A non-negative spike-and-slab lasso generalized linear stacking prediction modeling method for high-dimensional omics data.

BACKGROUND: High-dimensional omics data are increasingly utilized in clinical and public health research for disease risk prediction. Many previous sparse methods have been proposed that using prior knowledge, e.g., biological group structure information, to guide the model-building process. However, these methods are still based on a single model, offen leading to overconfident inferences and inferior generalization. RESULTS: We proposed a novel stacking strategy based on a non-negative spike-and-slab Lasso (nsslasso) generalized linear model (GLM) for disease risk prediction in the context of high-dimensional omics data. Briefly, we used prior biological knowledge to segment omics data into a set of sub-data. Each sub-model was trained separately using the features from the group via a proper base learner. Then, the predictions of sub-models were ensembled by a super learner using nsslasso GLM. The proposed method was compared to several competitors, such as the Lasso, grlasso, and gsslasso, using simulated data and two open-access breast cancer data. As a result, the proposed method showed robustly superior prediction performance to the optimal single-model method in high-noise simulated data and real-world data. Furthermore, compared to the traditional stacking method, the proposed nsslasso stacking method can efficiently handle redundant sub-models and identify important sub-models. CONCLUSIONS: The proposed nsslasso method demonstrated favorable predictive accuracy, stability, and biological interpretability. Additionally, the proposed method can also be used to detect new biomarkers and key group structures.

Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study.

BACKGROUND AIMS: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC. METHODS: We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells. RESULTS: Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells. CONCLUSIONS: Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.

A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data.

BACKGROUND: Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction. METHODS: We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application. RESULTS: The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer. CONCLUSIONS: This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.

Genome-wide screening of m6A profiling of cutaneous wound healing in diabetic mice.

OBJECTIVE: Impaired wound healing in diabetes mellitus (DM) is a major health burden on patients, their families, and society. The present study aimed to systematically profile the m6A modification landscape in cutaneous wounds in a diabetic mouse model. APPROACH: Diabetes was induced in mice through a single intraperitoneal injection of streptozotocin (STZ); a single intraperitoneal injection of PBS was made in control mice for comparisons. Both groups then received an 8-mm diameter, full-thickness dorsal body wound with a biopsy punch. Five days after wound surgery, western blot analysis of harvested wound tissues from both groups was used to assess the expression of m6A-related enzymes. Genome-wide profiling of m6A-tagged transcripts was performed through MeRIP-seq and RNA-seq. RESULTS: ALKBH5, an m6A eraser, was significantly upregulated, while METTL3, METTL14, and WTAP, m6A writers, were markedly downregulated in the diabetic wounds. Additionally, a total of 1335 m6A peaks were differentially expressed in MeRIP-seq and RNA-seq analyses, with 558 upregulated and 777 downregulated peaks. Finally, there was hypomethylated and hypermethylated differentiation at the gene and transcript levels. INNOVATION: The present study was the first to reveal the m6A landscape in diabetic wounds in an animal model. CONCLUSION: This study, by deeply analyzing the role of m6A modifications in diabetic wound healing, provides new insights and understanding into the molecular mechanisms of diabetic wound healing. Future research could further explore how m6A modifications regulate the wound healing process, thereby offering new potential targets for the treatment of diabetic wounds.

Prediction of lymph node status in patients with early-stage cervical cancer based on radiomic features of magnetic resonance imaging (MRI) images.

BACKGROUND: Lymph node metastasis is an important factor affecting the treatment and prognosis of patients with cervical cancer. However, the comparison of different algorithms and features to predict lymph node metastasis is not well understood. This study aimed to construct a non-invasive model for predicting lymph node metastasis in patients with cervical cancer based on clinical features combined with the radiomic features of magnetic resonance imaging (MRI) images. METHODS: A total of 180 cervical cancer patients were divided into the training set (n = 126) and testing set (n = 54). In this cross-sectional study, radiomic features of MRI images and clinical features of patients were collected. The least absolute shrinkage and selection operator (LASSO) regression was used to filter the features. Seven machine learning methods, including eXtreme Gradient Boosting (XGBoost), Logistic Regression, Multinomial Naive Bayes (MNB), Support Vector Machine (SVM), Decision Tree, Random Forest, and Gradient Boosting Decision Tree (GBDT) are used to build the models. Receiver operating characteristics (ROC) curve and area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the performance of the models. RESULTS: Of these 180 patients, 49 (27.22%) patients had lymph node metastases. Five of the 122 radiomic features and 3 clinical features were used to build predictive models. Compared with other models, the MNB model was the most robust, with its AUC, specificity, and accuracy on the testing set of 0.745 (95%CI: 0.740-0.750), 0.900 (95%CI: 0.807-0.993), and 0.778 (95%CI: 0.667-0.889), respectively. Furthermore, the AUCs of the MNB models with clinical features only, radiomic features only, and combined features were 0.698 (95%CI: 0.692-0.704), 0.632 (95%CI: 0.627-0.637), and 0.745 (95%CI: 0.740-0.750), respectively. CONCLUSION: The MNB model, which combines the radiomic features of MRI images with the clinical features of the patient, can be used as a non-invasive tool for the preoperative assessment of lymph node metastasis.

