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Lithium metal anode is the ultimate choice to obtain next-generation high-energy-density lithium batteries, while the dendritic lithium growth owing to the unstable lithium anode/electrolyte interface largely limits its practical application. Separator is an important component in batteries and separator engineering is believed to be a tractable and effective way to address the above issue. Separators can play the role of ion redistributors to guide the transport of lithium ions and regulate the uniform electrodeposition of Li. The electrolyte wettability, thermal shrinkage resistance, and mechanical strength are of importance for separators. Here, clay-originated two-dimensional (2D) holey amorphous silica nanosheets (ASN) to develop a low-cost and eco-friendly inorganic separator is directly adopted. The ASN-based separator has higher porosity, better electrolyte wettability, much higher thermal resistance, larger lithium transference number, and ionic conductivity compared with commercial separator. The large amounts of holes and rich surface oxygen groups on the ASN guide the uniform distribution of lithium-ion flux. Consequently, the Li//Li cell with this separator shows stable lithium plating/stripping, and the corresponding Li//LiFePO4 , Li//LiCoO2, and Li//NCM523 full cells also show high capacity, excellent rate performance, and outstanding cycling stability, which is much superior to that using the commercial separator.
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BACKGROUND: The underlying mechanisms for infantile bronchopneumonia development remain unknown. METHODS: Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2-/- dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs. RESULTS: The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-ß), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-ß was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-ß in GM-CSF-induced bone marrow-derived DCs. CONCLUSIONS: GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant. IMPACT: Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia. Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia. The results could provide therapeutic molecular target for the treatment of such disease.
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Broncopneumonia , Interferon Tipo I , Humanos , Lactente , Fator Estimulador de Colônias de Granulócitos e Macrófagos , NF-kappa B , Leucócitos MononuclearesRESUMO
As a broad-spectrum oral small molecule inhibitor targeting multikinase, sorafenib is currently approved for the clinical treatment of several types of cancer as a single agent. A considerable number of clinical trial results have indicated that combination therapies involving sorafenib have been shown to improve treatment efficacy and may lead to novel therapeutic applications. Ursolic acid (UA), a natural pentacyclic triterpene compound extracted from a great variety of traditional medicinal plants and most fruits and vegetables, exhibits a wide range of therapeutic potential, including against cancer, diabetes, brain disease, liver disease, cardiovascular diseases, and sarcopenia. In the present study, we investigated the antitumor effects of sorafenib in combination with ursolic acid and found that the two agents displayed significant synergistic antitumor activity in in vitro and in vivo tumor xenograft models. Sorafenib/UA induced selective apoptotic death and ferroptosis in various cancer cells by evoking a dramatic accumulation of intracellular lipid reactive oxygen species (ROS). Mechanistically, the combination treatment promoted Mcl-1 degradation, which regulates apoptosis. However, decreasing the protein level of SLC7A11 plays a critical role in sorafenib/UA-induced cell ferroptosis. Therefore, these results suggest that the synergistic antitumor effects of sorafenib combined with ursolic acid may involve the induction of Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis. Our findings may offer a novel effective therapeutic strategy for tumor treatment.
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Ferroptose , Neoplasias , Sistema y+ de Transporte de Aminoácidos , Apoptose , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Triterpenos , Ácido UrsólicoRESUMO
Novel all-hydrocarbon cross-linked aza-stapled peptides were designed and synthesized for the first time by ring-closing metathesis between two aza-alkenylglycine residues. Three aza-stapled peptidic analogues based on the peptide dual inhibitor of p53-MDM2/MDMX interactions were synthesized and screened for biological activities. Among the three aza-stapled peptides, aSPDI-411 displayed increased anti-tumor activity, binding affinities to both MDM2 and MDMX, and cell membrane permeability compared to its linear peptide counterpart.
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Proteínas Proto-Oncogênicas c-mdm2 , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/química , Sequência de Aminoácidos , Peptídeos/química , Ligação Proteica , HidrocarbonetosRESUMO
Acetaminophen (APAP) overdose-induced hepatotoxicity is the leading cause of drug-induced liver injury worldwide. The related injury pathogenesis is mainly focused on the liver. Here, the authors report that gut barrier disruption may also be involved in APAP hepatotoxicity. APAP administration led to gut leakiness and colonic epithelial chemokine (C-C motif) ligand 7 (CCL7) up-regulation. Intestinal epithelial cell (IEC)-specific CCL7 transgenic mice (CCL7tgIEC mice) showed markedly increased myosin light chain kinase phosphorylation, and elevated gut permeability and bacterial translocation into the liver compared to wild-type mice. Global transcriptome analysis revealed that the expression of hepatic proinflammatory genes was enhanced in CCL7tgIEC mice compared with wild-type animals. Moreover, CCL7 overexpression in intestinal epithelial cells significantly augmented APAP-induced acute liver injury. These data provide new evidence that dysfunction of CCL7-mediated gut barrier integrity may be an important contributor to APAP-induced hepatotoxicity.
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Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Quimiocina CCL7/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica , Intestinos/fisiopatologia , Animais , Translocação Bacteriana , Permeabilidade da Membrana Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Quimiocina CCL7/genética , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
BACKGROUND: Current diagnostic methods for Schistosoma japonicum infection are insensitive for low-density infections. Therefore, a new diagnostic assay based on recombinase polymerase amplification (RPA) technology was established and assessed for field applification. METHODS: The S.japonicum RPA assay was developed to target highly repetitive retrotransposon SjR2 gene of S japonicum, and its sensitivity and specificity were assessed by serial dilution of S. japonicum genomic DNA and other related worm genomic DNA respectively. The RPA diagnostic validity was first evaluated in 60 fecal samples from healthy people and patients, and then compared with other diagnostic tests in 200 high-risk individuals living in endemic areas. RESULTS: The real time RPA assay could detect 0.9 fg S. japonicum DNA within 15 min and distinguish S. japonicum from other worms. The validity analysis of RPA for the detection of S. japonicum in stool samples from 30 S. japonicum-infected patients and 30 healthy persons indicated 100% sensitivity and specificity. When testing 200 fecal or serum samples from a high-risk population, the percentage sensitivity of RPA was 100%, whereas that of indirect hemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA) were 80.3% and 85.2% respectively. In addition, the RPA presented better consistency with the stool-based tests than IHA and ELISA. Overall, the RPA was superior to other detection methods with respect to detection time, sensitivity, and convenience. CONCLUSIONS: This is the first time we applied the RPA technology to the field evaluation of S. japonicum infection. And the results suggest that RPA-based assays can be used as a promising point-of-care test for the diagnosis of schistosomiasis.
