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1.
Cardiovasc Diagn Ther ; 14(4): 509-524, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39263473

RESUMEN

Background: Radiation-induced heart disease (RIHD) is a serious complication of thoracic tumor radiotherapy that substantially affects the quality of life of cancer patients. Oxidative stress plays a pivotal role in the occurrence and progression of RIHD, which prompted our investigation of an innovative approach for treating RIHD using antioxidant therapy. Methods: We used 8-week-old male Sprague-Dawley (SD) rats as experimental animals and H9C2 cells as experimental cells. N-acetylcysteine (NAC) was used as an antioxidant to treat H9C2 cells after X-ray irradiation in this study. In the present study, the extent of cardiomyocyte damage caused by X-ray exposure was determined, alterations in oxidation/antioxidation levels were assessed, and changes in the expression of genes related to mitochondria were examined. The degree of myocardial tissue and cell injury was also determined. Dihydroethidium (DHE) staining, reactive oxygen species (ROS) assays, and glutathione (GSH) and manganese superoxide dismutase (Mn-SOD) assays were used to assess cell oxidation/antioxidation. Flow cytometry was used to determine the mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening. High-throughput transcriptome sequencing and bioinformatics analysis were used to elucidate the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure. Polymerase chain reaction (PCR) was used to verify the expression of differentially expressed genes. Results: X-ray irradiation damaged myocardial tissue and cells, resulting in an imbalance of oxidative and antioxidant substances and mitochondrial damage. NAC treatment increased cell counting kit-8 (CCK-8) levels (P=0.02) and decreased lactate dehydrogenase (LDH) release (P=0.02) in cardiomyocytes. It also reduced the level of ROS (P=0.002) and increased the levels of GSH (P=0.04) and Mn-SOD (P=0.01). The mitochondrial membrane potential was restored (P<0.001), and mPTP opening was inhibited (P<0.001). Transcriptome sequencing and subsequent validation analyses revealed a decrease in the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure, but antioxidant therapy did not reverse the related DNA damage. Conclusions: Antioxidants mitigated radiation-induced myocardial damage to a certain degree, but these agents did not reverse the associated DNA damage. These findings provide a new direction for future investigations by our research group, including exploring the treatment of RIHD-related DNA damage.

2.
ESC Heart Fail ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39275894

RESUMEN

BACKGROUND: Heart failure (HF) is the leading cause of morbidity and mortality worldwide. Stemness refers to the self-renewal and differentiation ability of cells. However, little is known about the heart's stemness properties. Thus, the current study aims to identify putative stemness-related biomarkers to construct a viable prediction model of HF and characterize the immune infiltration features of HF. METHODS: HF datasets from the Gene Expression Omnibus (GEO) database were adopted as the training and validation cohorts while stemness-related genes were obtained from GeneCards and previously published papers. Feature selection was performed using two machine learning algorithms. Nomogram models were then constructed to predict HF risk based on the selected key genes. Moreover, the biological functions of the key genes were evaluated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) pathway analyses, and gene set variation analysis (GSVA) and enrichment analysis (GSEA) were performed between the high- and low-risk groups. The immune infiltration landscape in HF was investigated, and the interaction network of key genes was analysed to predict potential targets and molecular mechanisms. RESULTS: Seven key genes, namely SMOC2, LUM, FNDC1, SCUBE2, CD163, BLM and S1PR3, were included in the proposed nomogram. This nomogram showed good predictive performance for HF diagnosis in the training and validation sets. GO and KEGG analyses revealed that the key genes were primarily associated with ageing, inflammatory processes and DNA oxidation. GSEA and GSVA identified various inflammatory and immune signalling pathways that were enriched between the high- and low-risk groups. The infiltration of 15 immune cell subsets suggests that adaptive immunity has an important role in HF. CONCLUSIONS: Our study identified a clinically significant stemness-related signature for predicting HF risk, with the potential to improve early disease diagnosis, optimize risk stratification and provide new strategies for treating patients with HF.

3.
J Plant Physiol ; 303: 154338, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39306910

RESUMEN

Drought stress limits plant growth and development. To cope with drought stress, abscisic acid (ABA) accumulates in plants. Although ABA-dependent drought tolerance pathways have been widely investigated, the feedback mechanisms and the negative regulatory roles within these pathways remain largely unknown. Here we characterize the roles of a C2H2 transcription factor, ZFP8, whose expression is repressed by ABA in the tolerance of drought stress. ZFP8-overexpressing plants were hyposensitive to ABA and exhibited less dehydration tolerance while ABA or drought-induced marker genes were more highly expressed in zfp8, suggesting that ZFP8 functions as a negative regulator in the ABA-mediated drought response. A transcriptome assay showed that ZFP8 positively regulates gene expression for cellular function and negatively regulates hormone and stress response gene expression. Moreover, we found that ZFP8 can interact with ABF2, one of the basic leucine zipper (bZIP) family transcription factor members, to inhibit its transcription activity. In conclusion, our results demonstrate a novel negative regulation pathway of ZFP8, which contributes to plants' ability to fine-tune their drought responses.

5.
Front Oncol ; 14: 1393833, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281383

RESUMEN

Background: Some studies have reported that sunburns and cutaneous melanoma (CM) risk is increasing, but a clear causal link has yet to be established. Methods: This current study conducted a two-sample Mendelian randomization (MR) approach to clarify the association and causality between sunburn history and CM using large-scale genome-wide association study data. Results: The inverse-variance weighted method result showed that sunburn might be associated with the risk of CM increasing (p = 2.21 × 10-23, OR = 1.034, 95% CI= 1.027-1.041), causally. The MR-Egger regression, weighted median method, simple mode method, and weighted mode method results showed similar results. Conclusion: This study offers evidence of sunburn history and increased risk of CM, and it shows that there might be common genetic basics regarding sunburns and CM susceptibility in Caucasian, European, or British ethnic groups.

6.
Cancer ; 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39306696

RESUMEN

BACKGROUND: Persistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node-negative, human epidermal growth factor receptor 2-positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking. METHODS: Data on patients with T1cN0M0-stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well-balanced cohorts for the NAT and AT groups. Kaplan-Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT. RESULTS: After PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35-0.77; p < .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37-0.98; p = .041). A logistic regression model revealed that White race and hormone receptor-negative status independently predicted pCR. CONCLUSIONS: For patients with T1cN0M0-stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.

7.
J Affect Disord ; 366: 196-209, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39214372

RESUMEN

OBJECTIVE: Stroke is a highly prevalent and disabling disease whose disease mechanisms are not fully understood. The discovery of disease-associated proteins with genetic evidence of pathogenicity provides an opportunity to identify new therapeutic targets. METHOD: We examined the observed and causal associations of thousands of plasma and inflammatory proteins that were measured using affinity-based proteomic assays. First, we pooled >3000 relevant proteins using a fixed-effects meta-analysis of 2 population-based studies involving 48,383 participants, then investigated the causal effects of stroke and its subtype-associated proteins by forward Mendelian randomization using cis-protein quantitative locus genetic tools identified from genome-wide association studies of these >48,000 individuals. To improve the accuracy of causal estimation, we implemented a systematic Mendelian randomization model that accounts for cascading imbalances between instruments and tested the robustness of causal estimation through multi-method analyses. To further validate the hypothesis that ginsenoside Rg1 monomer acts on the five protein targets screened for drug-targeted regulation, we conducted a comparative analysis of the mRNA (gene) expression levels of a limited number of genes in the brain tissues of different groups of SD rats. The druggability of the candidate proteins was investigated and the mechanism of action and potential targeting side effects were explored by Phenome-wide MR. RESULTS: Six circulating proteins were identified to have a significant genetic association with stroke (PFDR < 0.05). For example, in patients with cardioembolic stroke, higher genetically predicted APRT was associated with a lower risk of cardioembolic stroke (ORivw [95 % CI] = 0.641 [0.517, 0.795]; P = 5.25 × 10-5, ORSMR [95 % CI] = 0.572, [0.397, 0.825], PSMR = 0.003). Mediation analyses suggested that atrial fibrillation, angina pectoris, and heart failure may mediate the association of CD40L, LIFR, and UPA with stroke. Molecular docking revealed promising interactions between the identified proteins and glycosides. Transcriptomic sequencing in animal models indicated that ginsenoside Rg1 may act through APRT, IL15RA, and VSIR pathways, with APRT showing significant variability in mRNA sequencing expression. Phenome-wide MR of the six target proteins showed an overwhelming predominance of PFDR > 0.05, indicating less toxicity. CONCLUSIONS: The present study provides genetic evidence to support the potential efficacy of targeting the three druggable protein targets for the treatment of stroke. This is achieved by triangulating population genomic and proteomic data. Furthermore, the study validates the pathway mechanisms by which APRT, IL15RA, and VSIR dock ginsenoside Rg1 in animal models. This will help to prioritize stroke drug development.