Ginsenoside Rh1 regulates gastric cancer cell biological behaviours and transplanted tumour growth in nude mice via the TGF-ß/Smad pathway.

Gastric cancer (GC) is one of the most prevalent malignancies of the digestive tract. Ginsenoside Rh1 was reported to exert effects on GC. The current study set out to explore the mechanism underlying Ginsenoside Rh1 effects on GC. With oxaliplatin (OXA) serving as the positive control, human GC cells AGS were treated with 0, 10, 25, 50, 74, or 100 µM of ginsenoside Rh1 for 48 h. Proliferation, migration, invasion, and apoptosis were subsequently assessed by means of MTT, scratch test, Transwell, and TUNEL, respectively. AGS cells were further jointly treated with Rh1 and the TGF-ß/Smad pathway activator Kartogenin, followed by detection of TGF-ß/Smad pathway effects on AGS biological behaviours. Moreover, TGF-ß/Smad pathway activation was detected with a Western blot assay. Furthermore, xenograft tumour models were established and tumour growth was recorded. Ki-67 expression patterns and apoptosis were detected with immunohistochemistry and TUNEL, respectively. In vitro, Ginsenoside Rh1 repressed AGS cell proliferation, migration, and invasion, and further promoted apoptosis, with a concentration of 50 µM Rh1 exerting the equivalent effects as OXA. In vivo, Ginsenoside Rh1 inhibited GC proliferation and induced tumour cell apoptosis. Mechanistically, Ginsenoside Rh1 reduced TGF-ß1 and TGF-ß2 levels and Smad2 and Smad3 phosphorylation levels. Collectively, our findings highlighted that ginsenoside Rh1 inhibited GC cell growth and tumour growth in xenograft tumour models via inhibition of the TGF-ß/Smad pathway.

Strontium doped mesoporous silica nanoparticles accelerate osteogenesis and angiogenesis in distraction osteogenesis by activation of Wnt pathway.

Distraction osteogenesis (DO) is a powerful method to reconstruct segmented bone defects in the extremities. However, the main shortcoming of DO is the time-consuming consolidation period. To shorten the consolidation process, two biocompatible inorganic ions, strontium and silicone, were applied to design a biocompatible material to enhance bone mineralization ability during DO. In the present study, we integrated strontium into a one-pot synthesis of mesoporous silica nanoparticles to obtain strontium-doped mesoporous silica nanoparticles characterized by a homogeneous spherical morphology and uniform ion-releasing dynamics. This dual-ion releasing osteogenic and angiogenic drug delivery system was investigated to accelerate mineralization in DO. Osteogenesis was promoted by activation of the Wnt/ß-catenin pathway, while bone resorption was inhibited by reduction of the osteoclastogenic factor RANKL/OPG. In addition, angiogenesis may have been enhanced indirectly by secretion of vascular endothelial growth factor (VEGF) from bone marrow stem cells. Therefore, strontium-doped mesoporous silica nanoparticles could be a potential biomaterial candidate for accelerating consolidation during DO.

A Wearable Assistive Device for Blind Pedestrians Using Real-Time Object Detection and Tactile Presentation.

Nowadays, improving the traffic safety of visually impaired people is a topic of widespread concern. To help avoid the risks and hazards of road traffic in their daily life, we propose a wearable device using object detection techniques and a novel tactile display made from shape-memory alloy (SMA) actuators. After detecting obstacles in real-time, the tactile display attached to a user's hands presents different tactile sensations to show the position of the obstacles. To implement the computation-consuming object detection algorithm in a low-memory mobile device, we introduced a slimming compression method to reduce 90% of the redundant structures of the neural network. We also designed a particular driving circuit board that can efficiently drive the SMA-based tactile displays. In addition, we also conducted several experiments to verify our wearable assistive device's performance. The results of the experiments showed that the subject was able to recognize the left or right position of a stationary obstacle with 96% accuracy and also successfully avoided collisions with moving obstacles by using the wearable assistive device.

