Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.899
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Nature ; 613(7945): 676-681, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379225

RESUMO

The open-circuit voltage (VOC) deficit in perovskite solar cells is greater in wide-bandgap (over 1.7 eV) cells than in perovskites of roughly 1.5 eV (refs. 1,2). Quasi-Fermi-level-splitting measurements show VOC-limiting recombination at the electron-transport-layer contact3-5. This, we find, stems from inhomogeneous surface potential and poor perovskite-electron transport layer energetic alignment. Common monoammonium surface treatments fail to address this; as an alternative, we introduce diammonium molecules to modify perovskite surface states and achieve a more uniform spatial distribution of surface potential. Using 1,3-propane diammonium, quasi-Fermi-level splitting increases by 90 meV, enabling 1.79 eV perovskite solar cells with a certified 1.33 V VOC and over 19% power conversion efficiency (PCE). Incorporating this layer into a monolithic all-perovskite tandem, we report a record VOC of 2.19 V (89% of the detailed balance VOC limit) and over 27% PCE (26.3% certified quasi-steady state). These tandems retained more than 86% of their initial PCE after 500 h of operation.

2.
Nature ; 624(7991): 289-294, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37871614

RESUMO

Inverted perovskite solar cells (PSCs) promise enhanced operating stability compared to their normal-structure counterparts1-3. To improve efficiency further, it is crucial to combine effective light management with low interfacial losses4,5. Here we develop a conformal self-assembled monolayer (SAM) as the hole-selective contact on light-managing textured substrates. Molecular dynamics simulations indicate that cluster formation during phosphonic acid adsorption leads to incomplete SAM coverage. We devise a co-adsorbent strategy that disassembles high-order clusters, thus homogenizing the distribution of phosphonic acid molecules, and thereby minimizing interfacial recombination and improving electronic structures. We report a laboratory-measured power conversion efficiency (PCE) of 25.3% and a certified quasi-steady-state PCE of 24.8% for inverted PSCs, with a photocurrent approaching 95% of the Shockley-Queisser maximum. An encapsulated device having a PCE of 24.6% at room temperature retains 95% of its peak performance when stressed at 65 °C and 50% relative humidity following more than 1,000 h of maximum power point tracking under 1 sun illumination. This represents one of the most stable PSCs subjected to accelerated ageing: achieved with a PCE surpassing 24%. The engineering of phosphonic acid adsorption on textured substrates offers a promising avenue for efficient and stable PSCs. It is also anticipated to benefit other optoelectronic devices that require light management.

3.
Nature ; 618(7963): 74-79, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36977463

RESUMO

The tunable bandgaps and facile fabrication of perovskites make them attractive for multi-junction photovoltaics1,2. However, light-induced phase segregation limits their efficiency and stability3-5: this occurs in wide-bandgap (>1.65 electron volts) iodide/bromide mixed perovskite absorbers, and becomes even more acute in the top cells of triple-junction solar photovoltaics that require a fully 2.0-electron-volt bandgap absorber2,6. Here we report that lattice distortion in iodide/bromide mixed perovskites is correlated with the suppression of phase segregation, generating an increased ion-migration energy barrier arising from the decreased average interatomic distance between the A-site cation and iodide. Using an approximately 2.0-electron-volt rubidium/caesium mixed-cation inorganic perovskite with large lattice distortion in the top subcell, we fabricated all-perovskite triple-junction solar cells and achieved an efficiency of 24.3 per cent (23.3 per cent certified quasi-steady-state efficiency) with an open-circuit voltage of 3.21 volts. This is, to our knowledge, the first reported certified efficiency for perovskite-based triple-junction solar cells. The triple-junction devices retain 80 per cent of their initial efficiency following 420 hours of operation at the maximum power point.

