Search

Rechargeable aqueous zinc ion batteries (ZIBs) are considered as one of the most promising candidates for large-scale energy storage due to their high safety, environmental benignity, and low cost. Developing cathode materials with high specific capacity and long cycle performance is the key to the commercialization of ZIBs. In this work, a perovskite structured bimetallic oxide (NiMnO3) was synthesized and firstly used as cathode for ZIBs. Electrochemical tests show that the NiMnO3 exhibits a high capacity (280 mA h g−1 at 300 mA g−1), good cycling stability, and rate performance (152 mA h g−1 at 1000 mA g−1). The fast ion transportation and the significant capacitance contribution should be the reasons for remarkable rate performance. The zinc storage mechanism of NiMnO3 is the insertion and extraction reaction and the formation/dissolution of ZHS (ZnSO4·3Zn(OH)2·5H2O). The results suggest that the bimetallic oxide with perovskite structure could be a promising cathode material for ZIBs.

Redundancy of multinucleated mature osteoclasts, which results from the excessive fusion of mononucleated preosteoclasts (pOCs), leads to osteolytic diseases such as osteoporosis. Unfortunately, the currently available clinical drugs completely inhibit osteoclasts, thus interfering with normal physiological bone turnover. pOC-specific regulation may be more suitable for maintaining bone homeostasis. Here, circBBS9, a previously unidentified circular RNA, was found to exert regulatory effects via the circBBS9/miR-423-3p/Traf6 axis in pOCs. To overcome the long-standing challenge of spatiotemporal RNA delivery to cells, we constructed biomimetic nanoparticles to achieve the pOC-specific targeted delivery of circBBS9. pOC membranes (POCMs) were extracted to camouflage cationic polymer for RNA interference with circBBS9 (POCM-NPs@siRNA/shRNA circBBS9 ). POCM-NPs endowed the nanocarriers with improved stability, accurate pOC targeting, fusogenic uptake, and reactive oxygen species–responsive release. In summary, our findings may provide an alternative strategy for multinucleated cell–related diseases that involves restriction of mononucleated cell multinucleation through a spatiotemporally selective delivery system.

Protection of telomere 1 (POT1), the telomeric single-stranded DNA (ssDNA)-binding protein in the shelterin complex, has been implicated in the DNA damage response, tumorigenesis and aging. Telomere dysfunction induced by telomere deprotection could accelerate cellular senescence in primary human cells. While previous work demonstrated the biological mechanism of POT1 in aging and cancer, how POT1 is posttranscriptionally regulated remains largely unknown. To better understand the POT1 regulatory axis, we performed bioinformatic prediction, and selected candidates were further confirmed by dual-luciferase reporter assay. Collectively, our results revealed that miR-185 can significantly reduce POT1 mRNA and protein levels by directly targeting the POT1 3’-untranslated region (3’-UTR). Overexpression of miR-185 increased telomere dysfunction-induced foci (TIF) signals in both cancer cells and primary human fibroblasts. Elevated miR-185 led to telomere elongation in the telomerase-positive cell line HTC75, which was phenotypically consistent with POT1 knocking down. Moreover, miR-185 accelerated the replicative senescence process in primary human fibroblasts in a POT1-dependent manner. Interestingly, increased serum miR-185 could represent a potential aging-related biomarker. Taken together, our findings reveal miR-185 as a novel aging-related miRNA that targets POT1 and provide insight into the telomere and senescence regulatory network at both the intracellular and extracellular levels.

