TIE2 expression in hypertensive ICH and its therapeutic modulation with AKB-9778: Implications for brain vascular health.

Hypertensive intracerebral hemorrhage (ICH) is a devastating condition, the molecular underpinnings of which remain not fully understood. By leveraging high-throughput transcriptome sequencing and network pharmacology analysis, this study unveils the significant role of the tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) in ICH pathogenesis. Compared to controls, a conspicuous downregulation of TIE2 was observed in the cerebral blood vessels of hypertensive ICH mice. In vitro assays with human brain microvascular endothelial cells (HBMEC), HBEC-5i revealed that modulation of TIE2 expression significantly influences cellular proliferation, migration, and angiogenesis, mediated via the Rap1/MEK/ERK signaling pathway. Notably, the small molecule AKB-9778 was identified to target and activate TIE2, affecting the functional attributes of HBEC-5i. In vivo experiments further demonstrated that combining AKB-9778 with antihypertensive drugs could mitigate the incidence and volume of bleeding in hypertensive ICH mouse models, suggesting potential therapeutic implications.

Surfactant-Free Ultrasonication-Assisted Synthesis of 2d Tellurium Based on Metastable 1T'-MoTe2.

Elemental 2D materials (E2DMs) have been attracting considerable attention owing to their chemical simplicity and excellent/exotic properties. However, the lack of robust chemical synthetic methods seriously limits their potential. Here, a surfactant-free liquid-phase synthesis of high-quality 2D tellurium is reported based on ultrasonication-assisted exfoliation of metastable 1T'-MoTe2 . The as-grown 2D tellurium nanosheets exhibit excellent single crystallinity, ideal 2D morphology, surfactant-free surface, and negligible 1D by-products. Furthermore, a unique growth mechanism based on the atomic escape of Te atoms from metastable transition metal dichalcogenides and guided 2D growth in the liquid phase is proposed and verified. 2D tellurium-based field-effect transistors show ultrahigh hole mobility exceeding 1000 cm2  V-1  s-1 at room temperature attributing to the high crystallinity and surfactant-free surface, and exceptional chemical and operational stability using both solid-state dielectric and liquid-state electrical double layer. The facile ultrasonication-assisted synthesis of high-quality 2D tellurium paves the way for further exploration of E2DMs and expands the scope of liquid-phase exfoliation (LPE) methodology toward the controlled wet-chemical synthesis of functional nanomaterials.

On-chip electrocatalytic microdevices.

On-chip electrocatalytic microdevices (OCEMs) are an emerging electrochemical platform specialized for investigating nanocatalysts at the microscopic level. The OCEM platform allows high-precision electrochemical measurements at the individual nanomaterial level and, more importantly, offers unique perspectives inaccessible with conventional electrochemical methods. This protocol describes the critical concepts, experimental standardization, operational principles and data analysis of OCEMs. Specifically, standard protocols for the measurement of the electrocatalytic hydrogen evolution reaction of individual 2D nanosheets are introduced with data validation, interpretation and benchmarking. A series of factors (e.g., the exposed area of material, the choice of passivation layer and current leakage) that could have effects on the accuracy and reliability of measurement are discussed. In addition, as an example of the high adaptability of OCEMs, the protocol for in situ electrical transport measurement is detailed. We believe that this protocol will promote the general adoption of the OCEM platform and inspire further development in the near future. This protocol requires essential knowledge in chemical synthesis, device fabrication and electrochemistry.

Changes and significance of serum ubiquitin carboxyl-terminal hydrolase L1 and glial fibrillary acidic protein in patients with glioma.

