Search

Uncontrollable dendrite formation following the uneven deposition of lithium significantly affects the safety and service life of lithium metal batteries (LMBs). Therefore, a metal–organic framewor...

The translocation of transcription factor EB (TFEB) to the nucleus plays a pivotal role in the regulation of basic cellular processes, such as lysosome biogenesis and autophagy. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome, which is important in maintaining cellular homeostasis during environmental stress. Furthermore, oxidative stress is a critical cause for the progression of neurodegenerative diseases. Curcumin has anti-oxidative and anti-inflammatory activities, and is expected to have potential therapeutic effects in various diseases. In this study, we demonstrated that curcumin regulated TFEB export signalling via inhibition of glycogen synthase kinase-3β (GSK-3β); GSK-3β was inactivated by curcumin, leading to reduced phosphorylation of TFEB. We further showed that H2O2-induced oxidative stress was reduced by curcumin via the Nrf2/HO-1 pathway in human neuroblastoma cells. In addition, we showed that curcumin induced the degradation of amyloidogenic proteins, including amyloid-β precursor protein and α-synuclein, through the TFEB-autophagy/lysosomal pathway. In conclusion, curcumin regulates autophagy by controlling TFEB through the inhibition of GSK-3β, and increases antioxidant gene expression in human neuroblastoma cells. These results contribute to the development of novel cellular therapies for neurodegenerative diseases.

The qualitative and quantitative determination of marker protein is of great significance in the life sciences and in medicine. Here, we developed an electrochemical DNA biosensor for protein detection based on DNA self-assembly and the terminal protecting effects of small-molecule-linked DNA. This strategy is demonstrated using the small molecule biotin and its receptor protein streptavidin (SA). We immobilized DNA with a designed structure and sequence on the surface of the gold electrode, and we named it M1-Biotin DNA. M1-Biotin DNA selectively combines with SA to generate M1-Biotin-SA DNA and protects M1-Biotin DNA from digestion by EXO III; therefore, M1-Biotin DNA remains intact on the electrode surface. M1-Biotin-SA DNA was modified with methylene blue (MB); the MB reporter molecule is located near the surface of the gold electrode, which generates a substantial electrochemical signal during the detection of SA. Through this strategy, we can exploit the presence or absence of an electrochemical signal to provide qualitative target protein determination as well as the strength of the electrochemical signal to quantitatively analyze the target protein concentration. This strategy has been proven to be used for the quantitative analysis of the interaction between biotin and streptavidin (SA). Under optimal conditions, the detection limit of the proposed biosensor is as low as 18.8 pM, and the linear range is from 0.5 nM to 5 μM, showing high sensitivity. The detection ability of this DNA biosensor in complex serum samples has also been studied. At the same time, we detected the folate receptor (FR) to confirm that this strategy can be used to detect other proteins. Therefore, this electrochemical DNA biosensor provides a sensitive, low-cost, and fast target protein detection platform, which may provide a reliable and powerful tool for early disease diagnosis.

A microRNA (miRNA) detection platform composed of a rolling circle amplification (RCA) system and an allosteric deoxyribozyme system is proposed, which can detect miRNA-21 rapidly and efficiently. Padlock probe hybridization with the target miRNA is achieved through complementary base pairing and the padlock probe forms a closed circular template under the action of ligase, this circular template results in RCA. In the presence of DNA polymerase, RCA proceeds and a long chain with numerous repeating units is formed. In the presence of single-stranded DNA (H1 and H2), multi-component nucleic acid enzymes (MNAzymes) are formed that have the ability to cleave substrates. Finally, substrates containing fluorescent and quenching groups and magnesium ions are added to the system to activate the MNAzyme and the substrate cleavage reaction, thus achieving fluorescence intensity amplification. The RCA–MNAzyme system has dual signal amplification and presents a sensing platform that demonstrates broad prospects in the analysis and detection of nucleic acids.

The adoption of lithium metal anodes, which are ideal for constructing batteries with high specific energy, is limited by dendrite growth and poor cycle performance. Herein, an anion-regulated solid polymer electrolyte based on in-situ-polymerized poly(ethylene glycol ether acrylate) is prepared for dendrite-free lithium metal batteries. According to the space-charge theory, the growth of lithium dendrites is effectively inhibited by the improved electric field of solid polymer electrolyte on the lithium anode side. And this solid system achieves a lithium transfer number of 0.63, excellent ionic conduction on 2.16 × 10−5 S cm−1 at room temperature), a wide electrochemical stable window (4.8 V vs. Li+/Li) and excellent cycle performance. The flexible batteries (LiFePO4 cathode/solid polymer electrolyte/lithium metal) are assembled to power a light-emitting diode at room temperature. We highlight the anion regulated polymer solid electrolyte, which shows great potential for solid lithium metal batteries and flexible batteries.

The protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK), a key ER stress sensor of the unfolded protein response (UPR), can confer beneficial effects by facilitating the removal of cytosolic aggregates through the autophagy-lysosome pathway (ALP). In neurodegenerative diseases, the ALP ameliorates the accumulation of intracellular protein aggregates in the brain. Transcription factor-EB (TFEB), a master regulator of the ALP, positively regulates key genes involved in the cellular degradative pathway. However, in neurons, the role of PERK activation in mitigating amyloidogenesis by ALP remains unclear. In this study, we found that SB202190 selectively activates PERK independently of its inhibition of p38 mitogen-activated protein kinase, but not inositol-requiring transmembrane kinase/endoribonuclease-1α (IRE1α) or activating transcription factor 6 (ATF6), in human neuroblastoma cells. PERK activation by SB202190 was dependent on mitochondrial ROS production and promoted Ca2+-calcineurin activation. The activation of the PERK-Ca2+-calcineurin axis by SB202190 positively affects TFEB activity to increase ALP in neuroblastoma cells. Collectively, our study reveals a novel physiological mechanism underlying ALP activation, dependent on PERK activation, for ameliorating amyloidogenesis in neurodegenerative diseases.

Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human diploid fibroblast WI-38 cells measured with SA-β-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-α IL-6, and PAI-1 and increased the transcriptional levels of antioxidant genes, such as HO-1 and NQO1. Moreover, CO apparently enhanced the expression of Sirt1 through down-regulation of miR-34a. Next, to determine whether Sirt1 mediates the inhibitory effect of CO on cellular senescence, we pre-treated WI-38 cells with the Sirt1 inhibitor Ex527 and a miR-34a mimic followed by the administration of H2O2 and evaluated the expression of SASP and antioxidant genes as well as ROS production. According to our results, Sirt1 is crucial for the antiaging and antioxidant effects of CO. Finally, CO prolonged the lifespan of Caenorhabditis elegans and delayed high-fat diet-induced liver aging. Taken together, these findings demonstrate that CO reduces cellular senescence and liver aging through the regulation of miR-34a and Sirt1.

Endothelial senescence is the main risk factor that contributes to vascular dysfunction and the progression of vascular disease. Carbon monoxide (CO) plays an important role in preventing vascular dysfunction and in maintaining vascular physiology or homeostasis. The application of exogenous CO has been shown to confer protection in several models of cardiovascular injury or disease, including hypertension, atherosclerosis, balloon-catheter injury, and graft rejection. However, the mechanism by which CO prevents endothelial senescence has been largely unexplored. The aim of this study was to evaluate the effects of CO on endothelial senescence and to investigate the possible mechanisms underlying this process. We measured the levels of senescence-associated-β-galactosidase activity, senescence-associated secretory phenotype, reactive oxygen species (ROS) production, and stress granule in human umbilical vein endothelial cells and the WI-38 human diploid fibroblast cell line. We found that 5-fluorouracil (5FU)-induced ROS generation was inhibited by CO-releasing molecules (CORM)-A1 treatment, and endothelial senescence induced by 5FU was attenuated by CORM-A1 treatment. The SIRT1 inhibitor EX527 reversed the inhibitory effect of CO on the 5FU-induced endothelial senescence. Furthermore, SIRT1 deficiency abolished the stress granule formation by CO. Our results suggest that CO alleviates the endothelial senescence induced by 5FU through SIRT1 activation and may hence have therapeutic potential for the treatment of vascular diseases.

Lithium metal is considered an ideal anode material for next-generation high-energy-density batteries, owing to its high theoretical specific capacity and low reduction potential. However, the uncontrolled growth of Li dendrites during cycling has limited its industrial application. In this work, a poly (allyl diglycol carbonate)-based solid polymer electrolyte (PADC-SPE) combining the advantages of polyether and polycarbonate-based solid electrolytes was prepared by in-situ polymerization. According to space charge theory, the uniform free movement of lithium ions in the electrolyte can prevent electric field generation at the anode surface, facilitating the safe and ordered deposition of lithium ions. Therefore, PADC-SPE exhibited excellent ionic conductivity (1.96 × 10−5 S cm−1), a wide electrochemical window (5.5 V), and a high Li-ion transference number (t+ = 0.67) at room temperature. Surprisingly, a smooth surface was observed for the Li anode of Li/Li cells after constant-current charge–discharge cycling for 800 h. A LiFePO4/PADC–SPE/Li battery showed excellent high-temperature (60 °C) cycling performance, with a discharge specific capacity reaching 145.1 mAh g−1 at 0.3C and retaining 99.2% of its first-cycle value after 110 cycles. Based on this excellent performance, PADC-SPE represents a promising system for developing safe and high-performance Li metal batteries.

