Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 588
Filtrar
1.
Nature ; 621(7980): 840-848, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674084

RESUMO

In both cancer and infections, diseased cells are presented to human Vγ9Vδ2 T cells through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A11-4. Here we show how-in both humans and alpaca-multiple pAgs function as 'molecular glues' to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1-BTN2A1 association, abolishing pAg-mediated Vγ9Vδ2 T cell activation. Analyses using structure-based molecular-dynamics simulations, 19F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor-mediated γδ T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human γδ T cell function.


Assuntos
Butirofilinas , Ativação Linfocitária , Fosfoproteínas , Receptores de Antígenos de Linfócitos T gama-delta , Linfócitos T , Animais , Humanos , Antígenos CD/imunologia , Antígenos CD/metabolismo , Butirofilinas/imunologia , Butirofilinas/metabolismo , Camelídeos Americanos/imunologia , Simulação de Dinâmica Molecular , Fosfoproteínas/imunologia , Fosfoproteínas/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Cristalografia por Raios X , Ressonância Magnética Nuclear Biomolecular , Termodinâmica
2.
Proc Natl Acad Sci U S A ; 121(16): e2219055121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38536744

RESUMO

The past 15 y has seen much development in documentation of domestication of plants and animals as gradual traditions spanning millennia. There has also been considerable momentum in understanding the dispersals of major domesticated taxa across continents spanning thousands of miles. The two processes are often considered within different theoretical strains. What is missing from our repertoire of explanations is a conceptual bridge between the protracted process over millennia and the multiregional, globally dispersed nature of domestication. The evidence reviewed in this paper bears upon how we conceptualize domestication as an episode or a process. By bringing together the topics of crop domestication and crop movement, those complex, protracted, and continuous outcomes come more clearly into view.


Assuntos
Produtos Agrícolas , Domesticação , Animais , Produtos Agrícolas/genética
3.
Nucleic Acids Res ; 52(D1): D376-D383, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37870448

RESUMO

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.


Assuntos
Sítio Alostérico , Bases de Conhecimento , Humanos , Regulação Alostérica , Descoberta de Drogas , Ligantes , Proteoma , Mapas de Interação de Proteínas
4.
Proc Natl Acad Sci U S A ; 120(32): e2216532120, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37523561

RESUMO

We analyzed transcriptional data from 104 HPV+ (Human papillomavirus) HNSCC (head and neck squamous cell carcinoma) tumors together with two publicly available sources to identify highly robust transcriptional programs (modules) which could be detected consistently despite heterogeneous sequencing and quantification methodologies. Among 22 modules identified, we found a single module that naturally subclassifies HPV+ HNSCC tumors based on a bimodal pattern of gene expression, clusters all atypical features of HPV+ HNSCC biology into a single subclass, and predicts patient outcome in four independent cohorts. The subclass-defining gene set was strongly correlated with Nuclear factor kappa B (NF-κB) target expression. Tumors with high expression of this NF-κB module were rarely associated with activating PIK3CA alterations or viral integration, and also expressed higher levels of HPHPV E2 and had decreased APOBEC mutagenesis. Alternatively, they harbored inactivating alterations of key regulators of NF-κB, TNF receptor associated factor 3 (TRAF3), and cylindromatosis (CYLD), as well as retinoblastoma protein (RB1). HPV+ HNSCC cells in culture with experimental depletion of TRAF3 or CYLD displayed increased expression of the subclass-defining genes, as well as robust radio-sensitization, thus recapitulating both the tumor transcriptional state and improved treatment response observed in patient data. Across all gene sets investigated, methylation to expression correlations were the strongest for the subclass-defining, NF-κB-related genes. Increased tumor-infiltrating CD4+ T cells and increased Estrogen receptors alpha (ERα) expression were identified in NF-κB active tumors. Based on the relatively high rates of cure in HPV+ HNSCC, deintensification of therapy to reduce treatment-related morbidity is being studied at many institutions. Tumor subclassification based on oncogenic subtypes may help guide the selection of therapeutic intensity or modality for patients with HPV+ HNSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , NF-kappa B/genética , NF-kappa B/metabolismo , Fator 3 Associado a Receptor de TNF/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , Infecções por Papillomavirus/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , Papillomavirus Humano , Carcinogênese , Papillomaviridae/genética , Papillomaviridae/metabolismo
5.
Cell Mol Life Sci ; 81(1): 256, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866991

RESUMO

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats. Targeted deletion of Mettl3 in smooth muscle cells exacerbated hemodynamic consequences of hypoxia-induced PH and accelerated pulmonary vascular remodeling in vivo. Additionally, the absence of METTL3 markedly induced phenotypic switching in PASMCs in vitro. Mechanistically, METTL3 depletion attenuated m6A modification and hindered the processing of pri-miR-143/145, leading to a downregulation of miR-143-3p and miR-145-5p. Inhibition of hnRNPA2B1, an m6A mediator involved in miRNA maturation, similarly resulted in a significant reduction of miR-143-3p and miR-145-5p. We demonstrated that miR-145-5p targets Krüppel-like factor 4 (KLF4) and miR-143-3p targets fascin actin-bundling protein 1 (FSCN1) in PASMCs. The decrease of miR-145-5p subsequently induced an upregulation of KLF4, which in turn suppressed miR-143/145 transcription, establishing a positive feedback circuit between KLF4 and miR-143/145. This regulatory circuit facilitates the persistent suppression of contractile marker genes, thereby sustaining PASMC phenotypic switch. Collectively, hypoxia-induced upregulation of METTL3, along with m6A mediated regulation of miR-143/145, might serve as a protective mechanism against phenotypic switch of PASMCs. Our results highlight a potential therapeutic strategy targeting m6A modified miR-143/145-KLF4 loop in the treatment of PH.


Assuntos
Adenosina , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like , Metiltransferases , MicroRNAs , Miócitos de Músculo Liso , Artéria Pulmonar , Fator 4 Semelhante a Kruppel/metabolismo , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Artéria Pulmonar/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Miócitos de Músculo Liso/metabolismo , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Metiltransferases/metabolismo , Metiltransferases/genética , Ratos , Fenótipo , Masculino , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Músculo Liso Vascular/metabolismo , Camundongos Endogâmicos C57BL , Remodelação Vascular/genética , Ratos Sprague-Dawley , Humanos
6.
Nucleic Acids Res ; 51(W1): W129-W133, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37078611

RESUMO

Driver mutations can contribute to the initial processes of cancer, and their identification is crucial for understanding tumorigenesis as well as for molecular drug discovery and development. Allostery regulates protein function away from the functional regions at an allosteric site. In addition to the known effects of mutations around functional sites, mutations at allosteric sites have been associated with protein structure, dynamics, and energy communication. As a result, identifying driver mutations at allosteric sites will be beneficial for deciphering the mechanisms of cancer and developing allosteric drugs. In this study, we provided a platform called DeepAlloDriver to predict driver mutations using a deep learning method that exhibited >93% accuracy and precision. Using this server, we found that a missense mutation in RRAS2 (Gln72 to Leu) might serve as an allosteric driver of tumorigenesis, revealing the mechanism of the mutation in knock-in mice and cancer patients. Overall, DeepAlloDriver would facilitate the elucidation of the mechanisms underlying cancer progression and help prioritize cancer therapeutic targets. The web server is freely available at: https://mdl.shsmu.edu.cn/DeepAlloDriver.


Assuntos
Aprendizado Profundo , Neoplasias , Animais , Camundongos , Regulação Alostérica/genética , Sítio Alostérico , Neoplasias/genética , Proteínas/química , Carcinogênese/genética , Mutação
7.
Nucleic Acids Res ; 51(W1): W33-W38, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37070199

RESUMO

Increasing data in allostery are requiring analysis of coupling relationships among different allosteric sites on a single protein. Here, based on our previous efforts on reversed allosteric communication theory, we have developed AlloReverse, a web server for multiscale analysis of multiple allosteric regulations. AlloReverse integrates protein dynamics and machine learning to discover allosteric residues, allosteric sites and regulation pathways. Especially, AlloReverse could reveal hierarchical relationships between different pathways and couplings among allosteric sites, offering a whole map of allostery. The web server shows a good performance in re-emerging known allostery. Moreover, we applied AlloReverse to explore global allostery on CDC42 and SIRT3. AlloReverse predicted novel allosteric sites and allosteric residues in both systems, and the functionality of sites was validated experimentally. It also suggests a possible scheme for combined therapy or bivalent drugs on SIRT3. Taken together, AlloReverse is a novel workflow providing a complete regulation map and is believed to aid target identification, drug design and understanding of biological mechanisms. AlloReverse is freely available to all users at https://mdl.shsmu.edu.cn/AlloReverse/ or http://www.allostery.net/AlloReverse/.


Assuntos
Sirtuína 3 , Regulação Alostérica , Descoberta de Drogas , Sítio Alostérico , Proteínas/química
8.
J Am Chem Soc ; 146(42): 28770-28782, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39389036

RESUMO

The inferior oxidative stability of commercial carbonate electrolytes and overgrowth of the electrode-electrolyte interphase (EEI) have largely hindered the development of high-voltage lithium metal batteries. In this study, these challenges are addressed by designing Li+-solvent chelating solvation structures to inhibit solvent decomposition using cyano-alkyl-phosphate as a demonstration. Theoretical and experimental studies confirm that the -P═O and -C≡N groups within diethyl (2-cyanethyl) phosphonate exhibit a comparable ability to coordinate with Li+, facilitating the formation of seven-membered chelating structures. This unique solvation structure contributes to the formation of anion-derived inorganic-rich EEI with high stability and robustness, hindering the further decomposition of the electrolyte. Additionally, the cyano group has a strong complexation with the transition metal (TM) in the cathode to inhibit TM dissolution, thereby ensuring the structural stability of the cathode particle. Utilizing this special chelating structure, the designed electrolyte demonstrates favorable Li plating/stripping reversibility and promising oxidative stability in high-voltage batteries. Consequently, the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode exhibits a high capacity retention (90%) after operating 300 cycles. Under harsh testing conditions, the 4.6 V Li||NCM811 pouch cell with a capacity of 1.4 Ah (∼295 Wh kg-1 based on the total mass of the cell) retains 70% capacity after 80 cycles. This work provides new insights into the correlation between the solvation structure and oxidative stability of electrolytes, contributing significantly to the advancement of high-voltage lithium metal batteries.

9.
Cancer Sci ; 115(2): 477-489, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38081591

RESUMO

Inhibition of cholesterol de novo synthesis (DNS) by statins has controversial effects on the treatment of hepatocellular carcinoma (HCC). High fatty acid conditions have been reported to limit the effect of statins on metabolism diseases. Whether high fatty acid conditions interfere with the effect of statins on HCC remains unclear. Here, we reported that inhibiting cholesterol DNS with atorvastatin promoted the oncogenic capabilities of diethylnitrosamine (DEN) in mice fed high fatty acid diets (HFD). The combined analysis of metabolomics and transcriptomics revealed that arachidonic acid (AA) metabolism was the most significant changed pathway between mice with and without atorvastatin treatment. In vitro, in the presence of AA precursor linoleic acid (LA), atorvastatin promoted the proliferation and migration ability of HCC cell lines. However, in the absence of LA, these phenomena disappeared. TCGA and tissue microarray examination revealed that prostaglandin e synthase 2 (PTGES2), a key enzyme in AA metabolism, was associated with the poor outcome of HCC patients. Overexpression of PTGES2 promoted the proliferation and migration of HCC cell lines, and knockdown of PTGES2 inhibited the proliferation and migration of cells. Additionally, atorvastatin upregulated PTGES2 expression by enhancing Sterol-regulatory element binding protein 2 (SREBP2)-mediated transcription. Knockdown of PTGES2 reversed the proliferation and migration ability enhanced by atorvastatin. Overall, our study reveals that a high fatty acid background is one of the possible conditions limiting the application of statins in HCC, under which statins promote the progression of HCC by enhancing SREBP2-mediated PTGES2 transcription.


Assuntos
Carcinoma Hepatocelular , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ácidos Graxos/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ácido Araquidônico/farmacologia , Prostaglandina-E Sintases/genética , Atorvastatina/farmacologia , Linhagem Celular Tumoral , Colesterol , Proliferação de Células
10.
Hum Mol Genet ; 31(9): 1407-1416, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34761271

RESUMO

This study aimed to identify the genes and small RNAs (sRNAs) expressed by the human endogenous retrovirus K (HERV-K) HML2 and their associations with the immune process of systemic lupus erythematosus (SLE). RNA-Seq data including 99 SLE patients and 18 controls (GSE72420) was obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) as well as HML2-DEGs between SLE patients and normal controls were identified. Five HML2-DEGs involved in immune-regulating function were identified using weighted gene co-expression network analysis. The associations between these genes and the proportions of immune cells were determined by CIBERSORT. Ten candidate HML2-encoded sRNAs were identified based on specific criteria, and three of them were further validated in SLE patients by qRT-PCR. The diagnostic values of these three sRNAs were evaluated in SLE and lupus nephritis (LN). This study suggested that HML2 genes and their encoded sRNAs might be involved in the immune regulation and progress of SLE. These potential sRNAs might function as regulatory molecules and diagnostic biomarkers of SLE and LN.


Assuntos
Retrovirus Endógenos , Lúpus Eritematoso Sistêmico , Biomarcadores/metabolismo , Retrovirus Endógenos/genética , Humanos , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , RNA/metabolismo
11.
Cogn Affect Behav Neurosci ; 24(3): 517-526, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38273105

RESUMO

Sleep deprivation (SD) negatively affects many cognitive functions, such as language performance. However, what remains unclear is whether and how SD affects the language-related brain network based on gender and age differences. The current study of 86 healthy adults used resting-state functional magnetic resonance imaging (rs-fMRI) to measure language-related functional connectivity after full sleep or partial SD. Gender and age differences in functional connectivity were assessed across four linguistic aspects: phonetics, morphology, semantics, and syntax. The results showed that SD can affect the connectivity status of language-related brain networks, especially syntax-related networks. Furthermore, the influence of SD on the functional connectivity in language-related networks differed between male and female groups, and between younger and older groups. Specifically, there were gender differences in the temporal association cortex and age differences in the parietal association cortex, during full sleep versus partial SD. These findings highlight changes in the brain's functional connectivity in response to SD as a potential source of gender and age differences in brain function.


Assuntos
Mapeamento Encefálico , Encéfalo , Idioma , Imageamento por Ressonância Magnética , Caracteres Sexuais , Privação do Sono , Humanos , Masculino , Feminino , Adulto , Privação do Sono/fisiopatologia , Privação do Sono/diagnóstico por imagem , Adulto Jovem , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Vias Neurais/fisiopatologia , Vias Neurais/fisiologia , Vias Neurais/diagnóstico por imagem , Pessoa de Meia-Idade , Envelhecimento/fisiologia , Adolescente
12.
J Transl Med ; 22(1): 2, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166990

RESUMO

BACKGROUND: Diabetes mellitus (DM) is a progressive disease that involves multiple organs due to increased blood glucose, and diabetic retinopathy (DR) is the main complication of DM in the eyes and causes irreversible vision loss. In the pathogenesis of diabetic vascular disease, oxidative stress caused by hyperglycemia plays an important role in Müller cell impairment. In recent years, AdipoRon, an adiponectin analog that demonstrated important physiological functions in obesity, diabetes, inflammation, and cardiovascular diseases, demonstrated cellular protection from apoptosis and reduced inflammatory damage through a receptor-dependent mechanism. Here, we investigated how AdipoRon reduced oxidative stress and apoptosis in Müller glia in a high glucose environment. RESULTS: By binding to adiponectin receptor 1 on Müller glia, AdipoRon activated 5' adenosine monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase phosphorylation downstream, thereby alleviating oxidative stress and eventual apoptosis of cells and tissues. Transcriptome sequencing revealed that AdipoRon promoted the synthesis and expression of early growth response factor 4 (EGR4) and inhibited the cellular protective effects of AdipoRon in a high-glucose environment by reducing the expression of EGR4. This indicated that AdipoRon played a protective role through the EGR4 and classical AMPK pathways. CONCLUSIONS: This provides a new target for the early treatment of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Proteínas Quinases Ativadas por AMP/metabolismo , Retinopatia Diabética/tratamento farmacológico , Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo , Glucose , Fosforilação , Receptores de Adiponectina/metabolismo , Animais , Camundongos
13.
Invest New Drugs ; 42(3): 309-317, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700579

RESUMO

BACKGROUND: Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM: This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS: This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS: The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS: The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS: GOV: NCT05574998.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Endostatinas , Neoplasias Pulmonares , Paclitaxel , Pemetrexede , Proteínas Recombinantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Endostatinas/administração & dosagem , Endostatinas/efeitos adversos , Endostatinas/uso terapêutico , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Infusões Intravenosas , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Prospectivos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Pemetrexede/uso terapêutico , Adulto , Intervalo Livre de Progressão
14.
Chemistry ; 30(51): e202401739, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-38954398

RESUMO

Metal halide materials have recently drawn increasing research interest for their excellent opto-electronic properties and structural diversity, but their resulting rigid structures render them brittle and poor formability during manufacturing. Here we demonstrate a thermoplastic luminant hybrid lead halide solid by integrating lead bromide complex into tri-n-octylphosphine oxide (TOPO) matrix. The construction of the hybrid materials can be achieved by a simple dissolution process, in which TOPO molecules act as the solvents and ligands to yield the monodispersed clusters. The combination of these functional units enables the near-room-temperature melt-processing of the materials into targeted geometry by simple molding or printing techniques, which offer possibilities for fluorescent writing inks with outstanding self-healing capacity to physical damage. The intermarriage between metal halide clusters with functional molecules expands the range of practical applications for hybrid metal halide materials.

15.
Langmuir ; 40(11): 5557-5570, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38465803

RESUMO

Contact electrification (CE) is a common physical process by which triboelectric charges are generated through the mutual contact between two objects. Despite the ongoing debates on CE's mechanism, recent advancements in technology have elucidated the primary role of electron transfer in most CE processes. This discovery leads to the spawning of an emerging field, known as contact-electro-catalysis (CEC), which utilizes the electron transfer phenomenon during CE to initiate CEC. In this work, we provide the first comprehensive review of the recent progress of the solid-liquid interface-mediated CEC process, including its working principles, relationship with surface science, recent breakthroughs in applications, and future challenges. We aim to provide fundamental guidance for researchers to understand the reaction mechanism of the CEC process and to propose potential pathways to enhance CEC efficiency from a surface and interfacial science perspective. Later, recent application scenarios using the novel CEC techniques are summarized, including wastewater treatment, efficient generation of hydrogen peroxide (H2O2), lithium-ion battery recycling, and CO2 reduction. In general, CEC technology has opened a new avenue for catalysis, effectively expanding the range of catalyst options and holding promise as a solution to a variety of complex catalytic challenges in the future.

16.
Langmuir ; 40(16): 8427-8439, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38607689

RESUMO

This work aims to enhance the adsorption performance of Laponite @diatomite for organic pollutants by modifying it with cetyltrimethylammonium bromide (CTAB). The microstructure and morphology of the CTAB-modified Laponite @diatomite material were characterized using SEM, XRD, FTIR, BET, and TG. Furthermore, the influences of key parameters, containing pH, adsorbent dosage, reaction time, and reaction temperature, on the adsorption process were investigated. The kinetics, thermodynamics, and isotherm models of the adsorption process were analyzed. Finally, potential adsorption mechanisms were given based on the characterization. The research findings indicate that CTAB-La@D exhibits good adsorption performance toward Congo red (CR) over a broad pH range. The maximum adsorption capacity of CR was 451.1 mg/g under the optimum conditions (dosage = 10 mg, contact time = 240 min, initial CR concentration = 100 mg/L, temperature = 25 °C, and pH = 7). The adsorption process conformed to the pseudo-second-order kinetic model, and the adsorption isotherms indicated that the adsorption process of CR was more in line with the Langmuir model, and it was physical adsorption. Thermodynamic analysis illustrates that the adsorption process is exothermic and spontaneous. Additionally, the mechanisms of electrostatic adsorption and hydrophobic effect adsorption of CR were investigated through XPS and FTIR analysis. This work provides an effective pathway for designing high-performance adsorbents for the removal of organic dye, and the synthesized materials hold great capability for practical utilization in the treatment of wastewater.

17.
Crit Rev Food Sci Nutr ; : 1-11, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39108169

RESUMO

Both insufficient and excessive iodine intake can lead to thyroid-related disorders. Although China has made progress in eliminating iodine deficiency over the past few decades, the incidence of thyroid cancer is increasing. Currently, there is a lack of relevant research on the tradeoff between the benefits and risks of salt iodization in China. In this study, we developed a method that combines the total probability algorithm and disease burden to evaluate the appropriate amount of salt iodization. Following the principle of minimizing the comprehensive disease burden and using the metabolic model of human iodine nutrition. Based on the average national iodine level in water, the optimal iodine content in Chinese salt is determined to be 17 mg/kg. However, iodine content in water is not evenly distributed in China. Approximately 3.23% of administrative villages have water iodine concentrations exceeding 80 ug/L, eliminating the need for iodine fortification in salt. Approximately 83.51% of administrative villages need to continue implementing the salt iodization policy, with the optimal iodine content in salt ranging from 15 to 18 mg/kg. In 13.16% of administrative villages, the iodine content in salt is determined based on the local water iodine concentration, ranging from 0 to 15 mg/kg. Our study cracks open a window of insight suggesting that the optimal iodine content for salt is lower than the existing benchmark dictated by the prevailing policy in China. Hence, there is an urgent need to refine and advance the iodine supplementation strategy in salt to pave the way for precision medicine and health-centric iodine supplementation strategies.

18.
Environ Sci Technol ; 58(24): 10515-10523, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38622088

RESUMO

Hydrogen sulfide (H2S), a toxic gas abundant in natural gas fields and refineries, is currently being removed mainly via the Claus process. However, the emission of sulfur-containing pollutants is hard to be prevented and the hydrogen element is combined to water. Herein, we report an electron-mediated off-field electrocatalysis approach (OFEC) for complete splitting of H2S into H2 and S under ambient conditions. Fe(III)/Fe(II) and V(II)/V(III) redox mediators are used to fulfill the cycles for H2S oxidation and H2 production, respectively. Fe(III) effectively removes H2S with almost 100% conversion during its oxidation process. The H+ ions are reduced by V(II) on a nonprecious metal catalyst, tungsten carbide. The mediators are regenerated in an electrolyzer at a cell voltage of 1.05 V, close to the theoretical potential difference (1.02 V) between Fe(III)/Fe(II) and V(II)/V(III). In a laboratory bench-scale plant, the energy consumption for the production of H2 from H2S is estimated to be 2.8 kWh Nm-3 H2 using Fe(III)/Fe(II) and V(II)/V(III) mediators and further reduced to about 0.5 kWh Nm-3 H2 when employing well-designed heteropolyacid/quinone mediators. OFEC presents a cost-effective approach for the simultaneous production of H2 and elemental sulfur from H2S, along with the complete removal of H2S from industrial processes. It also provides a practical platform for electrochemical reactions involving solid precipitation and organic synthesis.


Assuntos
Sulfeto de Hidrogênio , Hidrogênio , Enxofre , Sulfeto de Hidrogênio/química , Hidrogênio/química , Catálise , Enxofre/química , Oxirredução , Eletroquímica , Técnicas Eletroquímicas
19.
Environ Sci Technol ; 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39453935

RESUMO

Top-down estimates of fossil fuel CO2 (FFCO2) emissions are crucial for tracking emissions and evaluating mitigation strategies. However, their practical application is hindered by limited data coverage and overreliance on NOx-to-CO2 emission ratios from emission inventories. We developed the Machine Learning-Driven Mapping Satellite-based XCO2en (ML-MSXE) model using the column-averaged dry-air mole fraction of CO2 enhancement (XCO2en) derived from OCO-2 and OCO-3 measurements to reconstruct the XCO2en distribution for monitoring FFCO2 emissions. Compared to the previous Machine Learning-Driven Deriving XCO2en from Mapped XCO2 (ML-DXEMX) model, ML-MSXE enhances the utilization of TROPOMI NO2 measurements, increasing their relative contribution from 4.3 to 21.7%, thereby improving XCO2en reconstruction accuracy and enhancing the ability to track emissions. Despite the COVID-19 lockdown, XCO2en levels in China rose from 1.33 ± 1.06 in 2019 to 1.39 ± 1.01 ppm in 2021. In February 2020, while the national average rate of XCO2en decline (16.3%) aligned with the reduction in FFCO2 emissions estimated by inventories, XCO2en further revealed varying rates of decline between cities. Furthermore, the spatial distribution of XCO2en identified hotspots where FFCO2 emissions might be underestimated by inventories. This study presents a space-based approach for monitoring FFCO2 emissions, offering valuable insights for assessing carbon neutrality progress and informing policy.

20.
J Fluoresc ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180574

RESUMO

The rapid development of fluorescence probe technology has promoted in-depth research in fields such as environment and life medicine. Traditional single channel fluorescent probes can achieve highly sensitive detection of targets, but they appear powerless in complex environments. In addition, in today's deteriorating resource environment, implementing multi target detection with one probe can effectively save preparation resources, which is in line with the development direction of fluorescent probes. To achieve this goal, designing and preparing multi-site probes is undoubtedly the first choice, but the complexity of their preparation is daunting. Herein, we propose the concept of cascade detection for the first time. After the probe completes the first target detection, the complex between the probe and the first target is achieved based on the characteristics of the first target to achieve subsequent target detection. Based on this, a metal-organic framework was used as a basic skeleton and the concept of serial reactions was applied. First, copper ions were detected through coordination. Then, the specificity of copper for sulfur-containing amino acids was utilized to detect the three types of amino acids, and the practical applications of the three probes were studied separately.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA