H19 lncRNA triggers ferroptosis, exacerbating ox-LDL-induced artery endothelial cell damage in vitro.

BACKGROUND: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. OBJECTIVE: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. METHODS: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. RESULTS: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. CONCLUSIONS: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL.

Zero-shot prediction of mutation effects with multimodal deep representation learning guides protein engineering.

Mutations in amino acid sequences can provoke changes in protein function. Accurate and unsupervised prediction of mutation effects is critical in biotechnology and biomedicine, but remains a fundamental challenge. To resolve this challenge, here we present Protein Mutational Effect Predictor (ProMEP), a general and multiple sequence alignment-free method that enables zero-shot prediction of mutation effects. A multimodal deep representation learning model embedded in ProMEP was developed to comprehensively learn both sequence and structure contexts from ~160 million proteins. ProMEP achieves state-of-the-art performance in mutational effect prediction and accomplishes a tremendous improvement in speed, enabling efficient and intelligent protein engineering. Specifically, ProMEP accurately forecasts mutational consequences on the gene-editing enzymes TnpB and TadA, and successfully guides the development of high-performance gene-editing tools with their engineered variants. The gene-editing efficiency of a 5-site mutant of TnpB reaches up to 74.04% (vs 24.66% for the wild type); and the base editing tool developed on the basis of a TadA 15-site mutant (in addition to the A106V/D108N double mutation that renders deoxyadenosine deaminase activity to TadA) exhibits an A-to-G conversion frequency of up to 77.27% (vs 69.80% for ABE8e, a previous TadA-based adenine base editor) with significantly reduced bystander and off-target effects compared to ABE8e. ProMEP not only showcases superior performance in predicting mutational effects on proteins but also demonstrates a great capability to guide protein engineering. Therefore, ProMEP enables efficient exploration of the gigantic protein space and facilitates practical design of proteins, thereby advancing studies in biomedicine and synthetic biology.

Characterization of the gut microbiota and fecal metabolome in the osteosarcoma mouse model.

Previous studies have reported the correlation between gut microbiota (GM), GM-derived metabolites, and various intestinal and extra-intestinal cancers. However, limited studies have investigated the correlation between GM, GM-derived metabolites, and osteosarcoma (OS). This study successfully established a female BALB/c nude mouse model of OS. Mice (n = 14) were divided into the following two groups (n = 7/group): OS group named OG, injected with Saos-2 OS cells; normal control group named NCG, injected with Matrigel. The GM composition and metabolites were characterized using 16S rDNA sequencing and untargeted metabolomics, respectively. Bioinformatics analysis revealed that amino acid metabolism was dysregulated in OS. The abundances of bone metabolism-related genera Alloprevotella, Rikenellaceae_RC9_gut_group, and Muribaculum were correlated with amino acid metabolism, especially histidine metabolism. These findings suggest the correlation between GM, GM-derived metabolites, and OS pathogenesis. Clinical significance: The currently used standard therapeutic strategies for OS, including surgery, chemotherapy, and radiation, are not efficacious. The findings of this study provided novel insights for developing therapeutic, diagnostic, and prognostic strategies for OS.

[Advances in Nanotechnology-Based Drug Delivery Systems in the Treatment of Hepatocellular Carcinoma].

Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.

Application of novel CRISPR tools in brain therapy.

In recent years, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based genome editing toolkit has been widely used to modify the genome sequence of organisms. As the CRISPR toolbox continues to grow and new CRISPR-associated (Cas) proteins are discovered, its applications have expanded beyond conventional genome editing. This now encompass epigenetic editing, gene expression control, and various other functions. Notably, these advancements are finding practical application in the treatment of brain diseases. Furthermore, the amalgamation of CRISPR and Chimeric Antigen Receptor T-cell (CAR-T) technologies has emerged as a potential approach for disease treatment. With this in mind, this review commences by offering a comprehensive overview of recent advancements in CRISPR gene editing tools. This encompasses an exploration of various Cas proteins, gene expression control, epigenetic editing, base editing and primer editing. Additionally, we present an in-depth examination of the manifold applications of these innovative CRISPR tools in the realms of brain therapeutics, such as neurodegenerative diseases, neurological syndromes and genetic disorders, epileptic disorders, and brain tumors, also explore the pathogenesis of these diseases. This includes their utilization in modeling, gene screening, therapeutic gene editing, as well as their emerging synergy with CAR-T technology. Finally, we discuss the remaining technical challenges that need to be addressed for effective utilization of CRISPR tools in disease treatment.

Clinical features and viral load variations of Mpox: a retrospective study in Chongqing, China.

PURPOSE: Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. METHOD: We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. RESULTS: As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. CONCLUSION: In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Comparison and optimization of different CRISPR/Cas9 donor-adapting systems for gene editing.

Gene knock-in in mammalian cells usually uses homology-directed repair (HDR) mechanism to integrate exogenous DNA template into the target genome site. However, HDR efficiency is often low, and the co-localization of exogenous DNA template and target genome site is one of the key limiting factors. To improve the efficiency of HDR mediated by CRISPR/Cas9 system, our team and previous studies fused different adaptor proteins with SpCas9 protein and expressed them. By using their characteristics of binding to specific DNA sequences, many different CRISPR/SpCas9 donor adapter gene editing systems were constructed. In this study, we used them to knock-in eGFP gene at the 3'-end of the terminal exon of GAPDH and ACTB genes in HEK293T cells to facilitate a comparison and optimization of these systems. We utilized an optimized donor DNA template design method, validated the knock-in accuracy via PCR and Sanger sequencing, and assessed the efficiency using flow cytometry. The results showed that the fusion of yGal4BD, hGal4BD, hLacI, hTHAP11 as well as N57 and other adaptor proteins with the C-terminus of SpCas9 protein had no significant effect on its activity. At the GAPDH site, the donor adapter systems of SpCas9 fused with yGal4BD, hGal4BD, hLacI and hTHAP11 significantly improved the knock-in efficiency. At the ACTB site, SpCas9 fused with yGal4BD and hGal4BD significantly improved the knock-in efficiency. Furthermore, increasing the number of BS in the donor DNA template was beneficial to enhance the knock-in efficiency mediated by SpCas9-hTHAP11 system. In conclusion, this study compares and optimizes multiple CRISPR/Cas9 donor adapter gene editing systems, providing valuable insights for future gene editing applications.

Global trends and research hotspots of PCSK9 and cardiovascular disease: a bibliometric and visual analysis.

Background: Cardiovascular disease (CVD) is a prevalent non-communicable disease globally and holds the position of being the primary cause of mortality worldwide. Consequently, considerable focus has been directed towards the prevention and management of CVD. PCSK9, a frequently targeted element in the treatment and prevention of CVD, can reduce cardiovascular risk by effectively lowering lipid levels even in the context of statin therapy. It also exhibits substantial potential in the diagnosis and treatment of familial hypercholesterolemia from genetic aspects. This bibliometric study aims to analyze and visualize the global trends and emerging hotspots of PCSK9 and CVD researches and provide researchers with new perspectives in further studies. Methods: The data was obtained from the Web of Science Core Collection database. A total of 2,474 publications related to PCSK9 and CVD published between January 2006 and July 2023 were included. The VOSviewer was used to analyze most-cited references, co-authorship, co-citation, co-occurrence and generate a collaborative network map of authors, countries, and institutions. CiteSpace was used to analyze author and institution centroids, keyword bursts, and timeline graphs. Result: A total of 2,474 articles related to CVD and PCSK9 were included. The number of articles and citations show an increasing trend from year to year. Publications were mainly from the United States. The most active institution was Amgen Inc. Watts, Gerald F. was the most prolific author. Atherosclerosis was the most published journal. Literature co-citation and keyword co-occurrence revealed that early studies focused on the lipid-lowering effects of PCSK9 inhibitors in the context of statins therapy, long-term efficacy, adverse effects, LDLR, diagnosis and treatment of familial hypercholesterolemia. In recent years, myocardial ischemic protection, CRISPR-based editing, and new therapeutic strategies for arteriosclerotic cardiovascular disease have gotten wide attention. The protein convertase, inflammation, beta-polyacetate, and inclisiran may be the important future research directions. Conclusion: This study analyses the current status and global trends in the CVD and PCSK9 studies comprehensively, which may provide researchers and policymakers with new and comprehensive perspectives on in this field of research.

Macrogenomics reveal the effects of inter-cropping perilla on kiwifruit: impact on inter-root soil microbiota and gene expression of carbon, nitrogen, and phosphorus cycles in kiwifruit.

Intercropping systems can improve soil fertility and health, however, soil microbial communities and functional genes related to carbon, nitrogen and phosphorus cycling under the intercropping system of mesquite and perilla have not been studied. Therefore, in the present study, different planting densities and varieties of Perilla frutescens (L.) Britt and kiwifruit were used for intercropping, and changes in soil microbial communities and carbon, nitrogen, and phosphorus cycling genes in kiwifruit inter-roots under inter-cropping conditions were investigated by macro-genome sequencing technology. The results showed that intercropping with Perill caused a decrease in most soil nutrients, soil enzyme activities, and had a significant impact on the microbial (bacteria and fungi) diversity. Inter-cropping increased the relative abundance of the dominant bacterial phylum "Proteobacteria" and "Actinobacteria" by 47 and 57%, respectively, but decreased the relative abundance of the dominant fungal phylum "Chordata" and "Streptophyta" by 11 and 20%, respectively, in the inter-root soil of kiwifruit, and had a significant impact on the microbial (bacteria and fungi) diversity. In addition, inter-cropping could greatly increase the inter-root soil carbon sequestration (PccA, korA/B/C/D, fhs, and rbcl/s), carbon degradation (abfD), organic nitrogen mineralization (GDH2), denitrification (napA/B, nirB, norB), organic phosphorus mineralization (phop, phn), and inorganic phosphorus solubilization (gcd, ppk) gene abundance. The gene co-occurrence network indicated that soil korB, nirB, and gnd key functional genes for carbon, nitrogen, and phosphorus cycling in kiwifruit inter-root soils and their expression was up-regulated in the inter-cropping group. Structural equation (SEM) further showed that soil total nitrogen, organic matter, total carbon and acid phosphatase had significant effects on microbial diversity (p < 0.05) and soil carbon cycling gene korB and phosphorus cycling gene purH (p < 0.001), while korB and purH had positive effects on kiwifruit quality. In conclusion, intercropping perilla in kiwifruit orchards changed the structure of bacterial and fungal communities in the inter-root soil of kiwifruit, but I believe that intercropping perilla stimulates carbon degradation, leading to carbon emission and serious loss of soil nutrients, and that prolonged intercropping may adversely affect the quality of kiwifruit, and thus its limitations should be noted in future studies.

Correction: Surface mobility gradient and emergent facilitation in glassy films.

Correction for 'Surface mobility gradient and emergent facilitation in glassy films' by Qiang Zhai et al., Soft Matter, 2024, https://doi.org/10.1039/D4SM00221K.

How does the level of enterprise digitalization affect value creation and realization? Testing of the dual path of "based on breakthrough" and "tending to compliance".

The construction of enterprise digitization serves as a "gateway" for the integration of the digital and real economies. As enterprises undergo robust digital transformations, it becomes crucial to delineate the pathway from enterprise digitization level to value creation and realization in order to maximize enterprise value. We select sample data from Chinese A-share listed companies from 2015 to 2021 as the research subject. Based on the fixed-effects model, we empirically test the impact of enterprise digitization level on both value creation and realization, as well as the mediating mechanism of entrepreneurship and internal control within it. The results indicate that the enterprise digitization level significantly enhances both value creation and realization. However, significant differences exist in the impact of the digitization level on value creation and realization among enterprises with different technological attributes and at different stages of the lifecycle. Further mechanism tests demonstrate that the "breakthrough-based" entrepreneurship and "compliance-based" internal control quality play effective mediating roles between enterprise digitization level and enterprise value. This study provides a new perspective for understanding the value creation and realization process in the digital context, and offers relevant insights for further stimulating and guiding enterprises of different types and stages to drive value enhancement with digital capabilities, thereby facilitating the deep integration of the digital with the real economy.

State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation.

Background: Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance. Methods: We measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects. Results: 30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV. Conclusion: 30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.

Advances in Chromatographic and Mass Spectrometric Techniques for Analyzing Reducing Monosaccharides and Their Phosphates in Biological Samples.

Reducing monosaccharides and their phosphates are critical metabolites in the central carbon metabolism pathway of living organisms. Variations in their content can indicate abnormalities in metabolic pathways and the onset of certain diseases, necessitating their analysis and detection. Reducing monosaccharides and their phosphates exhibit significant variations in content within biological samples and are present in many isomers, which makes the accurate quantification of reducing monosaccharides and their phosphates in biological samples a challenging task. Various analytical methods such as spectroscopy, fluorescence detection, colorimetry, nuclear magnetic resonance spectroscopy, sensor-based techniques, chromatography, and mass spectrometry are employed to detect monosaccharides and phosphates. In comparison, chromatography and mass spectrometry are highly favored for their ability to simultaneously analyze multiple components and their high sensitivity and selectivity. This review thoroughly evaluates the current chromatographic and mass spectrometric methods used for detecting reducing monosaccharides and their phosphates from 2013 to 2023, highlighting their efficacy and the advancements in these analytical technologies.

HiCervix: An Extensive Hierarchical Dataset and Benchmark for Cervical Cytology Classification.

Cervical cytology is a critical screening strategy for early detection of pre-cancerous and cancerous cervical lesions. The challenge lies in accurately classifying various cervical cytology cell types. Existing automated cervical cytology methods are primarily trained on databases covering a narrow range of coarse-grained cell types, which fail to provide a comprehensive and detailed performance analysis that accurately represents real-world cytopathology conditions. To overcome these limitations, we introduce HiCervix, the most extensive, multi-center cervical cytology dataset currently available to the public. HiCervix includes 40,229 cervical cells from 4,496 whole slide images, categorized into 29 annotated classes. These classes are organized within a three-level hierarchical tree to capture fine-grained subtype information. To exploit the semantic correlation inherent in this hierarchical tree, we propose HierSwin, a hierarchical vision transformer-based classification network. HierSwin serves as a benchmark for detailed feature learning in both coarse-level and fine-level cervical cancer classification tasks. In our comprehensive experiments, HierSwin demonstrated remarkable performance, achieving 92.08% accuracy for coarse-level classification and 82.93% accuracy averaged across all three levels. When compared to board-certified cytopathologists, HierSwin achieved high classification performance (0.8293 versus 0.7359 averaged accuracy), highlighting its potential for clinical applications. This newly released HiCervix dataset, along with our benchmark HierSwin method, is poised to make a substantial impact on the advancement of deep learning algorithms for rapid cervical cancer screening and greatly improve cancer prevention and patient outcomes in real-world clinical settings.

Bacterial cysteate dissimilatory pathway involves a racemase and d-cysteate sulfo-lyase.

The sulfite-reducing bacterium Bilophila wadsworthia, a common human intestinal pathobiont, is unique in its ability to metabolize a wide variety of sulfonates to generate sulfite as a terminal electron acceptor (TEA). The resulting formation of H2S is implicated in inflammation and colon cancer. l-cysteate, an oxidation product of l-cysteine, is among the sulfonates metabolized by B. wadsworthia, although the enzymes involved remain unknown. Here we report a pathway for l-cysteate dissimilation in B. wadsworthia RZATAU, involving isomerization of l-cysteate to d-cysteate by a cysteate racemase (BwCuyB), followed by cleavage into pyruvate, ammonia and sulfite by a d-cysteate sulfo-lyase (BwCuyA). The strong selectivity of BwCuyA for d-cysteate over l-cysteate was rationalized by protein structural modeling. A homolog of BwCuyA in the marine bacterium Silicibacter pomeroyi (SpCuyA) was previously reported to be a l-cysteate sulfo-lyase, but our experiments confirm that SpCuyA too displays a strong selectivity for d-cysteate. Growth of B. wadsworthia with cysteate as the electron acceptor is accompanied by production of H2S and induction of BwCuyA. Close homologs of BwCuyA and BwCuyB are present in diverse bacteria, including many sulfate- and sulfite-reducing bacteria, suggesting their involvement in cysteate degradation in different biological environments.

