43 research outputs found
ChemInform Abstract: Highly Enantioselective Nickel‐Catalyzed Intramolecular Reductive Cyclization of Alkynones.
No full textMechanism of miR-20b-5p targeting HIF-1α in regulating trophoblast function in recurrent spontaneous abortion
No full textAbstract Objective Recurrent spontaneous abortion (RSA) is a major pregnancy complication with unclear pathogenesis. This study aims to investigate the role of miR-20b-5p and its downstream target HIF-1α in trophoblast function and RSA pathogenesis. Methods Placental villous tissues from uRSA patients and healthy pregnant women were collected to assess trophoblast migration, invasion, apoptosis, and placental angiogenesis. The expression levels of miR-20b-5p and HIF-1α were analyzed using qPCR, Western blot, and immunohistochemistry. HTR-8/SVneo cells were transfected with miR-20b-5p mimics, si-miR-20b-5p, and si-HIF-1α to evaluate their effects on trophoblast function. Luciferase reporter assays were performed to confirm the regulatory relationship between miR-20b-5p and HIF-1α. Results Trophoblast cells isolated from uRSA patients exhibited impaired trophoblast invasion and increased trophoblast apoptosis, accompanied by increased trophoblast apoptosis. miR-20b-5p was significantly upregulated, whereas HIF-1α expression was downregulated in uRSA placental tissues. Overexpression of miR-20b-5p inhibited trophoblast migration, invasion, and endothelial-like differentiation, while its knockdown enhanced these functions. HIF-1α was identified as a direct target of miR-20b-5p, and its knockdown partially reversed the effects of miR-20b-5p inhibition. Conclusion miR-20b-5p negatively regulates trophoblast function by targeting HIF-1α, contributing to trophoblast dysfunction and RSA pathogenesis. The miR-20b-5p/HIF-1α axis may serve as a potential therapeutic target for RSA
Preliminary Analysis of Cervical Cancer Immunotherapy
No full textCervical cancer is one of the most common gynecologically malignancies worldwide. Although vaccine and cervical cancer screening including human papillomavirus testing, cytology testing, and colposcopy have developed rapidly in recent years, effectively reducing cervical cancer mortality, cervical cancer remains a malignancy with higher female fatality rates worldwide and has a high risk for socioeconomically disadvantaged groups. The combination of platinum-paclitaxel and chemotherapy, possibly with the addition of bevacizumab, is currently the treatment of choice for advanced cervical cancer, but it only has remission purposes. Therefore, new therapeutic strategies are needed for both locally advanced and metastatic cervical cancer. Here, we make a preliminary analysis of cervical cancer immunotherapy
Table1_Prognostic value of SOX9 in cervical cancer: Bioinformatics and experimental approaches.XLSX
No full textAmong gynecological cancers, cervical cancer is a common malignancy and remains the leading cause of cancer-related death for women. However, the exact molecular pathogenesis of cervical cancer is not known. Hence, understanding the molecular mechanisms underlying cervical cancer pathogenesis will aid in the development of effective treatment modalities. In this research, we attempted to discern candidate biomarkers for cervical cancer by using multiple bioinformatics approaches. First, we performed differential expression analysis based on cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas database, then used differentially expressed genes for weighted gene co-expression network construction to find the most relevant gene module for cervical cancer. Next, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the module genes, followed by using protein–protein interaction network analysis and Cytoscape to find the key gene. Finally, we validated the key gene by using multiple online sites and experimental methods. Through weighted gene co-expression network analysis, we found the turquoise module was the highest correlated module with cervical cancer diagnosis. The biological process of the module genes focused on cell proliferation, cell adhesion, and protein binding processes, while the Kyoto Encyclopedia of Genes and Genomes pathway of the module significantly enriched pathways related to cancer and cell circle. Among the module genes, SOX9 was identified as the hub gene, and its expression was associated with cervical cancer prognosis. We found the expression of SOX9 correlates with cancer-associated fibroblast immune infiltration in immune cells by Timer2.0. Furthermore, cancer-associated fibroblast infiltration is linked to cervical cancer patients’ prognosis. Compared to those in normal adjacent, immunohistochemical and real-time quantitative polymerase chain reaction (qPCR) showed that the protein and mRNA expression of SOX9 in cervical cancer were higher. Therefore, the SOX9 gene acts as an oncogene in cervical cancer, interactive with immune infiltration of cancer-associated fibroblasts, thereby affecting the prognosis of patients with cervical cancer.</p