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Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/métodos , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/diagnóstico , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , China/epidemiologia , DNA de Helmintos/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Testes de Hemaglutinação , Humanos , Masculino , Pessoa de Meia-Idade , Recombinases , Schistosoma japonicum/genética , Sensibilidade e Especificidade , Adulto JovemRESUMO
The ionization energies (IEs) of TiO and TiO2 and the 0 K bond dissociation energies (D0) and the heats of formation at 0 K (ΔH°f0) and 298 K (ΔH°f298) for TiO/TiO+ and TiO2/TiO2+ are predicted by the wave-function-based CCSDTQ/CBS approach. The CCSDTQ/CBS calculations involve the approximation to the complete basis set (CBS) limit at the coupled cluster level up to full quadruple excitations along with the zero-point vibrational energy (ZPVE), high-order correlation (HOC), core-valence (CV) electronic, spin-orbit (SO) coupling, and scalar relativistic (SR) effect corrections. The present calculations yield IE(TiO) = 6.815 eV and are in good agreement with the experimental IE value of 6.819â¯80 ± 0.000â¯10 eV determined in a two-color laser-pulsed field ionization-photoelectron (PFI-PE) study. The CCSDT and MRCI+Q methods give the best predictions to the harmonic frequencies: ωe (ωe+) = 1013 (1069) and 1027 (1059) cm-1 and the bond lengths re (re+) = 1.625 (1.587) and 1.621 (1.588) Å, for TiO (TiO+) compared with the experimental values. Two nearly degenerate, stable structures are found for TiO2 cation: TiO2+(C2v) structure has two equivalent TiO bonds, while the TiO2+(Cs) structure features a long and a short TiO bond. The IEs for the TiO2+(C2v)âTiO2 and TiO2+(Cs)âTiO2 ionization transitions are calculated to be 9.515 and 9.525 eV, respectively, giving the theoretical adiabatic IE value in good agreement with the experiment IE(TiO2) = 9.573â¯55 ± 0.000â¯15 eV obtained in the previous vacuum ultraviolet (VUV)-PFI-PE study of TiO2. The potential energy surface of TiO2+ along the normal vibrational coordinates of asymmetric stretching mode (ω3+) is nearly flat and exhibits a double-well potential with the well of TiO2+ (Cs) situated around the central well of TiO2+(C2v). This makes the theoretical calculation of ω3+ infeasible. For the symmetric stretching (ω1+), the current theoretical predictions overestimate the experimental value of 829.1 ± 2.0 cm-1 by more than 100 cm-1. This work together with the previous experimental and theoretical investigations supports the conclusion that the CCSDTQ/CBS approach is capable of providing reliable IE and D0 predictions for TiO/TiO+ and TiO2/TiO2+ with error limits less than or equal to 60 meV. The CCSDTQ/CBS calculations give the predictions of D0(Ti+-O) - D0(Ti-O) = 0.004 eV and D0(O-TiO) - D0(O-TiO+) = 2.699 eV, which are also consistent with the respective experimental determination of 0.008â¯32 ± 0.000â¯10 and 2.753â¯75 ± 0.000â¯18 eV.
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The high-resolution photoelectron spectra of Zr- were obtained via the slow-electron velocity-map imaging method. The electron affinity of Zr was measured to be 3494.67(72) cm-1 or 0.433 283(89) eV. The accuracy has been improved by a factor of 160 compared with the previous result. The fine structures of Zr- were also well resolved: 251.0(37) (4F5/2), 579.6(8) (4F7/2), and 971.7(12) cm-1 (4F9/2) above the ground state 4F3/2.
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We report the high-resolution photoelectron spectra of negative vanadium ions obtained via the slow-electron velocity-map imaging method. The electron affinity of V was determined to be 4255.9(18) cm-1 or 0.527 66(20) eV. The accuracy was improved by a factor of 60 with regard to the previous measurement. The fine structure of V- was well resolved: 35.9(11) (5D1), 103.8(12) (5D2), 204.17(74) (5D3), and 330.58(40) cm-1 (5D4) above the ground state 5D0, respectively.
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The state-to-state photodissociation of CO2 is investigated in the VUV range of 11.94-12.20 eV by using two independently tunable vacuum ultraviolet (VUV) lasers and the time-sliced velocity-map-imaging-photoion (VMI-PI) method. The spin-allowed CO(X(1)Σ(+); v = 0-18) + O((1)D) and CO(X(1)Σ(+); v = 0-9) + O((1)S) photoproduct channels are directly observed from the measurement of time-sliced VMI-PI images of O((1)D) and O((1)S). The total kinetic energy release (TKER) spectra obtained based on these VMI-PI images shows that the observed energetic thresholds for both the O((1)D) and O((1)S) channels are consistent with the thermochemical thresholds. Furthermore, the nascent vibrational distributions of CO(X(1)Σ(+); v) photoproducts formed in correlation with O((1)D) differ significantly from that produced in correlation with O((1)S), indicating that the dissociation pathways for the O((1)D) and O((1)S) channels are distinctly different. For the O((1)S) channel, CO(X(1)Σ(+); v) photoproducts are formed mostly in low vibrational states (v = 0-2), whereas for the O((1)D) channel, CO(X(1)Σ(+); v) photoproducts are found to have significant populations in high vibrationally excited states (v = 10-16). The anisotropy ß parameters for the O((1)D) + CO(X(1)Σ(+); v = 0-18) and O((1)S) + CO(X(1)Σ(+); v = 0-9) channels have also been determined from the VMI-PI measurements, indicating that CO2 dissociation to form the O((1)D) and O((1)S) channels is faster than the rotational periods of the VUV excited CO2 molecules. We have also calculated the excited singlet potential energy surfaces (PESs) of CO2, which are directly accessible by VUV excitation, at the ab initio quantum multi-reference configuration interaction level of theory. These calculated PESs suggest that the formation of CO(X(1)Σ(+)) + O((1)S) photoproducts occurs nearly exclusively on the 4(1)A' PES, which is generally repulsive with minor potential energy ripples along the OC-O stretching coordinate. The formation of CO(X(1)Σ(+)) + O((1)D) photofragments can proceed by non-adiabatic transitions from the 4(1)A' PES to the lower 3(1)A' PES of CO2via the seam of conical intersections at a near linear OCO configuration, followed by the direct dissociation on the 3(1)A' PES. The theoretical PES calculations are consistent with the experimental observation of prompt CO2 dissociation and high rotational and vibrational excitations for CO(X(1)Σ(+)) photoproducts.
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By employing two-color visible (VIS)-ultraviolet (UV) laser photoionization and pulsed field ionization-photoelectron (PFI-PE) techniques, we have obtained highly rotationally resolved photoelectron spectra for vanadium monocarbide cations (VC(+)). The state-to-state VIS-UV-PFI-PE spectra thus obtained allow unambiguous assignments for the photoionization rotational transitions, resulting in a highly precise value for the adiabatic ionization energy (IE) of vanadium monocarbide (VC), IE(VC) = 57512.0 ± 0.8 cm(-1) (7.13058 ± 0.00010 eV), which is defined as the energy of the VC(+)(X(3)Δ1; v(+) = 0; J(+) = 1) â VC(X(2)Δ3/2; v'' = 0; J'' = 3/2) photoionization transition. The spectroscopic constants for VC(+)(X(3)Δ1) determined in the present study include the harmonic vibrational frequency ωe(+) = 896.4 ± 0.8 cm(-1), the anharmonicity constant ωe(+)xe(+) = 5.7 ± 0.8 cm(-1), the rotational constants Be(+) = 0.6338 ± 0.0025 cm(-1) and αe(+) = 0.0033 ± 0.0007 cm(-1), the equilibrium bond length re(+) = 1.6549 ± 0.0003 Å, and the spin-orbit coupling constant A = 75.2 ± 0.8 cm(-1) for VC(+)(X(3)Δ1,2,3). These highly precise energetic and spectroscopic data are used to benchmark state-of-the-art CCSDTQ/CBS calculations. In general, good agreement is found between the theoretical predictions and experimental results. The theoretical calculations yield the values, IE(VC) = 7.126 eV; the 0 K bond dissociation energies: D0(V-C) = 4.023 eV and D0(V(+)-C) = 3.663 eV; and heats of formation: ΔH°(f0)(VC) = 835.2, ΔH°(f298)(VC) = 840.4, ΔH°(f0)(VC(+)) = 1522.8, and ΔH°(f298)(VC(+)) = 1528.0 kJ mol(-1).
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Vanadium monoxide cation VO(+)(X(3)Σ(-)) has been investigated by two-color visible (VIS)-ultraviolet (UV) pulsed field ionization-photoelectron (PFI-PE) methods. The unambiguous rotational assignment of rotationally selected and resolved VIS-UV-PFI-PE spectra thus obtained confirms the ground state term symmetry of VO(+) to be X(3)Σ(-). The rotational analysis also yields the rotational constants Be(+) = 0.5716 ± 0.0012 cm(-1) and αe(+) = 0.0027 ± 0.0005 cm(-1) for VO(+)(X(3)Σ(-)), from which the equilibrium bond distance of VO(+)(X(3)Σ(-)) is determined to be re(+) = 1.557 ± 0.002 Å. This PFI-PE study covers the vibrational bands, VO(+)(X(3)Σ(-); v(+) = 0, 1, 2, and 3) â VO(X(4)Σ(-); vâ³ = 0), which has made possible the determination of the vibrational constants for VO(+)(X(3)Σ(-)) to be ωe(+) = 1068.0 ± 0.7 cm(-1) and ωe(+)xe(+) = 5.5 ± 0.7 cm(-1). The present state-to-state measurement also yields a more precise value (58â¯380.0 ± 0.7 cm(-1) or 7.238â¯20 ± 0.000â¯09 eV) for the ionization energy of VO [IE(VO)]. This value along with the known IE(V) has allowed the determination of the difference between the 0 K bond dissociation energy (D0) of VO(+)(X(3)Σ(-)) and that of VO(X(4)Σ(-)) to be D0(V(+)-O) - D0(V-O) = IE(V) - IE(VO) = -3967 ± 1 cm(-1).
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By employing the infrared (IR)-ultraviolet (UV) laser excitation scheme, we have obtained rotationally selected and resolved pulsed field ionization-photoelectron (PFI-PE) spectra for vanadium methylidyne cation (VCH(+)). This study supports that the ground state electronic configuration for VCH(+) is 7σ(2)8σ(2)3π(4)9σ(1) (X(2)Σ(+)), and is different from that of 7σ(2)8σ(2)3π(4)1δ(1) (X(2)Δ) for the isoelectronic TiO(+) and VN(+) ions. This observation suggests that the addition of an H atom to vanadium carbide (VC) to form VCH has the effect of stabilizing the 9σ orbital relative to the 1δ orbital. The analysis of the state-to-state IR-UV-PFI-PE spectra has provided precise values for the ionization energy of VCH, IE(VCH) = 54,641.9 ± 0.8 cm(-1) (6.7747 ± 0.0001 eV), the rotational constant B(+) = 0.462 ± 0.002 cm(-1), and the v2(+) bending (626 ± 1 cm(-1)) and v3(+) V-CH stretching (852 ± 1 cm(-1)) vibrational frequencies for VCH(+)(X(2)Σ(+)). The IE(VCH) determined here, along with the known IE(V) and IE(VC), allows a direct measure of the change in dissociation energy for the V-CH as well as the VC-H bond upon removal of the 1δ electron of VCH(X(3)Δ1). The formation of VCH(+)(X(2)Σ(+)) from VCH(X(3)Δ1) by photoionization is shown to strengthen the VC-H bond by 0.3559 eV, while the strength of the V-CH bond remains nearly unchanged. This measured change of bond dissociation energies reveals that the highest occupied 1δ orbital is nonbonding for the V-CH bond; but has anti-bonding or destabilizing character for the VC-H bond of VCH(X(3)Δ1).
