Verrucisidinol and Verrucosidinol Acetate, Two Pyrone-Type Polyketides Isolated from a Marine Derived Fungus, Penicillium aurantiogriseum

The new secondary metabolites verrucosidinol (1) and its derivative verrucosidinol acetate (2), together with a potent neurotoxin verrucosidin (3), a congener norverrucosidin (4) and a mixture of two known phytotoxic metabolites terrestric acids (5 and 6), were isolated from the marine derived fungus Penicillium aurantiogriseum. Verrucosidinol has a ring-opened ethylene oxide moiety in the polyene α-pyrone skeleton, and verrucosidinol acetate is its acetate derivative. The chemical structures were determined by comparing with literature data and a combination of spectroscopic techniques, including high resolution mass spectrum and two-dimentional nuclear magnetic resonance spectroscopic analysis

Toxic Effects of Silica Nanoparticles on Zebrafish Embryos and Larvae

Silica nanoparticles (SiNPs) have been widely used in biomedical and biotechnological applications. Environmental exposure to nanomaterials is inevitable as they become part of our daily life. Therefore, it is necessary to investigate the possible toxic effects of SiNPs exposure. In this study, zebrafish embryos were treated with SiNPs (25, 50, 100, 200 μg/mL) during 4-96 hours post fertilization (hpf). Mortality, hatching rate, malformation and whole-embryo cellular death were detected. We also measured the larval behavior to analyze whether SiNPs had adverse effects on larvae locomotor activity. The results showed that as the exposure dosages increasing, the hatching rate of zebrafish embryos was decreased while the mortality and cell death were increased. Exposure to SiNPs caused embryonic malformations, including pericardial edema, yolk sac edema, tail and head malformation. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lower dose (25 and 50 μg/mL SiNPs) produced substantial hyperactivity while the higher doses (100 and 200 μg/mL SiNPs) elicited remarkably hypoactivity in dark periods. In summary, our data indicated that SiNPs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior. © 2013 Duan et al.published_or_final_versio

Identification of pathogenic fungi causing leaf spot of Urtica cannabina and Malus sieversii in the wild fruit forest of Tianshan Mountain, Xinjiang, China

Degradation of the wild apple trees in the wild fruit forest of Tianshan mountain of Xinjiang Province, China, has attracted great attention in recent years, and pathogens are believed to be an important responsible factor. We observed that Malus sieversii and its understory plant, Urtica cannabina, exhibited similar symptoms of leaf spot disease, and we suspect that they are caused by the same pathogens. DNA sequencing using ITS1 and ITS4 primers was applied to identify the pathogenic fungi from diseased leaves of U. cannabina and M. sieversii, which led to the identification of Alternaria sp. and Fusarium sp. as active pathogens causing same symptoms on leaves of both species. Our results implied that these two plants shared the same pathogenic fungi that cause leaf spot disease, and infection of the understory species U. cannabina might provide a reservoir of the pathogens which can attack M. sieversii and contribute at least in part, to the degradation of M. sieversii

Pipecolic Acid Confers Systemic Immunity by Regulating Free Radicals

Pipecolic acid (Pip), a non-proteinaceous product of lysine catabolism, is an important regulator of immunity in plants and humans alike. In plants, Pip accumulates upon pathogen infection and has been associated with systemic acquired resistance (SAR). However, the molecular mechanisms underlying Pip-mediated signaling and its relationship to other known SAR inducers remain unknown. We show that in plants, Pip confers SAR by increasing levels of the free radicals, nitric oxide (NO), and reactive oxygen species (ROS), which act upstream of glycerol-3-phosphate (G3P). Plants defective in NO, ROS, G3P, or salicylic acid (SA) biosynthesis accumulate reduced Pip in their distal uninfected tissues although they contain wild-type-like levels of Pip in their infected leaves. These data indicate that de novo synthesis of Pip in distal tissues is dependent on both SA and G3P and that distal levels of SA and G3P play an important role in SAR. These results also suggest a unique scenario whereby metabolites in a signaling cascade can stimulate each other\u27s biosynthesis depending on their relative levels and their site of action

miR-205-5p Mediated Downregulation of PTEN Contributes to Cisplatin Resistance in C13K Human Ovarian Cancer Cells

