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Flexible environmental phase change gel (EPCG) is a promising and attractive material for borehole sealing due to its relatively lower usage, tunable cross-linking time, and potential degradable properties. However, conventional borehole sealing materials lack a lower manufacturing cost, lower reaction temperature, remarkable antimold function, and admirable hole sealing performance for long-term high-performance borehole sealing. Hence, it remains a critical challenge to realize a flexible phase-change gel featuring tunable cross-linking time, antimold ability and degradability, and long-lasting moist performance for high-performance borehole sealing. Herein, we illustrate a facile approach to fabricate the borehole sealing materials based on environmentally friendly, antimold, long-lasting moist composite phase-change gel fabricated from a modified cellulose gel polymer network. The prepared phase change gel presents adjustable cross-linking time with the initial setting time of 30-60 min, which could be used to seal holes with different drilling parameters. Furthermore, the fabricated gel illustrates reliable water retentiveness performance and antimold ability, assuring the long-period borehole sealing effect. Furthermore, EPCG has been applied for borehole sealing and shows great sealing ability and gas extraction performance. Therefore, this work paves the way to fabricate a flexible phase-change gel featuring tunable cross-linking time, antimold ability, and long-lasting moist performance for high performance borehole sealing.
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Brain PET imaging often faces challenges from head motion (HM), which can introduce artifacts and reduce image resolution, crucial in clinical settings for accurate treatment planning, diagnosis, and monitoring. United Imaging Healthcare has developed NeuroFocus, an HM correction (HMC) algorithm for the uMI Panorama PET/CT system, using a data-driven, statistics-based approach. The HMC algorithm automatically detects HM using a centroid-of-distribution technique, requiring no parameter adjustments. This study aimed to validate NeuroFocus and assess the prevalence of HM in clinical short-duration 18F-FDG scans. Methods: The study involved 317 patients undergoing brain PET scans, divided into 2 groups: 15 for HMC validation and 302 for evaluation. Validation involved patients undergoing 2 consecutive 3-min single-bed-position brain 18F-FDG scans-one with instructions to remain still and another with instructions to move substantially. The evaluation examined 302 clinical single-bed-position brain scans for patients with various neurologic diagnoses. Motion was categorized as small or large on the basis of a 5% SUV change in the frontal lobe after HMC. Percentage differences in SUVmean were reported across 11 brain regions. Results: The validation group displayed a large negative difference (-10.1%), with variation of 5.2% between no-HM and HM scans. After HMC, this difference decreased dramatically (-0.8%), with less variation (3.2%), indicating effective HMC application. In the evaluation group, 38 of 302 patients experienced large HM, showing a 10.9% ± 8.9% SUV increase after HMC, whereas most exhibited minimal uptake changes (0.1% ± 1.3%). The HMC algorithm not only enhanced the image resolution and contrast but also aided in disease identification and reduced the need for repeat scans, potentially optimizing clinical workflows. Conclusion: The study confirmed the effectiveness of NeuroFocus in managing HM in short clinical 18F-FDG studies on the uMI Panorama PET/CT system. It found that approximately 12% of scans required HMC, establishing HMC as a reliable tool for clinical brain 18F-FDG studies.
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Algoritmos , Encéfalo , Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Adulto , Fluordesoxiglucose F18 , Artefatos , Cabeça/diagnóstico por imagem , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
The cilium, a pivotal organelle crucial for cell signaling and proper cell function, relies on meticulous macromolecular transport from the cytoplasm for its formation and maintenance. While the intraflagellar transport (IFT) pathway has traditionally been the focus of extensive study concerning ciliogenesis and ciliary maintenance, recent research highlights a complementary and alternative mechanism-vesicle-assisted transport (VAT) in cytoplasm to cilium trafficking. Despite its potential significance, the VAT pathway remains largely uncharacterized. This review explores recent studies providing evidence for the dynamics of vesicle-related diffusion and transport within the live primary cilium, employing high-speed super-resolution light microscopy. Additionally, we analyze the spatial distribution of vesicles in the cilium, mainly relying on electron microscopy data. By scrutinizing the VAT pathways that facilitate cargo transport into the cilium, with a specific emphasis on recent advancements and imaging data, our objective is to synthesize a comprehensive model of ciliary transport through the integration of IFT-VAT mechanisms.
