Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.419
Filter
1.
Cell Death Dis ; 15(10): 732, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375330

ABSTRACT

Cervical cancer (CCa) patients with lymph node (LN) metastasis face poor prognoses and have limited treatment options. Aberrant N6-methyladenosine (m6A) modification of RNAs are known to promote tumor metastasis, but their role in CCa remains unclear. Our study reveals that HNRNPC, an alternative splicing (AS) factor and m6A reader, increases tumor-related variants through m6A-dependent manner, thereby promoting lymphatic metastasis in CCa. We found that HNRNPC overexpression correlates with lymphatic metastasis and poorer prognoses in CCa patients. Functionally, knocking down HNRNPC markedly inhibited the migration and invasion of several CCa cell lines, while supplementing HNRNPC restored the malignant phenotypes of these cells. Mechanistically, HNRNPC regulates exon skipping of FOXM1 by binding to its m6A-modified motif. Mutating the m6A site on FOXM1 weakened the interaction between HNRNPC and FOXM1 pre-RNA, leading to a reduction in the metastasis-related FOXM1-S variant. In conclusion, our findings demonstrate that m6A-dependent alternative splicing mediated by HNRNPC is essential for lymphatic metastasis in CCa, potentially providing novel clinical markers and therapeutic strategies for patients with advanced CCa.


Subject(s)
Alternative Splicing , Forkhead Box Protein M1 , Heterogeneous-Nuclear Ribonucleoprotein Group C , Lymphatic Metastasis , Uterine Cervical Neoplasms , Humans , Alternative Splicing/genetics , Forkhead Box Protein M1/metabolism , Forkhead Box Protein M1/genetics , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Heterogeneous-Nuclear Ribonucleoprotein Group C/metabolism , Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics , Cell Line, Tumor , Adenosine/analogs & derivatives , Adenosine/metabolism , Mice, Nude , Animals , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Mice , Middle Aged , Mice, Inbred BALB C
4.
Sci Rep ; 14(1): 23741, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39390015

ABSTRACT

Community detection is a critical component of network analysis and a hot topic in social computing. Detecting community structure in dynamic networks has important theoretical and practical implications for understanding the intrinsic function of networks and predicting network behavior. However, the majority of existing dynamic community detection methods adopt shallow models, which have limited ability to excavate complex non-linear structures and tend to generate undesirable community structures. In order to obtain an accurate and robust community structure in dynamic networks, we are inspired by network representation learning and utilize the deep learning to detect evolving communities in dynamic networks. In this paper, we propose a novel dynamic community detection method by fusing Deep Learning and Evolutionary Clustering (DLEC). This work attempts to combine deep learning and evolutionary clustering into a unified framework. First, we propose a matrix construction strategy to fully reveal the inherent community structures via the underlying community memberships. Then, we develop a novel multi-layer deep autoencoder framework that consists of multiple non-linear functions to extract the latent deep representation of the dynamic network. Based on the evolutionary clustering framework, a graph regularization term is introduced to ensure the smoothness of the community evolution. Finally, we employ the K-means clustering algorithm on the low-dimensional network space to obtain the community structure. Extensive experimental results on synthetic and real-world networks show that the proposed DLEC algorithm can effectively detect high-quality communities in dynamic networks.

