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The impact of functionality of biochar on pressing environmental issue of cadmium (Cd) and lead (Pb) co-contamination in simultaneous soil and water systems has not sufficiently reported. This study investigated the impact of Fe- and Mg-functionalized wheat straw biochar (Fe-WSBC and Mg-WSBC) on Cd and Pb adsorption/immobilization through batch sorption and column leaching trials. Importantly, Fe-WSBC was more effective in adsorbing Cd and Pb (82.84 and 111.24 mg g-1), regeneration ability (removal efficiency 94.32 and 92.365), and competitive ability under competing cations (83.15 and 84.36%) compared to other materials (WSBC and Mg-WSBC). The practical feasibility of Fe-WSBC for spiked river water verified the 92.57% removal of Cd and 85.73% for Pb in 50 mg L-1 and 100 mg L-1 contamination, respectively. Besides, the leaching of Cd and Pb with Fe-WSBC under flow-through conditions was lowered to (0.326 and 17.62 mg L-1), respectively as compared to control (CK) (0.836 and 40.40 mg L-1). In short, this study presents the applicable approach for simultaneous remediation of contaminated water and soil matrices, offering insights into environmentally friendly green remediation strategies for heavy metals co-contaminated matrices.
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Cadmio , Carbón Orgánico , Restauración y Remediación Ambiental , Plomo , Contaminantes del Suelo , Suelo , Triticum , Contaminantes Químicos del Agua , Carbón Orgánico/química , Cadmio/química , Triticum/química , Plomo/química , Contaminantes del Suelo/química , Contaminantes del Suelo/análisis , Adsorción , Contaminantes Químicos del Agua/química , Restauración y Remediación Ambiental/métodos , Suelo/químicaRESUMEN
Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.
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Microscopía por Crioelectrón , Humanos , Transportadoras de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/química , Transporte Biológico , Células HEK293 , Modelos Moleculares , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/química , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Péptidos/metabolismo , Péptidos/química , Conformación ProteicaRESUMEN
The cornea and sclera are distinct adjacent tissues, yet their stromal cells originate from common neural crest cells (NCCs). Sclerocornea is a disease characterized by an indistinguishable boundary between the cornea and sclera. Previously, we identified a RAD21 mutation in a sclerocornea pedigree. Here, we investigated the impacts of RAD21 on NCC activities during eye development. RAD21 deficiency caused upregulation of PCDHGC3. Both RAD21 knockdown and PCDHGC3 upregulation disrupted the migration of NCCs. Transcriptome analysis indicated that WNT9B had 190.9-fold higher expression in scleral stroma than in corneal stroma. WNT9B was also significantly upregulated by both RAD21 knockdown and PCDHGC3 overexpression, and knock down of WNT9B rescued the differentiation and migration of NCCs with RAD21 deficiency. Consistently, overexpressing wnt9b in Xenopus tropicalis led to ocular developmental abnormalities. In summary, WNT9B is a determinant factor during NCC differentiation into corneal keratocytes or scleral stromal cells and is affected by RAD21 expression.
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Transparent immunodeficient animal models not only enhance in vivo imaging investigations of visceral organ development but also facilitate in vivo tracking of transplanted tumor cells. However, at present, transparent and immunodeficient animal models are confined to zebrafish, presenting substantial challenges for real-time, in vivo imaging studies addressing specific biological inquiries. Here, we employed a mitf-/-/prkdc-/-/il2rg-/- triple-knockout strategy to establish a colorless and immunodeficient amphibian model of Xenopus tropicalis. By disrupting the mitf gene, we observed the loss of melanophores, xanthophores, and granular glands in Xenopus tropicalis. Through the endogenous mitf promoter to drive BRAFV600E expression, we confirmed mitf expression in melanophores, xanthophores and granular glands. Moreover, the reconstruction of the disrupted site effectively reinstated melanophores, xanthophores, and granular glands, further highlighting the crucial role of mitf as a regulator in their development. By crossing mitf-/- frogs with prkdc-/-/il2rg-/- frogs, we generated a mitf-/-/prkdc-/-/il2rg-/- Xenopus tropicalis line, providing a colorless and immunodeficient amphibian model. Utilizing this model, we successfully observed intravital metastases of allotransplanted xanthophoromas and migrations of allotransplanted melanomas. Overall, colorless and immunodeficient Xenopus tropicalis holds great promise as a valuable platform for tumorous and developmental biology research.
