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1.
Nature ; 621(7979): 635-641, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37524305

RESUMEN

Class B G-protein-coupled receptors (GPCRs), including glucagon-like peptide 1 receptor (GLP1R) and parathyroid hormone 1 receptor (PTH1R), are important drug targets1-5. Injectable peptide drugs targeting these receptors have been developed, but orally available small-molecule drugs remain under development6,7. Here we report the high-resolution structure of human PTH1R in complex with the stimulatory G protein (Gs) and a small-molecule agonist, PCO371, which reveals an unexpected binding mode of PCO371 at the cytoplasmic interface of PTH1R with Gs. The PCO371-binding site is totally different from all binding sites previously reported for small molecules or peptide ligands in GPCRs. The residues that make up the PCO371-binding pocket are conserved in class B GPCRs, and a single alteration in PTH2R and two residue alterations in GLP1R convert these receptors to respond to PCO371. Functional assays reveal that PCO371 is a G-protein-biased agonist that is defective in promoting PTH1R-mediated arrestin signalling. Together, these results uncover a distinct binding site for designing small-molecule agonists for PTH1R and possibly other members of the class B GPCRs and define a receptor conformation that is specific only for G-protein activation but not arrestin signalling. These insights should facilitate the design of distinct types of class B GPCR small-molecule agonist for various therapeutic indications.


Asunto(s)
Imidazolidinas , Receptores Acoplados a Proteínas G , Compuestos de Espiro , Humanos , Arrestina/metabolismo , Sitios de Unión , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Imidazolidinas/farmacología , Ligandos , Péptidos/farmacología , Conformación Proteica , Receptor de Hormona Paratiroídea Tipo 1/agonistas , Receptor de Hormona Paratiroídea Tipo 1/clasificación , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/clasificación , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacos , Compuestos de Espiro/farmacología , Diseño de Fármacos
2.
Nature ; 603(7900): 271-275, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35038718

RESUMEN

In oxidation reactions catalysed by supported metal nanoparticles with oxygen as the terminal oxidant, the rate of the oxygen reduction can be a limiting factor. This is exemplified by the oxidative dehydrogenation of alcohols, an important class of reactions with modern commercial applications1-3. Supported gold nanoparticles are highly active for the dehydrogenation of the alcohol to an aldehyde4 but are less effective for oxygen reduction5,6. By contrast, supported palladium nanoparticles offer high efficacy for oxygen reduction5,6. This imbalance can be overcome by alloying gold with palladium, which gives enhanced activity to both reactions7,8,9; however, the electrochemical potential of the alloy is a compromise between that of the two metals, meaning that although the oxygen reduction can be improved in the alloy, the dehydrogenation activity is often limited. Here we show that by separating the gold and palladium components in bimetallic carbon-supported catalysts, we can almost double the reaction rate compared with that achieved with the corresponding alloy catalyst. We demonstrate this using physical mixtures of carbon-supported monometallic gold and palladium catalysts and a bimetallic catalyst comprising separated gold and palladium regions. Furthermore, we demonstrate electrochemically that this enhancement is attributable to the coupling of separate redox processes occurring at isolated gold and palladium sites. The discovery of this catalytic effect-a cooperative redox enhancement-offers an approach to the design of multicomponent heterogeneous catalysts.


Asunto(s)
Oro , Nanopartículas del Metal , Alcoholes , Aleaciones , Carbono , Catálisis , Oxidación-Reducción , Oxígeno , Paladio
3.
Circ Res ; 134(2): 165-185, 2024 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-38166463

RESUMEN

BACKGROUND: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance. METHODS AND RESULTS: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE-/-) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE-/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis. CONCLUSIONS: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Ratones , Animales , Eferocitosis , Factor 6 Asociado a Receptor de TNF/metabolismo , Aterosclerosis/metabolismo , Inflamación/genética , Ratones Noqueados , Fenotipo , Apolipoproteínas E , Factores Reguladores del Interferón/genética , Ratones Endogámicos C57BL
4.
Proc Natl Acad Sci U S A ; 120(27): e2216248120, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37368928

RESUMEN

The US global leadership in science and technology has greatly benefitted from immigrants from other countries, most notably from China in the recent decades. However, feeling the pressure of potential federal investigations since the 2018 launch of the China Initiative, scientists of Chinese descent in the United States now face higher incentives to leave the United States and lower incentives to apply for federal grants. Analyzing data pertaining to institutional affiliations of more than 200 million scientific papers, we find a steady increase in the return migration of scientists of Chinese descent from the United States to China. We also conducted a survey of scientists of Chinese descent employed by US universities in tenured or tenure-track positions (n = 1,304), with results revealing general feelings of fear and anxiety that lead them to consider leaving the United States and/or stop applying for federal grants. If the situation is not corrected, American science will likely suffer the loss of scientific talent to China and other countries.

