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BACKGROUND CONTEXT: A deep learning (DL) model for degenerative cervical spondylosis on MRI could enhance reporting consistency and efficiency, addressing a significant global health issue. PURPOSE: Create a DL model to detect and classify cervical cord signal abnormalities, spinal canal and neural foraminal stenosis. STUDY DESIGN/SETTING: Retrospective study conducted from January 2013 to July 2021, excluding cases with instrumentation. PATIENT SAMPLE: Overall, 504 MRI cervical spines were analyzed (504 patients, mean=58 years±13.7[SD]; 202 women) with 454 for training (90%) and 50 (10%) for internal testing. In addition, 100 MRI cervical spines were available for external testing (100 patients, mean=60 years±13.0[SD];26 women). OUTCOME MEASURES: Automated detection and classification of spinal canal stenosis, neural foraminal stenosis, and cord signal abnormality using the DL model. Recall(%), inter-rater agreement (Gwet's kappa), sensitivity, and specificity were calculated. METHODS: Utilizing axial T2-weighted gradient echo and sagittal T2-weighted images, a transformer-based DL model was trained on data labeled by an experienced musculoskeletal radiologist (12 years of experience). Internal testing involved data labeled in consensus by two musculoskeletal radiologists (reference standard, both with 12-years-experience), two subspecialist radiologists, and two in-training radiologists. External testing was performed. RESULTS: The DL model exhibited substantial agreement surpassing all readers in all classes for spinal canal (κ=0.78, p<0.001 vs. κ range=0.57-0.70 for readers) and neural foraminal stenosis (κ=0.80, p<0.001 vs. κ range=0.63-0.69 for readers) classification. The DL model's recall for cord signal abnormality (92.3%) was similar to all readers (range: 92.3-100.0%). Nearly perfect agreement was demonstrated for binary classification (normal/mild vs. moderate/severe) (κ=0.95, p<0.001 for spinal canal; κ=0.90, p<0.001 for neural foramina). External testing showed substantial agreement using all classes (κ=0.76, p<0.001 for spinal canal; κ=0.66, p<0.001 for neural foramina) and high recall for cord signal abnormality (91.9%). The DL model demonstrated high sensitivities (range:83.7%-92.4%) and specificities (range:87.8%-98.3%) on both internal and external datasets for spinal canal and neural foramina classification. CONCLUSIONS: Our DL model for degenerative cervical spondylosis on MRI showed good performance, demonstrating substantial agreement with the reference standard. This tool could assist radiologists in improving the efficiency and consistency of MRI cervical spondylosis assessments in clinical practice.

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The detection of DNA methyltransferase (MTase) was crucial for understanding gene expression regulation, cancer mechanisms, and various biological processes, contributing significantly to disease diagnosis and drug development. Herein, a nanopore sensor based on cascaded signal amplification of DNA walker and autocatalytic hybridization reaction (AHR) was developed for the ultrasensitive determination of various MTases. In the presence of Dam MTase, the hairpin structure HD underwent methylation and cleavage by DpnI endonuclease, forming T-DNA fragments. These T-DNA fragments were used to activate the DNA walker, which moved across the surface of magnetic beads step by step, generating a large quantity of initiator I by cleaving the substrate. The initiator I subsequently activated the AHR. The AHR included a hybridization chain reaction (HCR) amplifier and a catalytic hairpin assembly (CHA) convertor. The HCR amplifier generated multiple novel CHA triggers, which activated the CHA convertor. This, in turn, stimulated the HCR amplifier, creating an AHR circuit that resulted in the formation of numerous DNA nanowires. These DNA nanowires were adsorbed onto the G4-PAMAM-modified nanopore surface under the influence of an electric field, thereby altering the surface charge of the nanopore and changing the ionic rectification curve. The detection limit of the Dam MTase nanopore sensor reached 0.0002 U/mL. By modification of the recognition sites of the probes, this nanopore system could also be used for the detection of M.SssI MTase. Moreover, a four-input parallel concatenated logic circuit (AND//INHIBIT-OR) had been constructed and applied for the multivariate detection of Dam MTase and M.SssI MTase, presenting a novel conceptual model for advancing the construction of nanopore logic gate systems and their applications in biosensing.

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Parkinson's disease (PD) pathology speculates that neuromelanin (NM) and iron ions play a significant role in physiological and pathological conditions of PD. Because the difficult accessibility of NM has limited targeted research, synthetic melanin-like nanoparticles have been used to instead. In this report, the eumelanin and pheomelanin-like polydopamine (PDA) nanoparticles are prepared that can be used to simulate natural NM with or without chelating iron ion and studied the redox effects in vitro and in vivo on neuronal cells and PD. The synthetic pheomelanin-like PDA nanoparticles have much stronger redox activity than eumelanin-like PDA nanoparticles without or with iron ion. They can protect neurons by scavenging reactive oxygen species (ROS), while cause neuronal cell death and PD due to excessive binding of iron ions. This work provides new evidence for the relationship among two structural components of NM and iron in PD as well as displays the different effects on the roles of eumelanin and pheomelanin in redox activity under physiological or pathological conditions, which provide a new effective choice for cellular and animal models of PD and offer theoretical guidance for targeted treatment and mechanism research on PD.

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Background: The occurrence of blindness resulting from facial injection is a catastrophic complication that remains a significant safety concern for patients. The aim was to assess public awareness of blindness caused by hyaluronic acid injection. Methods: The Tencent questionnaire platform was used to gather self-reported demographic data, information about injection experience, and factors influencing the understanding of blindness. Additionally, we included an educational section on blindness caused by hyaluronic acid injection and evaluated the respondents' intention to undergo injections. Results: A total of 1000 respondents completed the questionnaire, 15.4% had received filler injections, and 53.7% expressed their consideration of facial filler injections. The majority of respondents (68.3%) reported being aware of the risk of blindness associated with filler injections, with professional health blogs, social media, and news serving as the primary sources of information. Furthermore, 93.4% of the respondents believed that plastic surgeons should discuss the risk of blindness with patients before injection. Conclusions: The majority of the respondents in this study were aware of the possibility of blindness resulting from filler injections. Health blogs, news outlets, and social media platforms are likely the primary channels through which the public obtains information on this topic.

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To address rotor imbalance and misalignment in oil transfer pumps, an innovative diagnostic framework using Residual Network (ResNet) is proposed. The model incorporates advanced signal processing algorithms and strategic sensor placement to enhance diagnostic efficacy. A fault simulation test rig captured vibration signals from eight key measurement points on the pump. One-dimensional and multi-dimensional signal processing techniques generated comprehensive datasets for training and validating the model. Sensor placement optimization, focusing on the bearing seat's axial direction, inlet flange's vertical direction, and outlet flange's axial direction, increased rotor fault sensitivity. Time-frequency data processed via Short-Time Fourier Transform (STFT) achieved the highest diagnostic accuracy, surpassing 98 %. This study highlights the importance of optimal signal processing and precise sensor placement in improving the accuracy of diagnosing rotor faults in oil transfer pumps, thus enhancing the operational reliability and efficiency of energy transportation systems.

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Cell membranes are primarily composed of lipids, membrane proteins, and carbohydrates, and the related studies of membrane components and structures at different stages of disease development, especially membrane proteins, are of great significance. Here, we investigate the chemical signature profiles of cell membranes as biomarkers for cancer cells via label-free surface-enhanced Raman scattering (SERS). A magnetic plasmonic nanoprobe was proposed by decorating magnetic beads with silver nanoparticles, allowing self-driven cell membrane-targeted accumulation within 5 min. SERS profiles of three types of breast cells were achieved under the plasmon enhancement effect of these nanoprobes. Membrane fingerprint spectra from breast cell lines were further classified with the convolutional neural network model, which perfectly distinguished between two breast cancer subtypes. We further tested various clinical samples using this method and obtained fingerprint spectra from primary cells and frozen slices. This study presents a practical, user-friendly approach for label-free and in situ analysis of cell membranes, which can work for early tumor screening and treatment assessment for tumors reliant on the Molecular profiles of cell membranes. Additionally, this method can be applied universally to explore cell membrane components of other cells, thus assisting Human Cell Atlas.

