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关键词： Ca2+ signals   NtBAG5   NtCaM   senescence   tobacco   yellowing  

摘要： Leaf yellowing critically impacts tobacco quality and economic value. The Bcl-2-associated athanogene (BAG) gene family regulates plant development and senescence, yet the role of NtBAG5 in tobacco remains poorly understood. Here, we demonstrate that NtBAG5 acts as a key promoter of leaf senescence. CRISPR/Cas9-generated NtBAG5 mutants exhibited delayed senescence, enhanced activities of antioxidant enzymes, and reduced malondialdehyde (MDA) content, whereas NtBAG5-overexpressing plants showed the opposite effects. Promoter-GUS analysis revealed high NtBAG5 expression in roots and stems. Hormone treatments indicated that NtBAG5 expression is upregulated by ABA, ETH, IAA, and GA (at late stage) but downregulated by MeJA. Mechanistically, NtBAG5 interacts with calmodulin (CaM) via its BAG domain and IQ motif, as confirmed by yeast two-hybrid and BiFC assays. Ca2 + was found to modulate CaM conformation and strengthen the NtBAG5-CaM interaction. Silencing NtCaM via VIGS induced severe leaf yellowing and growth defects. Our results reveal that the NtBAG5-CaM complex, regulated by Ca2 + and hormones, modulates leaf senescence through the antioxidant system, providing new insights for improving tobacco quality.

关键词： CAEVMD   multiscale convolutional neural networks   CAM   SAM   sparse penalty  

摘要： Rolling bearings inevitably generate noise during operation, which reduces diagnostic accuracy. In this paper, we propose a center-frequency-learning Variational Modal Decomposition (VMD) combined with a Convolutional Autoencoder (CAE) (CAEVMD) to process noisy signals and extract fault features, using a multiscale Convolutional Neural Network (CNN) for bearing fault diagnosis. First, the noisy signal is fed into the VMD for decomposition. The decomposed modal signal is sparsely penalized to suppress the modal noise. The sparsely penalized modal component is encoded, compressed, decoded, and reconstructed. The reconstructed output signal shows reduced noise. Secondly, the fault features are extracted using a multiscale dilated Convolutional Neural Network, combined with the Spatial Attention Mechanism (SAM) and the Channel Attention Mechanism (CAM), for fault diagnosis. Validated on the Western Reserve University bearing dataset and the simulated bearing experimental dataset, the experimental results show that the proposed network model achieves high diagnostic accuracy across different noise conditions, outperforms the comparative methods, and demonstrates high accuracy, robustness, and good generalization.

关键词： Inflammatory bowel disease   polyphenols   polysaccharides   short-chain fatty acids   probiotics   microbiota   antioxidants   anti-inflammatory  

摘要： Inflammatory bowel disease (IBD) is a chronic autoimmune condition whose pathogenesis has not been fully elucidated, and current treatments are not definitive and often carry several side effects. The Complementary and Alternative Medicine (CAM) offers a new approach to conventional medicine. However, their clinical application and mechanisms remain ***: The aim of this review is to evaluate the anti-inflammatory, impact on microbiota and antioxidant efficacy of currently available CAM for ***: The literature collection was obtained from Google Scholar, MEDLINE, PubMed and Web of Science (WOS). Studies in both human and animal models, published in English language between 2018 and 2024, were selected. Sixty-seven studies were included in the current review after inclusion and exclusion screening ***: Mostly, studies showed significant anti-inflammatory, gut microbiota restoring, antioxidant effects of polyphenols, polysaccharides, emodin, short-chain fatty acids (SCFA;including butyrate, propionate and acetate), and probiotics although some contrasting results were noted. Current evidence shows that polyphenols exhibit the most consistent result in alleviating IBD pathophysiology, primarily due to their significant SCFA-elevating ***: Future studies may focus on human studies, narrowing down on individual factors which may change natural product's metabolism. Further research studies are also essential to obtain therapeutic recommendations.

关键词： deep learning   pneumothorax   CAD   chest x-rays   pneumonia   chest radiographs  

摘要： Lung diseases remain a major global health concern, necessitating the development of advanced diagnostic methods. A chest x-ray is the most common diagnostic tool for lung diseases in medical practice. This research explores the application of deep learning in computer-aided diagnosis (CAD) for lung disease screening. The proposed computational model is evaluated against existing methodologies to assess its efficacy in detecting lung diseases using chest x-ray datasets. This study presents the development and evaluation of a DL-based classification model designed to automatically detect and differentiate pneumothorax and pneumonia from normal images of chest radiographs. The model is trained and validated using publicly available benchmark datasets to ensure its robustness and generalizability and then tested with images obtained from Maharishi Markandeshwar Institute of Medical Science and Research, Mullana, Ambala. The pre-processed images trained and tested with several pre-trained models based on CNN Vgg-16, EfficientNet, Inception, MobileNet, MobileNetV2, MobileNetV3small. MobileNetV3small achieved the highest accuracy of 97% in classifying lung diseases. This model also evaluates the match percentage of detected disease which helps medical experts identifying disease which otherwise are sometimes difficult to identify and helpful for new radiologists. The proposed model achieved high accuracy in diagnosing chest diseases using chest x-rays. Evaluation on the testing dataset demonstrated that the model significantly outperforms existing methods in terms of classification performance.

关键词： Cardiac magnetic resonance   coronary computerized tomography angiography   revascularizations   health economic   cost effective   cost saving   I10   I19  

摘要： AimsWhile the clinical benefits of non-invasive modalities to diagnose coronary artery disease (CAD) are well recognized, the economic implications of their use over invasive options remain unclear. This review aims to understand the health economic consequences of using non-invasive versus invasive modalities in symptomatic patients with low-to-intermediate pre-test probability (PTP) of CAD, and to explore whether economic and humanistic data can inform future investment decisions around non-invasive and invasive diagnostic *** and methodsWe performed a systematic review of MEDLINE and Embase, MEDLINE In-process, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Studies from January 1992 to January 2023 were included, if they were based in the UK, France, Germany, Italy, Japan, China, and/or the USA (published in any language). Risk of bias was assessed using the Drummond *** evaluated invasive techniques, including invasive catheterization angiography (ICA) and ICA with fractional flow reserve (ICA-FFR), as well as non-invasive modalities, including coronary computerized tomography angiography (CCTA), CCTA-FFR, cardiovascular magnetic resonance (CMR), stress electrocardiogram, myocardial perfusion scintigraphy-single photon emission computed tomography, positron emission tomography, and stress *** and methodsWe performed a systematic review of MEDLINE and Embase, MEDLINE In-process, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Studies from January 1992 to January 2023 were included, if they were based in the UK, France, Germany, Italy, Japan, China, and/or the USA (published in any language). Risk of bias was assessed using the Drummond *** evaluated invasive techniques, including invasive catheterization angiography (ICA) and ICA with fractional flow reserve (ICA-FFR), as well as non-invasive modaliti

关键词： Coronary artery disease   ischemic heart disease   cardiovascular magnetic resonance   myocardial perfusion scintigraphy by single photon emission computed tomography   health economic analysis   cost-effectiveness   I10   I19  

摘要： AimsThe health economic impacts of cardiovascular magnetic resonance (CMR) imaging and myocardial perfusion scintigraphy by single photon emission computed tomography (MPS-SPECT) as diagnostic modalities are not well understood. This review is based on a wider systematic review and aims to compare CMR and MPS-SPECT as first-line, non-invasive modalities for the diagnosis of symptomatic individuals with a low-to-intermediate pre-test probability (PTP) of coronary artery disease (CAD).Materials and methodsWe performed a systematic review of MEDLINE and Embase, MEDLINE In-process, the Cochrane Database of Systematic reviews and the Cochrane Central Register of Controlled Trials. Studies from January 1992 to January 2023 were included, if they were based in the UK, France, Germany, Italy, Japan, China, and/or the USA (published in any language). Risk of bias was assessed using the Drummond *** relevant reports were identified. In the USA, CMR was consistently cost-effective compared with MPS-SPECT for patients with a low-to-intermediate PTP of CAD;resource use and associated costs, as well as total costs, were lower. For patients with a low-to-intermediate PTP of CAD in Europe, CMR was cost-effective in Germany, while in the UK increases in quality-adjusted life-years were found but cost savings were mixed. This review found only 13 reports on the economic benefits of CMR over MPS-SPECT, with just three providing cost-effectiveness outcomes, highlighting the need for further research across different settings and ***, findings suggest that the cost savings from using CMR compared with MPS-SPECT for patients with a low-to-intermediate PTP of CAD support prioritized investment;however, confirmatory research is needed given the limited number of cost-effectiveness analyses identified in this review.

关键词： cinnamyl alcohol dehydrogenase7   histamine   Phytophthora parasitica   plant susceptibility   small-molecule aldehyde reductase  

摘要： Negative immune regulator CAD7 is a non-canonical member of the CAD (cinnamyl alcohol dehydrogenase) family in plants. However, little is known on its biochemical functions and underlying mechanisms of immune regulation. Here, we show that Arabidopsis thaliana AtCAD7 harbours substrate-binding residues divergent from lignin-forming CADs (AtCAD4/5), being conserved with bacterial alcohol dehydrogenases EcYahK and EcYjgB. Comparative enzymatic analysis revealed that AtCAD7 exhibits a broad substrate preference for diverse small-molecule aldehydes, including histamine-derived intermediates, being distinct from the canonical lignin-forming AtCAD5. Metabolomic analyses revealed that AtCAD7-overexpression transformants were affected in the biosynthesis and metabolism of amino acids, whereas AtCAD7-silencing lines were activated in the phenylpropanoid pathway and increased in flavonoid accumulation. Histamine was elevated in AtCAD7-overexpression lines and functional validation revealed its promoted effect on plant susceptibility to Phytophthora parasitica. In contrast, phytoalexins scopolin and chlorogenic acid were enriched in AtCAD7-silencing lines, accompanied by upregulated expression of phenylpropanoid pathway-related genes. Functional validation demonstrated that scopolin and chlorogenic acid enhanced plant resistance to P. parasitica. Collectively, our study uncovers that CAD7 functions as a metabolic hub linking small-molecule aldehyde reductase activity to immune suppression, providing a potential novel target for developing crops with enhanced resistance to Phytophthora pathogens.

关键词： End-of-life dreams and visions   end-of-life experiences   delirium   CAM   palliative care  

摘要： Objectives End-of-life dreams and visions (ELDVs) and delirium frequently occur near death but differ in core features. Clinical differentiation becomes challenging when they co-occur. This case report illustrates the interplay between ELDVs and delirium, examines the limits of current diagnostic criteria in mixed cases, and outlines a nuanced approach to *** We report the case of an elderly Brazilian woman with metastatic cancer who exhibited both ELDVs and delirium. Mental status was serially assessed using the Confusion Assessment Method (CAM). ELDV accounts were prospectively triangulated across patient, family, and clinician reports to enhance reliability and contextual *** The patient's experiences showed ELDV hallmarks - vivid, realistic encounters with deceased relatives, biographical relevance, and preparatory themes - yet many were affectively distressing and occurred alongside fluctuating attention and consciousness consistent with delirium. CAM effectively identified delirium but could not, on its own, distinguish ELDVs within delirious states. When co-occurring, ELDVs often emerged during "windows of lucidity" marked by preserved autobiographical context, intact recall with subsequent coherent narration, and insight, despite intense emotional valence. Distress alone was not discriminatory, probably being shaped by psychosocial and cultural factors. These observations indicate the need to supplement CAM with qualitative and phenomenological criteria, including content, vividness, biographical meaning, insight, cultural fit, and acuity/*** To our knowledge, this is the first case to map evolving end-of-life mental status using serial CAM while prospectively documenting ELDVs via triangulated reports. The findings highlight the complexity of differentiating co-occurring ELDVs and delirium and challenge the sufficiency of CAM alone. An integrated approach - combining CAM screening with structured ELDV assess

关键词： CAD   De novo synthesis of pyrimidine   Icaritin   Liver cancer   miR-18b-5p  

摘要： Cancer cells show abnormal nucleotide metabolism and prefer the de novo synthesis pathway. As the key enzymes, Carbamoyl-phosphate synthetase 2, Aspartate transcarbamoylase, and Dihydroorotase (CAD) is overactivated in cancer and promotes pyrimidine de novo synthesis, supplying cancer cells with DNA and RNA biosynthesis precursors. Therefore, the development of drugs targeting CAD might inhibit cancer progression and transformation. Icaritin (ICT) is an isoprenoid flavonoid derivative with a wide range of anticancer activities, however, the mechanism of ICT in regulating pyrimidine biosynthesis in cancer remains unclear. MicroRNAs are involved in carcinogenesis by regulating the expression of target genes, and ICT has been shown to regulate the expression of miRNAs leading to suppressing cancer progression. Using both human normal hepatocytes and liver cancer cells, we found that CAD expression was significantly elevated in cancer cells. Interestingly, although ICT treatment reduced CAD protein levels in liver cancer cells, it increased CAD transcriptional activity. Dual-luciferase reporter assays confirmed miR-18b-5p as a direct regulator of CAD. By transfecting miR-18b-5p mimics or inhibitors, we showed ICT upregulates miR-18b-5p to suppress CAD, inhibiting liver cancer cell proliferation, migration, and colony formation. Furthermore, in a human liver cancer xenograft mouse model, ICT treatment markedly reduced tumor growth and decreased Ki-67 expression, consistent with the in vitro results, CAD protein expression was downregulated, while its mRNA level was upregulated, further supporting a post-transcriptional regulatory mechanism. Overall, ICT plays an anti-liver cancer role by increasing miR-18b-5p at the post-transcriptional level to inhibit CAD expression, which may interfere with the de novo synthesis of pyrimidine and development of liver cancer. © 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature