Polymer electrolyte membrane water electrolysis (PEMWE) has been regarded as a promising technology for renewable hydrogen production. However, acidic oxygen evolution reaction (OER) catalysts with ...long‐term stability impose a grand challenge in its large‐scale industrialization. In this review, critical factors that may lead to catalyst's instability in couple with potential solutions are comprehensively discussed, including mechanical peeling, substrate corrosion, active‐site over‐oxidation/dissolution, reconstruction, oxide crystal structure collapse through the lattice oxygen‐participated reaction pathway, etc. Last but not least, personal prospects are provided in terms of rigorous stability evaluation criteria, in situ/operando characterizations, economic feasibility and practical electrolyzer consideration, highlighting the ternary relationship of structure evolution, industrial‐relevant activity and stability to serve as a roadmap towards the ultimate application of PEMWE.
The large‐scale application of polymer electrolyte membrane water electrolysis (PEMWE) is suffering from long‐term stability challenges in anodic oxygen evolution reaction (OER). This review provides a thorough discussion of degradation mechanisms, catalyst design principles and future research opportunities to serve as a cornerstone for overcoming the dilemma in acidic OER stability and achieving the industrialization of water electrolysis.
Current pharmaceutical research and development (R&D) is a high-risk investment which is usually faced with some unexpected even disastrous failures in different stages of drug discovery. One main ...reason for R&D failures is the efficacy and safety deficiencies which are related largely to absorption, distribution, metabolism and excretion (ADME) properties and various toxicities (T). Therefore, rapid ADMET evaluation is urgently needed to minimize failures in the drug discovery process. Here, we developed a web-based platform called ADMETlab for systematic ADMET evaluation of chemicals based on a comprehensively collected ADMET database consisting of 288,967 entries. Four function modules in the platform enable users to conveniently perform six types of drug-likeness analysis (five rules and one prediction model), 31 ADMET endpoints prediction (basic property: 3, absorption: 6, distribution: 3, metabolism: 10, elimination: 2, toxicity: 7), systematic evaluation and database/similarity searching. We believe that this web platform will hopefully facilitate the drug discovery process by enabling early drug-likeness evaluation, rapid ADMET virtual screening or filtering and prioritization of chemical structures. The ADMETlab web platform is designed based on the Django framework in Python, and is freely accessible at
http://admet.scbdd.com/
.
Double-negative acoustic metamaterials (AMMs) offer the promising ability of superlensing for applications in ultrasonography, biomedical sensing and nondestructive evaluation. However, the ...systematic design and realization of broadband double-negative AMMs are stilling missing, which hinder their practical implementations. In this paper, under the simultaneous increasing or non-increasing mechanisms, we develop a unified topology optimization framework involving different microstructure symmetries, minimal structural feature sizes and dispersion extents of effective parameters. The optimization framework is applied to conceive the heuristic resonance-cavity-based and space-coiling metamaterials with broadband double negativity. Meanwhile, we demonstrate the essences of double negativity derived from the novel artificial multipolar LC (inductor-capacitor circuit) and Mie resonances which can be induced by controlling mechanisms in optimization. Furthermore, abundant numerical simulations validate the corresponding double negativity, negative refraction, enhancement of evanescent waves and subwavelengh imaging. Finally, we experimentally show the desired broadband subwavelengh imaging by using the 3D-printed optimized space-coiling metamaterial. The present design methodology provides an ideal approach for constructing the constituent “atoms” of metamaterials according to any artificial physical and structural requirements. In addition, the optimized broadband AMMs and superlens lay the structural foundations of subwavelengh imaging technology.
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•Unified topology optimization framework is developed for designing double-negative acoustic metamaterials (AMMs).•Representative resonance-cavity-based and space-coiling microstructures are explored.•Broadband double negativity originating from novel multipolar LC or Mie resonances can be induced systematically.•Desired broadband subwavelength imaging of topology-optimized AMMs is verified experimentally.
Conjugated coordination polymers have become an emerging category of redox‐active materials. Although recent studies heavily focus on the tailoring of metal centers in the complexes to achieve stable ...electrochemical performance, the effect on different substitutions of the bridging bonds has rarely been studied. An innovative tailoring strategy is presented toward the enhancement of the capacity storage and the stability of metal–organic conjugated coordination polymers. Two nanostructured d‐π conjugated compounds, NiC6H2(NH)4n (Ni‐NH) and NiC6H2(NH)2S2n (Ni‐S), are evaluated and demonstrated to exhibit hybrid electrochemical processes. In particular, Ni‐S delivers a high reversible capacity of 1164 mAh g−1, an ultralong stability up to 1500 cycles, and a fully recharge ability in 67 s. This tailoring strategy provides a guideline to design future effective conjugated coordination‐polymer‐based electrodes.