5.
Front Oncol ; 14: 1443123, 2024.
Article in English | MEDLINE | ID: mdl-39386195

ABSTRACT

Background: Oral leukoplakia (OL) is the most common potentially malignant disease of the oral cavity. In recent years, studies have identified a correlation between the gut microbiota (GM) and oral cancer, in addition, inflammation-related proteins have been reported to play an important role in the development of OL. However, the causal relationship between gut microbiota and OL, as well as whether cytokines play a mediating role, remain unclear. Methods: In this Mendelian randomization (MR) study, the genome-wide association studies (GWAS) (n=18340) of the MiBioGen consortium microbiome was used as exposure data. Genetic variation data related to OL were extracted from the Finngen R9 project (513 cases of OL and 411668 controls). The 91 inflammation-related proteins obtained in the literature serve as potential mediators. Two-sample Mendelian randomization analysis was applied to infer causality using Inverse Variance Weighted (IVW), MR Egger, weighted media, simple mode and weighted mode method. Subsequently, sensitivity analysis was conducted to ensure the robustness of the MR results. In addition, we conducted reverse MR analysis to alleviate reverse causality. Finally, we used mediation analysis to determine the pathway mediated by inflammation-related proteins from the gut microbiota to OL. Results: The five bacterial taxa in the gut microbiota indicate a potential causal relationship with the development of OL. Notably, family Clostridiaceae1 was negatively correlated with the risk of OL development, while genus Dorea, genus Ruminococcus1, genus Senegalimasilia and genus Veillonella were positively associated with the risk of OL development. In addition, this study identified a potential causal relationship between interleukin-10 receptor subunit alpha (IL-10RA), interleukin-18 receptor 1(IL18-R1) and the occurrence of OL. In addition, intermediary analysis indicates that IL18-R1 mediated the pathway between the gut microbiota genus Senegalimasilia and OL. Conclusions: In summary, our research emphasize the complex relationship between gut microbiota, inflammation-related proteins and OL. The identified associations and mediating effects provide new insights into potential therapeutic approaches for targeting the gut microbiota in the management of OL, and contribute to its prevention, diagnosis and treatment.

6.
Front Psychiatry ; 15: 1338481, 2024.
Article in English | MEDLINE | ID: mdl-39328349

ABSTRACT

Introduction: The causality between personality and psychiatric traits and lung cancer (LC) remains unclear. Therefore, we aimed to elucidate the causality between these traits and LC. Methods: Bidirectional two-sample Mendelian randomization (MR) and bibliometric approaches were conducted to estimate the causality between personality (neuroticism, extraversion, agreeableness, conscientiousness, and openness) and psychiatric (schizophrenia, attention-deficit/hyperactivity disorder [ADHD], major depressive disorder, autism spectrum disorder, bipolar disorder, insomnia, and anxiety) traits and LC and its subtypes (lung squamous cell carcinoma, lung adenocarcinoma, and small cell LC). Summary data of these traits were extracted from large datasets (17,375-462,341 participants). Inverse variance weighting was used as the primary MR analysis, with supplementary models, including MR-Egger and weighted medians. Sensitivity analyses were conducted to detect pleiotropy. Bibliometric data were retrieved from the Web of Science Core Collection, Scopus, and PubMed. The main mapping techniques adopted were co-word, collaboration, and citation analyses. Results: Schizophrenia was associated with an increased risk of LC (odds ratio [OR] = 1.077, 95% confidence interval [CI] = 1.030-1.126, P = 0.001). Moreover, LC increased the risk of ADHD (OR = 1.221, 95% CI = 1.096-1.362, P < 0.001). No significant bidirectional associations were observed between other mental traits and LC and its subtypes. Causality, psychiatry, and psychiatric comorbidity are emerging keywords. Research dynamics and landscapes were revealed. Conclusion: This study suggests that schizophrenia is a risk factor for LC and that LC is a risk factor for ADHD. Furthermore, causality, psychiatry, and psychiatric comorbidity have become emerging research trends in related fields.

7.
J Dent Sci ; 19(4): 1972-1982, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39347054

ABSTRACT

Background/purpose: Understanding the relationship between maxillary sinus and posterior root apices is critical in preventing dental treatment complications. This study aimed to analyze and showcase the relationship between the posterior root apices and the maxillary sinus floor, the distance to the buccal cortical bone, and their correlation with age, gender, and sides. Materials and methods: Cone-beam computed tomography images were collected from 94 patients with a total of 478 maxillary posterior teeth and 997 roots. The shortest distance from root apices to the closest border of maxillary sinus and the outer buccal cortical bone margin were measured and grouped for statistical analysis for the differences (P < 0.05). Results: The root apices of maxillary molars and single-rooted second premolars were located closer to the maxillary sinus compared to first premolars (P < 0.01). The buccal root of two-rooted first premolar had the shortest horizontal distance to the buccal cortical bone among all roots (P < 0.01). The lowest position of the maxillary sinus floor was mostly located at the palatal side (P < 0.01) and between the buccal and palatal root apices (P < 0.01) in the maxillary premolars and molars, respectively. Increasing age would lead to longer distances between the root apices and the maxillary sinus (P < 0.01). Additionally, male patients had thicker buccal cortical bone than female patients (P < 0.01). Conclusion: Different tooth positions, age, and gender significantly impact the relationships between root apices and the maxillary sinus and buccal cortical plates, informing patient-centered and individually tailored approaches for more effective and safer surgical endodontic treatment.

