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1.
Nature ; 621(7978): 300-305, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37704763

RESUMO

Crystal phase is a key factor determining the properties, and hence functions, of two-dimensional transition-metal dichalcogenides (TMDs)1,2. The TMD materials, explored for diverse applications3-8, commonly serve as templates for constructing nanomaterials3,9 and supported metal catalysts4,6-8. However, how the TMD crystal phase affects the growth of the secondary material is poorly understood, although relevant, particularly for catalyst development. In the case of Pt nanoparticles on two-dimensional MoS2 nanosheets used as electrocatalysts for the hydrogen evolution reaction7, only about two thirds of Pt nanoparticles were epitaxially grown on the MoS2 template composed of the metallic/semimetallic 1T/1T' phase but with thermodynamically stable and poorly conducting 2H phase mixed in. Here we report the production of MoS2 nanosheets with high phase purity and show that the 2H-phase templates facilitate the epitaxial growth of Pt nanoparticles, whereas the 1T' phase supports single-atomically dispersed Pt (s-Pt) atoms with Pt loading up to 10 wt%. We find that the Pt atoms in this s-Pt/1T'-MoS2 system occupy three distinct sites, with density functional theory calculations indicating for Pt atoms located atop of Mo atoms a hydrogen adsorption free energy of close to zero. This probably contributes to efficient electrocatalytic H2 evolution in acidic media, where we measure for s-Pt/1T'-MoS2 a mass activity of 85 ± 23 A [Formula: see text] at the overpotential of -50 mV and a mass-normalized exchange current density of 127 A [Formula: see text] and we see stable performance in an H-type cell and prototype proton exchange membrane electrolyser operated at room temperature. Although phase stability limitations prevent operation at high temperatures, we anticipate that 1T'-TMDs will also be effective supports for other catalysts targeting other important reactions.

2.
Nature ; 589(7843): 620-626, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33408414

RESUMO

Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available1-3. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97)4-6, a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-Go complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain. The steroidal core of glucocorticoids is packed against the 'toggle switch' residue W6.53, which senses the binding of a ligand and induces activation of the receptor. Active GPR97 uses a quaternary core and HLY motif to fasten the seven-transmembrane bundle and to mediate G protein coupling. The cytoplasmic side of GPR97 has an open cavity, where all three intracellular loops interact with the Go protein, contributing to the high basal activity of GRP97. Palmitoylation at the cytosolic tail of the Go protein was found to be essential for efficient engagement with GPR97 but is not observed in other solved GPCR complex structures. Our work provides a structural basis for ligand binding to the seven-transmembrane domain of an adhesion GPCR and subsequent G protein coupling.


Assuntos
Microscopia Crioeletrônica , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Glucocorticoides/química , Glucocorticoides/metabolismo , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/ultraestrutura , Sítios de Ligação , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/ultraestrutura , Humanos , Ligantes , Lipoilação , Modelos Moleculares , Ligação Proteica , Receptores Acoplados a Proteínas G/metabolismo
3.
Nature ; 600(7887): 164-169, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34789875

RESUMO

In the clades of animals that diverged from the bony fish, a group of Mas-related G-protein-coupled receptors (MRGPRs) evolved that have an active role in itch and allergic signals1,2. As an MRGPR, MRGPRX2 is known to sense basic secretagogues (agents that promote secretion) and is involved in itch signals and eliciting pseudoallergic reactions3-6. MRGPRX2 has been targeted by drug development efforts to prevent the side effects induced by certain drugs or to treat allergic diseases. Here we report a set of cryo-electron microscopy structures of the MRGPRX2-Gi1 trimer in complex with polycationic compound 48/80 or with inflammatory peptides. The structures of the MRGPRX2-Gi1 complex exhibited shallow, solvent-exposed ligand-binding pockets. We identified key common structural features of MRGPRX2 and describe a consensus motif for peptidic allergens. Beneath the ligand-binding pocket, the unusual kink formation at transmembrane domain 6 (TM6) and the replacement of the general toggle switch from Trp6.48 to Gly6.48 (superscript annotations as per Ballesteros-Weinstein nomenclature) suggest a distinct activation process. We characterized the interfaces of MRGPRX2 and the Gi trimer, and mapped the residues associated with key single-nucleotide polymorphisms on both the ligand and G-protein interfaces of MRGPRX2. Collectively, our results provide a structural basis for the sensing of cationic allergens by MRGPRX2, potentially facilitating the rational design of therapies to prevent unwanted pseudoallergic reactions.


Assuntos
Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Prurido/metabolismo , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/química , Receptores de Neuropeptídeos/metabolismo , Alérgenos/imunologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Sítios de Ligação , Sequência Consenso , Microscopia Crioeletrônica , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Humanos , Modelos Moleculares , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/ultraestrutura , Receptores Acoplados a Proteínas G/imunologia , Receptores Acoplados a Proteínas G/ultraestrutura , Receptores de Neuropeptídeos/imunologia , Receptores de Neuropeptídeos/ultraestrutura
4.
Chem Rev ; 124(7): 4479-4539, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38552165

RESUMO

Crystal phase, a critical structural characteristic beyond the morphology, size, dimension, facet, etc., determines the physicochemical properties of nanomaterials. As a group of layered nanomaterials with polymorphs, transition metal dichalcogenides (TMDs) have attracted intensive research attention due to their phase-dependent properties. Therefore, great efforts have been devoted to the phase engineering of TMDs to synthesize TMDs with controlled phases, especially unconventional/metastable phases, for various applications in electronics, optoelectronics, catalysis, biomedicine, energy storage and conversion, and ferroelectrics. Considering the significant progress in the synthesis and applications of TMDs, we believe that a comprehensive review on the phase engineering of TMDs is critical to promote their fundamental studies and practical applications. This Review aims to provide a comprehensive introduction and discussion on the crystal structures, synthetic strategies, and phase-dependent properties and applications of TMDs. Finally, our perspectives on the challenges and opportunities in phase engineering of TMDs will also be discussed.

5.
Proc Natl Acad Sci U S A ; 120(30): e2216329120, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37478163

RESUMO

To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to the same hormone-receptor pair [R.P. Xiao, Sci STKE 2001, re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402, 181-184 (1999); Y. Daaka, L. M. Luttrell, R. J. Lefkowitz, Nature 390, 88-91 (1997)]. Not only these questions lie in the heart of hormone actions and receptor signaling but also dissecting mechanisms underlying these questions could offer therapeutic routes for refractory diseases, such as kidney injury (KI) or X-linked nephrogenic diabetes insipidus (NDI). Here, we identified that Gs-biased signaling, but not Gi activation downstream of EP4, showed beneficial effects for both KI and NDI treatments. Notably, by solving Cryo-electron microscope (cryo-EM) structures of EP3-Gi, EP4-Gs, and EP4-Gi in complex with endogenous prostaglandin E2 (PGE2)or two synthetic agonists and comparing with PGE2-EP2-Gs structures, we found that unique primary sequences of prostaglandin E2 receptor (EP) receptors and distinct conformational states of the EP4 ligand pocket govern the Gs/Gi transducer coupling selectivity through different structural propagation paths, especially via TM6 and TM7, to generate selective cytoplasmic structural features. In particular, the orientation of the PGE2 ω-chain and two distinct pockets encompassing agonist L902688 of EP4 were differentiated by their Gs/Gi coupling ability. Further, we identified common and distinct features of cytoplasmic side of EP receptors for Gs/Gi coupling and provide a structural basis for selective and biased agonist design of EP4 with therapeutic potential.


Assuntos
Dinoprostona , Transdução de Sinais , Dinoprostona/metabolismo , Transdução de Sinais/fisiologia , Receptores de Prostaglandina/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Hormônios , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Receptores de Prostaglandina E Subtipo EP3/metabolismo
6.
Circulation ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38328928

RESUMO

BACKGROUND: Heart failure (HF), which is the terminal stage of many cardiovascular diseases, is associated with low survival rates and a severe financial burden. The mechanisms, especially the molecular mechanism combined with new theories, underlying the pathogenesis of HF remain elusive. We demonstrate that phosphorylation-regulated dynamic liquid-liquid phase separation of HIP-55 (hematopoietic progenitor kinase 1-interacting protein of 55 kDa) protects against HF. METHODS: Fluorescence recovery after photobleaching assay, differential interference contrast analysis, pull-down assay, immunofluorescence, and immunohistochemical analysis were used to investigate the liquid-liquid phase separation capacity of HIP-55 and its dynamic regulation in vivo and in vitro. Mice with genetic deletion of HIP-55 and mice with cardiac-specific overexpression of HIP-55 were used to examine the role of HIP-55 on ß-adrenergic receptor hyperactivation-induced HF. Mutation analysis and mice with specific phospho-resistant site mutagenesis were used to identify the role of phosphorylation-regulated dynamic liquid-liquid phase separation of HIP-55 in HF. RESULTS: Genetic deletion of HIP-55 aggravated HF, whereas cardiac-specific overexpression of HIP-55 significantly alleviated HF in vivo. HIP-55 possesses a strong capacity for phase separation. Phase separation of HIP-55 is dynamically regulated by AKT-mediated phosphorylation at S269 and T291 sites, failure of which leads to impairment of HIP-55 dynamic phase separation by formation of abnormal aggregation. Prolonged sympathetic hyperactivation stress induced decreased phosphorylation of HIP-55 S269 and T291, dysregulated phase separation, and subsequent aggregate formation of HIP55. Moreover, we demonstrated the important role of dynamic phase separation of HIP-55 in inhibiting hyperactivation of the ß-adrenergic receptor-mediated P38/MAPK (mitogen-activated protein kinase) signaling pathway. A phosphorylation-deficient HIP-55 mutation, which undergoes massive phase separation and forms insoluble aggregates, loses the protective activity against HF. CONCLUSIONS: Our work reveals that the phosphorylation-regulated dynamic phase separation of HIP-55 protects against sympathetic/adrenergic system-mediated heart failure.

7.
Nat Mater ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589543

RESUMO

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

8.
Chem Rev ; 123(23): 13489-13692, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37962496

RESUMO

As a key structural parameter, phase depicts the arrangement of atoms in materials. Normally, a nanomaterial exists in its thermodynamically stable crystal phase. With the development of nanotechnology, nanomaterials with unconventional crystal phases, which rarely exist in their bulk counterparts, or amorphous phase have been prepared using carefully controlled reaction conditions. Together these methods are beginning to enable phase engineering of nanomaterials (PEN), i.e., the synthesis of nanomaterials with unconventional phases and the transformation between different phases, to obtain desired properties and functions. This Review summarizes the research progress in the field of PEN. First, we present representative strategies for the direct synthesis of unconventional phases and modulation of phase transformation in diverse kinds of nanomaterials. We cover the synthesis of nanomaterials ranging from metal nanostructures such as Au, Ag, Cu, Pd, and Ru, and their alloys; metal oxides, borides, and carbides; to transition metal dichalcogenides (TMDs) and 2D layered materials. We review synthesis and growth methods ranging from wet-chemical reduction and seed-mediated epitaxial growth to chemical vapor deposition (CVD), high pressure phase transformation, and electron and ion-beam irradiation. After that, we summarize the significant influence of phase on the various properties of unconventional-phase nanomaterials. We also discuss the potential applications of the developed unconventional-phase nanomaterials in different areas including catalysis, electrochemical energy storage (batteries and supercapacitors), solar cells, optoelectronics, and sensing. Finally, we discuss existing challenges and future research directions in PEN.

9.
Biochem Biophys Res Commun ; 690: 149311, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016246

RESUMO

Carbon dots (CDs) are an emerging class of fluorescent quantum dot nanomaterials that have attracted considerable scientific attention for biomedical or bioimaging applications due to their physicochemical and biochemical properties. With the emergence of massive novel synthetic CDs applying to biomedical fields of science, evaluating their biosafety before any biological application is essential. However, there is no universal protocol or routine procedures for toxicity detection and biosafety assessment of CDs in general biological environments. Herein, we provide an ideal and fast operating system to detect the biotoxicity of CDs, which has been preliminary practiced. Briefly, the obtained CDs will be evaluated by in vitro cytotoxicity assay using cell counting kit-8, lactate dehydrogenase assay kit, and flow cytometry. Meanwhile, the model creature zebrafish is employed to perform in vivo evaluation by measuring body length, hatching rate, heart rate, and morphological observation. Our operating procedure condenses previous scattered biosafety detection methods into a rapid standard evaluation protocol that can be applied to early biotoxicity screening of CDs. This protocol will accelerate CDs biological exploitation and guide future industrialized biosafety assessment in large-scale applications.


Assuntos
Nanoestruturas , Pontos Quânticos , Animais , Carbono/toxicidade , Carbono/química , Peixe-Zebra , Pontos Quânticos/toxicidade , Pontos Quânticos/química , Corantes Fluorescentes/química
10.
Small ; 20(8): e2306663, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37817371

RESUMO

The Nickel-based catalysts have a good catalytic effect on the 5-hydroxymethylfurfural electrooxidation reaction (HMFOR), but limited by the conversion potential of Ni2+ /Ni3+ , 1.35 V versus RHE, the HMF electrooxidation potential of nickel-based catalysts is generally greater than 1.35 V versus RHE. Considering fluorine has the highest Pauling electronegativity and similar atomic radius of oxygen, the introduction of fluorine into the lattice of metal oxides might promote the adsorption of intermediate species, thus improving the catalytic performance. F is successfully doped into the lattice structure of NiCo2 O4 spinel oxide by the strategy of hydrothermal reaction and low-temperature fluorination. As is confirmed by in situ electrochemical impedance spectroscopy and Raman spectroscopy, the introduction of F weakens the interaction force of metal-oxygen covalent bonds of the asymmetric MT -O-MO backbone and improves the valence of Ni in tetrahedra structure, which makes it easier to be oxidized to higher valence active Ni3+ under the action of electric field and promotes the adsorption of OH- , while the decrease of Co valence enhances the adsorption of HMF with the catalyst. Combining the above reasons, F-NiCo2 O4 shows superb electrocatalytic performance with a potential of only 1.297 V versus RHE at a current density of 20 mA cm-2 , which is lower than the most catalyst.

11.
Small ; : e2402827, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017030

RESUMO

Oxygen vacancy (Vo), as one of the most common surface defects, significantly influence the physiochemical properties of metal oxides. However, it remains a challenge for existing techniques to visualize the evolution of Vo during redox process due to its heterogeneous distribution, small size, and dynamic nature. Herein, the real-time monitoring of such microscopic interfacial events is reported by advantage of the high-contrast fluorescence response of carbon dots (H-CDs) to Vo. The green emissive H-CDs possess a unique disc-shaped structure and exceptional hydrophilicity, allowing their tight adhesion to the surfaces of Vo-rich MgO by simple mixing. Subsequently, a water involved interfacial reaction occurred between H-CDs and Vo, resulting in gradual quenching of the original green emission and simultaneously emergence of bright red fluorescence. Moreover, the spatiotemporal diffusion dynamics and reaction kinetics are investigated by confocal laser scanning microscopy, revealing the time-dependent reorganization and structural heterogeneity at the interface. The finding provides a new toolbox for in situ imaging of Vo-triggered phenomena at a microscopic level, which will be helpful in promoting the rational design of oxide materials.

12.
Small ; 20(24): e2311136, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38148296

RESUMO

Dual-engineering involved of grain boundaries (GBs) and oxygen vacancies (VO) efficiently engineers the material's catalytic performance by simultaneously introducing favorable electronic and chemical properties. Herein, a novel SnO2 nanoplate is reported with simultaneous oxygen vacancies and abundant grain boundaries (V,G-SnOx/C) for promoting the highly selective conversion of CO2 to value-added formic acid. Attributing to the synergistic effect of employed dual-engineering, the V,G-SnOx/C displays highly catalytic selectivity with a maximum Faradaic efficiency (FE) of 87% for HCOOH production at -1.2 V versus RHE and FEs > 95% for all C1 products (CO and HCOOH) within all applied potential range, outperforming current state-of-the-art electrodes and the amorphous SnOx/C. Theoretical calculations combined with advanced characterizations revealed that GB induces the formation of electron-enriched Sn site, which strengthens the adsorption of *HCOO intermediate. While GBs and VO synergistically lower the reaction energy barrier, thus dramatically enhancing the intrinsic activity and selectivity toward HCOOH.

13.
Small ; : e2311172, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351480

RESUMO

Ruthenium oxide is currently considered as the promising alternative to Ir-based catalysts employed for proton exchange membrane water electrolyzers but still faces the bottlenecks of limited durability and slow kinetics. Herein, a 2D amorphous/crystalline heterophase ac-Cr0.53 Ru0.47 O2-δ substitutional solid solution with pervasive grain boundaries (GBs) is developed to accelerate the kinetics of acidic oxygen evolution reaction (OER) and extend the long-term stability simultaneously. The ac-Cr0.53 Ru0.47 O2-δ shows a super stability with a slow degradation rate and a remarkable mass activity of 455 A gRu -1 at 1.6 V vs RHE, which is ≈3.6- and 5.9-fold higher than those of synthesized RuO2 and commercial RuO2 , respectively. The strong interaction of Cr-O-Ru local units in synergy with the specific 2D structural characteristics of ac-Cr0.53 Ru0.47 O2-δ dominates its enhanced stability. Meanwhile, high-density GBs and the shortened Ru-O bonds tailored by amorphous/crystalline structure and Cr-O-Ru interaction regulate the adsorption and desorption rates of oxygen intermediates, thus accelerating the overall acidic OER kinetics.

14.
Basic Res Cardiol ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724618

RESUMO

Cardiovascular disease is the main factor contributing to the global burden of diseases, and the cardiotoxicity caused by anticancer drugs is an essential component that cannot be ignored. With the development of anticancer drugs, the survival period of cancer patients is prolonged; however, the cardiotoxicity caused by anticancer drugs is becoming increasingly prominent. Currently, cardiovascular disease has emerged as the second leading cause of mortality among long-term cancer survivors. Anticancer drug-induced cardiotoxicity has become a frontier and hot topic. The discovery of epigenetics has given the possibility of environmental changes in gene expression, protein synthesis, and traits. It has been found that epigenetics plays a pivotal role in promoting cardiovascular diseases, such as heart failure, coronary heart disease, and hypertension. In recent years, increasing studies have underscored the crucial roles played by epigenetics in anticancer drug-induced cardiotoxicity. Here, we provide a comprehensive overview of the role and mechanisms of epigenetics in anticancer drug-induced cardiotoxicity.

