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Intercalating linear-organic-ions into the MoS2 interlayer is beneficial for optimizing electrons/ions' capacitive storage behavior. The chain length, as an important parameter of linear organic ions, can lead to differences in the dispersion, polarity, critical micelle concentration of organic ions, and steric hindrance to the growth of MoS2 nanosheets. Up until now, the relationship between chain length, synthesis of intercalated-MoS2, and capacitive energy storage has not been unveiled. Herein, we have designed an in situ-intercalation route that is simple, efficient, and high yield for inserting four types of linear organic ions into the interlayer of MoS2 to synthesize four types of in situ-intercalated MoS2 samples. After organic-ion intercalation, the expanded interlayer spacing achieved the introduction of intercalation-type pseudocapacitors, as confirmed by ex situ XRD. Improved extra capacitance is verified due to the enlarged ion storage space from a synergistic spatial effect in the broken-shell-hollow ball. Additionally, the generation of high-valent Mo (+5 and +6) and S-vacancies is beneficial for energy storage. More importantly, according to density functional theory (DFT) calculations, as the chain length increases, the number of negative adsorption sites and the total adsorption ability also increase, leading to significantly improved specific capacitance. This work will provide an archetype for the preparation of in situ-intercalated layered materials and unveil capacitive energy storage that relies on the organic-ion chain length.
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The ORF9b protein, derived from the nucleocapsid's open-reading frame in both SARS-CoV and SARS-CoV-2, serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response. Despite its significance, the precise regulatory mechanisms underlying its function remain elusive. In the present study, we unveil that the ORF9b protein of SARS-CoV-2, including emerging mutant strains like Delta and Omicron, can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway, despite certain mutations present among these strains. Moreover, our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70 (TOM70) as a substrate receptor, bridging ORF9b with heat shock protein 90 alpha (HSP90α) and Cullin 5 (CUL5) to form a complex. Within this complex, CUL5 triggers the ubiquitination and degradation of ORF9b, acting as a host antiviral factor, while HSP90α functions to stabilize it. Notably, treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b, leading to a pronounced inhibition of SARS-CoV-2 replication. Single-cell sequencing data revealed an up-regulation of HSP90α in lung epithelial cells from COVID-19 patients, suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90α to evade the host immunity. Our study identifies the CUL5-TOM70-HSP90α complex as a critical regulator of ORF9b protein stability, shedding light on the intricate host-virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.
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COVID-19 , Proteínas Cullin , Proteínas HSP90 de Choque Térmico , SARS-CoV-2 , Ubiquitinación , Replicación Viral , Humanos , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Replicación Viral/genética , Proteínas HSP90 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/metabolismo , COVID-19/virología , COVID-19/genética , COVID-19/metabolismo , COVID-19/inmunología , Ubiquitinación/genética , Células HEK293 , Benzoquinonas/farmacología , Estabilidad Proteica , Células Vero , Proteínas Virales/genética , Proteínas Virales/metabolismo , Lactamas MacrocíclicasRESUMEN
Molybdenum disulfide (MoS2), a typical layered material, has important applications in various fields, such as optoelectronics, catalysis, electronic devices, sensors, and supercapacitors. Extensive research has been carried out on few-layered MoS2 in the field of electrochemistry due to its large specific surface area, abundant active sites and short electron transport path. However, the preparation of few-layered MoS2 is a significant challenge. This work presents a simple one-pot hydrothermal method for synthesizing few-layered MoS2. Furthermore, it investigates the exfoliation effect of different amounts of sodium borohydride (NaBH4) as a stripping agent on the layer number of MoS2. Na+ ions, as alkali metal ions, can intercalate between layers to achieve the purpose of exfoliating MoS2. Additionally, NaBH4 exhibits reducibility, which can effectively promote the formation of the metallic phase of MoS2. Few-layered MoS2, as an electrode for supercapacitor, possesses a wide potential window of 0.9 V, and a high specific capacitance of 150 F g-1 at 1 A g-1. This work provides a facile method to prepare few-layered two-dimensional materials for high electrochemical performance.
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A-kinase anchoring protein 95 (AKAP95) functions as a scaffold for protein kinase A. Prior work by our group has shown that AKAP95, in coordination with Connexin 43 (Cx43), modulates the expression of cyclin D and E proteins, thus affecting the cell cycle progression in lung cancer cells. In the current study, we confirmed that AKAP95 forms a complex with Cx43. Moreover, it associates with cyclins D1 and E1 during the G1 phase, leading to the formation of protein complexes that subsequently translocate to the nucleus. These findings indicate that AKAP95 might facilitate the nuclear transport of cyclins D1 and E1. Throughout this process, AKAP95 and Cx43 collectively regulate the expression of cyclin D, phosphorylate cyclin E1 proteins, and target their specific ubiquitin ligases, ultimately impacting cell cycle progression.
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This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S-acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO-NPs. This observation suggests that the toxicity of CuO-NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu-NPs.
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Supervivencia Celular , Cobre , Lisosomas , Macrólidos , Nanopartículas del Metal , Mitocondrias , Cobre/toxicidad , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Animales , Humanos , Nanopartículas del Metal/toxicidad , Macrólidos/toxicidad , Ratones , Supervivencia Celular/efectos de los fármacos , Línea Celular , MasculinoRESUMEN
Ionic electroactive polymer (iEAP) actuators are recognized as exceptional candidates for artificial muscle development, with significant potential applications in bionic robotics, space exploration, and biomedical fields. Here, we developed a new iEAP actuator utilizing high-purity single-walled carbon nanotubes (SWCNTs)-reinforced poly(3, 4-ethylenedioxythiophene)/poly(4-styrenesulfonate) (PEDOT: PSS, PP) hybrid electrodes and a Nafion/EMIBF4 ion-exchange membrane via a straightforward and efficient spray printing technique. The SWCNT/PP actuator exhibits significantly enhanced electric conductivity (262.9 S/cm) and specific capacitance (22.5 mF/cm2), benefitting from the synergistic effect between SWCNTs and PP. These improvements far surpass those observed in activated carbon aerogel bucky-gel-electrode-based actuators. Furthermore, we evaluated the electroactive behaviors of the SWCNT/PP actuator under alternating square-wave voltages (1-3 V) and frequencies (0.01-100 Hz). The results reveal a substantial bending displacement of 6.44 mm and a high bending strain of 0.61% (at 3 V, 0.1 Hz), along with a long operating stability of up to 10,000 cycles (at 2 V, 1 Hz). This study introduces a straightforward and efficient spray printing technique for the successful preparation of iEAP actuators with superior electrochemical and electromechanical properties as intended, which hold promise as artificial muscles in the field of bionic robotics.
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Ti3C2Tx MXene, as a common two-dimensional material, has a wide range of applications in electrochemical energy storage. However, the surface forces of few-layer or monolayer Ti3C2Tx MXene lead to easy agglomeration, which hinders the demonstration of its performance due to the characteristics of layered materials. Herein, we report a facile method for preparing monolayer Ti3C2Tx MXene on nickel foam to achieve a self-supporting structure for supercapacitor electrodes under high electrostatic fields. Moreover, the specific capacitance varies with the deposition of different-concentration monolayer Ti3C2Tx MXene on nickel foam. As a result, Ti3C2Tx/NF has a high specific capacitance of 319 mF cm-2 at 2 mA cm-2 and an excellent long-term cycling stability of 94.4% after 7000 cycles. It was observed that the areal specific capacitance increases, whereas the mass specific capacitance decreases with the increasing loading mass. Attributable to the effect of the high electrostatic field, the self-supporting structure of the Ti3C2Tx/NF becomes denser as the concentration of the monolayer Ti3C2Tx MXene ink increases, ultimately affecting its electrochemical performance. This work provides a simple way to overcome the agglomeration problem of few-layer or monolayer MXene, then form a self-supporting electrode exhibiting excellent electrochemical performance.
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Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow-derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell-cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid-binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.
Osteoporosis is a common disease, usually diagnosed by decreased bone density and increased fragility. The people with osteoporosis has higher risk of fractures. Nearly one-third of the aged people will suffer from osteoporosis-related fractures and even lose their lives because of this. Therefore, there is an urgent need for early intervention and effective treatment options for osteoporosis in the aging population. Bone tissue is a highly dynamic tissue that undergoes continuous remodeling throughout an individual's entire life. The balance of remodeling depends on the bone formation mediated by osteoblasts and bone resorption by osteoclasts. When this balance is disrupted, osteoporosis occurs. Thus, the aim of our research is to explore the behind mechanism of this imbalance. Here, we demonstrate that the loss of Arid1a, a chromatin remodeler, leads to chromatin reprogramming that restricts access to promoters by transcription factors such as Jun/Fos, thereby suppressing osteoclast activation and bone resorption. Our findings offer insights into the epigenetic mechanisms underlying osteoporosis and suggest potential strategies for its prevention and treatment.
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Diferenciación Celular , Proteínas de Unión al ADN , Epigénesis Genética , Osteoclastos , Osteogénesis , Factores de Transcripción , Regulación hacia Arriba , Animales , Osteoclastos/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Osteogénesis/genética , Ratones , Ensamble y Desensamble de Cromatina , Lectinas/metabolismo , Lectinas/genética , Femenino , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Ratones Noqueados , Macrófagos/metabolismoRESUMEN
Strain-hardening cementitious composite (SHCC) has the obvious advantages of excellent material properties such as its high tensile and compressive strengths, high tensile strain capacity, and excellent durability against multi-cracking performance with very fine crack widths. In particular, the multi-cracking performance of SHCC during structural utilization is obviously reduced compared to that of SHCC in uniaxial tension tests using dumbbell-shaped specimens of small size. The corresponding tensile strain capacity of SHCC during structural utilization is, thus, significantly decreased compared to that of SHCC in uniaxial tension tests. However, the reduction in the ductility of SHCC during structural utilization has not been sufficiently understood, and further study is required. This paper presents an experimental investigation into the ductility variation of flexural-failed and shear-failed SHCC members as well as the ductility improvement of SHCC members with steel reinforcement compared with that of SHCC in uniaxial tension tests using small-sized specimens. This study focuses on not only the decrease in the crack elongation performance of the SHCC material during structural utilization but also the increase in the crack elongation performance of SHCC members with steel reinforcement. The results demonstrate that the crack elongation performance of flexural-failed and shear-failed SHCC members is significantly reduced compared to that of SHCC in the uniaxial tension tests. Moreover, it was confirmed that steel reinforcement can effectively improve the SHCC member, increasing the strain-hardening capacity and multi-cracking performance. The load-carrying capacity of the flexural-failed SHCC member with steel reinforcement seemed to increase linearly with an increase in the reinforcement ratio, accompanied by an increase in the distribution of multiple fine cracks in the flexural-failed SHCC member with steel reinforcement.
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The staple food crop winter bread wheat (Triticum aestivum) acquires competence to flower in late spring after experiencing prolonged cold in temperate winter seasons, through the physiological process of vernalization. Prolonged cold exposure results in transcriptional repression of the floral repressor VERNALIZATION 2 (TaVRN2) and activates the expression of the potent floral promoter VERNALIZATION 1 (TaVRN1). Cold-induced TaVRN1 activation and TaVRN2 repression are maintained in post-cold vegetative growth and development, leading to an epigenetic 'memory of winter cold', enabling spring flowering. When and how the cold memory is reset in wheat is essentially unknown. Here we report that the cold-induced TaVRN1 activation is inherited by early embryos, but reset in subsequent embryo development, whereas TaVRN2 remains silenced through seed development, but is reactivated rapidly by light during seed germination. We further found that a chromatin reader mediates embryonic resetting of TaVRN1 and that chromatin modifications play an important role in the regulation of TaVRN1 expression and thus the floral transition, in response to developmental state and environmental cues. The findings define a two-step molecular mechanism for re-establishing vernalization requirement in common wheat, ensuring that each generation must experience winter cold to acquire competence to flower in spring.
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Flores , Triticum , Estaciones del Año , Cromatina/metabolismo , Regiones Promotoras Genéticas , Regulación de la Expresión Génica de las PlantasRESUMEN
OBJECTIVE: Observational studies have suggested an association between frozen shoulder (FS) and carpal tunnel syndrome (CTS). However, due to challenges in establishing a temporal sequence, the causal relationship between these two conditions remains elusive. This study, based on aggregated data from large-scale population-wide genome-wide association studies (GWAS), investigates the genetic causality between FS and CTS. METHODS: Initially, a series of quality control measures were employed to select single nucleotide polymorphisms (SNPs) closely associated with the exposure factors. Two-sample Mendelian randomization (MR) was utilized to examine the genetic causality between FS and CTS, employing methods including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode approaches. Subsequently, sensitivity analyses were conducted to assess the robustness of the MR analysis results. RESULTS: IVW analysis results indicate a positive causal relationship between CTS and FS (p < 0.05, OR > 1), while a negative causal relationship between the two conditions was not observed. Heterogeneity tests suggest minimal heterogeneity in our IVW analysis results (p > 0.05). Multivariable MR testing also indicates no pleiotropy in our IVW analysis (p > 0.05), and stepwise exclusion tests demonstrate the reliability and stability of the MR analysis results. Gene Ontology (GO) pathway analysis reveals enrichment of genes regulated by the associated SNPs in the TGFß-related pathways. CONCLUSION: This study provides evidence of the genetic causal association between frozen shoulder and carpal tunnel syndrome and provides new insights into the genetics of fibrotic disorders.
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Bursitis , Síndrome del Túnel Carpiano , Humanos , Síndrome del Túnel Carpiano/diagnóstico , Síndrome del Túnel Carpiano/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Reproducibilidad de los ResultadosRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.
