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1.
Nature ; 627(8002): 101-107, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418886

RESUMO

Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase1-5. Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li+ in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li+ transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li+ solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm-1 at 25 °C and 11.9 mS cm-1 even at -70 °C, thus enabling 4.5-V graphite||LiNi0.8Mn0.1Co0.1O2 pouch cells (1.2 Ah, 2.85 mAh cm-2) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes.

2.
Nature ; 575(7784): 618-621, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31776491

RESUMO

All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun1-4. Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries5,6. When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.

3.
Small ; 20(15): e2308004, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37992242

RESUMO

In the electrochemical CO2 reduction reaction (CO2RR), the coverages of *CO and *H intermediates on a catalyst surface are critical for the selective generation of C1 or C2 products. In this work, we have synthesized several CuxZnyMnz ternary alloy electrocatalysts, including Cu8ZnMn, Cu8Zn6Mn, and Cu8ZnMn2, by varying the doping compositions of Zn and Mn, which are efficient in binding *CO and *H adsorbates in the CO2 electroreduction process, respectively. The increase of *H coverage allows to promotion of the CH4 and H2 formation, while the increase of the *CO coverage facilitates the production of C2H4 and CO. As a result, the Cu8ZnMn catalyst presented a high CO2-to-CH4 partial current density (-418 ± 22 mA cm-2) with a Faradaic efficiency of 55 ± 2.8%, while the Cu8Zn6Mn catalyst exhibited a CO2-to-C2H4 partial current density (-440 ± 41 mA cm-2) with a Faradaic efficiency of 58 ± 4.5%. The study suggests a useful strategy for rational design and fabrication of Cu electrocatalysts with different doping for tailoring the reduction products.

4.
Small ; 20(23): e2309568, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461520

RESUMO

Wounds in harsh environments can face long-term inflammation and persistent infection, which can slow healing. Wound spray is a product that can be rapidly applied to large and irregularly dynamic wounds, and can quickly form a protective film in situ to inhibit external environmental infection. In this study, a biodegradable A and B combined multi-functional spray hydrogel is developed with methacrylate-modified chitosan (CSMA1st) and ferulic acid (FA) as type A raw materials and oxidized Bletilla striata polysaccharide (OBSP) as type B raw materials. The precursor CSMA1st-FA/OBSP (CSOB-FA1st) hydrogel is formed by the self-cross-linking of dynamic Schiff base bonds, the CSMA-FA/OBSP (CSOB-FA) hydrogel is formed quickly after UV-vis light, so that the hydrogel fits with the wound. Rapid spraying and curing provide sufficient flexibility and rapidity for wounds and the hydrogel has good injectability, adhesive, and mechanical strength. In rats and miniature pigs, the A and B combined spray hydrogel can shrink wounds and promote healing of infected wounds, and promote the enrichment of fibrocyte populations. Therefore, the multifunctional spray hydrogel combined with A and B can protect irregular dynamic wounds, prevent wound infection and secondary injury, and be used for safe and effective wound treatment, which has a good prospect for development.


Assuntos
Quitosana , Hidrogéis , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Quitosana/química , Ratos , Suínos , Reagentes de Ligações Cruzadas/química , Ratos Sprague-Dawley , Porco Miniatura , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia
5.
Plant Cell Environ ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752443

RESUMO

Bamboo cultivation, particularly Moso bamboo (Phyllostachys edulis), holds significant economic importance in various regions worldwide. Bamboo shoot degradation (BSD) severely affects productivity and economic viability. However, despite its agricultural consequences, the molecular mechanisms underlying BSD remain unclear. Consequently, we explored the dynamic changes of BSD through anatomy, physiology and the transcriptome. Our findings reveal ruptured protoxylem cells, reduced cell wall thickness and the accumulation of sucrose and reactive oxygen species (ROS) during BSD. Transcriptomic analysis underscored the importance of genes related to plant hormone signal transduction, sugar metabolism and ROS homoeostasis in this process. Furthermore, BSD appears to be driven by the coexpression regulatory network of senescence-associated gene transcription factors (SAG-TFs), specifically PeSAG39, PeWRKY22 and PeWRKY75, primarily located in the protoxylem of vascular bundles. Yeast one-hybrid and dual-luciferase assays demonstrated that PeWRKY22 and PeWRKY75 activate PeSAG39 expression by binding to its promoter. This study advanced our understanding of the molecular regulatory mechanisms governing BSD, offering a valuable reference for enhancing Moso bamboo forest productivity.