8.
Micromachines (Basel) ; 15(9)2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39337732

ABSTRACT

The triboelectric nanogenerator (TENG) has the potential to serve as a high-entropy energy harvester, enabling the self-powered operation of Internet of Things (IoT) devices. True random number generator (TRNG) is a common feature of encryption used in IoT data communication, ensuring the security of transmitted information. The benefits of multiplexing TENG and TRNG in resource-constrained IoT devices are substantial. However, current designs are limited by the usage scenarios and throughput of the TRNG. Specifically, we propose a structurally and environmentally friendly design based on the contact-separation structure, integrating heat fluctuation and charge decay as entropy sources. Furthermore, filtering and differential algorithms are recommended for data processing based on TENG characteristics to enhance randomness. Finally, a TENG-based TRNG is fabricated, and its performance is verified. Test results demonstrate a random number throughput of 25 Mbps with a randomness test pass rate approaching 99%, demonstrating suitability for resource-constrained IoT applications.

9.
Front Nutr ; 11: 1430722, 2024.
Article in English | MEDLINE | ID: mdl-39257604

ABSTRACT

Background: Nutritional support has been identified as a potential intervention for cognitive frailty; however, the association between 25-hydroxyvitamin D [25-(OH)D], vitamin B12, and cognitive frailty remains ambiguous. Methods: This study utilized data from two cycles (2011-2012, 2013-2014) of the National Health and Nutrition Examination Survey (NHANES) to investigate this relationship. The researchers constructed a 41-item frailty index encompassing diverse aspects of physical functioning, psychological evaluation, and medical conditions, and evaluated each participant individually. The study utilized Spearman's rank correlation coefficient and univariate ordered logistic regression to assess the relationships between variables and cognitive frailty. Recursive feature elimination and cross-validation methods were employed to identify the most influential variables for building and optimizing multivariate ordered logistic regression models. Subgroup analyses and interaction tests were further conducted to validate the identified correlations. Results: The findings of this study confirm a negative linear correlation between 25-(OH)D levels and cognitive frailty in older adults. Specifically, a one-unit increase in 25-(OH)D levels was associated with a 12% reduction in the risk of cognitive frailty. The result was further supported by subgroup analyses and interaction tests. Conclusion: The existence of a negatively correlated linear association between 25-(OH)D levels and cognitive frailty in older adults is plausible, but further rigorously designed longitudinal studies are necessary to validate this relationship.

