Electrochemiluminescence in Microfluidic Channels: Influence of Mass Transport on the Tris(2,2'-bipyridyl)ruthenium(II)/Tripropylamine System at Semitransparent Electrodes.

Mass transport in laminar flow can improve the electrochemiluminescence (ECL) performance at the microchannel electrodes, depending on the device geometry and operating regimes. The known Ru(bpy)32+/tripropylamine (TPA) system was selected and studied in continuous microfluidics on semitransparent platinum electrodes. With this electrode material, ECL is mainly generated via a catalytic pathway. This mechanism was characterized under flow conditions by monitoring the ECL emission using linear sweep voltammetry and chronoamperometry. In parallel, ECL imaging of the electrode surface was conducted in order to characterize the ECL profiles above the electrode in the flow direction. Numerical simulations were carried out and then compared to experimental data to both confirm the ECL mechanism and assess the main kinetic parameters. A good agreement was obtained, demonstrating the influence of the operating regimes of the microchannel electrodes on the ECL performances. In the thin-layer regime, due to TPA depletion, ECL is located at the upstream edge of the electrode, while it is homogeneously distributed over the electrode surface in convective regimes. These characteristics will necessarily have to be taken into account in the design of dedicated ECL analytical microfluidic devices operating under continuous flow.

A Novel Tensor Ring Sparsity Measurement for Image Completion.

As a promising data analysis technique, sparse modeling has gained widespread traction in the field of image processing, particularly for image recovery. The matrix rank, served as a measure of data sparsity, quantifies the sparsity within the Kronecker basis representation of a given piece of data in the matrix format. Nevertheless, in practical scenarios, much of the data are intrinsically multi-dimensional, and thus, using a matrix format for data representation will inevitably yield sub-optimal outcomes. Tensor decomposition (TD), as a high-order generalization of matrix decomposition, has been widely used to analyze multi-dimensional data. In a direct generalization to the matrix rank, low-rank tensor modeling has been developed for multi-dimensional data analysis and achieved great success. Despite its efficacy, the connection between TD rank and the sparsity of the tensor data is not direct. In this work, we introduce a novel tensor ring sparsity measurement (TRSM) for measuring the sparsity of the tensor. This metric relies on the tensor ring (TR) Kronecker basis representation of the tensor, providing a unified interpretation akin to matrix sparsity measurements, wherein the Kronecker basis serves as the foundational representation component. Moreover, TRSM can be efficiently computed by the product of the ranks of the mode-2 unfolded TR-cores. To enhance the practical performance of TRSM, the folded-concave penalty of the minimax concave penalty is introduced as a nonconvex relaxation. Lastly, we extend the TRSM to the tensor completion problem and use the alternating direction method of the multipliers scheme to solve it. Experiments on image and video data completion demonstrate the effectiveness of the proposed method.

Distinct brain state dynamics of native and second language processing during narrative listening in late bilinguals.

The process of complex cognition, which includes language processing, is dynamic in nature and involves various network modes or cognitive modes. This dynamic process can be manifested by a set of brain states and transitions between them. Previous neuroimaging studies have shed light on how bilingual brains support native language (L1) and second language (L2) through a shared network. However, the mechanism through which this shared brain network enables L1 and L2 processing remains unknown. This study examined this issue by testing the hypothesis that L1 and L2 processing is associated with distinct brain state dynamics in terms of brain state integration and transition flexibility. A group of late Chinese-English bilinguals was scanned using functional magnetic resonance imaging (fMRI) while listening to eight short narratives in Chinese (L1) and English (L2). Brain state dynamics were modeled using the leading eigenvector dynamic analysis framework. The results show that L1 processing involves more integrated states and frequent transitions between integrated and segregated states, while L2 processing involves more segregated states and fewer transitions. Our work provides insight into the dynamic process of narrative listening comprehension in late bilinguals and sheds new light on the neural representation of language processing and related disorders.

Identification and Functional Analysis of Differentially Expressed Genes in Myzus persicae (Hemiptera: Aphididae) in Response to Trans-anethole.

Plant essential oils, with high bioactivity and biodegradability, provide promising alternatives to synthetic pesticides for pest control. Trans-anethole is the major component of essential oil from star anise, Illicium verum Hook. The compound has a strong contact toxicity against the green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae), which is a major insect pest of many vegetables and crops. However, little information is known about how M. persicae responds to trans-anethole at the molecular level. We conducted a comparative transcriptome analysis of M. persicae in response to a LD50 dose of trans-anethole. A total of 559 differentially expressed genes were detected in the treated individuals, with 318 genes up-regulated, and 241 genes down-regulated. Gene ontology (GO) analysis revealed that these genes were classified into different biological processes and pathways. We also found that genes encoding ATP-binding cassette (ABC) transporters, DnaJ, and cuticle proteins were dramatically up-regulated in response to trans-anethole. To study the function of these genes, we performed RNA interference (RNAi) analysis. Knockdown of an ABC transporter gene (ABCG4) and a DnaJ gene (DnaJC1) resulted in a significantly increased mortality rate in M. persicae following trans-anethole exposure, indicating the involvement of these two genes in the toxicity response to trans-anethole. The findings provide new insights into the mechanisms of M. persicae in coping with plant essential oils.

Shadow Electrochemiluminescence Microscopy of Single Mitochondria.

Mitochondria are the subcellular bioenergetic organelles. The analysis of their morphology and topology is essential to provide useful information on their activity and metabolism. Herein, we report a label-free shadow electrochemiluminescence (ECL) microscopy based on the spatial confinement of the ECL-emitting reactive layer to image single living mitochondria deposited on the electrode surface. The ECL mechanism of the freely-diffusing [Ru(bpy)3 ]2+ dye with the sacrificial tri-n-propylamine coreactant restrains the light-emitting region to a micrometric thickness allowing to visualize individual mitochondria with a remarkable sharp negative optical contrast. The imaging approach named "shadow ECL" (SECL) reflects the negative imprint of the local diffusional hindrance of the ECL reagents by each mitochondrion. The statistical analysis of the colocalization of the shadow ECL spots with the functional mitochondria revealed by classical fluorescent biomarkers, MitoTracker Deep Red and the endogenous intramitochondrial NADH, validates the reported methodology. The versatility and extreme sensitivity of the approach are further demonstrated by visualizing single mitochondria, which remain hardly detectable with the usual biomarkers. Finally, by alleviating problems of photobleaching and phototoxicity associated with conventional microscopy methods, SECL microscopy should find promising applications in the imaging of subcellular structures.

Bioengineered Artificial Extracellular Vesicles Presenting PD-L1 and Gal-9 Ameliorate New-Onset Type 1 Diabetes.

An important factor in the development of type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9), in ß-cells. Therefore, modulation of pancreas-infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating new-onset T1D. We genetically engineered macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict islet autoreactive T lymphocytes and protect ß-cells from destruction. Intriguingly, overexpression of Gal-9 stimulated macrophage polarization to the M2 phenotype with immunosuppressive attributes. Alternatively, both PD-L1- and Gal-9-presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhered to T cells via the interaction of programmed cell death protein 1/PD-L1 or T-cell immunoglobulin mucin 3/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T-cell apoptosis and splenic regulatory T (Treg) cell formation in vitro. Notably, PD-L1-Gal-9 aEVs efficaciously reversed new-onset hyperglycemia in NOD mice, prevented T1D progression, and decreased the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas, which together contributed to the preservation of residual ß-cell survival and mitigation of hyperglycemia.

Lactobacillus plantarum Zhang-LL Inhibits Colitis-Related Tumorigenesis by Regulating Arachidonic Acid Metabolism and CD22-Mediated B-Cell Receptor Regulation.

Colorectal cancer (CRC) is a significant health concern and is the third most commonly diagnosed and second deadliest cancer worldwide. CRC has been steadily increasing in developing countries owing to factors such as aging and epidemics. Despite extensive research, the exact pathogenesis of CRC remains unclear, and its causes are complex and variable. Numerous in vitro, animal, and clinical trials have demonstrated the efficacy of probiotics such as Lactobacillus plantarum in reversing the adverse outcomes of CRC. These findings suggest that probiotics play vital roles in the prevention, adjuvant treatment, and prognosis of CRC. In this study, we constructed a mouse model of CRC using an intraperitoneal injection of azomethane combined with dextran sodium sulfate, while administering 5-fluorouracil as well as high- and low-doses of L. plantarum Zhang-LL live or heat-killed strains. Weight changes and disease activity indices were recorded during feeding, and the number of polyps and colon length were measured after euthanasia. HE staining was used to observe the histopathological changes in the colons of mice, and ELISA was used to detect the expression levels of IL-1ß, TNF-α, and IFN-γ in serum. To investigate the specific mechanisms involved in alleviating CRC progression, gut microbial alterations were investigated using 16S rRNA amplicon sequencing and non-targeted metabolomics, and changes in genes related to CRC were assessed using eukaryotic transcriptomics. The results showed that both viable and heat-killed strains of L. plantarum Zhang-LL in high doses significantly inhibited tumorigenesis, colon shortening, adverse inflammatory reactions, intestinal tissue damage, and pro-inflammatory factor expression upregulation. Specifically, in the gut microbiota, the abundance of the dominant flora Acutalibacter muris and Lactobacillus johnsonii was regulated, PGE2 expression was significantly reduced, the arachidonic acid metabolism pathway was inhibited, and CD22-mediated B-cell receptor regulation-related gene expression was upregulated. This study showed that L. plantarum Zhang-LL live or heat-inactivated strains alleviated CRC progression by reducing the abundance of potentially pathogenic bacteria, increasing the abundance of beneficial commensal bacteria, mediating the arachidonic acid metabolism pathway, and improving host immunogenicity.

Physical, Mechanical, and Adhesive Properties of Novel Self-Adhesive Resin Cement.

Objective: To evaluate a newly developed self-adhesive resin cement on physical, mechanical, and adhesive properties and compare it with other commercial self-adhesive resin cements. Materials and Methods: Experimental self-adhesive resin cement (SARC) was formulated by our proprietary adhesive resin and filler technology. Maxcem Elite, RelyX Unicem 2, SpeedCem Plus, SmartCEM 2, and Calibra Universal 2 were selected for comparison. Working and setting times, film thickness, water sorption and solubility, flexural strength, and modulus were measured in accordance with ISO-4049. Consistency was tested according to modified ISO 4823. Shear bond strengths were conducted according to ISO 29022. The data were analyzed by one-way ANOVA and post hoc Tukey's tests (p ≤ 0.05). Results: All cements showed about 2-4 min working time and about 3-6 min setting time except that RelyX Unicem 2 has a longer working time (9'58") and setting time (10'18"). All cements meet ISO standards for film thickness (≤50 µm), water sorption (≤40 µg/mm3) except Maxcem Elite (46.19 µg/mm3), and water solubility (≤7.5 µg/mm3) except SmartCEM 2 (11.35 µg/mm3) and Calibra Universal (9.87 µg/mm3). Experimental SARC showed significantly higher flexural strength and modulus than other cements (p < 0.001). For self-curing, Experimental SARC has statistically higher bond strength than other cements (p < 0.001) except statistically the same as RelyX Unicem 2 (p > 0.05). For light-curing, Experimental SARC showed significantly higher bond strength than other cements (p < 0.001) except statistically the same as Maxcem Elite and RelyX Unicem 2 (p > 0.05). For dual-curing, the bond strength of Experimental SARC is significantly higher than that of other cements (p < 0.001). Conclusion: The newly developed self-adhesive resin cement exhibited favorable bonding capability and physical and mechanical properties compared to other commercial self-adhesive resin cements and is a good option for cementation of indirect restorations with potential long-term clinical success.

Leverage biomaterials to modulate immunity for type 1 diabetes.

The pathogeny of type 1 diabetes (T1D) is mainly provoked by the ß-cell loss due to the autoimmune attack. Critically, autoreactive T cells firsthand attack ß-cell in islet, that results in the deficiency of insulin in bloodstream and ultimately leads to hyperglycemia. Hence, modulating immunity to conserve residual ß-cell is a desirable way to treat new-onset T1D. However, systemic immunosuppression makes patients at risk of organ damage, infection, even cancers. Biomaterials can be leveraged to achieve targeted immunomodulation, which can reduce the toxic side effects of immunosuppressants. In this review, we discuss the recent advances in harness of biomaterials to immunomodulate immunity for T1D. We investigate nanotechnology in targeting delivery of immunosuppressant, biological macromolecule for ß-cell specific autoreactive T cell regulation. We also explore the biomaterials for developing vaccines and facilitate immunosuppressive cells to restore immune tolerance in pancreas.

Ameliorative Effects of Bifidobacterium animalis subsp. lactis J-12 on Hyperglycemia in Pregnancy and Pregnancy Outcomes in a High-Fat-Diet/Streptozotocin-Induced Rat Model.

Bifidobacterium, a common probiotic, is widely used in the food industry. Hyperglycemia in pregnancy has become a common disease that impairs the health of the mother and can lead to adverse pregnancy outcomes, such as preeclampsia, macrosomia, fetal hyperinsulinemia, and perinatal death. Currently, Bifidobacterium has been shown to have the potential to mitigate glycolipid derangements. Therefore, the use of Bifidobacterium-based probiotics to interfere with hyperglycemia in pregnancy may be a promising therapeutic option. We aimed to determine the potential effects of Bifidobacterium animalis subsp. lactis J-12 (J-12) in high-fat diet (HFD)/streptozotocin (STZ)-induced rats with hyperglycemia in pregnancy (HIP) and respective fetuses. We observed that J-12 or insulin alone failed to significantly improve the fasting blood glucose (FBG) level and oral glucose tolerance; however, combining J-12 and insulin significantly reduced the FBG level during late pregnancy. Moreover, J-12 significantly decreased triglycerides and total cholesterol, relieved insulin and leptin resistance, activated adiponectin, and restored the morphology of the maternal pancreas and hepatic tissue of HIP-induced rats. Notably, J-12 ingestion ameliorated fetal physiological parameters and skeletal abnormalities. HIP-induced cardiac, renal, and hepatic damage in fetuses was significantly alleviated in the J-12-alone intake group, and it downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health. Furthermore, placental tissue damage in rats with HIP appeared to be in remission in the J-12 group. Upon exploring specific placental microbiota, we observed that J-12 affected the abundance of nine genera, positively correlating with FBG and leptin in rats and hippocampal mRNA levels of InsR and IGF-1R mRNA in the fetus, while negatively correlating with adiponectin in rats and hippocampal levels of AKT in the fetus. These results suggest that J-12 may affect the development of the fetal central nervous system by mediating placental microbiota via the regulation of maternal-related indicators. J-12 is a promising strategy for improving HIP and pregnancy outcomes.

A novel CAD/CAM resin composite block with high mechanical properties.

OBJECTIVE: To determine the mechanical properties of a newly-developed CAD/CAM resin composite block and compare with other resin composite blocks and a polymer-infiltrated ceramic block. METHODS: Experimental composite block was formulated by our proprietary resin and filler technologies and cured via Hot Isostatic Pressing (HIP). Bar-shaped specimens (1 × 4×12 - 13 mm, n = 10) for flexural strength, flexural modulus and modulus of resilience were sectioned from block materials and measured in accordance to modified ISO-6872. Cylinder specimens for compressive strength (2 × 4 mm, n = 8) and for diametral tensile strength (6 × 3 mm, n = 8) were milled from the block materials and tested according to ASTM-D695 and ANSI/ADA-Specification #27, respectively. Block specimens (5 mm, n = 3) for Vickers hardness were polished and measured for five indentations on each specimen. The data was analyzed by one-way ANOVA and post-hoc Tukey tests (p ≤ 0.05). RESULTS: Experimental composite block showed higher or significantly higher flexural strength, flexural modulus, modulus of resilience, compressive strength, diametral tensile strength and Vickers hardness than the other commercially available block materials except Vita Enamic for flexural modulus and hardness and Cerasmart for modulus of resilience. Some positive correlations were observed among the different mechanical properties. SIGNIFICANCE: New composite block exhibited higher mechanical properties as compared to commercially available composite block materials. Superior mechanical properties for resin composite block materials were obtained by composite and curing processing technologies. Resin composite blocks with higher mechanical properties are good options for the fabrication of CAD/CAM indirect restorations.

GLUT1 participates in tamoxifen resistance in breast cancer cells through autophagy regulation.

Tamoxifen is an estrogen modulator widely used in the treatment of patients with ESR/ER-positive breast cancer; however, resistance limits its clinical application. Autophagy alterations have recently been suggested as a new mechanism for tamoxifen resistance. Glucose transporter 1 (GLUT1) has been reported to be associated with the development and metastasis of breast cancer, but the relationship among GLUT1, autophagy, and endocrine resistance remains unclear. Our present study found that GLUT1 expression and autophagy flux were upregulated in the tamoxifen-resistant breast cancer cell line MCF-7/TAMR-1 and that knockdown of GLUT1 promoted sensitization to tamoxifen. Moreover, knockdown of GLUT1 significantly decreased the enhancement of autophagy flux in tamoxifen-resistant cell lines. Furthermore, inhibiting autophagy in tamoxifen-resistant cells resulted in sensitization to tamoxifen. We conclude that GLUT1 contributes to tamoxifen resistance in breast cancer and that tamoxifen-resistant cells become resensitized to tamoxifen after GLUT1 silencing. These findings suggest GLUT1 as a new factor clinically associated with resistance to tamoxifen.

Effect of Different Iron Sources on In-Situ Growth of Zeolitic Imidazolate Frameworks-8: For Efficient Oxygen Reduction Electrocatalysts.

Transition metal and nitrogen co-doped carbon-based catalysts (TM-N-C) have become the most promising catalysts for Pt/C due to their wide range of sources, low cost, high catalytic activity, excellent stability and strong resistance to poisoning, especially Fe-N-C metal-organic frameworks (MOFs), which are some of the most promising precursors for the preparation of Fe-N-C catalysts due to their inherent properties, such as their highly ordered three-dimensional framework structure, controlled porosity, and tuneable chemistry. Based on these, in this paper, different iron sources were added to synthesis a sort of zeolitic imidazole frameworks (ZIF-8). Then the imidazole salt in ZIF-8 was rearranged into high N-doped carbon by high-temperature pyrolysis to prepare the Fe-N-C catalyst. We studied the physical characteristics of the catalysts by different iron sources and their effects on the catalytic properties of the oxygen reduction reaction (ORR). From the point of morphology, various iron sources have a positive influence on maintaining the morphology of ZIF-8 polyhedron. Fe-N/C-Fe(NO3)3 has the same anion as zinc nitrate, and can maintain a polyhedral morphology after high-temperature calcination. It had the highest ORR catalytic activity compared to the other four catalyst materials, which proved that there is a certain relationship between morphology and performance. This paper will provide a useful reference and new models for the development of high-performance ORR catalysts without precious metals.

Cancer Cell-Erythrocyte Hybrid Membrane Coated Gold Nanocages for Near Infrared Light-Activated Photothermal/Radio/Chemotherapy of Breast Cancer.

BACKGROUND: The combination of radiotherapy (RT) and chemotherapy, as a standard treatment for breast cancer in the clinic, is unsatisfactory due to chemoradioresistance and severe side effects. METHODS AND RESULTS: To address these issues, a cancer cell-erythrocyte hybrid membrane-coated doxorubicin (DOX)-loaded gold nanocage (CM-EM-GNCs@DOX) was constructed for near-infrared light (NIR)-activated photothermal/radio/chemotherapy of breast cancer. CM-EM-GNCs@DOX inherited an excellent homologous target ability from the cancer cell membrane and an immune evasion capability from the erythrocyte membrane, together resulting in highly efficient accumulation in the tumor site with decreased clearance. Following the highly efficient uptake of CM-EM-GNCs@DOX in cancer cells, the RT efficacy was remarkably amplified due to the radiosensitization effect of CM-EM-GNCs@DOX, which reduced the needed radiotherapeutic dose. Importantly, with NIR irradiation, CM-EM-GNCs@DOX exerted a high photothermal effect, which not only ruptured CM-EM-GNCs@DOX to release DOX for precise and controllable chemotherapy, but also potentiated chemo/radiotherapy by photothermal therapy. CONCLUSION: Therefore, a highly efficient and safe combined photothermal/radio/chemotherapy approach was achieved in vitro and in vivo by CM-EM-GNCs@DOX, which provided a promising strategy for treating breast cancer.

Various Morphology of WO3 Modified Activated Carbon Supported Pd Catalysts with Enhanced Formic Acid Electrooxidation.

Activated carbon support Pd nanoparticles (NPs) modified by various WO3-shaped catalysts were prepared and applied as an efficient anode catalyst for direct formic acid fuel cells. Three forms of WO3 (nanosheets, nanoparticles, nanobars) modified activated carbon hybrids were first prepared via different syntheses, and then used as supports to synthesize three types of Pd-WO3/C catalysts by a NaBH4 reduction method. The morphology, structure, and electrochemical performances of the as-prepared Pd-WO3/C catalysts were characterized and analyzed. We can see that the noble metal particles loaded with activated carbon modified by WO3 exhibit small particle size and uniform dispersion from the transmission electron microscope image. The synthesized composite catalysts was used for the formic acid electrooxidation and showed excellent catalytic performance. The oxidation peak current density of the Pd/WO3-Nanosheets/C (40.04 mA·cm-2 was the highest, approximately 1.2 times that of Pd/C (33.00 mA·cm-2. Additionally, the long-term stability (i-t) test results show that the Pd/WO3-Nanosheets/C catalyst exhibits superior stability during formic acid electrooxidation. The reason for the increase in performance can be attributed to the following: the large specific surface area of WO3 decreases the adsorption strength of intermediates such as COad on Pd and prevents the accumulation of poisonous intermediates, thereby promoting the oxidation reaction of formic acid in the direct pathway; the catalyst-support interaction between precious metal Pd and WO3, substantially improving the catalytic performance of Pd-WO3/C catalysts.

Enabling phenotypic big data with PheNorm.

Objective: Electronic health record (EHR)-based phenotyping infers whether a patient has a disease based on the information in his or her EHR. A human-annotated training set with gold-standard disease status labels is usually required to build an algorithm for phenotyping based on a set of predictive features. The time intensiveness of annotation and feature curation severely limits the ability to achieve high-throughput phenotyping. While previous studies have successfully automated feature curation, annotation remains a major bottleneck. In this paper, we present PheNorm, a phenotyping algorithm that does not require expert-labeled samples for training. Methods: The most predictive features, such as the number of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes or mentions of the target phenotype, are normalized to resemble a normal mixture distribution with high area under the receiver operating curve (AUC) for prediction. The transformed features are then denoised and combined into a score for accurate disease classification. Results: We validated the accuracy of PheNorm with 4 phenotypes: coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. The AUCs of the PheNorm score reached 0.90, 0.94, 0.95, and 0.94 for the 4 phenotypes, respectively, which were comparable to the accuracy of supervised algorithms trained with sample sizes of 100-300, with no statistically significant difference. Conclusion: The accuracy of the PheNorm algorithms is on par with algorithms trained with annotated samples. PheNorm fully automates the generation of accurate phenotyping algorithms and demonstrates the capacity for EHR-driven annotations to scale to the next level - phenotypic big data.