Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.

The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. Furthermore, complex I inhibition synergizes with radiotherapy (RT) to selectively suppress the growth of LKB1-deficient tumors by inducing ferroptosis in mouse models. Our data demonstrate a multifaceted role of complex I in regulating ferroptosis and propose a ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.

Fully forward mode training for optical neural networks.

Optical computing promises to improve the speed and energy efficiency of machine learning applications1-6. However, current approaches to efficiently train these models are limited by in silico emulation on digital computers. Here we develop a method called fully forward mode (FFM) learning, which implements the compute-intensive training process on the physical system. The majority of the machine learning operations are thus efficiently conducted in parallel on site, alleviating numerical modelling constraints. In free-space and integrated photonics, we experimentally demonstrate optical systems with state-of-the-art performances for a given network size. FFM learning shows training the deepest optical neural networks with millions of parameters achieves accuracy equivalent to the ideal model. It supports all-optical focusing through scattering media with a resolution of the diffraction limit; it can also image in parallel the objects hidden outside the direct line of sight at over a kilohertz frame rate and can conduct all-optical processing with light intensity as weak as subphoton per pixel (5.40 × 1018- operations-per-second-per-watt energy efficiency) at room temperature. Furthermore, we prove that FFM learning can automatically search non-Hermitian exceptional points without an analytical model. FFM learning not only facilitates orders-of-magnitude-faster learning processes, but can also advance applied and theoretical fields such as deep neural networks, ultrasensitive perception and topological photonics.

Structural insights into immune escape at killer T cell epitope by SARS-CoV-2 Spike Y453F variants.

CD8+ T cell immunity, mediated by human leukocyte antigen (HLA) and T cell receptor (TCR), plays a critical role in conferring immune memory and protection against viral pathogens. The emergence of SARS-CoV-2 variants poses a serious challenge to the efficacy of current vaccines. Whereas numerous SARS-CoV-2 mutations associated with immune escape from CD8+ T cells have been documented, the molecular effects of most mutations on epitope-specific TCR recognition remain largely unexplored. Here, we studied an HLA-A24-restricted NYN epitope (Spike448-456) that elicits broad CD8+ T cell responses in COVID-19 patients characterized by a common TCR repertoire. Four natural mutations, N450K, L452Q, L452R, and Y453F, arose within the NYN epitope and have been transmitted in certain viral lineages. Our findings indicate that these mutations have minimal impact on the epitope's presentation by cell surface HLA, yet they diminish the affinities of their respective peptide-HLA complexes (pHLAs) for NYN peptide-specific TCRs, particularly L452R and Y453F. Furthermore, we determined the crystal structure of HLA-A24 loaded with the Y453F peptide (NYNYLFRLF), and subsequently a ternary structure of the public TCRNYN-I complexed to the original NYN-HLA-A24 (NYNYLYRLF). Our structural analysis unveiled that despite competent presentation by HLA, the mutant Y453F peptide failed to establish a stable TCR-pHLA ternary complex due to reduced peptide: TCR contacts. This study supports the idea that cellular immunity restriction is an important driving force behind viral evolution.

METTL16 promotes osteosarcoma progression by downregulating VPS33B in an m6 A-dependent manner.

N6-methyladenosine (m6 A) is one of the main epitranscriptomic modifications that accelerates the progression of malignant tumors by modifying RNA. Methyltransferase-like 16 (METTL16) is a newly identified methyltransferase that has been found to play an important oncogenic role in a few malignancies; however, its function in osteosarcoma (OS) remains unclear. In this study, METTL16 was found to be upregulated in OS tissues, and associated with poor prognosis in OS patients. Functionally, METTL16 substantially promoted OS cell proliferation, migration, and invasion in vitro and OS growth in vivo. Mechanistically, vacuolar protein sorting protein 33b (VPS33B) was identified as the downstream target of METTL16, which induced m6 A modification of VPS33B and impaired the stability of the VPS33B transcript, thereby degrading VPS33B. In addition, VPS33B was found to be downregulated in OS tissues, VPS33B knockdown markedly attenuated shMETTL16-mediated inhibition on OS progression. Finally, METTL16/VPS33B might facilitate OS progression through PI3K/AKT pathway. In summary, this study revealed an important role for the METTL16-mediated m6 A modification in OS progression, implying it as a promising target for OS treatment.

