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Dilanthanide complexes with one-electron delocalization are important targets for understanding the specific 4f/5d-bonding feature in lanthanide chemistry. Here, we report an isolable azide-bridged dicerium complex 3 [{(TrapenTMS)Ce}2(µ-N3)]⢠[Trapen = tris (2-aminobenzyl)amine; TMS = SiMe3], which is synthesized by the reaction of tripodal ligand-supported (TrapenTMS)CeIVCl complex 2 with NaN3. The structure and bonding nature of 3 are fully characterized by X-ray crystal diffraction analysis, electron paramagnetic resonance (EPR), magnetic measurement, cyclic voltammetry, X-ray absorption spectroscopy, and quantum-theoretical studies. Complex 3 presents a trans-bent central Ce-N3-Ce unit with a single electron of two mixed-valent Ce atoms. The unique low-temperature (2 K) anisotropic EPR signals [g = 1.135, 2.003, and 3.034] of 3 indicate that its spin density is distributed on the central Ce-N3-Ce unit with marked electron delocalization. Quantum chemical analyses show strong 4f/5d orbital mixing in the singly occupied molecular orbital of 3, which allows for the unpaired electron to extend throughout the cerium-azide-cerium unit via a multicentered one-electron (Ce-N3-Ce) interaction. This work extends the family of mixed-valent dilanthanide complexes and provides a paradigm for understanding the bonding motif of ligand-bridged dilanthanide complexes.
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It is well established that sevoflurane exposure leads to widespread neuronal cell death in the developing brain. Adenosine deaminase acting on RNA-1 (ADAR1) dependent adenosine-to-inosine (A-to-I) RNA editing is dynamically regulated throughout brain development. The current investigation is designed to interrogate the contributed role of ADAR1 in developmental sevoflurane neurotoxicity. Herein, we provide evidence to show that developmental sevoflurane priming triggers neuronal pyroptosis, apoptosis and necroptosis (PANoptosis), and elicits the release of inflammatory factors including IL-1ß, IL-18, TNF-α and IFN-γ. Additionally, ADAR1-P150, but not ADAR1-P110, depresses cellular PANoptosis and inflammatory response by competing with Z-DNA/RNA binding protein 1 (ZBP1) for binding to Z-RNA in the presence of sevoflurane. Further investigation demonstrates that ADAR1-dependent A-to-I RNA editing mitigates developmental sevoflurane-induced neuronal PANoptosis. To restore RNA editing, we utilize adeno-associated virus (AAV) to deliver engineered circular ADAR-recruiting guide RNAs (cadRNAs) into cells, which is capable of recruiting endogenous adenosine deaminases to promote cellular A-to-I RNA editing. As anticipated, AAV-cadRNAs diminishes sevoflurane-induced cellular Z-RNA production and PANoptosis, which could be abolished by ADAR1-P150 shRNA transfection. Moreover, AAV-cadRNAs delivery ameliorates developmental sevoflurane-induced spatial and emotional cognitive deficits without influence on locomotor activity. Taken together, these results illustrate that ADAR1-P150 exhibits a prominent role in preventing ZBP1-dependent PANoptosis through A-to-I RNA editing in developmental sevoflurane neurotoxicity. Application of engineered cadRNAs to rectify the compromised ADAR1-dependent A-to-I RNA editing provides an inspiring direction for possible clinical preventions and therapeutics.
Assuntos
Adenosina Desaminase , Adenosina , Edição de RNA , Proteínas de Ligação a RNA , Sevoflurano , Animais , Adenosina/metabolismo , Adenosina Desaminase/metabolismo , Adenosina Desaminase/genética , Apoptose/efeitos dos fármacos , Inosina/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/metabolismo , Piroptose/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
Synaptic dysfunction is one of the earliest pathological processes that contribute to the development of many neurological disorders, including Alzheimer's disease and frontotemporal lobar degeneration. However, the synaptic function of many disease-causative genes and their contribution to the pathogenesis of the related diseases remain unclear. In this study, we investigated the synaptic role of fused in sarcoma, an RNA-binding protein linked to frontotemporal lobar degeneration and amyotrophic lateral sclerosis, and its potential pathological role in frontotemporal lobar degeneration using pyramidal neuron-specific conditional knockout mice (FuscKO). We found that FUS regulates the expression of many genes associated with synaptic function in a hippocampal subregion-specific manner, concomitant with the frontotemporal lobar degeneration-linked behavioural disinhibition. Electrophysiological study and molecular pathway analyses further reveal that fused in sarcoma differentially regulates synaptic and neuronal properties in the ventral hippocampus and medial prefrontal cortex, respectively. Moreover, fused in sarcoma selectively modulates the ventral hippocampus-prefrontal cortex projection, which is known to mediate the anxiety-like behaviour. Our findings unveil the brain region- and synapse-specific role of fused in sarcoma, whose impairment might lead to the emotional symptoms associated with frontotemporal lobar degeneration.
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Esclerose Lateral Amiotrófica , Demência Frontotemporal , Degeneração Lobar Frontotemporal , Sarcoma , Animais , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Encéfalo/patologia , Demência Frontotemporal/genética , Degeneração Lobar Frontotemporal/patologia , Proteína FUS de Ligação a RNA/genética , Sarcoma/metabolismo , Sarcoma/patologiaRESUMO
N,N-dimethylformamide (DMF) is widely used in various industries, but its direct release into water poses high risks to human beings. Although a lot of DMF-degrading bacteria has been isolated, limited studies focus on the degradation preference among DMF and its analogues. In this study, an efficient DMF mineralization bacterium designated Aminobacter ciceronei DMFA1 was isolated from marine sediment. When exposed to a 0.2% DMF (â¼1900 mg/L), strain DMFA1 exhibited a degradation efficiency of 100% within 4 days. The observed growth using formamide as the sole carbon source implied the possible DMF degradation pathway of strain DMFA1. Meanwhile,the strain DMFA1 possesses a broad-spectrum substrate degradation, which could effectively degraded 0.2% N,N-dimethylacetamide (DMAC) and N-methylformamide (NMF). Genomic analysis further confirmed the supposed pathway through annotating the genes encoding N, N-dimethylformamidase (DMFase), formamidase, and formate dehydrogenase. The existence of sole DMFase indicating its substrate specificity controlled the preference of DMAc of strain DMFA1. By integrating multiple sequence alignment, homology modeling and molecular docking, the preference of the DMFase in strain DMFA1 towards DMAc are related to: 1) Mutations in key active site residues; 2) the absence of small subunit; and 3) no energy barrier for substrates entering the active site.
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Dimetilformamida , Phyllobacteriaceae , Humanos , Dimetilformamida/metabolismo , Especificidade por Substrato , Simulação de Acoplamento MolecularRESUMO
The conductivity type is one of the most fundamental transport properties of semiconductors, which is usually identified by fabricating the field-effect transistor, the Hall-effect device, etc. However, it is challenging to obtain an Ohmic contact if the sample is down to nanometer-scale because of the small size and intrinsic heterogeneity. Noncontact dielectric force microscopy (DFM) can identify the conductivity type of the sample by applying a DC gate voltage to the tip, which is effective in tuning the accumulation or depletion of charge carriers. Here, we further developed a dual-modulation DFM, which simplified the conductivity type identification from multiple scan times under different DC gate voltages to a single scan under an AC gate voltage. Taking single-walled carbon nanotubes as testing samples, the semiconducting-type sample exhibits a more significant charge carrier accumulation/depletion under each half-period of the AC gate voltage than the metallic-type sample due to the stronger rectification effect. The charge carrier accumulation or depletion of the p-type sample is opposite to that of the n-type sample at the same half-period of the AC gate voltage because of the reversed charge carrier type.
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Red mud (RM), a bauxite residue, contains hazardous radioactive wastes and alkaline material and poses severe surface water and groundwater contamination risks, necessitating recycling. Pretreated RM can be used to make adsorbents for water treatment. However, its performance is affected by many factors, resulting in a nonlinear correlation and coupling relationship. This study aimed to identify the best formula for an RM adsorbent using a mathematical model that examines the relationship between 11 formulation types (e.g., pore-assisting agent, component modifier, and external binder) and 9 properties (e.g., specific surface area, wetting angle, and Zeta potential). This model was built using a back-propagation neural network (BP) based on single-factor experimental data and orthogonal experimental data. The model trained and predicted the established network structure to obtain the optimal adsorbent formula. The RM particle adsorbents had a pH of 10.16, specific surface area (BET) of 48.92 m2·g-1, pore volume of 2.10 cm3·g-1, compressive strength (ST) of 1.12 KPa, and 24 h immersion pulverization rate (ηm) of 3.72%. In the removal of total phosphorus in flotation tailings backwater, it exhibited a good adsorption capacity (Q) and total phosphorous removal rate (η) of 48.63 mg·g-1 and 95.13%, respectively.
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Chelating agents are commonly employed in microelectronic processes to prevent metal ion contamination. The ligand fragments of a chelating agent largely determine its binding strength to metal ions. Identification of ligands with suitable characteristics will facilitate the design of chelating agents to enhance the capture and removal of metal ions from the substrate in microelectronic processes. This study employed quantum chemical calculations to simulate the binding process between eleven ligands and the hydrated forms of Ni2+, Cu2+, Al3+, and Fe3+ ions. The binding strength between the metal ions and ligands was quantified using binding energy and binding enthalpy. Additionally, we explored the binding interaction mechanisms and explained the differences in binding abilities of the eleven ligands using frontier molecular orbitals, nucleophilic indexes, electrostatic potentials, and energy decomposition calculations based on molecular force fields. Based on our computational results, promising chelating agent structures are proposed, aiming to guide the design of new chelating agents to address metal ion contamination issues in integrated circuit processes.
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DNA damage is assumed to accumulate in stem cells over time and their ability to withstand this damage and maintain tissue homeostasis is the key determinant of aging. Nonetheless, relatively few studies have investigated whether DNA damage does indeed accumulate in stem cells and whether this contributes to stem cell aging and functional decline. Here, we found that, compared with young mice, DNA double-strand breaks (DSBs) are reduced in the subventricular zone (SVZ)-derived neural stem cells (NSCs) of aged mice, which was achieved partly through the adaptive upregulation of Sirt1 expression and non-homologous end joining (NHEJ)-mediated DNA repair. Sirt1 deficiency abolished this effect, leading to stem cell exhaustion, olfactory memory decline, and accelerated aging. The reduced DSBs and the upregulation of Sirt1 expression in SVZ-derived NSCs with age may represent a compensatory mechanism that evolved to protect stem cells from excessive DNA damage, as well as mitigate memory loss and other stresses during aging.
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Ventrículos Laterais , Células-Tronco Neurais , Sirtuína 1 , Envelhecimento/genética , Animais , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Reparo do DNA , Ventrículos Laterais/metabolismo , Camundongos , Células-Tronco Neurais/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
Quantum key distribution (QKD) offers information-theoretic security based on the fundamental laws of physics. However, device imperfections, such as those in active modulators, may introduce side-channel leakage, thus compromising practical security. Attempts to remove active modulation, including passive decoy intensity preparation and polarization encoding, have faced theoretical constraints and inadequate security verification, thus hindering the achievement of a fully passive QKD scheme. Recent research [W. Wang et al., Phys. Rev. Lett. 130, 220801 (2023).PRLTAO0031-900710.1103/PhysRevLett.130.220801; 2V. Zapatero et al., Quantum Sci. Technol. 8, 025014 (2023).2058-956510.1088/2058-9565/acbc46] has systematically analyzed the security of a fully passive modulation protocol. Based on this, we utilize the gain-switching technique in combination with the postselection scheme and perform a proof-of-principle demonstration of a fully passive quantum key distribution with polarization encoding at channel losses of 7.2 dB, 11.6 dB, and 16.7 dB. Our work demonstrates the feasibility of active-modulation-free QKD in polarization-encoded systems.
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We propose a fully passive linear optical quantum key distribution (QKD) source that implements both random decoy-state and encoding choices with postselection only, thus eliminating all side channels in active modulators. Our source is general purpose and can be used in, e.g., BB84, the six-state protocol, and reference-frame-independent QKD. It can even potentially be combined with measurement-device-independent QKD to achieve robustness against side channels in both detectors and modulators. We also perform a proof-of-principle experimental source characterization to show its feasibility.
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The precise control of proliferation and differentiation of neural progenitors is crucial for the development of the central nervous system. Fused in sarcoma (FUS) is an RNA-binding protein pathogenetically linked to Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) disease, yet the function of FUS on neurodevelopment is remained to be defined. Here we report a pivotal role of FUS in regulating the human cortical brain and spinal cord development via the human iPSCs-derived organoids. We found that depletion of FUS via CRISPR/CAS9 leads to an enhancement of neural proliferation and differentiation in cortical brain-organoids, but intriguingly an impairment of these phenotypes in spinal cord-organoids. In addition, FUS binds to the mRNA of a Trk tyrosine kinase receptor of neurotrophin-3 (Ntrk3) and regulates the expression of the different isoforms of Ntrk3 in a tissue-specific manner. Finally, alleviated Ntrk3 level via shRNA rescued the effects of FUS-knockout on the development of the brain- and spinal cord-organoids, suggesting that Ntrk3 is involved in FUS-regulated organoids developmental changes. Our findings uncovered the role of FUS in the neurodevelopment of the human CNS.
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Esclerose Lateral Amiotrófica , Degeneração Lobar Frontotemporal , Humanos , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Organoides/metabolismo , Corpos de Inclusão/metabolismo , Degeneração Lobar Frontotemporal/genética , Esclerose Lateral Amiotrófica/metabolismo , Medula Espinal/metabolismo , Encéfalo/metabolismoRESUMO
Although previous studies have found relationships between anger, forgiveness, and well-being, none have examined whether forgiveness mediates the relationship between trait anger and subjective well-being. To address this gap, this study constructed and tested a relevant moderated mediating model. We also considered the moderating effects of the COVID-19 lockdown situation, which has indirectly deteriorated well-being. The participants included 1,274 individuals who were recruited in April 2022. In sum, the results showed negative relationships between the trait anger and forgiveness and well-being, with a positive association between forgiveness and well-being. Moreover, forgiveness mediated the association between trait anger and subjective well-being, whereas the lockdown situation regulated the effects of trait anger on forgiveness and subjective well-being; specifically, forgiveness and well-being were more susceptible to trait anger among individuals under the lockdown situation. These findings suggest that forgiveness mediates the relationship between trait anger and well-being, while trait anger negatively predicts forgiveness and subjective well-being. Furthermore, the lockdown situation increases the negative predictive effects of anger on forgiveness and subjective well-being. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04500-9.
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Glyoxalase I (GLYI) is part of the glyoxalase system; its major function is the detoxification of α-ketoaldehydes, including the potent and cytotoxic methylglyoxal (MG). Methylglyoxal disrupts mitochondrial respiration and increases production of reactive oxygen species (ROS), which also increase during pathogen infection of plant tissues; however, there have been few studies relating the glyoxalase system to the plant pathogen response. We used the promoter of VvGLYI-4 to screen the upstream transcription factors and report a NAC (NAM/ATAF/CUC) domain-containing transcription factor VvNAC72 in grapevine, which is localized to the nucleus. Our results show that VvNAC72 expression is induced by downy mildew, Plasmopara viticola, while the transcript level of VvGLYI-4 decreases. Further analysis revealed that VvNAC72 can bind directly to the promoter region of VvGLYI-4 via the CACGTG element, leading to inhibition of VvGLYI-4 transcription. Stable overexpression of VvNAC72 in grapevine and tobacco showed a decreased expression level of VvGLYI-4 and increased content of MG and ROS, as well as stronger resistance to pathogen stress. Taken together, these results demonstrate that grapevine VvNAC72 negatively modulates detoxification of MG through repression of VvGLYI-4, and finally enhances resistance to downy mildew, at least in part, via the modulation of MG-associated ROS homeostasis through a salicylic acid-mediated defense pathway.
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Lactoilglutationa Liase/metabolismo , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Vitis/microbiologia , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Lactoilglutationa Liase/genética , Oomicetos/patogenicidade , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Aldeído Pirúvico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/microbiologia , Fatores de Transcrição/genética , Vitis/genética , Vitis/metabolismoRESUMO
Tert-butylperoxy-2-ethylhexanoate (TBPEH) and tert-butyl peroxybenzoate (TBPB) promote the radical acylation of allyl ester with benzaldehyde to synthesize new carbonyl-containing compounds under solvent-free and metal-free conditions. This reaction is compatible with electron-donating and halogen groups and has excellent atom utilization and chemical selectivity. Furthermore, the synthetic compounds can further apply to the preparation of lactone, piperidine, tetrazole and oxazole.
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Benzaldeídos , Ésteres , Ésteres/química , PeróxidosRESUMO
Antibody-drug conjugates (ADCs) are complex pharmaceutical molecules that combine monoclonal antibodies with biologically active drugs through chemical linkers. ADCs are designed to specifically kill disease cells by utilizing the target specificity of antibodies and the cytotoxicity of chemical drugs. However, the traditional ADCs were only applied to a few disease targets because of some limitations such as the huge molecular weight, the uncontrollable coupling reactions, and a single mechanism of action. Here we report a simple, one-pot, successive reaction method to produce dual payload conjugates with the site-specifically engineered cysteine and p-acetyl-phenylalanine using Herceptin (trastuzumab), an anti-HER2 antibody drug widely used for breast cancer treatment, as a tool molecule. This strategy enables antibodies to conjugate with two mechanistically distinct cytotoxic drugs through different functional groups sequentially, therefore, rendering the newly designed ADCs with functional diversity and the potential to overcome drug resistance and enhance the therapeutic efficacy.
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Cisteína/química , Imunoconjugados/química , Cinética , Trastuzumab/químicaRESUMO
BACKGROUND: Aberrant proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) are major pathological phenomenon in hypertension. MicroRNAs (miRNAs/miRs) serve crucial roles in the progression of hypertension. We aimed to determine the role of miR-96-5p in the proliferation, migration, and apoptosis of VSMCs and its underlying mechanisms. METHODS: Angiotensin II (Ang II) was employed to treat VSMCs, and the expression of miR-96-5p was detected by RT-qPCR. Then, miR-96-5p mimic was transfected into VSMCs. Cell Counting Kit-8 assay, flow cytometry, transwell assay, and wound healing assay were applied to measure proliferation, cell cycle, and migration of VSMCs. The expression of proteins associated with proliferation, migration, and apoptosis was assessed. A luciferase reporter assay was applied to confirm the target binding between miR-96-5p and nuclear factors of activated T-cells 5 (NFAT5). Subsequently, siRNA was used to silence NFAT5, and cell proliferation, migration, and apoptosis were assessed. RESULTS: The results revealed that the expression of miR-96-5p was downregulated in Ang II-induced VSMCs. MiR-96-5p overexpression inhibited cell proliferation and migration but promoted cell apoptosis, enhanced the percentages of cells in the G1 and G2 phases, and reduced those in the S phase, accompanied by changes in the expression associated proteins. NFAT5 was confirmed as a direct target of miR-96-5p. NFAT5 silencing had the same results with miR-96-5p overexpression on VSMC proliferation, migration, and apoptosis, whereas miR-96-5p inhibitor reversed these effects. CONCLUSIONS: Our findings concluded that miR-96-5p could regulate proliferation, migration, and apoptosis of VSMCs induced by Ang II via targeting NFAT5.
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Angiotensina II/farmacologia , Apoptose/efeitos dos fármacos , MicroRNAs/fisiologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/fisiologia , Fatores de Transcrição/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Fatores de Transcrição/fisiologiaRESUMO
The first isolable silylene-germylene complexâ 5 was assembled by a salt metathesis reaction between the germylene anionâ 3 and the N-heterocyclic chlorosilyleneâ 4, and structurally characterized. The central structure of 5 demonstrates a remarkable gauche-bent geometry with the silylene and germylene units, which are interconnected by a Si-Ge bond with a length of 2.4498(9)â Å. This value is not only perceptibly longer than the distances known in doubly bonded germasilenes, and also slightly longer than those in germylsilanes. The DFT calculations on 5 confirmed a nearly nonpolar SiI -GeI single-bond nature and its bonding orbital, as well as the aromaticity of the C3 NGe-rings in 3 and 5. The latter increases the molecular stability of 3 and 5, and makes the preparation of silylene-germylene complexâ 5 a reality.
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Low temperature scanning tunneling microscopy (LT-STM) has been applied to investigate the adsorption of acetylene (C2H2) on the rutile TiO2(110) surface at 77 K. Through in situ exposing and ex situ annealing experiments we unambiguously demonstrate that C2H2 molecules adsorb weakly on top of the Ti5c ions. Moreover, our data clearly reveal that the oxygen vacancy (Ov) cannot directly adsorb C2H2 molecules but can activate its next-nearest Ti5c ions which register as a binding site for C2H2 molecules with enhanced stability. Further increasing the C2H2 coverage leads to the stepwise formation of c-(4 × 2) and c-(2 × 2) ordered structures before final saturation at around 0.68 monolayer. The saturated film is characterized by dominating C2H2 dimers and other minority linear clusters whose intermolecular distances are slightly larger than the intervals between Ti5c ions yet significantly shorter than the C2H2 dimers in the gas phase. We propose that such clustered C2H2 may serve as potential precursors for the polymerization reactions on metal oxide surfaces.
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The first isolable Ge5-spiropentadiene 1 was synthesized via the reduction of (iPr3Si)2NGeCl (3) with potassium. The crystal structure of 1 reveals a spirocyclic Ge5 skeleton containing two Ge-Ge double bonds (avg. 2.34 Å), which are fettered in two Ge3 rings with a dihedral angle of 70.193°. The DFT calculations and orbital analysis show that the σ-delocalization of the Ge5 skeleton and the 2π-delocalized aromatic Ge3 rings enhance the stability of molecule 1.
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Measurement-device-independent quantum key distribution (MDI-QKD) can eliminate all detector side channels and it is practical with current technology. Previous implementations of MDI-QKD all used two symmetric channels with similar losses. However, the secret key rate is severely limited when different channels have different losses. Here we report the results of the first high-rate MDI-QKD experiment over asymmetric channels. By using the recent 7-intensity optimization approach, we demonstrate>10×higher key rate than the previous best-known protocols for MDI-QKD in the situation of large channel asymmetry, and extend the secure transmission distance by more than 20-50 km in standard telecom fiber. The results have moved MDI-QKD towards widespread applications in practical network settings, where the channel losses are asymmetric and user nodes could be dynamically added or deleted.