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1.
Sci Total Environ ; 932: 172879, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697529

RESUMO

Omega-3 polyunsaturated fatty acids (ω3-PUFA) are central to the growth and reproduction of aquatic consumers. Dissolved nutrients in aquatic ecosystems strongly affect algal taxonomic composition and thus the production and transfer of specific ω3-PUFA to consumers at higher trophic levels. However, most studies were conducted in nutrient-poor, oligotrophic lakes, leading to an insufficient understanding of how water nutrients affect algal ω3-PUFA and their trophic transfer in consumers in highly eutrophic lakes. We conducted a field investigation in a highly eutrophic lake and collected basal food sources (phytoplankton, periphyton and macrophytes) and aquatic consumers (invertebrates, zooplankton and fish), and measured their fatty acid (FA) composition. Our results showed that periphyton and phytoplankton were both important sources of ω3-PUFA supporting the highly eutrophic lake food web. High water nutrient levels led to low ω3-PUFA levels in phytoplankton and periphyton, resulting in decreased nutritional quality. Consequently, ω3-PUFA of invertebrates and zooplankton reflected variations in ω3-PUFA of phytoplankton and periphyton, respectively. The ω3-PUFA levels of fish decreased as phytoplankton and periphyton ω3-PUFA decreased. Among fish, the Redfin Culter (Cultrichthys erythropterus) and Bar Cheek Goby (Rhinogobius giurinus) exhibited significantly higher levels of EPA and DHA compared to the Pond Loach (Misgurnus anguillicaudatus), which may have been caused by their different feeding modes. Decreases in the ω3-PUFA levels of basal food sources may be one of the causes leading to the reduction of trophic links in aquatic food webs. Our study elucidated the sources and fate of ω3-PUFA in highly eutrophic lakes, complemented previous studies in oligo- and mesotrophic lakes, and emphasized the role of high-quality food sources. Our results offer new perspectives for the conservation and management of highly eutrophic lake ecosystems.

2.
Iran J Public Health ; 53(1): 1-11, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38694869

RESUMO

Background: Influenza is the first infectious disease that implements global monitoring and is one of the major public health issues in the world. Air pollutants have become an important global public health issue, in recent years, and much epidemiological and clinical evidence has shown that air pollutants are associated with respiratory diseases. Methods: We comprehensively searched articles published up to 15 November 2022 in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals, and Wanfang Database. The search strategies were based on keyword combinations related to influenza and air pollutants. The air pollutants included particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3). Meta-analysis was performed using the R programming language (R4.2.1). Results: A total of 2926 records were identified and 1220 duplicates were excluded. Finally, 19 studies were included in the meta-analysis according to inclusion and exclusion criteria. We observed a significant association between partial air pollutants (PM2.5, NO2, PM10 and SO2) and the incidence risk of influenza. The RRs were 1.0221 (95% CI: 1.0093~1.0352), 1.0395 (95% CI: 1.0131~1.0666), 1.007 (95% CI: 1.0009~1.0132), and 1.0352 (95% CI. 1.0076~1.0635), respectively. However, there was no significant relationship between CO and O3 exposure and influenza, and the RRs were 1.2272 (95% CI: 0.9253~1.6275) and 1.0045 (95% CI: 0.9930~1.0160), respectively. Conclusion: Exposure to PM2.5, NO2, PM10, and SO2 was significantly associated with influenza, which may be risk factors for influenza. The association of CO and O3 with influenza needs further investigation.

3.
Polymers (Basel) ; 16(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611268

RESUMO

The enzyme catalysis conversion of lignocellulosic biomass into valuable chemicals and fuels showed a bright outlook for replacing fossil resources. However, the high cost and easy deactivation of free enzymes restrict the conversion process. Immobilization of enzymes in metal-organic frameworks (MOFs) is one of the most promising strategies due to MOF materials' tunable building units, multiple pore structures, and excellent biocompatibility. Also, MOFs are ideal support materials and could enhance the stability and reusability of enzymes. In this paper, recent progress on the conversion of cellulose, hemicellulose, and lignin by MOF-immobilized enzymes is extensively reviewed. This paper focuses on the immobilized enzyme performances and enzymatic mechanism. Finally, the challenges of the conversion of lignocellulosic biomass by MOF-immobilized enzyme are discussed.