An innovative tailoring strategy toward the enhancement of the capacity storage and stability of d‐π metal‐organic conjugated coordination polymers is proposed. The tailored compound Ni‐S shows a high reversible capacity of 1164 mAh g−1, an ultralong stability up to 1500 cycles, and a fully recharge ability of only 67 s.
Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer‐related death worldwide. However, the clinical diagnosis and treatment modalities are still relatively limited, which ...urgently require the development of new effective technologies. Recently, nanotechnology has gained extensive attention in HCC surveillance, imaging and pathological diagnosis, and therapeutic strategies. Typically, nanomedicines have been focused on early HCC diagnosis and precise treatment of advanced HCC, which has developed and improved a variety of new technologies and agents for future clinical practice. Furthermore, strategies of facilitating drug release and delivery in current treatment processes such as ablation, systematic therapy, transcatheter arterial chemoembolization, molecular targeted therapy, and immune‐modulating therapy have also been studied widely. This review summarizes the recent advances in this area according to current clinical HCC guidelines: 1) Nanoparticle‑based HCC surveillance; 2) Nanotechnology for HCC diagnosis; 3) Therapeutic advances for HCC Management; 4) Limitations of applications in nanotechnology for HCC; 5) Conclusions and perspectives. Although there are still many limitations and difficulties to overcome, the investigations of nanomedicines are believed to show potential applications in clinical practice.
Schematic illustration of nanotechnology development for hepatocellular carcinoma (HCC). The advancement of nanotechnology actually runs through the whole process of HCC surveillance, diagnosis, and clinical management. In addition to monitoring tumor markers such as α‐fetoprotein detection, assisting imaging diagnosis and traditional treatment, many promising new nano‐strategies like immune regulator are emerging.
Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial ...function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process.
Young (5–6 months), middle-aged (11-13 months), old (20–24 months) Nrf2−/− (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology.
Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle.
Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.
•Muscle mass/function and mitochondrial homeostasis are impaired during aging in mice.•Decline of muscle mass/function is linked with mitochondrial dysfunction during aging.•Nrf2 deficiency has few effect on frailty/sarcopenia and mitochondria in young mice.•Nrf2 deficiency worsens mitochondrial dysfunction, frailty/sarcopenia in older mice.
Spinal cord injury is linked to the interruption of neural pathways, which results in irreversible neural dysfunction. Neural repair and neuroregeneration are critical goals and issues for ...rehabilitation in spinal cord injury, which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies. Besides the involvement of endogenous stem cells in neurogenesis and neural repair, exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases. However, to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury, appropriate interventional measures (e.g., neuromodulation) should be adopted. Neuromodulation techniques, such as noninvasive magnetic stimulation and electrical stimulation, have been safely applied in many neuropsychiatric diseases. There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system; namely, by exciting, inhibiting, or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury. Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth, encourages the formation of new synaptic connections to promote neural plasticity, and improves motor function recovery in patients with spinal cord injury. With the development of biomaterial technology and biomechanical engineering, several emerging treatments have been developed, such as robots, brain-computer interfaces, and nanomaterials. These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury. However, large-scale clinical trials need to be conducted to validate their efficacy. This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence, to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.
•A systematic inverse-design strategy for pentamode metamaterials (PMs) is proposed.•Broadband isotropic/anisotropic PMs with customized properties are constructed.•Mechanisms for broadband ...single-mode range of exclusive longitudinal waves are revealed.•An inverse-design strategy for functional underwater devices using PMs is developed.•Pentamode metasurfaces are achieved to convert broadband propagating wave to evanescent surface mode for noise shielding.
