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1.
J Mol Biol ; 436(10): 168568, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583515

RESUMO

Porphyromonas gingivalis, an anaerobic CFB (Cytophaga, Fusobacterium, and Bacteroides) group bacterium, is the keystone pathogen of periodontitis and has been implicated in various systemic diseases. Increased antibiotic resistance and lack of effective antibiotics necessitate a search for new intervention strategies. Here we report a 3.5 Å resolution cryo-EM structure of P. gingivalis RNA polymerase (RNAP). The structure displays new structural features in its ω subunit and multiple domains in ß and ß' subunits, which differ from their counterparts in other bacterial RNAPs. Superimpositions with E. coli RNAP holoenzyme and initiation complex further suggest that its ω subunit may contact the σ4 domain, thereby possibly contributing to the assembly and stabilization of initiation complexes. In addition to revealing the unique features of P. gingivalis RNAP, our work offers a framework for future studies of transcription regulation in this important pathogen, as well as for structure-based drug development.

2.
Sci Total Environ ; 926: 171778, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513872

RESUMO

Cr(III)-substituted ferrihydrite (Fh-Cr(III)) is widespread in the surrounding environment of mining areas. Fh-Cr(III) is unstable and susceptible to the influence of environmental factors, such as dissolved organic matter (DOM) and light, so Cr species embedded in mineral crystal layers are likely to have more profound negative effects on the environment with the photochemical behaviors of minerals. However, the photochemical behaviors of Fh-Cr(III) in the presence of DOM remains poorly understood. For this reason, citric acid (CA) was chosen as the representative DOM to study its combined effects with visible light irradiation on Fh-Cr(III) dissolution and phase transition. The results showed that CA hindered the agglomeration of Fh-Cr(III) particles, thereby slowing the phase transition of Fh-Cr(III). However, CA exacerbated the release of Fe and Cr by maintaining Fh-Cr(III) under unstable crystal structure. Moreover, due to the occurrence of ligand-metal charge transfer (LMCT) in (CA)n-Fh-Cr(III) formed on the Fh-Cr(III) surface, the synergistic effect between CA and light irradiation greatly promoted the dissolution of Fh-Cr(III). In the mixed system of Fh-Cr(III) (3 g/L) and CA (5 mM) at initial pH 3.0, the maximum concentrations of TFe and TCr were 18.17 and 5.68 mg/L after 6 h of light reaction, which were 1.82 and 3.62 times of those in the corresponding system in the darkness. Meanwhile, the Fe(III)/Fe(II) cycling in solution and solid surfaces was affected by various reactive oxygen species (ROS) generated from the LMCT process, in which the photoproduced Fe(II) further accelerated Cr(III) dissolution under acidic solution. The fast release of Cr(III) may pose greater danger to the environment as the more toxic Cr(VI) can be easily formed through the oxidation of dissolved Cr(III). This work offers fresh insights into the migration and transformation of Cr elements in the natural environment.

3.
Behav Brain Res ; 465: 114958, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38485056

RESUMO

The lateral hypothalamic nucleus (LHy) is located in the dorsolateral hypothalamus of birds, and it is essential to many life processes. However, limited information is available about the role of LHy in mediating locomotive behaviors. In this work, we investigated the structure and function of LHy in pigeons (Columba livia) by Nissl staining, immunohistochemical (IHC) staining, insituhybridization (ISH) staining and constant current stimulation methods. The results showed that LHy appears crescent in shape, and three-dimensional coordinate value range of LHy is: A: 5.0-8.0 mm, L: 0.7-1.2 mm, D: 9.5-10.3 mm. The dopaminergic neurons in LHy were distributed in small amount and concentrated manner, while the glutamatergic neurons were distributed in a large number and uniform manner. The distribution of the above two neurons at each coronal level showed a significant positive correlation (R2 = 0.7516, P < 0.001). Our work demonstrated that LHy mainly mediates forward movement (P < 0.01) and ipsilateral lateral movement (P < 0.001), and these movements were significantly effected by electrical stimulation intensity. Our results showed that LHy can mediate the generation of directional behavior and this will provide technical support for the study of locomotor behavior regulation in birds.


Assuntos
Columbidae , Região Hipotalâmica Lateral , Animais , Hipotálamo/fisiologia , Neurônios
4.
ACS Appl Mater Interfaces ; 16(10): 12637-12646, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38441047

RESUMO

Sulfhydryl-based polyimides were synthesized by the nucleophilic ring-opening reaction of thiolactone monomers (BPDA-T, ODPA-T, BTDA-T) with polyethylenimine (PEI), and they were coated on carbon nanotubes as host materials (BPTP@CNT, ODTP@CNT, and BTTP@CNT) of the sulfur cathode. BPTP@CNT/S, ODTP@CNT/S, and BTTP@CNT/S as cathode materials not only promote the covalent bonding of sulfur and polysulfide with sulfhydryl-based polyimides but also reduce the shuttle effect of soluble polysulfide in the redox process. Moreover, sulfhydryl-based polyimides can help improve the compatibility and interfacial contact between sulfur and conductive carbon while alleviating the volume expansion of the cathode. In addition, the conductive network of carbon nanotubes improves the electronic conductivity of the cathode materials. The BTTP@CNT/S cathode showed superior stability (the initial capacity was 902 mAh g-1 at 1C, and the capacity retention rate was 88.58% after 500 cycles) and the initial capacity could reach 718 mAh g-1 when the sulfur loading was 4.8 mg cm-2 (electrolyte/sulfur ratio: 10 µL mg-1), which fully proves the feasibility of the large-scale application of sulfhydryl-based polyimide materials.

5.
Mol Oncol ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38327028

RESUMO

Stage pIIIA/N2 non-small cell lung cancer (NSCLC) is primarily treated by complete surgical resection combined with neoadjuvant/adjuvant therapies. However, up to 40% of patients experience tumor recurrence. Here, we studied 119 stage pIIIA/N2 NSCLC patients who received complete surgery plus adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). The paired tumor and resection margin samples were analyzed using next-generation sequencing (NGS). Although all patients were classified as negative resection margins by histologic methods, NGS revealed that 47.1% of them had molecularly positive surgical margins. Patients who tested positive for NGS-detected residual tumors had significantly shorter disease-free survival (DFS) (P = 0.002). Additionally, metastatic lymph node ratio, erb-b2 receptor tyrosine kinase 2 (ERBB2) mutations, and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations were also independently associated with DFS. We used these four features to construct a COX model that could effectively estimate recurrence risk and prognosis. Notably, mutational profiling through broad-panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.

6.
Sci Total Environ ; 918: 170351, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38307288

RESUMO

Iron and manganese (hydrogen) oxides (IMHOs) exhibit excellent redox capabilities for environmental pollutants and are commonly used in situ chemical oxidation (ISCO) technologies for the degradation of organic pollutants. However, the coexisting dissolved organic matter (DOMs) in surface environments would influence the degradation behavior and fate of organic pollutants in IMHOs-based ISCO. This review has summarized the interactions and mechanisms between DOMs and IMHOs, as well as the properties of DOM-IMHOs complexes. Importantly, the promotion or inhibition impact of DOM was discussed from three perspectives. First, the presence of DOMs may hinder the accessibility of active sites on IMHOs, thus reducing their efficiency in degrading organic pollutants. The formation of compounds between DOMs and IMHOs alters their stability and activity in the degradation process. Second, the presence of DOMs may also affect the generation and transport of active species, thereby influencing the oxidative degradation process of organic pollutants. Third, specific components within DOMs also participate and affect the degradation pathways and rates. A comprehensive understanding of the interaction between DOMs and IMHOs helps to better understand and predict the degradation process of organic pollutants mediated by IMHOs in real environmental conditions and contributes to the further development and application of IMHO-mediated ISCO technology.

7.
Comput Struct Biotechnol J ; 23: 278-286, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38173876

RESUMO

G protein-coupled receptors (GPCRs) play a pivotal role in fundamental biological processes and disease development. GPCR isoforms, derived from alternative splicing, can exhibit distinct signaling patterns. Some highly-truncated isoforms can impact functional performance of full-length receptors, suggesting their intriguing regulatory roles. However, how these truncated isoforms interact with full-length counterparts remains largely unexplored. Here, we computationally investigated the interaction patterns of three human GPCRs from three different classes, ADORA1 (Class A), mGlu2 (Class C) and SMO (Class F) with their respective truncated isoforms because their homodimer structures have been experimentally determined, and they have truncated isoforms deposited and identified at protein level in Uniprot database. Combining the neural network-based AlphaFold2 and two physics-based protein-protein docking tools, we generated multiple complex structures and assessed the binding affinity in the context of atomistic molecular dynamics simulations. Our computational results suggested all the four studied truncated isoforms showed potent binding to their counterparts and overlapping interfaces with homodimers, indicating their strong potential to block homodimerization of their counterparts. Our study offers insights into functional significance of GPCR truncated isoforms and supports the ubiquity of their regulatory roles.

8.
Proteins ; 92(2): 206-218, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37795805

RESUMO

Therapeutic monoclonal antibodies are the most rapidly growing class of molecular medicine, and they are beneficial to the treatment of a broad spectrum of human diseases. However, the aggregation of antibodies during the process of manufacture, distribution, and storage poses significant challenges, potentially compromising efficacy and inducing adverse immune responses. We previously conceived a QTY (glutamine, threonine, tyrosine) code, a simple tool for enhancing protein water-solubility by systematically pairwise replacing hydrophobic residues L (leucine), V (valine)/I (isoleucine), and F (phenylalanine). The QTY code offers a promising alternative to traditional methods of controlling aggregation in integral transmembrane proteins. In this study, we designed variants of four antibodies applying the QTY code, changing only the ß-sheets. Through the structure-based aggregation analysis, we found that these QTY antibody variants demonstrated significantly decreased aggregation propensity compared to their wild-type counter parts. Our results of molecular dynamics simulations showed that the design by QTY code is capable of maintaining the antigen-binding affinity and structural stability. Our structural informatic and computational study suggests that the QTY code offers a significant potential in mitigating antibody aggregation.


Assuntos
Anticorpos Monoclonais , Tirosina , Humanos , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/química , Tirosina/metabolismo , Simulação de Dinâmica Molecular , Treonina , Biologia Computacional/métodos
9.
J Environ Manage ; 351: 119876, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38157577

RESUMO

The removal of organic pollutants by biochar has been extensively studied. However, the differences in the removal mechanisms of contaminants by biochar obtained from different preparation techniques have not been thoroughly elucidated. In this study, the catalytic performances of hydrochar (HC) and pyrochar (PC) were compared in the dark and light. Owing to more persistent free radicals (PFRs), greater defects and stronger charge transfer ability on the surface, PC could produce a certain concentration of superoxide radicals (•O2-) even in the dark, making its degradation efficiency for benzoic acid (BA) 11% higher than that of HC. On the contrary, when the light was turned on, HC rather than PC can generate a higher amount of hydroxyl radical (•OH), resulting in an 11% higher degradation efficiency of BA compared to PC. The improvement of catalytic performance in HC originated from its oxygen-containing functional groups (OFGs), which was beneficial for its effective production of singlet oxygen (1O2) and ·OH under light exposure. For PC, its photocatalytic activity depended mainly on the formation of 1O2 induced by the triplet of DOM (dissolved organic matter), but the lack of oxidative ·OH in its system leads to a lower degradation efficiency than that of HC. To prove the universal applicability of this rule for biochar materials, HC and PC materials obtained from soybean residue were also prepared for degrading BA. This work is devoted to an in-depth exploration of the catalytic activation mechanism of biochar obtained by different technological methods, and can create conditions for the generation of more dominant reactive oxygen species (ROS) on biochar, thus providing the guidance for environmental remediation.


Assuntos
Carvão Vegetal , Superóxidos , Espécies Reativas de Oxigênio , Radicais Livres/química , Carvão Vegetal/química , Superóxidos/química , Oxigênio/química
10.
Nat Neurosci ; 26(12): 2081-2089, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37996529

RESUMO

It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme pyruvate kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity.


Assuntos
Glicólise , Fosforilação Oxidativa , Animais , Camundongos , Fosfotransferases/metabolismo , Estresse Oxidativo , Glucose/metabolismo
11.
Int J Mol Sci ; 24(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003455

RESUMO

Chemokine receptors play crucial roles in fundamental biological processes. Their malfunction may result in many diseases, including cancer, autoimmune diseases, and HIV. The oligomerization of chemokine receptors holds significant functional implications that directly affect their signaling patterns and pharmacological responses. However, the oligomerization patterns of many chemokine receptors remain poorly understood. Furthermore, several chemokine receptors have highly truncated isoforms whose functional role is not yet clear. Here, we computationally show homo- and heterodimerization patterns of four human chemokine receptors, namely CXCR2, CXCR7, CCR2, and CCR7, along with their interaction patterns with their respective truncated isoforms. By combining the neural network-based AlphaFold2 and physics-based protein-protein docking tool ClusPro, we predicted 15 groups of complex structures and assessed the binding affinities in the context of atomistic molecular dynamics simulations. Our results are in agreement with previous experimental observations and support the dynamic and diverse nature of chemokine receptor dimerization, suggesting possible patterns of higher-order oligomerization. Additionally, we uncover the strong potential of truncated isoforms to block homo- and heterodimerization of chemokine receptors, also in a dynamic manner. Our study provides insights into the dimerization patterns of chemokine receptors and the functional significance of their truncated isoforms.


Assuntos
Simulação de Dinâmica Molecular , Transdução de Sinais , Humanos , Dimerização , Isoformas de Proteínas
12.
Nat Commun ; 14(1): 5836, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730807

RESUMO

Hydrogen spillover is the migration of activated hydrogen atoms from a metal particle onto the surface of catalyst support, which has made significant progress in heterogeneous catalysis. The phenomenon has been well researched on oxide supports, yet its occurrence, detection method and mechanism on non-oxide supports such as metal-organic frameworks (MOFs) remain controversial. Herein, we develop a facile strategy for efficiency enhancement of hydrogen spillover on various MOFs with the aid of water molecules. By encapsulating platinum (Pt) nanoparticles in MOF-801 for activating hydrogen and hydrogenation of C=C in the MOF ligand as activated hydrogen detector, a research platform is built with Pt@MOF-801 to measure the hydrogenation region for quantifying the efficiency and spatial extent of hydrogen spillover. A water-assisted hydrogen spillover path is found with lower migration energy barrier than the traditional spillover path via ligand. The synergy of the two paths explains a significant boost of hydrogen spillover in MOF-801 from imperceptible existence to spanning at least 100-nm-diameter region. Moreover, such strategy shows universality in different MOF and covalent organic framework materials for efficiency promotion of hydrogen spillover and improvement of catalytic activity and antitoxicity, opening up new horizons for catalyst design in porous crystalline materials.

13.
Heliyon ; 9(8): e18324, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37554834

RESUMO

Aging is the strongest risk factor for cardiovascular disease, with progressive decline in the function of vascular endothelial cells (ECs) with age. Systematic analyses of the effects of aging on different cardiac EC types remain limited. Here, we constructed a scRNA atlas of EC transcriptomes in young and old mouse hearts. We identified 10 EC subclusters. The multidimensionally differential genes (DEGs) analysis across different EC clusters shows molecular changes with aging, showing the increase in the overall inflammatory microenvironment and the decrease in angiogenesis and cytoskeletal support capacity of aged ECs. And we performed an in-depth analysis of 3 special ECs, Immunology, Proliferating and Angiogenic. The Immunology EC seems highly associated with some immune regulatory functions, which decline with aging at different degrees. Analysis of two types of neovascular ECs, Proliferating, Angiogenic, implied that Angiogenic ECs can differentiate into multiple EC directions after initially originating from proliferating ECs. And aging leads to a decrease in the ability of vascular angiogenesis and differentiation. Finally, we summarized the effects of aging on cell signaling communication between different EC clusters. This cardiac EC atlas offers comprehensive insights into the molecular regulations of cardiovascular aging, and provides new directions for the prevention and treatment of age-related cardiovascular disease.

14.
Microbiol Spectr ; 11(4): e0076823, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37395668

RESUMO

The function of Seryl-tRNA synthetase in fungi during gene transcription regulation beyond translation has not been reported. Here, we report a seryl-tRNA synthetase, ThserRS, which can negatively regulate laccase lacA transcription in Trametes hirsuta AH28-2 under exposure to copper ion. ThserRS was obtained through yeast one-hybrid screening using a bait sequence of lacA promoter (-502 to -372 bp). ThserRS decreased while lacA increased at the transcription level in T. hirsuta AH28-2 in the first 36 h upon CuSO4 induction. Then, ThserRS was upregulated, and lacA was downregulated. ThserRS overexpression in T. hirsuta AH28-2 resulted in a decrement in lacA transcription and LacA activity. By comparison, ThserRS silencing led to increased LacA transcripts and activity. A minimum of a 32-bp DNA fragment containing two putative xenobiotic response elements could interact with ThserRS, with a dissociation constant of 919.9 nM. ThserRS localized in the cell cytoplasm and nucleus in T. hirsuta AH28-2 and was heterologously expressed in yeast. ThserRS overexpression also enhanced mycelial growth and oxidative stress resistance. The transcriptional level of several intracellular antioxidative enzymes in T. hirsuta AH28-2 was upregulated. Our results demonstrate a noncanonical activity of SerRS that acts as a transcriptional regulation factor to upregulate laccase expression at an early stage after exposure to copper ions. IMPORTANCE Seryl-tRNA synthetase is well known for the attachment of serine to the corresponding cognate tRNA during protein translation. In contrast, its functions beyond translation in microorganisms are underexplored. We performed in vitro and cell experiments to show that the seryl-tRNA synthetase in fungi with no UNE-S domain at the carboxyl terminus can enter the nucleus, directly interact with the promoter of the laccase gene, and negatively regulate the fungal laccase transcription early upon copper ion induction. Our study deepens our understanding of the Seryl-tRNA synthetase noncanonical activities in microorganisms. It also demonstrates a new transcription factor for fungal laccase transcription.


Assuntos
Saccharomyces cerevisiae , Serina-tRNA Ligase , Saccharomyces cerevisiae/metabolismo , Trametes/genética , Trametes/metabolismo , Serina-tRNA Ligase/metabolismo , Lacase/genética , Lacase/metabolismo , Cobre/metabolismo , Íons
15.
Nanoscale ; 15(31): 12961-12971, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37462542

RESUMO

Lithium-sulfur (Li-S) batteries are severely restricted for practical application due to the polysulfide shuttle effect, Li dendrites and thermal runaway. The use of PEO-based polymer composite electrolytes (PCEs) as an alternative strategy suffers from limited lithium-ion conductivity with deficient long-range transfer route. Herein, Li6.4La3Zr1.4Ta0.6O12 (LLZTO) nanoparticles modified with an in situ-synthesized zwitterionic covalent organic framework layer (denoted as LLZTO@HUT4) were introduced into PEO-based PCEs. Zwitterionic HUT4 modified the lithiophobic LiOH/Li2CO3 layer on the surface of LLZTO nanoparticles, which could notably promote Li+ ion transport for superior electrochemical performance of PCEs. Additionally, the intermediate layer HUT4 located between LLZTO and PEO could further improve the mechanical properties of electrolytes due to the enhanced inorganic/organic interface compatibility and intermolecular interaction. As a result, the obtained LLZTO@HUT4-15%/PEO electrolyte exhibited a competent ionic conductivity of 0.73 mS cm-1 with a Li+ transference number of up to 0.74 at 60 °C. The assembled S@CNT|LLZTO@HUT4-15%/PEO|Li coin cell delivered a considerable initial discharge capacity of 1018 mA h g-1 at 0.2 C, with approximately 92.1% capacity retention after 100 cycles, elucidating an obviously suppressed shuttle effect.

16.
Ren Fail ; 45(1): 2237124, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37482915

RESUMO

BACKGROUND: The treatment of refractory nephrotic syndrome (RNS) is full of challenges and the role of rituximab (RTX) is not well-established, thus this study aims to demonstrate the role of RTX in RNS. METHODS: This was a multicenter retrospective study of all adult patients receiving RTX for RNS. Patients enrolled were divided into two groups according to pathological pattern: 20 patients as a group of podocytopathy (including minimal change disease [MCD] and focal and segmental glomerulosclerosis [FSGS]), and 26 patients as membranous nephropathy (MN) group. The remission rate, relapse rate, adverse effects, and predictors of remission were analyzed. RESULTS: A total of 75 patients received RTX for RNS and 48 were available for analysis after exclusion criteria. No significant difference in the remission rate at 6 or 12 months was observed between the MCD/FSGS and MN cases (p > 0.05). The median duration of the first complete remission (CR) was 1 month in the podocytopathy group and 12.5 months in the MN group. Three relapses were associated with infection as the ultimate outcome, and 6 out of 48 remained refractory representing a response rate of 87.5% in RNS. Clinical predictors of cumulative CR were estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and mean arterial pressure (MAP) ≤103 mmHg at the beginning of therapy in patients with MN. No serious adverse effects were reported. CONCLUSIONS: RTX appears to be effective in RNS across various clinical and pathological subtypes, exhibiting a low relapse rate and minimal significant side effects in the majority of patients.


Assuntos
Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Nefrose Lipoide , Síndrome Nefrótica , Humanos , Adulto , Rituximab/efeitos adversos , Estudos Retrospectivos , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Resultado do Tratamento , Nefrose Lipoide/tratamento farmacológico , Glomerulonefrite Membranosa/tratamento farmacológico , Recidiva , Doença Crônica , Imunossupressores/uso terapêutico
17.
Angew Chem Int Ed Engl ; 62(38): e202309104, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37500601

RESUMO

Polychlorinated (hetero)arenes have shown great promise for organic optoelectronics applications. However, the harsh synthetic routes for polychlorinated compounds and the possible luminescence quenching from the compact intermolecular π-π stacking induced by chlorine atoms limit their investigations and applications in luminescent materials. Herein, two isomeric polychlorinated polycyclic aromatic hydrocarbon (PAH) compounds JY-1-Cl and JY-2-Cl consisting of rigidified aryl ketones and amine are designed and synthesized under mild conditions through nucleophilic chlorination intermediated by an electron donor-acceptor complex. Among them, as a result of the strong π-π interactions induced by chlorine atoms, JY-2-Cl exhibits bright monomer and dimer emissions with dual thermally activated delayed fluorescence (TADF) characters. Notably, compared with the non-chlorinated compounds, a high photoluminescence quantum yield is maintained after introducing multiple chlorine atoms into JY-2-Cl. The first dual-TADF organic light-emitting diodes are also successfully fabricated with maximum external quantum efficiency as high as 29.1 % by employing JY-2-Cl as emitter. This work presents a new paradigm and synthesis of polychlorinated amine-carbonyl PAHs and demonstrates the great potential of the chlorinated materials for luminescent applications.

18.
ACS Appl Mater Interfaces ; 15(30): 36738-36747, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37487247

RESUMO

Shaping covalent organic frameworks (COFs) into macroscopic objects for practical application remains a huge challenge. Herein, a new thiadiazole-derived COF macroscopic ultralight aerogel (NNS-VCOF) was prepared through acid-catalyzed aldol condensation between 2,5-dimethyl-1,3,4-thiadiazole and a tritopic aromatic aldehyde derivative. NNS-VCOF aerogel shows extremely low density (ca. 0.020 g cm-3), excellent mechanical properties (compression modulus of 16.65 kPa), thermal insulation properties (low thermal conductivity of 0.03270 W m-1 K-1 at 25 °C), and flame retardancy (quickly self-extinguishing after ignition) due to its three-dimensional sponge-like architecture and special nitrogen heterocyclic framework. To our delight, NNS-VCOF aerogel not only can be used as an outstanding macroscopic material but also shows efficient photocatalytic hydrogen evolution properties in a powder state because of the superhydrophilicity and appropriate optical properties.

19.
Chemosphere ; 337: 139281, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37364642

RESUMO

The easy recombination of photoexcited electron-hole pairs is a serious constraint for the application of photocatalysts. In this work, a range of BiOClxI1-x solid solutions with abundant oxygen vacancies (BiOClxI1-x-OVs) were synthesized. In particular, the optimal BiOCl0.5I0.5-OVs sample exhibited almost 100% removal of bisphenol A (BPA) within 45 min visible light exposure, which was 22.4, 3.1 and 4.5 times greater than BiOCl, BiOCl-OVs and BiOCl0.5I0.5, respectively. Besides, the apparent quantum yield of BPA degradation reaches 0.24%, better than some other photocatalysts. Benefiting from the synergism of oxygen vacancies and solid solution, BiOCl0.5I0.5-OVs gained an enhanced photocatalytic capacity. Oxygen vacancies induced an intermediate defective energy level in BiOClxI1-x-OVs materials, promoting the generation of photogenerated electrons and the molecular oxygen adsorption to produce more active oxygen radicals. Meanwhile, the fabricated solid solution structure enhanced the internal electric field between BiOCl layers, achieving rapid migration of photoexcited electrons and effective segregation of photoinduced charge carriers. Thus, this study provides a viable idea to solve the problems of poor visible light absorption of BiOCl-based photocatalysts and easy reorganization of electrons and holes in the photocatalysts.


Assuntos
Eletricidade , Oxigênio , Espécies Reativas de Oxigênio , Adsorção , Elétrons
20.
Nat Commun ; 14(1): 3468, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37308490

RESUMO

EGFR exon 20 insertion (20ins)-positive non-small-cell lung cancer (NSCLC) is an uncommon disease with limited therapeutic options and dismal prognosis. Here we report the activity, tolerability, potential mechanisms of response and resistance for dual targeting EGFR 20ins with JMT101 (anti-EGFR monoclonal antibody) plus osimertinib from preclinical models and an open label, multi-center phase 1b trial (NCT04448379). Primary endpoint of the trial is tolerability. Secondary endpoints include objective response rate, duration of response, disease control rate, progression free survival, overall survival, the pharmacokinetic profile of JMT101, occurrence of anti-drug antibodies and correlation between biomarkers and clinical outcomes. A total of 121 patients are enrolled to receive JMT101 plus osimertinib 160 mg. The most common adverse events are rash (76.9%) and diarrhea (63.6%). The confirmed objective response rate is 36.4%. Median progression-free survival is 8.2 months. Median duration of response is unreached. Subgroup analyses were performed by clinicopathological features and prior treatments. In patients with platinum-refractory diseases (n = 53), confirmed objective response rate is 34.0%, median progression-free survival is 9.2 months and median duration of response is 13.3 months. Responses are observed in distinct 20ins variants and intracranial lesions. Intracranial disease control rate is 87.5%. Confirmed intracranial objective response rate is 25%.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Anticorpos Monoclonais , Éxons
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