Surface mobility gradient and emergent facilitation in glassy films.

Confining glassy polymers into films can substantially modify their local and film-averaged properties. We present a lattice model of film geometry with void-mediated facilitation behaviors but free from any elasticity effect. We analyze the spatially varying viscosity to delineate the transport properties of glassy films. The film mobility measurements reported by Yang et al., Science, 2010, 328, 1676 are successfully reproduced. The flow exhibits a crossover from a simple viscous flow to a surface-dominated regime as the temperature decreases. The propagation of a highly mobile front induced by the free surface is visualized in real space. Our approach provides a microscopic treatment of the observed glassy phenomena.

Solar-powered detection of organic dyes using nitrogen-doped N-TiO2/Ag2O nanorod arrays.

Organic pollutant detection has caused widespread concern regarding due to their potential environmental and human health risks. In this work, a nitrogen-doped titanium dioxide/silver oxide (N-TiO2/Ag2O) composite has been designed as a sensitive photoelectrochemical (PEC) monitoring platform of organic dyes. Sensitive determination relies on the outstanding PEC performance of N-TiO2/Ag2O. The improved PEC performance stems from the effective separation of photocarriers and the extended light response range provided by the narrowing bandgap and a p-n junction with N-TiO2/Ag2O. The N-TiO2/Ag2O electrode exhibits a photocurrent density of up to 2.2 mA/cm2, demonstrating three times increase compared with the photocurrent density observed with the pure TiO2 film. The linear detection range for rhodamine B (RhB), methylene blue (MB), and methyl orange (MO) is 0.2 ng/mL to 10 µg/mL with an ultrasensitive detection limit of 0.2 ng/mL without bias voltage. Due to the outstanding photocurrent density and sensitive response to organic pollutants, the N-TiO2/Ag2O PEC sensor provided a promising analytical method to detect environmental organic dyes.

Research on improved YOLOv8n based potato seedling detection in UAV remote sensing images.

Introduction: Accurate detection of potato seedlings is crucial for obtaining information on potato seedlings and ultimately increasing potato yield. This study aims to enhance the detection of potato seedlings in drone-captured images through a novel lightweight model. Methods: We established a dataset of drone-captured images of potato seedlings and proposed the VBGS-YOLOv8n model, an improved version of YOLOv8n. This model employs a lighter VanillaNet as the backbone network in-stead of the original YOLOv8n model. To address the small target features of potato seedlings, we introduced a weighted bidirectional feature pyramid network to replace the path aggregation network, reducing information loss between network layers, facilitating rapid multi-scale feature fusion, and enhancing detection performance. Additionally, we incorporated GSConv and Slim-neck designs at the Neck section to balance accuracy while reducing model complexity. Results: The VBGS-YOLOv8n model, with 1,524,943 parameters and 4.2 billion FLOPs, achieves a precision of 97.1%, a mean average precision of 98.4%, and an inference time of 2.0ms. Comparative tests reveal that VBGS-YOLOv8n strikes a balance between detection accuracy, speed, and model efficiency compared to YOLOv8 and other mainstream networks. Specifically, compared to YOLOv8, the model parameters and FLOPs are reduced by 51.7% and 52.8% respectively, while precision and a mean average precision are improved by 1.4% and 0.8% respectively, and the inference time is reduced by 31.0%. Discussion: Comparative tests with mainstream models, including YOLOv7, YOLOv5, RetinaNet, and QueryDet, demonstrate that VBGS-YOLOv8n outperforms these models in terms of detection accuracy, speed, and efficiency. The research highlights the effectiveness of VBGS-YOLOv8n in the efficient detection of potato seedlings in drone remote sensing images, providing a valuable reference for subsequent identification and deployment on mobile devices.

Extravascular administration of IGF1R antagonists protects against aortic aneurysm in rodent and porcine models.

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.