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Histone lysine acylation, including acetylation and crotonylation, plays a pivotal role in gene transcription in health and diseases. However, our understanding of histone lysine acylation has been limited to gene transcriptional activation. Here, we report that histone H3 lysine 27 crotonylation (H3K27cr) directs gene transcriptional repression rather than activation. Specifically, H3K27cr in chromatin is selectively recognized by the YEATS domain of GAS41 in complex with SIN3A-HDAC1 co-repressors. Proto-oncogenic transcription factor MYC recruits GAS41/SIN3A-HDAC1 complex to repress genes in chromatin, including cell-cycle inhibitor p21. GAS41 knockout or H3K27cr-binding depletion results in p21 de-repression, cell-cycle arrest, and tumor growth inhibition in mice, explaining a causal relationship between GAS41 and MYC gene amplification and p21 downregulation in colorectal cancer. Our study suggests that H3K27 crotonylation signifies a previously unrecognized, distinct chromatin state for gene transcriptional repression in contrast to H3K27 trimethylation for transcriptional silencing and H3K27 acetylation for transcriptional activation.
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Cromatina , Histonas , Camundongos , Animais , Cromatina/genética , Histonas/metabolismo , Lisina/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica , AcetilaçãoRESUMO
Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine metabolism as monotherapy often exhibits limited efficacy, and the underlying mechanisms are incompletely understood. Here we report that activation of polyamine catabolism promotes glutamine metabolism, leading to a targetable vulnerability in lung cancer. Genetic and pharmacological activation of spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme of polyamine catabolism, enhances the conversion of glutamine to glutamate and subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress to support lung cancer cell proliferation and survival. Simultaneous glutamine limitation and SAT1 activation result in ROS accumulation, growth inhibition, and cell death. Importantly, pharmacological inhibition of either one of glutamine transport, glutaminase, or GSH biosynthesis in combination with activation of polyamine catabolism synergistically suppresses lung cancer cell growth and xenograft tumor formation. Together, this study unveils a previously unappreciated functional interconnection between polyamine catabolism and glutamine metabolism and establishes cotargeting strategies as potential therapeutics in lung cancer.
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Neoplasias Pulmonares , Humanos , Glutamina , Poliaminas/metabolismo , Pulmão/metabolismo , Morte Celular , Acetiltransferases/genética , Acetiltransferases/metabolismo , Espermina/metabolismoRESUMO
The commercialization of silicon anode for lithium-ion batteries has been hindered by severe structure fracture and continuous interfacial reaction against liquid electrolytes, which can be mitigated by solid-state electrolytes. However, rigid ceramic electrolyte suffers from large electrolyte/electrode interfacial resistance, and polymer electrolyte undergoes poor ionic conductivity, both of which are worsened by volume expansion of silicon. Herein, by dispersing Li1.3Al0.3Ti1.7(PO4)3 (LATP) into poly(vinylidene fluoride)-hexafluoropropylene (PVDF-HFP) and poly(ethylene oxide) (PEO) matrix, the PVDF-HFP/PEO/LATP (PHP-L) solid-state electrolyte with high ionic conductivity (1.40 × 10-3 S cm-1), high tensile strength and flexibility is designed, achieving brilliant compatibility with silicon nanosheets. The chemical interactions between PVDF-HFP and PEO, LATP increase amorphous degree of polymer, accelerating Li+ transfer. Good flexibility of the PHP-L contributes to adaptive structure variation of electrolyte with silicon expansion/shrinkage, ensuring swift interfacial ions transfer. Moreover, the solid membrane with high tensile limits electrode structural degradation and eliminates continuous interfacial growth to form stable 2D solid electrolyte interface (SEI) film, achieving superior cyclic performance to liquid electrolytes. The Si//PHP-L15//LiFePO4 solid-state full-cell exhibits stable lithium storage with 81% capacity retention after 100 cycles. This work demonstrates the effectiveness of composite solid electrolyte in addressing fundamental interfacial and performance challenges of silicon anodes.
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The maintenance of nuclear shape is essential for cellular homeostasis and disruptions in this process have been linked to various pathological conditions, including cancer, laminopathies, and aging. Despite the significance of nuclear shape, the precise molecular mechanisms controlling it are not fully understood. In this study, we have identified the YEATS domain-containing protein 4 (GAS41) as a previously unidentified factor involved in regulating nuclear morphology. Genetic ablation of GAS41 in colorectal cancer cells resulted in significant abnormalities in nuclear shape and inhibited cancer cell proliferation both in vitro and in vivo. Restoration experiments revealed that wild-type GAS41, but not a YEATS domain mutant devoid of histone H3 lysine 27 acetylation or crotonylation (H3K27ac/cr) binding, rescued the aberrant nuclear phenotypes in GAS41-deficient cells, highlighting the importance of GAS41's binding to H3K27ac/cr in nuclear shape regulation. Further experiments showed that GAS41 interacts with H3K27ac/cr to regulate the expression of key nuclear shape regulators, including LMNB1, LMNB2, SYNE4, and LEMD2. Mechanistically, GAS41 recruited BRD2 and the Mediator complex to gene loci of these regulators, promoting their transcriptional activation. Disruption of GAS41-H3K27ac/cr binding caused BRD2, MED14 and MED23 to dissociate from gene loci, leading to nuclear shape abnormalities. Overall, our findings demonstrate that GAS41 collaborates with BRD2 and the Mediator complex to control the expression of crucial nuclear shape regulators.
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Núcleo Celular , Neoplasias Colorretais , Fatores de Transcrição , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Animais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Núcleo Celular/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Linhagem Celular Tumoral , Proliferação de Células , Camundongos , Histonas/metabolismo , Camundongos Nus , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Células HCT116 , Proteínas que Contêm BromodomínioRESUMO
Human serum albumin (HSA) serves as a crucial indicator for therapeutic monitoring and biomedical diagnosis. In this study, a near infrared (NIR) fluorescent probe, termed BTPA, characterized a donor-π-acceptor (D-π-A) structure based on bridged triphenylamine (TPA) was developed. BTPA exhibited outstanding sensitivity and selectivity towards HSA among various analysts, with a remarkable 50-fold fluorescence enhancement with a significant Stokes shift (â¼190 nm) and a wide linear detection range of 0-20 µM of HSA. Especially, BTPA displayed selectivity for discrimination of HSA from BSA. Job's Plot analysis suggested a 1:1 stoichiometry for the formation of the BTPA-HSA complex. Displacement assays and molecular docking demonstrated that BTPA binds to subdomain IB of HSA which could effectively avoid interference from most drugs. Besides, BTPA have good biocompatibility and could detect of exogenous HSA with a relatively low fluorescence background. For practical applications, BTPA was tested for detecting HSA levels in human urine without any pretreatment, showing detection capability in the range of 0-10 µM with a fast response (<30 s), a limit of detection (LOD) of 0.12 µM and good recoveries (81.7-92.9 %), highlighting the high performance of bridged triphenylamine-based probe BTPA.
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Lithium (Li) metal batteries (LMBs) are deemed as ones of the most promising energy storage devices for next electrification applications. However, the uneven Li electroplating process caused by the diffusion-limited Li+ transportation at the Li metal surface inherently promotes the formation of dendritic morphology and instable Li interphase, while the sluggish Li+ transfer kinetic can also cause lithiation-induced stress on the cathode materials suffering from serious structural stability. Herein, a novel electrolyte designing strategy is proposed to accelerate the Li+ transfer by introducing a trace of large organic polar molecules of lithium phytate (LP) without significantly altering the electrolyte structure. The LP molecules can afford a competitive solvent attraction mechanism against the solvated Li+, enhancing both the bulk and interfacial Li+ transfer kinetic, and creating better anode/cathode interfaces to suppress the side reactions, resulting in much improved cycling efficiency of LMBs. Using LP-based electrolyte, the performance of LMB pouch cell with a practical capacity of ~1.5â Ah can be improved greatly. This strategy opens up a novel electrolyte designing route for reliable LMBs.
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The solid electrolyte interphase (SEI) membrane on the Li metal anode tends to breakdown and undergo reconstruction during operation, causing Li metal batteries to experience accelerated decay. Notably, an SEI membrane with self-healing characteristics can help considerably in stabilizing the Li-electrolyte interface; however, uniformly fixing the repairing agent onto the anode remains a challenging task. By leveraging the noteworthy film-forming attributes of bis(fluorosulfonyl)imide (FSI-) anions and the photopolymerization property of the vinyl group, the ionic liquid 1-vinyl-3-methylimidazolium bis(fluorosulfonyl)imide (VMI-FSI) was crosslinked with polyethylene oxide (PEO) in this study to form a self-healing film fixing FSI- groups as the repairing agent. When they encounter lithium metal, the FSI- groups are chemically decomposed into LiF & Li3N, which assist forming SEI membrane on lithium sheet and repairing SEI membrane in the cracks lacerated by lithium dendrite. Furthermore, the FSI- anions exchanged from film are electrochemically decomposed to generate inorganic salts to strengthen the SEI membrane. Benefiting from the self-healing behavior of the film, Li/LiCoO2 cells with the loading of 16.3â mg cm-2 exhibit the initial discharge capacities of 183.0â mAh â g-1 and are stably operated for 500â cycles with the retention rates of 81.4 % and the average coulombic efficiency of 99.97 %, operated between 3.0-4.5â V vs. Li+/Li. This study presents a new design approach for self-healing Li metal anodes and durable lithium metal battery.
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BACKGROUND & AIMS: Hepatocellular nodular lesions (HNLs) constitute a heterogeneous group of disorders. Differential diagnosis among these lesions, especially high-grade dysplastic nodules (HGDNs) and well-differentiated hepatocellular carcinoma (WD-HCC), can be challenging, let alone biopsy specimens. We aimed to develop a deep learning system to solve these puzzles, improving the histopathologic diagnosis of HNLs (WD-HCC, HGDN, low-grade DN, focal nodular hyperplasia, hepatocellular adenoma), and background tissues (nodular cirrhosis, normal liver tissue). METHODS: The samples consisting of surgical and biopsy specimens were collected from 6 hospitals. Each specimen was reviewed by 2 to 3 subspecialists. Four deep neural networks (ResNet50, InceptionV3, Xception, and the Ensemble) were used. Their performances were evaluated by confusion matrix, receiver operating characteristic curve, classification map, and heat map. The predictive efficiency of the optimal model was further verified by comparing with that of 9 pathologists. RESULTS: We obtained 213,280 patches from 1115 whole-slide images of 738 patients. An optimal model was finally chosen based on F1 score and area under the curve value, named hepatocellular-nodular artificial intelligence model (HnAIM), with the overall 7-category area under the curve of 0.935 in the independent external validation cohort. For biopsy specimens, the agreement rate with subspecialists' majority opinion was higher for HnAIM than 9 pathologists on both patch level and whole-slide images level. CONCLUSIONS: We first developed a deep learning diagnostic model for HNLs, which performed well and contributed to enhancing the diagnosis rate of early HCC and risk stratification of patients with HNLs. Furthermore, HnAIM had significant advantages in patch-level recognition, with important diagnostic implications for fragmentary or scarce biopsy specimens.
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Carcinoma Hepatocelular , Aprendizado Profundo , Hiperplasia Nodular Focal do Fígado , Neoplasias Hepáticas , Inteligência Artificial , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologiaRESUMO
Nanostructured transitional metal compounds (TMCs) have demonstrated extraordinary promise for high-efficient and rapid lithium storage. However, good performance is usually limited to electrodes with low mass loading (≤1.0 mg cm-2 ) and is difficult to realize at higher mass loading due to increased electrons/ions transport limitations in the thicker electrode. Herein, the multi-dimensional synergistic nanoarchitecture design of graphene-wrapped MnO@carbon microcapsules (capsule-like MnO@C-G) is reported, which demonstrates impressive mass loading-independent lithium storage properties. Highly porous MnO nanoclusters assembled by 0D nanocrystals facilitate sufficient electrolyte infiltration and shorten the solid-state ions transport path. 1D carbon shell, 2D graphene, and 3D continuous network with tight interconnection accelerate electrons transport inside the thick electrode. The capsule-like MnO@C-G delivers ultrahigh gravimetric capacity retention of 91.0% as the mass loading increases 4.3 times, while the areal capacities increase linearly with the mass loading at various current densities. Specifically, the capsule-like MnO@C electrode delivers a remarkable areal capacity of 2.0 mAh cm-2 at a mass loading of 3.0 mg cm-2 . Moreover, the capsule-like MnO@C also demonstrates excellent performance in full battery applications. This study demonstrates the effectiveness of multi-dimensional synergistic nanoarchitecture in achieving mass loading-independent performance, which can be extended to other TMCs for electrochemical energy storage.
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Titanium dioxide (TiO2 ) is a promising anode material for sodium-ion batteries (SIBs), which suffer from the intrinsic sluggish ion transferability and poor conductivity. To overcome these drawbacks, a facile strategy is developed to synergistically engineer the lattice defects (i.e., heteroatom doping and oxygen vacancy generation) and the fine microstructure (i.e., carbon hybridization and porous structure) of TiO2 -based anode, which efficiently enhances the sodium storage performance. Herein, it is successfully realized that the Si-doping into the MIL-125 metal-organic framework structure, which can be easily converted to SiO2 /TiO2-x @C nanotablets by annealing under inert atmosphere. After NaOH etching SiO2 /TiO2-x @C which contains unbonded SiO2 and chemically bonded SiOTi, thus the lattice Si-doped TiO2-x @C (Si-TiO2-x @C) nanotablets with rich Ti3+ /oxygen vacancies and abundant inner pores are developed. When examined as an anode for SIB, the Si-TiO2-x @C exhibits a high sodium storage capacity (285 mAh g-1 at 0.2 A g-1 ), excellent long-term cycling, and high-rate performances (190 mAh g-1 at 2 A g-1 after 2500 cycles with 95.1% capacity retention). Theoretical calculations indicate that the rich Ti3+ /oxygen vacancies and Si-doping synergistically contribute to a narrowed bandgap and lower sodiation barrier, which thus lead to fast electron/ion transfer coefficients and the predominant pseudocapacitive sodium storage behavior.
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An optimization model for the parameters of the pressure-resistant lens of an optical particle counter, based on Gaussian optics theory, was established to increase the measurement accuracy of the counter for high-pressure natural gas. Comparing the experimental and calculated values of the calibrated model, when the pressure-resistant lens is displaced by 2 mm under atmospheric pressure, the relative error of the measured body deformation is 0.15%. When the air pressure varies in the range 0.10-5.09 MPa, the maximum relative error of optical measurement volume deformation with the change of refractive index is 0.13%, which shows that the model has high reliability and accuracy.
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The key to gene therapy is the design of biocompatible and efficient delivery systems. In this work, a glutathione (GSH)-activated aggregation-induced-emission (AIE) cationic amphiphilic lipid, termed QM-SS-KK, was prepared for nonviral gene delivery. QM-SS-KK was composed of a hydrophilic biocompatible lysine tripeptide headgroup, a GSH-triggered disulfide linkage, and a hydrophobic AIE fluorophore QM-OH (QM: quinoline-malononitrile) tail. The peptide moiety could not only efficiently compact DNA but also well modulate the dispersion properties of QM-SS-KK, leading to the fluorescence-off state before GSH treatment. The cleavage of disulfide in QM-SS-KK by GSH generated AIE signals in situ with a tracking ability. The liposomes consisted of QM-SS-KK, and 1,2-dioleoylphosphatidylethanolamine (DOPE) (QM-SS-KK/DOPE) delivered plasmid DNAs (pDNAs) into cells with high efficiency. In particular, QM-SS-KK/DOPE had an enhanced transfection efficiency (TE) in the presence of 10% serum, which was two times higher than that of the commercial transfection agent PEI25K. These results highlighted the great potential of peptide and QM-based fluorescence AIE lipids for gene delivery applications.
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Técnicas de Transferência de Genes , Lipídeos , Lipídeos/química , Transfecção , Lipossomos/química , Terapia Genética , DNA/genética , Glutationa/genética , Cátions/químicaRESUMO
OBJECTIVE: Hard-to-heal wounds are a global health challenge, and effective treatments are still lacking. Moist exposed burn ointment (MEBO) and maggots are traditional treatments for promoting wound healing. This study was a preliminary exploration of combined maggot therapy and MEBO in the treatment of hard-to-heal wounds. METHOD: A coexistence experiment was conducted to determine the survival rates of maggots in MEBO. The maggots were placed in two different existence conditions: one set in MEBO (MEBO group), and another set as the control group (no MEBO) to compare survival rates. Case reports describe the use of the combined application of MEBO and maggots in the treatment of patients with hard-to-heal wounds. RESULTS: The coexistence experiment indicated that maggots in the MEBO group had a higher survival rate. From the therapeutic effect of the clinical cases (n=7), the combined application was safe and effective, with all the reported wounds eventually healing. CONCLUSION: Based on the findings of this study, we believe the combined application of MEBO and maggots is a promising way of promoting wound healing. Further studies and clinical trials are needed to elucidate the mechanism of the combined application in promoting wound healing and to more persuasively clarify the therapeutic effect.
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Sitosteroides , Cicatrização , Animais , Desbridamento , Humanos , Larva , Sitosteroides/farmacologiaRESUMO
Melanoma is a main factor that leads to skin cancer, and early diagnosis and treatment can significantly reduce the mortality of patients. Skin lesion boundary segmentation is a key to accurately localizing a lesion in dermoscopic images. However, the irregular shape and size of the lesions and the blurred boundary of the lesions pose significant challenges for researchers. In recent years, pixel-level semantic segmentation strategies based on convolutional neural networks have been widely used, but many methods still suffer from the inaccurate segmentation of fuzzy boundaries. In this paper, we proposed a multi-scale hybrid attentional convolutional neural network (MHAU-Net) for the precise localization and segmentation of skin lesions. MHAU-Net has four main components: multi-scale resolution input, hybrid residual attention (HRA), dilated convolution, and atrous spatial pyramid pooling. Multi-scale resolution inputs provide richer visual information, and HRA solves the problem of blurred boundaries and enhances the segmentation results. The Dice, mIoU, average specificity, and sensitivity on the ISIC2018 task 1 validation set were 93.69%, 90.02%, 92.7% and 93.9%, respectively. The segmentation metrics are significantly better than the latest DCSAU-Net, UNeXt, and U-Net, and excellent segmentation results are achieved on different datasets. We performed model robustness validations on the Kvasir-SEG dataset with an overall sensitivity and average specificity of 95.91% and 96.28%, respectively.
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Dermatopatias , Neoplasias Cutâneas , Humanos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Redes Neurais de Computação , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Progressão da DoençaRESUMO
The administration of ACEI/ARB (angiotensin-converting enzyme inhibitors/Angiotension II receptor blockers) in COVID-19 (coronavirus disease 2019) patients with hypertension exhibits a lower risk of mortality compared with ACEI/ARB non-users. In this context, an important question arises: is ACEI or ARB more suitable for the treatment of hypertensive COVID-19 patients? Taken into consideration the following four rationales, ARB may offer a more significant benefit than ACEI for the short-term treatment of hypertensive COVID-19 patients: 1. ACEI has no inhibition on non-ACE-mediated Ang II production under infection conditions, whereas ARB can function properly regardless of how Ang II is produced; 2. ACEI-induced bradykinin accumulation may instigate severe ARDS while ARB has no effects on kinin metabolism; 3. ARB alleviates viscous sputa production and inflammatory reaction significantly in contrast to ACEI; 4. ARB may attenuate the lung fibrosis induced by mechanical ventilation in severe patients and improve their prognosis significantly compared with ACEI. To examine the advantages of ARB over ACEI on hypertensive COVID-19 patients, retrospective case-control studies comparing the clinical outcomes for COVID-19 patients receiving ARB or ACEI treatment is strikingly needed in order to provide guidance for the clinical application.
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Bloqueadores do Receptor Tipo 2 de Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Tratamento Farmacológico da COVID-19 , Hipertensão/tratamento farmacológico , HumanosRESUMO
Uneven lithium (Li) electrodeposition hinders the wide application of high-energy-density Li metal batteries (LMBs). Current efforts mainly focus on the side-reaction suppression between Li and electrolyte, neglecting the determinant factor of mass transport in affecting Li deposition. Herein, guided Li+ mass transport under the action of a local electric field near magnetic nanoparticles or structures at the Li metal interface, known as the magnetohydrodynamic (MHD) effect, are proposed to promote uniform Li deposition. The modified Li+ trajectories are revealed by COMSOL Multiphysics simulations, and verified by the compact and disc-like Li depositions on a model Fe3 O4 substrate. Furthermore, a patterned mesh with the magnetic Fe-Cr2 O3 core-shell skeleton is used as a facile and efficient protective structure for Li metal anodes, enabling Li metal batteries to achieve a Coulombic efficiency of 99.5 % over 300 cycles at a high cathode loading of 5.0â mAh cm-2 . The Li protection strategy based on the MHD interface design might open a new opportunity to develop high-energy-density LMBs.
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Oxygen redox in Li-rich oxides may boost the energy density of lithium-ion batteries by incorporating oxygen chemistry in solid cathodes. However, oxygen redox in the bulk usually entangles with voltage hysteresis and oxygen release, resulting in a prolonged controversy in literature on oxygen transformation. Here, we report spectroscopic evidence of peroxo species formed and confined in silicate cathodes amid oxygen redox at high voltage, accompanied by Co2+ /Co3+ redox dominant at low voltage. First-principles calculations reveal that localized electrons on dangling oxygen drive the O-O dimerization. The covalence between the binding cation and the O-O dimer determines the degree of electron transfer in oxygen transformation. Dimerization induces irreversible structural distortion and slow kinetics. But peroxo formation can minimize the voltage drop and volume expansion in cumulative cationic and anionic redox. These findings offer insights into oxygen redox in the bulk for the rational design of high-energy-density cathodes.
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The wide applications of Ni-rich LiNi1- x-y Cox Mny O2 cathodes are severely limited by capacity fading and voltage fading during the cycling process resulting from the pulverization of particles, interfacial side reactions, and phase transformation. The canonical surface modification approach can improve the stability to a certain extent; however, it fails to resolve the key bottlenecks. The preparation of Li(Ni0.4 Co0.2 Mn0.4 )1- x Tix O2 on the surface of LiNi0.8 Co0.1 Mn0.1 O2 particles with a coprecipitation method is reported. After sintering, Ti diffuses into the interior and mainly distributes along surface and grain boundaries. A strong surface and grain boundary strengthening are simultaneously achieved. The pristine particles are fully pulverized into first particles due to mechanical instability and high strains, which results in serious capacity fading. In contrast, the strong surface and the grain boundary strengthening can maintain the structural integrity, and therefore significantly improve the cycle stability. A general and simple strategy for the design of high-performance Ni-rich LiNi1- x - y Cox Mny O2 cathode is provided and is applicable to surface modification and grain-boundary regulation of other advanced cathodes for batteries.
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This work reports a facile strategy to synthesize carbon-coated Li2CoSiO4/C particles with rich nanostructures by a two-step scheme starting with a low-temperature hydrothermal method. The size and morphology of particle aggregates can be regulated by the (OH-) concentration and viscosity of the precursor solution, a mixture of ethylene glycol and deionized water, for the hydrothermal synthesis. In addition to the good electrical conductivity from the carbon coating, the size of the primary nanoparticles and the mesopore associated with the aggregations play an important role in improving the electrochemical properties of polyanionic Li2CoSiO4. The low-dimensional belt-like and sheet-like Li2CoSiO4/C nanomaterials present a higher reversible capacity 136.6 mAh g-1 and 147 mAh g-1, respectively, in the first charging-discharging cycle between 2 V and 4.6 V. XRD, SEM/TEM, and EDS are used to characterize the crystalline structure and aggregation patterns. TGA and Raman spectra are employed to analyze the carbon coating on different morphologies. The analysis of electrochemical impedance spectroscopy highlights the critical role of the interface between the electrolyte and particles. This study provides insights into the rational design and synthesis of high-performance polyanionic cathodes including silicates.
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The present study was conducted to determine whether atorvastatin reduces hypertension-induced vascular remodelling and whether its effects involve protein kinase D (PKD) and extracellular signal-regulated kinase 5 (ERK5). We used 16-week-old spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats. The blood pressure and serum lipid concentration were measured. Changes in the vascular morphology and histology were examined using H&E, Masson' s trichrome, and Sirius Red staining. The media thickness (MT), ratio of MT to lumen diameter (LD) (MT/LD), collagen volume fraction (CVF) and hydroxyproline content were measured to evaluate vascular remodelling. Atorvastatin (50 mg/kg/day) was administered for 8 weeks. Increased blood pressure and vascular remodelling were more prominent in SHRs than in WKY rats. SHRs also had elevated PKD and ERK5 activation. The systolic blood pressure, MT/LD ratio, and hydroxyproline content were positively correlated with the activation level of PKD and ERK5 in SHRs. Atorvastatin significantly attenuated the activation of PKD and ERK5. Overall, this study demonstrated that atorvastatin could reverse vascular remodelling in SHRs. The PKD/ERK5 signalling pathway might be important for elucidating the beneficial pleiotropic effects of atorvastatin on vascular remodelling.