Objective The aim of this study was to obtain the time range of non-industrial fresh watermelon juice (FWJ), which is widely used in the catering industry under different storage conditions, with safe-drinkable quality, and the drinking time range of fresh juice with good nutritional quality and sensory quality. Method The quality of non-industrial FWJ was audited by assessing the shelf life of non-industrial FWJ through microbial safety, nutritional, and sensory quality investigating during 24 h of storage at 4, 25, and 37°C. Results According to the microbial safety quality, the safe drinking time of FWJ was within 12, 4, and 4 h when stored at 4, 25, and 37°C, respectively. Based on the nutritional and sensory quality, FWJ was drinking with good quality within 2 h, and with just acceptable quality for no more than 4 h when stored at 4 or 25°C. Electronic nose and gas chromatography-mass spectrometry (GC-MS) could effectively distinguish and identify the changes in volatile components in FWJ under different storage conditions. Conclusion It is a feasible method to predict the shelf life of non-industrial FWJ by this method, and hence to guarantee non-industrial FWJ being drinking with safety and health, and it might be used in many other fresh juice shelf life predictions.

Spinal cord injury (SCI) is a devastating disease that may lead to lifelong disability. Thus, seeking for valid drugs that are beneficial to promoting axonal regrowth and elongation after SCI has gained wide attention. Metformin, a glucose-lowering agent, has been demonstrated to play roles in various central nervous system (CNS) disorders. However, the potential protective effect of metformin on nerve regeneration after SCI is still unclear. In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway. Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo. Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE). Moreover, treatment with Nrf2 inhibitor ML385 partially abolished its antioxidant effect. We also found that the Nrf2 transcription was partially reduced by LY294002 in vitro. Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction. Overall, our present study suggests that metformin administration may provide a potential therapy for SCI.

Axon retraction greatly limits functional recovery after spinal cord injury (SCI) and neuron polarization, which affects processes including axon formation and development, is a promising target for promoting axon regeneration. Increasing microtubule stability has been demonstrated to improve intrinsic axon regeneration processes and is critically related to endoplasmic reticulum (ER)-mitochondria interactions. We used real-time polymerase chain reaction, Western blotting, and immunofluorescence to screen a variety of natural compounds, and found that Loureirin B (LrB) effectively promoted neuron polarization and axon regeneration in vitro and in vivo. LrB significantly inhibited ER stress and thereby promoted mitochondrial functions by regulating mitochondrial fusion. Further, LrB reactivated the Akt/GSK-3β pathway, which plays critical roles in cell survival and microtubule stabilization. Taken together, our results suggest that the effects of LrB on neuron regeneration involve the inhibition of ER stress-induced mitochondrial dysfunction and activation of the Akt/GSK-3β pathway, which further promotes microtubule stabilization. LrB may therefore be a promising candidate for facilitating recovery following SCI.

Background Genetic overexpression or pharmacological activation of heme oxygenase (HO) are identified as potential therapeutic target for spinal cord injury (SCI); however, the role of carbon monoxide (CO), which is a major product of haem degenerated by HO, in SCI remains unknown. Applying hemin or chemicals which may regulate HO expression or activity to increase CO production are inadequate to elaborate the direct role of CO. Here, we assessed the effect of CO releasing molecule-3 (CORM-3), the classical donor of CO, in SCI and explained its possible protective mechanism. Methods Rat SCI model was performed with a vascular clip (30 g) compressing at T9 vertebral level for 1 min and CO was delivered immediately after SCI by CORM-3. The neurological deficits and neuron survival were assessed. Inflammasome and inositol-requiring enzyme 1 (IRE1) pathway were measured by western blot and immunofluorescence. For in vitro study, oxygen glucose deprivation (OGD) simulated the SCI-inflammasome change in cultured the primary neurons. Findings CORM-3 suppressed inflammasome signaling and pyroptosis occurrence, which consequently alleviated neuron death and improved motor functional recovery following SCI. As a pivotal sensor involving in endoplasmic reticulum stress-medicated inflammasome signaling, IRE1 and its downstream X-box binding protein 1 (XBP1) were activated in SCI tissues as well as in OGD neurons; while inhibition of IRE1 by STF-083010 in SCI rats or by si-RNA in OGD neurons suppressed inflammasome signaling and pyroptosis. Interestingly, the SCI/OGD-stimulated IRE1 activation was attenuated by CORM-3 treatment. Interpretations CO may alleviate neuron death and improve motor functional recovery in SCI through IRE1 regulation, and administration of CO could be a promising therapeutic strategy for SCI.

Let n be a positive integer. For any integer a, we say that is idempotent modulo n if a2≡a(mod n). The n-modular Erdos-Burgess constant is the smallest positive integer l such that any l integers contain one or more integers, whose product is idempotent modulo n. We gave a sharp lower bound of the n-modular Erdos-Burgess constant, in particular, we determined the n-modular Erdos-Burgess constant in the case when n was a prime power or a product of pairwise distinct primes.

The land that is suitable for settlement or live is shortage in Lhasa River Basin (LRB). Alluvial fan is a candidate resource to suitable land in this situation. However, the basic information of alluvial fans, for example its distribution and land-use types, is little known. In this study, Google earth, ArcGIS and visual interpretation were used to get the outlines, areas, quantity and distribution of alluvial fans. Meanwhile, the land use, the distance from alluvial fans to roads, places (town and village) and rivers (including stream) are analyzed. The results show that there are 826 alluvial fans in LRB and the total area is 1166.03 km². The quantity of alluvial fans with area between 0.1 km2 and 1 km2 is 517, which is dominated in all. The quantity of alluvial fans is concentrated in the east of LRB, but that area is mainly distributed in the west. The area of Grassland is the largest in all land use types which is account for 68.70% of alluvial fans. Although cropland area is accounted by 2.16% of alluvial fans, it is accounted by 18.98% of the LRB’s cropland area. The quantity of alluvial fans within in 5km distance to tertiary road, village, and river (including stream) are accounted of 93.70%, 53.63% and 77.38% respectively. Therefore, alluvial fans have played an import role in LRB, and may have huge utilization potential in the future.

Intervertebral disc degeneration (IDD) is a complicated pathological condition blamed for low back pain. Mitochondrion is of vital importance for cellular homeostasis, and mitochondrial dysfunction is considered to be one of the major causes of cellular damage. Mitophagy is a cellular process to eliminate impaired mitochondria and showed protective effects in various diseases; however, its role in IDD is still not clear. Here, we explore the role of Parkin-mediated mitophagy in IDD. In this study, we found that Parkin was upregulated in degenerative nucleus pulposus (NP) tissues in vivo as well as in TNF-α stimulated NP cells in vitro. Knockdown of Parkin by siRNA showed that Parkin is crucial for apoptosis and mitochondrion homeostasis in NP cells. Further study showed that upregulation of Parkin by salidroside may eliminate impaired mitochondria and promote the survival of NP cells through activation of mitophagy in vitro. In in vivo study, we found that salidroside could inhibit the apoptosis of NP cells and ameliorate the progression of IDD. These results suggested that Parkin is involved in the pathogenesis of IDD and may be a potential therapeutic target for IDD.

Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood‐spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV‐FGF1 in PC12 cells after H2O2 treatment. Furthermore, the autophagy levels were not changed in PRDX1‐suppressing cells that were treated by AAV‐FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti‐ROS activity after SCI.

Fibroblast growth factor 13 (FGF13), a nonsecretory protein of the FGF family, plays a crucial role in developing cortical neurons by stabilizing the microtubule. In previous studies, we showed that regulation of microtubule dynamics was instrumental for both growth cone initiation and for promoting regrowth of injured axon. However, the expression and effect of FGF13 in spinal cord or after spinal cord injury (SCI) remains undefined. Here, we demonstrated a role of FGF13 in regulating microtubule dynamics and in enhancing axon regeneration after SCI. Administration of FGF13 not only promoted neuronal polarization, axon formation, and growth cone initiation in vitro, but it also facilitated functional recovery following SCI. In addition, we found that upregulation of FGF13 in primary cortical neurons was accompanied by enhanced mitochondrial function, which is essential for axon regeneration. Our study has defined a novel mechanism underlying the beneficial effect of FGF13 on axon regeneration, pointing out that FGF13 may serve as a potential candidate for treating SCI or other central nervous system (CNS) injury.

Fruit thinning is a cultivation technique that is widely applied in horticulture in order to obtain high-quality horticultural crops. This practice results in the discarding of a large number of thinned unripe fruits in orchards each year, which produces a great waste of agricultural resources and causes soil pollution that may be an important reservoir for pest and plant diseases. Current studies showed that bioactive compounds such as polyphenols, organic acids, monosaccharides and starches are present in unripe fruits. Therefore, we reviewed the bioactive components obtained from thinned unripe fruits, their revalorization for the food industry, their beneficial effects for human health and the methods for obtaining these components. We also performed a calculation of the costs and benefits of obtaining these bioactive compounds, and we proposed future research directions. This review provides a reference for the effective utilization and industrial development of thinned unripe fruits obtained from horticultural crops. Furthermore, revalorizing the waste from this cultural practice may increase the economic benefits and relieve the environmental stress.

Esophageal cancer is one of the most common type of malignancies. Telomerase activity, which is absent or weakly detected in the majority of human somatic cells, is elevated in esophageal cancer. Although azidothymidine (AZT), a reverse transcriptase inhibitor, has been utilized as a treatment for tumors, its role in treating esophageal cancer has not been confirmed. The aim of the present study was to determine the effect of AZT on telomerase activity and the proliferation of the human esophageal cancer cell line TE-11. A telomeric repeat amplification assay was utilized to detect telomerase activity following treatment of TE-11 cells with AZT. The effect of AZT on TE-11 cell cycle distribution was determined by flow cytometry. Cellular DNA damage was evaluated by a comet assay and an MTT assay demonstrated that AZT significantly inhibited the viability of TE-11 cells, in a time-and dose-dependent manner. In addition, TE-11 cells treated with various concentrations of AZT exhibited a significant reduction in telomerase activity and percentage of cells in the G1/G0 phase, and an increase in the percentage of cells in the S phase. High doses of AZT caused DNA damage, and enhanced the expression levels of γ-H2A histone family member X and phosphorylated checkpoint kinase 2 in TE-11 cells. These results demonstrated that AZT effectively inhibits proliferation of the TE-11 human esophageal cancer cell line in vitro. The growth inhibitory effects were associated with a reduction in telomerase activity, S and G2/M phase cell cycle arrest, and enhanced DNA damage, suggesting that AZT may be utilized in the clinic for the treatment of esophageal cancer.

Spinal cord injury (SCI) is a devastating neurological disorder that usually leads to a loss of motor and sensory function in patients. The expression of hypoxia inducible factor-1α (HIF-1α) is increased, and exerts a protective role after traumatic SCI. However, the endogenous activity of HIF-1α is insufficient for promoting functional recovery. The present study tested the potential effect of the sustained activation of HIF-1α by the prolylhydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) on anti-apoptotic process and the regulation of axonal regeneration after SCI. Here, we found that treatment with DMOG significantly increased the expression of HIF-1α and that the stabilization of HIF-1α induced by DMOG not only decreased the expression of apoptotic proteins to promote neural survival, but also enhanced axonal regeneration by regulating microtubule stabilization