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Anuros , Pez Cebra , Animales , Citoplasma , Xenopus/genética , Pez Cebra/genética , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismoRESUMEN
Neural progenitor cells (NPCs) derived from human pluripotent stem cells(hPSCs) provide major cell sources for repairing damaged neural circuitry and enabling axonal regeneration after spinal cord injury (SCI). However, the injury niche and inadequate intrinsic factors in the adult spinal cord restrict the therapeutic potential of transplanted NPCs. The Sonic Hedgehog protein (Shh) has crucial roles in neurodevelopment by promoting the formation of motorneurons and oligodendrocytes as well as its recently described neuroprotective features in response to the injury, indicating its essential role in neural homeostasis and tissue repair. In this study, we demonstrate that elevated SHH signaling in hNPCs by inhibiting its negative regulator, SUFU, enhanced cell survival and promoted robust neuronal differentiation with extensive axonal outgrowth, counteracting the harmful effects of the injured niche. Importantly, SUFU inhibition in NPCs exert non-cell autonomous effects on promoting survival and neurogenesis of endogenous cells and modulating the microenvironment by reducing suppressive barriers around lesion sites. The combined beneficial effects of SUFU inhibition in hNPCs resulted in the effective reconstruction of neuronal connectivity with the host and corticospinal regeneration, significantly improving neurobehavioral recovery in recipient animals. These results demonstrate that SUFU inhibition confers hNPCs with potent therapeutic potential to overcome extrinsic and intrinsic barriers in transplantation treatments for SCI.
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The application of soil amendment (SA) and the cultivation of low Cd-accumulating varieties have been a widely favored strategy to enable the safe utilization of Cd-contaminated arable land. However, little has been reported on the reciprocal effects of SA on the Cd mitigation and nutritional quality of different wheat varieties. In this study, we evaluated the impact of an SA on agronomic traits, Cd accumulation, translocation and mineral nutrition of 12 wheat varieties in an acidic field with a Cd concentration of 0.46 mg/kg. The results showed that the SA significantly reduced soil DTPA Cd (42.3 %) and resulted in a slight decrease in wheat grain yield (4.24-9.72 %, average 7.62 %). Similarly, the SA significantly reduced grain Cd concentrations (average 61.65 %) while increased the concentrations of beneficial elements such as Mo and Se in all wheat varieties. However, this intervention also led to a reduction in the concentration of essential mineral elements (such as Ca, Fe, and Mn) in whole wheat grain and starchy endosperm, as well as a reduction in their proportion in the bran. Based on genotypic differences, Huaimai 33, Zhenmai 168, Sumai 188 and Yangmai 28 were considered to be the relatively most promising wheat varieties for achieving a balance among food safety, nutritional quality, and economic yield in this region. Taken together, this study highlights the varietal differences in Cd mitigation and mineral accumulation in different wheat varieties in response to the SA, offering new perspectives for phytoremediation and biofortification strategies for Cd-contaminated farmland.
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Cadmio , Contaminantes del Suelo , Cadmio/análisis , Suelo , Triticum , Biofortificación , Contaminantes del Suelo/análisis , Minerales , Grano Comestible/químicaRESUMEN
OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Ratones , Animales , Degeneración del Disco Intervertebral/patología , Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Apoptosis , Modelos Animales de Enfermedad , Macrófagos/metabolismoRESUMEN
Background: Low back pain or sciatic pain because of lumbar intervertebral disc herniation (LDH) is caused by mechanical compression and/or an inflammatory component on the nerve root. However, it is difficult to define to what extent each component contributes to the pain. This study attempted to explore the effects of macrophage polarization on clinical symptoms in patients experiencing LDH after surgery, and investigated the association between macrophage cell percentages and clinical efficacy. Methods: This study retrospectively harvested nucleus pulposus (NP) tissue samples from 117 patients. Clinical symptoms and efficacy using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated at different time points preoperatively and postoperatively. CD68, CCR7, CD163, and CD206 were selected as macrophage phenotypic markers. Results: Seventy-six samples showed positive expression of macrophage markers in NP samples of patients with LDH, whereas 41 patients displayed negative results. No significant differences were detected between the two groups, involvement of several demographic data, and preoperative clinical findings. With respect to the macrophage-positive group, no significant correlation was detected between the positive rate of the four markers and the VAS score or ODI after surgery. However, patients with NP samples positive for CD68 and CCR7 expression showed significantly lower VAS scores 1 week after surgery compared with those in the negative group. Moreover, the improvement in VAS score showed a strong positive correlation with CD68- and CCR7-positive cell percentages. Conclusions: Our results indicated that pro-inflammatory M1 macrophages may be associated with the reduction of chronic pain after surgery. Therefore, these findings contribute to better personalized pharmacological interventions for patients with LDH, considering the heterogeneity of pain.
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Hybrid incompatibility as a kind of reproductive isolation contributes to speciation. The nucleocytoplasmic incompatibility between Xenopus tropicalis eggs and Xenopus laevis sperm (te×ls) leads to specific loss of paternal chromosomes 3L and 4L. The hybrids die before gastrulation, of which the lethal causes remain largely unclear. Here, we show that the activation of the tumor suppressor protein P53 at late blastula stage contributes to this early lethality. We find that in stage 9 embryos, P53-binding motif is the most enriched one in the up-regulated Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) peaks between te×ls and wild-type X. tropicalis controls, which correlates with an abrupt stabilization of P53 protein in te×ls hybrids at stage 9. Inhibition of P53 activity via either tp53 knockout or overexpression of a dominant-negative P53 mutant or Murine double minute 2 proto-oncogene (Mdm2), a negative regulator of P53, by mRNA injection can rescue the te×ls early lethality. Our results suggest a causal function of P53 on hybrid lethality prior to gastrulation.
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Semen , Proteína p53 Supresora de Tumor , Animales , Masculino , Ratones , Cromosomas/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Semen/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Xenopus/metabolismo , Xenopus laevis/genética , Xenopus laevis/metabolismoRESUMEN
Transposable elements (TEs) are abundant in metazoan genomes and have multifaceted effects on host fitness. However, the mechanisms underlying the functions of TEs are still not fully understood. Here, we combine Hi-C, ATAC-seq, and ChIP-seq assays to report the existence of multimegabase supersized loop (SSL) clusters in the Xenopus tropicalis sperm. We show that SSL anchors are inaccessible and devoid of the architectural protein CTCF, RNA polymerase II, and modified histones. Nearly all SSL anchors are marked by Helitrons, a class II DNA transposon. Molecular dynamics simulations indicate that SSL clusters are likely formed via a molecular agent-mediated chromatin condensation process. However, only slightly more SSL anchor-associated genes are expressed at late embryo development stages, suggesting that SSL anchors might only function in sperm. Our work shows an evolutionarily distinct and sperm-specific genome structure marked by a subset of Helitrons, whose establishment and function remain to be explored.
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Elementos Transponibles de ADN , Semen , Animales , Masculino , Xenopus/genética , Elementos Transponibles de ADN/genética , Histonas/genética , Cromatina/genéticaRESUMEN
Diabetes patients with painful diabetic neuropathy (PDN) show severe spinal atrophy, suggesting pathological changes of the spinal cord contributes to central sensitization. However, the cellular changes and underlying molecular mechanisms within the diabetic spinal cord are less clear. By using a rat model of type 1 diabetes (T1D), we noted an extensive and irreversible spinal astrocyte degeneration at an early stage of T1D, which is highly associated with the chronification of PDN. Molecularly, acetylation of astrocytic signal transducer and activator of transcription-3 (STAT3) that is essential for maintaining the homeostatic astrocytes population was significantly impaired in the T1D model, resulting in a dramatic loss of spinal astrocytes and consequently promoting pain hypersensitivity. Mechanistically, class IIa histone deacetylase, HDAC5 were aberrantly activated in spinal astrocytes of diabetic rats, which promoted STAT3 deacetylation by direct protein-protein interactions, leading to the PDN phenotypes. Restoration of STAT3 signaling or inhibition of HDAC5 rescued astrocyte deficiency and attenuated PDN in the T1D model. Our work identifies the inhibitory axis of HDAC5-STAT3 induced astrocyte deficiency as a key mechanism underlying the pathogenesis of the diabetic spinal cord that paves the way for potential therapy development for PDN.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Neuropatías Diabéticas , Animales , Ratas , Acetilación , Astrocitos/patología , Neuropatías Diabéticas/patología , Histona Desacetilasas/genéticaRESUMEN
Chronic pain is a maladaptive condition affecting 7%- 10% of the population worldwide and can be accompanied by depression, anxiety, and insomnia. In particular, chronic pain is becoming more common due to the increasing incidence of diabetes mellitus, cancer, systemic (body-wide) autoimmune, trauma, and infections that attack nerve tissues with an aging global population. Upon stimuli, pain responses are evoked from nociceptive primary sensory neurons in the peripheral nervous system (PNS). Still, pathological changes leading to central sensitization of the pain circuitry in the central nervous system (CNS) is a key mechanism underlying pain maintenance. In humans, chronic pain can last for years, even after the observable signs and symptoms of the primary inflammation or damage have resolved. It is clear that astrocytes, the most abundant cell type in the CNS, are highly involved in regulating pain signaling under health and disease. Multiple astrocyte subsets and diversified activation states driven by intrinsic and extrinsic cues have recently been identified in the spinal cord and brain, playing complex roles in pain development and resolution. Targeting detrimental astrocyte subtypes and activity is considered a promising pain management strategy. Here, we integrate the latest findings to review differential astrocytes activities in distinct regions of the CNS during pain pathophysiology and discuss the underlying molecular mechanisms that control their mode of action in beneficial or/and harmful aspects of pain. Finally, we provide a translational overview of current progress for pain therapies via modulating astrocytic activity.
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Astrocitos , Dolor Crónico , Humanos , Astrocitos/metabolismo , Dolor Crónico/metabolismo , Médula Espinal , Encéfalo , Sistema Nervioso CentralRESUMEN
In humans, germline TP53 mutations predispose carriers to a wide spectrum of cancers, which is known as Li-Fraumeni syndrome (LFS). To date, the association of melanomas with LFS remains unestablished. No melanomas have been reported in any P53-modified mouse models either. In this study, we show that targeted disruption of P53 at the DNA-binding domain in Xenopus tropicalis recapitulates LFS, with the formation of soft-tissue sarcomas and pancreatic ductal adenocarcinoma. Interestingly, 19% of the 14-month-old tp53Δ7/Δ7 homozygotes and 18% of tp53+/Δ7 heterozygotes spontaneously developed small nevi and non-invasive melanomas. Large invasive melanomas were also observed in other older homozygous mutants, with about 7.9% penetrance. Our data suggest that more dermatologic investigation of LFS patients should be able to settle the association of melanoma with LFS in epidemiology. Our model is also valuable for further investigation of the molecular mechanism underlying melanoma progression upon germline alteration of the tp53 locus.
