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1.
Nature ; 615(7950): 50-55, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36859583

RESUMEN

The newly discovered nickelate superconductors so far only exist in epitaxial thin films synthesized by a topotactic reaction with metal hydrides1. This method changes the nickelates from the perovskite to an infinite-layer structure by deintercalation of apical oxygens1-3. Such a chemical reaction may introduce hydrogen (H), influencing the physical properties of the end materials4-9. Unfortunately, H is insensitive to most characterization techniques and is difficult to detect because of its light weight. Here, in optimally Sr doped Nd0.8Sr0.2NiO2H epitaxial films, secondary-ion mass spectroscopy shows abundant H existing in the form of Nd0.8Sr0.2NiO2Hx (x ≅ 0.2-0.5). Zero resistivity is found within a very narrow H-doping window of 0.22 ≤ x ≤ 0.28, showing unequivocally the critical role of H in superconductivity. Resonant inelastic X-ray scattering demonstrates the existence of itinerant interstitial s (IIS) orbitals originating from apical oxygen deintercalation. Density functional theory calculations show that electronegative H- occupies the apical oxygen sites annihilating IIS orbitals, reducing the IIS-Ni 3d orbital hybridization. This leads the electronic structure of H-doped Nd0.8Sr0.2NiO2Hx to be more two-dimensional-like, which might be relevant for the observed superconductivity. We highlight that H is an important ingredient for superconductivity in epitaxial infinite-layer nickelates.

2.
Exp Cell Res ; 433(2): 113829, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37879548

RESUMEN

Chronic subdural hematoma (CSDH) remains a neurosurgical condition and a healthy burden especially in elderly patients. This study focuses on the functions of rapamycin and its related molecular mechanisms in CSDH management. A rat model of CSDH was induced, which developed significant hematoma on day 5 after operation. The rats were treated with rapamycin or atorvastatin, a drug with known effect on hematoma alleviation, or treated with rapamycin and atorvastatin in combination. The atorvastatin or rapamycin treatment reduced the hematoma development, blood-brain barrier permeability, neurological dysfunction in CSDH rats, and the combination treatment showed more pronounced effects. Human brain microvascular endothelial cells hCMEC/D3 were stimulated by hematoma samples to mimic a CSDH condition in vitro. The drug treatments elevated the cell junction-related factors and reduced the pro-inflammatory cytokines both in rat hematoma tissues and in hCMEC/D3 cells. Rapamycin suppressed the mTOR and STAT3 signaling pathways. Overexpression of mTOR or the STAT3 agonist suppressed the alleviating effects of rapamycin on CSDH. In summary, this study demonstrates that rapamycin promotes hematoma resorption and enhances endothelial cell function by suppressing the mTOR/STAT3 signaling.


Asunto(s)
Hematoma Subdural Crónico , Sirolimus , Anciano , Animales , Humanos , Ratas , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Células Endoteliales/metabolismo , Hematoma Subdural Crónico/tratamiento farmacológico , Hematoma Subdural Crónico/metabolismo , Transducción de Señal , Factor de Transcripción STAT3/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Serina-Treonina Quinasas TOR/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Sirolimus/farmacología , Sirolimus/uso terapéutico
3.
Acta Pharmacol Sin ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902501

RESUMEN

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

4.
Appl Opt ; 63(1): 77-84, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38175011

RESUMEN

In this paper, an ANLVENet speckle suppression method in holographic phase fringe patterns with different level noises is proposed based on FFDNet, combined with asymmetric pyramid non-local block with a verge extraction module. The experimental results are compared to three network models and several representative algorithms. It is shown that the ANLVENet method not only has better superiority in the speckle suppression with different noise levels, but also preserves more details of the image edge. In addition, another speckle noise model is applied in the phase fringe patterns to prove the stronger generalization of the ANLVENet algorithm. The proposed method is suitable for suppressing the speckle with different levels in a large noise range under complex environmental conditions.

5.
Angew Chem Int Ed Engl ; 62(18): e202218299, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-36882989

RESUMEN

Transition-metal-catalyzed asymmetric carbon-carbon bond formation to forge phosphonates with an α-chiral carbon center through C(sp3 )-C(sp3 ) and C(sp2 )-C(sp3 ) couplings has been successful. However, the enantioselective C(sp)-C(sp3 ) coupling has not yet been disclosed. Reported herein is an unprecedented enantioconvergent cross-coupling of alkynyl bromides and α-bromo phosphonates to deliver chiral α-alkynyl phosphonates.