6.
Mol Pharm ; 21(7): 3321-3329, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38843501

RESUMO

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [99mTc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro. In HeLa cell experiments, the uptake of [99mTc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumor-bearing mice, [99mTc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [99mTc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [99mTc]Tc-CNPN is a promising tumor imaging agent that targets PARP.


Assuntos
Indazóis , Piperidinas , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Humanos , Camundongos , Piperidinas/química , Piperidinas/farmacocinética , Indazóis/química , Indazóis/farmacocinética , Células HeLa , Inibidores de Poli(ADP-Ribose) Polimerases/farmacocinética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Poli(ADP-Ribose) Polimerase-1/metabolismo , Feminino , Tecnécio/química , Nitrilas/química , Nitrilas/farmacocinética , Camundongos Nus , Camundongos Endogâmicos BALB C
7.
Int J Mol Sci ; 25(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38256119

RESUMO

To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5-9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging.


Assuntos
Proteínas Ribossômicas , Infecções Estafilocócicas , Animais , Camundongos , Distribuição Tecidual , Infecções Estafilocócicas/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Cianetos , Inflamação/diagnóstico por imagem
8.
J Environ Sci (China) ; 138: 585-596, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135422

RESUMO

We developed a single-particle optical particle counter with polarization detection (SOPC) for the real-time measurement of the optical size and depolarization ratio (defined as the ratio of the vertical component to the parallel component of backward scattering) of atmospheric particles, the polarization ratio (DR) value can reflect the irregularity of the particles. The SOPC can detect aerosol particles with size larger than 500 nm and the maximum particle count rate reaches ∼1.8 × 105 particles per liter. The SOPC uses a modulated polarization laser to measure the optical size of particles according to forward scattering signal and the DR value of the particles by backward S and P signal components. The sampling rate of the SOPC was 106 #/(sec·channel), and all the raw data were processed online. The calibration curve was obtained by polystyrene latex spheres with sizes of 0.5-10 µm, and the average relative deviation of measurement was 3.96% for sub 3 µm particles. T-matrix method calculations showed that the DR value of backscatter light at 120° could describe the variations in the aspect ratio of particles in the above size range. We performed insitu observations for the evaluation of the SOPC, the mass concentration constructed by the SOPC showed good agreement with the PM2.5 measurements in a nearby state-controlled monitoring site. This instrument could provide useful data for source appointment and regulations against air pollution.


Assuntos
Poluição do Ar , Monitoramento Ambiental , Monitoramento Ambiental/métodos , Tamanho da Partícula , Luz , Microesferas
9.
Angew Chem Int Ed Engl ; 63(17): e202316907, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38436539

RESUMO

The efficient ethanol electrosynthesis from CO2 is challenging with low selectivity at high CO2 electrolysis rates, due to the competition with H2 and other reduction products. Copper-based bimetallic electrocatalysts are potential candidates for the CO2-to-ethanol conversion, but the secondary metal has mainly been focused on active components (such as Ag, Sn) for CO2 electroreduction, which also promote selectivity of ethylene or other reduction products rather than ethanol. Limited attention has been given to alkali-earth metals due to their inherently active chemical property. Herein, we rationally synthesized a (111) facet-oriented nano Cu2Mg (designated as Cu2Mg(111)) intermetallic compound with high-density ordered Cu3-Mg sites. The in situ Raman spectroscopy and density function theory calculations revealed that the Cu3 - δ $_{^{\rm{{\rm \delta} }} }$ --Mg- δ $_{^{\rm{{\rm \delta} }} }$ + active sites allowed to increase *CO surface coverage, decrease reaction energy for *CO-CO coupling, and stabilize *CHCHOH intermediates, thus promoting the ethanol formation pathway. The Cu2Mg(111) catalyst exhibited a high FEC2H5OH of 76.2±4.8 % at 600 mA⋅cm-2, and a peak value of |jC2H5OH| of 720±34 mA⋅cm-2, almost 4 times of that using conventional Cu2Mg with (311) facets, comparable to the best reported values for the CO2-to-ethanol electroreduction.

10.
Small ; 19(23): e2207374, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36896986

RESUMO

The high-rate ethanol electrosynthesis from CO2 is challenging due to the low selectivity and poor activity, which requires the competition with other reduction products and H2 . Here, the electrochemical reconstruction of Cs3 Cu2 Cl5 perovskite to form surface Cl-bonded, low-coordinated Cs modified Cu(200) nanocubes (CuClCs), is demonstrated. Density functional theory calculations reveal that the CuClCs structure possesses low Bader charges and a large coordination capacity; and thus, can promote the CO2 -to-ethanol pathway via stabilizing C-O bond in oxygenate intermediates. The CuClCs catalyst exhibits outstanding partial current densities for producing ethanol (up to 2124 ± 54 mA cm-2 ) as one of the highest reported values in the electrochemical CO2 or CO reduction. This work suggests an attractive strategy with surface alkali-metal cations for ampere-level CO2 -to-ethanol electrosynthesis.

11.
Mol Pharm ; 20(1): 630-640, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36398935

RESUMO

To seek a novel 99mTc-labeled quinolone derivative for bacterial infection SPECT imaging that aims to lower nontarget organ uptake, a novel norfloxacin 6-hydrazinoicotinamide (HYNIC) derivative (HYNICNF) was designed and synthesized. It was radiolabeled with different coligands, such as tricine, trisodium triphenylphosphine-3,3',3″-trisulfonate (TPPTS), sodium triphenylphosphine-3-monosulfonate (TPPMS), and ethylenediamine-N,N'-diacetic acid (EDDA), to obtain three 99mTc-labeled norfloxacin HYNIC complexes, namely, [99mTc]Tc-tricine-TPPTS-HYNICNF, [99mTc]Tc-tricine-TPPMS-HYNICNF, and [99mTc]Tc-EDDA-HYNICNF. These complexes were purified (RCP > 95%) and evaluated in vitro and in vivo for targeting bacteria. All three complexes are hydrophilic, maintain good stability, and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection demonstrated that [99mTc]Tc-EDDA-HYNICNF showed a higher abscess uptake and lower nontarget organ uptake and was able to distinguish bacterial infection and sterile inflammation. Single photon emission computed tomography (SPECT) image study in bacterial infection mice showed there was a visible accumulation in the infection site, suggesting that [99mTc]Tc-EDDA-HYNICNF is a potential radiotracer for bacterial infection imaging.


Assuntos
Infecções Bacterianas , Tecnécio , Camundongos , Animais , Norfloxacino , Distribuição Tecidual , Compostos de Organotecnécio/metabolismo , Compostos Radiofarmacêuticos/metabolismo
12.
Mol Pharm ; 20(9): 4528-4536, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37661815

RESUMO

Cyclin-dependent kinases (CDKs), especially cyclin-dependent kinase 4/6 (CDK4/6), have been targets for the development of specific tumor imaging agents. Palbociclib is a highly selective CDK4/6 inhibitor. In this study, to develop a novel 18F-labeled palbociclib derivative for specific tumor imaging, we designed and synthesized a ligand (NOTA-PBB) consisting of palbociclib as the targeted pharmacophore and NOTA as the macrocyclic bifunctional chelator. The corresponding [18F]AlF-NOTA-PBB complex was prepared with high radiochemical purity (98.4 ± 0.15%) and yield (58.7 ± 4.5%) within 35 min without requiring HPLC purification through a simple one-step 18F-labeling strategy of NOTA-AlF chelation chemistry. The radiotracer was lipophilic (log P = 0.095 ± 0.003) and had good stability in vitro and in vivo. The cellular uptake studies performed on the MCF-7 breast cancer cell line (ER-positive and HER2-negative) showed that radioactive uptake was blocked by preincubating with a molar dose of palbociclib and it had a nanomolar binding affinity to CDK4/6 (IC50 = 16.23 ± 1.84 nM), demonstrating a CDK4/6-mediated uptake mechanism. Its ex vivo biodistribution in nude mice-bearing MCF-7 tumors showed obvious tumor uptake and a high tumor/muscle ratio of [18F]AlF-NOTA-PBB, and tumor uptake was inhibited with 100 µg of palbociclib, demonstrating specific binding to CDK4/6. Radioactivity accumulation in MCF-7 tumors was observed in PET imaging with [18F]AlF-NOTA-PBB. Based on the results of this work, [18F]AlF-NOTA-PBB has the promising capability as a CDK4/6-targeted tumor imaging agent.


Assuntos
Neoplasias , Animais , Camundongos , Quinase 4 Dependente de Ciclina , Camundongos Nus , Distribuição Tecidual , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Quelantes
13.
Mol Pharm ; 20(6): 2942-2950, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37083360

RESUMO

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a 99mTc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic 99mTc-labeled complex ([99mTc]Tc-DP-FAPI) was obtained by kit formulation. In vitro cellular uptake and saturation binding assays were performed in FAP-transfected HT-1080 cells (FAP-HT-1080). The biodistribution was characterized, and micro-single-photon emission computed tomography (SPECT) imaging was performed in BALB/c nude mice bearing U87 MG tumors. Furthermore, a first-in-man application was performed in four healthy volunteers and three patients with gastrointestinal tumors. In vitro, the nanomolar Kd values of [99mTc]Tc-DP-FAPI indicated that it had significantly high target affinity for FAP. Biodistribution and micro-SPECT imaging studies showed that [99mTc]Tc-DP-FAPI exhibited high uptake and high tumor-to-nontargeted ratios. The calculated effective dose for [99mTc]Tc-DP-FAPI was approximately <5 mSv in four healthy volunteers. In three patients with gastrointestinal tumors, [99mTc]Tc-DP-FAPI quantitative SPECT/CT revealed high and reliable uptake. [99mTc]Tc-DP-FAPI exhibited high selectivity and affinity for FAP in vitro. The safety and effectiveness of [99mTc]Tc-DP-FAPI in primary tumor imaging have been confirmed by animal and clinical studies, revealing the potential clinical application value of this tracer.


Assuntos
Neoplasias , Animais , Humanos , Camundongos , Fibroblastos/metabolismo , Camundongos Nus , Neoplasias/genética , Neoplasias/metabolismo , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos
14.
Mikrochim Acta ; 190(8): 328, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37495854

RESUMO

Thrombin, a crucial enzyme involved in blood coagulation and associated diseases, requires accurate detection of its activity and screening of inhibitors for clinical diagnosis and drug discovery. To address this, an electrochemiluminescence (ECL) method was developed to detect thrombin activity based on the sensitization of Ti3C2Tx MXene, which could sensitize the Ru(bpy)32+ ECL system greatly. The thrombin-cleavable substrate bio-S-G-R-P-V-L-G-C was used as recognizer to evaluate the activity of thrombin. Under the optimal conditions, the limit of detection for thrombin in serum was 83 pU/mL (S/N = 3) with a linear range from 0.1 nU/mL to 1 µU/mL. Moreover, the developed ECL biosensor was employed to screen for thrombin inhibitors from Artemisiae argyi Folium. Four potential thrombin inhibitors (isoquercitrin, nepetin, L-camphor, L-borneol) were screened out with inhibition rates beyond 50%, among which isoquercitrin had the best inhibition rate of 90.26%. Isoquercitrin and nepetin were found to be competitive inhibitors of thrombin, with [Formula: see text] values of 0.91 µM and 2.18 µM, respectively. Molecular docking results showed that these compounds could interact with the active sites of thrombin through hydrogen bonds including ASP189, SER195, GLY216, and GLY219. The electrochemical biosensor constructed provides a new idea for the detection of thrombin activity and screening of its inhibitors.


Assuntos
Técnicas Biossensoriais , Trombina , Simulação de Acoplamento Molecular , Medições Luminescentes/métodos , Técnicas Biossensoriais/métodos
15.
Angew Chem Int Ed Engl ; 62(43): e202309319, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37673793

RESUMO

Electroreduction of CO2 to multi-carbon (C2+ ) products is a promising approach for utilization of renewable energy, in which the interfacial water quantity is critical for both the C2+ product selectivity and the stability of Cu-based electrocatalytic sites. Functionalization of long-chain alkyl molecules on a catalyst surface can help to increase its stability, while it also tends to block the transport of water, thus inhibiting the C2+ product formation. Herein, we demonstrate the fine tuning of interfacial water by surface assembly of toluene on Cu nanosheets, allowing for sustained and enriched CO2 supply but retarded water transfer to catalytic surface. Compared to bare Cu with fast cathodic corrosion and long-chain alkyl-modified Cu with main CO product, the toluene assembly on Cu nanosheet surface enabled a high Faradaic efficiency of 78 % for C2+ and a partial current density of 1.81 A cm-2 . The toluene-modified Cu catalyst further exhibited highly stable CO2 -to-C2 H4 conversion of 400 h in a membrane-electrode-assembly electrolyzer, suggesting the attractive feature for both efficient C2+ selectivity and excellent stability.

16.
Angew Chem Int Ed Engl ; 62(11): e202218970, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36688728

RESUMO

Although great progress has been made in new electrolytes for lithium metal batteries (LMBs), the intrinsic relationship between electrolyte composition and cell performance remains unclear due to the lack of valid quantization method. Here, we proposed the concept of negative center of electrostatic potential (NCESP) and Mayer bond order (MBO) to describe solvent capability, which highly relate to solvation structure and oxidation potential, respectively. Based on established principles, the selected electrolyte with 1.7 M LiFSI in methoxytrimethylsilane (MOTMS)/ (trifluoromethyl)trimethylsilane (TFMTMS) shows unique hyperconjugation nature to stabilize both Li anode and high-voltage cathode. The 4.6 V 30 µm Li||4.5 mAh cm-2 lithium cobalt oxide (LCO) (low N/P ratio of 1.3) cell with our electrolyte shows stable cycling with 91 % capacity retention over 200 cycles. The bottom-up design concept of electrolyte opens up a general strategy for advancing high-voltage LMBs.

17.
Small ; 18(8): e2106433, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34898005

RESUMO

Electrochemical CO2 reduction to valuable multi-carbon (C2+ ) products is attractive but with poor selectivity and activity due to the low-efficient CC coupling. Herein, a lithium vacancy-tuned Li2 CuO2 with square-planar [CuO4 ] layers is developed via an electrochemical delithiation strategy. Density functional theory calculations reveal that the lithium vacancies (VLi ) lead to a shorter distance between adjacent [CuO4 ] layers and reduce the coordination number of Li+ around each Cu, featuring with a lower energy barrier for COCO coupling than pristine Li2 CuO2 without VLi . With the VLi percentage of ≈1.6%, the Li2- x CuO2 catalyst exhibits a high Faradaic efficiency of 90.6 ± 7.6% for C2+ at -0.85 V versus reversible hydrogen electrode without iR correction, and an outstanding partial current density of -706 ± 32 mA cm-2 . This work suggests an attractive approach to create controllable alkali metal vacancy-tuned Cu catalytic sites toward C2+ products in electrochemical CO2 reduction.

18.
Mol Pharm ; 19(1): 160-171, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34904839

RESUMO

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts (CAFs) in a majority of human epithelial cancers. With low expression in normal organs, FAP has become a promising molecular target for tumor theranostics. To develop a lower cost and more widely available alternative to positron emission tomography (PET), two isocyanide-containing FAP inhibitors (CN-C5-FAPI and CN-PEG4-FAPI) were synthesized and radiolabeled with 99mTc to obtain [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ in high yields (>95%). They showed good stability in saline and mouse serum. The partition coefficient (log P) values of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were -0.86 ± 0.03 and -2.38 ± 0.07, respectively, indicating that they were good hydrophilic complexes. The low nanomolar IC50 values of CN-C5-FAPI and CN-PEG4-FAPI indicated that they had specificity to FAP. In vitro cellular uptake and blocking experiments implied a FAP-targeted uptake mechanism. The nanomolar Kd values from the saturation binding assay indicated that they had significantly high target affinity to FAP. The biodistribution and blocking study in BALB/c nude mice bearing U87MG tumors showed that both exhibited specific tumor uptake. [99mTc][Tc-(CN-PEG4-FAPI)6]+ showed a higher tumor uptake and a higher tumor/nontarget ratio than [99mTc][Tc-(CN-C5-FAPI)6]+. The results of micro-single-photon emission computed tomography (SPECT) imaging studies of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were in accordance with the biodistribution results, suggesting that [99mTc][Tc-(CN-PEG4-FAPI)6]+ is a promising tumor imaging agent for targeting FAP.


Assuntos
Proteínas de Membrana/antagonistas & inibidores , Compostos Radiofarmacêuticos , Tecnécio , Animais , Linhagem Celular Tumoral , Endopeptidases/metabolismo , Feminino , Glioblastoma/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Tomografia Computadorizada de Emissão de Fóton Único
19.
Bioorg Med Chem Lett ; 73: 128918, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926798

RESUMO

In order to develop 99mTc-labeled complexes with bisphosphonate isocyanide as novel bone imaging agents, two bisphosphonate isocyanide derivatives (CNALN and CNPAM) were synthesized and radiolabeling was performed for preparing the corresponding [99mTc]Tc(I) complexes. [99mTc]Tc-CNALN and [99mTc]Tc-CNPAM were obtained with high radiochemical purity and showed good in vitro stability. Both of them were hydrophilic and had high affinity to hydroxyapatite. The biodistribution studies in mice revealed [99mTc]Tc-CNALN showed higher bone/background ratios at 60 min post-injection. In single photon emission computed tomography (SPECT) imaging study, [99mTc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent.


Assuntos
Difosfonatos , Compostos de Organotecnécio , Animais , Cianetos , Difosfonatos/química , Camundongos , Compostos de Organotecnécio/química , Compostos Radiofarmacêuticos/farmacologia , Tecnécio/química , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos
20.
Ear Hear ; 43(1): 165-180, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34288631

RESUMO

OBJECTIVES: Emotional expressions are very important in social interactions. Children with cochlear implants can have voice emotion recognition deficits due to device limitations. Mandarin-speaking children with cochlear implants may face greater challenges than those speaking nontonal languages; the pitch information is not well preserved in cochlear implants, and such children could benefit from child-directed speech, which carries more exaggerated distinctive acoustic cues for different emotions. This study investigated voice emotion recognition, using both adult-directed and child-directed materials, in Mandarin-speaking children with cochlear implants compared with normal hearing peers. The authors hypothesized that both the children with cochlear implants and those with normal hearing would perform better with child-directed materials than with adult-directed materials. DESIGN: Thirty children (7.17-17 years of age) with cochlear implants and 27 children with normal hearing (6.92-17.08 years of age) were recruited in this study. Participants completed a nonverbal reasoning test, speech recognition tests, and a voice emotion recognition task. Children with cochlear implants over the age of 10 years also completed the Chinese version of the Nijmegen Cochlear Implant Questionnaire to evaluate the health-related quality of life. The voice emotion recognition task was a five-alternative, forced-choice paradigm, which contains sentences spoken with five emotions (happy, angry, sad, scared, and neutral) in a child-directed or adult-directed manner. RESULTS: Acoustic analyses showed substantial variations across emotions in all materials, mainly on measures of mean fundamental frequency and fundamental frequency range. Mandarin-speaking children with cochlear implants displayed a significantly poorer performance than normal hearing peers in voice emotion perception tasks, regardless of whether the performance is measured in accuracy scores, Hu value, or reaction time. Children with cochlear implants and children with normal hearing were mainly affected by the mean fundamental frequency in speech emotion recognition tasks. Chronological age had a significant effect on speech emotion recognition in children with normal hearing; however, there was no significant correlation between chronological age and accuracy scores in speech emotion recognition in children with implants. Significant effects of specific emotion and test materials (better performance with child-directed materials) in both groups of children were observed. Among the children with cochlear implants, age at implantation, percentage scores of nonverbal intelligence quotient test, and sentence recognition threshold in quiet could predict recognition performance in both accuracy scores and Hu values. Time wearing cochlear implant could predict reaction time in emotion perception tasks among children with cochlear implants. No correlation was observed between the accuracy score in voice emotion perception and the self-reported scores of health-related quality of life; however, the latter were significantly correlated with speech recognition skills among Mandarin-speaking children with cochlear implants. CONCLUSIONS: Mandarin-speaking children with cochlear implants could have significant deficits in voice emotion recognition tasks compared with their normally hearing peers and can benefit from the exaggerated prosody of child-directed speech. The effects of age at cochlear implantation, speech and language development, and cognition could play an important role in voice emotion perception by Mandarin-speaking children with cochlear implants.


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Adolescente , Adulto , Criança , Humanos , Qualidade de Vida , Reconhecimento de Voz
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