The prognostic impact of pathogenic stromal cell-associated genes in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) stands as the most prevalent subtype among lung cancers. Interactions between stromal and cancer cells influence tumor growth, invasion, and metastasis. However, the regulatory mechanisms of stromal cells in the lung adenocarcinoma tumor microenvironment remain unclear. This study seeks to elucidate the regulatory connections among critical pathogenic genes and their associated expression variations within distinct stromal cell subtypes. METHOD: Analysis and investigation were conducted on a total of 114,019 single-cell RNA data and 346 The Cancer Genome Atlas (TCGA) LUAD-related samples using bioinformatics and statistical algorithms. Differential gene expression analysis was performed for tumor samples and controls, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differential genes between stromal cells and other cell clusters were identified and intersected with the differential genes from TCGA. We employed a combination of LASSO regression and multivariable Cox regression to identify the ultimate set of pathogenic gene. Survival models were trained to predict the relationship between patient survival and these pathogenic genes. Analysis of transcription factor (TF) cell specificity and pseudotime trajectories within stromal cell subpopulations revealed that vascular endothelial cells (ECs) and matrix cancer-associated fibroblasts (CAFs) are key in regulation of the prognosis-associated genes CAV2, COL1A1, TIMP1, ETS2, AKAP12, ID1 and COL1A2. RESULTS: Seven pathogenic genes associated with LUAD in stromal cells were identified and used to develop a survival model. High expression of these genes is linked to a greater risk of poor survival. Stromal cells were categorized into eight subtypes and one unannotated cluster. Mesothelial cells, vascular endothelial cells (ECs), and matrix cancer-associated fibroblasts (CAFs) showed cell-specific regulation of the pathogenic genes. CONCLUSIONS: The seven disease-causing genes in vascular ECs and matrix CAFs can be used to detect the survival status of LUAD patients, providing new directions for future targeted drug design.

Melt memory in random ethylene-1-alkene copolymers.

Chain flexibility or stiffness based polymer conformation plays a crucial role in affecting the dynamics and kinetics of polymers, which is related to the hierarchical architecture of chains. A series of random copolymers of ethylene and 1-alkenes including 1-hexene, 1-octene, and 1-dodecene were synthesized with metallocene catalysts. The crystallization behavior and memory effect in random ethylene-1-alkene copolymers with different side groups were investigated via differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). Rheological tests were performed for understanding their dynamical behavior. The results show that the melting peak and the viscosity decrease but the orthorhombic crystal dimensions increase with co-unit contents increasing in the copolymers. It was found that the scaling relationship between the zero shear viscosity (η0) and molecular weight (Mn) of the copolymers containing ethylene-1-hexene and ethylene-1-octene is 3.6, which is higher than the classical scaling value of 3.4. The memory of crystals in the melt is enhanced with the increase of 1-alkene contents but is independent of the types of 1-alkenes. The enhanced melt memory effect in the copolymers was proposed due to the effect of the 1-alkene based side groups on the dynamics of polymer chains. The present work would be helpful to understand the chain stiffness based polymer dynamics and processing of polyolefins and copolymers prepared with the metallocene catalyst.

Limitations and modifications in the clinical application of calcium sulfate.

Calcium sulfate and calcium sulfate-based biomaterials have been widely used in non-load-bearing bone defects for hundreds of years due to their superior biocompatibility, biodegradability, and non-toxicity. However, lower compressive strength and rapid degradation rate are the main limitations in clinical applications. Excessive absorption causes a sharp increase in sulfate ion and calcium ion concentrations around the bone defect site, resulting in delayed wound healing and hypercalcemia. In addition, the space between calcium sulfate and the host bone, resulting from excessively rapid absorption, has adverse effects on bone healing or fusion techniques. This issue has been recognized and addressed. The lack of sufficient mechanical strength makes it challenging to use calcium sulfate and calcium sulfate-based biomaterials in load-bearing areas. To overcome these defects, the introduction of various inorganic additives, such as calcium carbonate, calcium phosphate, and calcium silicate, into calcium sulfate is an effective measure. Inorganic materials with different physical and chemical properties can greatly improve the properties of calcium sulfate composites. For example, the hydrolysis products of calcium carbonate are alkaline substances that can buffer the acidic environment caused by the degradation of calcium sulfate; calcium phosphate has poor degradation, which can effectively avoid the excessive absorption of calcium sulfate; and calcium silicate can promote the compressive strength and stimulate new bone formation. The purpose of this review is to review the poor properties of calcium sulfate and its complications in clinical application and to explore the effect of various inorganic additives on the physicochemical properties and biological properties of calcium sulfate.

Surface modification of zinc oxide and its application in polypropylene with excellent fire performance and ultra-violet resistance.

Despite the advantages of easy moulding and excellent mechanical properties, there are still some shortcomings with polypropylene (PP) such as high flammability and poor ultra-violet (UV) resistance. In this work, modified zinc oxide (mZnO) was prepared by reacting zinc oxide nanoparticles (ZnO) with polysiloxanes, and the effect of mZnO on the effectiveness of intumescent flame-retardant and on the UV aging resistance of polypropylene were investigated. By introducing 16 wt% (intumescent flame-retardant /mZnO) and 0.3 wt% maleic anhydride-grafted PP (MAH-g-PP), the limiting oxygen index increased to 32.7 %, and passed UL-94V-0 rating. In comparison to the controls, the peak heat release rate and the peak smoke release rate were 88.5 % and 80 % lower, respectively. In addition, PP samples showed improved mechanical properties, with a 5 % increase in tensile properties compared to the pure PP sample. After 100 h of UV irradiation, the surface of the samples was relatively flat and smooth, and the carbonyl index decreased from 81.1 of neat PP to 26.7. PP composites with 100 h aging treatment still had excellent flame retardancy and mechanical properties. The results showed that mZnO was effective in improving the flame retardancy, mechanical properties and light aging tolerance of PP. This study provides a novel approach to fabricate long-life flame-retardant PP composites with low additive content.

Boerechalasins A-G, cytochalasans from the fungus Boeremia exigua with anti-inflammatory and cytotoxic activities.

Seven previously undescribed cytochalasans, namely, boerechalasins A-G, together with one analogue, were characterized from the solid culture of the fungus Boeremia exigua. Their structures and absolute configurations were elucidated on the basis of extensive spectroscopic analysis as well as electronic circular dichroism calculations. Remarkably, boerechalasin F possessed an unusual sulfoxide moiety that might be derived from methionine, while boerechalasin G had an unusual 5-methylcyclohexane-1,2,3-triol substituent at N-2 position. Boerechalasins A and E exhibited inhibitory activities against nitric oxide production in LPS-induced RAW264.7 macrophages with IC50 values of 21.9 and 5.7 µM, respectively. Boerechalasin F displayed cytotoxicity against human MCF‒7 cells with an IC50 value of 22.8 µM.

Cross-linked polyaniline for production of long lifespan aqueous iron||organic batteries with electrochromic properties.

Aqueous iron batteries are appealing candidates for large-scale energy storage due to their safety and low-cost aspects. However, the development of aqueous Fe batteries is hindered by their inadequate long-term cycling stability. Here, we propose the synthesis and application as positive electrode active material of cross-linked polyaniline (C-PANI). We use melamine as the crosslinker to improve the electronical conductivity and electrochemical stability of the C-PANI. Indeed, when the C-PANI is tested in combination with a Fe metal negative electrode and 1 M iron trifluoromethanesulfonate (Fe(TOF)2) electrolyte solution, the coin cell can deliver a specific capacity of about 110 mAh g-1 and an average discharge voltage of 0.55 V after 39,000 cycles at 25 A g-1 with a test temperature of 28 °C ± 1 °C. Furthermore, mechanistic studies suggest that Fe2+ ions are bonded to TOF- anions to form positively charged complexes Fe(TOF)+, which are stored with protons in the C-PANI electrode structures. Finally, we also demonstrate the use of C-PANI in combination with a polymeric hydrogel electrolyte to produce a flexible reflective electrochromic lab-scale iron battery prototype.

Brominated flame retardants coated separators for high-safety lithium-sulfur batteries.

Lithium-sulfur batteries (LSBs) have become highly promising next-generation secondary lithium batteries owing to their high theoretical energy density and abundance of sulfur. Nevertheless, the large-scale application of LSBs is still restricted by the shuttle effect of lithium polysulfide (LiPSs) and the potential fire hazard caused by flammable electrolytes. Herein, three electrolyte-insoluble brominated flame retardants (BFRs) are selected and coated on both sides of commercial polypropylene separators by a facile slurry coating method. The effects of the three BFRs on the safety and electrochemical properties of LSBs are characterized and compared. The coating modification separators greatly improves the flame retardancy of LSBs through radical elimination mechanism. The self-extinguishing time of the electrolyte is reduced from 0.66 s/mg to 0.20 s/mg. Moreover, it is demonstrated that the oxygen (O)-containing BFRs exert a significant adsorption capacity and are more advantageous than O-free BFRs in LSBs. In addition, octabromoether (BDDP) coated separator is more effective in trapping LiPSs than decabromodiphenyl ether (DBDPO) due to higher O content, which can mitigate the shuttle effect and enhance the cycle and rate performance of LSBs. This simple coating strategy for separators with BFRs offers a strongly competitive option for the large-scale production of high-safety LSBs.

Unsupervised construction of gene regulatory network based on single-cell multi-omics data of colorectal cancer.

Identifying gene regulatory networks (GRNs) at the resolution of single cells has long been a great challenge, and the advent of single-cell multi-omics data provides unprecedented opportunities to construct GRNs. Here, we propose a novel strategy to integrate omics datasets of single-cell ribonucleic acid sequencing and single-cell Assay for Transposase-Accessible Chromatin using sequencing, and using an unsupervised learning neural network to divide the samples with high copy number variation scores, which are used to infer the GRN in each gene block. Accuracy validation of proposed strategy shows that approximately 80% of transcription factors are directly associated with cancer, colorectal cancer, malignancy and disease by TRRUST; and most transcription factors are prone to produce multiple transcript variants and lead to tumorigenesis by RegNetwork database, respectively. The source code access are available at: https://github.com/Cuily-v/Colorectal_cancer.

Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance.

Immunological protection of transplanted stem cell-derived islet (SC-islet) cells is yet to be achieved without chronic immunosuppression or encapsulation. Existing genetic engineering approaches to produce immune-evasive SC-islet cells have so far shown variable results. Here, we show that targeting human leukocyte antigens (HLAs) and PD-L1 alone does not sufficiently protect SC-islet cells from xenograft (xeno)- or allograft (allo)-rejection. As an addition to these approaches, we genetically engineer SC-islet cells to secrete the cytokines interleukin-10 (IL-10), transforming growth factor ß (TGF-ß), and modified IL-2 such that they promote a tolerogenic local microenvironment by recruiting regulatory T cells (Tregs) to the islet grafts. Cytokine-secreting human SC-ß cells resist xeno-rejection and correct diabetes for up to 8 weeks post-transplantation in non-obese diabetic (NOD) mice. Thus, genetically engineering human embryonic SCs (hESCs) to induce a tolerogenic local microenvironment represents a promising approach to provide SC-islet cells as a cell replacement therapy for diabetes without the requirement for encapsulation or immunosuppression.

Environmental benign foam finishing with a hyperbranched polyphosphonate flame retardant for polyethylene terephthalate fabric.

It is still a big challenge for textile industry in improving fire resistance and reducing melt dripping with minimal loss on the physical properties of polyethylene terephthalate (PET) fabrics. In this work, a highly-effective hyperbranched flame retardant (DT) was first synthesized by ester exchange without using any organic solvent. Then, the DT foam was prepared and blade coated on PET fabric to improve the fire performance. The prepared PET fabric with only 2.7% weight gain of DT was self-extinguished and did not produce any molten dripping during the vertical flammable test. The peak heat release rate and total heat release of the PET fabric sample with 19.4% DT were decreased by 42.0% and 57.1%, respectively compared with that of the control PET. Besides, the as-prepared PET fabric sample showed better physical properties such as breaking strength, vapor permeability, air permeability, antistatic property, and softness than the control PET fabric sample. The DT foam finishing process did not involve any organic solvent and consumed less water and energy compared with conventional fabric treatments. It is expected that this work provides a facile and eco-friendly strategy for fabricating flame retardant PET fabric with excellent comprehensive performances.