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By employing the two-color visible (VIS)-ultraviolet (UV) laser photoexcitation scheme and the pulsed field ionization-photoelectron (PFI-PE) detection, we have obtained rovibronically selected and resolved photoelectron spectra for niobium carbide cation (NbC(+)). The fully rotationally resolved state-to-state VIS-UV-PFI-PE spectra thus obtained allow the unambiguous assignments of rotational photoionization transitions, indicating that the electronic configuration and term symmetry of NbC(+)(XÌ) ground state are 10σ(2) 5π(4) 11σ(2) (XÌ(1)Σ(+)). Furthermore, the rotational analysis of these spectra yields the ionization energy of NbC [IE(NbC)] to be 56,369.2 ± 0.8 cm(-1) (6.9889 ± 0.0001 eV) and the rotation constant B0 (+) = 0.5681 ± 0.0007 cm(-1). The latter value allows the determination of the bond distance r0 (+) = 1.671 ± 0.001 Å for NbC(+)(XÌ(1)Σ(+)). Based on conservation of energy, the IE(NbC) determined in the present study along with the known IE(Nb) gives the difference of 0 K bond dissociation energies (D0's) for NbC(+) and NbC, D0(NbC(+)) - D0(NbC) = -1855.4 ± 0.9 cm(-1) (-0.2300 ± 0.0001 eV). The energetic values and the B0 (+) constant determined in this work are valuable for benchmarking state-of-the-art ab initio quantum calculations of 4d transition metal-containing molecules.
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Titanium carbide and its cation (TiC/TiC(+)) have been investigated by the two-color visible (VIS)-ultraviolet (UV) resonance-enhanced photoionization and pulsed field ionization-photoelectron (PFI-PE) methods. Two visible excitation bands for neutral TiC are observed at 16,446 and 16,930 cm(-1). Based on rotational analyses, these bands are assigned as the respective TiC((3)Π1) â TiC(X(3)Σ(+)) and TiC((3)Σ(+)) â TiC(X(3)Σ(+)) transition bands. This assignment supports that the electronic configuration and term symmetry for the neutral TiC ground state are 7σ(2)8σ(1)9σ(1)3π(4) (X(3)Σ(+)). The rotational constant and the corresponding bond distance of TiC(X(3)Σ(+); vâ³ = 0) are determined to be B0â³ = 0.6112(10) cm(-1) and r0â³ = 1.695(2) Å, respectively. The rotational analyses of the VIS-UV-PFI-PE spectra for the TiC(+)(X; v(+) = 0 and 1) vibrational bands show that the electronic configuration and term symmetry for the ionic TiC(+) ground state are 7σ(2)8σ(1)3π(4) (X(2)Σ(+)) with the v(+) = 0 â 1 vibrational spacing of 870.0(8) cm(-1) and the rotational constants of B(e)(+) = 0.6322(28) cm(-1), and α(e)(+) = 0.0085(28) cm(-1). The latter rotational constants yield the equilibrium bond distance of r(e)(+) = 1.667(4) Å for TiC(+)(X(2)Σ(+)). The cleanly rotationally resolved VIS-UV-PFI-PE spectra have also provided a highly precise value of 53 200.2(8) cm(-1) [6.5960(1) eV] for the adiabatic ionization energy (IE) of TiC. This IE(TiC) value along with the known IE(Ti) has made possible the determination of the difference between the 0 K bond dissociation energy (D0) of TiC(+)(X(2)Σ(+)) and that of TiC(X(3)Σ(+)) to be D0(Ti(+)-C) - D0(Ti-C) = 0.2322(2) eV. Similar to previous experimental observations, the present state-to-state PFI-PE study of the photoionization transitions, TiC(+)(X(2)Σ(+); v(+) = 0 and 1, N(+)) â TiC((3)Π1; v', J'), reveals a strong decreasing trend for the photoionization cross section as |ΔN(+)| = |N(+) - J'| is increased. The maximum |ΔN(+)| change of 7 observed here is also consistent with the previous experimental results for the 3d transition-metal carbides, oxides, and nitrides. However, the VIS-UV-PFI-PE spectra for TiC(+)(X(2)Σ(+); v(+) = 0 and 1, N(+)) are found to display only the negative ΔN(+) (N(+)-J'≤ 0) transitions, indicating that the cross sections for the formation of positive ΔN(+) (N(+)-J' > 0) transitions by both the channel coupling mechanism and direct photoionization are negligibly small.
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Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function of Radix Bupleuri aqueous extract in SCZ in mouse models. The SCZ mouse model was established by MK-801 injection and feeding of Radix Bupleuri aqueous extract or combined antibiotics. Radix Bupleuri aqueous extract significantly improved the aberrant behaviors and neuronal damage in SCZ mice, upregulated SYP and PSD-95 expression and BDNF levels in hippocampal homogenates, down-regulated DA and 5-HT levels, and suppressed microglial activation in SCZ mice. Moreover, Radix Bupleuri aqueous extract improved the integrity of the intestinal tract barrier. The 16â¯S rRNA sequencing of feces showed that Radix Bupleuri extract modulated the composition of gut flora. Lactobacillus abundance was decreased in SCZ mice and reversed by Radix Bupleuri aqueous extract administration which exhibited a significant negative correlation with IL-6, IL-1ß, DA, and 5-HT, and a significant positive correlation with BDNF levels in hippocampal tissues. The abundance of Parabacteroides and Alloprevotella was increased in SCZ mice. It was reversed by Radix Bupleuri aqueous extract administration, which exhibited a positive correlation with IL-6, IL-1ß, and 5-HT and a negative correlation with BDNF. In conclusion, Radix Bupleuri aqueous extract attenuates the inflammatory response in hippocampal tissues and modulates neurotransmitter levels, exerting its neuroprotective effect in SCZ. Meanwhile, the alteration of intestinal flora may be involved in this process, which is expected to be an underlying therapeutic option in treating SCZ.
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Bupleurum , Microbioma Gastrointestinal , Extratos Vegetais , Esquizofrenia , Humanos , Animais , Camundongos , Maleato de Dizocilpina , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo , Interleucina-6 , Serotonina , Modelos Animais de Doenças , Interleucina-1betaRESUMO
OBJECTIVE: This study was performed to investigate the effectiveness of two surgical procedures, autologous patellar tendon graft reconstruction and trans-tibial plateau pull-out repair, using a pig model. The primary focus was to assess the repair capability of medial meniscus posterior portion (MMPP) deficiency, the overall structural integrity of the meniscus, and protection of the femoral and tibial cartilage between the two surgical groups. The overall aim was to provide experimental guidelines for clinical research using these findings. METHODS: Twelve pigs were selected to establish a model of injury to the MMPP 10 mm from the insertion point of the tibial plateau. They were randomly divided into three groups of four animals each: reconstruction (autologous tendon graft reconstruction of the MMPP), pull-out repair (suture repair of the MMPP via a trans-tibial plateau bone tunnel), and control (use of a normal medial meniscus as the negative control). The animals were euthanized 12 weeks postoperatively for evaluation of the meniscus, assessment of tendon bone healing, and gross observation of knee joint cartilage. The tibial and femoral cartilage injuries were evaluated using the International Society for Cartilage Repair (ICRS) grade and Mankin score. Histological and immunohistochemical staining was conducted on the meniscus-tendon junction area, primary meniscus, and tendons. The Ishida score was used to evaluate the regenerated meniscus in the reconstruction group. Magnetic resonance imaging (MRI) was used to evaluate meniscal healing. RESULTS: All 12 pigs recovered well after surgery; all incisions healed without infection, and no obvious complications occurred. Gross observation revealed superior results in the reconstruction and pull-out repair groups compared with the control group. In the tibial cartilage, the reconstruction group had ICRS grade I injury whereas the pull-out repair and control groups had ICRS grade II and III injury, respectively. The Mankin score was significantly different between the reconstruction and control groups; histological staining showed that the structure of the regenerated meniscus in the reconstruction group was similar to that of the original meniscus. Immunohistochemical staining showed that the degree of type I and II collagen staining was similar between the regenerated meniscus and the original meniscus in the reconstruction group. The Ishida score was not significantly different between the regenerated meniscus and the normal primary meniscus in the reconstruction group. MRI showed that the MMPP in the reconstruction and pull-out repair groups had fully healed, whereas that in the control group had not healed. CONCLUSION: Autologous patellar tendon graft reconstruction of the MMPP can generate a fibrocartilage-like regenerative meniscus. Both reconstruction and pull-out repair can preserve the structural integrity of the meniscus, promote healing of the MMPP, delay meniscal degeneration, and protect the knee cartilage.
Assuntos
Doenças das Cartilagens , Menisco , Ligamento Patelar , Animais , Doenças das Cartilagens/cirurgia , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/cirurgia , Menisco/cirurgia , Ligamento Patelar/diagnóstico por imagem , Ligamento Patelar/cirurgia , Ligamento Patelar/patologia , SuínosRESUMO
OBJECTIVE: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B (LDHB) has been detected in breast cancer but the function of LDHB remains unknown. METHODS: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer (NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation. RESULTS: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers. CONCLUSIONS: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.
Assuntos
Neoplasias da Mama , Progressão da Doença , Células Matadoras Naturais , L-Lactato Desidrogenase , Microambiente Tumoral , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Humanos , Feminino , Animais , Camundongos , L-Lactato Desidrogenase/metabolismo , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Ativação Linfocitária , Isoenzimas/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Movimento Celular , Prognóstico , Regulação Neoplásica da Expressão GênicaRESUMO
Considerable amount of high-value transition metals components can be recycled in spent ternary lithium-ion batteries. In this study, we utilized the conductive agent carbon black, obtained from the leaching waste resulting from the chemical recovery of spent lithium-nickel-manganese-cobalt (NCM) oxide cathode materials. This process allows us to create valuable bifunctional catalysts for the oxygen reduction reaction and oxygen evolution reaction (ORR/OER), facilitated by a facile cold plasma activation method, as a part of lithium batteries circular economy. The activated conductive agent (RCA-30) exhibited an ORR half-wave potential of 0.74 V (vs. RHE) in 0.1 mol/L KOH solution, and an OER overpotential of 360 mV at 10 mA cm-2 in 1 mol/L KOH electrolyte, owing to nitrogen doping of carbon black and activation of surface metal oxides. The complete zinc-air batteries incorporating the activated catalysts at the cathode exhibited an open circuit potential of up to 1.48 V and sustained cycling for 100 h at a current density of 5 mA cm-2. Additionally, the activated catalysts contributed to a power density of 92 mW cm-2 and a full discharge capacity of 640 mAh/g.
RESUMO
We have successfully measured the vacuum ultraviolet (VUV) laser photoionization efficiency and pulsed field ionization-photoelectron (PFI-PE) spectra of cold titanium dioxide (TiO(2)) prepared by a supersonically cooled laser ablation source. The VUV-PFI-PE spectrum thus obtained exhibits long progressions of the v(2)(+)(a(1)) bending and the combination of v(1)(+)(a(1)) stretching and v(2)(+)(a(1)) bending vibrational modes of the TiO(2)(+)(X(2)B(2)) ion. The pattern of Franck-Condon factors observed indicates that the O-Ti-O bond angle of the TiO(2)(+)(X(2)B(2)) ion is significantly different from that of the TiO(2)(X(1)A(1)) neutral, whereas the change of the Ti-O bond distance is very minor upon the photoionization transition. The analysis of the PFI-PE bands has made possible the determination of the adiabatic ionization energy for TiO(2), IE(TiO(2)) = 77215.9 ± 1.2 cm(-1) (9.57355 ± 0.00015 eV), the harmonic vibrational frequencies, ω(1)(+) = 829.1 ± 2.0 cm(-1) and ω(2)(+) = 248.7 ± 0.6 cm(-1), and the anharmonic coefficients, χ(11)(+) = 5.57 ± 0.65 cm(-1), χ(22)(+) = 0.08 ± 0.06 cm(-1), and χ(12)(+) = -4.51 ± 0.30 cm(-1) for the TiO(2)(+)(X(2)B(2)) ground state.