Lithium metal shows great promise as an anode material for high-performance next-generation batteries due to its low redox potential, low weight, and high specific capacity. However, the uncontrolled growth of lithium dendrites during charge–discharge cycling limits the practical application of lithium metal anodes. In this work, an anion-inhibited solid framework polymer electrolyte (SFPE) was prepared through the polymerization of vinyl polyhedral oligomeric silsesquioxane (VPOSS) and diallyl dicarbonate (DDC) as a means to suppress lithium dendrite formation. The structure of the electrolyte was found to reduce the electric field at the anode surface by restricting the free movement of the anions (TFSI−) of the lithium salt, which facilitated the orderly, uniform, and safe deposition of lithium ions on the anode. The SFPE presented a high lithium ion transference number (0.63), a wide window of electrochemical stability (5.6 V versus Li+/Li), and high ionic conductivity (0.31 mS cm−1) at 25 °C. A LiFePO4/Li cell containing the SFPE achieved a specific discharge capacity of 165 mAh g−1 and a capacity retention of 91.3% after 200 cycles at 0.1 C (1 C = 180 mAh g−1) and 25 °C, and the lithium anode surface remained smooth after 600 h of constant-current charge–discharge cycling. Based on these results, this SFPE is an excellent candidate for use in high-performance lithium metal batteries.

The EarlyCDT®-Lung test was the first autoantibody-based diagnostic tool for lung cancer, which was developed with a panel of recombinant protein antigens. To confirm whether the antibody test developed with linear peptide antigens has a similar power to that developed with the whole protein molecules, the present work was then undertaken to develop an in-house enzyme-linked immunosorbent assay with linear peptide antigens derived from annexin A1 (ANXA1) and DEAD box protein 53 (DDX53), which have been used to develop the EarlyCDT®-Lung test. A total of 272 patients with non-small cell lung cancer (NSCLC) and 227 control subjects matched in age and smoking history were recruited. Student's t test showed that the levels of circulating IgG to ANXA1-derived peptide antigens were significantly higher in patients with NSCLC than control subjects (t = 5.66, P 0.0001), in which the increased anti-ANXA1 IgG levels were observed only in patients at stages I, II, or III, but not in those at stage IV. However, the levels of circulating IgG to DDX53-derived peptide antigens were not significantly altered in NSCLC (t = 1.78, P = 0.076). Receiver operating characteristic analysis showed that the sensitivity against specificity of90% was 23.7% for ANXA1 IgG assay and 13.8% for DDX53 IgG assay. This work suggests that the linear peptide antigen derived from ANXA1 may be suitable for the development of diagnostic tool for lung cancer although further screening is needed to identify more such peptide antigens derived from tumor-associated antigens.

Lithium metal anode is regarded as promising potential electrode for next-generation secondary batteries. However, the security issues caused by the growth of lithium dendrites hinder the development of lithium metal batteries. In this study, we prepare a single-ion conducting polymer electrolyte with semi-interpenetrating polymer network based on poly(lithium 4-styrenesulfonate). By eliminating the large electric fields near the lithium anode, the growth of lithium dendrite is suppressed effectively according to space-charge theory. The structurally optimized poly(lithium 4-styrenesulfonate)@polymethylmethacrylate single-ion conducting polymer electrolyte containing 2 wt% ethylene glycol dimethacrylate exhibits extremely high lithium ion transference number (0.91), promising ionic conductivity (0.97 × 10−3 S cm−1 at 25 °C) along with wide electrochemical window of 4.7 V (vs. Li+/Li). Furthermore, the LiFePO4/membrane/Li cell achieves stable cycling performance (capability retention rate of 93.8% after 78 cycles at 1 C (1 C = 170 mAh g−1) and high coulombic efficiency 99.4%) along with superior discharge rate capability at room temperature. These excellent performances show that the single-ion conducting polymer electrolyte is a potential candidate for safe lithium metal batteries.

Dopamine (DA) existed as small-molecules can serve as a versatile platform for secondary surface modified reactions in biomedical engineering and biosensors especially a surface plasmon resonance (SPR) sensor. For sensing modification purposes, the environment of DA polymerization may be varied. This study involved using DA for the modification of a gold film under different conditions. It was anticipated that the change of environmental conditions would have an influence on the immobilization reaction of DA onto the gold film, and hence the impact on the SPR phenomenon. These conditions included varying pH, using different kinds of buffers, varying DA concentrations in buffer solutions as well as the DA immobilization time which reflected the length of time that the gold film was being exposed to DA. It was found that both neutral and mildly alkaline conditions offered favorable immobilization environments with 2 mg/mL dopamine in pH 8.6 Tris buffer, producing the optimum reactive result on gold. It was observed that the SPR phenomenon became non-existence at pH 9.5 for 2-hour DA immobilization time. Under the optimum environmental condition, the critical DA immobilization time for the disappearance of SPR phenomenon was estimated to be 277 min (approx. 4.6 hours). The results from this work have produced a series of valuable data served as a good foundation for surface modification using DA.

Thymic lymphoma is a highly invasive and even metastatic cancer. This study investigated the effects of mesenchymal stem cells (MSCs) transfusion on cell cycle, cell proliferation, CD3 expression, mutation frequency of T cell receptor using mouse model of thymic lymphoma. C57BL/6J young mouse models of thymoma were injected with MSCs. Six months later, the thymus was taken for pathological examination and flow cytometry studies. The cells were labeled with anti-CD4, CD8, CD3, propidium iodide, or CFDA-SE, cell cycle, proliferation kinetics, and mutation frequency of T cell receptor, respectively. Pathologic results showed that control had clear corticomedular structure with regularly shaped lymphocytes. After radiation, the thymus structure was completely destroyed, with lymphoid tumor cells diffusely distributed and heavily stained, and large nuclei. Transfusion of MSCs resulted in normal thymus structure. Cytometry studies showed that there were more CD4-/CD8- T cells in the thymus of irradiated mice than in control; transfusion of MSCs led to reduced CD4-/CD8- T cells. In irradiated mice, there were less CD4+/CD8+ T cells than in control and MSCs transfusion groups. It was observed that there were more cells arrested in G1 phase in the thymus cells and CD4-/CD8- T cells in irradiated mice than in other 2 groups, whereas there were more cells arrested in S phase in CD4+/CD8+ and CD4+/CD8- T cells in irradiated mice than in the other mice. In the thymus cells, and CD4+/CD8+ and CD4+/CD8- T cells, irradiated mice group had significantly less parent, G2, G3, and G4 cells, and more cells at higher generations, and also higher proliferation index. In CD4-/CD8- T cells, irradiated mice had significantly more parent, G2, and G3 cells, and less G4, G5, G6, and propidium iodide, as compared with the other 2 groups. The expression of CD3 in CD4/CD8 T cells was significantly higher than in control. MSCs transfusion improved CD3 expression, but was still less than the control. Irradiation resulted in very high mutation frequency of T cell receptor, which was barely affected by MSCs transfusion. Mesenchymal stem cell transfusion is able to restore the cell cycle and cell proliferation, but not CD3 expression and mutation frequency of T cell receptor in irradiated mice to control level.

Recurrent cervical cancer is a clinically complex disease that is difficult to treat. There are numerous treatment options, but the results achieved by each are poor. External-beam radiation therapy of the pelvic lymph drainage area, in combination with intracavitary afterloading or the interstitial implantation of a radiation source (i.e., brachytherapy), are the current standard radiotherapy regimens used in high-risk clinical targets. However, there are few reports concerning the use of iodine-125 (125I) seed implantation brachytherapy in recurrent cervical cancer, and the effects of treatment and adverse reactions have not yet been systematically evaluated. In the present study one such case is reported, in which the patient was successfully treated with intensity-modulated radiotherapy (IMRT) in combination with 125I seed implantation. The patient, a 47-year-old woman, was initially diagnosed with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer, and received a radical hysterectomy, left lateral adnexectomy and pelvic lymph node dissection. A follow-up examination 23 months later revealed vaginal invasion and a solitary lump in the cervical stump with a maximum diameter of 38 mm. The patient was subsequently diagnosed with recurrent cervical cancer and was treated with six cycles of docetaxel and nedaplatin chemotherapy, alongside IMRT and interstitial 125I seed implantation. At the point of manuscript submission, the patient's progression-free survival time was 33 months and long-term adverse reactions were acceptable. The response of this patient indicates that 125I seed implantation could be used as a complementary treatment for recurrent cervical cancer and may also prove to be a reliable means for the comprehensive treatment of primary cervical cancer, as the patient had characteristics similar to primary cervical cancer, although this hypothesis could not be confirmed in the present study.