Cisplatin resistance is a major cause of treatment failure in advanced ovarian cancer. The limited evidence shows the paradoxical regulation of miR-205 on chemotherapy resistance in cancer. Herein, we found that miR-205-5p was enormously increased in cisplatin-resistant C13K ovarian cancer cells compared with its cisplatin-sensitive OV2008 parental cells using miRNA microarrays, which was further verified by quantitative PCR. Furthermore, we confirmed that inhibition of miR-205-5p upregulated PTEN and subsequently attenuated its downstream target p-AKT, which inversed C13K cells from cisplatin resistance to sensitivity. Our data suggest that miR-205-5p contributes to cisplatin resistance in C13K ovarian cancer cells may via targeting PTEN/AKT pathway

Retinal image synthesis from multiple-landmarks input with generative adversarial networks

Background Medical datasets, especially medical images, are often imbalanced due to the different incidences of various diseases. To address this problem, many methods have been proposed to synthesize medical images using generative adversarial networks (GANs) to enlarge training datasets for facilitating medical image analysis. For instance, conventional methods such as image-to-image translation techniques are used to synthesize fundus images with their respective vessel trees in the field of fundus image. Methods In order to improve the image quality and details of the synthetic images, three key aspects of the pipeline are mainly elaborated: the input mask, architecture of GANs, and the resolution of paired images. We propose a new preprocessing pipeline named multiple-channels-multiple-landmarks (MCML), aiming to synthesize color fundus images from a combination of vessel tree, optic disc, and optic cup images. We compared both single vessel mask input and MCML mask input on two public fundus image datasets (DRIVE and DRISHTI-GS) with different kinds of Pix2pix and Cycle-GAN architectures. A new Pix2pix structure with ResU-net generator is also designed, which has been compared with the other models. Results and conclusion As shown in the results, the proposed MCML method outperforms the single vessel-based methods for each architecture of GANs. Furthermore, we find that our Pix2pix model with ResU-net generator achieves superior PSNR and SSIM performance than the other GANs. High-resolution paired images are also beneficial for improving the performance of each GAN in this work. Finally, a Pix2pix network with ResU-net generator using MCML and high-resolution paired images are able to generate good and realistic fundus images in this work, indicating that our MCML method has great potential in the field of glaucoma computer-aided diagnosis based on fundus image

A blockchain-based Shamir's Threshold Cryptography Scheme for data protection in Industrial internet of Things settings

The Industrial Internet of Things (IIoT), a typical Internet of Things (IoT) application, integrates the global industrial system with other advanced computing, analysis, and sensing technologies through Internet connectivity. Due to the limited storage and computing capacity of edge and IIoT devices, data sensed and collected by these devices are usually stored in the cloud. Encryption is commonly used to ensure privacy and confidentiality of IIoT data. However, the key used for data encryption and decryption is usually directly stored and managed by users or third-party organizations, which has security and privacy implications. To address this potential security and privacy risk, we propose a Shamir threshold cryptography scheme for IIoT data protection using blockchain: STCChain. Specifically, in our solution, the edge gateway uses a symmetric key to encrypt the data uploaded by the IoT device and stores it in the cloud. The symmetric key is protected by a private key generated by the edge gateway. To prevent the loss of the private key and privacy leakage, we use a Shamir secret sharing algorithm to divide the private key, encrypt it, and publish it on the blockchain. We implement a prototype of STCChain using Xuperchain, and the results show that STCChain can effectively prevent attackers from stealing data as well as ensuring the security of the encryption key

Orally Administered Crocin Protects Against Cerebral Ischemia/Reperfusion Injury Through the Metabolic Transformation of Crocetin by Gut Microbiota

Our pilot study suggested that orally administered crocin was hardly absorbed into circulatory system, but it was effective against cerebral ischemic/reperfusion (I/R) injury. The pharmacologically active component and targeting site of crocin remain elusive. In this study, the cerebral-protective effect of crocin was evaluated on a rat transient middle cerebral artery occlusion (MCAO) model. Our data showed that oral administration of crocin had better effectiveness in cerebral protection than an intravenous injection. Neither crocin nor its metabolite crocetin were determined in the brain of cerebral I/R rats, indicating a target site of periphery. Abundant crocetin was detected in plasma after oral administration instead of intravenous injection of crocin. Meanwhile, orally administered crocetin showed similar cerebral protection to that of crocin, but this exciting effect was not clearly observed by intravenous administration of crocetin, indicating the importance of crocetin in gut. Moreover, orally administered crocin showed less cerebral-protective effect in pseudo germ-free (pGF) MCAO rats. In vitro and in vivo experiments confirmed that crocin could be deglycosylated to crocetin in gut content of normal rats, rather than that of pGF rats, indicating that gut microbiota facilitated the transformation of crocin into crocetin, which played a key role in the activation of the pharmacological effect. Metabolomic study revealed that microbial-host co-metabolic molecules were significantly perturbed after oral administration of crocin, indicating a regulation on intestinal ecosystem. It was further suggested that gut microbiota may be the potential target of the cerebral-protective effect of crocin