15.
Opt Express ; 32(10): 17535-17550, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858935

RESUMO

Physical processes in the Fourier domain play a crucial role in various applications such as spectroscopy, quantum technology, ranging, radio-astronomy, and telecommunications. However, the presence of stochastic noise poses a significant challenge in the detection of broadband spectral waveforms, especially those with limited power. In this study, we propose and experimentally demonstrate a cross-phase modulation (XPM) based spectral Talbot amplifier to recover the broadband spectral waveforms in high fidelity. Through the combination of spectral phase filtering and XPM nonlinear effect in an all-fiber configuration, we demonstrate spectral purification of THz-bandwidth spectral waveforms submerged in strong noise. The proposed spectral Talbot amplifier provides tunable amplification factors from 3 to 10, achieved by flexible control on the temporal waveform of the pump and the net dispersion. We demonstrate up to 10-dB remarkable improvement on optical signal-to-noise ratio (OSNR) while preserving the spectral envelope. Furthermore, our system allows frequency-selective reconstruction of noisy input spectra, introducing a new level of flexibility for spectral recovery and information extraction. We also evaluate numerically the impact of pump intensity deviation on the reconstructed spectral waveforms. Our all-optical approach presents a powerful means for effective recovery of broadband spectral waveforms, enabling information extraction from a noise-buried background.

16.
Opt Express ; 32(11): 19508-19516, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859084

RESUMO

In this paper, we presented a novel double-layer light-trapping structure consisting of nanopores and nanograting positioned on both the surface and bottom of a gallium oxide-based solar-blind photodetector. Utilizing the finite element method (FEM), we thoroughly investigated the light absorption enhancement capabilities of this innovative design. The simulation results show that the double-layer nanostructure effectively combines the light absorption advantages of nanopores and nanogratings. Compared with thin film devices and devices with only nanopore or nanograting structures, double-layer nanostructured devices have a higher light absorption, achieving high light absorption in the solar blind area.

17.
Ann Hematol ; 103(2): 525-532, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37940719

RESUMO

ABL tyrosine kinase inhibitors (TKIs) act an irreplaceable role in the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The treatment of these diseases has been revolutionized by the application of immunotherapeutic modalities. However, diseases with ABL kinase domain mutation T315I are resistant to the majority of TKIs, which is responsible for treatment failure. Olverembatinib is a third-generation TKI that has been approved for the treatment of T315I-mutated chronic myeloid leukemia (CML) in China; its usage in Ph+ ALL needs further exploration. Here, we present two cases with relapsed T315I mutation Ph+ ALL who received the combination regimen of blinatumomab and olverembatinib. This regimen, which has not been reported yet, was safe and effective as the patients achieved minimal residual disease (MRD) negative after 1 cycle of therapy. The management of these cases provides evidence of this new chemo-free regimen as an efficient approach for relapsed or refractory(R/R)Ph+ ALL.


Assuntos
Alcinos , Anticorpos Biespecíficos , Benzamidas , Cromossomo Filadélfia , Piperidinas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Pirazóis , Piridinas , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Mutação
18.
Diabetes Obes Metab ; 26(3): 1040-1049, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38086546

RESUMO

AIM: To assess whether sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce myocardial infarction (MI) incidence in patients with or without type 2 diabetes. METHODS: PubMed, Embase, Web of Science, the Cochrane library, and https://ClinicalTrials.gov were searched up to 7 May 2022. Randomized controlled trials (RCTs) and cohort studies reporting the effects of SGLT2 inhibitor treatment on MI incidence were included. Relative risks (RRs) with a 95% confidence interval (CI) for MI incidence were extracted and pooled. Subgroup analysis and meta-regression were performed to explore the heterogeneity. RESULTS: This meta-analysis included 54 RCTs and 32 cohort studies, with data from six SGLT2 inhibitors and 3 394 423 individuals. In the overall analysis, SGLT2 inhibitors significantly reduced MI incidence in RCTs (RR 0.9, 95% CI 0.84-0.96) and cohort studies (RR 0.89, 95% CI 0.83-0.94). In RCTs, the results of the subgroup analysis revealed no significant alterations in outcomes based on different SGLT2 inhibitor types, control drug types, cardiovascular disease (CVD) status and sources of outcome extraction (p for interaction >0.05). In cohort studies, the presence or absence of CVD led to similar effects of SGLT2 inhibitors on decreasing MI incidence (p for interaction = 0.179). However, variations in results were observed based on the type of control group in cohort studies (p for interaction = 0.036). Meta-regression results did not reveal an association between baseline cardiovascular risk factors, follow-up length, or MI incidence. CONCLUSIONS: In both RCTs and cohort studies, SGLT2 inhibitors reduced MI incidence. The cardioprotective effects of SGLT2 inhibitors were observed in patients with and without a history of CVD.


Assuntos
Diabetes Mellitus Tipo 2 , Infarto do Miocárdio , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/induzido quimicamente , Glucose/uso terapêutico , Sódio
19.
Br J Clin Pharmacol ; 90(1): 232-238, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37626010

RESUMO

AIMS: To evaluate the performance of chat generative pretrained transformer (ChatGPT) in key domains of clinical pharmacy practice, including prescription review, patient medication education, adverse drug reaction (ADR) recognition, ADR causality assessment and drug counselling. METHODS: Questions and clinical pharmacist's answers were collected from real clinical cases and clinical pharmacist competency assessment. ChatGPT's responses were generated by inputting the same question into the 'New Chat' box of ChatGPT Mar 23 Version. Five licensed clinical pharmacists independently rated these answers on a scale of 0 (Completely incorrect) to 10 (Completely correct). The mean scores of ChatGPT and clinical pharmacists were compared using a paired 2-tailed Student's t-test. The text content of the answers was also descriptively summarized together. RESULTS: The quantitative results indicated that ChatGPT was excellent in drug counselling (ChatGPT: 8.77 vs. clinical pharmacist: 9.50, P = .0791) and weak in prescription review (5.23 vs. 9.90, P = .0089), patient medication education (6.20 vs. 9.07, P = .0032), ADR recognition (5.07 vs. 9.70, P = .0483) and ADR causality assessment (4.03 vs. 9.73, P = .023). The capabilities and limitations of ChatGPT in clinical pharmacy practice were summarized based on the completeness and accuracy of the answers. ChatGPT revealed robust retrieval, information integration and dialogue capabilities. It lacked medicine-specific datasets as well as the ability for handling advanced reasoning and complex instructions. CONCLUSIONS: While ChatGPT holds promise in clinical pharmacy practice as a supplementary tool, the ability of ChatGPT to handle complex problems needs further improvement and refinement.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Serviço de Farmácia Hospitalar , Farmácia , Humanos , Farmacêuticos , Competência Clínica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle
20.
Analyst ; 149(4): 1221-1228, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38221877

RESUMO

Cancer-targeted nanotechnology has a new trend in the design and preparation of new materials with functions for imaging and therapeutic applications simultaneously. As a new type of carbon nanomaterial, the inherent core-shell structured carbon dots (CDs) can be designed to provide a modular nanoplatform for integration of bioimaging and therapeutic capabilities. Here, core-shell structured CDs are designed and synthesized from levofloxacin and arginine and named Arg-CDs, in which levofloxacin-derived chromophores with up-conversion fluorescence are densely packed into the carbon core while guanidine groups are located on the shell, providing nitric oxide (NO) for photodynamic therapy of tumors. Moreover, the chromophores in the carbon core irradiated by visible LED light generate large amounts of reactive oxygen species (ROSs) that will oxidize the guanidine groups located on the shell of the Arg-CDs and further increase the NO releasing capacity remarkably. The as-synthesized Arg-CDs show excellent biocompatibility, bright up-conversion fluorescence, and a light-controlled ROS & NO releasing ability, which can be a potential light-modulated nanoplatform to integrate bioimaging and therapeutic functionalities.


Assuntos
Neoplasias , Pontos Quânticos , Humanos , Óxido Nítrico , Carbono , Fluorescência , Levofloxacino , Neoplasias/patologia , Espécies Reativas de Oxigênio , Guanidinas/uso terapêutico , Pontos Quânticos/toxicidade
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