Disruption of SIRT7 Increases the Efficacy of Checkpoint Inhibitor via MEF2D Regulation of Programmed Cell Death 1 Ligand 1 in Hepatocellular Carcinoma Cells.

BACKGROUND & AIMS: Immune checkpoint inhibitors have some efficacy in the treatment of hepatocellular carcinoma (HCC). Programmed cell death 1 ligand 1 (PD-L1), expressed on some cancer cells, binds to the receptor programmed cell death 1 (PDCD1, also called PD1) on T cells to prevent their proliferation and reduce the antigen-tumor immune response. Immune cells that infiltrate some types of HCCs secrete interferon gamma (IFNG). Some HCC cells express myocyte enhancer factor 2D (MEF2D), which has been associated with shorter survival times of patients. We studied whether HCC cell expression of MEF2D regulates expression of PD-L1 in response to IFNG. METHODS: We analyzed immune cells from 20 fresh HCC tissues by flow cytometry. We analyzed 225 fixed HCC tissues (from 2 cohorts) from patients in China by immunohistochemistry and obtained survival data. We created mice with liver-specific knockout of MEF2D (MEF2DLPC-KO mice). We knocked out or knocked down MEF2D, E1A binding protein p300 (p300), or sirtuin 7 (SIRT7) in SMMC-7721, Huh7, H22, and Hepa1-6 HCC cell lines, some incubated with IFNG. We analyzed liver tissues from mice and cell lines by RNA sequencing, immunoblot, dual luciferase reporter, and chromatin precipitation assays. MEF2D protein acetylation and proteins that interact with MEF2D were identified by coimmunoprecipitation and pull-down assays. H22 cells, with MEF2D knockout or without (controls), were transplanted into BALB/c mice, and some mice were given antibodies to deplete T cells. Mice bearing orthotopic tumors grown from HCC cells, with or without knockout of SIRT7, were given injections of an antibody against PD1. Growth of tumors was measured, and tumors were analyzed by immunohistochemistry and flow cytometry. RESULTS: In human HCC specimens, we found an inverse correlation between level of MEF2D and numbers of CD4+ and CD8+ T cells; level of MEF2D correlated with percentages of PD1-positive or TIM3-positive CD8+ T cells. Knockout of MEF2D from H22 cells reduced their growth as allograft tumors in immune-competent mice but not in immune-deficient mice or mice with depletion of CD8+ T cells. When MEF2D-knockout cells were injected into immune-competent mice, they formed smaller tumors that had increased infiltration and activation of T cells compared with control HCC cells. In human and mouse HCC cells, MEF2D knockdown or knockout reduced expression of PD-L1. MEF2D bound the promoter region of the CD274 gene (encodes PD-L1) and activated its transcription. Overexpression of p300 in HCC cells, or knockout of SIRT7, promoted acetylation of MEF2D and increased its binding, along with acetylated histones, to the promoter region of CD274. Exposure of HCC cells to IFNG induced expression of p300 and its binding MEF2D, which reduced the interaction between MEF2D and SIRT7. MEF2D-induced expression of PD-L1 upon IFNG exposure was independent of interferon-regulatory factors 1 or 9. In HCC cells not exposed to IFNG, SIRT7 formed a complex with MEF2D that attenuated expression of PD-L1. Knockout of SIRT7 reduced proliferation of HCC cells and growth of tumors in immune-deficient mice. Compared with allograft tumors grown from control HCC cells, in immune-competent mice, tumors grown from SIRT7-knockout HCC cells expressed higher levels of PD-L1 and had reduced infiltration and activation of T cells. In immune-competent mice given antibodies to PD1, allograft tumors grew more slowly from SIRT7-knockout HCC cells than from control HCC cells. CONCLUSIONS: Expression of MEF2D by HCC cells increases their expression of PD-L1, which prevents CD8+ T-cell-mediated antitumor immunity. When HCC cells are exposed to IFNG, p300 acetylates MEF2D, causing it to bind the CD274 gene promoter and up-regulate PD-L1 expression. In addition to promoting HCC cell proliferation, SIRT7 reduced acetylation of MEF2D and expression of PD-L1 in HCC cells not exposed to IFNG. Strategies to manipulate this pathway might increase the efficacy of immune therapies for HCC.

Selective Capacitive Removal of Heavy Metal Ions from Wastewater over Lewis Base Sites of S-Doped Fe-N-C Cathodes via an Electro-Adsorption Process.

The pollution of toxic heavy metals is becoming an increasingly important issue in environmental remediation because these metals are harmful to the ecological environment and human health. Highly efficient selective removal of heavy metal ions is a huge challenge for wastewater purification. Here, highly efficient selective capacitive removal (SCR) of heavy metal ions from complex wastewater over Lewis base sites of S-doped Fe-N-C cathodes was originally performed via an electro-adsorption process. The SCR efficiency of heavy metal ions can reach 99% in a binary mixed solution [NaCl (100 ppm) and metal nitrate (10 ppm)]. Even the SCR efficiency of heavy metal ions in a mixed solution containing NaCl (100 ppm) and multicomponent metal nitrates (10 ppm for each) can approach 99%. Meanwhile, the electrode also demonstrated excellent cycle performance. It has been demonstrated that the doping of S can not only enhance the activity of Fe-N sites and improve the removal ability of heavy metal ions but also combine with heavy metal ions by forming covalent bonds of S- clusters on Lewis bases. This work demonstrates a prospective way for the selective removal of heavy metal ions in wastewater.

Capacitive Removal of Fluoride Ions via Creating Multiple Capture Sites in a Modulatory Heterostructure.

Fluoride pollution has become a major concern because of its adverse effects on human health. However, the removal capacity of defluorination agents in traditional methods is far from satisfactory. Herein, capacitive removal of F- ions via creating multiple capture sites in a modulatory heterostructure has been originally demonstrated. The heterostructure of uniformly dispersed Al2O3 coating on hollow porous nitrogen-doped carbon frameworks was precisely synthesized by atomic layer deposition. An exceptional F- ion removal efficiency at 1.2 V (95.8 and 92.9% in 5 and 10 mg/L F- solutions, respectively) could be finally achieved, with a good regeneration ability after 20 consecutive defluorination cycles. Furthermore, we investigated the removal mechanisms of F- ions by in situ Raman, in situ X-ray diffraction, and ex situ X-ray photoelectron spectroscopy measurements. The promotional removal capacity was realized by the multiple capture sites of the reversible conversion of Al-F species and the insertion of F- ions into the carbon skeleton. This work offers an important new pathway and deep understanding for efficient removal of F- ions from wastewater.

Capacitive Removal of Heavy Metal Ions from Wastewater via an Electro-Adsorption and Electro-Reaction Coupling Process.

Heavy metals widely exist in wastewater, which is a serious threat to human health or water environment. Highly efficient removal of heavy metal ions from wastewater is a major challenge to wastewater treatment. In this work, capacitive removal of heavy metal ions from wastewater via an electro-adsorption and electro-reaction coupling process was originally demonstrated. The removal efficiency of heavy metal ions in the binary-component solutions containing metal nitrate (10 mg/L) and NaCl (100 mg/L) can reach 99%. Even the removal efficiency of heavy metal ions can be close to 99% in the multi-component solution containing all the seven metal nitrates (10 mg/L for each) and 100 mg/L NaCl. Meanwhile, the electro-adsorption and electro-reaction coupling process maintained excellent regeneration ability even after 20 cycles. Furthermore, the heavy metal ions removal mechanism was proven to be the pseudocapacitive intercalation of heavy metal ions into the layered structure of the employed W18O49/graphene in the electro-adsorption and electro-reaction coupling process. This work demonstrates great potential for general applicability to wastewater treatment.

Reductions in mortality resulting from COVID-19 quarantine measures in China.

BACKGROUND: To explore the impact of quarantine measures on the cause of death. METHODS: We use time series analysis with the data from death cause surveillance database of Suzhou from January 2017 to December 2019 to estimate the expected deaths from January to June 2020 and compare these expected deaths with the reported numbers of deaths. RESULTS: After the implementation of epidemic prevention measures in Suzhou in the first 3 months, overall number of all-cause deaths declined for 5.36, 7.54 and 7.02% compared with predicted numbers. The number of deaths from respiratory causes and traffic accidents declined shapely by 30.1 and 26.9%, totally. When quarantine measures were released (April-June), however, the observed numbers of total deaths exceeded the predicted deaths. People aged over 70 accounted for 91.6% of declined death number in respiratory causes and people aged over 60 accounted for 68.0% of declined death number in traffic accidents. Women over the age of 80 benefited the most from respiratory prevention (accounts for 41% of all reductions), whereas women aged over 60 benefited the most from traffic control (44%). CONCLUSIONS: Overall, the whole population benefited from the epidemic prevention measures especially elderly females. This study is a useful supplement to encourage the government to develop regular preventive measures under the era of normalized epidemic.

IL-1ß Impaired Diabetic Wound Healing by Regulating MMP-2 and MMP-9 through the p38 Pathway.

Diabetes mellitus is one of the most prominent metabolic disorders in the world, and insulin resistance in diabetic patients leads to several complications including increased inflammation and delayed wound healing. Fibroblast migration and reepithelialization play a significant role in wound healing. In this study, we explored the effects of IL-1ß signaling on proliferation and migration of human fibroblasts from diabetic wound tissues. We observed elevated levels of IL-1ß in samples from diabetic patients when compared to normal wound tissues. At high concentrations, IL-1ß inhibited cell proliferation and migration in ex vivo fibroblast cultures. Moreover, expression of matrix metalloproteinases (MMPs) was upregulated, and tissue inhibitor of metalloproteinases (TIMPs) was downregulated in diabetic wound tissues and cells. These effects were regulated by levels of IL-1ß. Furthermore, IL-1ß induced p38 phosphorylation thereby activating the p38 MAPK pathway that in turn regulated the expression of MMPs and TIMPs. Together, our study identifies a novel mechanism behind delayed wound closure in diabetes mellitus that involves IL-1ß-dependent regulation of cell proliferation and migration.

Tcf7l1 Acts as a Suppressor for the Self-Renewal of Liver Cancer Stem Cells and Is Regulated by IGF/MEK/ERK Signaling Independent of ß-Catenin.

Tcf7l1, which is a key effector molecule of the Wnt/ß-catenin signaling pathway, is highly expressed in various cancers, and it promotes tumor growth. In this study, we demonstrated that unlike its tumor-promoting effects in several other types of cancers, Tcf7l1 expression is downregulated in hepatocarcinoma compared with their adjacent nontumor counterparts. Underexpression of Tcf7l1 is correlated with poorer survival. In liver cancer stem cell (CSC) populations, Tcf7l1 expression is downregulated. Ectopic expression of Tcf7l1 attenuates the self-renewal abilities of liver CSCs. Mechanistically, Tcf7l1 regulates the self-renewal abilities of liver CSCs through transcriptional repression of the Nanog gene, and the effect is independent of ß-catenin. Moreover, we found that Tcf7l1 expression is controlled by extracellular insulin-like growth factor (IGF) signaling, and we demonstrated for the first time that IGF signaling stimulates Tcf7l1 phosphorylation and degradation through the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Overall, our results provide some new insights into how extracellular signals modulate the self-renewal of liver CSCs and highlight the inhibitory roles of Tcf7l1 in cancer. Stem Cells 2019;37:1389-1400.

Trans fatty acid intake among Chinese population: a longitudinal study from 1991 to 2011.

OBJECTIVE: This study was aimed to roughly describe individual Trans Fatty Acids (TFAs) intake and the percentage of energy intake(E%), and identify major food sources in the Chinese population, taking gender, age, and regional distribution into the consideration, as well as examining temporal changes over the course of 20 years. METHOD: This multi-center study, covering nine provinces among populations aged ≥ 3 in China, was conducted to collect food consumption information from 1991 to 2011. A classical assessment method was used to estimate the level of dietary TFA intake. RESULTS: Over the 20-year period, the intake of TFAs in Chinese populations had increased, but remained at a relatively lower level (from 0.25 g/d(0.11% for E%) to 0.53 g/d(0.24% for E%)) compared with that of other countries and the World Health Organization (WHO) recommended level. Collectively, males and participants aged 19-60 generally consumed more TFA-containing foods. People in eastern regions consumed more TFAs and had a higher E% than those in western area. Industrial sources of TFAs, especially vegetable oil, ranked as the principal food sources of TFAs in the Chinese population. Natural sources of TFAs have gradually increased in proportion among children and adolescents. CONCLUSIONS: TFA intake and the E% are commonly under the recommended level in the general population in China. Presently, restriction of vegetable oil could be a crucial method to reduce TFA intake. It would be critical to facilitate and promote public health that food recommendations might be based on the dietary preferences for population separated by different ages and regions.

Capacitive Deionization of Saline Water by Using MoS2-Graphene Hybrid Electrodes with High Volumetric Adsorption Capacity.

Capacitive deionization (CDI) has received wide attention as an emerging water treatment technology because of its low energy consumption, low cost, and high efficiency. However, the conventional carbon electrode materials for CDI have low densities, which occupy large volumes and are disadvantageous for use in limited space (e.g., in household or on offshore platforms). In order to miniaturize the CDI device, it is quite urgent to develop high volumetric adsorption capacity (VAC) electrode materials. To overcome this issue, we rationally designed and originally developed high VAC MoS2-graphene hybrid electrodes for CDI. It is interesting that MoS2-graphene hybrid electrode has a much higher NaCl VAC of 14.3 mg/cm3 with a gravimetric adsorption capacity of 19.4 mg/g. It has been demonstrated that the adsorption capacity is significantly enhanced because of the rapid ion transport of MoS2 and high electrical conductivity of graphene. In situ Raman spectra and high-angle annular dark-field scanning transmission electron microscopy tests demonstrated a favorable Faradaic reaction, which was crucial to enhancing the NaCl VAC of the MoS2-graphene hybrid electrode. This work opens a new avenue for miniaturizing future CDI devices.

Scalping of aroma compounds from food simulants into polyethylene terephthalate laminated steel.

BACKGROUND: Aroma scalping is a very common problem and can affect the sensory quality of packaged food. To study the aroma scalping characteristics of polyethylene terephthalate laminated steel (PET-LS), the sorption kinetics of six common aroma compounds (2-pentanone, 2-heptanone, hexanal, citral, butyl acetate, isopentyl acetate) in foods were assessed for drawn-redrawn cans made with PET-LS. RESULTS: Storage temperature and initial concentration were proved as important factors to affect compound sorption and diffusion for flavors. The correlation between logarithm of equilibrium absorption ln M∞ and reciprocal of absolute temperature 1/T showed good linear relationship (R2 = 0.9380-0.9998) at 4 °C, 20 °C and 50 °C, and the M∞ obtained by the experiment was very close to the predicted value at 37 °C. At low initial concentration (below 500 µL L-1 ), the absorption capacity and initial concentration showed a slow linear growth trend, whereas there was a rapid change at high initial concentration. The values of diffusion coefficient D were on the order of 10-11 -10-12  m2  day-1 , which were lower than reported for other polymer materials (linear low-density polyethylene, polybutylene succinate, polylactic acid). CONCLUSION: The equilibrium absorption amount of each flavor component was dependent on the temperature under the same concentration (500 µL L-1 ). The Fickian diffusion model was used for fitting the experimental kinetics values satisfactorily (R2 = 0.9158-0.9885). © 2019 Society of Chemical Industry.

Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR-T containing either CD28 or 4-1BB.

T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD19 CAR-T. The first 5 patients were treated with CD28-CAR and the other 5 patients were treated with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group, 3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune-suppressive factor level.

Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA+ Metastatic Colorectal Cancers.

Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in treatment of hematological malignancies, but its applications in solid tumors need further exploration. In this study, we investigated CAR-T therapy targeting carcino-embryonic antigen (CEA)-positive colorectal cancer (CRC) patients with metastases to evaluate its safety and efficacy. Five escalating dose levels (DLs) (1 × 105 to 1 × 108/CAR+/kg cells) of CAR-T were applied in 10 CRC patients. Our data showed that severe adverse events related to CAR-T therapy were not observed. Of the 10 patients, 7 patients who experienced progressive disease (PD) in previous treatments had stable disease after CAR-T therapy. Two patients remained with stable disease for more than 30 weeks, and two patients showed tumor shrinkage by positron emission tomography (PET)/computed tomography (CT) and MRI analysis, respectively. Decline of serum CEA level was apparent in most patients even in long-term observation. Furthermore, we observed persistence of CAR-T cells in peripheral blood of patients receiving high doses of CAR-T therapy. Importantly, we observed CAR-T cell proliferation especially in patients after a second CAR-T therapy. Taken together, we demonstrated that CEA CAR-T cell therapy was well tolerated in CEA+ CRC patients even in high doses, and some efficacy was observed in most of the treated patients.