10.
Medicine (Baltimore) ; 103(22): e38432, 2024 May 31.
Article in English | MEDLINE | ID: mdl-39259061

ABSTRACT

Acute myeloid leukemia (AML), an uncommonly low 5-year survival and high mortality rate, is a potentially catastrophic diagnosed subtype of leukemia. The development of new prognostic markers is urgently needed to guide its treatment. Necroptosis is a newly defined biological process for regulating cell death, and previous studies have confirmed that the abnormality of the physical function can lead to multiple malignancies. Here, we performed necroptosis-related genes (NRGs) to build a predictive model in the Cancer Genome Atlas (TCGA)-AML patients, thus exploring the correlation between the NRG prognosis signature (NRG score) of this model and immune infiltration, pathway activity, clinical features, and immunotherapy. Besides, we computed the statistical measure Spearman rank correlation between the NRG score and the Log IC50 values of therapeutic agents. Subsequently, we divided the TCGA-AML cohort into 2 groups, one with high scores and the other with low scores depending on the model score. AML patients with high NRG scores exhibited a lower estimated overall survival (OS) rate than those with low NRG scores, which was confirmed in the validation set. The prognostic value of the constructed NRG signature to the AML, independent of other variables, was demonstrated by uni- and multivariate stepwise regression analysis. When comparing the infiltrating states of specialized cells associated with immune system from the 2 groups, B cells naive, Plasma cells, and monocytes represented significant differences among various subgroups of samples. Moreover, the 30 hallmark-related pathways related to necroptosis characteristics were remarkably different between the high/low NRG score groups. And patients showed remarkable NRG score distribution in clinical features of bone marrow lymphocyte, category, and FAB classifications. Besides, we found that the BIRB0796, VX680, Vorinostat, and Axitinib positively related with NRG score, whereas CI. 1040, PD. 0325901, Z.L LNle. CHO, and AZD6244 negatively correlated with the NRG score. These drugs may provide a reference for subsequent treatment.


Subject(s)
Leukemia, Myeloid, Acute , Necroptosis , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/mortality , Prognosis , Necroptosis/genetics , Male , Female , Middle Aged , Biomarkers, Tumor/genetics , Aged , Adult
11.
Environ Pollut ; 362: 124980, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39293651

ABSTRACT

The characteristic of semi-volatility enables persistent organic pollutants (POPs) almost ubiquitous in the environment. There is increasing concern about the potential risks of exposure to POPs due to their lipophilicity and readily bioaccumulation. Lipid droplets (LDs) are highly dynamic lipid storage organelles, alterations of intracellular LDs play a vital role in the progression of many prevalent metabolic diseases, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). This article systematically reviewed the biological processes involved in LDs metabolism, the role of LDs proteins and LDs in metabolic diseases, and summarized updating researches on involvement of POPs in the progression of LDs-related metabolic diseases and potential mechanisms. POPs might change the physiological functions of LDs, also interfere the processes of adipogenesis and lipolysis by altering LDs synthesis, decomposition and function. However, further studies are still needed to explore the underlying mechanism of POPs-induced metabolic diseases, which can offer scientific evidences for metabolic disease prevention.

12.
Bone Joint Res ; 13(9): 497-506, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39278635

ABSTRACT

Aims: Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments. Methods: This retrospective study included 3,814 adult patients who received local treatment - surgery and/or radiotherapy - for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher's exact test, and Kaplan-Meier curve. Results: Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians' experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion: This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs.

13.
bioRxiv ; 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39282325

ABSTRACT

Summary: DNA sequencing is becoming more affordable and faster through advances in high-throughput technologies. This rise in data availability has contributed to the development of novel algorithms to elucidate previously obscure features and led to an increased reliance on complex workflows to integrate such tools into analyses pipelines. To facilitate the analysis of DNA sequencing data, we created metapipeline-DNA, a highly configurable and extensible pipeline. It encompasses a broad range of processing including raw sequencing read alignment and recalibration, variant calling, quality control and subclonal reconstruction. Metapipeline-DNA also contains configuration options to select and tune analyses while being robust to failures. This standardizes and simplifies the ability to analyze large DNA sequencing in both clinical and research settings. Availability: Metapipeline-DNA is an open-source Nextflow pipeline under the GPLv2 license and is freely available at https://github.com/uclahs-cds/metapipeline-DNA.

14.
J Geriatr Cardiol ; 21(8): 791-798, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39308500

ABSTRACT

BACKGROUND: The prevention of coronary artery disease (CAD) faces dual challenges: the aspirin-induced gastrointestinal injury, and the residual cardiovascular risk after statin treatment. Geraniol acetate (Gefarnate) is an anti-ulcer drug. It was reported that geraniol might participate in lipid metabolism through a variety of pathways. The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia. METHODS: In this prospective, open-label, randomized, controlled trial, 69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group, received gefarnate (100 mg/3 times a day) combined with statin and statin alone, respectively. At baseline and after one-month treatment, the levels of plasma triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol were tested. RESULTS: After one-month gefarnate treatment, triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L (P = 0.0018), LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L (P = 0.0004), HDL-C level increased from 0.97 mmol/L to 1.17 mmol/L (P = 0.0228). Based on statin therapy, gefarnate could significantly reduce the plasma triglyceride level (P = 0.0148) and increase the plasma HDL-C level (P = 0.0307). Although the LDL-C and total cholesterol levels tended to decrease, there was no statistically significant difference. CONCLUSIONS: The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia. This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

15.
Food Chem ; 463(Pt 3): 141250, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39305637

ABSTRACT

Myricetin (MYR) is a flavonoid with favorable biological activities. In this study, MYR oxidation products (MYRox) were generated through enzymatic oxidation of MYR using horseradish peroxidase. The results showed enzymatic oxidation enhanced the water solubility and antibacterial activity against Staphylococcus aureus (S. aureus) of MYR. Further experiments showed the antibacterial effects of MYRox were conferred by MYR organic phase oxidation products (MYRoo). Both MYR and MYRoo could disrupt the cell membrane integrity, bind to the genomic DNA, affect protein synthesis and degradation, and alter the ROS levels in S. aureus. However, they exerted these effects with different strengths and ways. Finally, MYR or MYRoo can be used as an inhibitor against S. aureus in the cabbage food system, with MYRoo having better effect. This study demonstrated that enzymatic oxidation is an effective approach to improve the water solubility and antibacterial activity of MYR, enhancing its potential application in food preservation.

16.
Nat Commun ; 15(1): 8013, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39271661

ABSTRACT

Enhancing drought tolerance in crops and understanding the underlying mechanisms have been subject of intense research. The precise function and molecular mechanisms of B-box zinc finger proteins (BBX) remain elusive. Here, we report a natural allele of BBX18 (BBX18TT) that encodes a C-terminal truncated protein. While most wild tomato germplasms contain the BBX18CC allele and show more drought tolerant, modern cultivated tomatoes mostly carry BBX18TT allele and are more drought sensitive. Knockout of BBX18 leads to improved drought tolerance in transgenic plants of cultivated tomato. Ascorbate peroxidase 1 (APX1) is identified as a BBX18-interacting protein that acts as a positive regulator of drought resistance in tomato. Chromatin immunoprecipitation sequencing analyses reveal that BBX18 binds to a unique cis-acting element of the APX1 promoter and represses its gene expression. This study provides insights into the molecular mechanism underlying drought resistance mediated by the BBX18-APX1 module in plants.


Subject(s)
Droughts , Gene Expression Regulation, Plant , Plant Proteins , Plants, Genetically Modified , Solanum lycopersicum , Transcription Factors , Zinc Fingers , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Zinc Fingers/genetics , Promoter Regions, Genetic/genetics , Ascorbate Peroxidases/metabolism , Ascorbate Peroxidases/genetics , Alleles
17.
J Immunother Cancer ; 12(9)2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39237260

ABSTRACT

OBJECTIVE: Pancreatic cancer is an incurable malignant disease with extremely poor prognosis and a complex tumor microenvironment. We sought to characterize the role of Annexin A1 (ANXA1) in pancreatic cancer, including its ability to promote efferocytosis and antitumor immune responses. METHODS: The tumor expression of ANXA1 and cleaved Caspase-3 (c-Casp3) and numbers of tumor-infiltrating CD68+ macrophages in 151 cases of pancreatic cancer were examined by immunohistochemistry and immunofluorescence. The role of ANXA1 in pancreatic cancer was investigated using myeloid-specific ANXA1-knockout mice. The changes in tumor-infiltrating immune cell populations induced by ANXA1 deficiency in macrophages were assessed by single-cell RNA sequencing and flow cytometry. RESULTS: ANXA1 expression in pancreatic cancer patient samples correlated with the number of CD68+ macrophages. The percentage of ANXA1+ tumor-infiltrating macrophages negatively correlated with c-Casp3 expression and was significantly associated with worse survival. In mice, myeloid-specific ANXA1 deficiency inhibited tumor growth and was accompanied by the accumulation of apoptotic cells in pancreatic tumor tissue caused by inhibition of macrophage efferocytosis, which was dependent on cGAS-STING pathway-induced type I interferon signaling. ANXA1 deficiency significantly remodeled the intratumoral lymphocyte and macrophage compartments in tumor-bearing mice by increasing the number of effector T cells and pro-inflammatory macrophages. Furthermore, combination therapy of ANXA1 knockdown with gemcitabine and anti-programmed cell death protein-1 antibody resulted in synergistic inhibition of pancreatic tumor growth. CONCLUSION: This research uncovers a novel role of macrophage ANXA1 in pancreatic cancer. ANXA1-mediated regulation of efferocytosis by tumor-associated macrophages promotes antitumor immune response via STING signaling, suggesting potential treatment strategies for pancreatic cancer.


Subject(s)
Annexin A1 , Macrophages , Membrane Proteins , Nucleotidyltransferases , Pancreatic Neoplasms , Tumor Microenvironment , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Animals , Humans , Mice , Tumor Microenvironment/immunology , Annexin A1/metabolism , Annexin A1/genetics , Macrophages/metabolism , Macrophages/immunology , Nucleotidyltransferases/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , Signal Transduction , Female , Male , Mice, Knockout , Efferocytosis
18.
J Org Chem ; 89(19): 14341-14347, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39292538

ABSTRACT

We developed a mild, rapid process employing AgF and thioamides to produce α,α-difluoromethylene amines efficiently. This method exhibited remarkable tolerance toward various functional groups present in N-sulfonylthioamides, thereby broadening the scope of difluoromethylene sulfonamides through a straightforward approach. Additionally, we applied this approach to synthesize various perfluoroalkyl amines, establishing practical synthetic routes for exploring these compounds in pharmaceutical chemistry and materials science.

19.
Steroids ; 212: 109516, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39313103

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist tert-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with tert-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.

20.
Article in English | MEDLINE | ID: mdl-39324494

ABSTRACT

OBJECTIVE: Supported by remote signal processing techniques and wireless communication technology, remote electronic fetal monitoring (REFM) has emerged as a promising alternative to traditional electronic fetal monitoring (TEFM) in clinical practice. The aim of this study was to evaluate the comparability, accessibility, and clinical utility of REFM in contrast to TEFM. METHODS: This was a multicenter prospective cohort study. A cohort of 2900 pregnant women were enrolled from three medical centers between June 1, 2021 and June 31, 2022. Among them, 800 utilized REFM, with 760 of them completing the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) assessments using the devices for 1 month. The control group comprised 2100 pregnant women who did not use REFM. Additionally, 80 pregnant women concurrently employed both REFM and TEFM, and their respective curve coincidence rates were determined through curve fitting. Primary outcomes encompassed pregnancy outcomes in both groups, average curve coincidence rates between REFM and TEFM, as well as SDS and SAS scores. RESULTS: Among the 760 pregnant women who completed SAS and SDS assessments, their average SAS scores before and after 1 month of REFM usage were 43.09 ± 8.04 and 41.58 ± 6.59, respectively. Concurrently, the average SDS scores before and after 1 month of REFM usage were 45.45 ± 9.60 and 44.80 ± 9.17, respectively. A statistically significant decrease was observed in SAS scores (P = 0.005), whereas no significant difference was noted in SDS scores (P = 0.340). Furthermore, a statistically significant difference in the rate of adverse pregnancy outcomes (neonatal asphyxia) emerged between the two groups, those who employed REFM and those who did not (P = 0.021). In the subset of 80 pregnant women employing both REFM and TEFM, all 80 results showed precise congruence between the two methods. The average coincidence rate was determined to be 79.45% ± 12.64%. CONCLUSION: REFM contributes to improved pregnancy outcomes and exhibits a high level of concordance with TEFM, thereby accurately reflecting the quality of fetal heart monitoring. Additionally, REFM effectively mitigates pregnant women's anxiety. Thus, REFM demonstrates comparability, accessibility, and clinical utility.

SELECTION OF CITATIONS
SEARCH DETAIL