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Síndrome de Li-Fraumeni , Nevo , Neoplasias Cutáneas , Animales , ADN , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Humanos , Lactante , Síndrome de Li-Fraumeni/complicaciones , Síndrome de Li-Fraumeni/genética , Ratones , Nevo/complicaciones , Neoplasias Cutáneas/genética , Proteína p53 Supresora de Tumor/genética , Xenopus/genéticaRESUMEN
BACKGROUND: The true diploid frog, Xenopus tropicalis (X. tropicalis) is an excellent genetic model organism. To date, the CRISPR/Cas-mediated genome editing methods established in this species are mostly based on SpCas9 that requires the stringent NGG protospacer-adjacent motif (PAM) for target recognition, which limits its genome editing scope. Thus, it is highly desirable to circumvent this limitation. RESULTS: Through one-cell stage injection of Cas/gRNAs into X. tropicalis embryos, we evaluated the mutagenic efficiency of 8 different Cas variants using T7EI assay, Sanger DNA sequencing, or deep sequencing. Our data indicate that SaCas9 and KKH SaCas9 are highly effective in frogs, which could be used for direct phenotyping in G0 embryos. In contrast, VQR Cas9, xCas9 3.7, SpG Cas9, and SpRY Cas9 were ineffective in X. tropicalis embryos and no activity was detected for iSpyMac Cas9. We also found that LbCas12a/crRNA RNP complexes with paired crRNAs efficiently induced small fragment deletions in X. tropicalis embryos. CONCLUSION: SaCas9 and KKH SaCas9 are robust genome editing tools in X. tropicalis embryos. LbCas12a/crRNA RNP complexes are useful for inducing DNA fragment deletions in frog embryos. These tools expand the CRISPR/Cas genome editing scope in X. tropicalis and increase the flexibility for various genome editing applications in frogs.
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Mitochondria, the only semiautonomous organelles in mammalian cells, possess a circular, double-stranded genome termed mitochondrial DNA (mtDNA). While nuclear genomic DNA compaction, chromatin compartmentalization and transcription are known to be regulated by phase separation, how the mitochondrial nucleoid, a highly compacted spherical suborganelle, is assembled and functions is unknown. Here we assembled mitochondrial nucleoids in vitro and show that mitochondrial transcription factor A (TFAM) undergoes phase separation with mtDNA to drive nucleoid self-assembly. Moreover, nucleoid droplet formation promotes recruitment of the transcription machinery via a special, co-phase separation that concentrates transcription initiation, elongation and termination factors, and retains substrates to facilitate mtDNA transcription. We propose a model of mitochondrial nucleoid self-assembly driven by phase separation, and a pattern of co-phase separation involved in mitochondrial transcriptional regulation, which orchestrates the roles of TFAM in both mitochondrial nucleoid organization and transcription.
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ADN Mitocondrial/genética , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica/genética , Mitocondrias/genética , Proteínas Mitocondriales/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética/genética , Animales , Condensados Biomoleculares/fisiología , Línea Celular , Genoma Mitocondrial/genética , Células HEK293 , Células HeLa , Humanos , Ratones , Mitocondrias/metabolismoRESUMEN
The assembled camshaft has obvious advantages in material optimization and flexible manufacturing. As the most important surface modification technique, the heat treatment process is utilized in this work to promote the desired compressive residual stress on the near-surface of the 100Cr6 steel assembled cam. The Johnson-Mehl-Avrami equation and Koistinen-Marbuger law are integrated into the ABAQUS software via user subroutines to simulate the evolution of diffusional transformation and diffusionless transformation, respectively. The linear mixture law is used for describing the coupled thermomechanical and metallurgical behaviors in the quenching of steel cam. The influences of various quenchants and the probable maximum phase volume fractions on surface residual stress or hardness are analyzed. Results show that a greater amount of martensite volume fraction and a slower martensitic transformation rate are beneficial for the compressive stress retention. Compared with the conventional quenching oil, the fast oil quenched cam surface has higher final compressive stress and hardness.