6.
J Am Chem Soc ; 144(9): 3989-3997, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35192328

RESUMEN

Chiral phosphine-containing skeletons are important motifs in bioactive natural products, pharmaceuticals, chiral catalysts, and ligands. Herein, we report a general and modular platform to access chiral α-aryl phosphorus compounds via a Ni/photoredox-catalyzed enantioconvergent reductive cross-coupling between α-bromophosphates and aryl iodides. This dual catalytic regime exhibited high efficiency and good functional group compacity. A wide variety of substrates bearing a diverse set of functional groups could be converted into chiral phosphates in good to excellent yields and enantioselectivities. The utility of the method was also demonstrated by the development of a new phosphine ligand and the synthesis of enzyme inhibitor derivatives. The detailed mechanistic studies supported a radical chain process and revealed a unique distinction compared with traditional reductive cross-coupling.


Asunto(s)
Níquel , Fosfatos , Catálisis , Yoduros , Níquel/química
7.
Small ; 18(23): e2107664, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35527335

RESUMEN

Incorporation of ceramic materials into separators has been frequently applied in both research and industry to improve the overall high-temperature performances of lithium ion batteries. However, inorganic ceramic particles tend to form aggregation in separators and even fall off in the separator matrix due to the inferior combination between ceramic particles and polymer matrix, giving rise to a decrease in separator porosity and thus the degradation of battery performances. Herein, a single-layer core-shell architecture is designed to reinforce the polymer matrix through encircling Al2 O3 particles by poly(vinylidene fluoride) with strong inter-molecular interaction. The 3D-reinforced microstructure effectively improves pore distribution and thermal stability to resist the dimensional deformation at high temperatures, thus giving rise to a high Coulombic efficiency of 99.16% and 87.5% capacity retention after 500 cycles at 80 °C for LiFePO4 /Li batteries. In particular, the excellent performances of the proposed separator microstructure are confirmed with a thickness value of commercial separators. This work provides a promising strategy to fabricate a core-shell structural composite separator for stable lithium ion batteries at high temperatures.

8.
Appl Microbiol Biotechnol ; 105(6): 2473-2484, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33625548

RESUMEN

Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.


Asunto(s)
Microbioma Gastrointestinal , Trasplante de Riñón , Microbiota , Humanos , Riñón , Trasplante de Riñón/efectos adversos , ARN Ribosómico 16S/genética
9.
Clin Trials ; 18(6): 673-680, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34693772

RESUMEN

BACKGROUND: Contemporary Phase I oncology trials often include efficacy expansion in various tumor indications post dose finding. Preliminary anti-tumor activity from efficacy expansion can aid Go/No-Go decision for Phase 2 or Phase 3 initiation. Tumor cohorts in efficacy expansion are commonly analyzed independently in practice, which are often underpowered due to small sample size. Pooled analysis is also sometimes conducted, but it ignores the heterogeneity of the anti-tumor activity across cohorts. METHODS: We propose an optimal one-stage design and analysis strategy for the efficacy expansion to assess whether the treatment is effective. Allowing heterogeneous anti-tumor effects across tumor cohorts, inactive cohorts are pruned, and the potentially active cohorts are pooled together to gain study power. For a prospective design with a target power, the total sample size across all cohorts is minimized; or for an ad hoc analysis with pre-specified sample size for each cohort, the pruning criteria are optimized to achieve maximum power. The global type I error is controlled after proper multiplicity adjustment, and a penalty adjusted significance level is used for the pooled test. RESULTS: Simulation studies show that the proposed optimal design has desirable operating characteristics in increasing the overall power and detecting more true positive tumor cohorts. CONCLUSION: The proposed optimal design and analysis strategy provides a practical approach to design and analyze heterogeneous efficacy expansion cohorts in a basket setting with global type I and type II error being controlled.


