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Perovskite nanocrystals (PCNs) exhibit a significant quantum confinement effect that enhances multiexciton generation, making them promising for photocatalytic CO2 reduction. However, their conversion efficiency is hindered by poor exciton dissociation. To address this, we synthesized ferrocene-methanol-functionalized CsPbBr3 (CPB/FcMeOH) using a ligand engineering approach. By manipulating the electronic coupling between ligands and the PCN surface, facilitated by the increased dipole moment from hydrogen bonding in FcMeOH molecules, we effectively controlled exciton dissociation and interfacial charge transfer. Under 5 h of irradiation, the CO yield of CPB/FcMeOH reached 772.79 µmol g-1, 4.95 times higher than pristine CPB. This high activity is due to the formation of hydrogen-bonded FcMeOH clusters on the CPB surface. The nonpolar disruption and strong dipole moment of FcMeOH molecules enhance electronic coupling between the FcMeOH ligands and the CPB surface, reducing the surface barrier energy. Consequently, exciton dissociation and interfacial charge transfer are promoted, efficiently utilizing multiple excitons in quantum-confined domains. Transient absorption spectroscopy confirms that CPB/FcMeOH exhibits optimized exciton behavior with fast internal relaxation, trapping, and a short recombination time, allowing photogenerated charges to more rapidly participate in CO2 reduction.
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BACKGROUND: Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI), but the underlying pathogenesis remains largely unknown. METHODS AND RESULTS: We generated eukaryotic translation initiation factor 5 (Eif5) conditional knockout mice aiming to investigate the function of eIF5 during oocyte growth and follicle development. Here, we demonstrated that Eif5 deletion in mouse primordial and growing oocytes both resulted in the apoptosis of oocytes within the early-growing follicles. Further studies revealed that Eif5 deletion in oocytes downregulated the levels of mitochondrial fission-related proteins (p-DRP1, FIS1, MFF and MTFR) and upregulated the levels of the integrated stress response-related proteins (AARS1, SHMT2 and SLC7A1) and genes (Atf4, Ddit3 and Fgf21). Consistent with this, Eif5 deletion in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased adenosine triphosphate content and mtDNA copy numbers, and excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Meanwhile, Eif5 deletion in oocytes led to a significant increase in the levels of DNA damage response proteins (γH2AX, p-CHK2 and p-p53) and proapoptotic proteins (PUMA and BAX), as well as a significant decrease in the levels of anti-apoptotic protein BCL-xL. CONCLUSION: These findings indicate that Eif5 deletion in mouse oocytes results in the apoptosis of oocytes within the early-growing follicles via mitochondrial fission defects, excessive ROS accumulation and DNA damage. This study provides new insights into pathogenesis, genetic diagnosis and potential therapeutic targets for POI. KEY POINTS: Eif5 deletion in oocytes leads to arrest in oocyte growth and follicle development. Eif5 deletion in oocytes impairs the translation of mitochondrial fission-related proteins, followed by mitochondrial dysfunction. Depletion of Eif5 causes oocyte apoptosis via ROS accumulation and DNA damage response pathway.
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Apoptose , Dano ao DNA , Camundongos Knockout , Oócitos , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Oócitos/metabolismo , Dano ao DNA/genética , Feminino , Apoptose/genética , Dinâmica Mitocondrial/genética , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Fator de Iniciação de Tradução Eucariótico 5A , Folículo Ovariano/metabolismo , Folículo Ovariano/crescimento & desenvolvimentoRESUMO
Phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) contributes to vascular remodeling in hypoxic pulmonary hypertension (PH). Recent studies have suggested that circular RNAs (circRNAs) may play important roles in the vascular remodeling of hypoxia-induced PH. However, whether circRNAs cause pulmonary vascular remodeling by regulating the phenotypic transformation in PH has not been investigated. Microarray and RT-qPCR analysis identified that circLMBR1, a novel circRNA, decreased in mouse lung tissues of the hypoxia-SU5416 PH model, as well as in human PASMCs and mouse PASMCs exposed to hypoxia. Overexpression of circLMBR1 in the Semaxinib (SU5416) mouse model ameliorated hypoxia-induced PH and vascular remodeling in the lungs. Notably, circLMBR1 was mainly distributed in the nucleus and bound to the splicing factor PUF60. CircLMBR1 suppressed the phenotypic transformation of human PASMCs and vascular remodeling by inhibiting PUF60 expression. Furthermore, we identified U2AF65 as the downstream regulatory factor of PUF60. U2AF65 directly interacted with the pre-mRNA of the contractile phenotype marker smooth muscle protein 22-α (SM22α) and inhibited its splicing. Meanwhile, hypoxia exposure increased the formation of the PUF60-U2AF65 complex, thereby inhibiting SM22α production and inducing the transition of human PASMCs from a contractile phenotype to a synthetic phenotype. Overall, our results verified the important role of circLMBR1 in the pathological process of PH. We also proposed a new circLMBR1/PUF60-U2AF65/pre-SM22α pathway that could regulate the phenotypic transformation and proliferation of human PASMCs. This study may provide new perspectives for the diagnosis and treatment of PH.
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DDB1-Cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte. The depletion of Dcaf2 in germ cells by crossing Dcaf2fl/fl mice with stimulated by retinoic acid gene 8(Stra8)-Cre mice caused a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further studies showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins, cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG), decreasing of cell proliferation, increasing of DNA damage and apoptosis. Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells, which is exacerbated by co-overexpression of p21 and TDG. The findings indicate that DCAF2 maintains the proliferation and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG during the S phase.
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Ultrasound (US) generates toxic reactive oxygen species (ROS) by acting on sonosensitizers for cancer treatment, and the mechanical damage induced by cavitation effects under US is equally significant. Therefore, designing a novel sonosensitizer that simultaneously possesses efficient ROS generation and enhanced mechanical effects is promising. In this study, carbon-doped zinc oxide nanoparticles (C-ZnO) are constructed for mechano-sonodynamic cancer therapy. The presence of carbon (C) doping optimizes the electronic structure, thereby enhancing the ROS generation triggered by US, efficiently inducing tumor cell death. On the other hand, the high specific surface area and porous structure brought about by C doping enable C-ZnO to enhance the mechanical stress induced by cavitation bubbles under US irradiation, causing severe mechanical damage to tumor cells. Under the dual effects of sonodynamic therapy (SDT) and mechanical therapy mediated by C-ZnO, excellent anti-tumor efficacy is demonstrated both in vitro and in vivo, along with a high level of biological safety. This is the first instance of utilizing an inorganic nanomaterial to achieve simultaneous enhancement of ROS production and US-induced mechanical effects for cancer therapy. This holds significant importance for the future development of novel sonosensitizers and advancing the applications of US in cancer treatment.
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Estruturas Metalorgânicas , Nanopartículas , Espécies Reativas de Oxigênio , Terapia por Ultrassom , Óxido de Zinco , Óxido de Zinco/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Animais , Terapia por Ultrassom/métodos , Linhagem Celular Tumoral , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Carbono/química , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.
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Background and Aims: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing. Methods: Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2). FL1 and FL2 patients were divided into two groups, those with either hyperlipidemia or non-hyperlipidemia based on their blood lipids. Potential keystone species within the groups were identified using univariate analysis and a specificity-occupancy plot. Significant difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence analysis. Results: Decreased gut bacterial diversity was found in patients with NAFLD. Firmicutes/Bacteroidetes decreased as NAFLD progressed. Faecalibacterium and Ruminococcus 2 were the most representative fatty-related bacteria. Glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count were selected as the most significant biochemical indexes. Calculation of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing FL1. Conclusions: Faecalibacterium and Ruminococcus 2, combined with glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count distinguished NAFLD. We speculate that regulating the health of gut microbiota may release NAFLD, in addition to providing new targets for clinicians to treat NAFLD.
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Intra-articular injection of drugs is an effective strategy for osteoarthritis (OA) treatment. However, the complex microenvironment and limited joint space result in rapid clearance of drugs. Herein, a nanogel-based strategy is proposed for prolonged drug delivery and microenvironment remodeling. Nanogel is constructed through the functionalization of hyaluronic acid (HA) by amide reaction on the surface of Kartogenin (KGN)-loaded zeolitic imidazolate framework-8 (denoted as KZIF@HA). Leveraging the inherent hydrophilicity of HA, KZIF@HA spontaneously forms nanogels, ensuring extended drug release in the OA microenvironment. KZIF@HA exhibits sustained drug release over one month, with low leakage risk from the joint cavity compared to KZIF, enhanced cartilage penetration, and reparative effects on chondrocytes. Notably, KGN released from KZIF@HA serves to promote extracellular matrix (ECM) secretion for hyaline cartilage regeneration. Zn2+ release reverses OA progression by promoting M2 macrophage polarization to establish an anti-inflammatory microenvironment. Ultimately, KZIF@HA facilitates cartilage regeneration and OA alleviation within three months. Transcriptome sequencing validates that KZIF@HA stimulates the polarization of M2 macrophages and secretes IL-10 to inhibit the JNK and ERK pathways, promoting chondrocytes recovery and enhancing ECM remodeling. This pioneering nanogel system offers new therapeutic opportunities for sustained drug release, presenting a significant stride in OA treatment strategies.
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BACKGROUND: Pulmonary hypertension (PH) is a complex vascular disorder, characterized by pulmonary vessel remodeling and perivascular inflammation. Pulmonary arterial smooth muscle cells (PASMCs) pyroptosis is a novel pathological mechanism implicated of pulmonary vessel remodeling. However, the involvement of circRNAs in the process of pyroptosis and the underlying regulatory mechanisms remain inadequately understood. METHODS: Western blotting, PI staining and LDH release were used to explore the role of circLrch3 in PASMCs pyroptosis. Moreover, S9.6 dot blot and DRIP-PCR were used to assess the formation of R-loop between circLrch3 and its host gene Lrch3. Chip-qPCR were used to evaluate the mechanism of super enhancer-associated circLrh3, which is transcriptionally activated by the transcription factor Tbx2. RESULTS: CircLrch3 was markedly upregulated in hypoxic PASMCs. CircLrch3 knockdown inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circLrch3 can form R-loop with host gene to upregulate the protein and mRNA expression of Lrch3. Furthermore, super enhancer interacted with the Tbx2 at the Lrch3 promoter locus, mediating the augmented transcription of circLrch3. CONCLUSION: Our findings clarify the role of a super enhancer-associated circLrch3 in the formation of R-loop with the host gene Lrch3 to modulate pyroptosis in PASMCs, ultimately promoting the development of PH.
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Miócitos de Músculo Liso , Artéria Pulmonar , Piroptose , RNA Circular , Piroptose/genética , RNA Circular/genética , RNA Circular/metabolismo , Animais , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Miócitos de Músculo Liso/metabolismo , Ratos , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Hipóxia Celular/genética , Músculo Liso Vascular/metabolismo , Masculino , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Regulação da Expressão Gênica , Elementos Facilitadores Genéticos/genética , Hipóxia/genética , Hipóxia/metabolismo , Super IntensificadoresRESUMO
Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.
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Antineoplásicos , Receptores Frizzled , Neoplasias , Via de Sinalização Wnt , Humanos , Receptores Frizzled/metabolismo , Receptores Frizzled/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Animais , Terapia de Alvo Molecular/métodosRESUMO
Porous organic cages (POCs) represent a notable category of porous materials, showing remarkable material properties due to their inherent porosity. Unlike extended frameworks which are constructed by strong covalent or coordination bonds, POCs are composed of discrete molecular units held together by weak intermolecular forces. Their structure and chemical traits can be systematically tailored, making them suitable for a range of applications including gas storage and separation, molecular separation and recognition, catalysis, and proton and ion conduction. This review provides a comprehensive overview of POCs, covering their synthesis methods, structure and properties, computational approaches, and applications, serving as a primer for those who are new to the domain. A special emphasis is placed on the growing role of computational methods, highlighting how advanced data-driven techniques and automation are increasingly aiding the rapid exploration and understanding of POCs. We conclude by addressing the prevailing challenges and future prospects in the field.
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Photodynamic therapy's antitumor efficacy is hindered by the inefficient generation of reactive oxygen species (ROS) due to the photogenerated electron-hole pairs recombination of photosensitizers (PS). Therefore, there is an urgent need to develop efficient PSs with enhanced carrier dynamics. Herein, we designed Schottky junctions composed of cobalt tetroxide and palladium nanocubes (Co3O4@Pd) with a built-in electric field as effective PS. The built-in electric field enhanced photogenerated charge separation and migration, resulting in the generation of abundant electron-hole pairs and allowing effective production of ROS. Thanks to the built-in electric field, the photocurrent intensity and carrier lifetime of Co3O4@Pd were approximately 2 and 3 times those of Co3O4, respectively. Besides, the signal intensity of hydroxyl radical and singlet oxygen increased to 253.4% and 135.9%, respectively. Moreover, the localized surface plasmon resonance effect of Pd also enhanced the photothermal conversion efficiency of Co3O4@Pd to 40.50%. In vitro cellular level and in vivo xenograft model evaluations demonstrated that Co3O4@Pd could generate large amounts of ROS, trigger apoptosis, and inhibit tumor growth under near-infrared laser irradiation. Generally, this study reveals the contribution of the built-in electric field to improving photodynamic performance and provides new ideas for designing efficient inorganic PSs.
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Cobalto , Neoplasias , Óxidos , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Neoplasias/tratamento farmacológico , Raios InfravermelhosRESUMO
AIMS: Alzheimer's disease (AD) is a significant global health concern, and it is crucial that we find effective methods to prevent or slow down AD progression. Recent studies have highlighted the essential role of blood vessels in clearing Aß, a protein that contributes to AD. Scientists are exploring blood biomarkers as a potential tool for future AD diagnosis. One promising method that may help prevent AD is remote ischemic conditioning (RIC). RIC involves using sub-lethal ischemic-reperfusion cycles on limbs. However, a comprehensive understanding of how RIC can prevent AD and its long-term effectiveness is still lacking. Further research is essential to fully comprehend the potential benefits of RIC in preventing AD. METHODS: Female wild-type (WT) and APP/PS1 transgenic rats, aged 12 months, underwent ovariectomy and were subsequently assigned to WT, APP/PS1, and APP/PS1 + RIC groups. RIC was conducted five times a week for 4 weeks. The rats' depressive and cognitive behaviors were evaluated using force swimming, open-field tests, novel objective recognition, elevated plus maze, and Barnes maze tests. Evaluation of the neurovascular unit (NVU), synapses, vasculature, astrocytes, and microglia was conducted using immunofluorescence staining (IF), Western blot (WB), and transmission electron microscopy (TEM). Additionally, the cerebro-vasculature was examined using micro-CT, and cerebral blood flow (CBF) was measured using Speckle Doppler. Blood-brain barrier (BBB) permeability was determined by measuring the Evans blue leakage. Finally, Aß levels in the rat frontal cortex were measured using WB, ELISA, or IF staining. RESULTS: RIC enhanced memory-related protein expression and rescued depressive-like behavior and cognitive decline in APP/PS1 transgenic rats. Additionally, the intervention protected NVU in the rat frontal cortex, as evidenced by (1) increased expression of TJ (tight junction) proteins, pericyte marker PDGFRß, and glucose transporter 1 (GLUT1), as well as decreased VCAM1; (2) mitigation of ultrastructure impairment in neuron, cerebral vascular, and astrocyte; (3) upregulation of A2 astrocyte phenotype markers and downregulation of A1 phenotype markers, indicating a shift toward a healthier phenotype. Correspondingly, RIC intervention alleviated neuroinflammation, as evidenced by the decreased Iba1 level, a microglia marker. Meanwhile, RIC intervention elevated CBF in frontal cortex of the rats. Notably, RIC intervention effectively suppressed Aß toxicity, as demonstrated by the enhancement of α-secretase and attenuation of ß-secretase (BACE1) and γ- secretase and Aß1-42 and Aß1-40 levels as well. CONCLUSION: Chronic RIC intervention exerts vascular and neuroprotective roles, suggesting that RIC could be a promising therapeutic strategy targeting the BBB and NVU during AD development.
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Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Ratos , Feminino , Animais , Barreira Hematoencefálica/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Camundongos Transgênicos , Ratos Transgênicos , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/terapia , Modelos Animais de Doenças , Presenilina-1/genética , Presenilina-1/metabolismoRESUMO
Brain-derived estrogen (BDE2) is gaining attention as an endogenous neurotransmitter. Recent research has revealed that selectively removing the aromatase gene, the pivotal enzyme responsible for BDE2 synthesis, in forebrain neurons or astrocytes can lead to synaptic loss and cognitive impairment. It is worth noting that remote ischemia post-conditioning (RIP), a non-invasive technique, has been shown to activate natural protective mechanisms against severe ischemic events. The aim of our study was to investigate whether RIP triggers aromatase-BDE2 signaling, shedding light on its neuroprotective mechanisms after global cerebral ischemia (GCI) in ovariectomized rats. Our findings are as follows: (1) RIP was effective in mitigating ischemic damage in hippocampal CA1 neurons and improved cognitive function after GCI. This was partially due to increased Aro-BDE2 signaling in CA1 neurons. (2) RIP intervention efficiently enhanced pro-survival kinase pathways, such as AKT, ERK1/2, CREB, and suppressed CaMKIIα signaling in CA1 astrocytes induced by GCI. Remarkably, inhibiting CaMKIIα activity led to elevated Aro-BDE2 levels and replicated the benefits of RIP. (3) We also identified the positive mediation of Cav1.2, an LVGCC calcium channel, on CaMKIIα-Aro/BDE2 pathway response to RIP intervention. (4) Significantly, either RIP or CaMKIIα inhibition was found to alleviate reactive astrogliosis, which was accompanied by increased pro-survival A2-astrocyte protein S100A10 and decreased pro-death A1-astrocyte marker C3 levels. In summary, our study provides compelling evidence that Aro-BDE2 signaling is a critical target for the reparative effects of RIP following ischemic insult. This effect may be mediated through the CaV1.2-CaMKIIα signaling pathway, in collaboration with astrocyte-neuron interactions, thereby maintaining calcium homeostasis in the neuronal microenvironment and reducing neuronal damage after ischemia.
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Aromatase , Isquemia Encefálica , Canais de Cálcio Tipo L , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Hipocampo , Pós-Condicionamento Isquêmico , Neurônios , Ovariectomia , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Feminino , Neurônios/metabolismo , Neurônios/patologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Pós-Condicionamento Isquêmico/métodos , Canais de Cálcio Tipo L/metabolismo , Aromatase/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Astrócitos/metabolismo , RatosRESUMO
Photo-catalytic CO2 reduction with perovskite quantum dots (QDs) shows potential for solar energy storage, but it encounters challenges due to the intricate multi-electron photoreduction processes and thermodynamic and kinetic obstacles associated with them. This study aimed to improve photo-catalytic performance by addressing surface barriers and utilizing multiple-exciton generation in perovskite QDs. A facile surface engineering method was employed, involving the grafting of ferrocene carboxylic acid (FCA) onto CsPbBr3 (CPB) QDs, to overcome limitations arising from restricted multiple-exciton dissociation and inefficient charge transfer dynamics. Kelvin Probe Force Microscopy and XPS spectral confirmed successfully creating an FCA-modulated microelectric field through the Cs active site, thus facilitating electron transfer, disrupting surface barrier energy, and promoting multi-exciton dissociations. Transient absorption spectroscopy showed enhanced charge transfer and reduced energy barriers, resulting in an impressive CO2-to-CO conversion rate of 132.8 µmol g-1 h-1 with 96.5% selectivity. The CPB-FCA catalyst exhibited four-cycle reusability and 72 h of long-term stability, marking a significant nine-fold improvement compared to pristine CPB (14.4 µmol g-1 h-1). These results provide insights into the influential role of FCA in regulating intramolecular charge transfer, enhancing multi-exciton dissociation, and improving CO2 photoreduction on CPB QDs. Furthermore, these findings offer valuable knowledge for controlling quantum-confined exciton dissociation to enhance CO2 photocatalysis.