Intervertebral disc degeneration (IDD) is a multifactorial disease with few efficacious clinical drugs, which has been demonstrated to be associated with nucleus pulposus (NP) cells apoptosis and degeneration of the extracellular matrix (ECM). Interleukin (IL)‑1β, a common proinflammatory cytokine, is considered to be one of key regulators in IDD development. Andrographolide (AG), extracted from Andrographis paniculata, has been suggested to possess marked anti‑inflammatory properties. However, the effects of AG on IDD has not been well explored. The present study aimed to investigate the effects and the mechanisms of AG on IDD in human NP cells. NP cells were treated with IL‑1β in the absence or presence of AG to investigate the effects on cell viability, cellular apoptosis, production of ECM and matrix metalloproteinase (MMP)‑3, MMP‑9 and MMP‑13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)‑4 and ADAMTS‑5. It was identified that IL‑1β‑induced NP cellular apoptosis was significantly inhibited by AG treatment. Furthermore, AG mitigated the IL‑1β‑induced degeneration of the ECM, which was paralleled by a decrease in MMPs and ADAMTS levels. In addition, AG exhibited marked inhibitory properties against the activation of Toll‑like receptors (TLRs), Myeloid differentiation factor 88 (MyD88) and the nuclear translocation of Nuclear factor kappa‑light‑chain‑enhancer of activated B cells (NF‑κB). Taken together, these results demonstrated that AG treatment mitigated IL‑1β‑induced NP cells degeneration through the TLR4/MyD88/NF‑κB signaling pathway, and suggested that AG may be a potential agent for IDD prevention and therapy.

Proper selection and effective delivery of combination drugs targeting multiple pathophysiological pathways key to spinal cord injury (SCI) hold promise to address the thus far scarce clinical therapeutics for improving recovery after SCI. In this study, we aim to develop a clinically feasible way for targeted delivery of multiple drugs with different physiochemical properties to the SCI site, detail the underlying mechanism of neural recovery, and detect any synergistic effect related to combination therapy. Methods: Liposomes (LIP) modified with a scar-targeted tetrapeptide (cysteine-alanine-glutamine-lysine, CAQK) were first constructed to simultaneously encapsulate docetaxel (DTX) and brain-derived neurotrophic factor (BDNF) and then were further added into a thermosensitive heparin-modified poloxamer hydrogel (HP) with affinity-bound acidic fibroblast growth factor (aFGF-HP) for local administration into the SCI site (CAQK-LIP-GFs/DTX@HP) in a rat model. In vivo fluorescence imaging was used to examine the specificity of CAQK-LIP-GFs/DTX binding to the injured site. Multiple comprehensive evaluations including biotin dextran amine anterograde tracing and magnetic resonance imaging were used to detect any synergistic effects and the underlying mechanisms of CAQK-LIP-GFs/DTX@HP both in vivo (rat SCI model) and in vitro (primary neuron). Results: The multiple drugs were effectively delivered to the injured site. The combined application of GFs and DTX supported neuro-regeneration by improving neuronal survival and plasticity, rendering a more permissive extracellular matrix environment with improved regeneration potential. In addition, our combination therapy promoted axonal regeneration via moderation of microtubule function and mitochondrial transport along the regenerating axon. Conclusion: This novel multifunctional therapeutic strategy with a scar-homing delivery system may offer promising translational prospects for the clinical treatment of SCI.

This paper describes the application of a microscopic defocusing image system to track 3D particle motions in microflow around a microcubic array near a microchannel wall surface. The measurement principle and calibration method were evaluated to provide accurate 3D microparticle location. Particle trajectories were measured in two microchannels. Measured velocity profiles of Hele–Shaw flows for two Reynolds numbers agreed well with theoretical profiles. Three-dimensional particle tracking in fluid flow around a microcubic array exhibited quasi-periodic and non-periodic trajectory modes. The experimental results indicated that 3D particle motions are spatially and time dependent even when the flow rate is constant, and microparticle trajectories may deviate from steady flow streamlines.

MicroRNAs (miRNAs) play a pivotal role in carcinogenesis. Dysregulation of miRNAs, both oncogenic miRNAs and tumour-suppressive miRNAs, is closely associated with cancer development and progression. The levels of miRNAs could be changed epigenetically by DNA methylation in the 5' untranslated region (UTR) of pre-mature miRNAs. To investigate whether DNA methylation alters the expression of miR-129 in lung cancer, we did DNA methylation assays and found that 5' UTR region of miR-129-2 gene was absolutely methylated in both A549 and SPCA-1 lung cancer cells, but totally un-methylated in 95-D cells. The expression of miR-129 was restored by 5-Aza-2'-deoxycytidine (DAC), a de-methylation agent, in both A549 and SPCA-1 cells, resulting in attenuated cell migration and invasion ability, and decreased protein level of NF-κB, which indicates the involvement of NF-κB pathway. To further illustrate the roles of miR-129 in lung tumourigenesis, we overexpressed miR-129 in lung cancer cells by transfection of miR-129 mimics, and found arrested cell proliferation at G2/M phase of cell cycle and inhibited cell invasion. These findings strongly suggest that miR-129 is a tumour suppressive miRNA, playing important roles in the development and progression of human lung cancer.

The secreted frizzled-related protein 2 (SFRP2) plays a pivotal role in the Wnt pathway, however, it functions as an agonist or an antagonist is still controversial. We profiled SFRP2 expression in several lung cancer cell lines, and found that A549 and 95-D exhibited the lowest and the highest level of SFRP2, respectively. Then we employed the SFRP2-overexpressing plasmid and siRNA to transfect A549 and 95-D cells, respectively. Through MTT assays, we found that SFRP2 knockdown inhibited cell proliferation, and halted the 95-D cells in G1 phase of the cell cycle by downregulation of CCND1 and CDK4, indicating that SFRP2 has the ability of promoting lung cancer cell proliferation. We further checked the cell properties of migration and invasion, using wound scratch assay and Transwell assays. The data showed decreased migrated and invasive 95-D cells after SFRP2 knockdown, and the observations were the opposite in the overexpressing model, implying that SFRP2 promoted lung cancer cell invasion. Moreover, the canonical Wnt pathway was also studied through detection of β-catenin by western blotting. In the SFRP2 overexpressing model, A549 cells presented stronger expression of β-catenin compared with controls, while it was the opposite in 95-D cells. These results suggested that SFRP2 serves as a Wnt agonist in lung cancer cells. Together, the findings of this study implied that SFRP2 is not only an agonist of Wnt pathway, but also a cancer promoting protein for lung cancer, indicating SFRP2 as a promising therapeutic target for lung cancer treatment.

Telomeric repeat binding factor 2 (TRF2) is essential for telomere maintenance and has been implicated in DNA damage response and aging. Telomere dysfunction induced by TRF2 inhibition can accelerate cellular senescence in human fibroblasts. While previous work has demonstrated that a variety of factors can regulate TRF2 expression transcriptionally and post-translationally, whether microRNAs (miRNAs) also participate in post-transcriptionally modulating TRF2 levels remains largely unknown. To better understand the regulatory pathways that control TRF2, we carried out a large-scale luciferase reporter screen using a miRNA expression library and identified four miRNAs that could target human TRF2 and significantly reduce the level of endogenous TRF2 proteins. In particular, our data revealed that miR-23a could directly target the 3′ untranslated region (3′UTR) of TRF2. Overexpression of miR-23a not only reduced telomere-bound TRF2 and increased telomere dysfunction-induced foci (TIFs), but also accelerated senescence of human fibroblast cells, which could be rescued by ectopically expressed TRF2. Our findings demonstrate that TRF2 is a specific target of miR-23a, and uncover a previously unknown role for miR-23a in telomere regulation and cellular senescence.

A {\it good drawing} of a graph $G$ is a drawing where the edges are non-self-intersecting and each two edges have at most one point in common, which is either a common end vertex or a crossing. The {\it crossing number} of a graph $G$ is the minimum number of pairwise intersections of edges in a good drawing of $G$ in the plane. The {\it $n$-dimensional augmented cube} $AQ_n$, proposed by S.A. Choudum and V. Sunitha, is an important interconnection network with good topological properties and applications. In this paper, we obtain an upper bound on the crossing number of $AQ_n$ less than $26/324^{n}-(2n^2+7/2n-6)2^{n-2}$., 39 pages