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Backgrounds: Observational studies suggest that air pollutants, including particulate matter and nitrogen compounds, could elevate asthma and allergic rhinitis health risks. Nevertheless, the exact nature of the causal relationship between air pollution and asthma and allergic rhinitis remains unknown. This study utilizes the Mendelian randomization (MR) technique to explore the potential causal links between air pollution components (PM2.5, PM2.5-10, PM10, NO2, and nitrogen dioxide) and the incidence of allergic rhinitis and asthma. Methods: A MR study utilized summary statistics from GWAS that are publicly accessible. The inverse variance weighting (IVW) approach served as the foundational analysis technique. To ensure robustness, supplementary methodologies such as the weighted median, MR-Egger regression, simple mode, and weighted model were also applied. Heterogeneity was evaluated using Cochran's Q test, and the presence of pleiotropy was determined through MR-Egger regression. The MR-PRESSO test was employed for outlier detection, and the analysis's sensitivity was scrutinized via a leave-one-out strategy. Results: The IVW technique showed a strong correlation between PM10 and asthma (OR = 0.625, 95% CI = 0.396-0.988, p = 0.044). No significant associations were found between asthma and other air pollutants such as PM2.5, PM2.5-10, NO2, or nitrogen dioxide. Similarly, allergic rhinitis showed no causal relationships with any studied air pollution metrics. Pleiotropy was absent in the findings. Sensitivity analyses, employing the leave-one-out method, confirmed the stability of these results, unaffected by individual single nucleotide polymorphisms (SNPs). Conclusion: This Mendelian randomization study establishes a causal link between PM10 exposure and asthma, suggesting that interventions to reduce air pollution may decelerate the adverse progression of asthma.
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Poluição do Ar , Asma , Análise da Randomização Mendeliana , Material Particulado , Rinite Alérgica , Asma/genética , Asma/epidemiologia , Asma/etiologia , Humanos , Rinite Alérgica/genética , Rinite Alérgica/epidemiologia , Rinite Alérgica/etiologia , Poluição do Ar/efeitos adversos , Material Particulado/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Exposição Ambiental/efeitos adversos , CausalidadeRESUMO
INTRODUCTION: Deep vein thrombosis (DVT) is a medical condition characterized by forming a blood clot, or thrombus, in one of the deep veins, typically in the legs. It is a type of venous thromboembolism, which refers to the formation of blood clots in the veins. It is caused by Virchow's triad (stasis, hypercoagulation, and endothelial injury). OBJECTIVE: Our main objective is to explore the effectiveness and safety of rivaroxaban and edoxaban in treating lower extremity DVT. METHODS: We conducted a retrospective study involving 406 patients subjected to DVT treatment using direct oral anticoagulants (edoxaban and rivaroxaban) at our hospital. We recruited adult patients (aged 18 years and more) diagnosed with lower extremity DVT and received treatment with either rivaroxaban or edoxaban as the primary anticoagulant therapy for DVT. We excluded patients who received treatment with other anticoagulant medications (warfarin and heparin) as the primary therapy for DVT. RESULTS: The groups showed statistically significant differences in red blood cell count and hemoglobin levels, with the edoxaban group having high values. However, the 2 groups observed no statistically significant differences in creatinine clearance, white blood cell count, platelet count, C-reactive protein, and D-dimer levels. The difference in the incidence of pulmonary embolism between the 2 groups was statistically significant (P value < 0.001). The edoxaban group had fewer pulmonary embolism patients than the rivaroxaban group. The reduction in recurrent thrombosis was significantly higher in the rivaroxaban group compared to the edoxaban group. There were no significant differences in the major bleeding at various sites across the 2 treatment groups (P > 0.05). CONCLUSIONS: Rivaroxaban's pharmacokinetic profile includes rapid absorption and a relatively short half-life. It means that once administered, rivaroxaban quickly reaches its peak concentration in the blood and is subsequently eliminated from the body within a relatively short period. Edoxaban's pharmacokinetic profile may include slower absorption and a longer half-life than rivaroxaban. It can result in a slower rate of achieving peak concentration and a more prolonged presence in the bloodstream. These results emphasize the need for careful consideration of anticoagulant therapy in patients with underlying cancer and underscore the importance of managing risks while providing adequate anticoagulation to prevent thrombotic events.
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The unsynchronized growth of the large yellow croaker (Larimichthys crocea), which impacts growth efficiency, poses a challenge for aquaculture practitioners. In our study, juvenile stocks of large yellow croaker were sorted by size after being cultured in offshore cages for 4 months. Subsequently, individuals from both the fast-growing (FG) and slow-growing (SG) groups were sampled for analysis. High-throughput RNA-Seq was employed to identify genes and pathways that are differentially expressed during varying growth rates, which could suggest potential physiological mechanisms that influence growth rate. Our transcriptome analysis identified 382 differentially expressed genes (DEGs), comprising 145 upregulated and 237 downregulated genes in comparison to the SG group. GO and KEGG enrichment analyses indicated that these DEGs are predominantly involved in signal transduction and biochemical metabolic pathways. Quantitative PCR (qPCR) results demonstrated that cat, fasn, idh1, pgd, fgf19, igf2, and fads2 exhibited higher expression levels, whereas gadd45b and gadd45g showed lower expression compared to the slow-growing group. In conclusion, the differential growth rates of large yellow croaker are intricately associated with cellular proliferation, metabolic rates of the organism, and immune regulation. These findings offer novel insights into the molecular mechanisms and regulatory aspects of growth in large yellow croaker and enhance our understanding of growth-related genes.
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Perfilação da Expressão Gênica , Perciformes , Transcriptoma , Animais , Perciformes/genética , Perciformes/crescimento & desenvolvimento , Proteínas de Peixes/genéticaRESUMO
PBAT-modified starch blended film are thermoplastic biodegradable materials with good properties and a wide range of applications. In this study, L-02 cells were used as an in vitro toxicity evaluation system for risk assessment of PBAT-modified starch films with migration studies obtained in different food simulants. Determination of total migration and organic matter revealed that the results were in accordance with the standard except for the total organic matter under 95% (v/v) ethanol food simulant which exceeded the standard. The CCK-8 assay showed that these compounds affect the cell viability of L-02 cells. It was observed that the compounds made the cells express increased AST, ALT, TNF-α, IL-6, IL-1ß, and ROS, and decreased SOD, GSH, and ATP. In addition, we explored the effect of migration in PBAT-modified starch composites on protein and gene expression levels in L-02 cells using a transcriptomic approach and found that the AMPK signaling pathway was affected. The expression of AMPK signaling pathway-related proteins was detected by Western Blot, and the expression levels of p-AMPK/AMPK were found to be upregulated, and those of p-mTOR/mTOR, SIRT1, PGC-1α, NRF1 and TFAM were downregulated. The above data suggest that the compounds migrating into the PBAT-modified starch film when exposed to food may induce oxidative stress and inflammation in hepatocytes, and may cause damage to hepatocytes through the AMPK pathway.
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Avian influenza virus (AIV) H7N9 diseases have been recently reported, raising concerns about a potential pandemic. Thus, there is an urgent need for effective therapeutics for AIV H7N9 infections. Herein, camelid immunization and yeast two-hybrid techniques were used to identify potent neutralizing nanobodies (Nbs) targeting the H7 subtype hemagglutinin. First, we evaluated the binding specificity and hemagglutination inhibition activity of the screened Nbs against the H7 subtype hemagglutinin. Nb-Z77, with high hemagglutination inhibition activity was selected from the screened Nbs to optimize the yeast expression conditions and construct oligomeric forms of Nb-Z77 using various ligation methods. The oligomers Nb-Z77-DiGS, Nb-Z77-TriGS, Nb-Z77-Fc and Nb-Z77-Foldon were successfully constructed and expressed. Nb-Z77-DiGS and Nb-Z77-Foldon exhibited considerably greater activity than did Nb-Z77 against H7 subtype hemagglutinin, with median effective concentrations of 384.7 and 27.33 pM and binding affinity values of 213 and 5.21 pM, respectively. Nb-Z77-DiGS and Nb-Z77-Foldon completely inhibited the hemagglutination activity of the inactivated virus H7-Re1 at the lowest concentration of 0.938 µg/mL. This study screened a strain of Nb with high hemagglutination inhibition activity and enhanced its antiviral activity through oligomerization, which may have great potential for developing effective agents for the prevention, diagnosis, and treatment of AIV H7 subtype infection.
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Glicoproteínas de Hemaglutininação de Vírus da Influenza , Anticorpos de Domínio Único , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/química , Animais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Humanos , Testes de Inibição da Hemaglutinação , Influenza Aviária/imunologia , Influenza Aviária/virologia , Influenza Aviária/prevenção & controle , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologiaRESUMO
Microplastics are a growing concern in mangrove ecosystems; however, their effects on archaeal communities and related ecological processes remain unclear. We conducted in situ biofilm-enrichment experiments to investigate the ecological influence of polyethylene (PE) and polypropylene microplastics on archaeal communities in the sediments of mangrove ecosystems. The archaeal community present on microplastics was distinct from that of the surrounding sediments at an early stage but became increasingly similar over time. Bathyarchaeota, Thaumarchaeota, Euryarchaeota, and Asgardaeota were the most abundant phyla. Methanolobus, an archaeal biomarker, was enriched in PE biofilms, and significantly controlled by homogeneous selection in the plastisphere, indicating an increased potential risk of methane emission. The dominant archaeal assembly process in the sediments was deterministic (58.85%-70.47%), while that of the PE biofilm changed from stochastic to deterministic during the experiment. The network of PE plastispheres showed less complexity and competitive links, and higher modularity and stability than that of sediments. Functional prediction showed an increase in aerobic ammonia oxidation during the experiment, whereas methanogenesis and chemoheterotrophy were significantly higher in the plastisphere. This study provides novel insights into the impact of microplastic pollution on archaeal communities and their mediating ecological functions in mangrove ecosystems.
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Archaea , Biofilmes , Sedimentos Geológicos , Microplásticos , Polietileno , Polipropilenos , Áreas Alagadas , Archaea/efeitos dos fármacos , Archaea/metabolismo , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Microplásticos/toxicidade , Biofilmes/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , EcossistemaRESUMO
Major biological discoveries are made by interrogating living organisms with light. However, the limited penetration of un-scattered photons within biological tissues limits the depth range covered by optical methods. Deep-tissue imaging is achieved by combining light and ultrasound. Optoacoustic imaging exploits the optical generation of ultrasound to render high-resolution images at depths unattainable with optical microscopy. Recently, laser ultrasound has been suggested as a means of generating broadband acoustic waves for high-resolution pulse-echo ultrasound imaging. Herein, an approach is proposed to simultaneously interrogate biological tissues with light and ultrasound based on layer-by-layer coating of silica optical fibers with a controlled degree of transparency. The time separation between optoacoustic and ultrasound signals collected with a custom-made spherical array transducer is exploited for simultaneous 3D optoacoustic and laser ultrasound (OPLUS) imaging with a single laser pulse. OPLUS is shown to enable large-scale anatomical characterization of tissues along with functional multi-spectral imaging of chromophores and assessment of cardiac dynamics at ultrafast rates only limited by the pulse repetition frequency of the laser. The suggested approach provides a flexible and scalable means for developing a new generation of systems synergistically combining the powerful capabilities of optoacoustics and ultrasound imaging in biology and medicine.
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Lasers , Microscopia , UltrassonografiaRESUMO
BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and the main cause of non-traumatic amputation, with no ideal treatment. Multiple cell-derived exosomes have been reported to improve the progression of DPN. Blood therapy is thought to have a powerful repairing effect. However, whether it could also improve DPN remains unclear. RESULTS: In this study, we found that microRNA (miRNA) expression in plasma-derived exosomes of healthy rats (hplasma-exos) was significantly different from that of age-matched DPN rats. By injection of hplasma-exos into DPN rats, the mechanical sensitivity of DPN rats was decreased, the thermal sensitivity and motor ability were increased, and the nerve conduction speed was accelerated. Histological analysis showed myelin regeneration of the sciatic nerve, increased intraepidermal nerve fibers, distal local blood perfusion, and enhanced neuromuscular junction and muscle spindle innervation after hplasma-exos administration. Compared with plasma exosomes in DPN, miR-20b-3p was specifically enriched in exosomes of healthy plasma and was found to be re-upregulated in the sciatic nerve of DPN rats after hplasma-exos treatment. Moreover, miR-20b-3p agomir improved DPN symptoms to a level similar to hplasma-exos, both of which also alleviated autophagy impairment induced by high glucose in Schwann cells. Mechanistic studies found that miR-20b-3p targeted Stat3 and consequently reduced the amount of p-Stat3, which then negatively regulated autophagy processes and contributed to DPN improvement. CONCLUSIONS: This study demonstrated that miRNA of plasma exosomes was different between DPN and age-matched healthy rats. MiR-20b-3p was enriched in hplasma-exos, and both of them could alleviated DPN symptoms. MiR-20b-3p regulated autophagy of Schwann cells in pathological states by targeting Stat3 and thereby inhibited the progression of DPN.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Exossomos , MicroRNAs , Doenças do Sistema Nervoso Periférico , Animais , Ratos , Diabetes Mellitus Experimental/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismoRESUMO
The aim of this study was to investigate the survival rate, biochemical indices, and metabolome changes of the large yellow croaker after 48 h of live transportation. Two hundred and forty large yellow croakers (body weight: 23.4 ± 5.3 g, total length: 12.2 ± 0.7 cm) were used in this experiment. The transport buckets were filled with fresh seawater and the parameters of the water were a temperature of 16 ± 0.5 °C and a dissolved oxygen content of 6.0-7.2 mg/L. Large yellow crokers were first divided to 0, 10, 20, and 30 mg/L MS-222 groups to observe the 12 h survival rate. The survival rate of 10 mg/L MS-222 group (T1) was the 95%, highest of all, and was further analyzed. The results of liver biochemical indices indicated inhibition of gluconeogenesis and pentose phosphate pathway metabolism. In addition, metabolomics analysis identified significantly differentially expressed metabolites between T1 group and 0 mg/L MS-222 control (C) groups. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) results revealed that the pathways of amino acid metabolism, especially the lysine, aspartate, and homoserine in the liver were significantly affected. In conclusion, the combination of metabolomics and liver biochemical assays provided a characterization of the response mechanism of L. crocea exposed to live transportation.
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Metabolômica , Perciformes , Animais , Perciformes/genética , Perciformes/metabolismo , Proteínas de Peixes/genéticaRESUMO
Alzheimer's disease (AD) is one of the major neurological disorders causing death in the elderly worldwide. As a neurodegenerative disease that is difficult to prevent and cure, the pathogenesis of AD is complex and there is no effective cure. A variety of natural products derived from plants have been reported to have promising anti-AD activities, including flavonoids, terpenes, phenolic acids and alkaloids, which can effectively relieve the symptoms of AD in a variety of ways. This paper mainly reviews the pharmacological activity and mechanisms of natural products against AD. Although the clinical efficacy of these plants still needs to be determined by further high-quality studies, it may also provide a basis for future researchers to study anti-AD in depth.
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Doença de Alzheimer , Produtos Biológicos , Humanos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Produtos Biológicos/farmacologiaRESUMO
Nonylphenol (NP) exposure can trigger neurotoxicity and cause learning and memory impairment. Nicotinamide mononucleotide (NMN) has a therapeutic effect on neurodegenerative diseases, but the role of NMN on NP-induced learning and memory impairment is not known. Here, we examined the mitigative effect of NMN on the impaired learning and memory ability of rats exposed to NP. The NP impaired learning and memory in rats, while the low-dose intervention with NMN significantly prolonged the step-through latency of the PAT and improved the NAMPT and NMNAT1 content in brain tissue. At the same time, the NMN intervention also increased the content of 5-HTR1A, 5-HTR4, and 5-HTR6 related to learning and memory in the hippocampus. In line with this, we found that the NMN intervention activated the SIRT1/MAO-A pathway in brain tissue. NMN intervention, especially at 125 mg/kg doses, may improve rats' NP-induced learning and memory impairment via the central 5-HT system and the NAD+/SIRT1/MAO-A pathway in the brain.
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NAD , Mononucleotídeo de Nicotinamida , Ratos , Animais , NAD/metabolismo , Serotonina , Sirtuína 1/genética , Sirtuína 1/metabolismo , MonoaminoxidaseRESUMO
In this study, decolorized pectic polysaccharides (D-ACLP) with molecular weight (Mw) distribution of 3483- 2,023,656 Da were prepared from Amaranth caudatus leaves. Purified polysaccharides (P-ACLP) with the Mw of 152,955 Da were further isolated from D-ACLP through gel filtration. The structure of P-ACLP was analyzed by 1D and 2D NMR spectra. P-ACLP were identified as rhamnogalacturonan-I (RG-I) containing dimeric arabinose side chains. The main chain of P-ACLP was composed of â4)-α-GalpA-(1â, â2)-ß-Rhap-(1â, â3)-ß-Galp-(1â and â6)-ß-Galp-(1â. There was a branched chain of α-Araf-(1â2)-α-Araf-(1â connected to the O-6 position of â3)-ß-Galp-(1â. The GalpA residues were partially methyl esterified at O-6 and acetylated at O-3. The 28-day consecutive gavage of D-ALCP (400 mg/kg) significantly elevated the hippocampal glucagon-like peptide-1 (GLP-1) levels in rats. The concentrations of butyric acid and total short chain fatty acids in the cecum contents also increased significantly. Moreover, D-ACLP could significantly increase the gut microbiota diversity and dramatically up-regulated the abundance of Actinobacteriota (phylum) and unclassified Oscillospiraceae (genus) in intestinal bacteria. Taking together, D-ACLP might promote the hippocampal GLP-1 level through the beneficial regulation of butyric acid-producing bacteria in gut microbiota. This study contributed to making full use of Amaranth caudatus leaves for cognitive dysfunction intervention in food industry.
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Núcleo Caudado , Polissacarídeos , Animais , Ratos , Polissacarídeos/química , Pectinas/química , Espectroscopia de Ressonância Magnética , Folhas de PlantaRESUMO
It is crucial to monitor the status of aquaculture objects in recirculating aquaculture systems (RASs). Due to their high density and a high degree of intensification, aquaculture objects in such systems need to be monitored for a long time period to prevent losses caused by various factors. Object detection algorithms are gradually being used in the aquaculture industry, but it is difficult to achieve good results for scenes with high density and complex environments. This paper proposes a monitoring method for Larimichthys crocea in a RAS, which includes the detection and tracking of abnormal behavior. The improved YOLOX-S is used to detect Larimichthys crocea with abnormal behavior in real time. Aiming to solve the problems of stacking, deformation, occlusion, and too-small objects in a fishpond, the object detection algorithm used is improved by modifying the CSP module, adding coordinate attention, and modifying the part of the structure of the neck. After improvement, the AP50 reaches 98.4% and AP50:95 is also 16.2% higher than the original algorithm. In terms of tracking, due to the similarity in the fish's appearance, Bytetrack is used to track the detected objects, avoiding the ID switching caused by re-identification using appearance features. In the actual RAS environment, both MOTA and IDF1 can reach more than 95% under the premise of fully meeting real-time tracking, and the ID of the tracked Larimichthys crocea with abnormal behavior can be maintained stably. Our work can identify and track the abnormal behavior of fish efficiently, and this will provide data support for subsequent automatic treatment, thus avoiding loss expansion and improving the production efficiency of RASs.
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Perciformes , Animais , Peixes , Aquicultura/métodosRESUMO
Ocean-caught large yellow croaker (Larimichthys crocea) represents an important germplasm resource for the breeding of this species; however, these fish tend to show poor survival in captivity and would be unsuitable breeding purposes. As an alternative to the use of wild-caught croakers, germ cell transplantation has been proposed using the L. crocea specimens as donors and yellow drum (Nibea albiflora) as recipients. In this regard, the identification of L. crocea and N. albiflora germ cells is an essential prerequisite for establishing a germ cell transplantation protocol for these fish. In this study, we cloned the 3' untranslated regions (UTR) of the vasa, dnd, and nanos2 genes in N. albiflora using the rapid amplification of cDNA ends (RACE) method and then aligned and analyzed the sequences of the corresponding genes in L. crocea and N. albiflora. On the basis of gene sequence differences, we designed species-specific primers and probes for RT-PCR analysis and in situ hybridization. RT-PCR analysis revealed that these species-specific primers exclusively amplified DNA from gonads of the respective species, thus confirming that we had six specific primer pairs that could be used to distinguish the germ cells in L. crocea and N. albiflora. Using in situ hybridization analysis, we established that whereas Lcvasa and Nadnd probes showed high species specificity, the probes for Navasa and Lcdnd showed a less specificity. In situ hybridization using Lcvasa and Nadnd thus enabled us to visualize the germ cells in these two species. Using these species-specific primers and probes, we can reliably distinguish the germ cells of L. crocea and N. albiflora, thereby establishing an effective approach for the post-transplantation identification of germ cells when using L. crocea and N. albiflora as donors and recipients, respectively.
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Células Germinativas , Perciformes , Animais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Perciformes/genética , Hibridização In Situ , Gônadas , Proteínas de Peixes/genéticaRESUMO
Retinal Müller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Müller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Müller glia in diabetic retinopathy (DR). Here, we found that AQP11 expression, primarily located at the endfeet of Müller glia, was down-regulated with diabetes progression, accompanied by intracellular edema, which was alleviated by intravitreal injection of lentivirus-mediated AQP11 overexpression. Similarly, intracellular edema of hypoxia-treated rat Müller cell line (rMC-1) was aggravated by AQP11 inhibition, while attenuated by AQP11 overexpression, accompanied by enhanced function in glutamate metabolism and reduced cell death. The down-regulation of AQP11 was also verified in the Müller glia from the epiretinal membranes (ERMs) of proliferative DR (PDR) patients. Mechanistically, down-regulation of AQP11 in DR was mediated by the HIF-1α-dependent and independent miRNA-AQP11 axis. Overall, we deciphered the AQP11 down-regulation, mediated by miRNA-AQP11 axis, resulted in Müller drainage dysfunction and subsequent intracellular edema in DR, which was partially reversed by AQP11 overexpression. Our findings propose a novel mechanism for the pathogenesis of DME, thus targeting AQP11 regulation provides a new therapeutic strategy for DME.
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Aquaporinas , Diabetes Mellitus , Retinopatia Diabética , Edema Macular , MicroRNAs , Ratos , Animais , Retinopatia Diabética/patologia , MicroRNAs/genética , Regulação para Baixo , Aquaporinas/metabolismoRESUMO
Chronic, non-healing wounds constitute a major health problem, and the current therapeutic options are limited. Therefore, pharmaceuticals that can be locally applied to complicated wounds are urgently needed. Such treatments should directly target the underlying causes, which include diabetes mellitus, chronic local pressure and/or vascular insufficiency. A common consequence of these disorders is impaired wound angiogenesis. Here, we investigated the effect of topical application of a nitric oxide-releasing phosphodiesterase 5 inhibitor (TOP-N53)-containing liquid hydrogel on wound repair in mice. The drug-loaded hydrogel promoted re-epithelialization and angiogenesis in wounds of healthy and healing-impaired diabetic mice. Using a non-invasive label-free optoacoustic microscopy approach combined with automated vessel analysis, we show that the topical application of TOP-N53 formulation increases the microvascular network density and promotes the functionality of the newly formed blood vessels, resulting in enhanced blood perfusion of the wounds. These results demonstrate a remarkable healing-stimulating activity of topically applied TOP-N53 formulation, supporting its further development as a wound therapeutic.
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Optoacoustic mesoscopy combines rich optical absorption contrast with high spatial resolution at tissue depths beyond reach for microscopic techniques employing focused light excitation. The mesoscopic imaging performance is commonly hindered by the use of inaccurate delay-and-sum reconstruction approaches and idealized modeling assumptions. In principle, image reconstruction performance could be enhanced by simulating the optoacoustic signal generation, propagation, and detection path. However, for most realistic experimental scenarios, the underlying total impulse response (TIR) cannot be accurately modelled. Here we propose to capture the TIR by scanning of a sub-resolution sized absorber. Significant improvement of spatial resolution and depth uniformity is demonstrated over 3 mm range, outperforming delay-and-sum and model-based reconstruction implementations. Reconstruction performance is validated by imaging subcutaneous murine vasculature and human skin in vivo. The proposed experimental calibration and reconstruction paradigm facilitates quantitative inversions while averting complex physics-based simulations. It can readily be applied to other imaging modalities employing TIR-based reconstructions.
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Objective: This study is aimed at screening the potential ideal lead compounds from natural drug library (ZINC database), which had potential inhibition effects against proprotein converse subtilisin/kexin type 9 (PCSK9), and contributing to enrich the practical basis of PCSK9 inhibitor screening. Methods: A series of computer-aided virtual screening techniques were used to identify potential inhibitors of PCSK9. Structure-based virtual screening by LibDock was carried out to calculate the LibDock scores, followed by ADME (absorption, distribution, metabolism, and excretion) and toxicity predictions. Molecule docking was next employed to demonstrate the binding affinity and mechanism between the candidate ligands and PCSK9 macromolecule. Finally, molecular dynamics simulation was performed to evaluate the stability of ligand-PCSK9 complex under natural circumstance. Results: Two novel natural compounds ZINC000004099069 and ZINC000014952116 from the ZINC database were found to bind with PCSK9 with a higher binging affinity together with more favorable interaction energy. Also, they were predicted to be non-CYP2D6 inhibitors, together with low rodent carcinogenicity and AMES mutagenicity as well as hepatotoxicity. Molecular dynamics simulation analysis demonstrated that these two complex ZINC000004099069- and ZINC000014952116-PCSK9 had more favorable potential energy compared to the reference ligand, which could exist stably whether in vivo or in vitro. Conclusion: This study elucidated that ZINC000004099069 and ZINC000014952116 were finally screened as safe and potential drug candidates, which may have great significance in the development of PCSK9 inhibitor development.
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Doenças Cardiovasculares , Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/metabolismo , Inibidores de PCSK9 , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Ligantes , Subtilisina , ZincoRESUMO
Vision-based object detection of PCB (printed circuit board) assembly scenes is essential in accelerating the intelligent production of electronic products. In particular, it is necessary to improve the detection accuracy as much as possible to ensure the quality of assembly products. However, the lack of object detection datasets in PCB assembly scenes is the key to restricting intellectual PCB assembly research development. As an excellent representative of the one-stage object detection model, YOLOv3 (you only look once version 3) mainly relies on placing predefined anchors on the three feature pyramid layers and realizes recognition and positioning using regression. However, the number of anchors distributed in each grid cell of different scale feature layers is usually the same. The ERF (effective receptive field) corresponding to the grid cell at different locations varies. The contradiction between the uniform distribution of fixed-size anchors and the ERF size range in different feature layers will reduce the effectiveness of object detection. Few people use ERF as a standard for assigning anchors to improve detection accuracy. To address this issue, firstly, we constructed a PCB assembly scene object detection dataset, which includes 21 classes of detection objects in three scenes before assembly, during assembly, and after assembly. Secondly, we performed a refined ERF analysis on each grid of the three output layers of YOLOv3, determined the ERF range of each layer, and proposed an anchor allocation rule based on the ERF. Finally, for the small and difficult-to-detect TH (through-holes), we increased the context information and designed improved-ASPP (Atrous spatial pyramid pooling) and channel attention joint module. Through a series of experiments on the object detection dataset of the PCB assembly scene, we found that under the framework of YOLOv3, anchor allocation based on ERF can increase mAP (mean average precision) from 79.32% to 89.86%. At the same time, our proposed method is superior to Faster R-CNN (region convolution neural network), SSD (single shot multibox detector), and YOLOv4 (you only look once version 4) in the balance of high detection accuracy and low computational complexity.
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Algoritmos , Redes Neurais de Computação , Sistemas Computacionais , Eletrônica , Projetos de PesquisaRESUMO
Skull bone development is a dynamic and well-coordinated process playing a key role in maturation and maintenance of the bone marrow (BM), fracture healing, and progression of diseases such as osteoarthritis or osteoporosis. At present, dynamic transformation of the growing bone (osteogenesis) as well as its vascularization (angiogenesis) remain largely unexplored due to the lack of suitable in vivo imaging techniques capable of noninvasive visualization of the whole developing calvaria at capillary-level resolution. We present a longitudinal study on skull bone development using ultrasound-aided large-scale optoacoustic microscopy (U-LSOM). Skull bone morphogenesis and microvascular growth patterns were monitored in three common mouse strains (C57BL/6J, CD-1, and Athymic Nude-Foxn1nu) at the whole-calvaria scale over a 3-month period. Strain-specific differences in skull development were revealed by quantitative analysis of bone and vessel parameters, indicating the coupling between angiogenesis and osteogenesis during skull bone growth in a minimally invasive and label-free manner. The method further enabled identifying BM-specific sinusoidal vessels, and superficial skull vessels penetrating into BM compartments. Our approach furnishes a new high-throughput longitudinal in vivo imaging platform to study morphological and vascular skull alterations in health and disease, shedding light on the critical links between blood vessel formation, skull growth, and regeneration. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).