Asunto(s)
Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Accidente Cerebrovascular , Transcriptoma , Accidente Cerebrovascular/genética , Humanos , Animales , Ratas , Proteómica , Ratas Sprague-Dawley , Masculino , Multiómica
8.
Artículo en Inglés | MEDLINE | ID: mdl-39173993

RESUMEN

BACKGROUND: Motor impairments and sensory processing abnormalities are prevalent in autism spectrum disorder (ASD), closely related to the core functions of the primary motor cortex (M1) and the primary somatosensory cortex (S1). Currently, there is limited knowledge about potential therapeutic targets in the subregions of M1 and S1 in ASD patients. This study aims to map clinically significant functional subregions of M1 and S1. METHODS: Resting-state functional magnetic resonance imaging data (NTD = 266) from Autism Brain Imaging Data Exchange (ABIDE) were used for subregion modeling. We proposed a distance-weighted sparse representation algorithm to construct brain functional networks. Functional subregions of M1 and S1 were identified through consensus clustering at the group level. Differences in the characteristics of functional subregions were analyzed, along with their correlation with clinical scores. RESULTS: We observed symmetrical and continuous subregion organization from dorsal to ventral aspects in M1 and S1, with M1 subregions conforming to the functional pattern of the motor homunculus. Significant intergroup differences and clinical correlations were found in the dorsal and ventral aspects of M1 (p < 0.05/3, Bonferroni correction) and the ventromedial BA3 of S1 (p < 0.05/5). These functional characteristics were positively correlated with autism severity. All subregions showed significant results in the ROI-to-ROI intergroup differential analysis (p < 0.05/80). LIMITATIONS: The generalizability of the segmentation model requires further evaluation. CONCLUSIONS: This study highlights the significance of M1 and S1 in ASD treatment and may provide new insights into brain parcellation and the identification of therapeutic targets for ASD.


Asunto(s)
Trastorno del Espectro Autista , Imagen por Resonancia Magnética , Corteza Motora , Corteza Somatosensorial , Humanos , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/fisiopatología , Corteza Motora/diagnóstico por imagen , Corteza Motora/fisiopatología , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Corteza Somatosensorial/diagnóstico por imagen , Corteza Somatosensorial/fisiopatología , Adulto , Adulto Joven , Adolescente , Mapeo Encefálico/métodos , Niño
9.
Heliyon ; 10(15): e35012, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39157309

RESUMEN

Background: LIN9, a gene associated with various cancers, is considered a tumor suppressor. However, the role of LIN9 in lung adenocarcinoma (LUAD) remains unknown. In this study, we aimed to assess the role of LIN9 in the occurrence and prognosis of LUAD. Methods: Using three-tier HTSeq count RNA sequencing data from The Cancer Genome Atlas, we assessed LIN9 expression for the LUAD dataset using the DESeq2 R package and RT-qPCR experiments. Biological functions were assessed using gene set enrichment analysis (clusterProfiler and GOplot). The expression of LIN9 and the infiltration of immune cells were assessed by Single-sample gene set enrichment analysis. We conducted correlation study using clinical characteristics and receiver operating characteristic curve analysis. The predictive value of LIN9 was determined using univariate and multivariate Cox regression as well as Kaplan-Meier analysis. Additionally, functional studies were conducted to validate its role in the progression of LUAD. Results: Expression of LIN9 was significantly elevated in LUAD, primarily influencing cell cycle, division, and signaling pathways. High LIN9 expression correlated positively with the infiltration of Th2 cells and inversely with that of plasmacytoid dendritic cells. Furthermore, LIN9 was associated with older age and advanced clinical stages, posing risks to overall, progression-free, and disease-specific survival. LIN9 served as a good diagnostic marker, particularly in females, patients aged over 65, and those with clinical N1-3 and M1 stages. Elevated LIN9 expression enhanced proliferation, migration, and invasion of LUAD cells. Conclusion: High LIN9 expression potentially contributes to LUAD occurrence through cell cycle regulation and chromosomal modification. It promotes the malignant characteristics of LUAD cells and holds prognostic value for affected patients.

10.
J Leukoc Biol ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39213175

RESUMEN

Hormone receptor-positive breast cancer (HR+ BRCA) with high-risk factors such as lymph node metastasis has a relatively poor prognosis. However, the biological basis of tumor cell migration is still poorly understood, especially as some of the metastatic events occur at an early stage. Here, we identified that carbohydrate sulfotransferase 4 (CHST4), which has an important role in lymphocyte homing, was abnormally down-regulated in HR+ BRCA and associated with lymph node metastasis. By enrichment analysis and immune infiltration evaluation, we predicted the potential ability of CHST4 to enhance immune cell infiltration. Then, IHC staining further demonstrated the contribution of CHST4 to the infiltration abundance of CD8+ T cells and CD4+ T cells in HR+ BRCA. IHC staining of MECA-79 further identified the correlation between CHST4 and sulfated perpheral lymphonode vascular addressin (PNAd). Finally, we demonstrated that CHST4 was connected to increased tumor-immune cell communication by analyzing single-cell sequencing data. In summary, our study provided novel insights into the regulation of HR+ BRCA immune infiltration by CHST4.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1129-1135, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39192409

RESUMEN

OBJECTIVE: To investigate the correlation of peripheral blood T lymphocyte subsets with overall survival (OS) and clinical baseline characteristics in mantle cell lymphoma (MCL). METHODS: The clinical data of 55 MCL patients who were newly diagnosed in the Department of Hematology, Second Hospital of Shanxi Medical University from January 2012 to July 2022 were analyzed retrospectively. The percentages of T lymphocyte subsets and CD4+/CD8+ ratio in peripheral blood were detected by flow cytometry, and their correlation with clinical characteristics of patients were analyzed. Kaplan-Meier method was used for survival analysis and survival curves were drawn. Log-rank test was used for univariate analysis, while Cox proportional hazards model was used for multivariate analysis. RESULTS: The median follow-up was 40(1-68) months, and the median overall survival (OS) was 47 months. Among the 55 patients, 30(54.5%) patients had a decrease in peripheral blood CD4+T lymphocyte, while 17(30.9%) patients had a increase in peripheral blood CD8+T lymphocyte, and 20(36.4%) patients had a decrease in CD4+/CD8+ ratio. There were no significant correlations between CD4+/CD8+ ratio and sex, age, Ki-67, B symptoms, leukocytes, hemoglobin, lymphocytes, platelets, albumin, lactate dehydrogenase (LDH), ß2-microglobulin, splenomegaly, bone marrow invasion, primary site and MIPI score. Survival analysis showed that patients with CD4+T cell >23.3%, CD8+T cell ≤33.4% and CD4+/CD8+ ratio >0.6 had longer OS (P =0.020, P <0.001, P <0.001). Univariate analysis showed that Ki-67>30%, LDH>250 U/L, splenomegaly, bone marrow involvement, CD4+T cells ≤23.3%, CD8+ T cells >33.4%, CD4+/CD8+ ratio ≤0.6 were adverse prognostic factors affecting OS of MCL patients. Multivariate analysis showed that CD4+/CD8+ ratio ≤0.6 (HR =4.382, P =0.005) was an independent adverse prognostic factor for OS of MCL patients. CONCLUSIONS: Low CD4+/CD8+ ratio is associated with poor prognosis in MCL, and the CD4+/CD8+ ratio can be used as an important indicator to evaluate the prognosis risk in MCL patients.