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Aim: This research aimed to construct a clinical model for forecasting the likelihood of lung metastases in differentiated thyroid carcinoma (DTC) with intermediate- to high-risk. Methods: In this study, 375 DTC patients at intermediate to high risk were included. They were randomly divided into a training set (70%) and a validation set (30%). A nomogram was created using the training group and then validated in the validation set using calibration, decision curve analysis (DCA) and receiver operating characteristic (ROC) curve. Results: The calibration curves demonstrated excellent consistency between the predicted and the actual probability. ROC analysis showed that the area under the curve in the training cohort was 0.865 and 0.845 in the validation cohort. Also, the DCA curve indicated that this nomogram had good clinical utility. Conclusion: A user-friendly nomogram was constructed to predict the lung metastases probability with a high net benefit.
[Box: see text].
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The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.
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Microcystis , Microcystis/efeitos dos fármacos , Microcystis/crescimento & desenvolvimento , Microcystis/metabolismo , Microcistinas/biossíntese , Biomassa , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Toxinas Marinhas/biossíntese , Parabenos/farmacologia , Antioxidantes/metabolismoRESUMO
Learning universal representations of 3-D point clouds is essential for reducing the need for manual annotation of large-scale and irregular point cloud datasets. The current modus operandi for representative learning is self-supervised learning, which has shown great potential for improving point cloud understanding. Nevertheless, it remains an open problem how to employ auto-encoding for learning universal 3-D representations of irregularly structured point clouds, as previous methods focus on either global shapes or local geometries. To this end, we present a cascaded self-supervised point cloud representation learning framework, dubbed Curriculumformer, aiming to tame curriculum pre-training for enhanced point cloud understanding. Our main idea lies in devising a progressive pre-training strategy, which trains the Transformer in an easy-to-hard manner. Specifically, we first pre-train the Transformer using an upsampling strategy, which allows it to learn global information. Then, we follow up with a completion strategy, which enables the Transformer to gain insight into local geometries. Finally, we propose a Multi-Modal Multi-Modality Contrastive Learning (M4CL) strategy to enhance the ability of representation learning by enriching the Transformer with semantic information. In this way, the pre-trained Transformer can be easily transferred to a wide range of downstream applications. We demonstrate the superior performance of Curriculumformer on various discriminant and generative tasks, outperforming state-of-the-art methods. Moreover, Curriculumformer can also be integrated into other off-the-shelf methods to promote their performance. Our code is available at https://github.com/Fayeben/Curriculumformer.
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To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 µmol) and catechol (100 µmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery.
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Microplastics are well known as contaminants in marine environments. With the development of biofilms, most microplastics will eventually sink and deposit in benthic environment. However, little research has been done on benthic toxic dinoflagellates, and the effects of microplastics on benthic dinoflagellates are unknown. Prorocentrum lima is a cosmopolitan toxic benthic dinoflagellate, which can produce a range of polyether metabolites, such as diarrhetic shellfish poisoning (DSP) toxins. In order to explore the impact of microplastics on marine benthic dinoflagellates, in this paper, we studied the effects of polystyrene (PS) on the growth and toxin production of P. lima. The molecular response of P. lima to microplastic stress was analyzed by transcriptomics. We selected 100 nm, 10 µm and 100 µm PS, and set three concentrations of 1 mg L-1, 10 mg L-1 and 100 mg L-1. The results showed that PS exposure had limited effects on cell growth, but increased the OA and extracellular polysaccharide content at high concentrations. After exposure to PS MPs, genes associated with DSP toxins synthesis, carbohydrate synthesis and energy metabolism, such as glycolysis, TCA cycle and pyruvate metabolism, were significantly up-regulated. We speculated that after exposure to microplastics, P. lima may increase the synthesis of DSP toxins and extracellular polysaccharides, improve the level of energy metabolism and gene expression of ABC transporter, thereby protecting algal cells from damage. Our findings provide new insights into the effects of microplastics on toxic benthic dinoflagellates.
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Dinoflagellida , Microplásticos , Poliestirenos , Dinoflagellida/efeitos dos fármacos , Dinoflagellida/genética , Dinoflagellida/fisiologia , Microplásticos/toxicidade , Toxinas Marinhas , Poluentes Químicos da Água/toxicidade , Transcriptoma/efeitos dos fármacosRESUMO
Microplastics (MPs) and okadaic acid (OA) are known to coexist in marine organisms, potentially impacting humans through food chain. However, the combined toxicity of OA and MPs remains unknown. In this study, mice were orally administered OA at 200⯵g/kg bw and MPs at 2â¯mg/kg bw. The co-exposure group showed a significant increase in malondialdehyde (MDA) content and significant decreases in superoxide dismutase (SOD) activity and glutathione (GSH) level compared to the control, MPs and OA groups (p < 0.05). Additionally, the co-exposure group exhibited significantly higher levels of IL-1ß and IL-18 compared to other groups (p < 0.05). These results demonstrated that co-exposure to MPs and OA induces oxidative stress and exacerbates inflammation. Histological and cellular ultrastructure analyses suggested that this combined exposure may enhance gut damage and compromise barrier integrity. Consequently, the concentration of OA in the small intestine of the co-exposure group was significantly higher than that in the OA group. Furthermore, MPs were observed in the lamina propria of the gut in the co-exposure group. Transcriptomic analysis revealed that the co-exposure led to increased expression of certain genes related to the NF-κB/NLRP3 pathway compared to the OA and MPs groups. Overall, this combined exposure may disrupt the intestinal barrier, and promote inflammation through the NF-κB/NLRP3 pathway. These findings provide precious information for the understanding of health risks associated with MPs and phycotoxins.
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Intestino Delgado , Microplásticos , Ácido Okadáico , Estresse Oxidativo , Poliestirenos , Animais , Microplásticos/toxicidade , Camundongos , Ácido Okadáico/toxicidade , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Intestino Delgado/ultraestrutura , Poliestirenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Malondialdeído/metabolismo , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
3D Gaussian Splatting (3D-GS) has emerged as a significant advancement in the field of Computer Graphics, offering explicit scene representation and novel view synthesis without the reliance on neural networks, such as Neural Radiance Fields (NeRF). This technique has found diverse applications in areas such as robotics, urban mapping, autonomous navigation, and virtual reality/augmented reality, just name a few. Given the growing popularity and expanding research in 3D Gaussian Splatting, this paper presents a comprehensive survey of relevant papers from the past year. We organize the survey into taxonomies based on characteristics and applications, providing an introduction to the theoretical underpinnings of 3D Gaussian Splatting. Our goal through this survey is to acquaint new researchers with 3D Gaussian Splatting, serve as a valuable reference for seminal works in the field, and inspire future research directions, as discussed in our concluding section.
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Nuclear medicine in China started in 1956 and, with the rapid development of the economy and continuous breakthroughs in precision medicine, has made significant progress in recent years. Almost 13,000 staff members in nearly 1,200 hospitals serve more than 3.9 million patients each year. Over the past decade, the radiopharmaceutical industry has developed rapidly, with the initial formation of a complete industrial chain of production of various radiopharmaceuticals for both clinical use and basic research. Advanced equipment such as PET/CT scanners is being manufactured domestically and even installed abroad. Recently, research into screening and synthesizing new target probes and their translation into the clinic has gained more attention, with various new tracers with potential clinical value being thoroughly studied. Simultaneously, 68Ga- and 177Lu-labeled tumor-targeted probes and others have been implemented for theranostics in an increasing number of hospitals and would be helped by approval from the National Medical Products Administration. Over the next 10-20 y, with the launch of the Mid- and Long-Term Development Plan for Medical Isotopes (2021-2035) by the Chinese government, there is great potential for nuclear medicine in China. With the rise in independent innovation in manufacturing, the shortage of radiopharmaceuticals will be effectively curtailed. We anticipate that the scale of nuclear medicine will at least double by 2035, covering all high-grade hospitals and leading to the aim of "one county, one department" in China.
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Medicina Nuclear , Medicina de Precisão , Humanos , China , Compostos RadiofarmacêuticosRESUMO
Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.
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Toxinas Marinhas , Mytilus , Animais , Toxinas Marinhas/toxicidade , Microplásticos/metabolismo , Plásticos/metabolismo , Mytilus/metabolismo , Frutos do MarRESUMO
In this study, the biochemical response of Phaeodactylum tricornutum to varying concentrations of inorganic selenium (Se) was investigated. It was observed that, when combined with fulvic acid, P. tricornutum exhibited enhanced uptake and biotransformation of inorganic Se, as well as increased microalgal lipid biosynthesis. Notably, when subjected to moderate (5 and 10 mg/L) and high (20 and 40 mg/L) concentrations of selenite under fulvic acid treatment, there was a discernible redirection of carbon flux towards lipogenesis and protein biosynthesis from carbohydrates. In addition, the key parameters of microalgae-based biofuels aligned with the necessary criteria outlined in biofuel regulations. Furthermore, the Se removal capabilities of P. tricornutum, assisted by fulvic acid, were coupled with the accumulation of substantial amounts of organic Se, specifically SeCys. These findings present a viable and successful approach to establish a microalgae-based system for Se uptake and biotransformation.
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Benzopiranos , Biocombustíveis , Biotransformação , Diatomáceas , Diatomáceas/metabolismo , Benzopiranos/metabolismo , Ácido Selenioso/metabolismo , Microalgas/metabolismoRESUMO
Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin-eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.
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OBJECTIVE: The purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment. PATIENTS AND METHODS: Sixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren's syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray-Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal-Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P < 0.05). RESULTS: OTU principal component analysis revealed a significant difference between healthy individuals and those with RC-SS. In the saliva of patients with rampant caries, the relative abundance of Firmicutes increased significantly at the phylum level. Further, Streptocpccus, Veillonella, Prevotella, and Dialister increased, while Neisseria and Haemophilus decreased at the genus level. Veillonella increased in the plaque samples of patients with rampant caries. CONCLUSION: Both salivary and dental plaque composition were significantly different between healthy individuals and patients with rampant caries. This study provides a microbiological basis for exploring the etiology of rampant caries. CLINICAL RELEVANCE: This study provides basic information on the flora of the oral cavity in adults with rampant caries in China. These findings could serve as a reference for the treatment of this disease.
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Cárie Dentária , Microbiota , Síndrome de Sjogren , Adulto , Humanos , Cárie Dentária/microbiologia , Síndrome de Sjogren/complicações , RNA Ribossômico 16S/genética , Suscetibilidade à Cárie Dentária , Saliva/microbiologia , Bactérias , Microbiota/genética , Açúcares , DietaRESUMO
The uMI Panorama is a novel PET/CT system using silicon photomultiplier and application-specific integrated circuit technologies and providing exceptional spatial and time-of-flight (TOF) resolutions. The objective of this study was to assess the physical performance of the uMI Panorama in accordance with the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. Methods: Spatial resolution, sensitivity, count rate performance, accuracy, image quality, and TOF resolution were evaluated in accordance with the guidelines outlined in the NEMA NU 2-2018 standard. Energy resolution was determined using the same dataset acquired for the count rate performance evaluation. Images from a Hoffman brain phantom, a mini-Derenzo phantom, and 3 patient studies were evaluated to demonstrate system performance. Results: The transaxial spatial resolution at full width at half maximum was measured as 2.88 mm with a 1-cm offset from the center axial field of view. The sensitivity at the center axial field of view was 20.1 kcps/MBq. At an activity concentration of 73.0 kBq/mL, the peak noise-equivalent count rate (NECR) reached 576 kcps with a scatter fraction of approximately 33.2%. For activity concentrations at or below the peak NECR, the maximum relative count rate error among all slices remained consistently below 3%. When assessed using the NEMA image quality phantom, overall image contrast recovery ranged from 63.2% to 88.4%, whereas background variability ranged from 4.2% to 1.1%. TOF resolution was 189 ps at 5.3 kBq/mL and was consistently lower than 200 ps for activity concentrations at or below the peak NECR. The patient studies demonstrated that scans at 2 min/bed produced images characterized by low noise and high contrast. Clear delineation of nuclei, spinal cords, and other substructures of the brain was observed in the brain PET images. Conclusion: uMI Panorama, the world's first commercial PET system with sub-200-ps TOF resolution, demonstrated fine spatial and fast TOF resolutions, robust count rate performance, and high quantification accuracy across a wide range of activity levels. This advanced technology offers enhanced diagnostic capability for detecting small and low-contrast lesions while showing promising potential under high-count-rate imaging scenarios.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and there is a huge unmet need to find safer and more effective drugs. Vitamin K has been found to regulate lipid metabolism in the liver. However, the effects of vitamin K2 on NAFLD is unclear. This study aims to evaluate the preventive and therapeutic effects of vitamin K2 in the process of fatty liver formation and to explore molecular mechanisms the associated with lipid metabolism. A non-alcoholic fatty liver model was established by high-fat diet administration for three months. Vitamin K2 significantly reduced the body weight, abdominal circumference and body fat percentage of NAFLD mice. Vitamin K2 also showed histological benefits in reducing hepatic steatosis. NAFLD mice induced by high-fat diet showed increased HMGR while vitamin K2 intervention could reverse the pathological lterations. Adiponectin (APN) is an endogenous bioactive polypeptide or protein secreted by adipocytes. We detected APN, SOD, AlaDH and other indicators that may affect the state of high-fat diet mice, but the experimental results showed that the above indicators did not change significantly. It is worth noting that the effect of vitamin K2 supplementation on the lipid-lowering effect of uc OC in vivo needs to be further explored. This study first reported the protective effect of vitamin K2 on high-fat diet-induced NAFLD in mice. The protective effect of vitamin K2 may be related to the improvement of lipid metabolism disorder in NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/patologia , Vitamina K 2/metabolismo , Dieta Hiperlipídica , Fígado/metabolismo , Metabolismo dos Lipídeos , Adiponectina/metabolismo , Camundongos Endogâmicos C57BLRESUMO
To bring about a revolution in energy storage through Li-ion batteries, it is crucial to develop a scalable preparation method for Si-based composite anodes. However, the severe volume expansion and poor ionic transport properties of Si-based composites present significant challenges. Previous research focused on SiO and nano Si/C composites to address these issues. In this study, mechanical milling was used to introduce a SiOx layer onto the surface of Si by mixing Si and SiO2 in a 1 : 1 mass ratio. The resulting Si+SiO2 composites (denoted as SS50) exhibited an initial coulombic efficiency (ICE) of 73.5% and high rate performance. To further stabilize the overall structure, kerosene was introduced as a carbon source precursor to generate a coating layer. The resulting multiphase composite structure (SiOx+SiO2+C), designated as SS50-900C, demonstrated a capacity retention of 79.5% over 280 cycles at its capacity of 487 mA h g-1. These results suggest that a cost-effective mechanical ball milling refinement of Si+SiO2 and a gas-phase encapsulation process can significantly improve the electrochemical performance of Si-based composites.