4.
Mol Cell ; 81(18): 3820-3832.e7, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34233158

RESUMO

A metabolic imbalance between lipid synthesis and degradation can lead to hepatic lipid accumulation, a characteristic of patients with non-alcoholic fatty liver disease (NAFLD). Here, we report that high-fat-diet-induced sterol regulatory element-binding protein (SREBP)-1c, a key transcription factor that regulates lipid biosynthesis, impairs autophagic lipid catabolism via altered H2S signaling. SREBP-1c reduced cystathionine gamma-lyase (CSE) via miR-216a, which in turn decreased hepatic H2S levels and sulfhydration-dependent activation of Unc-51-like autophagy-activating kinase 1 (ULK1). Furthermore, Cys951Ser mutation of ULK1 decreased autolysosome formation and promoted hepatic lipid accumulation in mice, suggesting that the loss of ULK1 sulfhydration was directly associated with the pathogenesis of NAFLD. Moreover, silencing of CSE in SREBP-1c knockout mice increased liver triglycerides, confirming the connection between CSE, autophagy, and SREBP-1c. Overall, our results uncover a 2-fold mechanism for SREBP-1c-driven hepatic lipid accumulation through reciprocal activation and inhibition of hepatic lipid biosynthesis and degradation, respectively.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Fígado Gorduroso/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Autofagia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/fisiologia , Linhagem Celular Tumoral , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/fisiopatologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Lipogênese , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transdução de Sinais/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/fisiologia , Triglicerídeos/metabolismo
5.
Nature ; 603(7899): 73-78, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35038717

RESUMO

All-perovskite tandem solar cells hold the promise of surpassing the efficiency limits of single-junction solar cells1-3; however, until now, the best-performing all-perovskite tandem solar cells have exhibited lower certified efficiency than have single-junction perovskite solar cells4,5. A thick mixed Pb-Sn narrow-bandgap subcell is needed to achieve high photocurrent density in tandem solar cells6, yet this is challenging owing to the short carrier diffusion length within Pb-Sn perovskites. Here we develop ammonium-cation-passivated Pb-Sn perovskites with long diffusion lengths, enabling subcells that have an absorber thickness of approximately 1.2 µm. Molecular dynamics simulations indicate that widely used phenethylammonium cations are only partially adsorbed on the surface defective sites at perovskite crystallization temperatures. The passivator adsorption is predicted to be enhanced using 4-trifluoromethyl-phenylammonium (CF3-PA), which exhibits a stronger perovskite surface-passivator interaction than does phenethylammonium. By adding a small amount of CF3-PA into the precursor solution, we increase the carrier diffusion length within Pb-Sn perovskites twofold, to over 5 µm, and increase the efficiency of Pb-Sn perovskite solar cells to over 22%. We report a certified efficiency of 26.4% in all-perovskite tandem solar cells, which exceeds that of the best-performing single-junction perovskite solar cells. Encapsulated tandem devices retain more than 90% of their initial performance after 600 h of operation at the maximum power point under 1 Sun illumination in ambient conditions.

6.
Nano Lett ; 24(8): 2574-2580, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38349338

RESUMO

The highly programmable and responsive molecular recognition properties of DNA provide unparalleled opportunities for fabricating dynamic nanostructures capable of structural transformation in response to various external stimuli. However, they typically operate in tightly controlled environments because certain conditions (ionic strength, pH, temperature, etc.) must be met for DNA duplex formation. In this study, we adopted site-specific enzymatic ligation and DNA-based layer-by-layer thin film fabrication to build shape-morphing DNA-linked nanoparticle films operational in a broad range of environments. The ligated films remained intact in unusual conditions such as pure water and high temperature causing dissociation of DNA duplexes and showed predictable and reversible shape morphing in response to various environmental changes and DNA exchange reactions. Furthermore, domain-selective ligation combined with photoinduced interlayer mixing allowed for the fabrication of unusual edge-sealed double-layered films through midlayer etching, which is difficult to realize by other methods.


Assuntos
Nanopartículas , Nanoestruturas , DNA/química , Água , Temperatura
7.
Clin Infect Dis ; 78(2): 470-475, 2024 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-37787062

RESUMO

BACKGROUND: Tetanus, a life-threatening infection, has become rare in the United States since introduction of tetanus toxoid-containing vaccines (TTCVs), recommended as a childhood series followed by decennial boosters beginning at age 11-12 years; vaccination uptake is high in children but suboptimal in adults. The objective of this study was to estimate the prevalence of sero-immunity to tetanus among persons aged ≥6 years in the United States and to identify factors associated with tetanus sero-immunity. Understanding population protection against tetanus informs current and future vaccine recommendations. METHODS: Anti-tetanus toxoid antibody concentrations were measured for participants of the 2015-2016 National Health and Nutrition Examination Survey (NHANES) aged ≥6 years for whom surplus serum samples were available using a microsphere-based multiplex antibody capture assay. Prevalence of sero-immunity, defined as ≥0.10 IU/mL, was estimated overall and by demographic characteristics. Factors associated with tetanus sero-immunity were examined using multivariable regression. RESULTS: Overall, 93.8% of the US population aged ≥6 years had sero-protection against tetanus. Prevalence of sero-immunity was above 90% across racial/ethnic categories, sex, and poverty levels. By age, ≥ 90% had protective sero-immunity through age 69 years, but prevalence of sero-immunity declined thereafter, with 75.8% of those aged ≥80 years having protective sero-immunity. Older age (adjusted prevalence ratio [aPR]: 0.89, 95% confidence interval [CI]: .85-.92) and being born outside the United States (aPR: 0.96, 95% CI: .93-.98) were significantly associated with lower prevalence of sero-immunity. CONCLUSIONS: The majority of the US population has vaccine-induced sero-immunity to tetanus, demonstrating the success of the vaccination program.


Assuntos
Tétano , Adulto , Criança , Humanos , Estados Unidos/epidemiologia , Idoso , Tétano/epidemiologia , Tétano/prevenção & controle , Inquéritos Nutricionais , Toxoide Tetânico , Vacinação , Imunização Secundária , Anticorpos Antibacterianos
8.
Lab Invest ; 104(8): 102092, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38857783

RESUMO

Recent studies have shown that novel antibody-drug conjugates (ADCs) can improve clinical outcomes in patients with HER2-low breast cancers. This study aimed to investigate alteration of HER2 status during breast cancer progression with an emphasis on HER2-low status. Using 386 paired samples of primary and recurrent breast cancers, HER2 discordance rate between primary and matched recurrent samples, the relationships between HER2 discordance and clinicopathological characteristics and clinical outcomes of the patients were analyzed. HER2 discordance rate between primary breast cancer and first recurrence was 25.9% (κ = 0.586) with mostly zero-to-low (10.6%) or low-to-zero (9.3%) conversion. There was no significant difference in the discordant rates according to type or location of the recurrence. Of 70 cases with a second recurrence, HER2 discordance rate between the primary tumor and the second recurrence was 27.1% (κ = 0.554). HER2 discordance was associated with lower HER2 level, lymphovascular invasion, and progesterone receptor positivity of the primary tumor. In further analyses, HER2-zero-to-low conversion was associated with lymph node metastasis and hormone receptor (HR) positivity, whereas HER2-low-to-zero conversion was associated with HR negativity and triple-negative subtype. In survival analyses, HER2 discordance was associated with decreased overall survival of patients in the HR-positive group but not in the HR-negative group. Furthermore, patients with HER2-low-to-zero converted tumors showed worse overall survival compared with those with HER2-low concordant tumors. In conclusion, HER2 status changes during breast cancer progression in significant proportions, mostly between zero and low status. As HER2 instability increases during progression and affects clinical outcome, HER2 status needs to be reevaluated in recurrent settings.