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Background: Freezing of gait (FOG) is one of the most disabling gait disturbances in Parkinson's disease (PD), affecting mobility and balance severely, thereby leading to an increased risk of falls. Objectives: The purpose of this systematic review and meta-analysis was to investigate the effects of transcranial magnetic stimulation on FOG in PD. Methods: Based on PRISMA guidelines, we searched the databases of MEDLINE (PubMed), Cochrane Library, PEDro, Embase, and Web of Science. Studies of the English language published up to July 2023 were searched. We retrieved for studies of randomized controlled trials (RCTs) of transcranial magnetic stimulation to treat FOG after PD and screened by inclusion and exclusion criteria. Risk of bias was assessed using the Cochrane Collaboration's tool (Revman5.30). Characteristics of RCTs were extracted. The heterogeneity of the trials was measured by I2 statistic. The effect size was expressed by a standardized mean difference (SMD) with a 95% confidence interval (CI). Results: A total of 488 articles were screened, after screening sixteen RCTs involved in 408 patients were included in the qualitative analysis, and 15 RCTs were included in meta-analysis. The outcome measures included FOG-Q, walking time, TUG, and UPDRS. Six studies used FOG-Q as outcome measure, six studies used walking time, four studies used TUG, and six studies used UPDRS. Compared with placebo treatment, transcranial magnetic stimulation has positive significant effects in improving gait status with increased walking speed (SMD = -0.41, 95% CI = -0.75 to -0.06, I2 = 7% p = 0.02), FOG-Q scores (SMD = -0.55, 95% CI = -0.89 to -0.21, I2 = 29%, p = 0.002), UPDRS scores (SMD = -1.08, 95% CI = -1.39 to -0.78, I2 = 49%, P < 0.001) and the time of TUG (SMD = -0.56, 95% CI = -0.88 to -0.23, I2 = 25%, p = 0.02) decreased. Conclusion: Transcranial magnetic stimulation could significantly improving gait conditions in PD patients with FOG. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42023434286.
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Dynamic 3D covalent organic frameworks (COFs) have shown concerted structural transformation and adaptive gas adsorption due to the conformational diversity of organic linkers. However, the isolation and observation of COF rotamers constitute undergoing challenges due to their comparable free energy and subtle rotational energy barrier. Here, we report the atomic-level observation and structural evolution of COF rotamers by cryo-3D electron diffraction and synchrotron powder X-ray diffraction. Specifically, we optimize the crystallinity and morphology of COF-320 to manifest its coherent dynamic responses upon adaptive inclusion of guest molecules. We observe a significant crystal expansion of 29 vol% upon hydration and a giant swelling with volume change up to 78 vol% upon solvation. We record the structural evolution from a non-porous contracted phase to two narrow-pore intermediate phases and the fully opened expanded phase using n-butane as a stabilizing probe at ambient conditions. We uncover the rotational freedom of biphenylene giving rise to significant conformational changes on the diimine motifs from synclinal to syn-periplanar and anticlinal rotamers. We illustrate the 10-fold increment of pore volumes and 100% enhancement of methane uptake capacity of COF-320 at 100 bar and 298 K. The present findings shed light on the design of smarter organic porous materials to maximize host-guest interaction and boost gas uptake capacity through progressive structural transformation.
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Water availability (WA) is a key factor influencing the carbon cycle of terrestrial ecosystems under climate warming, but its effects on gross primary production (EWA-GPP ) at multiple time scales are poorly understood. We used ensemble empirical mode decomposition (EEMD) and partial correlation analysis to assess the WA-GPP relationship (RWA-GPP ) at different time scales, and geographically weighted regression (GWR) to analyze their temporal dynamics from 1982 to 2018 with multiple GPP datasets, including near-infrared radiance of vegetation GPP, FLUXCOM GPP, and eddy covariance-light-use efficiency GPP. We found that the 3- and 7-year time scales dominated global WA variability (61.18% and 11.95%), followed by the 17- and 40-year time scales (7.28% and 8.23%). The long-term trend also influenced 10.83% of the regions, mainly in humid areas. We found consistent spatiotemporal patterns of the EWA-GPP and RWA-GPP with different source products: In high-latitude regions, RWA-GPP changed from negative to positive as the time scale increased, while the opposite occurred in mid-low latitudes. Forests had weak RWA-GPP at all time scales, shrublands showed negative RWA-GPP at long time scales, and grassland (GL) showed a positive RWA-GPP at short time scales. Globally, the EWA-GPP , whether positive or negative, enhanced significantly at 3-, 7-, and 17-year time scales. For arid and humid zones, the semi-arid and sub-humid zones experienced a faster increase in the positive EWA-GPP , whereas the humid zones experienced a faster increase in the negative EWA-GPP . At the ecosystem types, the positive EWA-GPP at a 3-year time scale increased faster in GL, deciduous broadleaf forest, and savanna (SA), whereas the negative EWA-GPP at other time scales increased faster in evergreen needleleaf forest, woody savannas, and SA. Our study reveals the complex and dynamic EWA-GPP at multiple time scales, which provides a new perspective for understanding the responses of terrestrial ecosystems to climate change.
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Ecossistema , Água , Florestas , Ciclo do Carbono , Mudança ClimáticaRESUMO
Single-atom nanozymes (SAzymes), with well-defined and uniform atomic structures, are an emerging type of natural enzyme mimics. Currently, it is important but challenging to rationally design high-performance SAzymes and deeply reveal the interaction mechanism between SAzymes and substrate molecules. Herein, this work reports the controllable fabrication of a unique Cu-N1S2-centred SAzyme (Cu-N/S-C) via a chemical vapor deposition-based sulfur-engineering strategy. Benefiting from the optimized geometric and electronic structures of single-atom sites, Cu-N/S-C SAzyme shows boosted enzyme-like activity, especially in catalase-like activity, with a 13.8-fold increase in the affinity to hydrogen peroxide (H2O2) substrate and a 65.2-fold increase in the catalytic efficiency when compared to Cu-N-C SAzyme with Cu-N3 sites. Further theoretical studies reveal that the increased electron density around single-atom Cu is achieved through electron redistribution, and the efficient charge transfer between Cu-N/S-C and H2O2 is demonstrated to be more beneficial for the adsorption and activation of H2O2. The as-designed Cu-N/S-C SAzyme possesses an excellent antitumor effect through the synergy of catalytic therapy and oxygen-dependent phototherapy. This study provides a strategy for the rational design of SAzymes, and the proposed electron redistribution and charge transfer mechanism will help to understand the coordination environment effect of single-atom metal sites on H2O2-mediated enzyme-like catalytic processes.
Assuntos
Peróxido de Hidrogênio , Neoplasias , Humanos , Engenharia , Engenharia Química , Fototerapia , Catálise , Gases , Neoplasias/terapiaRESUMO
Single-atom nanozymes (SAzymes) are emerging natural enzyme mimics and have attracted much attention in the biomedical field. SAzymes with MetalâNx sites designed on carbon matrixes are currently the mainstream in research. It is of great significance to further expand the types of SAzymes to enrich the nanozyme library. Single-atom alloys (SAAs) are a material in which single-atom metal sites are dispersed onto another active metal matrix, and currently, there is limited research on their enzyme-like catalytic performance. In this work, a biodegradable Pt1Pd SAA is fabricated via a simple galvanic replacement strategy, and for the first time reveals its intrinsic enzyme-like catalytic performance including catalase-, oxidase-, and peroxidase-like activities, as well as its photodynamic effect. Experimental characterizations demonstrate that the introduction of single-atom Pt sites contributes to enhancing the affinity of Pt1Pd single-atom alloy nanozyme (SAAzyme) toward substrates, thus exhibiting boosted catalytic efficiency. In vitro and in vivo experiments demonstrate that Pt1Pd SAAzyme exhibits a photo-controlled therapeutic effect, with a tumor inhibition rate of up to 100%. This work provides vital guidance for opening the research direction of SAAs in enzyme-like catalysis.