BACKGROUND: Brain gliomas are malignant tumors with high postoperative recurrence rates. Early prediction of prognosis using specific indicators is of great significance. AIM: To assess changes in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) levels in patients with glioma pre-and postoperatively. METHODS: Between June 2018 and June 2021, 91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group. Sixty healthy volunteers were included in the control group. Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery. UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery. The patients were followed-up until February 2022. Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels, which could assist in predicting postoperative glioma recurrence. RESULTS: UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy (P < 0.05). However, UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery (P < 0.05). There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex, age, pathological type, tumor location, or number of lesions (P > 0.05). Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with grade III-IV tumors (P < 0.05). Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter ≤ 5 cm than in those with diameter > 5 cm, in which the differences were statistically significant (P < 0.05). Glioma recurred in 22 patients. The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group (P < 0.05). Receiver operating characteristic curves were plotted. The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775, respectively. However, the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels. CONCLUSION: UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma.

Filling the Gap between Heteroatom Doping and Edge Enrichment of 2D Electrocatalysts for Enhanced Hydrogen Evolution.

Composition modulation and edge enrichment are established protocols to steer the electronic structures and catalytic activities of two-dimensional (2D) materials. It is believed that a heteroatom enhances the catalytic performance by activating the chemically inert basal plane of 2D crystals. However, the edge and basal plane have inherently different electronic states, and how the dopants affect the edge activity remains ambiguous. Here we provide mechanistic insights into this issue by monitoring the hydrogen evolution reaction (HER) performance of phosphorus-doped MoS2 (P-MoS2) nanosheets via on-chip electrocatalytic microdevices. Upon phosphorus doping, MoS2 nanosheet gets catalytically activated and, more importantly, shows higher HER activity in the edge than the basal plane. In situ transport measurement demonstrates that the improved HER performance of P-MoS2 is derived from intrinsic catalytic activity rather than charge transfer. Density functional theory calculations manifest that the edge sites of P-MoS2 are energetically more favorable for HER. The finding guides the rational design of edge-dominant P-MoS2, reaching a minuscule onset potential of ∼30 mV and Tafel slope of 48 mV/dec that are benchmarked against other activation methods. Our results disclose the hitherto overlooked edge activity of 2D materials induced by heteroatom doping that will provide perspectives for preparing next-generation 2D catalysts.

Dual-emission 3D supramolecular framework hydrogel beads: highly selective detection of antibiotics and mechanism research.

Ratiometric fluorescent probes based on coordination polymers (CPs) have been widely applied in optical applications. Therefore, it is very important to develop a dual-emitting gel material based on coordination polymers for specific recognition of molecules. Cu-atda (H2atda = 3,3'-(4-amino-1,2,4-triazol-3,5-diyl) dibenzoic acid) is synthesized with a porous structure and a large number of amino sites exposed on the surface, which can be regarded as a carrier for fluorescent molecules and well disperse in the SA hydrogel network. A dual-emission Eu3+ functionalized CP hydrogel bead (9A/Cu-atda@Eu3+/SA, 9A = 9-anthraldehyde and SA = sodium alginate) is successfully prepared, which presents ratiometric fluorescence detection of flumequine with a low detection limit (48 nM) and high selectivity. Furthermore, it also displays an excellent fluorescence quenching effect on nitrofuran antibiotics, exhibiting a dual functional performance. In addition, the fluorescence response mechanisms of flumequine and nitrofuran antibiotics are discussed in depth. As a portable material, visualization 9A/Cu-atda@Eu3+/SA beads provide an extensive and convenient application prospect for real-time monitoring of antibiotics in the water environment.

Confronting the Challenges in Lithium Anodes for Lithium Metal Batteries.

With the low redox potential of -3.04 V (vs SHE) and ultrahigh theoretical capacity of 3862 mAh g-1 , lithium metal has been considered as promising anode material. However, lithium metal battery has ever suffered a trough in the past few decades due to its safety issues. Over the years, the limited energy density of the lithium-ion battery cannot meet the growing demands of the advanced energy storage devices. Therefore, lithium metal anodes receive renewed attention, which have the potential to achieve high-energy batteries. In this review, the history of the lithium anode is reviewed first. Then the failure mechanism of the lithium anode is analyzed, including dendrite, dead lithium, corrosion, and volume expansion of the lithium anode. Further, the strategies to alleviate the lithium anode issues in recent years are discussed emphatically. Eventually, remaining challenges of these strategies and possible research directions of lithium-anode modification are presented to inspire innovation of lithium anode.

