[Clinical Analysis of Epstein-Barr Virus Infection after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To analyze the risk factors of Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its impact on survival. METHODS: The clinical data of 347 patients who underwent their first allo-HSCT in our hospital from January 2014 to June 2021 were retrospectively analyzed. Patients were divided into EBV (n =114) and Non-EBV (n =233) groups according to whether they were infected with EBV. The incidence of EBV infection after allo-HSCT was calculated, and the risk factors of EBV infection were analyzed. RESULTS: A total of 114(32.8%) patients presented EBV infection (all peripheral blood EBV-DNA were positive). EBV infection occurred in 88 patients within 100 days after transplantation, which accounted for 77.2% of all patients with EBV infection. 5 cases (1.44%) were confirmed as post-transplant lymphoproliferative disorder (PTLD). The median onset time of patients was 57(7-486) days after transplantation. Multivariate analysis showed that the use of ATG/ATG-F, occurrence of CMV viremia, and grade III-IV aGVHD were risk factors for EBV infection. Furthermore, compared to BUCY, the use of intensified preconditioning regimens containing FA/CA was significantly increased the risk of EBV infection. CONCLUSION: EBV infection is a common complication after allo-HSCT. Intensified preconditioning regimens, use of ATG/ATG-F, CMV viremia and grade III to IV aGVHD increase the risk of EBV infection after allo-HSCT.

An insect lac blanket-mimetic and degradable shellac hydrogel/chitosan packaging film with controllable gas permeation for fresh-cut vegetables preservation.

Fresh-cut products are extremely perishable due to the processing operations, and the atmosphere environment, especially CO2, O2 and H2O, could profoundly affect their shelf life. Herein, an insect "lac blanket"-mimetic and facile strategy was proposed for fresh-cut vegetables preservation, employing porous shellac hydrogel microparticles as gas "switches" in chitosan film to regulate CO2, O2 and H2O vapor permeability. Thus, the shellac hydrogel/chitosan hybrid film presented the controllable and wide range of gas permeability, compared with the chitosan film. The shellac-COOH nanoscale vesicles aggregated to form shellac hydrogel network via hydrophobic binding. The shellac hydrogel microparticles played a certain lubricating effect on the hybrid film casting solution. The hydrogen bond network between shellac hydrogel and chitosan contributed to the excellent mechanical properties of the hybrid film. The hybrid film also exhibited remarkable water-resistant, antifogging properties, optical transparency and degradability. The hybrid packaging films prepared through this strategy could adjust the internal gas (CO2, O2, H2O and ethylene) contents within the packages, and further exhibited admirable preservation performance on three fresh-cut vegetables with different respiratory metabolisms. This gas permeation-controlled strategy has great potential in fresh food preservation and various other applications that need a modified atmosphere.

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors.

Worldwide, gastrointestinal (GI) cancer is recognized as one of the leading malignancies diagnosed in both genders, with mortality largely attributed to metastatic dissemination. It has been identified that in GI cancer, a variety of signaling pathways and key molecules are modified, leading to the emergence of an immunotolerance phenotype. Such modifications are pivotal in the malignancy's evasion of immune detection. Thus, a thorough analysis of the pathways and molecules contributing to GI cancer's immunotolerance is vital for advancing our comprehension and propelling the creation of efficacious pharmacological treatments. In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigen-related cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12.

The dynamics of B-cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real-world study.

BACKGROUND: The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. METHODS: In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. RESULTS: We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037). CONCLUSION: Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.

Highly efficient removal of tannic acid from wastewater using biomimetic porous materials.

To effectively remove tannic acid (TA) from wastewater, using green and natural materials has attracted increasing attention. Inspired by Galla Chinensis (GC) with high content of TA, this study synthesized a biomimetic porous adsorbent to mimic the GC structure using dialdehyde tapioca starch (DTS) and gelatin (GL). The TA adsorption performance and mechanism of synthetic porous material were investigated. Results revealed that the porous material exhibited a maximum TA adsorption capacity of 1072.01 mg/g, along with a high removal rate of 95.16% under the conditions of a DTS-GL mass ratio of 1:1, DTS aldehyde content of 48.16%, a solid content of 5%, and a pH of 2 at 25 °C. The adsorption of TA by DTS was not affected by water-soluble cationic and anion. The adsorption kinetics of TA on the porous material followed the pseudo-second-order model, and this Langmuir adsorption model (R2 = 0.9954) which were well described the adsorption of TA by the material, indicating that the adsorption primarily occurred in a monolayer. FTIR, XRD, DSC, TG, XPS, and SEM-EDS were employed to characterize the structure characteristics of the porous material. The cross-linking between DTS and GL by Schiff base reaction imparted a chemical structure could absorb TA by hydrogen bonding. The TA desorption rates of in 30% acetone and 40% ethanol solutions were 88.76% and 91.03%, respectively. The porous material prepared by the GC-inspired approach holds promise as an ideal choice for loading polyphenolic compounds and provides a new perspective for the design and application of bioinspired engineering materials.