5.
PLoS Pathog ; 19(5): e1011384, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37196026

RESUMEN

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.


Asunto(s)
COVID-19 , Quirópteros , Animales , Humanos , Pangolines/genética , SARS-CoV-2/genética , Virulencia , Filogenia , ARN Viral , Tropismo
6.
Chem Rev ; 123(9): 6359-6411, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-36459432

RESUMEN

The direct transformation of methane to methanol remains a significant challenge for operation at a larger scale. Central to this challenge is the low reactivity of methane at conditions that can facilitate product recovery. This review discusses the issue through examination of several promising routes to methanol and an evaluation of performance targets that are required to develop the process at scale. We explore the methods currently used, the emergence of active heterogeneous catalysts and their design and reaction mechanisms and provide a critical perspective on future operation. Initial experiments are discussed where identification of gas phase radical chemistry limited further development by this approach. Subsequently, a new class of catalytic materials based on natural systems such as iron or copper containing zeolites were explored at milder conditions. The key issues of these technologies are low methane conversion and often significant overoxidation of products. Despite this, interest remains high in this reaction and the wider appeal of an effective route to key products from C-H activation, particularly with the need to transition to net carbon zero with new routes from renewable methane sources is exciting.

7.
J Immunol ; 211(9): 1367-1375, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37695685

RESUMEN

A better understanding of the regulatory mechanisms governing the development of memory CD8+ T cells could provide instructive insights into vaccination strategies and T cell-based immunotherapies. In this article, we showed that CD160 surface protein is required for CD8+ T cell memory formation. In the response to acute lymphocytic choriomeningitis virus infection in a mouse model, CD160 ablation resulted in the failure of the development of all three memory CD8+ T cell subsets (central, effective, and tissue-resident memory), concomitant with a skewed differentiation into short-lived effector T cells. Such memory-related defect was manifested by a diminished protection from viral rechallenge. Mechanistically, CD160 deficiency led to downregulation of 4-1BB in activated CD8+ T cells, which contributes to the impaired cell survival and decreased respiratory capacity. The nexus between CD160 and 4-1BB was substantiated by the observation that ectopic introduction of 4-1BB was able to largely complement the loss of CD160 in memory CD8+ T cell development. Collectively, our studies discovered that CD160, once thought to be a coinhibitor of T cell signaling, is an essential promoter of memory CD8+ T cell development via activation of the costimulatory molecule 4-1BB.

8.
Proc Natl Acad Sci U S A ; 119(47): e2212183119, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36375070

RESUMEN

About one in six Asian Americans have fallen victim to anti-Asian racism during the COVID-19 pandemic [J. Lee, K. Ramakrishnan, aapidata.com/blog/discrimination-survey-2022/]. By examining anti-Asian racism in the United States primarily as a domestic issue, most prior studies have overlooked the connections between shifting US-China relations and Americans' prejudices against the Chinese in China and, by extension, East Asian Americans. This study investigates the patterns and perceptual bases of nationality-based prejudices against Chinese amid the COVID-19 pandemic in the United States. Our nationally representative online survey experiment reveals that Americans assess a hypothetical Chinese person in China as inferior in multiple social and psychological characteristics to an otherwise identical Japanese person in Japan or East Asian American. Furthermore, subjects who perceive China as more threatening to America's national interests assess Chinese more negatively, especially in terms of trustworthiness and morality, suggesting that perceived China threats propel Americans' negative stereotypes about Chinese. A contextual analysis further indicates that counties with a higher share of Trump voters in 2016 tend to perceive all East Asian-origin groups similarly as a racial outgroup. By contrast, residents in predominantly Democrat-voting counties tend to perceive Chinese in China more negatively relative to Asian Americans, despite broadly viewing East Asians more favorably. Overall, this study underscores the often-overlooked relationships between the prevailing anti-Asian sentiments in the United States and the US-China geopolitical tensions and America's domestic political polarization.


Asunto(s)
COVID-19 , Racismo , Humanos , Estados Unidos/epidemiología , COVID-19/epidemiología , Pandemias , Prejuicio , Racismo/psicología , Asiático/psicología , Principios Morales , China
9.
Nano Lett ; 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38825790

RESUMEN

The core task of neuromorphic devices is to effectively simulate the behavior of neurons and synapses. Based on the functionality of ferroelectric domains with the advantages of low power consumption and high-speed response, great progress has been made in realizing neuromimetic behaviors such as ferroelectric synaptic devices. However, the correlation between the ferroelectric domain dynamics and neuromimetic behavior remains unclear. Here, we reveal the correlation between domain/domain wall dynamics and neuromimetic behaviors from a microscopic perspective in real-time by using high temporal and spatial resolution in situ transmission electron microscopy. Furthermore, we propose utilizing ferroelectric microstructures for the simultaneous simulation of neuronal and synaptic plasticity, which is expected to improve the integration and performance of ferroelectric neuromorphic devices. We believe that this work to study neuromimetic behavior from the perspective of domain dynamics is instructive for the development of ferroelectric neuromorphic devices.

10.
Nano Lett ; 24(31): 9442-9450, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39054654

RESUMEN

The inherent properties of boron nitride nanotubes (BNNTs) can be further enhanced through the control of their anisotropy. In particular, horizontally aligned BNNTs (HABNNTs) exhibit considerable potential for various applications. However, directly synthesizing HABNNTs is difficult owing to the random floating of BNNTs and the absence of directional forces. Here, we employed a simple, efficient, and universal "surface-like growth" strategy to synthesize high-density and high-quality HABNNTs in the W2B5/Zn precursor system. First, the floating range of BNNTs was restricted to the vicinity of the precursor, and then, directional forces were applied to induce BNNT directional growth along the substrate surface. Experiments and simulations confirmed that the HABNNT orientation could be controlled through manipulation of the directional forces. Furthermore, the strategy was employed for HABNNTs synthesis using the MoB2/Zn, further demonstrating the universality of the approach. Overall, this work offers a fresh perspective on the synthesis of HABNNTs, further expanding their potential applications.

11.
J Proteome Res ; 23(1): 40-51, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-37993262

RESUMEN

Differentiated multipotent pancreatic progenitors have major advantages for both modeling pancreas development and preventing or treating diabetes. Despite significant advancements in inducing the differentiation of human pluripotent stem cells into insulin-producing cells, the complete mechanism governing proliferation and differentiation remains poorly understood. This study used large-scale mass spectrometry to characterize molecular processes at various stages of human embryonic stem cell (hESC) differentiation toward pancreatic progenitors. hESCs were induced into pancreatic progenitor cells in a five-stage differentiation protocol. A high-performance liquid chromatography-mass spectrometry platform was used to undertake comprehensive proteome and phosphoproteome profiling of cells at different stages. A series of bioinformatic explorations, including coregulated modules, gene regulatory networks, and phosphosite enrichment analysis, were then conducted. A total of 27,077 unique phosphorylated sites and 8122 proteins were detected, including several cyclin-dependent kinases at the initial stage of cell differentiation. Furthermore, we discovered that ERK1, a member of the MAPK cascade, contributed to proliferation at an early stage. Finally, Western blotting confirmed that the phosphosites from SIRT1 and CHEK1 could inhibit the corresponding substrate abundance in the late stage. Thus, this study extends our understanding of the molecular mechanism during pancreatic cell development.


Asunto(s)
Células Madre Embrionarias Humanas , Células Madre Pluripotentes , Humanos , Proteómica/métodos , Diferenciación Celular/genética , Páncreas/metabolismo , Células Madre Pluripotentes/metabolismo
12.
BMC Genomics ; 25(1): 918, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358679

RESUMEN

BACKGROUND: Thermal stress is a major environmental factor affecting fish development and survival. Common carp (Cyprinus carpio) are susceptible to heat stress in their embryonic and larval phases, but the thermal stress response of alternative splicing during common carp embryogenesis remains poorly understood. RESULTS: Using RNA-seq data from eight developmental stages and four temperatures, we constructed a comprehensive profile of alternative splicing (AS) during the embryogenesis of common carp, and found that AS genes and events are widely distributed among all stages. A total of 5,835 developmental stage-specific AS (SAS) genes, 21,368 temperature-specific differentially expressed genes (TDEGs), and 2,652 temperature-specific differentially AS (TDAS) genes were identified. Hub TDAS genes in each developmental stage, such as taf2, hnrnpa1, and drg2, were identified through protein-protein interaction (PPI) network analysis. The early developmental stages may be more sensitive to temperature, with thermal stress leading to a massive increase in the number of expressed transcripts, TDEGs, and TDAS genes in the morula stage, followed by the gastrula stage. GO and KEGG analyses showed that from the morula stage to the neurula stage, TDAS genes were more involved in intracellular transport, protein modification, and localization processes, while from the optic vesicle stage to one day post-hatching, they participated more in biosynthetic processes. Further subgenomic analysis revealed that the number of AS genes and events in subgenome B was generally higher than that in subgenome A, and the homologous AS genes were significantly enriched in basic life activity pathways, such as mTOR signaling pathway, p53 signaling pathway, and MAPK signaling pathway. Additionally, lncRNAs can play a regulatory role in the response to thermal stress by targeting AS genes such as lmnl3, affecting biological processes such as apoptosis and axon guidance. CONCLUSIONS: In short, thermal stress can affect alternative splicing regulation during common carp embryogenesis at multiple levels. Our work complemented some gaps in the study of alternative splicing at both levels of embryogenesis and thermal stress in C. carpio and contributed to the comprehension of environmental adaptation formation in polyploid fishes during embryogenesis.


Asunto(s)
Empalme Alternativo , Carpas , Desarrollo Embrionario , Respuesta al Choque Térmico , Animales , Carpas/genética , Carpas/embriología , Carpas/metabolismo , Desarrollo Embrionario/genética , Respuesta al Choque Térmico/genética , Regulación del Desarrollo de la Expresión Génica , Perfilación de la Expresión Génica , Mapas de Interacción de Proteínas , Proteínas de Peces/genética , Proteínas de Peces/metabolismo
13.
J Am Chem Soc ; 146(8): 5693-5701, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38335459

RESUMEN

Rationally modulating the binding strength of reaction intermediates on surface sites of copper-based catalysts could facilitate C-C coupling to generate multicarbon products in an electrochemical CO2 reduction reaction. Herein, theoretical calculations reveal that cascade Ag-Cu dual sites could synergistically increase local CO coverage and lower the kinetic barrier for CO protonation, leading to enhanced asymmetric C-C coupling to generate C2H4. As a proof of concept, the Cu3N-Ag nanocubes (NCs) with Ag located in partial Cu sites and a Cu3N unit center are successfully synthesized. The Faraday efficiency and partial current density of C2H4 over Cu3N-Ag NCs are 7.8 and 9.0 times those of Cu3N NCs, respectively. In situ spectroscopies combined with theoretical calculations confirm that Ag sites produce CO and Cu sites promote asymmetric C-C coupling to *COCHO, significantly enhancing the generation of C2H4. Our work provides new insights into the cascade catalysis strategy at the atomic scale for boosting CO2 to multicarbon products.

14.
J Am Chem Soc ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39353154

RESUMEN

Solar-driven carbon dioxide (CO2) reduction into C2+ products such as ethylene represents an enticing route toward achieving carbon neutrality. However, due to sluggish electron transfer and intricate C-C coupling, it remains challenging to achieve highly efficient and selective ethylene production from CO2 and H2O beyond capitalizing on Cu-based catalysts. Herein, we report a judicious design to attain asymmetric C-C coupling through interfacial defect-rendered tandem catalytic centers within a sulfur-vacancy-rich MoSx/Fe2O3 photocatalyst sheet, enabling a robust CO2 photoreduction to ethylene without the need for copper, noble metals, and sacrificial agents. Specifically, interfacial S vacancies induce adjacent under-coordinated S atoms to form Fe-S bonds as a rapid electron-transfer pathway for yielding a Z-scheme band alignment. Moreover, these S vacancies further modulate the strong coupling interaction to generate a nitrogenase-analogous Mo-Fe heteronuclear unit and induce the upward shift of the d-band center. This bioinspired interface structure effectively suppresses electrostatic repulsion between neighboring *CO and *COH intermediates via d-p hybridization, ultimately facilitating an asymmetric C-C coupling to achieve a remarkable solar-to-chemical efficiency of 0.565% with a superior selectivity of 84.9% for ethylene production. Further strengthened by MoSx/WO3, our design unveils a promising platform for optimizing interfacial electron transfer and offers a new option for C2+ synthesis from CO2 and H2O using copper-free and noble metal-free catalysts.

15.
Kidney Int ; 105(6): 1200-1211, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38423183

RESUMEN

Podocyte injury and loss are hallmarks of diabetic nephropathy (DN). However, the molecular mechanisms underlying these phenomena remain poorly understood. YAP (Yes-associated protein) is an important transcriptional coactivator that binds with various other transcription factors, including the TEAD family members (nuclear effectors of the Hippo pathway), that regulate cell proliferation, differentiation, and apoptosis. The present study found an increase in YAP phosphorylation at S127 of YAP and a reduction of nuclear YAP localization in podocytes of diabetic mouse and human kidneys, suggesting dysregulation of YAP may play a role in diabetic podocyte injury. Tamoxifen-inducible podocyte-specific Yap gene knockout mice (YappodKO) exhibited accelerated and worsened diabetic kidney injury. YAP inactivation decreased transcription factor WT1 expression with subsequent reduction of Tead1 and other well-known targets of WT1 in diabetic podocytes. Thus, our study not only sheds light on the pathophysiological roles of the Hippo pathway in diabetic podocyte injury but may also lead to the development of new therapeutic strategies to prevent and/or treat DN by targeting the Hippo signaling pathway.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Diabetes Mellitus Experimental , Nefropatías Diabéticas , Ratones Noqueados , Fosfoproteínas , Podocitos , Transducción de Señal , Factores de Transcripción , Proteínas WT1 , Proteínas Señalizadoras YAP , Podocitos/metabolismo , Podocitos/patología , Animales , Proteínas WT1/metabolismo , Proteínas WT1/genética , Proteínas Señalizadoras YAP/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/genética , Humanos , Fosforilación , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Factores de Transcripción de Dominio TEA/metabolismo , Vía de Señalización Hippo , Ratones , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Masculino , Ratones Endogámicos C57BL , Tamoxifeno/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética
16.
BMC Immunol ; 25(1): 16, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347480

RESUMEN

OBJECTIVE: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation. METHODS: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. RESULTS: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. CONCLUSION: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.


Asunto(s)
Artemisininas , Síndrome de Sjögren , Ratones , Animales , Ratones Endogámicos NOD , Interleucina-17 , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Síndrome de Sjögren/tratamiento farmacológico , Artemisininas/farmacología , Artemisininas/uso terapéutico
17.
Small ; : e2403660, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004850

RESUMEN

All-solid-state lithium metal batteries (ASSLMBs) have emerged as the most promising next-generation energy storage devices. However, the unsatisfactory ionic conductivity of solid electrolytes at room temperature has impeded the advancement of solid-state batteries. In this work, a multifunctional composite solid electrolyte (CSE) is developed by incorporating boron nitride nanotubes (BNNTs) into polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP). BNNTs, with a high aspect ratio, trigger the dissociation of Li salts, thus generating a greater population of mobile Li+, and establishing long-distance Li+ transport pathways. PVDF-HFP/BNNT exhibits a high ionic conductivity of 8.0 × 10-4 S cm-1 at room temperature and a Li+ transference number of 0.60. Moreover, a Li//Li symmetric cell based on PVDF-HFP/BNNT demonstrates robust cyclic performance for 3400 h at a current density of 0.2 mA cm-2. The ASSLMB formed from the assembly of PVDF-HFP/BNNT with LiFePO4 and Li exhibits a capacity retention of 93.2% after 850 cycles at 0.5C and 25 °C. The high-voltage all-solid-state LiCoO2/Li cell based on PVDF-HFP/BNNT also exhibits excellent cyclic performance, maintaining a capacity retention of 96.4% after 400 cycles at 1C and 25 °C. Furthermore, the introduction of BNNTs is shown to enhance the thermal conductivity and flame retardancy of the CSE.

18.
Small ; : e2406685, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39385649

RESUMEN

Layered double hydroxides (LDHs), especially high-entropy LDHs (HE-LDHs), have gained increasing attention. However, HE-LDHs often possess poor thermal stability, restricting their applications in thermo-catalysis. Herein, a novel complexing nucleation method is proposed for engineering HE-LDHs with enhanced thermal stability. This approach precisely controls the nucleation of metal ions with different solubility products, achieving homogeneous nucleation and effectively mitigating phase segregation and transformation at elevated temperatures. The prepared HE-LDH sample demonstrated exceptional thermal stability at temperatures up to 300 °C, outperforming all previously reported LDHs. Importantly, these HE-LDHs preserve both Lewis and Brønsted acidic sites, enabling the 100% removal of aromatic sulfides and alkaline nitrogen compounds from fuel oils in thermo-catalytic oxidation reactions. Experimental and characterization findings reveal that the metal-hydroxide bonds in the prepared HE-LDHs are strengthened by associated hydroxyl groups, inducing negative thermal expansion and augmenting the presence of acidic sites, thereby ensuring structural stability and enhancing catalytic activity. This study not only proposes a strategy for engineering HE-LDHs with remarkable thermal stability but also highlights potential applications of LDHs in thermo-catalysis.

19.
Opt Express ; 32(2): 1406-1420, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38297693

RESUMEN

The noise figure (NF) of a fiber amplifier is one of the key measures of amplification performance, which characterizes the quality of the amplified signal. Residual stresses are inevitably generated during the manufacturing process of optical fibers, and this can lead to changes in the refractive index (RI) distribution of the fiber. Further, the change in RI distribution causes the mode-field characteristics of the fiber to change as well, and this ultimately has an impact on the NF performance of the amplifier. However, until now, there have been fewer studies on the effect of residual stress on the NF of the fiber amplifiers. In this work, we took a commercial single-mode bismuth-doped fiber (BDF) as an example and used a self-developed stress test device to measure its residual stress and refractive index distribution and compare it with that of a passive fiber. We also comprehensively compared the distribution of residual stress and refractive index of the fiber at different pump powers and pump wavelengths. Finally, we performed numerical simulations of the bismuth-doped fiber amplifier (BDFA) based on the BDF under the theoretical mode field area and BDF after the expansion of the mode field area due to stresses to compare the NF performance. The results demonstrate that: the entire cross-section (core and cladding) of the BDF exhibits tensile stress (>0 MPa), where the residual stress at the core of the BDF is nearly 9.8 MPa higher than that of the passive fiber; The residual stress makes the mode-field area of the BDF expand by 26.7% compared with the theoretical values, which ultimately makes the NF of the BDFA rise from 4.6 dB to 4.7 dB; The stress at the BDF core is exacerbated by pump excitation, where it is elevated by about 26% and 5% compared to vacancy at 1240 nm and 1310 nm pumps, which is most likely attributed to thermal effects. Therefore, it is necessary to consider the effect of residual stresses in the fabrication of optical fibers to better achieve the radius of the expected indicators. This work contributes to the better development of O-band BDFAs, especially for pre-simulation of the actual performance of BDFAs with a practical reference.

20.
Phys Rev Lett ; 133(6): 066503, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39178458

RESUMEN

Topotactic reduction utilizing metal hydrides as reagents has emerged as an effective approach to achieve exceptionally low oxidization states of metal ions and unconventional coordination networks. This method opens avenues to the development of entirely new functional materials, with one notable example being the infinite-layer nickelate superconductors. However, the reduction effect on the atomic reconstruction and electronic structures-crucial for superconductivity-remains largely unresolved. We designed two sets of control Nd_{0.8}Sr_{0.2}NiO_{2} thin films and used secondary ion mass spectroscopy to highlight the absence of reduction-induced hydrogen intercalation. X-ray absorption spectroscopy revealed a significant linear dichroism with dominant Ni 3d_{x2-y2} orbitals on superconducting samples, indicating a Ni single-band nature of infinite-layer nickelates. Consistent with the superconducting T_{c}, the Ni 3d orbitals asymmetry manifests a domelike dependence on the reduction duration. Our results unveil the critical role of reduction in modulating the Ni-3d orbital polarization and its impact on the superconducting properties.

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