Asunto(s)
Relación CD4-CD8 , Linfoma de Células del Manto , Humanos , Linfoma de Células del Manto/sangre , Pronóstico , Estudios Retrospectivos , Linfocitos T CD8-positivos , Modelos de Riesgos Proporcionales , Masculino , Femenino , Subgrupos de Linfocitos T , Persona de Mediana Edad
12.
J Colloid Interface Sci ; 677(Pt B): 234-249, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39146812

RESUMEN

The low efficiency of charge carrier separation is a major limitation hindering the application of photocatalytic technology. Constructing S-scheme heterojunction photocatalysts not only effectively promotes the separation of charge carriers, but also maximizes the oxidative and reductive capabilities of the two monomers. In this study S-scheme heterogeneous InVO4/Bi5O7I photocatalyst was synthesized by hydrothermal method combined with calcination. The optimal sample 20 % InVO4/Bi5O7I can completely deactivate Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in 30 min, remove 20 mg/L TC 76.0 % in 60 min and 20 mg/L BPA 93.0 % in 90 min. Intermediate products of TC and BPA degradation were detected using LC-MS, and possible degradation pathways were proposed. The photocurrent and electrochemical impedance spectroscopy (EIS) tests confirm that InVO4/Bi5O7I exhibits excellent photocurrent intensity and photocarrier migration ability, which are crucial reasons for the enhancement of the photocatalytic performance of the InVO4/Bi5O7I composite. Capture experiments indicate that OH, O2-, h+ and e-are reactive species. EPR further confirms the generation of OH and O2-. Combined with Kelvin probe force microscopy (KPFM) and band structure analysis, it is proposed that InVO4/Bi5O7I has an S-scheme charge transfer mechanism.

13.
Fish Shellfish Immunol ; 151: 109744, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38960107

RESUMEN

MicroRNAs (miRNAs) have been demonstrated to act as crucial modulators with considerable impacts on the immune system. Cottonseed meal is often used as a protein source in aqua feed, cottonseed meal contains gossypol, which is harmful to animals. However, there is a lack of research on the role of miRNAs in fish exposed to gossypol stress. To determine the regulatory effects of miRNAs on gossypol toxicity, Cyprinus carpio were given to oral administration of 20 mg/kg gossypol for 7 days, and the gossypol concentration in the tissues was tested. Then, we detected spleen index, histology, immune enzyme activities of fish induced by gossypol. The results of miRNA sequencing revealed 8 differentially expressed miRNAs in gossypol group, and miR-214_L-1R+4 was found involved in immune response induced by gossypol. The potential targets of miR-214_L-1R+4 were predicted, and found a putative miR-214_L-1R+4 binding site in the 3'UTR of MyD88a. Furthermore, dual-luciferase reporter assays displayed miR-214_L-1R+4 decreased MyD88a expression through binding to the 3'UTR of MyD88a. Moreover, miR-214_L-1R+4 antagomir were intraperitoneally administered to C. carpio, down-regulated miR-214_L-1R+4 could increase MyD88a expression, as well as inflammatory cytokines and anti-inflammatory cytokines expression. These findings revealed that miR-214_L-1R+4 via the MyD88-dependent signaling pathway modulate the immune response to gossypol in C. carpio spleen.