Andrographolide inhibits murine embryonic neuronal development through PFKFB3-mediated glycolytic pathway.

Dysregulation of neuronal development may cause neurodevelopmental disorders. However, how to regulate embryonic neuronal development and whether this regulation can be medical interrupted are largely unknown. This study aimed to investigate whether and how andrographolide (ANP) regulates embryonic neuronal development. The pregnant mice at embryonic day 10.5 (E10.5) were administrated with ANP, and the embryonic brains were harvested at E17.5 or E18.5. Immunofluorescence (IF), Immunohistochemistry (IHC) performed to determine whether ANP is critical in regulating neuronal development. Real-time quantitative PCR, western blotting, cell counting kit-8 assay, Flow Cytometry assay, Boyden Chamber Migration assay carried out to evaluate whether ANP regulates neuronal proliferation and migration. Protein-protein interaction, CO-immunoprecipitation and IF staining carried out to evaluate whether ANP regulates the interaction between PFKFB3, NeuN and TBR1. Knockdown or overexpression of PFKFB3 by adenovirus infection were used to determine whether ANP inhibits neuronal development through PFKFB3 mediated glycolytic pathway. Our data indicated that ANP inhibited the maturation of embryonic neurons characterized by suppressing neuronal proliferation and migration. ANP regulated the interaction between PFKFB3, NeuN, and TBR1. Knockdown of PFKFB3 aggravated ANP mediated inhibition of neuronal proliferation and migration, while overexpression of PFKFB3 attenuated ANP mediated neuronal developmental suppression. In summary, ANP suppressed the expression of PFKFB3, and interrupted the interaction between TRB1 and NeuN, resulting in suppressing neuronal proliferation, migration and maturation and eventually inhibiting murine embryonic neuronal development.

Identification of adaptor proteins by incorporating deep learning and PSSM profiles.

Adaptor proteins, also known as signal transduction adaptor proteins, are important proteins in signal transduction pathways, and play a role in connecting signal proteins for signal transduction between cells. Studies have shown that adaptor proteins are closely related to some diseases, such as tumors and diabetes. Therefore, it is very meaningful to construct a relevant model to accurately identify adaptor proteins. In recent years, many studies have used a position-specific scoring matrix (PSSM) and neural network methods to identify adaptor proteins. However, ordinary neural network models cannot correlate the contextual information in PSSM profiles well, so these studies usually process 20×N (N > 20) PSSM into 20×20 dimensions, which results in the loss of a large amount of protein information; This research proposes an efficient method that combines one-dimensional convolution (1-D CNN) and a bidirectional long short-term memory network (biLSTM) to identify adaptor proteins. The complete PSSM profiles are the input of the model, and the complete information of the protein is retained during the training process. We perform cross-validation during model training and test the performance of the model on an independent test set; in the data set with 1224 adaptor proteins and 11,078 non-adaptor proteins, five indicators including specificity, sensitivity, accuracy, area under the receiver operating characteristic curve (AUC) metric and Matthews correlation coefficient (MCC), were employed to evaluate model performance. On the independent test set, the specificity, sensitivity, accuracy and MCC were 0.817, 0.865, 0.823 and 0.465, respectively. Those results show that our method is better than the state-of-the art methods. This study is committed to improve the accuracy of adaptor protein identification, and laid a foundation for further research on diseases related to adaptor protein. This research provided a new idea for the application of deep learning related models in bioinformatics and computational biology.

Factors Influencing Nonunion and Fracture Following Biological Intercalary Reconstruction for Lower-Extremity Bone Tumors: A Systematic Review and Pooled Analysis.