In Situ, Fusion-Free, Multiplexed Detection of Small Extracellular Vesicle miRNAs for Cancer Diagnostics.

Tumor-derived small extracellular vesicle (sEV) microRNAs (miRNAs) are emerging biomarkers for cancer diagnostics. Conventional sEV miRNA detection methods necessitate the lysis of sEVs, rendering them laborious and time-consuming and potentially leading to damage or loss of miRNAs. Membrane fusion-based in situ detection of sEV miRNAs involves the preparation of probe-loaded vesicles (e.g., liposomes or cellular vesicles), which are typically sophisticated and require specialist equipment. Membrane perforation methods employ chemical treatments that can induce severe miRNA degradation or leaks. Inspired by previous studies that loaded nucleic acids into EVs or cells using hydrophobic tethers for therapeutic applications, herein, we repurposed this strategy by conjugating a hydrophobic tether onto molecular beacons to aid their transportation into sEVs, allowing for in situ detection of miRNAs in a fusion-free and multiplexing manner. This method enables simultaneous detection of multiple miRNA species within serum-derived sEVs for the diagnosis of prostate cancer, breast cancer, and gastric cancer with an accuracy of 83.3%, 81.8%, and 100%, respectively, in a cohort of 66 individuals, indicating that it holds a high application potential in clinical diagnostics.

Functionalized DNA Origami-Enabled Detection of Biomarkers.

Biomarkers are crucial physiological and pathological indicators in the host. Over the years, numerous detection methods have been developed for biomarkers, given their significant potential in various biological and biomedical applications. Among these, the detection system based on functionalized DNA origami has emerged as a promising approach due to its precise control over sensing modules, enabling sensitive, specific, and programmable biomarker detection. We summarize the advancements in biomarker detection using functionalized DNA origami, focusing on strategies for DNA origami functionalization, mechanisms of biomarker recognition, and applications in disease diagnosis and monitoring. These applications are organized into sections based on the type of biomarkers - nucleic acids, proteins, small molecules, and ions - and concludes with a discussion on the advantages and challenges associated with using functionalized DNA origami systems for biomarker detection.

Monolithic 3D integration of 2D materials-based electronics towards ultimate edge computing solutions.

Three-dimensional (3D) hetero-integration technology is poised to revolutionize the field of electronics by stacking functional layers vertically, thereby creating novel 3D circuity architectures with high integration density and unparalleled multifunctionality. However, the conventional 3D integration technique involves complex wafer processing and intricate interlayer wiring. Here we demonstrate monolithic 3D integration of two-dimensional, material-based artificial intelligence (AI)-processing hardware with ultimate integrability and multifunctionality. A total of six layers of transistor and memristor arrays were vertically integrated into a 3D nanosystem to perform AI tasks, by peeling and stacking of AI processing layers made from bottom-up synthesized two-dimensional materials. This fully monolithic-3D-integrated AI system substantially reduces processing time, voltage drops, latency and footprint due to its densely packed AI processing layers with dense interlayer connectivity. The successful demonstration of this monolithic-3D-integrated AI system will not only provide a material-level solution for hetero-integration of electronics, but also pave the way for unprecedented multifunctional computing hardware with ultimate parallelism.

CD34+ stromal cells/telocytes and their role in mouse lung development: Light microscopy, immunofluorescence, ultrastructural and scanning electron microscopy evidence.

Telocytes (TCs), a novel type of mesenchymal or interstitial cell with specific, very long and thin cellular prolongations, have been found in various mammalian organs and have potential biological functions. However, their existence during lung development is poorly understood. This study aimed to investigate the existence, morphological features, and role of CD34+ SCs/TCs in mouse lungs from foetal to postnatal life using primary cell culture, double immunofluorescence, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The immunofluorescence double staining profiles revealed positive expression of CD34 and PDGFR-α, Sca-1 or VEGFR-3, and the expression of these markers differed among the age groups during lung development. Intriguingly, in the E18.5 stage of development, along with the CD34+ SCs/TCs, haematopoietic stem cells and angiogenic factors were also significantly increased in number compared with those in the E14.5, E16.5, P0 and P7. Subsequently, TEM confirmed that CD34+ SCs/TCs consisted of a small cell body with long telopodes (Tps) that projected from the cytoplasm. Tps consisted of alternating thin and thick segments known as podomers and podoms. TCs contain abundant endoplasmic reticulum, mitochondria and secretory vesicles and establish close connections with neighbouring cells. Furthermore, SEM revealed characteristic features, including triangular, oval, spherical, or fusiform cell bodies with extensive cellular prolongations, depending on the number of Tps. Our findings provide evidence for the existence of CD34+ SCs/TCs, which contribute to vasculogenesis, the formation of the air‒blood barrier, tissue organization during lung development and homoeostasis.

Enhanced therapeutic potential of Flotillins-modified MenSCs by improve the survival, proliferation and migration.

Menstrual blood-derived endometrial stem cells (MenSCs) have attracted increasing interest due to their excellent safety, and lack of ethical dilemma as well as their ability to be periodically obtained in a noninvasive manner. However, although preclinical research as shown the therapeutic potential of MenSCs in several diseases, their poor cell survival and low engraftment at disease sites reduce their clinical efficacy. Flotillins (including Flot1 and Flot2) are implicated in various cellular processes, such as vesicular trafficking, signal transduction, cell proliferation, migration and apoptosis. In this study, we aimed to determine the effects of Flotillins on MenSCs survival, proliferation and migration. Our experimental results show that MenSCs were modified to overexpress Flot1 and/or Flot2 without altering their intrinsic characteristics. Flot1 and Flot2 co-overexpression promoted MenSC viability and proliferation capacity. Moreover, Flot1 or Flot2 overexpression significantly promoted the migration and inhibited the apoptosis of MenSCs compared with the negative control group, and these effects were stronger in the Flot1 and Flot2 gene co-overexpression group. However, these effects were significantly reversed after Flot1 and/or Flot2 knockdown. In conclusion, our results indicate that Flot1 and Flot2 overexpression in MenSCs improved their proliferation and migration and inhibited their apoptosis, and this might be an effective approach to improve the efficiency of cell-based therapies.

Anisotropic fluid flows in black phosphorus nanochannels.

With the development of advanced micro/nanoscale technologies, two-dimensional materials have emerged from laboratories and have been applied in practice. To investigate the mechanisms of solid-liquid interactions in potential applications, molecular dynamics simulations are employed to study the flow behavior of n-dodecane (C12) molecules confined in black phosphorus (BP) nanochannels. Under the same external conditions, a significant difference in the velocity profiles of fluid molecules is observed when flowing along the armchair and zigzag directions of the BP walls. The average velocity of C12 molecules flowing along the zigzag direction is 9-fold higher than that along the armchair direction. The friction factor at the interface between C12 molecules and BP nanochannels and the orientations of C12 molecules near the BP walls are analyzed to explain the differences in velocity profiles under various flow directions, external driving forces, and nanochannel widths. The result shows that most C12 molecules are oriented parallel to the flow direction along the zigzag direction, leading to a relatively smaller friction factor hence a higher average velocity. In contrast, along the armchair direction, most C12 molecules are oriented perpendicular to the flow direction, leading to a relatively larger friction factor and thus a lower average velocity. This work provides important insights into understanding the anisotropic liquid flows in nanochannels.

Tradeoffs between pH, dissolved organic carbon, and mineral ions regulate cadmium uptake by Solanum hyperaccumulators in calcareous soil.

Soil solution pH and dissolved organic carbon (DOC) influence cadmium (Cd) uptake by hyperaccumulators but their tradeoff in calcareous soils is unclear. This study investigated the mechanisms of Solanum nigrum L. and Solanum alatum Moench in calcareous soil using a combination of concentration gradient experiments (0.6-100 mg Cd kg-1) and soil solution composition analysis. The results showed that the soil solution pH of S. nigrum remained stable despite Cd stress. On average, the soil solution pH of S. alatum was 0.23 units higher than that of S. nigrum, although pH decreased significantly under high Cd stress. In addition, the concentrations of potassium (K) and calcium (Ca) in the soil solution of S. nigrum increased and decreased under low and high levels of Cd stress, respectively. In S. alatum, the K and Ca concentrations in the soil solution generally increased with increasing Cd stress levels. Moreover, the level of DOC in the soil solution of both plants was higher under Cd stress compared to the control, and a gradually increasing trend with Cd stress level was observed in S. alatum. Consequently, the bioconcentration factors of the roots (2.62-19.35) and shoots (1.20-9.59) of both plants were >1, while the translocation factors were <1, showing an obstacle of Solanum hyperaccumulators in transferring Cd into their aboveground parts. Redundancy analysis revealed that the Cd concentration in S. nigrum roots was significantly negatively correlated with the soil solutions of K and Ca. In contrast, Cd concentrations in S. alatum roots and shoots were significantly positively correlated with soil solution DOC, K, and Ca but negatively correlated with pH. Our results suggest that calcareous soil neutralizes the acidity of released protons but does not affect cation exchange, inhibiting DOC in assisting the translocation of Cd within plants.

Integrated simulation-surrogate-optimization modeling framework for multiple tradeoffs among socioeconomic and ecological targets in reservoir operations.

Integrated reservoir water quantity and quality management is significant for water supply security and river ecosystem health. However, the spatiotemporal heterogeneity of water quality and the nonuniform response of multiple indicators to operation changes make it difficult to determine optimal operation schedules. This study proposes a coupled simulation-surrogate-optimization modeling approach for compromising multiple water quantity and quality targets in reservoir operations. The Environmental Fluid Dynamics Code (EFDC) was used to simulate spatiotemporal reservoir water quality dynamics. Subsequently, an ecological damage assessment method was established, accounting for the spatiotemporal heterogeneity of multiple water quality indicators and the nonlinear relationship between the water quality deterioration and ecological damage. To quickly simulate the ecological damage, a surrogate model was developed using the nonlinear autoregressive network with exogenous inputs (NARX). Finally, the surrogate model was integrated into a reservoir operation optimization model for compromising socioeconomic and ecological targets. By applying the methods to China's Danjiangkou Reservoir as a case, it was shown that more even nutrient distribution in the reservoir increased water eutrophication area while reducing concentration peak values, which helped decrease the ecological damage. Operation changes could lead to opposite effects on in-reservoir and downstream ecological targets, increasing operation optimization complexity. Both ecological and socioeconomic benefits significantly increased (by 9.4%-16.4%) during dry years under the optimized operation scheme, implying that synergies were obtained. This study offers implications and a management tool for reservoir operations to address the multiple tradeoffs among socioeconomic and ecological benefits.

Circular RNA ARHGAP5 inhibits cisplatin resistance in cervical squamous cell carcinoma by interacting with AUF1.

Cervical squamous cell carcinoma (CSCC) is one of the leading causes of cancer death in women worldwide. Patients with advanced cervical carcinoma always have a poor prognosis once resistant to cisplatin due to the lack of effective treatment. It is urgent to investigate the molecular mechanisms of cisplatin resistance. Circular RNAs (circRNAs) are known to exert their regulatory functions in a series of malignancies. However, their effects on CSCC remain to be elucidated. Here, we found that cytoplasmic circARHGAP5, derived from second and third exons of the ARHGAP5 gene, was downregulated in cisplatin-resistant tissues compared with normal cervix tissues and untreated cervical cancer tissues. In addition, experiments from overexpression/knockdown cell lines revealed that circARHGAP5 could inhibit cisplatin-mediated cell apoptosis in CSCC cells both in vitro and in vivo. Mechanistically, circARHGAP5 interacted with AU-rich element RNA-binding protein (AUF1) directly. Overexpression of AUF1 could also inhibit cell apoptosis mediated by cisplatin. Furthermore, we detected the potential targets of AUF1 related to the apoptotic pathway and found that bcl-2-like protein 11 (BIM) was not only negatively regulated by AUF1 but positively regulated by circARHGAP5, which indicated that BIM mRNA might be degraded by AUF1 and thereby inhibited tumor cell apoptosis. Collectively, our data indicated that circARHGAP5 directly bound to AUF1 and prevented AUF1 from interacting with BIM mRNA, thereby playing a pivotal role in cisplatin resistance in CSCC. Our study provides insights into overcoming cancer resistance to cisplatin treatment.

170†GHz quasi-optical sub-harmonic mixer with a back-to-back lenses packaging based on HDI.

The paper presents a 170 GHz quasi-optical sub-harmonic mixer with a 3D-printed back-to-back lenses packaging. The quasi-optical mixer is comprised by a pair of antiparallel GaAs Schottky diodes, a patch antenna for receiving local oscillator (LO) pump signal, a symmetric-slit patch antenna for receiving radio frequency (RF) signal, dual 3D-printed lenses and a matching network. The quasi-optical mixer with a pair of antiparallel GaAs Schottky diodes is designed on a multilayer build-up printed circuit board (PCB) utilizing commercially low-cost and high-density interconnect (HDI) technology. The LO and RF antennas are placed on the front and back of the multilayer build-up substrate, respectively, thus significantly simplifying the quasi-optical design. Furthermore, dual 3D-printed lenses placed back-to-back are proposed for LO and RF antennas radiation gain enhancement and mechanical robustness. Additionally, the buried planar reflectors in the substrate maintain effective radiation isolation between the antennas. For facilitating coupling efficiency of signal power into the Schottky diodes and signal isolation between the LO pump signal and RF signal, a compact matching network with low-loss quasi-coaxial via transition structure is integrated in the mixer circuit. The measured single-sideband conversion loss is from 11.3 to 15.4 dB in an operation range of 160 to 180 GHz. The measured radiation patterns agree well with the simulated results.

Electrochemical detection of the oxidative damage of a potential pyrimido[5,4-g]pteridine-derived antitumor agent toward DNA.

In this work, we design and synthesize 2,2'-(7,9-dimethyl-2,4,6,8-tetraoxo-6,7,8,9-tetrahydropyrimido[5,4-g]pteridine-1,3(2H,4H)-diyl)bis(N,N-bis(2-chloroethyl)acetamide) (PT-MCA) as a novel DNA intercalator and potential antitumor agent. Electrochemical analysis reveals the redox process of PT-MCA on the electrode surface. The bioelectrochemical sensors are obtained by modifying the surface of GCE with calf thymus DNA (ctDNA), poly (dG), poly (dA), and G-quadruplex, respectively. The DNA oxidative damage induced by PT-MCA is investigated by comparing the peak intensity change of dGuo and dAdo and monitoring the peaks of the oxidation products of guanine and/or adenine (8-oxoGua and/or 2,8-oxoAde). UV-vis absorption and fluorescence spectra and gel electrophoresis are further employed to understand the intercalation of PT-MCA into DNA base pairs. Moreover, PT-MCA is proved to exhibit stronger anti-proliferation activity than mitoxantrone against both 4T1 and B16-F10 cancer cells. At last, the oxidative damage of PT-MCA toward ctDNA is not interfered by the coexistence of ions and also can be detected in real serums.

Image restoration algorithm for terahertz FMCW radar imaging.

The terahertz frequency modulation continuous-wave (THz FMCW) imaging technology has been widely used in non-destructive testing applications. However, THz FMCW real-aperture radar usually has a small depth of field and poor lateral resolution, thus restricting the high-precision imaging application. This paper proposes a 150-220 GHz FMCW Bessel beam imaging system, effectively doubling the depth of field and unifying the lateral resolution compared to the Gaussian beam quasi-optical system. Moreover, a THz image restoration algorithm based on local gradients and convolution kernel priors is proposed to eliminate further the convolution effect introduced by the Bessel beam, thereby enhancing the lateral resolution to 2 mm. It effectively improves the image under-restoration or over-restoration caused by the mismatch between the ideal and actual point spread function. The imaging results of the resolution test target and semiconductor device verify the advantages of the proposed system and algorithm.

Effect of folic acid supplementation in the association between short sleep duration and gestational diabetes mellitus.

PURPOSE: To examine whether or not folic acid (FA) supplementation may modify the relationships between duration or quality of sleep and gestational diabetes mellitus (GDM) risk. METHODS: In a case-control study of patients with GDM and controls, mothers were interviewed face-to-face at enrollment. The Pittsburgh Sleep Quality Scale was used to assess duration and quality of sleep during early pregnancy, and information on FA supplementation and covariates was obtained using a semiquantitative questionnaire. RESULTS: Among 396 patients with GDM and 904 controls, GDM risk increased by 328% and 148% among women with short (< 7 h) and long (≥ 9 h) sleep durations, respectively, compared to those averaging 7-8.9 h sleep. Mothers with poor sleep quality increased their GDM risk by an average of 75% (all p < 0.05). The effect of short sleep duration on GDM risk was much weaker among women with adequate FA supplementation (taking supplements containing ≥ 0.4 mg FA daily for each day of the first three months of pregnancy) than that among women with inadequate FA supplementation, with a p-value for interaction = 0.003. There were no significant effects of FA on links among long duration and poor quality of sleep with GDM risk. CONCLUSIONS: Sleep duration and quality in early gestation were related to increased GDM risks. FA supplementation may reduce GDM risk associated with short sleep duration.

A new approach to COVID-19 data mining: A deep spatial-temporal prediction model based on tree structure for traffic revitalization index.

The outbreak of the COVID-19 epidemic has had a huge impact on a global scale and its impact has covered almost all human industries. The Chinese government enacted a series of policies to restrict the transportation industry in order to slow the spread of the COVID-19 virus in early 2020. With the gradual control of the COVID-19 epidemic and the reduction of confirmed cases, the Chinese transportation industry has gradually recovered. The traffic revitalization index is the main indicator for evaluating the degree of recovery of the urban transportation industry after being affected by the COVID-19 epidemic. The prediction research of traffic revitalization index can help the relevant government departments to know the state of urban traffic from the macro level and formulate relevant policies. Therefore, this study proposes a deep spatial-temporal prediction model based on tree structure for the traffic revitalization index. The model mainly includes spatial convolution module, temporal convolution module and matrix data fusion module. The spatial convolution module builds a tree convolution process based on the tree structure that can contain directional features and hierarchical features of urban nodes. The temporal convolution module constructs a deep network for capturing temporal dependent features of the data in the multi-layer residual structure. The matrix data fusion module can perform multi-scale fusion of COVID-19 epidemic data and traffic revitalization index data to further improve the prediction effect of the model. In this study, experimental comparisons between our model and multiple baseline models are conducted on real datasets. The experimental results show that our model has an average improvement of 21%, 18%, and 23% in MAE, RMSE and MAPE indicators, respectively.

Ultra-wideband signal generation and fusion algorithm for high-resolution terahertz FMCW radar imaging.

The terahertz frequency modulated continuous wave (THz FMCW) imaging has proved to be a novel nondestructive testing (NDT) technology for non-metal materials, and the large bandwidth is usually required to meet high range resolution demands in many applications such as multilayer sample under test (SUT). However, broadband THz hardware is difficult to design. In this paper, an ultra-wideband THz FMCW generation method is proposed, which provides frequency modulation bandwidths of up to 386 GHz by time-division multiplexing. Furthermore, an ultra-wideband signal fusion algorithm (USFA) is also proposed and significantly improves the range resolution to 0.46 mm in air. Results from the artificially constructed multilayer structure demonstrate the superiority and effectiveness of our method quantitatively.

MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles in a mouse model.

Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.