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1.
Ecol Evol ; 14(9): e70314, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39279795

RESUMO

The global climate change has resulted in substantial modifications to the distribution patterns of narrowly distributed species across different time periods, leading to an imminent threat to the survival of some vulnerable species. Chimonobambusa tumidissinoda J. R. Xue & T. P. Yi ex Ohrnb., a bamboo species endemic to the transition zone from the Yunnan-Guizhou Plateau to the Sichuan Basin with high economic and ecological value, exhibits a limited range and rarity. Utilizing eight environmental variables and 56 occurrence records, we employed the MaxEnt model to predict the potential distribution range of C. tumidissinoda under current and future climate scenarios. The findings revealed that precipitation of the driest month (Bio14), elevation and isothermality (Bio3) were the crucial factors determining the species' distribution, accounting for 31.24%, 28.27% and 17.24% of data variability, respectively. The distribution centroid of C. tumidissinoda is anticipated to shift towards higher latitudes in response to future climate change, and the projected habitat suitability is expected to expand under ssp245 and ssp585 scenarios while remaining unchanged or contracting under the ssp126 scenario. Despite these expansions, the suitable habitats remain limited, with the largest being approximately 2.08 × 104 km2, indicating a significant threat to its survival. Our study provides insights into the adaptive responses of C. tumidissinoda to climate change, enriching scientific knowledge for developing effective conservation measurements as well as sustainable utilization.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39329500

RESUMO

INTRODUCTION: Transient global ischaemia in rodents causes selective loss of hippocampal CA1 neurons, but the potential involvement of endocytic pathways has not been fully explored. The aim of this study was to investigate the changes in early endosomes in the CA1 subfield after ischaemia and reperfusion. MATERIALS AND METHODS: A four-vessel occlusion (4-VO) model was established in Wistar rats to induce 13 minutes of global cerebral ischaemia. Neuronal death was detected by Fluoro-Jade B (FJ-B) staining at various intervals after reperfusion, and intracellular membrane changes in ischaemic neurons were revealed using DiOC6(3), a lipophilic fluorescent probe. Ras-related protein Rab5 (Rab5) immunostaining was performed to detect changes in early endosomes in ischaemic neurons. Western blot analysis was used to confirm the morphological observations on Rab5 in the CA1 hippocampal subfield. RESULTS: FJ-B staining confirmed progressive neuronal death in the CA1 subfield in ischaemic rats after reperfusion. DiOC6(3) staining revealed abnormally increased membranous components in ischaemic CA1 neurons. Specifically, early endosomes, as labelled by Rab5 immunostaining, significantly increased in number and size in CA1 neurons at 1.5 and 2 days post-reperfusion, followed by rupture at day 3 and a decrease in staining intensity at day 7 post-reperfusion. Western blot analysis confirmed a significant upregulation of Rab5 protein levels at day 2, which returned to near control levels by day 7. CONCLUSIONS: Our study revealed significant changes in the dynamics of early endosomes in CA1 neurons after ischaemia-reperfusion injury. The initial increase in the area fraction of early endosomes in CA1 neurons may reflect an upregulation of endocytic activity, whereas the fragmentation and reduction of early endosomes at the later stage may indicate a failure of adaptive mechanisms of ischaemic neurons against ischaemia-induced death. Understanding the temporal dynamics of early endosomes provides critical insights into the cellular mechanisms that govern fate of CA1 hippocampal neuronsl after ischaemia/reperfusion.

3.
Int J Colorectal Dis ; 39(1): 143, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289199

RESUMO

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.