9.
BMC Plant Biol ; 24(1): 367, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38711041

RESUMO

BACKGROUND: The formation of shoots plays a pivotal role in plant organogenesis and productivity. Despite its significance, the underlying molecular mechanism of de novo regeneration has not been extensively elucidated in Capsicum annuum 'Dempsey', a bell pepper cultivar. To address this, we performed a comparative transcriptome analysis focusing on the differential expression in C. annuum 'Dempsey' shoot, callus, and leaf tissue. We further investigated phytohormone-related biological processes and their interacting genes in the C. annuum 'Dempsey' transcriptome based on comparative transcriptomic analysis across five species. RESULTS: We provided a comprehensive view of the gene networks regulating shoot formation on the callus, revealing a strong involvement of hypoxia responses and oxidative stress. Our comparative transcriptome analysis revealed a significant conservation in the increase of gene expression patterns related to auxin and defense mechanisms in both callus and shoot tissues. Consequently, hypoxia response and defense mechanism emerged as critical regulators in callus and shoot formation in C. annuum 'Dempsey'. Current transcriptome data also indicated a substantial decline in gene expression linked to photosynthesis within regenerative tissues, implying a deactivation of the regulatory system governing photosynthesis in C. annuum 'Dempsey'. CONCLUSION: Coupled with defense mechanisms, we thus considered spatial redistribution of auxin to play a critical role in the shoot morphogenesis via primordia outgrowth. Our findings shed light on shoot formation mechanisms in C. annuum 'Dempsey' explants, important information for regeneration programs, and have broader implications for precise molecular breeding in recalcitrant crops.


Assuntos
Capsicum , Perfilação da Expressão Gênica , Brotos de Planta , Transcriptoma , Capsicum/genética , Capsicum/crescimento & desenvolvimento , Capsicum/fisiologia , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas/metabolismo
10.
BMC Plant Biol ; 24(1): 527, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38858674

RESUMO

BACKGROUND: Angelica Gigas (Purple parsnip) is an important medicinal plant that is cultivated and utilized in Korea, Japan, and China. It contains bioactive substances especially coumarins with anti-inflammatory, anti-platelet aggregation, anti-cancer, anti-diabetic, antimicrobial, anti-obesity, anti-oxidant, immunomodulatory, and neuroprotective properties. This medicinal crop can be genetically improved, and the metabolites can be obtained by embryonic stem cells. In this context, we established the protoplast-to-plant regeneration methodology in Angelica gigas. RESULTS: In the present investigation, we isolated the protoplast from the embryogenic callus by applying methods that we have developed earlier and established protoplast cultures using Murashige and Skoog (MS) liquid medium and by embedding the protoplast in thin alginate layer (TAL) methods. We supplemented the culture medium with growth regulators namely 2,4-dichlorophenoxyaceticacid (2,4-D, 0, 0.75, 1.5 mg L- 1), kinetin (KN, 0, 0.5, and 1.0 mg L- 1) and phytosulfokine (PSK, 0, 50, 100 nM) to induce protoplast division, microcolony formation, and embryogenic callus regeneration. We applied central composite design (CCD) and response surface methodology (RSM) for the optimization of 2,4-D, KN, and PSK levels during protoplast division, micro-callus formation, and induction of embryogenic callus stages. The results revealed that 0.04 mg L- 1 2,4-D + 0.5 mg L- 1 KN + 2 nM PSK, 0.5 mg L- 1 2,4-D + 0.9 mg L- 1 KN and 90 nM PSK, and 1.5 mg L- 1 2,4-D and 1 mg L- 1 KN were optimum for protoplast division, micro-callus formation and induction embryogenic callus. MS basal semi-solid medium without growth regulators was good for the development of embryos and plant regeneration. CONCLUSIONS: This study demonstrated successful protoplast culture, protoplast division, micro-callus formation, induction embryogenic callus, somatic embryogenesis, and plant regeneration in A. gigas. The methodologies developed here are quite useful for the genetic improvement of this important medicinal plant.


Assuntos
Angelica , Reguladores de Crescimento de Plantas , Técnicas de Embriogênese Somática de Plantas , Protoplastos , Angelica/embriologia , Reguladores de Crescimento de Plantas/farmacologia , Técnicas de Embriogênese Somática de Plantas/métodos , Protoplastos/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos
11.
Artigo em Inglês | MEDLINE | ID: mdl-38753066

RESUMO

PURPOSE: The tumor immune microenvironment can change after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). We aimed to investigate the effects of NAC on PD-L1 (SP142) status and its clinical significance in TNBC. METHODS: Paired samples of biopsy and resection specimens were collected from 182 patients with TNBC before and after NAC. PD-L1 (SP142) expression in immune cells in pre- and post-NAC breast cancer samples and the changes between them were analyzed, along with their relationships with the clinicopathological features and clinical outcomes of the patients. RESULTS: Of the 182 patients, 61 (33.5%) achieved pathologic complete response (pCR) after NAC. PD-L1 (SP142) positivity, defined as immune cell staining in ≥ 1% of tumor area, was a predictor for pCR. PD-L1-positive immune cells significantly increased after NAC (2.8% to 5.2% on average) in 109 patients with measurable residual disease. Alteration of PD-L1 status was observed in 24 (22.0%) of the 109 patients with measurable residual tumors after NAC, and all PD-L1 status-converted patients, except one, revealed negative-to-positive conversion. Regarding chemotherapeutic agents, the use of platinum agents was associated with a significant increase in PD-L1-positive immune cells after NAC. In survival analyses, a positive PD-L1 status after NAC and increase of PD-L1-positive immune cells after NAC were associated with better recurrence-free survival of the patients. CONCLUSION: PD-L1 (SP142) status changes after NAC, mostly as a positive conversion. As PD-L1 (SP142) status can convey prognostic and predictive information, it needs to be tested before and after NAC.

12.
Small ; 20(16): e2307175, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38032159

RESUMO

Cu2ZnSn(S,Se)4 (CZTSSe) thin film solar cells are an attractive choice for a bottom cell of the low-cost and environmental tandem solar cells with perovskite. However, the progress in developing efficient perovskite/CZTSSe tandem solar cells has been hindered by the lack of high performance of the CZTSSe bottom cell. Here, an efficient CZTSSe bottom cell is demonstrated by adopting a facile and effective CsF treatment process. It is found that the CsF treatment not only facilitates grain growth and improves phase homogeneity by suppressing the detrimental deep-level defects and secondary phases, but also induces larger band bending and stronger drift force at the P-N junction. As a result, the carrier extraction/transport can be effectively accelerated, while reducing the interfacial recombination. These combined effects eventually result in a significant performance enhancement from 8.38% to 10.20%. The CsF-treated CZTSSe solar cell is finally applied to the mechanically-stacked perovskite/CZTSSe 4-terminal tandem cell by coupling a semi-transparent perovskite top cell, which exhibits the highest reported tandem efficiency of 23.01%.

13.
Small ; 20(23): e2310734, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38143290

RESUMO

Achieving satisfactory bone tissue regeneration in osteoporotic patients with ordinary biomaterials is challenging because of the decreased bone mineral density and aberrant bone microenvironment. In addressing this issue, a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold with magnesium hydroxide (M) and extracellular matrix (E) is introduced, enabling the consecutive release of bioactive agents. 4HR and SP induced the phosphorylation of p38 MAPK and ERK in human umbilical vein endothelial cells (HUVECs), thereby upregulating VEGF expression level. The migration and tube-forming ability of endothelial cells can be promoted by the scaffold, which accelerates the formation and maturation of the bone. Moreover, 4HR played a crucial role in the inhibition of osteoclastogenesis by interrupting the IκB/NF-κB signaling pathway and exhibiting SP, thereby enhancing the migration and angiogenesis of HUVECs. Based on such a synergistic effect, osteoporosis can be suppressed, and bone regeneration can be achieved by inhibiting the RANKL pathway in vitro and in vivo, which is a commonly known mechanism of bone physiology. Therefore, the study presents a promising approach for developing a multifunctional regenerative material for sophisticated osteoporotic bone regeneration.


Assuntos
Regeneração Óssea , Células Endoteliais da Veia Umbilical Humana , Osteoporose , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Alicerces Teciduais , Regeneração Óssea/efeitos dos fármacos , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Alicerces Teciduais/química , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Osteogênese/efeitos dos fármacos
14.
Small ; : e2402371, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597692

RESUMO

Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation displays, but suffer from carrier imbalance arising from lower hole injection compared to electron injection. A defect engineering strategy is reported to tackle transport limitations in nickel oxide-based inorganic hole-injection layers (HILs) and find that hole injection is able to enhance in high-performance InP QLEDs using the newly designed material. Through optoelectronic simulations, how the electronic properties of NiOx affect hole injection efficiency into an InP QD layer, finding that efficient hole injection depends on lowering the hole injection barrier and enhancing the acceptor density of NiOx is explored. Li doping and oxygen enriching are identified as effective strategies to control intrinsic and extrinsic defects in NiOx, thereby increasing acceptor density, as evidenced by density functional theory calculations and experimental validation. With fine-tuned inorganic HIL, InP QLEDs exhibit a luminance of 45 200 cd m-2 and an external quantum efficiency of 19.9%, surpassing previous inorganic HIL-based QLEDs. This study provides a path to designing inorganic materials for more efficient and sustainable lighting and display technologies.

15.
Nat Mater ; 22(12): 1507-1514, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37903926

RESUMO

Pseudo-halide (PH) anion engineering has emerged as a surface passivation strategy of interest for perovskite-based optoelectronics; but until now, PH anions have led to insufficient defect passivation and thus to undesired deep impurity states. The size of the chemical space of PH anions (>106 molecules) has so far limited attempts to explore the full family of candidate molecules. We created a machine learning workflow to speed up the discovery process using full-density functional theory calculations for training the model. The physics-informed machine learning model allowed us to pinpoint promising molecules with a head group that prevents lattice distortion and anti-site defect formation, and a tail group optimized for strong attachment to the surface. We identified 15 potential bifunctional PH anions with the ability to passivate both donors and acceptors, and through experimentation, discovered that sodium thioglycolate was the most effective passivant. This strategy resulted in a power-conversion efficiency of 24.56% with a high open-circuit voltage of 1.19 volts (24.04% National Renewable Energy Lab-certified quasi-steady-state) in inverted perovskite solar cells. Encapsulated devices maintained 96% of their initial power-conversion energy during 900 hours of one-sun operation at the maximum power point.

16.
Osteoporos Int ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953946

RESUMO

Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures. PURPOSE: The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. METHODS: 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. RESULTS: The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). CONCLUSION: Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

17.
FASEB J ; 37(8): e23104, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37486753

RESUMO

A new target that stimulates bone formation is needed to overcome limitations of current anti-osteoporotic drugs. Myokines, factors secreted from muscles, may modulate it. In this study, we investigated the role of aortic carboxypeptidase-like protein (ACLP), which is highly expressed in skeletal muscles, on bone formation. MC3T3-E1 cells and/or calvaria osteoblasts were treated with recombinant N-terminal mouse ACLP containing a signal peptide [rmACLP (N)]. The expression and secretion of ACLP were higher in skeletal muscle and differentiated myotube than in other tissues and undifferentiated myoblasts, respectively. rmACLP (N) increased bone formation, ALP activity, and phosphorylated p38 mitogen-activated protein (MAP) kinase in osteoblasts; reversal was achieved by pre-treatment with a TGF-ß receptor inhibitor. Under H2 O2 treatment, rmACLP (N) increased osteoblast survival, phosphorylated p38 MAP kinase, and the nuclear translocation of FoxO3a in osteoblasts. H2 O2 treatment caused rmACLP (N) to suppress its apoptotic, oxidative, and caspase-9 activities. rmACLP (N)-stimulated osteoblast survival was reversed by pre-treatment with a p38 inhibitor, a TGF-ß-receptor II blocking antibody, and a FoxO3a shRNA. Conditioned media (CM) from muscle cells stimulated osteoblast survival under H2 O2 treatment, in contrast to CM from ACLP knockdown muscle cells. rmACLP (N) increased the expressions of FoxO3a target anti-oxidant genes such as Sod2, Trx2, and Prx5. In conclusion, ACLP stimulated the differentiation and survival of osteoblasts. This led to the stimulation of bone formation by the activation of p38 MAP kinase and/or FoxO3a via TGF-ß receptors. These findings suggest a novel role for ACLP in bone metabolism as a putative myokine.


Assuntos
Carboxipeptidases , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Camundongos , Diferenciação Celular/fisiologia , Carboxipeptidases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Osteogênese , Osteoblastos/metabolismo , Fosforilação
18.
Eur Radiol ; 34(4): 2233-2243, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37731096

RESUMO

OBJECTIVE: We aimed to compare the image quality and focal lesion detection ability of hepatobiliary phase (HBP) images obtained using compressed sensing (CS) and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) in patients with liver cirrhosis. MATERIALS AND METHODS: We retrospectively included 244 gadoxetic acid-enhanced liver MRI from 244 patients with cirrhosis obtained by two HBP images using CS and CAIPIRINHA from July 2020 to December 2020. The optimized resolution and scan time for CS-HBP and CAIPIRINHA-HBP were 0.9 × 0.9 × 1.5 mm3 and 15 s and 1.3 × 1.3 × 3 mm3 and 16 s, respectively. We compared the image quality between the two sets of images in 244 patients and focal lesion (n = 294) analyses for 112 patients. RESULTS: CS-HBP showed comparable overall image quality (3.7 ± 0.9 vs. 3.6 ± 0.8, p = 0.680), superior liver edge sharpness (3.9 ± 0.6 vs. 3.6 ± 0.5, p < 0.001), and fewer respiratory motion artifacts (4.0 ± 0.7 vs. 3.8 ± 0.5, p < 0.001), but higher non-respiratory artifacts (3.4 ± 0.7 vs. 3.6 ± 0.6, p < 0.001) and subjective image noise (3.5 ± 0.8 vs. 3.6 ± 0.7, p = 0.014) than CAIPIRINHA-HBP. CS-HBP showed a higher signal-to-noise ratio in the liver than CAIPIRINHA-HBP (20.9 ± 9.0 vs. 18.9 ± 7.1, p = 0.008). The pooled sensitivity, specificity, and AUC were 90.0%, 77.5%, and 0.84 for CS-HBP and 73.5%, 82.4%, and 0.78 for CAIPIRINHA-HBP, respectively. CONCLUSIONS: CS-HBP showed better focal lesion detection ability, comparable overall image quality, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and noise compared to CAIPIRINHA-HBP. Thus, CS-HBP could be recommended for liver MRI in patients with cirrhosis to improve diagnostic performance. CLINICAL RELEVANCE STATEMENT: Thin-slice CS-HBP may be useful for detecting sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A while maintaining comparable subjective image quality. KEY POINTS: • Compared with controlled aliasing in parallel imaging results in higher acceleration, compressed sensing hepatobiliary phase yielded thinner slices and shorter scan time at a higher accelerating factor. • Compressed sensing hepatobiliary phase showed comparable overall image quality, superior liver edge sharpness, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and subjective image noise than controlled aliasing in parallel imaging results in higher acceleration-hepatobiliary phase. • Compressed sensing hepatobiliary phase can detect sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Meios de Contraste , Estudos Retrospectivos , Imageamento Tridimensional/métodos , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Aceleração , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Artefatos , Aumento da Imagem/métodos
19.
Ann Allergy Asthma Immunol ; 132(4): 457-462.e2, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37977324

RESUMO

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Humanos , Estudos Prospectivos , Eosinófilos , Anticorpos Monoclonais/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Antiasmáticos/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA