In Situ Transmission Electron Microscopy Methods for Lithium-Ion Batteries.

In situ Transmission Electron Microscopy (TEM) stands as an invaluable instrument for the real-time examination of the structural changes in materials. It features ultrahigh spatial resolution and powerful analytical capability, making it significantly versatile across diverse fields. Particularly in the realm of Lithium-Ion Batteries (LIBs), in situ TEM is extensively utilized for real-time analysis of phase transitions, degradation mechanisms, and the lithiation process during charging and discharging. This review aims to provide an overview of the latest advancements in in situ TEM applications for LIBs. Additionally, it compares the suitability and effectiveness of two techniques: the open cell technique and the liquid cell technique. The technical aspects of both the open cell and liquid cell techniques are introduced, followed by a comparison of their applications in cathodes, anodes, solid electrolyte interphase (SEI) formation, and lithium dendrite growth in LIBs. Lastly, the review concludes by stimulating discussions on possible future research trajectories that hold potential to expedite the progression of battery technology.

Bioprinted dermis with human adipose tissue-derived microvascular fragments promotes wound healing.

Tissue-engineered skin is an effective material for treating large skin defects in a clinical setting. However, its use is limited owing to vascular complications. Human adipose tissue-derived microvascular fragments (HaMVFs) are vascularized units that form vascular networks by rapid reassembly. In this study, we designed a vascularized bionic skin tissue using a three-dimensional (3D) bioprinter of HaMVFs and human fibroblasts encapsulated in a hybrid hydrogel composed of GelMA, HAMA, and fibrinogen. Tissues incorporating HaMVFs showed good in vitro vascularization and mechanical properties after UV crosslinking and thrombin exposure. Thus, the tissue could be sutured appropriately to the wound. In vivo, the vascularized 3D bioprinted skin promoted epidermal regeneration, collagen maturation in the dermal tissue, and vascularization of the skin tissue to accelerate wound healing. Overall, vascularized 3D bioprinted skin with HaMVFs is an effective material for treating skin defects and may be clinically applicable to reduce the necrosis rate of skin grafts.

Si-Based High-Entropy Anode for Lithium-Ion Batteries.

Up to now, only a small portion of Si has been utilized in the anode for commercial lithium-ion batteries (LIBs) despite its high energy density. The main challenge of using micron-sized Si anode is the particle crack and pulverization due to the volume expansion during cycling. This work proposes a type of Si-based high-entropy alloy (HEA) materials with high structural stability for the LIB anode. Micron-sized HEA-Si anode can deliver a capacity of 971 mAhg-1 and retains 93.5% of its capacity after 100 cycles. In contrast, the silicon-germanium anode only retains 15% of its capacity after 20 cycles. This study has discovered that including HEA elements in Si-based anode can decrease its anisotropic stress and consequently enhance ductility at discharged state. By utilizing in situ X-ray diffraction and transmission electron microscopy analyses, a high-entropy transition metal doped Lix (Si/Ge) phase is found at lithiated anode, which returns to the pristine HEA phase after delithiation. The reversible lithiation and delithiation process between the HEA phases leads to intrinsic stability during cycling. These findings suggest that incorporating high-entropy modification is a promising approach in designing anode materials toward high-energy density LIBs.

Angiopoietin-like 4 promotes epidermal stem cell proliferation and migration and contributes to cutaneous wound re-epithelialization.

Proliferation and migration of epidermal stem cells (EpSCs) are essential for epithelialization during skin wound healing. Angiopoietin-like 4 (ANGPTL4) has been reported to play an important role in wound healing, but the mechanisms involved are not fully understood. Here, we investigate the contribution of ANGPTL4 to full-thickness wound re-epithelialization and the underlying mechanisms using Angptl4-knockout mice. Immunohistochemical staining reveals that ANGPTL4 is significantly upregulated in the basal layer cells of the epidermis around the wound during cutaneous wound healing. ANGPTL4 deficiency impairs wound healing. H&E staining shows that ANGPTL4 deficiency significantly reduces the thickness, length and area of the regenerated epidermis postwounding. Immunohistochemical staining for markers of EpSCs (α6 integrin and ß1 integrin) and cell proliferation (PCNA) shows that the number and proliferation of EpSCs in the basal layer of the epidermis are reduced in ANGPTL4-deficient mice. In vitro studies show that ANGPTL4 deficiency impedes EpSC proliferation, causes cell cycle arrest at the G1 phase and reduces the expressions of cyclins D1 and A2, which can be reversed by ANGPTL4 overexpression. ANGPTL4 deletion suppresses EpSC migration, which is also rescued by ANGPTL4 overexpression. Overexpression of ANGPTL4 in EpSCs accelerates cell proliferation and migration. Collectively, our results indicate that ANGPTL4 promotes EpSC proliferation by upregulating cyclins D1 and A2 expressions and accelerating the cell cycle transition from G1 to S phase and that ANGPTL4 promotes skin wound re-epithelialization by stimulating EpSC proliferation and migration. Our study reveals a novel mechanism underlying EpSC activation and re-epithelialization during cutaneous wound healing.

