Absence of near-ambient superconductivity in LuH2±xNy.

A recent study demonstrated near-ambient superconductivity in nitrogen-doped lutetium hydride1. This stimulated a worldwide interest in exploring room-temperature superconductivity at low pressures. Here, by using a high-pressure and high-temperature synthesis technique, we have obtained nitrogen-doped lutetium hydride (LuH2±xNy), which has a dark-blue colour and a structure with the space group [Formula: see text] as evidenced by X-ray diffraction. This structure is the same as that reported in ref. 1, with a slight difference in lattice constant. Raman spectroscopy of our samples also showed patterns similar to those observed in ref. 1. Energy-dispersive X-ray spectroscopy confirmed the presence of nitrogen in the samples. We observed a metallic behaviour from 350 K to 2 K at ambient pressure. On applying pressures from 2.1 GPa to 41 GPa, we observed a gradual colour change from dark blue to violet to pink-red. By measuring the resistance at pressures ranging from 0.4 GPa to 40.1 GPa, we observed a progressively improved metallic behaviour; however, superconductivity was not observed above 2 K. Temperature dependence of magnetization at high pressure shows a very weak positive signal between 100 K and 320 K, and the magnetization increases with an increase in magnetic field at 100 K. All of these are not expected for superconductivity above 100 K. Thus, we conclude the absence of near-ambient superconductivity in this nitrogen-doped lutetium hydride at pressures below 40.1 GPa.

Deep Learning Radiomics Nomogram Based on Enhanced CT to Predict the Response of Metastatic Lymph Nodes to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

BACKGROUND: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). METHODS: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively. RESULTS: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis. CONCLUSIONS: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment.

Pixel-reassigned line-scanning microscopy for fast volumetric super-resolution imaging.

Super-resolution microscopy has revolutionized the field of biophotonics by revealing detailed 3D biological structures. Nonetheless, the technique is still largely limited by the low throughput and hampered by increased background signals for dense or thick biological specimens. In this paper, we present a pixel-reassigned continuous line-scanning microscope for large-scale high-speed 3D super-resolution imaging, which achieves an imaging resolution of 0.41 µm in the lateral direction, i.e., a 2× resolution enhancement from the raw images. Specifically, the recorded line images are first reassigned to the line-excitation center at each scanning position to enhance the resolution. Next, a modified HiLo algorithm is applied to reduce the background signals. Parametric models have been developed to simulate the imaging results of randomly distributed fluorescent beads. Imaging experiments were designed and performed to verify the predicted performance on various biological samples, which demonstrated an imaging speed of 3400 pixels/ms on millimeter-scale specimens. These results confirm the pixel-reassigned line-scanning microscopy is a facile and powerful method to realize large-area super-resolution imaging on thick or dense biological samples.

Compressive sensing-based multi-focus line-scanning two-photon microscopy for fast 3D imaging.

Fast 3D volume imaging methods have been playing increasingly important roles in biological studies. In this article, we present the design and characterization of a multi-focus line-scanning two-photon microscope. Specifically, a digital micromirror device (DMD) is employed to generate a randomly distributed focus array on a plane (i.e., x-z) via binary holography. Next, a galvanometric mirror scans the focus array in a direction normal to the plane (i.e., y-axis) over the imaging volume. For sparse samples, e.g., neural networks in a brain, 1-3 foci are used together with compressive sensing algorithm to achieve a volume imaging rate of 15.5 volumes/sec over 77 × 120 × 40 µm3. High-resolution optical cross-sectional images on selected planes and regions can be generated by sequentially scanning the laser focus generated on the x-z plane with good imaging speeds (e.g., 107 frames/sec over 80 × 120 × 40 µm3). In the experiments, microbeads, pollens, and mouse brain slices have been imaged to characterize the point spread function and volume image rate and quality at different sampling ratios. The results show that the multi-focus line-scanning microscope presents a fast and versatile 3D imaging platform for deep tissue imaging and dynamic live animal studies.

Trapping Hydrogen Molecules between Perfect Graphene.

There is a lack of deep understanding of hydrogen intercalation into graphite due to many challenges faced during characterization of the systems. Therefore, a suitable route to trap isolated hydrogen molecules (H2) between the perfect graphite lattices needs to be found. Here we realize the formation of hydrogen bubbles in graphite with controllable density, size, and layer number. We find that the molecular H2 cannot be diffused between nor escape from the defect-free graphene lattices, and it remains stable in the pressurized bubbles up to 400 °C. The internal pressure of H2 inside the bubbles is strongly temperature dependent, and it decreases as the temperature rises. The proton permeation rate can be estimated at a specific plasma power. The producing method of H2 bubbles offers a useful way for storing hydrogen in layered materials, and these materials provide a prospective research platform for studying nontrivial quantum effects in confined H2.

The zinc finger and BTB domain containing protein ZBTB20 regulates plasma triglyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes.

BACKGROUND AND AIMS: Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride-rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here, we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism. APPROACH AND RESULTS: Hepatocyte-specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in postheparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, whereas plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20-deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high-fat diet-induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel-shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver-specific under physiological conditions. CONCLUSIONS: Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism and could be a therapeutic target for hypertriglyceridemia.

Comparison of short- and long-term outcomes between laparoscopic and open gastrectomy for locally advanced gastric cancer following neoadjuvant chemotherapy: a propensity score matching analysis.

BACKGROUND: This study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) in patients with locally advanced gastric cancer (LAGC) who received neoadjuvant chemotherapy (NACT). METHODS: We retrospectively analyzed patients who underwent gastrectomy for LAGC (cT2-4aN+M0) after NACT from January 2015 to December 2019. The patients were divided into a LG group and an open gastrectomy (OG) group. The short- and long-term outcomes in both groups were examined following propensity score matching. RESULTS: We retrospectively reviewed 288 patients with LAGC who underwent gastrectomy following NACT. Of these 288 patients, 218 were enrolled; after 1:1 propensity score matching, each group comprised 81 patients. The LG group had significantly lower estimated blood loss than the OG group [80 (50-110) vs. 280 (210-320) mL, P < 0.001) but a longer operation time [205 (186.5-222.5) vs. 182 (170-190) min, P < 0.001], a lower postoperative complication rate (24.7% vs. 42.0%, P = 0.002), and a shorter postoperative hospitalization period [8 (7-10) vs. 10 (8-11.5) days, P = 0.001]. Subgroup analysis revealed that patients who underwent laparoscopic distal gastrectomy had a lower rate of postoperative complications than patients in the OG group (18.8% vs. 38.6%, P = 0.034); however, such a pattern was not seen in patients who underwent total gastrectomy (32.3% vs. 45.9%, P = 0.251). The 3-year matched cohort analysis showed no significant difference in overall survival or recurrence-free survival (log-rank P = 0.816 and P = 0.726, respectively) (71.3% and 65.0% in OG vs. 69.1% and 61.7% in LG, respectively). CONCLUSION: In the short term, LG following NACT is safer and more effective than OG. However, the long-term results are comparable.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Response of aquatic plant decomposition to invasive algal organic matter mediated by the co-metabolism effect in eutrophic lakes.

The decomposition of aquatic plant residues changes by the invasive algal organic matter in eutrophic lakes, however, the driving mechanisms of these biogeochemistry processes are still far from clear. In this study, a series of microcosms was constructed to simulate the mixed decomposition processes of aquatic plant residues with invasive algae as long as 205 days. Three aquatic plants (Potamogeton malaianus, Nymphoides peltatum, and Phragmites australis) and algae were collected from a typical eutrophic lake. The addition of algae promoted the decomposition of three plant residues based on the mass loss, and the positive co-metabolism effect was produced. The co-metabolism intensity was 8%-25% on the water surface and 19%-45% on the water-sediment interface, respectively. In addition, the response of three aquatic plant residues to the algal organic matter was different with their co-metabolism intensities in the order of P. australis > P. malaianus > N. peltatum on both the water surface and water-sediment interface. The phylum number of bacteria attached to the surface of plant residues increased from 27 to 52. The abundance of Bacteroidetes, which had the function of decomposing refractory organic matter, increased most significantly at the final incubation. At present, shallow lakes are under the double pressure of eutrophication and global warming, and the intensity and duration of algal blooms are increasing. Therefore, the co-metabolism effect of the residue decomposition process described here may change the carbon cycle strength and increase the greenhouse gas emissions of lakes and need to be taken into account in future lake management.

Single-shot optical sectioning microscopy based on structured illumination.

In this Letter, we present a single-shot 3D-resolved structured illumination microscopy (SIM) based on a digital micromirror device (DMD), a galvanometric mirror, and the HiLo algorithm. During imaging, the DMD rapidly generates sinusoidal and plane illuminations in the focal region. By synchronizing the DMD with a galvanometric scanner and exploiting the unique data readout process of the camera, the emissions from the specimen under two different illuminations, i.e., structured and uniform illumination, are projected to different regions on a camera, achieving high-resolution single-exposure optical sectioning at the camera's limiting speed, i.e., 200 Hz, without sacrificing the resolution. A model has been developed to guide the design and optimization of the optical system. Imaging experiments on pollen and mouse kidney samples have been performed to verify the predicted performance. The results show that the single-shot SIM with the HiLo algorithm achieves comparable resolution to the standard two-shot HiLo method with a twofold speed enhancement, which may find important applications in biophotonics, e.g., visualizing high-speed biological events in vivo.

Deep learning improves the ability of sgRNA off-target propensity prediction.

BACKGROUND: CRISPR/Cas9 system, as the third-generation genome editing technology, has been widely applied in target gene repair and gene expression regulation. Selection of appropriate sgRNA can improve the on-target knockout efficacy of CRISPR/Cas9 system with high sensitivity and specificity. However, when CRISPR/Cas9 system is operating, unexpected cleavage may occur at some sites, known as off-target. Presently, a number of prediction methods have been developed to predict the off-target propensity of sgRNA at specific DNA fragments. Most of them use artificial feature extraction operations and machine learning techniques to obtain off-target scores. With the rapid expansion of off-target data and the rapid development of deep learning theory, the existing prediction methods can no longer satisfy the prediction accuracy at the clinical level. RESULTS: Here, we propose a prediction method named CnnCrispr to predict the off-target propensity of sgRNA at specific DNA fragments. CnnCrispr automatically trains the sequence features of sgRNA-DNA pairs with GloVe model, and embeds the trained word vector matrix into the deep learning model including biLSTM and CNN with five hidden layers. We conducted performance verification on the data set provided by DeepCrispr, and found that the auROC and auPRC in the "leave-one-sgRNA-out" cross validation could reach 0.957 and 0.429 respectively (the Pearson value and spearman value could reach 0.495 and 0.151 respectively under the same settings). CONCLUSION: Our results show that CnnCrispr has better classification and regression performance than the existing states-of-art models. The code for CnnCrispr can be freely downloaded from https://github.com/LQYoLH/CnnCrispr.

A molecular toolbox for interrogation of membrane contact sites.

Membrane contact sites (MCSs) are specialized subcellular compartments formed by closely apposed membranes from two organelles. The intermembrane gap is separated by a distance ranging from 10 to 35 nm. MCSs are typically maintained through dynamic protein-protein and protein-lipid interactions. These intermembrane contact sites constitute important intracellular signalling hotspots to mediate a plethora of cellular processes, including calcium homeostasis, lipid metabolism, membrane biogenesis and organelle remodelling. In recent years, a series of genetically encoded probes and chemogenetic or optogenetic actuators have been invented to aid the visualization and interrogation of MCSs in both fixed and living cells. These molecular tools have greatly accelerated the pace of mechanistic dissection of membrane contact sites at the molecular level. In this review, we present an overview on the latest progress in this endeavour, and provide a general guide to the selection of methods and molecular tools for probing interorganellar membrane contact sites.

Circular RNA hsa_circ_0008285 inhibits colorectal cancer cell proliferation and migration via the miR-382-5p/PTEN axis.

Abundant evidence has showed that circular RNA (circRNA) plays an important role in cancer. Nonetheless, little is known about the roles and mechanisms of specific circRNAs in different cancer types. Hsa_circ_0008285 (circ_0008285), derived from the coding gene chromodomain y-like protein (CDYL), is upregulated in hepatocellular carcinoma and mantle cell lymphoma. However, we previously found, by analyzing two independent high-throughput sequencing datasets, that it was reduced in colon cancer. In this study, we explored the function and mechanism of circ_0008285 in the progression of colorectal cancer (CRC). First, the downregulated expression of circ_0008285 in CRC tissues and cell lines was confirmed using RT-qPCR analysis. In addition, the expression level of circ_0008285 was inversely correlated with tumor size, lymphatic metastasis, and tumor-node-metastasis (TNM) stage through clinicopathological parameter analysis. Functionally, knockdown of circ_0008285 promoted CRC cell proliferation and migration in vitro. Mechanistically, by using RNA-sequencing, bioinformatics analysis, dual-luciferase reporter assay, and western blotting, we determined that circ_0008285 suppressed the PI3K/AKT pathway via the miR-382-5p/PTEN axis. In conclusion, our data demonstrate a tumor suppressor role for circ_0008285 in CRC and suggest circ_0008285 as a potential target for CRC treatment.

Docetaxel-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles in human breast cancer and human cervical cancer therapy.

Taxane-based chemotherapy-loaded drug delivery systems have great potential for cancer treatment. The docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS) nanoparticles and the docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate) (PAM-PBLG) nanoparticles were designed using a modified nanoprecipitation method. The particle size, encapsulation efficiency (EE), and in vitro release characteristics of the nanoparticles were tested. The effects of the two nanoparticles on the cellular uptake and cell viability on human cervical cancer cell line Hela and the human breast cancer cell line MCF-7 were compared. Furthermore, their antitumor efficiency was evaluated through in vivo tumour growth experiment in comparison with free DTX. PAM-PBLG-b-TPGS nanoparticles displayed high EE, smaller diameter, and a nice releasing profile. Besides, based on the high EE and 'self-controlled' drug release of the DTX-loaded PAM-PBLG-b-TPGS nanoparticles, they exhibited stronger cytotoxicity (lower survival rate) and higher uptake rate than DTX-loaded PAM-PBLG nanoparticles in Hela cells and MCF-7 cells. Furthermore, compared with DTX-loaded PAM-PBLG nanoparticles and free DTX, DTX-loaded PAM-PBLG-b-TPGS nanoparticles produced a potent anti-tumour effect. Thus, the DTX-loaded PAM-PBLG-b-TPGS nanoparticles provide a novel attractive nanocarrier for the DTX delivery of chemotherapy to human breast cancer cells and human cervical cancer cells.

An Intelligent Nanoscale Insulin Delivery System.

Insulin injection relies on strict blood glucose monitoring. However, existing techniques and algorithms for blood glucose monitoring cannot be completed in a timely way. In this study, we have developed a new intelligent glucose-sensitive insulin delivery system to stabilize blood glucose levels in the body. This system does not require real-time detection of blood glucose. First, we successfully synthesized a nanoscale material called PAM-PAspPBA-b-PEG by using chemical methods. We then conducted TEM, DLS, and ¹H-NMR analyses to characterize the physicochemical properties, such as size, molecular composition, and configuration of the nanomaterial. We verified the glucose responsibility of the insulin loading nanoscale material in vitro and evaluated its safety and effect on mice in vivo. Results showed that insulin-loaded PAM-PAspPBA-b-PEG is glucose-sensitive, safer and more effective than regular insulin injection. This study provides a basis for future development of smart insulin delivery systems.

TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance.

A nanocarrier system of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.

BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c APCs stimulatory capacity. This role is impaired in ATB patients manifested by low expression of HLA-DR and low production of IL-6. This previous unappreciated role for BTLA may have implications in the prevention and treatment of patients with ATB.

Regulation of plasma lipid homeostasis by hepatic lipoprotein lipase in adult mice.

LPL is a pivotal rate-limiting enzyme to catalyze the hydrolysis of TG in circulation, and plays a critical role in regulating lipid metabolism. However, little attention has been paid to LPL in the adult liver due to its relatively low expression. Here we show that endogenous hepatic LPL plays an important physiological role in plasma lipid homeostasis in adult mice. We generated a mouse model with the Lpl gene specifically ablated in hepatocytes with the Cre/LoxP approach, and found that specific deletion of hepatic Lpl resulted in a significant decrease in plasma LPL contents and activity. As a result, the postprandial TG clearance was markedly impaired, and plasma TG and cholesterol levels were significantly elevated. However, deficiency of hepatic Lpl did not change the liver TG and cholesterol contents or glucose homeostasis. Taken together, our study reveals that hepatic LPL is involved in the regulation of plasma LPL activity and lipid homeostasis.

Iron Oxide Nanoparticles Induce Autophagosome Accumulation through Multiple Mechanisms: Lysosome Impairment, Mitochondrial Damage, and ER Stress.

Magnetite (iron oxide, Fe3O4) nanoparticles have been widely used for drug delivery and magnetic resonance imaging (MRI). Previous studies have shown that many metal-based nanoparticles including Fe3O4 nanoparticles can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. To investigate the biosafety of Fe3O4 and PLGA-coated Fe3O4 nanoparticles, some experiments related to the mechanism of autophagy induction by these nanoparticles have been investigated. In this study, the results showed that Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticles could be taken up by the cells through cellular endocytosis. Fe3O4 nanoparticles extensively impair lysosomes and lead to the accumulation of LC3-positive autophagosomes, while PLGA-coated Fe3O4 nanoparticles reduce this destructive effect on lysosomes. Moreover, Fe3O4 nanoparticles could also cause mitochondrial damage and ER and Golgi body stresses, which induce autophagy, while PLGA-coated Fe3O4 nanoparticles reduce the destructive effect on these organelles. Thus, the Fe3O4 nanoparticle-induced autophagosome accumulation may be caused by multiple mechanisms. The autophagosome accumulation induced by Fe3O4 was also investigated. The Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticle-treated mice were sacrificed to evaluate the toxicity of these nanoparticles on the mice. The data showed that Fe3O4 nanoparticle treated mice would lead to the extensive accumulation of autophagosomes in the kidney and spleen in comparison to the PLGA-coated Fe3O4 and PLGA nanoparticles. Our data clarifies the mechanism by which Fe3O4 induces autophagosome accumulation and the mechanism of its toxicity on cell organelles and mice organs. These findings may have an important impact on the clinical application of Fe3O4 based nanoparticles.