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[This corrects the article DOI: 10.1371/journal.pone.0088863.].

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ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR), the dried root and rhizome of Sophora tonkinensis Gagnep., is commonly used in the treatment of tonsillitis and pharyngitis, throat soreness and throat obstruction, swelling and aching of gum, etc. in China or other Asian countries. STR is usually used as the core herb in traditional Chinese medicine preparations, such as "Biyanling Tablets", "Fufang Muji Granules" and "Ganyanling Injections", etc. AIM OF THE REVIEW: This review aimed to provide a comprehensive analysis of STR in terms of botany, traditional use, phytochemistry, ethnopharmacology, pharmacology, pharmacokinetics, toxicology and detoxification strategy, to provide a rational application in future research. MATERIALS AND METHODS: The information involved in the study was gathered from a variety of electronic resources, including China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations. RESULTS: Till now, a total of 333 chemical components have been identified in STR, including 85 alkaloids, 124 flavonoids, 24 triterpenes, 27 triterpene saponins, 34 organic acids, 8 polysaccharides, etc. STR and its main active constituents have cardiovascular protection, anti-tumor activity, anti-inflammatory activity, antipyretic activity, analgesic activity, antibacterial activity, antifungal activity, antiviral activity, and hepatoprotective activity, etc. However, toxic effects of STR on the liver, nerves, heart, and gastrointestinal tract have also been observed. To mitigate these risks, STR needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. The pharmacokinetics of STR in vivo and traditional and clinical prescriptions containing STR have been sorted out. Despite the potential therapeutic benefits of STR, further research is warranted to elucidate its hepatotoxicity, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and mechanisms. CONCLUSION: This review serves to emphasize the therapeutic potential of STR and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the toxicological properties of STR, with particular emphasis on its hepatotoxicity and neurotoxicity. Such research endeavors have the potential to standardize the rational application of STR for optimal therapeutic outcomes.

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Litopenaeus vannamei is a widely distributed euryhaline aquatic animal, affected by low salinity, which can impact its disease resistance and immunity. However, there is a limited understanding of the adaptation mechanisms of L. vannamei with different genetic backgrounds to low salinity. Therefore, the present study aimed to compare the immunity characteristics and transcriptomics of L. vannamei low salt-tolerant (FG I/J) and low salt-sensitive (control) families. Also, the disease resistance and immune parameters (including [THC], hemolymph cell viability, lysozyme activity [LZM], phenoloxidase content [PO], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) of the FG I/J and control families of L. vannamei under low salinity (5‰) and ambient salinity (24‰) were examined. Additionally, hepatopancreas transcriptomics of the FG I/J and control families were analyzed at a salinity of 5‰. The results showed that the FG I/J family had higher disease resistance to Vibrio parahaemolyticus and stronger immunological capacity than the control family. Transcriptomic analysis showed significantly enriched energy metabolism and immune regulation pathways. Therefore, we speculated that energy metabolism provides sufficient energy for immunological modulation in the FG I/J family to deal with long-term low-salt stress and achieve high growth and survival rates.

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Resistência à Doença , Perfilação da Expressão Gênica , Penaeidae , Tolerância ao Sal , Transcriptoma , Animais , Penaeidae/imunologia , Penaeidae/genética , Resistência à Doença/genética , Resistência à Doença/imunologia , Tolerância ao Sal/genética , Vibrio parahaemolyticus/fisiologia , Vibrio parahaemolyticus/imunologia , Vibrioses/imunologia , Hepatopâncreas/imunologia , Hepatopâncreas/metabolismo , Salinidade , Imunidade Inata , Hemolinfa/metabolismo , Hemolinfa/imunologia , Metabolismo Energético/genética , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo

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Alzheimer's disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aß(25-35) in glial (BV-2 and SW-1783) and neuron (SH-SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA-Trpv1-Nrf2 pathway.

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Due to past massive usage and persistent nature, pentachlorophenol (PCP) residues are prevalent in environments, posing a potential threat to various organisms such as sessile filter-feeding bivalves. Although humoral immunity and its crosstalk with cellular one are crucial for the maintaining of robust antimicrobic capability, little is known about the impacts of PCP on these critical processes in bivalve mollusks. In this study, pathogenic bacterial challenge and plasma antimicrobic capability assays were carried out to assess the toxic effects of PCP on the immunity of a common bivalve species, blood clam (Tegillarca granosa). Moreover, the impacts of PCP-exposure on the capabilities of pathogen recognition, hemocyte recruitment, and pathogen degradation were analyzed as well. Furthermore, the activation status of downstream immune-related signalling pathways upon PCP exposure was also assessed. Data obtained illustrated that 28-day treatment with environmentally realistic levels of PCP resulted in evident declines in the survival rates of blood clam upon Vibrio challenge along with markedly weakened plasma antimicrobic capability. Additionally, the levels of lectin and peptidoglycan-recognition proteins (PGRPs) in plasma as well as the expression of pattern recognition receptors (PRRs) in hemocytes were found to be significantly inhibited by PCP-exposure. Moreover, along with the downregulation of immune-related signalling pathway, markedly fewer chemokines (interleukin 8 (IL-8), IL-17, and tumor necrosis factor α (TNF-α)) in plasma and significantly suppressed chemotactic activity of hemocytes were also observed in PCP-exposed blood clams. Furthermore, compared to that of the control, blood clams treated with PCP had markedly lower levels of antimicrobic active substances, lysozyme (LZM) and antimicrobial peptides (AMP), in their plasma. In general, the results of this study suggest that PCP exposure could significantly impair the antimicrobic capability of blood clam via undermining humoral immunity and disrupting humoral-cellular crosstalk.

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Hemócitos , Imunidade Humoral , Pentaclorofenol , Animais , Pentaclorofenol/toxicidade , Imunidade Humoral/efeitos dos fármacos , Hemócitos/efeitos dos fármacos , Hemócitos/imunologia , Imunidade Celular/efeitos dos fármacos , Bivalves/efeitos dos fármacos , Bivalves/imunologia , Poluentes Químicos da Água/toxicidade , Arcidae/efeitos dos fármacos , Vibrio/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos

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As proactivity becomes vital for organizational success, retaining proactive employees becomes increasingly important, making the relationship between a proactive personality and turnover intention a key research topic. While existing studies have largely depicted turnover as a consequence of dissatisfaction and have identified negative indirect relationships, this study seeks to challenge that perspective by proposing that, in today's boundaryless career environment, people also engage in voluntary turnover for career advancement. Using a self-regulation career management model, we propose that proactive employees set ambitious career goals influenced by career aspirations, leading them to seek external opportunities and thus exhibit higher turnover intention. However, when organizations implement career management practices, this relationship weakens as proactive employees perceive opportunities to achieve their goals within their current organizations. We tested these hypotheses with a sample of 342 respondents using the SPSS macro PROCESS. The findings support our propositions, revealing a positive indirect effect through career aspirations, which diminishes when perceived organizational career management is strong.

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Two-photon high-speed fluorescence calcium imaging stands as a mainstream technique in neuroscience for capturing neural activities with high spatiotemporal resolution. However, challenges arise from the inherent tradeoff between acquisition speed and image quality, grappling with a low signal-to-noise ratio (SNR) due to limited signal photon flux. Here, a contrast-enhanced video-rate volumetric system, integrating a tunable acoustic gradient (TAG) lens-based high-speed microscopy with a TAG-SPARK denoising algorithm is demonstrated. The former facilitates high-speed dense z-sampling at sub-micrometer-scale intervals, allowing the latter to exploit the spatial redundancy of z-slices for self-supervised model training. This spatial redundancy-based approach, tailored for 4D (xyzt) dataset, not only achieves >700% SNR enhancement but also retains fast-spiking functional profiles of neuronal activities. High-speed plus high-quality images are exemplified by in vivo Purkinje cells calcium observation, revealing intriguing dendritic-to-somatic signal convolution, i.e., similar dendritic signals lead to reverse somatic responses. This tailored technique allows for capturing neuronal activities with high SNR, thus advancing the fundamental comprehension of neuronal transduction pathways within 3D neuronal architecture.

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Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule, which has been shown to play an important role in plant growth and development by coupling with various phytohormones. However, the relationship between H2S and cytokinin (CTK) and the mechanisms by which H2S and CTK affect root growth remain poorly understood. Endogenous CTK was analyzed by UHPLC-ESI-MS/MS. Persulfidation of cytokinin oxidase/dehydrogenases (CKXs) was analyzed by mass spectrometry (MS). ckx2/CKX2wild-type (WT), OE CKX2 and ckx2/CKX2Cys(C)62alanine(A) transgenic lines were isolated with the ckx2 background. H2S is linked to CTK content by CKX2, which regulates root system architecture (RSA). Persulfidation at cysteine (Cys)62 residue of CKX2 enhances CKX2 activity, resulting in reduced CTK content. We utilized 35S-LCD/oasa1 transgenic lines to investigate the effect of endogenous H2S on RSA, indicating that H2S reduces the gravitropic set-point angle (GSA), shortens root hairs, and increases the number of lateral roots (LRs). The persulfidation of CKX2Cys62 changes the elongation of cells on the upper and lower flanks of LR elongation zone, confirming that Cys62 of CKX2 is the specificity target of H2S to regulate RSA in vivo. In conclusion, this study demonstrated that H2S negatively regulates CTK content and affects RSA by persulfidation of CKX2Cys62 in Arabidopsis thaliana.

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The impact of logistics development on the economy covers many aspects, such as production, cost, employment, international trade, etc. It is an indispensable part of the modern economy, which helps to improve overall economic efficiency and social prosperity. This study studies the spatiotemporal dynamic evolution characteristics of China's logistics development from 2008 to 2018 and explores its impact on economic growth in multiple dimensions of time and space. The research findings indicate the following: (1) From 2008 to 2018, China's logistics development level (LDL) exhibited a clear upward trend. The differences between the eastern, central, and western regions showed fluctuating downward patterns, ultimately converging towards a high-level concentration. Concerning spatial distribution, China's logistics development demonstrated a trend towards the west and south. However, the spatial pattern of "strong in the east and weak in the west " has existed for a long time. Moreover, the "T-shaped" pattern between coastal provinces and those along the Yangtze River Basin deepened, and the LDL in the central and western regions significantly improved. (2) The advancement of China's LDL effectively promotes its economic growth, confirming that the Belt and Road Initiative enhances the role of logistics development in driving economic growth. Regarding regional differences, logistics development positively influences economic growth in the eastern and western regions, with a less significant impact on the central region. Regarding the strength of influence, logistics development has a more substantial effect on promoting high-ranking provinces in the entire country, the eastern region, and the central region, as well as boosting economic growth in low-ranking provinces in the western region.

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Copper, a vital mineral nutrient, possesses redox qualities that make it both beneficial and toxic to organisms. Excessive environmental copper exposure can result in neurological damage and cognitive decline in humans. Astrocytes, the predominant glial cells in the brain, are particularly vulnerable to pollutants, but the mechanism of copper-induced damage to astrocytes remains elusive. The aim of this study was to determine the role of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in initiating NLRP3 inflammasome-induced astrocyte pyroptosis and chronic inflammation under conditions of copper overload. Our findings indicated that copper exposure elevated mitochondrial ROS (mtROS) levels, resulting in mitochondrial damage in astrocytes. This damage caused the release of mitochondrial DNA (mtDNA) into the cytoplasm, which subsequently activated the cGAS-STING pathway. This activation resulted in interactions between STING and NLRP3 proteins, facilitating the assembly of the NLRP3 inflammasome and inducing pyroptosis. Furthermore, depletion of mtROS mitigated copper-induced mitochondrial damage in astrocytes and reduced mtDNA leakage. Pharmacological inhibition of STING or STING transfection further reversed copper-induced pyroptosis and the inflammatory response. In conclusion, this study demonstrated that the leakage of mtDNA into the cytoplasm and the subsequent activation of the cGAS-STING-NLRP3 pathway may be potential mechanisms underlying copper-induced pyroptosis in astrocytes. These findings provided new insights into the toxicity of copper.

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Adipose tissue macrophages (ATMs) play important roles in maintaining adipose tissue homeostasis and orchestrating metabolic inflammation. Given the extensive functional heterogeneity and phenotypic plasticity of ATMs, identification of the authentically pathogenic ATM subpopulation under obese setting is thus necessitated. Herein, we performed single-nucleus RNA sequencing (snRNA-seq) and unraveled a unique maladaptive ATM subpopulation defined as ATF4hiPDIA3hiACSL4hiCCL2hi inflammatory and metabolically activated macrophages (iMAMs), in which PDIA3 is required for the maintenance of their migratory and pro-inflammatory properties. Mechanistically, ATF4 serves as a metabolic stress sensor to transcribe PDIA3, which then imposes a redox control on RhoA activity and strengthens the pro-inflammatory and migratory properties of iMAMs through RhoA-YAP signaling. Administration of Pdia3 small interfering RNA (siRNA)-loaded liposomes effectively repressed adipose inflammation and high-fat diet (HFD)-induced obesity. Together, our data support that strategies aimed at targeting iMAMs by suppressing PDIA3 expression or activity could be a viable approach against obesity and metabolic disorders in clinical settings.

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Tecido Adiposo , Macrófagos , Doenças Metabólicas , Camundongos Endogâmicos C57BL , Obesidade , Isomerases de Dissulfetos de Proteínas , Animais , Obesidade/metabolismo , Obesidade/patologia , Macrófagos/metabolismo , Camundongos , Tecido Adiposo/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Masculino , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Inflamação/patologia

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Diagnostic imaging, particularly MRI, plays a key role in the evaluation of many spine pathologies. Recent progress in artificial intelligence and its subset, machine learning, has led to many applications within spine MRI, which we sought to examine in this review. A literature search of the major databases (PubMed, MEDLINE, Web of Science, ClinicalTrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search yielded 1226 results, of which 50 studies were selected for inclusion. Key data from these studies were extracted. Studies were categorized thematically into the following: Image Acquisition and Processing, Segmentation, Diagnosis and Treatment Planning, and Patient Selection and Prognostication. Gaps in the literature and the proposed areas of future research are discussed. Current research demonstrates the ability of artificial intelligence to improve various aspects of this field, from image acquisition to analysis and clinical care. We also acknowledge the limitations of current technology. Future work will require collaborative efforts in order to fully exploit new technologies while addressing the practical challenges of generalizability and implementation. In particular, the use of foundation models and large-language models in spine MRI is a promising area, warranting further research. Studies assessing model performance in real-world clinical settings will also help uncover unintended consequences and maximize the benefits for patient care.

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Inter-metalloid clusters in Zintl chemistry have been extensively studied due to their unique electronic structures and potential applications. In this work, we explored a series of actinide endohedral inter-metalloid clusters of the group 15 elements [An@Bi12]4- (An = Th-U) and [An@Sb12]4- using density functional theory (DFT). [Th@Bi12]4- and [U@Bi12]4- exhibit Cs symmetry, while [Pa@Bi12]4- and [An@Sb12]4- (An = Th-U) have C1 structures. Bonding analyses such as bond order, molecular orbitals (MO) and quantum theory of atoms in molecules (QTAIM) show covalent An-Bi/An-Sb bonding in the clusters. All these clusters are highly stable according to the studied formation reactions and may be accessible experimentally. Compared with [An@Bi12]4-, [An@Sb12]4- possesses stronger bonding interactions, mainly arising from the higher electrostatic interaction energy. For clusters with the same group 15 elements, the bonding interactions increase gradually from Th to U, which is mainly determined by the covalent interactions of An-Bi/An-Sb bonding. This work is expected to provide potential avenues for the construction of robust inter-metalloid clusters of the group 15 elements.