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COVID-19 , Receptores ErbB , Transducción de Señal , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Receptores ErbB/genética , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib/uso terapéutico , Síndrome Post Agudo de COVID-19 , Fibrosis Pulmonar/metabolismo , SARS-CoV-2/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Single-layer tunnel lining using shotcrete has the significant advantages of reducing the tunnel excavation volume and saving construction materials, which has been gradually applied in tunnel construction. The high-performance concretes are generally adopted in single-layer tunnel lining for enhancing the bearing capacity of the tunnel lining, whereas the single-layer tunnel lining may still induce damages due to the adverse conditions such as shallow buried depth of the tunnel, and further study related to its application condition is thus required. This paper presents a study of the single-layer tunnel lining with shotcrete employed for supporting the large-span tunnel, in which the reinforcement ribs are also adopted in the single-layer lining for improving the lining stiffness and strength. The study is implemented using numerical simulation, focusing on the safety and performance variation of the single-layer tunnel lining influenced from the varied lining thicknesses and shallow buried depths of the tunnel. The results shows that the single-layer tunnel lining has the obvious advantage of toughness in significantly absorbing large deformation of surrounding rocks and improving the ability to resist lining cracking. The results also demonstrate that the single-layer tunnel lining with shotcrete and reinforcement ribs can safely support the large-span tunnel, in which the stability and safety of the large-span tunnel are confirmed from both the tunnel deformation and lining stresses. Moreover, the factors related to both the lining thickness and shallow buried depth of the tunnel have great influence on the single-layer tunnel lining with shotcrete and reinforcement ribs, in which the insufficient lining thickness and excessive shallow buried depth of the tunnel can induce the damages of the single-layer tunnel lining due to shotcrete stresses exceeding its strength. This study provides some references of employing the single-layer tunnel lining with shotcrete and reinforcement ribs for supporting large-span tunnel.
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It is important to develop simple and effective approaches for hypochlorite (OCl-) detection at trace levels due to its widespread use as a disinfectant especially for water treatments including drinking water. In this work, a simple, facile colorimetric sensor for the sensitive determination of hypochlorite was developed based on the oxidation of cysteine by OCl-, a process that prohibits the cysteine-triggered aggregation of Au nanoparticles (AuNPs) stabilized by polyvinylpyrrolidone. With this strategy, the concentration of OCl- could be detected with the naked eye and/or ultraviolet-visible spectroscopy, and the limit of detection for OCl- was 1.0 µM and 250 nM, respectively. Additionally, the proposed method shows excellent anti-interference capability against many other interfering ions and real water sample applicability.
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Aneurisma Falso , Aneurisma , Aneurisma Cardíaco , Infarto del Miocardio , Humanos , Aneurisma Falso/complicaciones , Aneurisma Falso/diagnóstico por imagen , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Imagen Multimodal , Aneurisma/complicaciones , Aneurisma Cardíaco/complicaciones , Aneurisma Cardíaco/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagenRESUMEN
Metastasis is the major cause of cancer deaths, and cancer cells evolve to adapt to various tumor microenvironments, which hinders the treatment of tumor metastasis. Platelets play critical roles in tumor development, especially during metastasis. Here, we elucidate the role of platelet mitochondria in tumor metastasis. Cancer cells are reprogrammed to a metastatic state through the acquisition of platelet mitochondria via the PINK1/Parkin-Mfn2 pathway. Furthermore, platelet mitochondria regulate the GSH/GSSG ratio and reactive oxygen species (ROS) in cancer cells to promote lung metastasis of osteosarcoma. Impairing platelet mitochondrial function has proven to be an efficient approach to impair metastasis, providing a direction for osteosarcoma therapy. Our findings demonstrate mitochondrial transfer between platelets and cancer cells and suggest a role for platelet mitochondria in tumor metastasis.
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Neoplasias Óseas , Osteosarcoma , Humanos , Especies Reactivas de Oxígeno/metabolismo , Plaquetas/metabolismo , Osteosarcoma/metabolismo , Neoplasias Óseas/metabolismo , Mitocondrias/metabolismo , Microambiente TumoralRESUMEN
Kunitz-like protease inhibitors (KTIs) have been identified to play critical roles in insect defense, but evidence for their involvement in drought stress is sparse. The aim of this study was to identify and functionally characterize a Kunitz-like protease inhibitor, GsKTI, from the wild soybean (Glycine soja) variety ED059. Expression patterns suggest that drought stress and insect herbivory may induce GsKTI transcript levels. Transgenic Arabidopsis lines overexpressing GsKTI have been shown to exhibit enhanced drought tolerance by regulating the ABA signaling pathway and increasing xylem cell number. Transgenic Arabidopsis leaves overexpressing GsKTI interfered with insect digestion and thus had a negative effect on the growth of Helicoverpa armigera. It is concluded that GsKTI increases resistance to drought stress and insect attack in transgenic Arabidopsis lines.