Simultaneous radical cystectomy and nephroureterectomy in the treatment of panurothelial carcinoma: a systematic review and single-arm meta-analysis

BackgroundPanurothelial carcinoma is a rare and aggressive malignancy that requires effective treatment strategies to enhance patient outcomes.MethodsWe conducted a systematic search of English publications in databases including PubMed, Embase, Cochrane Library, and Web of Science up to May 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS) and the Methodological Quality and Synthesis of Case Series and Case Reports tool. Data statistics and analysis were performed using Stata 15.1 software (StataSE, USA).ResultsSix studies involving 339 patients were included in the analysis. Meta-analysis revealed that Simultaneous Radical Cystectomy and Nephroureterectomy had 2-year and 5-year overall survival rates of 68% (95% CI 60%-76%, I2 = 12.4%, P < 0.001) and 44% (95% CI 36%-53%, I2 = 0, P < 0.001), respectively. The 2-year and 5-year progression-free survival rates were 91% (95% CI 86%-95%, I2 = 95%, P < 0.001) and 65% (95% CI 58%-73%, I2 = 91.5%, P < 0.001), respectively. The 2-year and 5-year cancer-specific survival rates were 73% (95% CI 66%-81%, I2 = 16.7%, P < 0.001) and 57% (95% CI 49%-66%, I2 = 0, P < 0.001), respectively. Additionally, the incidence of minor complications was 19% (95% CI 15%-23%, P < 0.01), major complications was 49% (95% CI 34%-63%, P < 0.01), and the intraoperative blood transfusion rate was 53% (95% CI 44%-61%, P < 0.01).ConclusionsSimultaneous radical cystectomy and nephroureterectomy represent feasible approaches for the treatment of Panurothelial carcinoma. Nonetheless, a comprehensive assessment of the surgical risks and benefits is imperative, and larger-scale prospective cohort studies are required to validate therapeutic efficacy. Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023426401

Integrative transcriptome and metabolome analysis reveals the mechanisms of light-induced pigmentation in purple waxy maize

IntroductionWaxy maize, mainly consumed at the immature stage, is a staple and vegetable food in Asia. The pigmentation in the kernel of purple waxy maize enhances its nutritional and market values. Light, a critical environmental factor, affects anthocyanin biosynthesis and results in pigmentation in different parts of plants, including in the kernel. SWL502 is a light-sensitive waxy maize inbred line with purple kernel color, but the regulatory mechanism of pigmentation in the kernel resulting in purple color is still unknown.MethodsIn this study, cyanidin, peonidin, and pelargonidin were identified as the main anthocyanin components in SWL502, evaluated by the ultra-performance liquid chromatography (UPLC) method. Investigation of pigment accumulation in the kernel of SWL502 was performed at 12, 17, and 22 days after pollination (DAP) under both dark and light treatment conditions via transcriptome and metabolome analyses.ResultsDark treatment affected genes and metabolites associated with metabolic pathways of amino acid, carbohydrate, lipid, and galactose, biosynthesis of phenylpropanoid and terpenoid backbone, and ABC transporters. The expression of anthocyanin biosynthesis genes, such as 4CL2, CHS, F3H, and UGT, was reduced under dark treatment. Dynamic changes were identified in genes and metabolites by time-series analysis. The genes and metabolites involved in photosynthesis and purine metabolism were altered in light treatment, and the expression of genes and metabolites associated with carotenoid biosynthesis, sphingolipid metabolism, MAPK signaling pathway, and plant hormone signal transduction pathway were induced by dark treatment. Light treatment increased the expression level of major transcription factors such as LRL1, myc7, bHLH125, PIF1, BH093, PIL5, MYBS1, and BH074 in purple waxy maize kernels, while dark treatment greatly promoted the expression level of transcription factors RVE6, MYB4, MY1R1, and MYB145.DiscussionThis study is the first report to investigate the effects of light on waxy maize kernel pigmentation and the underlying mechanism at both transcriptome and metabolome levels, and the results from this study are valuable for future research to better understand the effects of light on the regulation of plant growth