4.
Drug Saf ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689136

RESUMO

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, is efficacious and well tolerated for the treatment of moderate-to-severe plaque psoriasis. However, there are limited data on the real-world safety of ixekizumab in Chinese patient populations. We performed an observational study of ixekizumab for the treatment of moderate-to-severe plaque psoriasis in routine clinical practice in China. Here we present a further safety analysis of this study. METHODS: In this prospective, observational, single-arm, multicenter, post-marketing safety study, adults (≥18 years) with moderate-to-severe plaque psoriasis receiving ixekizumab were enroled at dermatology departments in hospitals across China and prospectively followed for 12 weeks or until their last dose of ixekizumab. In this analysis, we evaluated adverse events (AEs) of special interest (AESIs) identified using MedDRA® search strategies. We also analyzed AEs and AESIs occurring in greater than ten patients in subgroups by age (< 65/≥ 65 years), sex, body weight (< 60/60 kg to < 80/≥ 80 kg), renal impairment, hepatic impairment, history of tuberculosis, history of HBV infection, recent or active infection, history of allergic reaction/hypersensitivity, and number (0-1/2-4/5-7) of ixekizumab 80 mg injections after baseline until day 105. RESULTS: This analysis included 663/666 patients enrolled in the primary study. At least one AESI was reported in 224 (33.8%) patients and considered related to ixekizumab in 181 (27.3%); the most common were injection site reactions (n = 131, 19.8%), infections (n = 80, 12.1%), and allergic reactions/hypersensitivity events (n = 59, 8.9%). The proportion of patients with ≥ 1 AE was higher for females versus males (99/186, 53.2% versus 184/477, 38.6%, p = 0.0006). The proportion of patients with ≥ 1 AE increased with the number of ixekizumab injections after baseline [61/188 (32.4%) for zero to one injection, 151/338 (44.7%) for two to four injections, and 61/106 (57.5%) for five to seven injections; p = 0.0001]. CONCLUSIONS: In this real-world study, ixekizumab was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis, with no difference in safety across most patient subgroups.

5.
Dermatol Ther (Heidelb) ; 14(4): 907-918, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38536616

RESUMO

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). METHODS: A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. RESULTS: In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. CONCLUSION: Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

6.
Environ Res ; 252(Pt 1): 118754, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527719

RESUMO

Microchemical maps, also known as "chemoscapes", hold immense potential for reconstructing fish habitat utilization and guiding conservation efforts. This approach relies on matching the microchemical composition of fish calcified structures (e.g., otoliths) with the surrounding water's microchemistry. However, applying this method faces a major challenge: a clear understanding of the spatiotemporal variability and drivers of water microchemistry, particularly in vast, free-flowing river ecosystems like the Nu-Salween River, Southeast Asia's longest free-flowing river. We analyzed the spatiotemporal variability and influencing factors of water microchemistry (i.e., Na:Ca, Mg:Ca, Mn:Ca, Cu:Ca, Zn:Ca, Se:Ca, Sr:Ca, and Ba:Ca) in the upper Nu-Salween River, based on a two-year sampling. Five elemental ratios (excluding Na:Ca, Mg:Ca, and Zn:Ca) in water demonstrated significant spatiotemporal variability, with Cu:Ca having the largest spatial variation, and Mn:Ca and Sr:Ca showing the greatest temporal variation. More specifically, four elemental ratios (Cu:Ca, Se:Ca, Sr:Ca, and Ba:Ca), exhibited significant variations along the longitudinal gradient, and Mn:Ca, Cu:Ca, Sr:Ca, and Ba:Ca, showed significant differences between mainstreams and tributaries. Temporally, Mn:Ca, Cu:Ca, and Ba:Ca displayed higher values and variations during the wet season, opposing the seasonal patterns of Na:Ca, Mg:Ca, and Sr:Ca. The four-element (Ba:Ca, Sr:Ca, Mg:Ca, and Mn:Ca) forest model showed the highest classification accuracy of 93%. Linear mixed-effects models showed that spatial factors have the largest influence on the variances in water microchemistry (56.36 ± 28.64%). Our study highlights the feasibility and reliability of utilizing microchemistry to reconstruct fish habitat utilization, thereby unveiling promising avenues for a more accurate understanding of fish life history in large rivers characterized by high heterogeneity in water microchemistry. By proportionally accounting for contribution of different factors to water microchemistry variability and relating them to microchemical composition of fish calcified structures, key fish habitats (e.g., spawning grounds) and migratory routes can be more precisely identified and thus protected.

7.
Front Immunol ; 15: 1309992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476235

RESUMO

There is sufficient evidence indicating that keloid is strongly associated with atopic dermatitis (AD) across ethnic groups. However, the molecular mechanism underlying the association is not fully understood. The aim of this study is to discover the underlying mechanism of the association between keloid and AD by integrating comprehensive bioinformatics techniques and machine learning methods. The gene expression profiles of keloid and AD were downloaded from the Gene Expression Omnibus (GEO) database. A total of 449 differentially expressed genes (DEGs) were found to be shared in keloid and AD using the training datasets of GEO (GSE158395 and GSE121212). The hub genes were identified using the protein-protein interaction network and Cytoscape software. 20 of the most significant hub genes were selected, which were mainly involved in the regulation of the inflammatory and immune response. Through two machine learning algorithms of LASSO and SVM-RFE, CCR5 was identified as the most important key gene. Subsequently, upregulated CCR5 gene expression was confirmed in validation GEO datasets (GSE188952 and GSE32924) and clinical samples of keloid and AD. Immune infiltration analysis showed that T helper (Th) 1, 2 and 17 cells were significantly enriched in the microenvironment of both keloid and AD. Positive correlations were found between CCR5 and Th1, Th2 and Th17 cells. Finally, two TFs of CCR5, NR3C2 and YY1, were identified, both of which were downregulated in keloid and AD tissues. Our study firstly reveals that keloid and AD shared common inflammatory and immune pathways. Moreover, CCR5 plays a key role in the pathogenesis association between keloid and AD. The common pathways and key genes may shed light on further mechanism research and targeted therapy, and may provide therapeutic interventions of keloid with AD.


Assuntos
Dermatite Atópica , Queloide , Humanos , Algoritmos , Biologia Computacional , Aprendizado de Máquina , Receptores CCR5
8.
Nat Commun ; 15(1): 2038, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448448

RESUMO

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.


Assuntos
Cicatriz Hipertrófica , Humanos , Animais , Feminino , Camundongos , Coelhos , Cicatriz Hipertrófica/tratamento farmacológico , Espécies Reativas de Oxigênio , Disponibilidade Biológica , Diferenciação Celular , Metaloproteinases da Matriz
9.
Sci Data ; 11(1): 272, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448551

RESUMO

The Schizothoracinae fish are a natural group of cyprinids widely distributed in rivers and lakes in the Qinghai-Tibetan Plateau (QTP) and adjacent regions. These fish parallelly evolved with the QTP uplift and are thus important for uncovering geological history, the paleoclimatic environment, and the mechanisms of functional adaptation to environmental change. However, a dataset including species occurrences and functional traits, which are essential for resolving the above issues and guiding relevant conservation, remains unavailable. To fill this gap, we systematically compiled a comprehensive dataset on species occurrences and functional traits of Schizothoracinae fish from our long-term field samplings and various sources (e.g., publications and online databases). The dataset includes 7,333 occurrence records and 3,204 records of 32 functional traits covering all the genera and species of Schizothoracinae fish (i.e., 12 genera and 125 species or subspecies). Sampling records spanned over 180 years. This dataset will serve as a valuable resource for future research on the evolution, historical biogeography, responses to environmental change, and conservation of the Schizothoracinae fish.


Assuntos
Cyprinidae , Animais , Cyprinidae/fisiologia , Bases de Dados Factuais , Lagos , Fenótipo , Rios , China
10.
Int Immunopharmacol ; 131: 111867, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38493690

RESUMO

BACKGROUND: Dupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively contributing to clinical improvement in patients with atopic dermatitis (AD). As the second genome of human body, growing evidence suggests that the gut microbiome might relate to the host response to treatments. Little is known about the association between dupilumab treatment and gut microbiome in AD patients. OBJECTIVE: We aimed to characterize the gut microbiome among Chinese subjects with or without AD and determine the potential effect of dupilumab on the gut microbiome. RESULTS: The 16 s rRNA gene sequencing was conducted on 48 healthy controls (HC), 44 AD patients and 27 AD patients who received dupilumab for 16 weeks. Prior to treatment, we identified the changed beta-diversity, increased Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium and expanded Faecalibacterium among the AD patients compared to HC. After 16 weeks of dupilumab treatment, gut microbiome dysbiosis of the AD patients improved with reversed beta-diversity, closer bacterial connections, increased colonization of Bifidobacterium, Ruminococcus gnavus, and Coprococcus, which were negatively correlated with disease severity indicators. This shift was largely independent of the degree of clinical improvement. Bacterial function analysis revealed further metabolic alterations following dupilumab treatment, including up-regulated expression of genes involved in the indole pathway of tryptophan metabolism, corroborated by quantitative UHPLC-MS/MS analysis. CONCLUSION: Dupilumab treatment tends to help shift the gut microbial dysbiosis in AD patients to a healthier state, along with improved intestinal tryptophan metabolism, suggesting the gut flora and its metabolites may mediate part of the synergistic therapeutic effects on the host.


Assuntos
Anticorpos Monoclonais Humanizados , Dermatite Atópica , Microbioma Gastrointestinal , Humanos , Dermatite Atópica/tratamento farmacológico , Microbioma Gastrointestinal/genética , Triptofano/uso terapêutico , Disbiose/microbiologia , Espectrometria de Massas em Tandem , China
12.
J Mater Chem B ; 12(10): 2618-2627, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38376394

RESUMO

Methotrexate (MTX) is one of the first-line drugs used for the treatment of moderate to severe psoriasis. However, low bioavailability and systemic side effects of traditional oral and injectable MTX greatly limit its clinical application. Delivering MTX using dissolving microneedles (MNs) into psoriasis-like skin lesion could improve the in situ therapeutic effects with higher bioavailability and less side effects. Here, we propose a novel therapeutic approach for psoriasis involving MN-assisted percutaneous delivery of chitosan-coated hollow mesoporous silica nanoparticles containing MTX (MTX@HMSN/CS). The MTX@HMSN/CS-loaded MNs were strong enough to successfully penetrate the psoriasiform thickened epidermis, allowing MTX@HMSN/CS to be accurately delivered to the site of skin lesion following the rapid dissolution of MNs. MTX was then released continuously from HMSN/CS for at least one week to maintain effective therapeutic drug concentration for skin lesion with long-term anti-proliferative and anti-inflammatory effects. Incubation with MTX@HMSN/CS not only inhibited the proliferation of human immortalized keratinocytes (HaCaT cells), but also significantly reduced the expression of proinflammatory cytokines and chemokines. In addition, MTX@HMSN/CS-loaded MNs showed better efficacy in alleviating psoriasis-like skin inflammation than MTX-loaded MNs at the same dose. Compared to psoriasiform mice treated with 15.8 µg MTX-loaded MNs every day, 47.4 µg MTX@HMSN/CS-loaded MNs reduce the frequency of treatment to once every 3 days and achieve comparable amelioration. Therefore, MTX@HMSN/CS loaded MNs are a promising treatment strategy for psoriasis due to their durability, efficacy, convenience, and safety in relieving psoriasis-like skin inflammation.


Assuntos
Neuropatia Hereditária Motora e Sensorial , Nanopartículas , Psoríase , Animais , Camundongos , Humanos , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Neuropatia Hereditária Motora e Sensorial/tratamento farmacológico
13.
Adv Mater ; : e2313857, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335503

RESUMO

Touch is a general term to describe mechanical stimuli. It is extremely difficult to develop touch sensors that can detect different modes of contact forces due to their low sensitivity and data decoupling. Simultaneously conducting tactile and slip sensing presents significant challenges for the design, structure, and performance of sensors. In this work, a highly sensitive sandwich-structured sensor is achieved by exploiting the porosity and compressive modulus of the sensor's functional layer materials. The sensor shows an ultra-high sensitivity of 1167 kPa-1 and a low-pressure detection limit of 1.34 Pa due to its considerably low compression modulus of 23.8 Pa. Due to this ultra-high sensitivity, coupled with spectral analysis, it allows for dual-mode detection of both tactile and slip sensations simultaneously. This novel fabrication strategy and signal analysis method provides a new direction for the development of tactile/slip sensors.