Multimodal evaluation of the effects of low-intensity ultrasound on cerebral blood flow after traumatic brain injury in mice.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and destruction of the cerebrovascular system is a major factor in the cascade of secondary injuries caused by TBI. Laser speckle imaging (LSCI)has high sensitivity in detecting cerebral blood flow. LSCI can visually show that transcranial focused ultrasound stimulation (tFUS) treatment stimulates angiogenesis and increases blood flow. To study the effect of tFUS on promoting angiogenesis in Controlled Cortical impact (CCI) model. tFUS was administered daily for 10 min and for 14 consecutive days after TBI. Cerebral blood flow was measured by LSCI at 1, 3, 7 and 14 days after trauma. Functional outcomes were assessed using LSCI and neurological severity score (NSS). After the last test, Nissl staining and vascular endothelial growth factor (VEGF) were used to assess neuropathology. TBI can cause the destruction of cerebrovascular system. Blood flow was significantly increased in TBI treated with tFUS. LSCI, behavioral and histological findings suggest that tFUS treatment can promote angiogenesis after TBI.

LIPUS-induced neurogenesis:A potential therapeutic strategy for cognitive dysfunction in traumatic brain injury.

Traumatic brain injury (TBI) precipitates cellular membrane degeneration, phospholipid degradation, neuronal demise, impaired brain electrical activity, and compromised neuroplasticity, ultimately leading to acute and chronic brain dysfunction. Low-intensity pulsed ultrasound (LIPUS) is an emerging brain therapy with the characteristics of non-invasive, high spatial resolution, and high stimulation depth. Herein, we established a controlled cortical impact model to investigate the potential reparative mechanisms of LIPUS in TBI, employing a multi-faceted research methodology encompassing behavioral assessments, immunofluorescence, neuroelectrophysiology, scratch detection of primary cortical neurons, metabolomics and transcriptomics. Our findings demonstrate that LIPUS promotes hippocampal neurogenesis following brain injury, accomplished through the elevation of phosphatidylcholine levels in the hippocampus of TBI mice. Consequently, LIPUS enhances neural electrical activity and augments neural plasticity within the CA1 subregion of the hippocampus, effectively restoring neuronal function and cognitive capabilities in TBI mice. These findings shed light on the promising role of LIPUS in TBI brain rehabilitation, offering new perspectives and theoretical foundations for future studies in this domain.

Pyrylium-based derivatization for rapid labeling and enhanced detection of thiol in mass spectrometry imaging.

Many endogenous antioxidants, including glutathione (GSH), cysteine (Cys), cysteinyl-glycine (Cys-Gly) and homocysteine (Hcy) possess free thiol functional groups. In most cases, matrix-assisted laser desorption ionization (MALDI) analyses of trace amounts of thiol compounds are challenging because of their instability and poor ionization properties. We present a mass spectrometry imaging (MSI) approach for mapping of thiol compounds on brain tissue sections. Our derivatization reagents 1-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-2,4,6-trimethylpyridinium (MTMP) and 1-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-2,4,5-triphenylpyridinium (MTPP) facilitate the covalent charge-tagging of molecules containing free thiol group for the selective and rapid detection of GSH synthesis and metabolic pathway related metabolites by MALDI-MSI. The developed thiol-specific mass spectrometry imaging method realizes the quantitative detection of exogenous N-acetylcysteine tissue sections, and the detection limit in mass spectrometry imaging could reach 0.05 ng. We illustrate the capabilities of the developed method to mapping of thiol compounds on brain tissue from the chronic social defeat stress (CSDS) depression model mice.

Preoperative assessment of high-grade endometrial cancer using a radiomic signature and clinical indicators.

Aim: To develop and validate a radiomics-based combined model (ModelRC) to predict the pathological grade of endometrial cancer. Methods: A total of 403 endometrial cancer patients from two independent centers were enrolled as training, internal validation and external validation sets. Radiomic features were extracted from T2-weighted images, apparent diffusion coefficient map and contrast-enhanced 3D volumetric interpolated breath-hold examination images. Results: Compared with the clinical model and radiomics model, ModelRC showed superior performance; the areas under the receiver operating characteristic curves were 0.920 (95% CI: 0.864-0.962), 0.882 (95% CI: 0.779-0.955) and 0.881 (95% CI: 0.815-0.939) for the training, internal validation and external validation sets, respectively. Conclusion: ModelRC, which incorporated clinical and radiomic features, exhibited excellent performance in the prediction of high-grade endometrial cancer.

Accurate preoperative evaluation of the pathological grade of endometrial carcinoma is very important for the selection of treatment and prognosis. This study tried to develop a simple combined model based on radiomic features from endometrial carcinoma MRI and clinical features of patients. Compared with the clinical model and the radiomic model, the combined model showed superior performance. Therefore, this combined model would help patients and clinicians to make more rational decisions when choosing treatment strategies.

Data of MSCs combined with LITUS treatment to improve cognitive impairment in a moderate traumatic brain injury model in rats.

Here, we treated moderately traumatic brain injury (TBI) rats with different modalities, including transplantation with mesenchymal stem cells (MSCs), treatment with low-intensity transcranial ultrasound stimulation (LITUS), and a combination of the two. After the TBI rat model was established, MSCs (in situ injection within 24 h after injury), LITUS (continuous uninterrupted treatment for 28 days) or combined MSCs + LITUS were administered, and mNSS score, performance of behavior and multiple protein levels were compared between groups by behavioral observation, neurological function assessment and pathological analysis. Nestin, neuron-specific enolase (NSE), growth-associated protein 43 (GAP-43) and postsynaptic density protein (PSD-95) were significantly increased and glial fibrillary acidic protein (GFAP) was significantly decreased in the hippocampus of rats in the combination treatment group; brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α) and aquaporin-4 (AQP-4) were significantly decreased in the injured peripheral cortex. The result of mNSS scores was: TBI group > LITUS group > MSCs group > MSCs+LITUS group > sham group. The alternate correct rate of Y-maze was: sham group > MSCs+LITUS group > MSCs group > LITUS group > TBI group. This data compares the efficacy of MSCs, LITUS, and combination therapy on the level expression of stem cell differentiation related proteins, synaptic plasticity-related proteins, neurotrophic factors, inflammatory factors, and edema-related proteins after TBI by quantitative pathological examination. For a complete description, interpretation, and discussion of the data refer to the article in press [1].

Tannic acid - a bridge and suspending agent for lithium cobalt oxide and reduced graphene oxide: a lodestar for lithium-ion batteries.

ABSTRACTLithium cobalt oxide (LCO) has been employed as cathode material for 40 years. However, the low solubility of LCOs in water and strong electrostatic force and H-bonding between the LCOs particles limited the use of the aqueous binders in the LCO system. We report a feasible and universal approach to fabricating a complex cathode of LCO and reduced graphene oxide (RGO). Tannic acid (TA) could simultaneously disperse LCO and RGO particles. Meanwhile, the branched polyphenol TA acts as a 'bridge' molecule for connecting the LCO and RGO, confirmed by the SEM test. The rheology properties of the PVDF slurry of cathode materials (LCO, LCO/, RGO, and TA/LCO/RGO) were also determined. It could be found that the TA could act as a crosslinking agent for the LCO and RGO particles, increasing the viscosity and storage modulus of the slurry. The cell employed the TA/LCO/RGO slurry as the cathode material, have a higher areal capacity, and had a higher redox potential than employed LCO/RGO and LCO as cathode materials, all of which could be attributed to the addition of the TA. This green molecule can be used to fabricate environmentally friendly and possibly biodegradable electrochemical energy storage devices.

Deep learning and radiomics to predict the mitotic index of gastrointestinal stromal tumors based on multiparametric MRI.

Introduction: Preoperative evaluation of the mitotic index (MI) of gastrointestinal stromal tumors (GISTs) represents the basis of individualized treatment of patients. However, the accuracy of conventional preoperative imaging methods is limited. The aim of this study was to develop a predictive model based on multiparametric MRI for preoperative MI prediction. Methods: A total of 112 patients who were pathologically diagnosed with GIST were enrolled in this study. The dataset was subdivided into the development (n = 81) and test (n = 31) sets based on the time of diagnosis. With the use of T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) map, a convolutional neural network (CNN)-based classifier was developed for MI prediction, which used a hybrid approach based on 2D tumor images and radiomics features from 3D tumor shape. The trained model was tested on an internal test set. Then, the hybrid model was comprehensively tested and compared with the conventional ResNet, shape radiomics classifier, and age plus diameter classifier. Results: The hybrid model showed good MI prediction ability at the image level; the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and accuracy in the test set were 0.947 (95% confidence interval [CI]: 0.927-0.968), 0.964 (95% CI: 0.930-0.978), and 90.8 (95% CI: 88.0-93.0), respectively. With the average probabilities from multiple samples per patient, good performance was also achieved at the patient level, with AUROC, AUPRC, and accuracy of 0.930 (95% CI: 0.828-1.000), 0.941 (95% CI: 0.792-1.000), and 93.6% (95% CI: 79.3-98.2) in the test set, respectively. Discussion: The deep learning-based hybrid model demonstrated the potential to be a good tool for the operative and non-invasive prediction of MI in GIST patients.

Study of the mechanism by which MSCs combined with LITUS treatment improve cognitive dysfunction caused by traumatic brain injury.

Traumatic brain injury (TBI) substantially affects the quality of life of patients, and an effective therapy is unavailable. Previous studies have shown that mesenchymal stem cells (MSCs) and low-intensity transcranial ultrasound (LITUS) are effective treatments for neurological damage, inflammation, edema and cognitive impairment caused by TBI. However, it is unclear whether the combination of the two treatments exerts an additive effect. In this study, a rat TBI model was established using the controlled cortical impact (CCI) method. Neurological function was assessed by determining the rat modified neurological score (mNSS), and cognitive function was assessed using the Y-maze. Pathological changes in the injured tissue were observed using hematoxylin-eosin (HE) staining and immunohistochemistry (IHC), and western blot was performed to detect the expression levels of Nestin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), growth-associated protein-43 (GAP-43), postsynaptic density protein (PSD-95), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and aquaporin-4 (AQP-4). Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed to detect the expression levels of GAP-43, PSD-95, BDNF, TNF-α, and AQP-4 mRNA to investigate whether MSCs combined with LITUS exert an additive therapeutic effect of alleviating the cognitive dysfunction caused by TBI and the possible mechanisms involved. Rats exhibited cognitive dysfunction 28 days after TBI, and MSCs combined with LITUS treatment ameliorated the cognitive deficits caused by TBI via increasing Nestin, NSE, GAP-43, PSD-95, and BDNF expression and attenuating the inflammatory response and edema caused by TBI via reducing TNF-α and AQP-4 expression. According to these results, MSCs combined with LITUS is more effective than MSCs alone for the treatment of TBI, and the mechanism may be the promotion of neuronal proliferation and differentiation, and the attenuation of the inflammatory response and edema, which ameliorates the spatial learning memory impairment caused by TBI. MSCs combined with LITUS treatment represents a new approach for the clinical treatment of patients with TBI.

Multi-Parameter MR Radiomics Based Model to Predict 5-Year Progression-Free Survival in Endometrial Cancer.

Background: Relapse is the major cause of mortality in patients with resected endometrial cancer (EC). There is an urgent need for a feasible method to identify patients with high risk of relapse. Purpose: To develop a multi-parameter magnetic resonance imaging (MRI) radiomics-based nomogram model to predict 5-year progression-free survival (PFS) in EC. Methods: For this retrospective study, 202 patients with EC followed up for at least 5 years after hysterectomy. A radiomics signature was extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) and a dynamic contrast-enhanced three-dimensional volumetric interpolated breath-hold examination (3D-VIBE). The radiomics score (RS) was calculated based on the least absolute shrinkage and selection operator (LASSO) regression. We have developed a radiomics based nomogram model (ModelN) incorporating the RS and clinical and conventional MR (cMR) risk factors. The performance was evaluated by the receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA). Results: The ModelN demonstrated a good calibration and satisfactory discrimination, with a mean area under the curve (AUC) of 0.840 and 0.958 in the training and test cohorts, respectively. In comparison with clinical prediction model (ModelC), the discrimination ability of ModelN showed an improvement with P < 0.001 for the training cohort and P=0.032 for the test cohort. Compared to the radiomics prediction model (ModelR), ModelN discrimination ability showed an improvement for the training cohort with P = 0.021, with no statistically significant difference in the test cohort (P = 0.106). Calibration curves suggested a good fit for probability (Hosmer-Lemeshow test, P = 0.610 and P = 0.956 for the training and test cohorts, respectively). Conclusion: This multi-parameter nomogram model incorporating clinical and cMR findings is a valid method to predict 5-year PFS in patients with EC.

Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway.

BACKGROUND: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. METHODS: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)-EGFP infusion. RESULTS: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. CONCLUSION: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

Low-intensity pulsed ultrasound-generated singlet oxygen induces telomere damage leading to glioma stem cell awakening from quiescence.

Cancer stem cells, quiescent and drug resistant, have become a therapeutic target. Unlike high-intensity focused ultrasound directly killing tumor, low-intensity pulsed ultrasound (LIPUS), a new noninvasive physical device, promotes pluripotent stem cell differentiation and is primarily applied in tissue engineering but rarely in oncotherapy. We explored the effect and mechanism of LIPUS on glioma stem cell (GSC) expulsion from quiescence. Here, we observed that LIPUS led to attenuated expression of GSC biomarkers, promoted GSC escape from G0 quiescence, and significantly weakened the Wnt and Hh pathways. Of note, LIPUS transferred sonomechanical energy into cytochrome c and B5 proteins, which converted oxygen molecules into singlet oxygen, triggering telomere crisis. The in vivo and in vitro results confirmed that LIPUS enhanced the GSC sensitivity to temozolomide. These results demonstrated that LIPUS "waked up" GSCs to improve their sensitivity to chemotherapy, and importantly, we confirmed the direct targeted proteins of LIPUS in GSCs.

Plasmonic enhanced enzyme activity by catalytic cascade induced mutual benefit tumor starvation/immune/photothermal therapy.

Single tumor starvation therapy can activate other signaling pathways in tumor cells and easily induce tumor cell metastasis. This research proposes an intelligent nanoparticle, which is effectively combined with plasmonic and immunotherapy to realize a new strategy of "upstream consumption and downstream blocking" of nutrients in tumor sites. The intelligent nanoparticle (Ag-G/C@M) was composed of Ag NCs loaded with glucose oxidase (GOx), catalase (CAT) and coated with the tumor cytomembrane (M). Homologous targeting of tumor cytomembrane facilitated more delivery of Ag-G/C@M to tumor sites and then the plasmonic excited from Ag-G/C@M can increase the catalytic efficiency of the enzymatic reaction. Hydrogen peroxide (H2O2) produced by Ag-G/C@M through the consumption of glucose is further catalyzed by CAT to produce oxygen (O2). This self-reinforcing cascade reaction not only consumes the nutrients of tumor cells, but also the plasmonic-induced photothermal therapy can further stimulate the immune system to produce interferon-γ (IFN-γ), blocking angiogenesis and restricting the nutrient supply of tumor cells. This strategy takes the nutrition necessary for cell survival as the entry point, through endogenous continuous consumption of intracellular nutrients and containment of exogenous supplementation, combined with plasmonic thermal effect and immunotherapy to kill tumor cells, which provides a new way of treating cancer safely and effectively.

A Gas-Permeation Controllable Packaging Membrane with Porous Microspheres as Gas "Switches" for Efficient Preservation of Litchi.

Food wastage represented by the deterioration of perishable food like fruits and vegetables is a serious global problem with tremendous ethical, financial, and environmental costs. The atmosphere (CO2 and O2) has a crucial role in food storage and can regulate physiological food metabolism and microbial growth. Modified atmosphere packaging (MAP) is a promising method used to extend shelf life and preserve the quality of perishable food; yet, its use depends on the specific gas permeability and selectivity of polymer membranes to generate an atmosphere desirable for storage. In this study, we established and validated a new plant leaf-mimetic shellac-based MAP membrane embedded with chitosan porous microspheres loaded with antimicrobial tannic acid (TA-CPM) as gas "switches" for regulating O2 and CO2 permeability and CO2/O2 selectivity. The effects of different amounts of TA-CPM added into the hybrid membranes were examined for litchi preservation at room temperature. Our results showed that this hybrid TA-CPM/shellac packaging membrane could regulate the internal CO2 and O2 concentrations and the CO2/O2 ratio within the packages containing litchis by adjusting the addition amount of TA-CPM. The 0.05% TA-CPM/shellac and 0.10% TA-CPM/shellac packages, especially 0.05% TA-CPM/shellac, generated a more desirable CO2 and O2 atmosphere for litchi preservation compared with controls, which was reflected by the delaying of browning and rotting, maintaining of the natural color of the litchi pericarp, preservation of pulp quality, inhibition of polyphenol oxidase and guaiacol peroxidase activities, and reduction of oxidative cell damage in litchis. The results suggested that 0.05% TA-CPM/shellac and 0.10% TA-CPM/shellac packaging membranes, especially 0.05% TA-CPM/shellac, could generate an ideal atmosphere for litchi storage at room temperature, demonstrating that this permeation-controlled hybrid membrane has great potential in food preservation and other applications requiring a modified atmosphere.

Combination Analysis of a Radiomics-Based Predictive Model With Clinical Indicators for the Preoperative Assessment of Histological Grade in Endometrial Carcinoma.

BACKGROUND: Histological grade is one of the most important prognostic factors of endometrial carcinoma (EC) and when selecting preoperative treatment methods, conducting accurate preoperative grading is of great significance. PURPOSE: To develop a magnetic resonance imaging (MRI) radiomics-based nomogram for discriminating histological grades 1 and 2 (G1 and G2) from grade 3 (G3) EC. METHODS: This was a retrospective study included 358 patients with histologically graded EC, stratified as 250 patients in a training cohort and 108 patients in a test cohort. T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and a dynamic contrast-enhanced three-dimensional volumetric interpolated breath-hold examination (3D-VIBE) were performed via 1.5-Tesla MRI. To establish ModelADC, the region of interest was manually outlined on the EC in an apparent diffusion coefficient (ADC) map. To establish the radiomic model (ModelR), EC was manually segmented by two independent radiologists and radiomic features were extracted. The Radscore was calculated based on the least absolute shrinkage and selection operator regression. We combined the Radscore with carbohydrate antigen 125 (CA125) and body mass index (BMI) to construct a mixed model (ModelM) and develop the predictive nomogram. Receiver operator characteristic (ROC) and calibration curves were assessed to verify the prediction ability and the degree of consistency, respectively. RESULTS: All three models showed some amount of predictive ability. Using ADC alone to predict the histological risk of EC was limited in both the cohort [area under the curve (AUC), 0.715; 95% confidence interval (CI), 0.6509-0.7792] and test cohorts (AUC, 0.621; 95% CI, 0.515-0.726). In comparison with ModelADC, the discrimination ability of ModelR showed improvement (Delong test, P < 0.0001 for both the training and test cohorts). ModelM, established based on the combination of radiomic and clinical indicators, showed the best level of predictive ability in both the training (AUC, 0.925; 95% CI, 0.898-0.951) and test cohorts (AUC, 0.915; 95% CI, 0.863-0.968). Calibration curves suggested a good fit for probability (Hosmer-Lemeshow test, P = 0.673 and P = 0.804 for the training and test cohorts, respectively). CONCLUSION: The described radiomics-based nomogram can be used to predict EC histological classification preoperatively.

Diagnostic and therapeutic nanoenzymes for enhanced chemotherapy and photodynamic therapy.

Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O2 in tumor cells can cause resistance to drugs, we designed drug delivery liposomes (MnO2-PTX/Ce6@lips) loaded with catalase-like nanozymes of manganese dioxide nanoparticles (MnO2 NPs), paclitaxel (PTX) and chlorin e6 (Ce6) to consume tumor's native H2O2 and produce O2. Based on the catalysis of MnO2 NPs, a large amount of oxygen was produced by MnO2-PTX/Ce6@lips to burst the liposomes and achieve a responsive release of the loaded drug (paclitaxel), and the released O2 relieved the chemoresistance of tumor cells and provided raw materials for photodynamic therapy. Subsequently, MnO2 NPs were decomposed into Mn2+ in an acidic tumor environment to be used as contrast agents for magnetic resonance imaging. The MnO2-PTX/Ce6@lips enhanced the efficacy of chemotherapy and photodynamic therapy (PDT) in bearing-tumor mice, even achieving complete cure. These results indicated the great potential of MnO2-PTX/Ce6@lips for the modulation of the TME and the enhancement of chemotherapy and PDT along with MRI tracing in the treatment of tumors.