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Understanding the spatial organization of nucleoporins (Nups) with intrinsically disordered domains within the nuclear pore complex (NPC) is crucial for deciphering eukaryotic nucleocytoplasmic transport. Leveraging high-speed 2D single-molecule tracking and virtual 3D super-resolution microscopy in live HeLa cells, we investigated the spatial distribution of all eleven phenylalanine-glycine (FG)-rich Nups within individual NPCs. Our study reveals a nuanced landscape of FG-Nup conformations and arrangements. Five FG-Nups are steadfastly anchored at the NPC scaffold, collectively shaping a central doughnut-shaped channel, while six others exhibit heightened flexibility, extending towards the cytoplasmic and nucleoplasmic regions. Intriguingly, Nup214 and Nup153 contribute to cap-like structures that dynamically alternate between open and closed states along the nucleocytoplasmic transport axis, impacting the cytoplasmic and nuclear sides, respectively. Furthermore, Nup98, concentrated at the scaffold region, extends throughout the entire NPC while overlapping with other FG-Nups. Together, these eleven FG-Nups compose a versatile, capped trichoid channel spanning approximately 270 nm across the nuclear envelope. This adaptable trichoid channel facilitates a spectrum of pathways for passive diffusion and facilitated nucleocytoplasmic transport. Our comprehensive mapping of FG-Nup organization within live NPCs offers a unifying mechanism accommodating multiple transport pathways, thereby advancing our understanding of cellular transport processes.
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PURPOSE: Enzymolysis clearance strategy, characterized by releasing the non-reabsorbable radioactive fragment under the specific cleavage of enzymes, is confirmed to be a safe and effective way to reduce the renal radioactivity accumulation in mice. However, the effectiveness of this strategy in humans remains unknown. Human epidermal growth factor receptor 2 (HER2) is overexpressed in various types of tumors, and radiolabeled HER2 Affibody is believed to be an attractive tool for HER2-targeted theranostics. However, its wide application is limited by the high and persistent renal uptake. In this study, we intend to validate the effectiveness of enzymolysis clearance strategy in reducing renal accumulation by using a modified HER2 Affibody. MATERIALS AND METHODS: A new HER2 Affibody ligand, NOTA-MVK-ZHER2:2891, containing a cleavable Met-Val-Lys (MVK) linker was synthesized and labeled with 68Ga. The microPET imaging study was performed in SKOV-3 tumor mice to assess the uptakes of the control ligand and the MVK one in tumors and kidneys. Seven healthy volunteers were included for biodistribution and dosimetric studies with both the control and MVK ligands performed 1 week apart. Urine and blood samples from healthy volunteers were collected for in vivo metabolism study of the two ligands. Four HER2-positive and two HER2-negative patients were recruited for [68Ga]Ga-NOTA-MVK-ZHER2:2891 PET/CT imaging at 2 and 4 h post-injection (p.i.). RESULTS: [68Ga]Ga-NOTA-MVK-ZHER2:2891 was stable both in PBS and in mouse serum. MicroPET images showed that the tumor uptake of [68Ga]Ga-NOTA-MVK-ZHER2:2891 was comparable to that of [68Ga]Ga-NOTA-ZHER2:2891 at all the time points, while the kidney uptake was significantly reduced 40 min p.i. (P < 0.05). The biodistribution study in healthy volunteers showed that the kidney uptake of MVK ligand was significantly lower than that of the control ligand at 1 h p.i. (P < 0.05), with the SUVmean of 34.3 and 45.8, respectively, while the uptakes of the two ligands in the other organs showed negligible difference. The effective doses of the MVK ligand and the control one were 26.1 and 28.7 µSv/MBq, respectively. The enzymolysis fragment of [68Ga]Ga-NOTA-Met-OH was observed in the urine samples of healthy volunteers injected with the MVK ligand, indicating that the enzymolysis clearance strategy worked in humans. The PET/CT study of patients showed that the range of SUVmax of HER2-positive lesions was 9.4-21, while that of HER2-negative lesions was 2.7-6.2, which suggested that the MVK modification did not affect the ability of ZHER2:2891 structure to bind with HER2. CONCLUSION: We for the first time demonstrated that enzymolysis clearance strategy can effectively reduce renal radioactivity accumulation in humans. This strategy is expected to decrease renal radiation dose of peptide and small protein-based radiotracers, especially in the field of radionuclide therapy.