Feasibility of the novel vascular disrupting agent C118P for facilitating high-intensity focused ultrasound ablation of uterine fibroids.

OBJECTIVE: In this study, C118P, a novel vascular disrupting agent (VDA), was evaluated for its ability in improving the ablative effect of high-intensity focused ultrasound (HIFU) on uterine fibroids by reducing blood perfusion. METHODS: Eighteen female rabbits were infused with isotonic sodium chloride solution (ISCS), C118P or oxytocin for 30 min, and an HIFU ablation of the leg muscles was performed within the last 2 min. Blood pressure, heart rate and laser speckle flow imaging (LSFI) of the auricular blood vessels were recorded during perfusion. Ears with vessels, uterus and muscle ablation sites were collected and sliced for hematoxylin-eosin (HE) staining to compare vascular size, as well as nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) staining to observe necrosis after ablation. RESULTS: Analyses revealed that the perfusion of C118P or oxytocin steadily reduced blood perfusion in the ears to approximately half by the end of the perfusion, constricted the blood vessels of the ears and uterus, and improved HIFU ablation in the muscle tissues. C118P increased blood pressure and decreased heart rate. The degree of contraction of the auricular and uterine blood vessels was positively correlated. CONCLUSION: This study confirmed that C118P could reduce blood perfusion in various tissues and had a better synergistic effect with HIFU ablation of muscle (the same tissue type as fibroids) than did oxytocin. C118P could therefore possibly replace oxytocin in facilitating HIFU ablation of uterine fibroids; however, electrocardiographic monitoring is required.

An improved AdaBoost algorithm for identification of lung cancer based on electronic nose.

The research developed an improved intelligent enhancement learning algorithm based on AdaBoost, that can be applied for lung cancer breath detection by the electronic nose (eNose). First, collected the breath signals from volunteers by eNose, including healthy individuals and people who had lung cancer. Additionally, the signals' features were extracted and optimized. Then, multi sub-classifiers were obtained, and their coefficients were derived from the training error. To improve generalization performance, K-fold cross-validation was used when constructing each sub-classifier. The prediction results of a sub-classifier on the test set were then achieved by the voting method. Thus, an improved AdaBoost classifier would be built through heterogeneous integration. The results shows that the average precision of the improved algorithm classifier for distinguishing between people with lung cancer and healthy individuals could reach 98.47%, with 98.33% sensitivity and 97% specificity. And in 100 independent and randomized tests, the coefficient of variation of the classifier's performance hardly exceeded 4%. Compared with other integrated algorithms, the generalization and stability of the improved algorithm classifier are more superior. It is clear that the improved AdaBoost algorithm may help screen out lung cancer more comprehensively. Additionally, it will significantly advance the use of eNose in the early identification of lung cancer.

A facile approach to obtain super-hydrophobicity for cotton fiber fabrics.

It is a challenging task to directly apply emulsified silicone oil to the surface of cotton fabric to obtain superhydrophobic properties. In this work, a temperature-responsive microgel was first synthesized and the particle size and distribution of the microgel, thermo-responsiveness, and hydrophobicity of the microgel membrane were investigated. Then, through an emulsifying PMHS/water system with microgels as a Pickering emulsifier, a series of Pickering emulsions were obtained. The results showed that the emulsion had the best stability when the microgel content was 2.14 wt% and the mass ratio of PMHS/water was 3/7. The optical microscopy showed that the oil phase could be uniformly dispersed in aqueous solution, and the liquid phase particle size was about 10-22 µm. And stratification of the Pickering emulsion did not occur when placed at room temperature for over one month. Finally, when the addition of Pickering emulsion is 50 g L-1 and the rolling rate is 80%, through a simple two-dip-two-padding treatment, a cotton fabric can obtain the superhydrophobic effect with a static contact angle of 149.6° at 25 °C and 156.4° at 45 °C. The development of this work provides a simple method to make cotton fabric obtain superhydrophobic effects.

Potential predictive value of CT radiomics features for treatment response in patients with COVID-19.

INTRODUCTION: This study aims to explore the predictive value of CT radiomics and clinical characteristics for treatment response in COVID-19 patients. METHODS: Data were collected from clinical/auxiliary examinations and follow-ups of COVID-19 patients. Whole lung radiomics feature extraction was performed at baseline chest CT. Radiomics, clinical, and combined features (nomogram) were evaluated for predicting treatment response. RESULTS: Among 36 COVID-19 patients, mild, common, severe, and critical disease symptoms were found in 1, 21, 13, and 1 of them, respectively. Twenty-five (1 mild, 18 common, and 6 severe) patients showed a good response to treatment and 11 poor/fair responses. The clinical classification (p = 0.025) and serum creatinine (p = 0.010) on admission and small area emphasis (p = 0.036) from radiomics analysis significantly differed between the two groups. Predictive models were constructed based on the radiomics, clinical features, and nomogram showing an area under the curve of 0.651, 0.836, and 0.869, respectively. The nomogram achieved good calibration. CONCLUSION: This new, non-invasive, and low-cost prediction model that combines the radiomics and clinical features is useful for identifying COVID-19 patients who may not respond well to treatment.

Development and Characterization of Nanobody-Derived CD47 Theranostic Pairs in Solid Tumors.

Overexpression of CD47 is frequently observed in various types of human malignancies, inhibiting myeloid-mediated elimination of tumor cells and affecting the prognosis of cancer patients. By mapping biomarker expression, immuno-positron emission tomography has been increasingly used for patient screening and response monitoring. By immunization alpacas with recombinant human CD47, we prepared a CD47-targeting nanobody C2 and developed [68Ga]Ga-NOTA-C2, followed by an exploration of the diagnostic value in CD47-expressing tumor models including gastric-cancer patient-derived xenograft models. By fusing C2 to an albumin binding domain (ABD), we synthesized ABDC2, which had increased in vivo half-life and improved targeting properties. We further labeled ABDC2 with 68Ga/89Zr/177Lu to develop radionuclide theranostic pairs and evaluated the pharmacokinetics and theranostic efficacies of the agents in cell- and patient-derived models. Both C2 and ABDC2 specifically reacted with human CD47 with a high K D value of 23.50 and 84.57 pM, respectively. [68Ga]Ga-NOTA-C2 was developed with high radiochemical purity (99 >%, n = 4) and visualized CD47 expression in the tumors. In comparison to the rapid renal clearance and short half-life of [68Ga]Ga-NOTA-C2, both [68Ga]Ga-NOTA-ABDC2 and [89Zr]Zr-DFO-ABDC2 showed prolonged circulation and increased tumor uptake, with the highest uptake of [89Zr]Zr-DFO-ABDC2 occurring at 72 h post-injection. Moreover, [177Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed the tumor growth but was associated with toxicity, warranting further optimization of the treatment schedules. Taken together, we reported a series of nanobody-derived CD47-targeted agents, of which [68Ga]Ga-NOTA-C2 and [89Zr]Zr-DFO-ABDC2 are readily translatable. Optimization and translation of CD47-targeted theranostic pair may provide new prospects for CD47-targeted management of solid tumors.

Stability and Hopf bifurcation of an HIV infection model with two time delays.

This work focuses on an HIV infection model with intracellular delay and immune response delay, in which the former delay refers to the time it takes for healthy cells to become infectious after infection, and the latter delay refers to the time when immune cells are activated and induced by infected cells. By investigating the properties of the associated characteristic equation, we derive sufficient criteria for the asymptotic stability of the equilibria and the existence of Hopf bifurcation to the delayed model. Based on normal form theory and center manifold theorem, the stability and the direction of the Hopf bifurcating periodic solutions are studied. The results reveal that the intracellular delay cannot affect the stability of the immunity-present equilibrium, but the immune response delay can destabilize the stable immunity-present equilibrium through the Hopf bifurcation. Numerical simulations are provided to support the theoretical results.

Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer.

The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell-intrinsic oncogenic signaling are increasingly appreciated for their role in shaping the immune landscape. Recently, we identified Pygopus 2 (PYGO2) as the driver oncogene for the amplicon at 1q21.3 in prostate cancer. Here, using transgenic mouse models of metastatic prostate adenocarcinoma, we found that Pygo2 deletion decelerated tumor progression, diminished metastases, and extended survival. Pygo2 loss augmented the activation and infiltration of cytotoxic T lymphocytes (CTLs) and sensitized tumor cells to T cell killing. Mechanistically, Pygo2 orchestrated a p53/Sp1/Kit/Ido1 signaling network to foster a microenvironment hostile to CTLs. Genetic or pharmacological inhibition of Pygo2 enhanced the antitumor efficacy of immunotherapies using immune checkpoint blockade (ICB), adoptive cell transfer, or agents inhibiting myeloid-derived suppressor cells. In human prostate cancer samples, Pygo2 expression was inversely correlated with the infiltration of CD8+ T cells. Analysis of the ICB clinical data showed association between high PYGO2 level and worse outcome. Together, our results highlight a potential path to improve immunotherapy using Pygo2-targeted therapy for advanced prostate cancer.