Assuntos
Colonoscopia , Polietilenoglicóis , Humanos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Constipação Intestinal , Adulto , Relação Dose-Resposta a Droga , Idoso , Defecação/efeitos dos fármacos , Resultado do Tratamento , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/diagnóstico
4.
Neurosurg Rev ; 47(1): 560, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39242449

RESUMO

The role of a low-profile visualized intraluminal support stent (LVIS) and Enterprise in the treatment of unruptured intracranial aneurysms is well established. Although previous studies have investigated one single type of stent for the treatment of ruptured intracranial aneurysms (RIA), the safety and efficacy between the two types of stents has not been fully explored. Herein we conducted a study to compare the outcomes of the two stents for treatment of RIA. This is a prospective registry database of aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to a single institution between 2018 and 2021. We collected patient baseline information, secondary complications, follow-up angiographic data, long-term prognostic outcomes, and conducted propensity score matching (PSM) analysis with 1:1 ratio and a multivariable logistic regression to compare the outcomes of the two types of stents. A total of 231 patients with RIAs were included in this study, with 108 treated using the LVIS device and 123 treated using the Enterprise device. Before PSM analysis, only the incidence of poor prognosis after 12 months was higher in the Enterprise group comparing to the LVIS group (20% vs. 10%, P = 0.049). After PSM analysis, there was a higher occurrence of delayed cerebral ischemia (DCI) in the Enterprise group compared to the LVIS group (odds ratio [OR] 3.95, 95% confidence interval [CI] [1.20-13.01], P = 0.024). However, no significant difference in prognosis was observed after PSM adjustment. Furthermore, subgroup analysis revealed that patients with female (P = 0.019), hypertension (P = 0.048), and anterior circulation aneurysms (P = 0.019) receiving the Enterprise device had a higher risk of DCI. The overall efficacy of LVIS and Enterprise in the treatment of RIA is comparable, while the incidence of DCI in the LVIS group is lower than that in the Enterprise group after PSM analysis. Registration number: NCT05738083 ( https://clinicaltrials.gov/ ).


Assuntos
Aneurisma Roto , Embolização Terapêutica , Aneurisma Intracraniano , Pontuação de Propensão , Stents , Humanos , Aneurisma Intracraniano/terapia , Feminino , Masculino , Aneurisma Roto/terapia , Pessoa de Meia-Idade , Embolização Terapêutica/métodos , Embolização Terapêutica/instrumentação , Idoso , Adulto , Resultado do Tratamento , Estudos de Coortes , Procedimentos Endovasculares/métodos , Hemorragia Subaracnóidea/terapia
5.
Int J Pharm ; 664: 124582, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39142466

RESUMO

Chemotherapy agents for lung cancer often cause apoptotic resistance in cells, leading to suboptimal therapeutic outcomes. FIN56 can be a potential treatment for lung cancer as it induces non-apoptotic cell death, namely ferroptosis. However, a bottleneck exists in FIN56-induced ferroptosis treatment; specifically, FIN56 fails to induce sufficient oxidative stress and may even trigger the defense system against ferroptosis, resulting in poor therapeutic efficacy. To overcome this, this study proposed a strategy of co-delivering FIN56 and piperlongumine to enhance the ferroptosis treatment effect by increasing oxidative stress and connecting with the autophagy pathway. FIN56 and piperlongumine were encapsulated into silk fibroin-based nano-disruptors, named FP@SFN. Characterization results showed that the particle size of FP@SFN was in the nanometer range and the distribution was uniform. Both in vivo and in vitro studies demonstrated that FP@SFN could effectively eliminate A549 cells and inhibit subcutaneous lung cancer tumors. Notably, ferroptosis and autophagy were identified as the main cell death pathways through which the nano-disruptors increased oxidative stress and facilitated cell membrane rupture. In conclusion, nano-disruptors can effectively enhance the therapeutic effect of ferroptosis treatment for lung cancer through the ferroptosis-autophagy synergy mechanism, providing a reference for the development of related therapeutics.