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Animal interphase chromosomes are organized into topologically associating domains (TADs). How TADs are formed is not fully understood. Here, we combined high-throughput chromosome conformation capture and gene silencing to obtain insights into TAD dynamics in Xenopus tropicalis embryos. First, TAD establishment in X. tropicalis is similar to that in mice and flies and does not depend on zygotic genome transcriptional activation. This process is followed by further refinements in active and repressive chromatin compartments and the appearance of loops and stripes. Second, within TADs, higher self-interaction frequencies at one end of the boundary are associated with higher DNA occupancy of the architectural proteins CTCF and Rad21. Third, the chromatin remodeling factor ISWI is required for de novo TAD formation. Finally, TAD structures are variable in different tissues. Our work shows that X. tropicalis is a powerful model for chromosome architecture analysis and suggests that chromatin remodeling plays an essential role in de novo TAD establishment.
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Genoma , Modelos Moleculares , Conformación de Ácido Nucleico , Xenopus/genética , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas de Ciclo Celular/genética , Cromatina/genética , Cromatina/metabolismo , Ensamble y Desensamble de Cromatina , Biología Computacional/métodos , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica , Técnicas de Silenciamiento del Gen , Genómica/métodos , Fenotipo , Xenopus/embriología , Proteínas de Xenopus/genéticaRESUMEN
In the past decades, the energy consumption of nonrenewable fossil fuels has been increasing, which severely threatens human life. Thus, it is very urgent to develop renewable and reliable energy storage devices with features of environmental harmlessness and low cost. High power density, excellent cycle stability, and a fast charge/discharge process make supercapacitors a promising energy device. However, the energy density of supercapacitors is still less than that of ordinary batteries. As is known to all, the electrochemical performance of supercapacitors is largely dependent on electrode materials. In this review, we firstly introduced six typical transition metal oxides (TMOs) for supercapacitor electrodes, including RuO2, Co3O4, MnO2, ZnO, XCo2O4 (X = Mn, Cu, Ni), and AMoO4 (A = Co, Mn, Ni, Zn). Secondly, the problems of these TMOs in practical application are presented and the corresponding feasible solutions are clarified. Then, we summarize the latest developments of the six TMOs for supercapacitor electrodes. Finally, we discuss the developing trend of supercapacitors and give some recommendations for the future of supercapacitors.
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Cell-extracellular matrix (ECM) detachment is known to decrease extracellular signal-regulated kinase (ERK) signaling, an intracellular pathway that is central for control of cell behavior. How cell-ECM detachment is linked to downregulation of ERK signaling, however, is incompletely understood. We show here that focal adhesion protein Ras Suppressor 1 (RSU1) plays a critical role in cell-ECM detachment induced suppression of ERK signaling. We have identified prohibitin 2 (PHB2), a component of membrane lipid rafts, as a novel binding protein of RSU1, and mapped a major RSU1-binding site to PHB2 amino acids 150 to 206 in the C-terminal region of the PHB/SPFH (stomatin/prohibitin/flotillin/HflKC) domain. The PHB2 binding is mediated by multiple sites located in the N-terminal leucine-rich repeat region of RSU1. Depletion of PHB2 suppressed cell-ECM adhesion-induced ERK activation. Furthermore, cell-ECM detachment increased RSU1 association with membrane lipid rafts and interaction with PHB2. Finally, knockout of RSU1 or inhibition of RSU1 interaction with PHB2 by overexpression of the major RSU1-binding PHB2 fragment (amino acids 150-206) effectively suppressed the cell-ECM detachment induced downregulation of ERK signaling. Additionally, expression of venus-tagged wild-type RSU1 restored ERK signaling, while expression of venus-tagged PHB2-binding defective RSU1 mutant in which the N-terminal leucine-rich repeat region is deleted did not. Taken together, Our findings identify a novel RSU1-PHB2 signaling axis that senses cell-ECM detachment and links it to decreased ERK signaling.