Exploration and validation of m7G-related genes as signatures in the immune microenvironment and prognostic indicators in low-grade glioma.

OBJECTIVES: Currently, an increasing number of studies are focusing on the impact of m7G modification in cancer. This study aims to investigate the prognostic value of m7G-related genes in low-grade glioma (LGG). METHODS: LGG samples were obtained from the CGGA database, and normal samples were obtained from GTEx. Differentially expressed m7G-related genes were identified, and genes highly associated with macrophage M2 in LGG patients were identified by immuno-infiltration and WGCNA analysis. The intersection of differentially expressed m7G-related genes and macrophage M2-associated genes yielded candidate genes, and hub genes were identified using 5 algorithms in CytoHubba. Enrichment analysis verified the relevant pathways of hub genes, and their performance in tumor classification was evaluated. RESULTS: A total of 3329 differentially expressed m7G-related genes were identified. 1289 genes were highly associated with macrophage M2 in LGG patients. The intersection of m7G-related genes and results in WGCNA yielded 840 candidate genes, and six hub genes (STXBP1, CPLX1, PAB3A, APBA1, RIMS1, and GRIN2B) were identified. Hub genes were enriched in synaptic transmission-related pathways and showed good performance for tumor classification. There were significant differences in survival levels between clusters. CONCLUSIONS: The identified m7G-related genes may provide new insight into the treatment and prognosis of LGG.

Integrated Surface Modulation of Ultrahigh Ni Cathode Materials for Improved Battery Performance.

Ni-rich layered cathodes with ultrahigh nickel content (≥90%), for example LiNi0.9 Co0.1 O2 (NC0.9), are promising for next-generation high-energy Li-ion batteries (LIBs), but face stability issues related to structural degradation and side reactions during the electrochemical process. Here, surface modulation is demonstrated by integrating a Li+ -conductive nanocoating and gradient lattice doping to stabilize the active cathode efficiently for extended cycles. Briefly, a wet-chemistry process is developed to deposit uniform ZrO(OH)2 nanoshells around Ni0.905 Co0.095 (OH)2 (NC0.9-OH) hydroxide precursors, followed by high temperature lithiation to create reinforced products featuring Zr doping in the crust lattice decorated with Li2 ZrO3 nanoparticles on the surface. It is identified that the Zr4+ infiltration reconstructed the surface lattice into favorable characters such as Li+ deficiency and Ni3+ reduction, which are effective to combat side reactions and suppress phase degradation and crack formation. This surface control is able to achieve an optimized balance between surface stabilization and charge transfer, resulting in an extraordinary capacity retention of 96.6% after 100 cycles at 1 C and an excellent rate capability of 148.8 mA h g-1 at 10 C. This study highlights the critical importance of integrated surface modulation for high stability of cathode materials in next-generation LIBs.

miR-100-5p Promotes Epidermal Stem Cell Proliferation through Targeting MTMR3 to Activate PIP3/AKT and ERK Signaling Pathways.

Skin epidermal stem cells (EpSCs) play a critical role in wound healing and are ideal seed cells for skin tissue engineering. Exosomes from human adipose-derived stem cells (ADSC-Exos) promote human EpSC proliferation, but the underlying mechanism remains unclear. Here, we investigated the effect of miR-100-5p, one of the most abundant miRNAs in ADSC-Exos, on the proliferation of human EpSCs and explored the mechanisms involved. MTT and BrdU incorporation assays showed that miR-100-5p mimic transfection promoted EpSC proliferation in a time-dependent manner. Cell cycle analysis showed that miR-100-5p mimic transfection significantly decreased the percentage of cells in the G1 phase and increased the percentage of cells in the G2/M phase. Myotubularin-related protein 3 (MTMR3), a lipid phosphatase, was identified as a direct target of miR-100-5p. Knockdown of MTMR3 in EpSCs by RNA interference significantly enhanced cell proliferation, decreased the percentage of cells in the G1 phase and increased the percentage of cells in the S phase. Overexpression of MTMR3 reversed the proproliferative effect of miR-100-5p on EpSCs, indicating that miR-100-5p promoted EpSC proliferation by downregulating MTMR3. Mechanistic studies showed that transfection of EpSCs with miR-100-5p mimics elevated the intracellular PIP3 level, induced AKT and ERK phosphorylation, and upregulated cyclin D1, E1, and A2 expression, which could be attenuated by MTMR3 overexpression. Consistently, intradermal injection of ADSC-Exos or miR-100-5p-enriched ADSC-Exos into cultured human skin tissues significantly reduced MTMR3 expression and increased the thickness of the epidermis and the number of EpSCs in the basal layer of the epidermis. The aforementioned effect of miR-100-5p-enriched ADSC-Exos was stronger than that of ADSC-Exos and was reversed by MTMR3 overexpression. Collectively, our findings indicate that miR-100-5p promotes EpSC proliferation through MTMR3-mediated elevation of PIP3 and activation of AKT and ERK. miR-100-5p-enriched ADSC-Exos can be used to treat skin wound and expand EpSCs for generating epidermal autografts and engineered skin equivalents.