14.
Br J Dermatol ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38366639

RESUMO

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

16.
J Invest Dermatol ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38272207

RESUMO

The migration of γδ T lymphocytes toward skin lesions and their concomitant pathogenic IL-17A production play a crucial role in the pathogenesis of psoriasis. However, the regulatory mechanisms of IL-17A production by γδ T cells and their migration remain to be fully explored. Intracellular GRP78 is a molecular chaperone that regulates endoplasmic reticulum stress, whereas secretory GRP78, as a member of the resolution-associated molecular patterns, exerts immunoregulatory effects. In this study, we reported that both the intracellular GRP78 in skin lesions and secretory GRP78 in the serum were significantly decreased in patients with psoriasis. A GRP78 knockdown exacerbated imiquimod-induced skin inflammation, whereas the application of recombinant GRP78 protein or BIP inducer X (a GRP78 inducer) attenuated the dermatitis. Mechanistically, the GRP78 knockdown in keratinocytes enhanced the production of chemokines, specifically CCL20, which regulates γδ T-cell migration. Moreover, recombinant GRP78 was found to directly bind to γδ T cells to suppress its migration ability and proinflammatory capacities by downregulating the CCR6 and IL-17A expression. Collectively, our results uncovered a pivotal role of GRP78 in the pathogenesis of psoriasis, which was mainly exerted by regulating the interaction between keratinocytes and γδ T cells, and might provide a promising target for psoriasis therapy.

17.
Chin Med J (Engl) ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38192233

RESUMO

BACKGROUND: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. METHODS: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. RESULTS: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks 86.8% [92/106] vs. 82.4% [89/108] and maintained up to 52 weeks 91.3% [95/104] vs. 87.4% [90/103]. Most treatment-emergent adverse events were mild and not related to tildrakizumab. CONCLUSION: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05108766.

18.
Acad Radiol ; 31(3): 1014-1023, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37714721

RESUMO

RATIONALE AND OBJECTIVES: To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. MATERIALS AND METHODS: A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. RESULTS: The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. CONCLUSION: IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia.


Assuntos
Fibrossarcoma , Imageamento por Ressonância Magnética , Animais , Camundongos , Camundongos Nus , Imageamento por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Biomarcadores , Movimento (Física) , Fibrossarcoma/diagnóstico por imagem
19.
Ecology ; 105(2): e4211, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010728

RESUMO

Humans have long been fascinated by the mysteries surrounding fish migrations and addressing these complex behaviors often requires large data sets. Biogeochemical tags, including trace elements and stable isotopes, are the most accessible biomarkers for tracking fish migrations. However, access to standardized biogeochemical tag data is rarely available for migratory fish, which limits our understanding of the evolutionary origins, drivers, timing, and corridors of migration. This precludes the development of conservation strategies and the implementation of management actions. Here, we present MFishBT, a global, open-access database of Migratory Fish's Biogeochemical Tags. As of April 2023, the MFishBT contains biogeochemical records from 1,305 studies, of which 53% used element-to-calcium (E/Ca) ratios, 34% used isotopic ratios, and 13% used both. The database covers 17,413 field sampling locations (inland 47% vs. marine 53%) around the globe, comprising 490 migratory fish species of four classes, 44 orders/suborders, and 137 families. In total, 77 trace elements and 11 isotope systems were measured across various fish biological archives, including otoliths, scales, eye lenses, and vertebrae. E/Ca ratios were examined more frequently than isotopic ratios, led by Sr/Ca, Mg/Ca, Ba/Ca, and 87 Sr/86 Sr, δ13 C, and δ18 O. The MFishBT compiles 27,030, 16,222, and 2,481,714 records with biogeochemical data detected in the core, edge, and core-to-edge transects for biological archives of migratory fish. This is the most globally comprehensive open-access database on biogeochemical tags in migratory fish to date, and can serve a variety of needs in scientific research, conservation, and management. We encourage researchers to add more data sets to this database in the future. This database is released for noncommercial use only. There are no copyright restrictions, and please cite this paper when using these data, or a subset of these data, for publication.


Assuntos
Oligoelementos , Humanos , Animais , Peixes , Isótopos , Cálcio , Membrana dos Otólitos
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