OBJECTIVES: To determine nonunion rate, fracture rate, and their risk factors following biological intercalary reconstruction for lower extremity bone tumors. METHODS: A systematic review and pooled analysis were conducted. PubMed, Embase, and Wiley Cochrane Library were searched from inception up to June 01, 2020. Studies concerning biological intercalary reconstruction after resection of lower extremity bone tumors were included. Overall nonunion and fracture rates were calculated. For studies reporting patient outcomes individually with precise graft characteristics and fixation methods, the individual data were extracted. Patients with demographical and clinical characteristics, including age, sex, tumor location, graft characteristics, and fixation method, were pooled for a multivariate analysis. For each factor of interest, odds ratio (OR), 95% confidence interval (95% CI), and p-value from logistic regression were reported. RESULTS: A total of 2776 articles were identified from the initial literature search and 76 studies (2052 patients) were included. Sixty-nine studies were case series and seven were comparative studies. The overall nonunion rate was 19% (382/2052; range: 0%-53%), and the overall fracture rate was 17% (344/2052; range: 0%-75%). Thirty of the 76 studies (362 patients) reported patients' characteristics individually and were thus included in the pooled multivariate analysis. Intramedullary nail fixation was associated with a significantly higher nonunion rate compared to plate fixation (OR = 2.2, 95% CI: 1.23-4.10, p = 0.009). Reconstruction with a vascularized fibula graft had a statistically non-significant lower nonunion rate than reconstruction without the graft (OR = 0.6, 95% CI: 0.34-1.07, p = 0.086). Devitalized autografts had a lower fracture risk than allografts (OR = 0.3, 95% CI: 0.14-0.64, p = 0.002), and males tended to have higher fracture risk than females (OR = 2.1, 95% CI: 1.00-4.44, p = 0.049). CONCLUSIONS: Reconstruction with intramedullary nail fixation is related to an elevated risk of nonunion. Allografts and males have a higher fracture risk than devitalized autografts and females, respectively. Further high-quality comparative analyses with large sample sizes and adequate follow-up duration are needed to validate these findings.

Active meiosis during dinoflagellate blooms: A 'sex for proliferation' hypothesis.

In dinoflagellates, sexual reproduction is best known to be induced by adverse environmental conditions and culminate in encystment for survival ('sex for encystment'). Although increasing laboratory observations indicate that sex can lead to production of vegetative cells bypassing encystment, the occurrence of this alternative pathway in natural populations and its ecological roles remain poorly understood. Here we report evidence that sex in dinoflagellates can potentially be an instrument for bloom proliferation or extension. By bloom metatranscriptome profiling, we documented elevated expression of meiosis genes in two evolutionarily distinct species (Prorocentrum shikokuense and Karenia mikimotoi) during bloom, a timing unexpected of the 'sex for encystment' scenario. To link these genes to meiosis, we induced encystment and cyst germination in the cyst-forming species Scrippsiella acuminata, and found that five of these genes were upregulated during cyst germination, when meiosis occurs. Integrating data from all three species revealed that SPO11, MND1, and DMC1 were likely common between cyst-forming and non-encysting sex in dinoflagellates. Furthermore, flow cytometric analyses revealed consecutive rounds of DNA halving during blooms of P. shikokuense and K. mikimotoi, evidencing meiosis. These data provided novel evidence that sexual reproduction in dinoflagellates might serve to promote cell proliferation, and along with the consequent enhancement of genetic diversity facilitating resistance against pathogens and environmental stress, to boost or extend a bloom ('sex for proliferation'). The putative meiosis-specific genes and insights reported here will prove to be helpful for rigorously testing the hypothesis and addressing whether the two modes of sex are genetically predisposed (i.e. species-specific) or environmentally induced (switchable within species), and if the latter what triggers the switch.

Evaluation of different combination of pam2CSK4, poly (I:C) and imiquimod enhance immune responses to H9N2 avian influenza antigen in dendritic cells and duck.