Pentamode metamaterials (PMs), a kind of metafluids composed of complex solid medium, have shown enormous potential for both elastic wave and underwater acoustic wave manipulation. However, due to the lack of thorough understanding of the formation mechanism, most reported artificial and empirical PMs share very similar topological features, thus depriving the possibility of obtaining rigorous combination of wave parameters that are required to deliver desirable and prescribed properties and functionalities. To tackle this challenge, with the assumption of C2v, C4v and C6v symmetries in both square and triangle lattices, we propose a unified inverse strategy to systematically design and explore a series of novel isotropic or anisotropic PM microstructures through bottom-up topology optimization. Optimized PM microstructures are designed to provide customized effective mass density, elastic modulus, anisotropy degree and pentamode features on demand. We demonstrate that most optimized microstructures possess broadband single-mode range of exclusive longitudinal waves; some even feature record-breaking relative single-mode bandwidths exceeding 150%. Upon shielding lights on the beneficial topological features of the broadband PMs, we extract the main topological features to form simplified PM configurations, i.e., multiple symmetric solid blocks with slender rods, which can induce the multiform multiple-order rotational vibrations or the integration of the low-order rotational vibrations and anisotropic local resonances for the broadband single-mode nature. At a higher design level, we establish a dedicated inverse-design strategy, under the function-macrostructure-microstructure paradigm, to conceive a novel broadband subwavelength underwater pentamode shielding device, which enables the conversion of propagating acoustic wave to the evanescent surface wave mode within the frequency range 1000 Hz, 4000 Hz. Our study offers new possibilities for the practical realization of broadband PMs and underwater pentamode devices with rigorously tailored effective parameters, thus bring the PM-based technology within reach for practical applications.
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Poly‐m‐phenyleneisophthalamide (PMIA) with excellent chemical stability and breakdown strenth is regarded as the next generation of insulating paper in power system. However, the basic intensity of ...PMIA is not enough to match its operating cost, and it is promising to enhance the performance by nano composition. In this paper, the influence of nano‐TiO2ith a mass fraction of 1 to 5 wt% on insulating properties is studied, including breakdown voltage and bulk conductivity. The silane coupling agent aminopropyltriethoxysilane (APTES) together with the polydopamine (PDA) are used for modifying the fillers interface. The results show that, APTES covalent grafting and PDA physically coating can improve the dispersion and compatibility of nano‐TiO2 in aramid fiber matrix, thus regulating the interface trap characteristics and reducing the probability of electric field distortion in insulating paper. When the modified TiO2 content is 2 wt%, the breakdown voltage is the highest, which is 23.9 kV/mm, 54% higher than that of pure aramid paper. In addition, this article discusses the modification mechanism from molecular dynamic simulation and trap characteristics. Based on molecular dynamics calculation, three interface models of PMIA‐TiO2, PMIA‐TiO2/APTES, PMIA‐TiO2/APTES/PDA are constructed, and the synergistic effect of PDA is confirmed from the microscopic level.
For meta‐aramid paper, the micro‐modified doping effect of pure TiO2 is limited. The insulation properties of the composite were improved after the co‐modification of polydopamine and APTES, and reached the optimal value when the mass fraction is 2 wt% at low concentration.
Abstract
Background
Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 ...for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in more than 20 human malignancies, among which lung cancer is the leading cause of cancer-associated deaths worldwide. Thus, the mechanism of CXCR7 in the progression of lung cancer is urgently needed.
Methods
First, we explored CXCR4 and CXCR7 expression in human lung cancer specimens and cell lines by immunohistochemistry, western blot and flow cytometry. Then, we chose the human lung adenocarcinoma cell line A549 that stably overexpressed CXCR7 through the way of lentivirus-mediated transduction. Next, “wound healing” assay and transwell assay were applied to compare the cell migration and invasion ability, and stripe assay was used to evaluate the cell polarization. Last, our team established a mouse xenograft model of human lung cancer and monitored tumor proliferation and metastasis by firefly luciferase bioluminescence imaging in SCID/Beige mice.
Results
In clinical lung cancer samples, CXCR7 expression was almost not detected in normal tissue but upregulated in lung tumor tissue, whereas, CXCR4 was highly expressed in both normal and tumor tissues. Furthermore, overexpression of CXCR7 enhanced A549 cell migration and polarization in vitro. Besides, mouse xenograft model of human lung cancer showed that CXCR7 promoted primary lung tumor’s growth and metastasis to the second organ, such as liver or bone marrow in SCID/Beige mice in vivo.
Conclusions
This study describes the multiple functions of CXCR7 in lung cancer. Thus, these results suggest that CXCR7 may be a malignancy marker and may provide a novel target for anticancer therapy.
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