Asunto(s)
Carpas , Proteínas de Peces , Gosipol , MicroARNs , Factor 88 de Diferenciación Mieloide , Transducción de Señal , Animales , Carpas/inmunología , Carpas/genética , MicroARNs/genética , MicroARNs/metabolismo , Gosipol/farmacología , Gosipol/administración & dosificación , Transducción de Señal/efectos de los fármacos , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/metabolismo , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/genética
14.
Plants (Basel) ; 13(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38999577

RESUMEN

Fungi as heterotrophs are key participants in the decomposition of organic materials and the transformation of nutrients in agroecosystems. Ditch-buried straw return as a novel conservation management strategy can improve soil fertility and alter hydrothermal processes. However, how ditch-buried straw return strategies affect the soil fungal community is still unclear. Herein, a 7-year field trial was conducted to test the influences of burial depth (0, 10, 20, 30, and 40 cm) and the amount of ditch-buried straw (half, full, double) on the diversity, composition, and predicted functions of a soil fungal community, as well as the activities of carbon-degraded enzymes. Under the full amount of straw burial, the abundance of phylum Ascomycota was 7.5% higher as compared to other burial amount treatments. This further increased the activity of cellobiohydrolase by 32%, as revealed by the positive correlation between Ascomycota and cellobiohydrolase. With deeper straw burial, however, the abundance of Ascomycota and ß-D-glucopyranoside activity decreased. Moreover, genus Alternaria and Fusarium increased while Mortierella decreased with straw burial amount and depth. FUNgild prediction showed that plant fungal pathogens were 1- to 2-fold higher, whilst arbuscular mycorrhizal fungi were 64% lower under straw buried with double the amount and at a depth of 40 cm. Collectively, these findings suggest that ditch-buried straw return with a full amount and buried at a depth less than 30 cm could improve soil nutrient cycles and health and may be beneficial to subsequent crop production.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38948962

RESUMEN

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

16.
Dalton Trans ; 53(29): 12107-12118, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38978469

RESUMEN

As the development of aluminum-ion batteries is still in its infancy, researchers are still dedicated to exploring suitable host materials and investigating their aluminum intercalation behaviours. Here, a series of cyanido-bridged chain compounds with the formula {[FeIII(Tp)(CN)3]2[MII(H2O)2]}n (M = Ni, Co, Mn, Zn, Cu) are studied as cathode electrodes for aluminum-ion batteries with [EMIm]Cl-AlCl3 (1-ethyl-3-methylimidazolium chloride-AlCl3) ionic liquid as the electrolyte. The electrochemical properties suggested Fe3+/Fe2+ to be the redox-active couple during the aluminum intercalation and deintercalation processes of these compounds, and the observed maximum specific capacity obtained by the Fe-Co compound is 200 mA h g-1 despite the rapid specific capacity fading. To gain a deeper understanding of the capacity decay suffered by these compounds, further investigation was conducted to explore the evolution of compounds during the electrochemical measurements. It has been attributed to the following reasons: 1. thermodynamic instability results in the transformation/damage of two of the chain structures (for the Fe-Ni and Fe-Co compounds) during heat treatment on electrodes, a crucial step in electrode preparation; 2. the acidic nature of the electrolyte triggers the destruction of the chain structure, with the appearance of partial reduction of Fe3+ to Fe2+, and a new interaction of the cyano group with aluminum; 3. the high charge density of inserted Al ions makes the chain structure suffer from structural damage during both the charging and discharging processes. The progressive accumulation of trapped intercalated ions hampers their involvement in the reaction, consequently decreasing electrochemical reversibility.

17.
Oncologist ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39045652

RESUMEN

BACKGROUND: Neoadjuvant treatment has been developed as a systematic approach for patients with early breast cancer and has resulted in improved breast-conserving rate and survival. However, identifying treatment-sensitive patients at the early phase of therapy remains a problem, hampering disease management and raising the possibility of disease progression during treatment. METHODS: In this retrospective analysis, we collected 2-deoxy-2-[F-18] fluoro-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) images of primary tumor sites and axillary areas and reciprocal clinical pathological data from 121 patients who underwent neoadjuvant treatment and surgery in our center. The univariate and multivariate logistic regression analyses were performed to investigate features associated with pathological complete response (pCR). An 18F-FDG PET/CT-based prediction model was trained, and the performance was evaluated by receiver operating characteristic curves (ROC). RESULTS: The maximum standard uptake values (SUVmax) of 18F-FDG PET/CT were a powerful indicator of tumor status. The SUVmax values of axillary areas were closely related to metastatic lymph node counts (R = 0.62). Moreover, the early SUVmax reduction rates (between baseline and second cycle of neoadjuvant treatment) were statistically different between pCR and non-pCR patients. The early SUVmax reduction rates-based model showed great ability to predict pCR (AUC = 0.89), with all molecular subtypes (HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2-) considered. CONCLUSION: Our research proved that the SUVmax reduction rate of 18F-FDG PET/CT contributed to the early prediction of pCR, providing rationales for utilizing PET/CT in NAT in the future.

18.
Front Pharmacol ; 15: 1407140, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045046

RESUMEN

Nandina domestica: Thunb. is a traditional Chinese herbal drug that has long been used in China and Japan for the treatment of colds, fevers, asthma, chronic bronchitis, conjunctivitis, whooping cough, pharyngeal tumors, etc. Published data have reported at least 366 constituents from N. domestica, including alkaloids, flavonoids, lignans, terpenoids, phenolic acids and their derivatives, fatty acids, and others. Of these, the isoquinoline alkaloids are considered characteristic markers for N. domestica. These alkaloids also showed the most promising bioactivities. The crude extracts or semi-purified constituents of N. domestica exhibit a variety of activities, including antitumor, dermatological, anti-inflammatory, antioxidant, antimicrobial, and detoxification activities, as well as effects on respiratory system, etc. The fruit is considered poisonous when eaten raw, with nausea, vomiting, diarrhea, and abdominal pain as side effects after ingestion. Most traditional uses are supported by biological activities demonstrated in modern experimental studies, suggesting a potential medicinal value of N. domestica. However, more information is needed on its mechanisms of activity, pharmacokinetic profile of the constituents, and its safety and efficacy profile in humans.

19.
Multivariate Behav Res ; : 1-29, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997153

RESUMEN

Missingness in intensive longitudinal data triggered by latent factors constitute one type of nonignorable missingness that can generate simultaneous missingness across multiple items on each measurement occasion. To address this issue, we propose a multiple imputation (MI) strategy called MI-FS, which incorporates factor scores, lag/lead variables, and missing data indicators into the imputation model. In the context of process factor analysis (PFA), we conducted a Monte Carlo simulation study to compare the performance of MI-FS to listwise deletion (LD), MI with manifest variables (MI-MV, which implements MI on both dependent variables and covariates), and partial MI with MVs (PMI-MV, which implements MI on covariates and handles missing dependent variables via full-information maximum likelihood) under different conditions. Across conditions, we found MI-based methods overall outperformed the LD; the MI-FS approach yielded lower root mean square errors (RMSEs) and higher coverage rates for auto-regression (AR) parameters compared to MI-MV; and the PMI-MV and MI-MV approaches yielded higher coverage rates for most parameters except AR parameters compared to MI-FS. These approaches were also compared using an empirical example investigating the relationships between negative affect and perceived stress over time. Recommendations on when and how to incorporate factor scores into MI processes were discussed.

20.
Opt Express ; 32(12): 21577-21593, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38859508

RESUMEN

Phase measuring deflectometry (PMD) is a key measurement technology for specular surfaces form measurement. Compared with conventional PMD techniques, the near optical coaxial PMD (NCPMD) can achieve compact configuration, light weight and reducing measurement error caused by shadows of the surface structures through utilizing a plate beamsplitter. However, the introduction of the plate beamsplitter will affect the measurement accuracy of the NCPMD system. The refraction of the plate beamsplitter needs to be considered. In this work, a virtual system of NCPMD was established, and an error model of the NCPMD system by considering the refraction influence of the plate beamsplitter was presented to analyze the shape reconstruction error caused by the plate beamsplitter. Moreover, the calibration method of the beamsplitter and the ray tracing algorithm to achieve error compensation of the beamsplitter were proposed. The proposed error compensation method can effectively improve the measurement accuracy of NCPMD system which has been confirmed by surface measurement experiments.

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