Asunto(s)
Neoplasias , Proyectos de Investigación , Humanos , Oncología Médica , Neoplasias/tratamiento farmacológico , Estudios Prospectivos , Tamaño de la Muestra
10.
J Cell Biochem ; 119(2): 1879-1888, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28815768

RESUMEN

The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton-Jelly mesenchymal stromal cells derived micro-vesicles (hWJMSCs-MVs) on renal ischemia-reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24 h, 48 h, 1 and 2 weeks post-transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 levels in the serum. Tubular cell proliferation and apoptosis were identified by Ki67 immunostaining and TUNEL assay. Renal fibrosis was assessed by Masson's tri-chrome straining and alpha-smooth muscle actin (α-SMA) staining. The infiltration of inflammatory cells was detected by CD68+ staining. The transforming growth factor (TGF)-ß, hepatocyte growth factor (HGF), and α-SMA expression in the kidney was measured by Western blot. After renal transplantation, the rats treated with hWJMSCs-MVs improved survival rate and renal function. Moreover, MVs mitigated renal cell apoptosis, enhanced proliferation, and alleviated inflammation at the first 48 h. In the late period, abrogation of renal fibrosis was observed in the MVs group. MVs also could decrease the number of CD68+ macrophages in the kidney. Furthermore, MVs decreased the protein expression levels of α-SMA and TGF-ß1 and increased the protein expression level of HGF at any point (24 h, 48 h, 1 or 2 weeks). The administration of MVs immediately after renal transplantation could ameliorate IRI in both the acute and chronic stage.


Asunto(s)
Lesión Renal Aguda/terapia , Micropartículas Derivadas de Células/metabolismo , Trasplante de Riñón/efectos adversos , Células Madre Mesenquimatosas/metabolismo , Daño por Reperfusión/terapia , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Paro Cardíaco Inducido , Humanos , Interleucina-10/metabolismo , Masculino , Ratas , Daño por Reperfusión/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de von Willebrand/metabolismo
11.
J Card Surg ; 33(6): 322-329, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29785788

RESUMEN

PURPOSE: We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs). METHODS: We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery. RESULTS: A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05). CONCLUSION: Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery.


Asunto(s)
Gasto Cardíaco Bajo/mortalidad , Gasto Cardíaco Bajo/prevención & control , Procedimientos Quirúrgicos Cardíacos , Bases de Datos Bibliográficas , Hidrazonas/administración & dosificación , Inhibidores de Fosfodiesterasa/administración & dosificación , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Piridazinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Simendán
13.
Small ; 13(19)2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28296197

RESUMEN

Development of highly active and stable Pt-free oxygen reduction reaction catalysts from earth-abundant elements remains a grand challenge for highly demanded metal-air batteries. Ag-based alloys have many advantages over platinum group catalysts due to their low cost, high stability, and acceptable oxygen reduction reaction (ORR) performance in alkaline solutions. Nevertheless, compared to commercial Pt/C-20%, their catalytic activity still cannot meet the demand of commercialization. In this study, a kind of catalysts screening strategy on Agx Cu100-x nanoalloys is reported, containing the surface modification method, studies of activity enhancement mechanism, and applied research on zinc-air batteries. The results exhibit that the role of selective dealloying (DE) or galvanic displacement (GD) is limited by the "parting limitation", and this "parting limitation" determines the surface topography, position of d-band center, and ORR performance of Agx Cu100-x alloys. The GD-Ag55 Cu45 and DE-Ag25 Cu75 catalysts alloys present excellent ORR performance that is comparable to Pt/C-20%. The relationship between electronic perturbation and specific activity demonstrates that positive shift of the d-band center (≈0.12 eV, relative to Ag) for GD-Ag55 Cu45 is beneficial for ORR, which is contrary to Pt-based alloys (negative shift, ≈0.1 eV). Meanwhile, extensive electrochemical and electronic structure characterization indicates that the high work function of GD-Ag55 Cu45 (4.8 eV) is the reason behind their excellent durability for zinc-air batteries.

