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Abstract Background Activating the ubiquitin-proteasome system to dismantle disease- related proteins such as tau, β-amyloid, APP, and α-synuclein is an important focus in the research of neurodegenerative proteinopathy. By analyzing the serum RNA extracted from wild-type and Alzheimer’s disease (AD) transgenic mice at different ages (4, 8, and 12 months), this study revealed a new protective role of FBXL16 in AD, primarily through facilitating the degradation of disease-related proteins via the ubiquitin proteasome system. Methods Proteomic analysis were conducted using protein lysates from HEK293 cells overexpressing FBXL16 to identify potential interacting proteins that interact with FBXL16. Subsequent experiments demonstrated that FBXL16 promotes the proteasomal degradation of the APP protein, as evidenced by co-immunoprecipitation with MG132 and cycloheximide (CHX), immunohistochemistry (IHC) and immunocytochemistry (ICC). Memory and cognitive improvements were observed in 3×Tg AD mice through the use of a lentivirus-mediated approach to generate a brain-specific AD mouse model overexpressing FBXL16 via stereotaxic injection. Furthermore, a brain-specific conditional knockout (cko) FBXL16 mouse model was generated and employed to further confirm the functional role of FBXL 16 in AD via various behavioral tests including Morris water maze and Y-maze. Results The level of FBXL16 in the brains of transgenic APP/PSEN mice with AD decreased with age. Accelerated degradation of APP was observed when FBXL16 was overexpressed in the hippocampi of these AD mice via a lentivirus. This process led to notable improvements in cognitive impairments and reductions in neuroinflammation. Further studies using proteomics and bioinformatics techniques identified transcription factors and binding proteins associated with FBXL16, providing deeper insights into the potential role of FBXL16 in the regulation of AD. Finally, the in vivo effects of FBXL16 deficiency were further substantiated in cko mice, which overexpress Aβ but specifically lack FBXL16 in the brain region. Conclusions These findings suggest that FBXL16 could be a new regulator of AD. These findings provide a foundation for further research into drug development and potential therapeutic strategies to combat other related neurodegenerative proteinopathies.

Abstract The increasing incidence of cardiovascular diseases has resulted in an escalating need for natural dietary supplements with cardioprotective properties. This review provides a thorough analysis of laboratory and clinical studies conducted on dietary quercetin, a widely available flavonoid, and its influence on the management of cardiovascular health and disease. The references cited in this review were obtained from reputable databases, including SciFinder, Web of Science, and ClinicalTrials.gov, with a specific focus on the period spanning from 1999 to 2023 pertaining to this subject matter. Notably, a bibliometric approach was used to analyze the bibliometric attribute trends of the research on quercetin associated with vascular health for the first time. Numerous investigations conducted on animal and human subjects at different phases of cardiac illness have consistently shown that the administration of quercetin substances improves cardiac function, suggesting the potential efficacy of quercetin in the management of heart disease. Evidently, the consumption of quercetin through dietary sources holds promise in conferring significant cardiovascular benefits through physiological mechanisms and biochemical signaling pathways, thus positioning it as a promising dietary contender for the prevention of cardiovascular disorders. Renewable food resources, including lovage leaves, elderberry, and radish leaves, which are abundant in quercetin, exhibit significant potential for the development and production of novel healthcare products with the objective of preventing cardiovascular disorders. This review is anticipated to provide valuable insights for the advancement of cardioprotective functional foods in the foreseeable future.

Background: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application. Aim of Review: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development. Key scientific Concepts of Review: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated.

Valsa mali (V. mali) is a necrotrophic fungus responsible for apple Valsa canker, which significantly diminishes apple production yields and quality in China. Our serendipitous findings revealed that genistein significantly inhibits the mycelial growth of V. mali, with an inhibition rate reaching 42.36 ± 3.22% at a concentration of 10 µg/mL. Scanning electron microscopy analysis revealed that genistein caused significant changes in the structure of V. mali, including mycelial contraction, distortion, deformity, collapse, and irregular protrusions. Transmission electron microscopy analysis revealed leakage of cellular contents, blurred cell walls, ruptured membranes, and organelle abnormalities. Genistein has been shown to increase reactive oxygen species levels in V. mali mycelia, as demonstrated by 2′,7′-dichlorofluorescin diacetate staining. This increase was associated with a decrease in superoxide dismutase activity alongside increases in catalase and peroxidase activities. These changes collectively disrupted the oxidative equilibrium, leading to the induction of oxidative stress. The transcriptomic analysis revealed 13 genes enriched in this process, linked to unsaturated fatty acid biosynthesis (three downregulated DEGs), saturated fatty acid biosynthesis (three upregulated and six downregulated DEGs), and fatty acid metabolism (four upregulated and nine downregulated DEGs). Additionally, the downregulated DEGs VMIG_07417 and VMIG_08675, which are linked to ergosterol biosynthesis, indicate possible changes in membrane composition. In conjunction with the qRT-PCR results, it is hypothesized that genistein exerts an antifungal effect on V. mali through ROS-mediated lipid peroxidation. This finding has the potential to contribute to the development of novel biological control agents for industrial crops.

Metabolic reprogramming is a critical pathogenesis of colorectal cancer (CRC), referring to metabolic disorders that cancer cells make in response to the stimulating pressure. Metabolic reprogramming induces changes in genetic material and promotes CRC progression and has been proven to be an efficient target of CRC. As natural products have garnered interest due to notable pharmacological effects and potential in counteracting chemoresistance, an increasing body of research is delving into the impact of these natural products on the metabolic reprogramming associated with CRC. In this review, we collected published data from the Web of Science and PubMed, covering the period from January 1980 to October 2023. This article focuses on five central facets of metabolic alterations in cancer cells, glucose metabolism, mitochondrial oxidative phosphorylation (OXPHOS), amino acid metabolism, fatty acid synthesis, and nucleotide metabolism, to provide an overview of recent advancements in natural product interventions targeting metabolic reprogramming in CRC. Our analysis underscores the potential of natural products in disrupting the metabolic pathways of CRC, suggesting promising therapeutic targets for CRC and expanding treatment options for metabolic-associated ailments.

Intracerebral hemorrhage (ICH) is a critical condition characterized by a high prevalence, substantial mortality rates, and unpredictable clinical outcomes, which results in a serious threat to human health. Improving the timeliness and accuracy of prognosis assessment is crucial to minimizing mortality and long-term disability associated with ICH. Due to the complexity of ICH, the diagnosis of ICH in clinical practice heavily relies on the professional expertise and clinical experience of physicians. Traditional prognostic methods largely depend on the specialized knowledge and subjective judgment of healthcare professionals. Meanwhile, existing artificial intelligence (AI) methodologies, which predominantly utilize features derived from computed tomography (CT) scans, fall short of capturing the multifaceted nature of ICH. Although existing methods are capable of integrating clinical information and CT images for prognosis, the effectiveness of this fusion process still requires improvement. To surmount these limitations, the present study introduces a novel AI framework, termed the ICH Network (ICH-Net), which employs a joint-attention cross-modal network to synergize clinical textual data with CT imaging features. The architecture of ICH-Net consists of three integral components: the Feature Extraction Module, which processes and abstracts salient characteristics from the clinical and imaging data, the Feature Fusion Module, which amalgamates the diverse data streams, and the Classification Module, which interprets the fused features to deliver prognostic predictions. Our evaluation, conducted through a rigorous five-fold cross-validation process, demonstrates that ICH-Net achieves a commendable accuracy of up to 87.77%, outperforming other state-of-the-art methods detailed within our research. This evidence underscores the potential of ICH-Net as a formidable tool in prognosticating ICH, promising a significant advancement in clinical decision-making and patient care.

Texture synthesis technology is an important realistic rendering technology. Texture synthesis technology also has a good application prospect in image rendering and other fields. Convolutional neural network is a very popular technology in recent years. Convolutional neural network model can learn the features in data and realize intelligent processing through the feature learning in data. Later, with the rapid improvement of convolutional neural network, texture synthesis technology based on neural network came into being. The purpose of this paper is to study the texture synthesis method of ecological plant protection image based on convolutional neural network. By studying the context and research implications, the definition of textures as well as texture synthesis methods, convolutional neural networks, and based on convolutional neural network. In the experiment, the experimental environment is established, and the subjective evaluation and objective evaluation of the image texture synthesis method experiment are investigated and studied by using swap algorithm. The experimental results show that the method used in this paper is superior to other methods.

Breast cancer is one of most serious malignant tumors that affect women’s health. To carry out the early screening of breast cancer, mammography provides breast cancer images for doctors’ efficient diagnosis. However, breast cancer lumps can vary in size and shape, bringing difficulties for the accurate recognition of both humans and machines. Moreover, the annotation of such images requires expert medical knowledge, which increases the cost of collecting datasets to boost the performance of deep learning methods. To alleviate these problems, we propose an attention-based active learning framework for breast cancer segmentation in mammograms; the framework consists of a basic breast cancer segmentation model, an attention-based sampling scheme and an active learning strategy for labelling. The basic segmentation model performs multi-scale feature fusion and enhancement on the basis of UNet, thus improving the distinguishing representation capability of the extracted features for further segmentation. Afterwards, the proposed attention-based sampling scheme assigns different weights for unlabeled breast cancer images by evaluating their uncertainty with the basic segmentation model. Finally, the active learning strategy selects unlabeled images with the highest weights for manual labeling, thus boosting the performance of the basic segmentation model via retraining with new labeled samples. Testing on four datasets, experimental results show that the proposed framework could greatly improve segmentation accuracy by about 15% compared with an existing method, while largely decreasing the cost of data annotation.

As one of the most characteristic ingredients of glandular trichome secretions from Nicotiana tabacum L. (tobacco), natural cembrenediols, namely, (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (α-cembrenediol/α-CBD) and its C-4 epimer (β-cembrenediol/β-CBD), have attracted considerable attention for their potent antitumor, neuroprotective, antimicrobial, and other activities. Many researchers are committed to exploring the possibility of utilizing these two cembrenediols and their derivatives both in human medicine and in agricultural fungicides. To the best of our knowledge, this review is the first to provide a comprehensive summary of the chemical modifications and bioactivities of α- and β-CBD from their discovery to the present day; the review highlights their potential medicinal value for humans. The extensive references from 1962 to 2022 provided herein were systematically gathered from the SciFinder, Web of Science, and Google Scholar databases. We expect this review to assist in providing practical ideas for future drug development based on α- and β-CBD and in further facilitating the utilization of the tobacco cembrenediols.

Platycodon grandiflorum (Jacq.) A.DC is a perennial single-species herb in the Campanulaceae family, and its dried roots have been widely used for a long time to diffuse the lung, soothe the throat, dispel phlegm, and expel pus as a Chinese traditional medicine. In addition, P. grandiflorum compounds are homologous to those in medicines and foods approved by the Ministry of Health of China, and many related foods have been marketed. It has been reported that the glycosides in pentacyclic triterpenoids, also known as saponins, are the main biologically active constituents of P. grandiflorum. This article offers a systematic review of recently reported saponins isolated from P. grandiflorum over the past decade covering the literature from the beginning of 2017 through the end of 2022 and describes their structural diversity and pharmacological studies. To the best of our knowledge, a total of 74 natural saponins have been isolated to date. For this review, 131 references on saponins were obtained, and the information from these articles is compiled herein. This review may be of interest to pharmacognosists and natural-product chemists. This review provides new ideas for the development and utilization of natural saponins for clinical applications in the future. [ABSTRACT FROM AUTHOR]