Current commercial H9 avian influenza viruses (AIVs) vaccines cannot provide satisfactory antibody titers and protective immunity against AIVs in duck. Toll like receptors (TLR) ligand as AIVs adjuvants can activate dendritic cells to improve immune responses in multiple animals, while the studies were absent in duck. Therefore, we investigated TLR ligands pam2CSK4, poly (I:C) and/or imiquimod enhance immune responses to inactivated H9N2 avian influenza antigen (H9N2 IAIV) in peripheral blood monocyte-derived dendritic cells (MoDCs) and duck. In vitro, we observed that transcription factor NF-κB, Th1/Th2 type cytokines (IFN-γ, IL-2 and IL-6) and the ability of catching H9N2 IAIV antigen were significantly up-regulated when H9N2 IAIV along with TLR ligands (pam2CSK4, poly (I:C) and imiquimod, alone or combination) in duck MoDCs. Also, the best enhancement effects were showed in combination of pam2CSK4, poly (I:C) and imiquimod group, whereas IFN-α showed no significant enhancement in all experimental groups. In vivo, the results demonstrated that the percentages of CD4+/ CD8+ T lymphocytes, the levels of Th1/Th2 type cytokines and H9N2 HI titers were significant enhanced in combination of pam2CSK4, poly (I:C) and imiquimod group. However, pam2CSK4 alone or combining with imiquimod showed no enhancement or additive effects on Th1 cytokines (IFN-γ and IL-2), Th2 cytokines (IL-6) and HI titers in Muscovy duck, respectively. Taken together, our results concluded that not all TLR ligands showed enhancement of immune responses to H9N2 IAIV in duck. The combination of poly (I:C), imiquimod and pam2CSK4 that can be an effectively adjuvant candidate for H9N2 AIVs inactivated vaccine in duck, which provide novel insights in explore waterfowl vaccine.

Impact of Medical Community Model on Intravenous Alteplase Door-to-Needle Times and Prognosis of Patients With Acute Ischemic Stroke.

Objective: In this study, we retrospectively analyzed 795 AIS patients who received intravenous alteplase for thrombolytic therapy in one third-class hospital or three second-class hospitals in Dongyang City and sought to evaluate the effects of the medical community model on intravenous alteplase door-to-needle time (DNT) and prognosis of patients with acute ischemic stroke. Methods: According to whether the medical community model is established or not, 303 AIS patients (204 cases from the third-class hospital and 99 cases from three second-class hospitals) were assigned to control group unavailable to the medical community model and 492 AIS patients (297 cases from the third-class hospital, and 195 cases from three second-class hospitals) into observational group available to the medical community model. Results: A higher thrombolysis rate, a shorter DNT, more patients with DNT ≤ 60 min and DNT ≤ 45 min, a shorter ONT, lower National Institutes of Health Stroke Scale (NIHSS) scores at 24 h, 7 d, 14 d, and modified Rankin scale (mRS) scores at 3 months after thrombolytic therapy, a shorter length of hospital stay, and less hospitalization expense were found in the observational group than the control group. Subgroup analysis based on different-class hospitals revealed that the medical community model could reduce the DNT and ONT to increase the thrombolysis rate of AIS patients, especially in low-class hospitals. After the establishment of the medical community model, the AIS patients whether from the third-class hospital or three second-class hospitals exhibited lower NIHSS scores at 24 h, 7 d, 14 d after thrombolytic therapy (p < 0.05). After a 90-day follow-up for mRS scores, a significant difference was only noted in the mRS scores of AIS patients from the third-class hospital after establishing the medical community model (p < 0.05). It was also found that the medical community model led to reduced length of hospital stay and hospitalization expenses for AIS patients, especially for the second-class hospitals. Conclusion: The data suggest that the medical community model could significantly reduce intravenous alteplase DNT and improve the prognosis of patients with AIS.

H2 -Inhibited Organic Anodes for Fast and Long-Life Aqueous Aluminum Ion Batteries with a 3.5-Month Calendar Life.

Aqueous aluminum ion batteries are rarely constructed due to the unworkable Al metal and the preferential H2 evolution. Herein, organic anode with H2 -inhibition is optimized through tuning the polymerization degree and displays a high-rate and reversible storage of Al ions based on an enolation between Al ions and the carbonyl double bonds on the conjugated structures. The superiority of the optimal sample is researched, which is attributed to the raised state of lowest unoccupied molecule orbital (LUMO) with the doner N-N bridge and relatively small steric hindrance of the dimmer. When paired with active carbon, a high cycling life of 5000 cycles with a retention of 99.2% is obtained. A full battery constructed by this dimer and δ-MnO2 cathode delivers an average voltage of 1.0 V, high capacity of 263.8 mAh g-1 based on the mass of δ-MnO2 , and high-capacity retention of 88.8% after cycling for 300 cycles. More importantly, with a fully eliminated corrosion and passivation in AlCl3 and Al2 (SO4 )3 electrolytes, a long calendar stability of 104 days is achieved.

Ether-Water Hybrid Electrolyte Contributing to Excellent Mg Ion Storage in Layered Sodium Vanadate.

Magnesium ion batteries have potential for large-scale energy storage. However, the high charge density of Mg2+ ions establishes a strong intercalation energy barrier in host materials, causing sluggish diffusion kinetics and structural degradation. Here, we report that the kinetic and dissolution issues connected to cathode materials can be resolved simultaneously using a tetraethylene glycol dimethyl ether (TEGDME)-water hybrid electrolyte. The lubricating and shielding effect of water solvent could boost the swift transport of Mg2+, contributing to a high diffusion coefficient within the sodium vanadate (NaV8O20·nH2O) cathode. Meanwhile, the organic TEGDME component can coordinate with water to diminish its activity, thus providing the hybrid electrolyte with a broad electrochemical window of 3.9 V. More importantly, the TEGDME preferentially amassed at the interface, leading to a robust cathode electrolyte interface layer that suppresses the dissolution of vanadium species. Consequently, the NaV8O20·nH2O cathode achieved a specific capacity of 351 mAh g-1 at 0.3 A g-1 and a long cycle life of 1000 cycles in this hybrid electrolyte. A mechanism study revealed the reversible interaction of Mg2+ during cycles. This organic water hybrid electrolyte is effective for overcoming the difficulty of multivalent ion storage.

High-Rate Aqueous Aluminum-Ion Batteries Enabled by Confined Iodine Conversion Chemistry.

Most reported cathode materials for rechargeable aqueous Al metal batteries are based on an intercalative-type chemistry mechanism. Herein, iodine embedded in MOF-derived N-doped microporous carbon polyhedrons (I2 @ZIF-8-C) is proposed to be a conversion-type cathode material for aqueous aluminum-ion batteries based on "water-in-salt" electrolytes. Compared with the conventional Al-I2 battery using ionic liquid electrolyte, the proposed aqueous Al-I2 battery delivers much enhanced electrochemical performance in terms of specific capacity and voltage plateaus. Benefitting from the confined liquid-solid conversion of iodine in hierarchical N-doped microporous carbon polyhedrons and enhanced reaction kinetics of aqueous electrolytes, the I2 @ZIF-8-C electrode delivers high reversibility, superior specific capacity (≈219.8 mAh g-1 at 2 A g-1 ), and high rate performance (≈102.6 mAh g-1 at 8 A g-1 ). The reversible reaction between I2 and I- , with I3 - and I5 - as intermediates, is confirmed via ex situ Raman spectra and X-ray photoelectron spectroscopy. Furthermore, solid-state hydrogel electrolyte is employed to fabricate a flexible Al-I2 battery, which shows performance comparable to batteries using liquid electrolyte and can be integrated to power wearable devices as a reliable energy supply.

ErbB4 mediates amyloid ß-induced neurotoxicity through JNK/tau pathway activation: Implications for Alzheimer's disease.

Accumulation of amyloid ß (Aß) in the brain is a hallmark of Alzheimer's disease (AD). We previously showed that ErbB4 in parvalbumin (PV)-positive interneurons was associated with Aß-induced cognitive deficits; however, the underlying mechanism remains undetermined. Here we found that specific deletion of ErbB4 in PV neurons significantly attenuated oligomeric Aß-induced neuronal toxicity and inhibited Aß-induced decreases of PSD95 and synaptophysin. Moreover, specific ablation of ErbB4 in PV neurons altered activity-related protein c-Fos and decreased hippocampal PV neurons, especially in the dentate gyrus (DG) of hAPP-J20 mice. Furthermore, c-Jun N-terminal kinase (JNK), a protein downstream of ErbB4, was activated by Aß but not ErbB4's ligand neuregulin 1 (NRG1) ß1, suggesting different downstream pathways for Aß and NRG1ß1. JNK phosphorylation was inhibited by the ErbB4 inhibitor AG1478 and by pretreatment with NRG1ß1. More importantly, siRNA knockdown of ErbB4 decreased JNK phosphorylation and expression, tau phosphorylation at Ser396 and Thr 205, and Bax expression. Therefore, ErbB4 might mediate Aß-induced neuropathology through the JNK/tau pathway and represent a potential therapeutic target in patients with AD.