Assuntos
Autofagia , Ferroptose , Fibroínas , Neoplasias Pulmonares , Nanopartículas , Estresse Oxidativo , Ferroptose/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Autofagia/efeitos dos fármacos , Animais , Fibroínas/química , Fibroínas/farmacologia , Células A549 , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Dioxolanos/farmacologia , Dioxolanos/química , Dioxolanos/administração & dosagem , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Sinergismo Farmacológico , Piperidonas
6.
COPD ; 21(1): 2369541, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39087240

RESUMO

To investigate the clinical effects and application value of self-made disseminating and descending breathing exercises on home rehabilitation of patients with stable chronic obstructive pulmonary disease (COPD). Seeking to generate concepts for creating novel, convenient, and efficient COPD prognosis rehabilitation exercises aimed at enhancing the well-being and rehabilitation confidence of both COPD patients and their families. A total of 70 COPD patients admitted to our outpatient department from July 2019 to September 2021 were randomly divided into the exercise group (n = 35) and the control group (n = 35). The control group received routine breathing training, while the exercise group was treated with self-made disseminating and descending breathing exercises. The respiratory function, including pulmonary function (FVC, FEV1, FEV1/FVC) and respiratory muscle strength (MIP, MEP), exercise tolerance (6-min walking distance, 6MWT), Modified Medical Research Council Dyspnea Scale (mMRC, Borg), COPD quality of life score (CAT, SGRQ), anxiety and depression scores (HAMA, HAMD) were compared between the two groups after 12-week exercise. After 12-week training, the FEV1, MIP, and MEP in the exercise group were significantly higher than those in the control group (p < 0.001), and the 6MWT was significantly increased in the exercise group compared to the control group (p < 0.001); while the mMRC, Borg score, the scores of CAT, SGRQ, HAMA, and HAMD were found significantly lower than those in the control group (p < 0.001). The self-made disseminating and descending breathing exercises can improve respiratory function and reduce symptoms of dyspnea in COPD patients, while enhancing exercise tolerance and relieving anxiety and depression, and are worthy of clinical application.


Assuntos
Exercícios Respiratórios , Tolerância ao Exercício , Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Exercícios Respiratórios/métodos , Idoso , Pessoa de Meia-Idade , Dispneia/etiologia , Dispneia/reabilitação , Força Muscular , Depressão , Ansiedade/etiologia , Músculos Respiratórios/fisiopatologia , Teste de Caminhada , Volume Expiratório Forçado
7.
Chem Sci ; 15(31): 12189-12199, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39118610

RESUMO

Potassium-ion batteries (PIBs) are considered potential candidates for large-scale energy storage systems due to the abundant resources of potassium. Among various reported anode materials, bismuth anodes with the advantages of high theoretical specific capacity, low cost, and nontoxicity have attracted widespread attention. However, bismuth anodes experience significant volume changes during the charge/discharge process, leading to unsatisfactory cycling stability and rate performance. In this review, we focus on summarizing the research progress of bismuth anodes in PIBs. We discuss in detail the modification strategies for bismuth anodes in PIBs, including electrolyte optimization, morphology design, and hybridization with carbon materials. In addition, we attempt to propose possible future directions for the development of bismuth anodes in PIBs, aiming to expedite their practical application. It is believed that this review can assist researchers in more efficiently designing high-performance bismuth anode materials for PIBs.

8.
J Thorac Dis ; 16(7): 4238-4249, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39144338

RESUMO

Background: Distinguishing benign from malignant sub-centimeter solid pulmonary nodules (SSPNs) continues to be challenging in clinical practice. Earlier diagnosis is crucial for improving patient survival and prognosis. This study aimed to investigate the risk factors of malignant SSPNs and establish and validate a prediction model based on computed tomography (CT) characteristics to assist in their early diagnosis. Methods: A total of 261 consecutive participants with 261 SSPNs were retrospectively recruited between January 2012 and July 2023 from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Center 1), including 161 malignant lesions and 100 benign lesions. Patients were randomly assigned to the training set (n=183) and validation set (n=78) according to a 7:3 ratio. Malignant nodules were confirmed by pathology; and benign nodules were confirmed by follow-up or pathology. Clinical data and CT features were collected to estimate the independent predictors of malignancy of SSPN with multivariate logistic analysis. A clinical prediction model was subsequently established by logistic regression. Furthermore, an additional 69 consecutive patients with 69 SSPNs from The Fourth Hospital of Hebei Medical University (Center 2) between January 2022 and December 2022 were retrospectively included as an external cohort to validate the predictive efficacy of the model. The performance of the prediction model was assessed by sensitivity, specificity, and the area under the receiver operating characteristic curve. Results: There were 113 (61.7%), 48 (61.5%) and 28 (40.6%) malignant SSPNs in the training, internal and external validation sets, respectively. Multivariate logistic analysis revealed four independent predictors of malignant SSPNs: tumor-lung interface (P=0.002), spiculation (P=0.04), air bronchogram (P=0.047), and invisible at the mediastinal window (P=0.003). The area under the curve (AUC) for the prediction model in the training set was 0.875 [95% confidence interval (CI): 0.818, 0.933]; and the sensitivity and specificity were 94.7% and 68.6%, respectively. The AUCs in the internal and external validation set were (0.781; 95% CI: 0.664, 0.897) and (0.873; 95% CI: 0.791, 0.955), respectively; the sensitivity and specificity were 66.7% and 83.3% for the internal validation data, and 100.0% and 61.0% for the external validation data, respectively. Conclusions: The prediction model based on CT characteristics could be helpful for distinguishing malignant SSPNs from benign ones.

10.
Angew Chem Int Ed Engl ; : e202410494, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007424

RESUMO

Anion-reinforced solvation structure favors the formation of inorganic-rich robust electrode-electrolyte interface, which endows fast ion transport and high strength modulus to enable improved electrochemical performance. However, such a unique solvation structure inevitably injures the ionic conductivity of electrolytes and limits the fast-charging performance. Herein, a trade-off in tuning anion-reinforced solvation structure and high ionic conductivity is realized by the entropy-assisted hybrid ester-ether electrolyte. Anion-reinforced solvation sheath with more anions occupying the inner Na+ shell is constructed by introducing the weakly coordinated ether tetrahydrofuran into the commonly used ester-based electrolyte, which merits the accelerated desolvation energy and gradient inorganic-rich electrode-electrolyte interface. The improved ionic conductivity is attributed to the weakly diverse solvation structures induced by entropy effect. These enable the enhanced rate performance and cycling stability of Prussian blue||hard carbon full cells with high electrode mass loading. More importantly, the practical application of the designed electrolyte was further demonstrated by industry-level 18650 cylindrical cells.

11.
Plants (Basel) ; 13(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38999599

RESUMO

Dicranum Hedw. is a highly diverse and widely distributed genus within Dicranaceae. The species diversity and distribution of this genus in China, however, remain not well known. A new revision of Dicranum in China using morphological and molecular phylogenetic methods confirms that China has 39 species, including four newly reported species, D. bardunovii Tubanova & Ignatova, D. dispersum Engelmark, D. schljakovii Ignatova & Tubanova, and D. spadiceum J.E.Zetterst. Dicranum psathyrum Klazenga is transferred to Dicranoloma (Renauld) Renauld as a new synonym of Dicranoloma fragile Broth. Two species, Dicranum brevifolium (Lindb.) Lindb. and D. viride (Sull. & Lesq.) Lindb. are excluded from the bryoflora of China. A key to the Chinese Dicranum species is also provided. These results indicate an underestimation of the distribution range of numerous Dicranum species, underscoring the need for further in-depth investigations into the worldwide Dicranum diversity.

12.
Chem Sci ; 15(29): 11302-11310, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39055028

RESUMO

High-voltage LiNi0.5Mn1.5O4 (LNMO) is one of the most promising cathode candidates for rechargeable lithium-ion batteries (LIBs) but suffers from deteriorated cycling stability due to severe interfacial side reactions and manganese dissolution. Herein, a micro-nano porous spherical LNMO cathode was designed for high-performance LIBs. The disordered structure and the preferred exposure of the {111} facets can be controlled by the release of lattice oxygen in the high-temperature calcination process. The unique configuration of this material could enhance the structural stability and play a crucial role in inhibiting manganese dissolution, promoting the rapid transport of Li+, and reducing the volume strain during the charge/discharge process. The designed cathode exhibits a remarkable discharge capacity of 136.7 mA h g-1 at 0.5C, corresponding to an energy density of up to 636.4 W h kg-1, unprecedented cycling stability (capacity retention of 90.6% after 500 cycles) and superior rate capability (78.9% of initial capacity at 10C). The structurally controllable preparation strategy demonstrated in this work provides new insights into the structural design of cathode materials for LIBs.

13.
Entropy (Basel) ; 26(7)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39056917

RESUMO

This paper proposes a novel censored autoregressive conditional Fréchet (CAcF) model with a flexible evolution scheme for the time-varying parameters, which allows deciphering tail risk dynamics constrained by price limits from the viewpoints of different risk preferences. The proposed model can well accommodate many important empirical characteristics of financial data, such as heavy-tailedness, volatility clustering, extreme event clustering, and price limits. We then investigate tail risk dynamics via the CAcF model in the price-limited stock markets, taking entropic value at risk (EVaR) as a risk measurement. Our findings suggest that tail risk will be seriously underestimated in price-limited stock markets when the censored property of limit prices is ignored. Additionally, the evidence from the Chinese Taiwan stock market shows that widening price limits would lead to a decrease in the incidence of extreme events (hitting limit-down) but a significant increase in tail risk. Moreover, we find that investors with different risk preferences may make opposing decisions about an extreme event. In summary, the empirical results reveal the effectiveness of our model in interpreting and predicting time-varying tail behaviors in price-limited stock markets, providing a new tool for financial risk management.

14.
J Hazard Mater ; 476: 135228, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39024761

RESUMO

Peroxidase-like (POD-like) as a kind of new Fenton-like catalyst can effectively activate H2O2 to degrade organic pollutants in water, but improving the catalytic activity and stability of POD-like remains a challenging task. Here, we synthesized a novel dual single-atom nanoenzyme (DSAzyme) FeMn/N-CNTs with Fe-N4 and Mn-N4 bimetallic single-atom active centers by mimicking the active centers of natural enzymes and taking advantage of the synergistic effect between the dual metals. FeMn/N-CNTs DSAzyme showed significantly enhanced POD-like activity compared to monometallic-loaded Fe/N-CNTs and Mn/N-CNTs. Within the FeMn/N-CNTs/H2O2 system, bisphenol A (BPA) could be removed 100 % within 20 min. DFT calculations show that Mn-N4 in FeMn/N-CNTs can readily adsorb negatively charged BPA molecules and capture electrons. Meanwhile, Fe-N4 sites can easily adsorb H2O2 molecules, leading to their activation and splitting into strongly oxidizing hydroxyl radicals (·OH). Throughout this process, electrons are continuously recycled in BPA → Mn-N4 → Fe-N4 → H2O2, effectively promoting the regeneration of Fe2+. Practical studies on wastewater and cycling experiments have demonstrated the great potential of this method for remediating water environments.


Assuntos
Compostos Benzidrílicos , Peróxido de Hidrogênio , Ferro , Manganês , Fenóis , Poluentes Químicos da Água , Compostos Benzidrílicos/química , Ferro/química , Fenóis/química , Peróxido de Hidrogênio/química , Manganês/química , Poluentes Químicos da Água/química , Nanotubos de Carbono/química , Elétrons , Catálise , Águas Residuárias/química , Peroxidase/química , Peroxidase/metabolismo , Purificação da Água/métodos
15.
Phys Rev Lett ; 132(25): 256503, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996236

RESUMO

The recently discovered superconductivity with critical temperature T_{c} up to 80 K in the double-layer Nickelate La_{3}Ni_{2}O_{7-δ} under pressure has drawn great attention. Here, we report the positive muon spin relaxation (µ^{+}SR) study of polycrystalline La_{3}Ni_{2}O_{6.92} under ambient pressure. Zero-field µ^{+}SR experiments reveal the existence of magnetic order in La_{3}Ni_{2}O_{6.92} with T_{N}=154 K. The weak transverse field µ^{+}SR measurements reveal the bulk nature of magnetism. In addition, a small quantity of oxygen deficiencies can greatly broaden the internal magnetic field distribution sensed by muons.

16.
Chemistry ; : e202304106, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083260

RESUMO

Sodium-oxygen batteries have been regarded as promising energy storage devices due to their low overpotential and high energy density. Its applications, however, still face formidable challenges due to the lack of understanding about the influence of electrocatalysts on the discharge products. Here, a phosphorous and nitrogen dual-doped carbon (PNDC) based cathode is synthesized to increase the electrocatalytic activity and to stabilize the NaO2 superoxide nanoparticle discharge products, leading to enhanced cycling stability when compared to the nitrogen-doped carbon (NDC). The PNDC air cathode exhibits a low overpotential (0.36 V) and long cycling stability (120 cycles). The reversible formation/decomposition and stabilization of the NaO2 discharge products are clearly proven by in-situ synchrotron X-ray diffraction and ex-situ X-ray diffraction. Based on the density functional theory calculation, the PNDC has much stronger adsorption energy (-2.85 eV) for NaO2 than that of NDC (-1.80 eV), which could efficiently stabilize the NaO2 discharge products.

17.
N Engl J Med ; 391(3): 213-223, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39018531

RESUMO

BACKGROUND: The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown. METHODS: In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab. RESULTS: In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).


Assuntos
Anticorpos Monoclonais , Doença de Crohn , Ustekinumab , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Análise de Intenção de Tratamento , Indução de Remissão , Índice de Gravidade de Doença , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Endoscopia Gastrointestinal
18.
JAMA ; 332(11): 881-897, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39037800

RESUMO

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.


Assuntos
Anticorpos Monoclonais , Colite Ulcerativa , Quimioterapia de Indução , Quimioterapia de Manutenção , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Método Duplo-Cego , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Índice de Gravidade de Doença , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colonoscopia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos
19.
Chem Commun (Camb) ; 60(51): 6496-6499, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38836703

RESUMO

Cobalt substitution for manganese sites in Na0.44MnO2 initiates a dynamic structural evolution process, yielding a composite cathode material comprising intergrown P2 and P3 phases. The novel P2/P3 composite cathode exhibits a reversible phase transition process during Na+ extraction/insertion, showcasing its attractive battery performance in sodium-ion batteries.

20.
Inorg Chem ; 63(25): 11592-11603, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38861349

RESUMO

In order to take advantage of the distinct reversible multielectron transfer properties of polyoxometalates (POMs) and increase the electron density at the active sites during the electrochemical reduction of CO2 (CO2RR), a range of transition metal-doped polyoxometalates (TMSPOMs) was entrapped within the porphyrin-based framework of PCN-224 via an encapsulation method, known as TMSPOMs@PCN-224 (TMSPOMs = [XW11O39MII(H2O)]n-, [XW11O40VIV]n-, M = CoII, MnII; X = Si, n = 6; X = P, n = 5). The central elements (Si, P) and the incorporated transition metals (VIV, CoII, and MnII) both play a role in adjusting the electronic structure and electron transfer during the CO2RR process. Remarkably, the composite material with cobalt substitution displayed significantly improved performance. Through fine-tuning the POM loading, the electrocatalytic activity was optimized, leading to an impressive Faradaic efficiency for CO production (FECO) of 89.9% for SiW11Co@PCN-224, a significant improvement compared to the 12.1% FECO of PCN-224. Furthermore, the electrochemical stability of this catalyst was demonstrated over 20 h. Comparative analyses involving six composite materials indicated a relationship between the negative charge of the polyanions and their ability to facilitate effective electron transfer, ultimately enhancing the catalyst's performance. Meanwhile, these findings were supported by density functional theory (DFT) calculations.

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