14.
Small ; 13(15)2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28151572

RESUMEN

The electrocatalytic activity of Pt-based alloys exhibits a strong dependence on their electronic structures, but a relationship between electronic structure and oxygen reduction reaction (ORR) activity in Ag-based alloys is still not clear. Here, a vapor deposition based approach is reported for the preparation of Ag75 M25 (M = Cu, Co, Fe, and In) and Agx Cu100-x (x = 0, 25, 45, 50, 55, 75, 90, and 100) nanocatalysts and their electronic structures are determined by valence band spectra. The relationship of the d-band center and ORR activity exhibits volcano-shape behaviors, where the maximum catalytic activity is obtained for Ag75 Cu25 alloys. The ORR enhancement of Ag75 Cu25 alloys originates from the 0.12 eV upshift in d-band center relative to pure Ag, which is different from the downshift in the d-band center in Pt-based alloys. The activity trend for these Ag75 M25 alloys is in the order of Ag75 Cu25 > Ag75 Fe25 > Ag75 Co25 . These results provide an insight to understand the activity and stability enhancement of Ag75 Cu25 and Ag50 Cu50 catalysts by alloying.

15.
Plant J ; 80(1): 27-39, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25041272

RESUMEN

Eukaryotic gene expression is both promoted and inhibited by the reversible phosphorylation of the C-terminal domain of RNA polymerase II (pol II CTD). More than 20 Arabidopsis genes encode CTD phosphatase homologs, including four CTD phosphatase-like (CPL) family members. Although in vitro CTD phosphatase activity has been established for some CPLs, none have been shown to be involved in the phosphoregulation of pol II in vivo. Here we report that CPL4 is a CTD phosphatase essential for the viability of Arabidopsis thaliana. Mass spectrometry analysis identified the pol II subunits RPB1, RPB2 and RPB3 in the affinity-purified CPL4 complex. CPL4 dephosphorylates both Ser2- and Ser5-PO(4) of the CTD in vitro, with a preference for Ser2-PO(4). Arabidopsis plants overexpressing CPL4 accumulated hypophosphorylated pol II, whereas RNA interference-mediated silencing of CPL4 promoted hyperphosphorylation of pol II. A D128A mutation in the conserved DXDXT motif of the CPL4 catalytic domain resulted in a dominant negative form of CPL4, the overexpression of which inhibited transgene expression in transient assays. Inhibition was abolished by truncation of the phosphoprotein-binding Breast Cancer 1 C-terminal domain of CPL4, suggesting that both catalytic function and protein-protein interaction are essential for CPL4-mediated regulation of gene expression. We were unable to recover a homozygous cpl4 mutant, probably due to the zygotic lethality of this mutation. The reduction in CPL4 levels in CPL4(RNAi) plants increased transcript levels of a suite of herbicide/xenobiotic-responsive genes and improved herbicide tolerance, thus suggesting an additional role for CPL4 as a negative regulator of the xenobiotic detoxification pathway.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/enzimología , Regulación de la Expresión Génica de las Plantas , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas Fosfatasas/metabolismo , Estrés Fisiológico , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/metabolismo , Secuencia de Bases , Perfilación de la Expresión Génica , Herbicidas/toxicidad , Calor , Datos de Secuencia Molecular , Mutación Missense , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación , Plantas Modificadas Genéticamente , Estructura Terciaria de Proteína , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Nicotiana/efectos de los fármacos , Nicotiana/enzimología , Nicotiana/genética , Nicotiana/fisiología , Transcripción Genética , Xenobióticos/toxicidad
16.
Artículo en Inglés | MEDLINE | ID: mdl-38918324

RESUMEN

Renal ischemia-reperfusion injury (IRI) frequently occurs following kidney transplantation, and exosomes derived from umbilical cord mesenchymal stem cells (WJ-MSC-Exos) have shown promise in treating IRI in transplanted kidneys. Our study delved into the potential mechanism of WJ-MSC-Exos in ameliorating IRI in transplanted kidneys, revealing that miR-19b is abundantly present in WJ-MSC-Exos. Both in vivo and in vitro experiments demonstrated that the absence of miR-19b abolished the protective effects of WJ-MSC-Exos against renal IRI. Mechanistically, miR-19b suppressed glycogen synthase kinase-3ß (GSK3ß) expression, thereby stabilizing PDXK protein through direct binding. Treatment with WJ-MSC-Exos led to reduced PDXK levels and enhanced pyridoxine accumulation, ultimately mitigating IRI in transplanted kidneys and I/R-induced HK2 cell apoptosis. These findings elucidate the underlying mechanism of WJ-MSC-Exos in alleviating IRI in transplanted kidneys, unveiling novel therapeutic targets for post-kidney transplantation IRI and providing a solid theoretical foundation for the clinical application of WJ-MSC-Exos in IRI treatment post-transplantation.

17.
EClinicalMedicine ; 73: 102655, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38873632

RESUMEN

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. Funding: AbbVie Inc.

18.
Adv Sci (Weinh) ; : e2305252, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38685606

RESUMEN

The recent discovery of nickelate superconductivity represents an important step toward understanding the four-decade mastery of unconventional high-temperature superconductivity. However, the synthesis of the infinite-layer nickelate superconductors shows great challenges. Particularly, surface capping layers are usually unitized to facilitate the sample synthesis. This leads to an important question whether nickelate superconductors with d9 configuration and ultralow valence of Ni1+ are in metastable state and whether nickelate superconductivity can be robust? In this work, a series of redox cycling experiments are performed across the phase transition between perovskite Nd0.8Sr0.2NiO3 and infinite-layer Nd0.8Sr0.2NiO2. The infinite-layer Nd0.8Sr0.2NiO2 is quite robust in the redox environment and can survive the cycling experiments with unchanged crystallographic quality. However, as the cycling number goes on, the perovskite Nd0.8Sr0.2NiO3 shows structural degradation, suggesting stability of nickelate superconductivity is not restricted by the ultralow valence of Ni1+, but by the quality of its perovskite precursor. The observed robustness of infinite-layer Nd0.8Sr0.2NiO2 up to ten redox cycles further indicates that if an ideal high-quality perovskite precursor can be obtained, infinite-layer nickelate superconductivity can be very stable and sustainable under environmental conditions. This work provides important implications for potential device applications for nickelate superconductors.

19.
J Colloid Interface Sci ; 665: 500-509, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38547631

RESUMEN

Constructing a heterojunction by combining two semiconductors with similar band structures is a successful approach to obtaining photocatalysts with high efficiency. Herein, a CuPc/DR-MoS2 heterojunction involving copper phthalocyanine (CuPc) and molybdenum disulfide with S-rich vacancies (13.66%) is successfully prepared by the facile hydrothermal method. Experimental results and theoretical calculations firmly demonstrated that photoelectrons exhibit an S-scheme charge transfer mechanism in the CuPc/DR-MoS2 heterojunction. The S-scheme heterojunction system has proven significant advantages in promoting the charge separation and transfer of photogenerated carriers, enhancing visible-light responsiveness, and achieving robust photoredox capability. As a result, the optimized 3CuPc/DR-MoS2 S-scheme heterojunction exhibits photocatalytic yields of CO and CH4 at 200 and 111.6 µmol g-1h-1, respectively. These values are four times and 4.5 times greater than the photocatalytic yields of pure DR-MoS2. This study offers novel perspectives on the advancement of innovative and highly effective heterojunction photocatalysts.

20.
Nanoscale ; 16(9): 4352-4377, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38275275

RESUMEN

Semiconductor-based photocatalysis has attracted significant interest due to its capacity to directly exploit solar energy and generate solar fuels, including water splitting, CO2 reduction, pollutant degradation, and bacterial inactivation. However, achieving the maximum efficiency in photocatalytic processes remains a challenge owing to the speedy recombination of electron-hole pairs and the limited use of light. Therefore, significant endeavours have been devoted to addressing these issues. Specifically, well-designed heterojunction photocatalysts have been demonstrated to exhibit enhanced photocatalytic activity through the physical distancing of electron-hole pairs generated during the photocatalytic process. In this review, we provide a systematic discussion ranging from fundamental mechanisms to material strategies, focusing on TiO2-based heterojunction photocatalysts. Current efforts are focused on developing heterojunction photocatalysts based on TiO2 for a variety of photocatalytic applications, and these projects are explained and assessed. Finally, we offer a concise summary of the main insights and challenges in the utilization of TiO2-based heterojunction photocatalysts for photocatalysis. We expect that this review will serve as a valuable resource to improve the efficiency of TiO2-based heterojunctions for energy generation and environmental remediation.

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