Anti-stokes luminescent organic nanoparticles for frequency upconversion biomedical imaging.

Frequency upconversion optical imaging has attracted great attention due to its remarkable advantages over traditional down-conversion optical imaging. However, the development of frequency upconversion optical imaging is extremely limited. Herein, five derivatives with BODIPY structure (B1-B5) were developed to investigate its frequency upconversion luminescence (FUCL) performance by introducing electron-donating and electron-withdrawing groups. Except for the nitro group decorated derivative, the other derivatives have strong and stable FUCL around 520 nm under 635 nm light excitation. More importantly, B5 retains FUCL ability after self-assembly. When applied to FUCL imaging of cells, B5 nanoparticles can be enriched in the cytoplasm and show a good signal-to-noise ratio. Meanwhile, FUCL tumor imaging can be achieved after 1 h of injection. This study not only provides a potential agent for FUCL biomedical imaging but also develops a new strategy for designing FUCL agents that exhibit excellent performance.

Development and validation of a mutation-based model to predict immunotherapeutic efficacy in NSCLC.

Background: Immunotherapy has become increasingly important in the perioperative period of non-small-cell lung cancer (NSCLC). In this study, we intended to develop a mutation-based model to predict the therapeutic effificacy of immune checkpoint inhibitors (ICIs) in patients with NSCLC. Methods: Random Forest (RF) classifiers were generated to identify tumor gene mutated features associated with immunotherapy outcomes. Then the best classifier with the highest accuracy served for the development of the predictive model. The correlations of some reported biomarkers with the model were analyzed, such as TMB, PD-(L)1, KEAP1-driven co-mutations, and immune subtypes. The training cohort and validation cohorts performed survival analyses to estimate the predictive efficiency independently. Results: An 18-gene set was selected using random forest (RF) classififiers. A predictive model was developed based on the number of mutant genes among the candidate genes, and patients were divided into the MT group (mutant gene ≥ 2) and WT group (mutant gene < 2). The MT group (N = 54) had better overall survival (OS) compared to the WT group (N = 290); the median OS was not reached vs. nine months (P < 0.0001, AUC = 0.73). The robust predictive performance was confifirmed in three validation cohorts, with an AUC of 0.70, 0.57, and 0.64 (P < 0.05). The MT group was characterized by high tumor neoantigen burden (TNB), increased immune infifiltration cells such as CD8 T and macrophage cells, and upregulated immune checkpoint molecules, suggesting potential biological advantages in ICIs therapy. Conclusions: The predictive model could precisely predict the immunotherapeutic efficacy in NSCLC based on the mutant genes within the model. Furthermore, some immune-related features and cell expression could support robust efficiency.

Preparation and Application of Directed Vat Set Indigenous Freeze-Drying Lentilactobacillus hilgardii Q19 Starter in Winemaking.

In order to prepare a better direct vat set for malolactic fermentation (MLF) in high ethanol and low pH wines, the high-ethanol- and low-temperature-tolerant strain Lentilactobacillus hilgardii Q19, which was isolated from the eastern foothill of the Helan Mountain wine region in China, was used to prepare a direct vat set by vacuum freeze-drying. A superior freeze-dried lyoprotectant was obtained to create the starting culture by selecting, combining, and optimizing numerous lyoprotectants with higher protection for Q19 by using a single-factor experiment and response surface approach. Finally, the Lentilactobacillus hilgardii Q19 direct vat set was inoculated in Cabernet Sauvignon wine to carry out MLF on a pilot scale, with commercial starter culture Oeno1 as control. The volatile compounds, biogenic amines, and ethyl carbamate content were analyzed. The results showed that a combination of 8.5 g/100 mL skimmed milk powder, 14.5 g/100 mL yeast extract powder, and 6.0 g/100 mL sodium hydrogen glutamate offered better protection; with this lyoprotectant, there were (4.36 ± 0.34) × 1011 CFU/g cells after freeze-drying, and it showed an excellent ability to degrade L-malic acid and could successfully finish MLF. In addition, in terms of aroma and wine safety, compared with Oeno1, the quantity and complexity of volatile compounds were increased after MLF, and biogenic amines and ethyl carbamate were produced less during MLF. We conclude that the Lentilactobacillus hilgardii Q19 direct vat set could be applied as a new MLF starter culture in high-ethanol wines.

