actinomycetes strain was discovered to be the responsible molecule. This led to the hypothesis that the fungi transformed cyclo(Pro-Trp) synthesized by the actinomycetes as the biosynthetic precursors of notoamides in the chemical communication. Further analysis showed Streptomyces sp. WU20 was efficient in transforming amino acids into cyclo(Pro-Trp) and adding tryptophan as well as proline into the chemical communication enhanced the induction of the notoamide accumulation. Thus, we propose that the microbial transformation during the synthetic metabolically-mediated chemical communication might be a promising means of speeding up the discovery of novel bioactive molecules. The objective of this research was to clarify the mechanism of microbial transformation for the chemical communication. Besides, this research also highlights the utility of mass spectrometry-based metabolomics as an effective tool in the direct biochemical analysis of community metabolites.

A Novel Frequency Domain Impedance Sensor with a Perforated Cylinder Coaxial Design for In-Situ Measuring Soil Matric Potential.

Soil matric potential is an important parameter for agricultural and environmental research and applications. In this study, we developed a novel sensor to determine fast and in-situ the soil matric potential. The probe of the soil matric potential sensor comprises a perforated coaxial stainless steel cylinder filled with a porous material (gypsum). With a pre-determined gypsum water retention curve, the probe can determine the gypsum matric potential through measuring its water content. The matric potential of soil surrounding the probe is inferred by the reading of the sensor after the soil reaches a hydraulic equilibrium with the gypsum. The sensor was calibrated by determining the gypsum water retention curve using a pressure plate method and tested in three soil samples with different textures. The results showed that the novel sensor can determine the water retention curves of the three soil samples from saturated to dry when combined with a soil water content sensor. The novel sensor can respond fast to the changes of the soil matric potential due to its small volume. Future research could explore the application for agriculture field crop irrigation.