Integrative analysis of CBR1 as a prognostic factor associated with IDH-mutant glioblastoma in the Chinese population.

BACKGROUND: Glioblastoma multiforme (GBM) is a common primary intracranial tumor with poor prognosis. Common indicators in the clinical diagnosis of glioma include MGMT promoter methylation, isocitrate dehydrogenase (IDH) mutation, 1p/19q codeletion, and TERT mutation. Among these, IDH mutation is extremely important for GBM diagnosis and treatment. METHODS: The Chinese Glioma Population Database (CGGA) and Gene Expression Omnibus (GEO) data (GSE131273) related to glioma in the Chinese population were used for differential analysis (DGA) and weighted gene coexpression network analysis (WGCNA). The expression levels of hub genes between the IDH1 wild-type and mutant GBM cell lines were detected by RT-qPCR. Kaplan-Meier (KM) plotter was used to analyze hub gene expression levels and prognostic values. RESULTS: Eight hub genes were identified by WGCNA and different expression genes (DEG) analysis, namely, one upregulated gene (CRYAB) and seven downregulated genes (EFEMP2, RBP1, TAGLN2, CBR1, MSN, ALDH7A1, and MT1M). Four of these genes (ALDH7A1, MSN, CBR1, and MTM1) showed significant differences between IDH-wild-type and IDH-mutant GBM, verified at the cellular level. Moreover, the high expression of CBR1 was significantly correlated with poor overall survival (OS) in patients with IDH-mutant GBM, and we finally identified CBR1 as a specific prognostic factor in IDH-mutant GBM. CONCLUSION: Results revealed different gene expressions between IDH-wild-type and IDH-mutant GBM. These genes may help monitor the occurrence and development of glioma. CBR1 can be used as a prognostic marker to identify IDH-mutant glioblastoma patients.

Patient-derived orthotopic xenograft models of medulloblastoma lack a functional blood-brain barrier.

BACKGROUND: Novel targeted therapies for children diagnosed with medulloblastoma (MB), the most common malignant pediatric brain tumor, are urgently required. A major hurdle in the development of effective therapies is the impaired delivery of systemic therapies to tumor cells due to a specialized endothelial blood-brain barrier (BBB). Accordingly, the integrity of the BBB is an essential consideration in any preclinical model used for assessing novel therapeutics. This study sought to assess the functional integrity of the BBB in several preclinical mouse models of MB. METHODS: Dynamic contrast enhancement magnetic resonance imaging (MRI) was used to evaluate blood-brain-tumor barrier (BBTB) permeability in a murine genetically engineered mouse model (GEMM) of Sonic Hedgehog (SHH) MB, patient-derived orthotopic xenograft models of MB (SHH and Gp3), and orthotopic transplantation of GEMM tumor cells, enabling a comparison of the direct effects of transplantation on the integrity of the BBTB. Immunofluorescence analysis was performed to compare the structural and subcellular features of tumor-associated vasculature in all models. RESULTS: Contrast enhancement was observed in all transplantation models of MB. No contrast enhancement was observed in the GEMM despite significant tumor burden. Cellular analysis of BBTB integrity revealed aberrancies in all transplantation models, correlating to the varying levels of BBTB permeability observed by MRI in these models. CONCLUSIONS: These results highlight functional differences in the integrity of the BBTB and tumor vessel phenotype between commonly utilized preclinical models of MB, with important implications for the preclinical evaluation of novel therapeutic agents for MB.

Inhibition of CDK4/6 by Palbociclib Significantly Extends Survival in Medulloblastoma Patient-Derived Xenograft Mouse Models.

Purpose: Bioinformatics analysis followed by in vivo studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 MYC-amplified tumors that have the worst clinical prognosis.Experimental Design: A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets. The top hit from this analysis was validated in vivo using PDX models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice.Results: Informatics analysis identified the CDK4/6/CYCLIN D/RB pathway as a novel "druggable" pathway for multiple subgroups of medulloblastoma. Palbociclib, a highly specific inhibitor of CDK4/6, was found to inhibit RB phosphorylation and cause G1 arrest in PDX models of medulloblastoma. The drug caused rapid regression of Sonic hedgehog (SHH) and MYC-amplified group 3 medulloblastoma subcutaneous tumors and provided a highly significant survival advantage to mice bearing MYC-amplified intracranial tumors.Conclusions: Inhibition of CDK4/6 is potentially a highly effective strategy for the treatment of SHH and MYC-amplified group 3 medulloblastoma. Clin Cancer Res; 23(19); 5802-13. ©2017 AACR.