MOF-on-MOF Membrane with Cascading Functionality for Capturing Dichromate Ions and p-Arsanilic Acid Turn-On Sensing.

It is very significant that functional porous metal-organic frameworks are used to manufacture hierarchical components to achieve cascading functions that cannot be achieved by a single-layer metal-organic framework (MOF). Here, we report two cases of novel MOFs constructed by the same ligand, Cu(I)-tpt and Cu(II)-tpt (Htpt = 5-[4(1H-1,2,4-triazol-1-yl)]phenyl-2H-tetrazole), and prepared a Cu(II)-tpt-on-Cu(I)-tpt membrane by a layer-by-layer approach ignoring the lattice mismatch problem. The first Cu(I)-tpt layer is grown on an oriented Cu2O nanostructured array by a "one-pot" approach. The aligned second Cu(II)-tpt layer can be deposited using liquid-phase epitaxy. Notably, the prepared Cu(II)-tpt-on-Cu(I)-tpt membrane combines adsorption and fluorescence sensing, which exhibited significant adsorption for Cr2O72- (203.25 mg g-1) as typical highly poisonous ions with a fluorescence quenching response. Hence, based on the oxidation-reduction between Cr2O72- and p-arsanilic acid (p-ASA), the Cu(II)-tpt-on-Cu(I)-tpt membrane's ability to adsorb Cr2O72- could be used to design "on-off-on" mode fluorescence probes to detect p-ASA with high sensitivity (limit of detection (LOD) = 0.0556 µg L-1). p-ASA can be degraded into highly toxic inorganic arsenic compounds in the natural environment and has received widespread attention. Therefore, the integration of adsorption and fluorescence properties makes the Cu(II)-tpt-on-Cu(I)-tpt membrane a feasible multifunctional material for pollution control and detection.

Kirigami-Inspired Flexible and Stretchable Zinc-Air Battery Based on Metal-Coated Sponge Electrodes.

The development of efficient and low-cost flexible metal electrodes is significant for flexible rechargeable zinc-air batteries (ZABs). Herein, we reported a new type of flexible metal (zinc and nickel) electrode fabricated via a two-step deposition method on polyurethane sponges (PUS) for flexible ZABs. Compared to conventional electrodes, the metal-coated PUS electrodes exhibited great flexibility, softness, and natural mechanical resilience. In addition, a flexible sandwich-structured ZAB was assembled with the metal-coated PUS electrodes and in situ cross-linked polyacrylic acid (PAA)-KOH hydrogel electrolyte. The flexible ZAB presented stable discharge/charge performance even under complex rolling and twisting deformations. Moreover, inspired by the kirigami-strategy for device-level stretchability, a 100% stretchable fence-shaped ZAB and a 160% stretchable serpentine-shaped ZAB were cut from the above-mentioned flexible ZABs. The kirigami-inspired configuration enabled the battery performance to be stable during stretching, benefiting from the softness of the PUS@metal electrode. These flexible and stretchable ZABs would broaden the promising applications for portable and wearable energy storage devices.

MiR-330-3p functions as a tumor suppressor that regulates glioma cell proliferation and migration by targeting CELF1.