Runx1/3-driven adaptive endoplasmic reticulum stress pathways contribute to neurofibromagenesis.

Neurofibromatosis type 1 (NF1) patients are predisposed to develop plexiform neurofibromas (PNFs). Three endoplasmic reticulum (ER) stress response pathways restore cellular homeostasis. The unfolded protein response (UPR) sensors contribute to tumor initiation in many cancers. We found that all three UPR pathways were activated in mouse and human PNFs, with protein kinase RNA [PKR]-like ER kinase (PERK) the most highly expressed. We tested if neurofibroma cells adapt to ER stress, leading to their growth. Pharmacological or genetic inhibition of PERK reduced mouse neurofibroma-sphere number, and genetic inhibition in PERK in Schwann cell precursors (SCPs) decreased tumor-like lesion numbers in a cell transplantation model. Further, in a PNF mouse model, deletion of PERK in Schwann cells (SCs) and SCPs reduced tumor size, number, and increased survival. Mechanistically, loss of Nf1 activated PERK-eIF2α-ATF4 signaling and increased ATF4 downstream target gene p21 translocation from nucleus to cytoplasm. This nucleus-cytoplasm translocation was mediated by exportin-1. Runx transcriptionally activated ribosome gene expression and increased protein synthesis to allow SCs to adapt to ER stress and tumor formation. We propose that targeting proteostasis might provide cytotoxic and/or potentially durable novel therapy for PNFs.

Polydopamine-Coated Radiolabeled Microspheres for Combinatorial Radioembolization and Photothermal Cancer Therapy.

Transarterial radioembolization (TARE) is a local radionuclide therapy and is successfully used in hepatocellular carcinoma (HCC) treatment. Radioactive microspheres have been widely studied for TARE. Preparation of ideal radioactive microspheres is significant for clinical research and patient treatment. In this study, we have designed a novel multifunctional microsphere, i.e., polydopamine (PDA)-coated 177Lu-radiolabeled silica microspheres (MS) denoted as 177Lu-MS@PDA, which can be used for TARE and photothermal therapy (PTT). The radiostability of 177Lu-MS@PDA was significantly improved by coating 177Lu-MS with PDA. In addition, the coating of PDA makes microspheres have excellent photothermal performance. MicroSPECT/CT images showed that 177Lu-MS@PDA was accurately embolized and remained in the tumor during the observation time. At the time, it also showed that 177Lu-MS@PDA was very stable in vivo. Furthermore, the anti-tumor results demonstrated that TARE combined with PTT of 177Lu-MS@PDA can significantly inhibit tumor growth without obvious side effects. 177Lu-MS@PDA holds great potential as a promising radioactive microsphere for HCC.

MiR-216a-3p inhibits the proliferation and invasion of fibroblast-like synoviocytes by targeting dual-specificity phosphatase 5.

Dual-specificity phosphatase 5 (DUSP5) is a novel anti-inflammatory modulator in many inflammatory diseases. However, the role of DUSP5 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) remains unknown. In this study, we aimed to explore the biological function and regulation of DUSP5 in FLS. We found that lower DUSP5 expression level was detected in collagen-induced arthritis (CIA) and synoviocyte MH7A. Overexpression of DUSP5 markedly decreased the proliferation, migration, and invasion of MH7A, which correlated with suppressing the phosphorylation of extracellular signal-regulated kinase (ERK). Moreover, DUSP5 was identified as a novel target gene of miR-216a-3p, which was upregulated in FLS. Therefore, DUSP5 expression was negatively regulated by miR-216a-3p, and the effect of DUSP5 overexpression on FLS was reversed by miR-216a-3p mimics. Overall, our study demonstrates that DUSP5 is a miR-216a-3p target gene and its anti-inflammatory function in FLS via inactivation of ERK. These results revealed that the miR-216a-3p/DUSP5 pathway may play a crucial role in the malignant behavior of FLS, which may serve as a new target for the treatment of RA.

Radiogenomics study to predict the nuclear grade of renal clear cell carcinoma.

Purpose: To develop models based on radiomics and genomics for predicting the histopathologic nuclear grade with localized clear cell renal cell carcinoma (ccRCC) and to assess whether macro-radiomics models can predict the microscopic pathological changes. Method: In this multi-institutional retrospective study, a computerized tomography (CT) radiomic model for nuclear grade prediction was developed. Utilizing a genomics analysis cohort, nuclear grade-associated gene modules were identified, and a gene model was constructed based on top 30 hub mRNA to predict the nuclear grade. Using a radiogenomic development cohort, biological pathways were enriched by hub genes and a radiogenomic map was created. Results: The four-features-based SVM model predicted nuclear grade with an area under the curve (AUC) score of 0.94 in validation sets, while a five-gene-based model predicted nuclear grade with an AUC of 0.73 in the genomics analysis cohort. A total of five gene modules were identified to be associated with the nuclear grade. Radiomic features were only associated with 271 out of 603 genes in five gene modules and eight top 30 hub genes. Differences existed in the enrichment pathway between associated and un-associated with radiomic features, which were associated with two genes of five-gene signatures in the mRNA model. Conclusion: The CT radiomics models exhibited higher predictive performance than mRNA models. The association between radiomic features and mRNA related to nuclear grade is not universal.

A Cascade BIME-Triggered Near-IR Cyanine Nanoplatform for Enhanced Antibacterial Photodynamic Therapy.

The long-standing misuse of antibiotics has accelerated the emergence of drug-resistant bacteria, which gives rise to an urgent public health threat. Antibacterial photodynamic therapy (aPDT), as a burgeoning and promising antibacterial strategy, plays an essential role in avoiding the evolution of drug-resistant microbes. However, it is hard for conventional photosensitizers to achieve satisfactory antibacterial efficacy because of the complex bacterial infectious microenvironment (BIME). Herein, a cascade BIME-triggered near-infrared cyanine (HA-CY) nanoplatform has been developed via conjugating cyanine units to biocompatible hyaluronic acid (HA) for enhanced aPDT efficacy. The HA-CY nanoparticles can be dissociated under the overexpressed hyaluronidase in BIME to release a cyanine photosensitizer. Meanwhile, cyanine can be protonated under acidic BIME, where protonated cyanine can efficiently adhere to the surface of a negatively charged bacterial membrane and increase singlet oxygen production due to intramolecular charge transfer (ICT). Experiments in the cellular level and animal model proved that the BIME-triggered activation of aPDT could remarkably boost aPDT efficacy. Overall, this BIME-triggered HA-CY nanoplatform presents great promise for overcoming the dilemma of drug-resistant microbes.

Immunological Findings in a Group of Individuals Who Were Poor or Non-Responders to Standard Two-Dose SARS-CoV-2 Vaccines.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic. However, data on the poor or non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of this study was to comprehensively compare the immunological characteristics of poor or non-responders to SARS-CoV-2 vaccines in the 18-59-year group with those in the ≥60-year group using internationally recognized cut-off values. The main outcome was effective seroconversion characterized by an anti-SARS-CoV-2 spike IgG level of at least a four-fold increase from baseline. Profiling of naïve immune cells was analyzed prior to vaccination to demonstrate baseline immunity. The outcomes of effective seroconversion in patients aged 18-59 years with those in patients aged ≥60 years were compared. The quantitative level of anti-spike IgG was significantly lower in individuals aged ≥60 and men aged 18-59 years. There were 7.5% of poor or non-responders among the 18-59 years and 11.7% of poor or non-responders in the ≥60 years using a four-fold increase parameter. There were 37.0-58.1% with low lymphocyte count (<1000/mm3), 33.3-45.2% with low CD4 cell counts (<500/mm3), and 74.1-96.8% with low B cell counts (<100/mm3) in the non-seroconversion group. An individual with an anti-SARS-CoV-2 spike IgG titer below 50 BAU/mL might be considered a poor or non-responder between 14 and 90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended to poor or non-responders as soon as possible to reduce disease severity and mortality.

Mesoporous Gold Film with Surface Sulfur Modification to Enable Dendrite-Free Lithium Plating/Stripping for Long-Life Lithium Metal Anodes.

The formation of a lithiophilic phase is an effective method to inhibit the growth of lithium dendrites and obtain high-performance Li metal anodes (LMAs). Nonetheless, previous studies have overlooked the underlying mechanistic studies that modulate the structure of the lithiophilic phase as well as lithiophilicity. A self-supporting sulfur-modified mesoporous gold film on nickel foam (SMGF@NF) for LMAs is created with mesoporous structure, which can provide sufficient active sites for uniform lithium deposition. The synergistic promotion of lithiophilic gold and sulfur leads to uniform lithium nucleation and induces consistent lithium removal during lithium stripping. The doping of S promotes the decomposition of bistrifluoromethanesulfonimide lithium salt to generate lithium fluorde, thus forming a more stable solid electrolyte interface. Combining the multifaceted advantages of SMGF@NF, its lithium-plated electrode can achieve ultralong cycle life in symmetrical batteries (over 1000 h at 0.5 mA cm-2 and 1 mAh cm-2 ) and ultralow overpotential (≈10 mV). Meanwhile, the Li-SMGF@NF||LiFePO4 full cell achieves a high cycling performance and rate capability (92.4% capacity retention after 1000 cycles at 5 C). The study probes into the composite electrode surface composition and structure, revealing the mechanism of high-performance LMAs.

[Altitudinal pattern and driving factors of soil fungal community in the tropical forest of Jianfengling, Hai-nan, China]. / å°–å³°å²­çƒ­å¸¦æ£®æž—åœŸå£¤çœŸèŒç¾¤è½çš„æµ·æ‹”å˜åŒ–æ ¼å±€åŠé©±åŠ¨å› ç´ .

Fungi are an important group of soil microorganisms. Exploring the altitudinal pattern and driving factors of fungal composition and diversity is an important topic in the field of biodiversity and ecosystem function. We employed the Illumina high-throughput sequencing technology to investigate the variation and environmental control of fungal α-diversity and ß-diversity at the topsoil (0-20 cm) and subsoil (20-40 cm) across an altitudinal gra-dient of 400-1500 m in a tropical forest of Jianfengling Nature Reserve. The results showed that Ascomycota and Basidiomycota dominated soil fungal community, reaching a relative abundance of more than 90%. Fungal α-diversity at the topsoil exhibited no obvious altitudinal pattern, and that of the subsoil decreased with the increases in altitude. Higher fungal α-diversity was observed in the topsoil. Soil fungi ß-diversity was significantly affected by altitude. Morover, temperature was the driving force of the altitude pattern of fungi ß-diversity. The similarity of fungal community decreased significantly with the increases in geographical distance, but did not change with the increases in environmental distance. The similarity of rare phyla (Mortierellomycota, Mucoromycota and Rozellomycota) was significantly lower than that of rich phyla (Ascomycota and Basidiomycota), indicating that diffusion restriction determined the differentiation of fungal community structure along the altitude gradient. Our study demonstrated that the diversity of soil fungal community was affected by altitude. The rare phyla, rather than rich phyla, determined the altitudinal variation of fungi ß-diversity in Jianfengling tropical forest.

A clinically translatable kit for MRI/NMI dual-modality nanoprobes based on anchoring group-mediated radiolabeling.

Magnetic resonance imaging (MRI)/nuclear medicine imaging (NMI) dual-modality imaging based on radiolabeled nanoparticles has been increasingly exploited for accurate diagnosis of tumor and cardiovascular diseases by virtue of high spatial resolution and high sensitivity. However, significant challenges exist in pursuing truly clinical applications, including massive preparation and rapid radiolabeling of nanoparticles. Herein, we report a clinically translatable kit for the convenient construction of MRI/NMI nanoprobes relying on the flow-synthesis and anchoring group-mediated radiolabeling (LAGMERAL) of iron oxide nanoparticles. First, homogeneous iron oxide nanoparticles with excellent performance were successfully obtained on a large scale by flow synthesis, followed by the surface anchoring of diphosphonate-polyethylene glycol (DP-PEG) to simultaneously render the underlying nanoparticles biocompatible and competent in robust labeling of radioactive metal ions. Moreover, to enable convenient and safe usage in clinics, the DP-PEG modified nanoparticle solution was freeze-dried and sterilized to make a radiolabeling kit followed by careful evaluations of its in vitro and in vivo performance and applicability. The results showed that 99mTc labeled nanoprobes are effectively obtained with a labeling yield of over 95% in 30 minutes after simply injecting Na[99mTcO4] solution into the kit. In addition, the Fe3O4 nanoparticles sealed in the kit can well stand long-term storage even for 300 days without deteriorating the colloidal stability and radiolabeling yield. Upon intravenous injection of the as-prepared radiolabeled nanoprobes, high-resolution vascular images of mice were obtained by vascular SPECT imaging and magnetic resonance angiography, demonstrating the promising clinical translational value of our radiolabeling kit.