INTRODUCTION: Glioma is a common type of neoplasm that occurs in the central nervous system. miRNAs have been demonstrated to act as critical regulators of carcinogenesis and tumor progression in multiple cancers, but the molecular mechanism of miR-330-3p in glioma remained unclear. The purpose of the study was to explore the role of miR-330-3p in glioma cell reproduction and migration. MATERIAL AND METHODS: The expression levels of miR-330-3p and CELF1 in 27 glioma tissue specimens and human glioma cell lines were examined by qRT-PCR and western blot. The TargetScan database was used to predict the relationship between miR-330-3p and CELF1. Then the target relationship was verified using dual-luciferase reporter assay. The effects of miR-330-3p/CELF1 on glioma cell proliferation were evaluated by MTT and colony formation assay. Wound healing assay was employed to measure the migration ability of glioma cells. RESULTS: MiR-330-3p was found lowly expressed in glioma tissues and cells compared with adjacent tissues and normal astrocytes, while CELF1 expression was relatively high in the glioma tissues and cells. Dual-luciferase reporter assay confirmed that miR-330-3p could directly target CELF1. Furthermore, miR-330-3p could down-regulate the expression of CELF1, therefore suppressing glioma cell reproduction and migration. CONCLUSIONS: MiR-330-3p inhibited the propagation and migration of glioma cells by repressing CELF1 expression.

Down-regulation of SEPT9 inhibits glioma progression through suppressing TGF-ß-induced epithelial-mesenchymal transition (EMT).

Malignant glioma is a highly aggressive cancer, known as one of the most dangerous types of primary brain tumor occurring in the central nervous system (CNS). Septin 9 (SEPT9) has been involved in tumor growth. However, its exact roles in regulating glioma development have not been fully understood. In the present study, we found that SEPT9 expression levels were markedly up-regulated in glioma tissues and cell lines. High expression of SEPT9 predicted a poor overall survival in patients with glioma. SEPT9 knockdown significantly reduced the proliferation, migration and invasion of glioma cells. Moreover, epithelial-mesenchymal transition (EMT) markers, including N-cadherin, matrix metalloproteinase-9 (MMP9), Vimentin and Twist, were significantly reduced by SEPT9 knockdown; however, the expression of E-cadherin was elevated by SEPT9 silence. This EMT process in glioma cells was dependent on the expression transforming growth factor (TGF)-ß1. In addition, the clinical analysis suggested that SEPT9 gene expression had a positive correlation with TGF-ß1 in patients with primary glioma at different grades. Furthermore, knockdown of SEPT9 significantly reduced the glioma progression in vivo. The anti-metastasis regulated by the knockdown of SEPT9 was further confirmed in mouse model, as evidenced by the reduced number of lung metastatic nodules. Our results supported that reducing SEPT9 expression could inhibit glioma progression through the suppression of EMT induced by TGF-ß1.

A dual-emitting Tb(iii)&Yb(iii)-functionalized coordination polymer: a "turn-on" sensor for N-methylformamide in urine and a "turn-off" sensor for methylglyoxal in serum.

Fluorescent materials with lanthanide cations encapsulated in MOFs are currently used in numerous applications, especially in biosensors. Therefore, herein, two novel composites were designed and developed based on a Tb(iii)&Yb(iii)-functionalized Cu(ii)-coordination polymer, possessing higher thermal and water stability and fascinating fluorescence properties. The first bimetallic composite Tb@Cu-Hcbpp demonstrated broad ligand-centered emission and weak typical Tb3+ ion emission; moreover, it was used as an excellent ratiometric fluorescent sensor for the metabolic product NMF of DMF in the human body (LOD = 0.02 µM). In addition, the Yb3+ ions were doped into Tb@Cu-Hcbpp to improve the fluorescence performance of the green Tb3+ ion emission. Among the series of Tb1-xYbx@Cu-Hcbpp samples (x = 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35 and 0.40), Tb0.85Yb0.15@Cu-Hcbpp showed maximum enhanced fluorescence intensity (almost 9.6 times that of the pure terbium system), but exhibited high fluorescence quenching efficiency for methylglyoxal (MGO), which could be used for the sensitive detection of MGO (LOD = 0.25 µM). Furthermore, the developed biosensors were successfully applied for the detection of NMF and MGO in urine and serum samples, and satisfactory results were obtained, showing good potential of these biosensors in practical applications such as in disease diagnosis and biochemical research.