CT-based radiomics combined with clinical features for invasiveness prediction and pathological subtypes classification of subsolid pulmonary nodules
No full textPurpose: To construct optimal models for predicting the invasiveness and pathological subtypes of subsolid nodules (SSNs) based on CT radiomics and clinical features. Materials and Methods: This study was a retrospective study involving two centers. A total of 316 patients with 353 SSNs confirmed as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) were included from January 2019 to February 2023. Models based on CT radiomics and clinical features were constructed for classification of AAH/AIS and MIA, MIA and IAC, as well as lepidic-predominant adenocarcinoma (LPA) and acinar-predominant adenocarcinoma (APA). Receiver operating characteristic (ROC) curve was used to evaluate the model performance. Finally, the nomograms based on the optimal models were established. Results: The nomogram based on the combined model (AAH/AIS versus MIA) consisting of lobulation, the GGN-vessel relationship, diameter, CT value, consolidation tumor ratio (CTR) and rad-score performed the best (AUC=0.841), while age, CT value, CTR and rad-score were the significant features for distinguishing MIA from IAC, the nomogram based on these features performed the best (AUC=0.878). There were no significant differences in clinical features between LPA and APA, while the radiomics model based on rad-score showed good performance for distinguishing LPA from APA (AUC=0.926). Conclusions: The nomograms based on radiomics and clinical features could predict the invasiveness of SSNs accurately. Moreover, radiomics models showed good performance in distinguishing LPA from APA
Knock-In Mice with Myo3a Y137C Mutation Displayed Progressive Hearing Loss and Hair Cell Degeneration in the Inner Ear
No full textMyo3a is expressed in cochlear hair cells and retinal cells and is responsible for human recessive hereditary nonsyndromic deafness (DFNB30). To investigate the mechanism of DFNB30-type deafness, we established a mouse model of Myo3a kinase domain Y137C mutation by using CRISPR/Cas9 system. No difference in hearing between 2-month-old Myo3a mutant mice and wild-type mice was observed. The hearing threshold of the ≥6-month-old mutant mice was significantly elevated compared with that of the wild-type mice. We observed degeneration in the inner ear hair cells of 6-month-old Myo3a mutant mice, and the degeneration became more severe at the age of 12 months. We also found structural abnormality in the cochlear hair cell stereocilia. Our results showed that Myo3a is essential for normal hearing by maintaining the intact structure of hair cell stereocilia, and the kinase domain plays a critical role in the normal functions of Myo3a. This mouse line is an excellent model for studying DFNB30-type deafness in humans
Table_1_Primary Malignant Melanoma of the Cervix: An Integrated Analysis of Case Reports and Series.docx
No full textMelanoma, also known as malignant melanoma, is a type of malignant tumour that originates from melanocytes in the basal layer of the epidermis. Primary malignant melanomas of the female genital tract are rare. Similarly, primary malignant melanoma of cervix, which originates from cervical melanocytes, is an extremely rare disease and the second most common type of female melanoma in women aged between 15 to 44 years worldwide. To date, primary malignant melanoma of the cervix is characterized by poor patient prognosis and little consensus exists regarding the best treatment therapy. The situation is worsened by lack of clinical studies with large samples. Notably, surgery remains the preferred treatment option for patients with primary malignant melanomas of the cervix. Current treatments are based on Federation International of Gynecology and Obstetrics(2018) staging with reference to National Comprehensive Cancer Network guidelines. This study is in order to find a more suitable treatment modality for primary malignant melanoma of cervix. Therefore, we first conducted an integrated analysis of case reports and series to assess the impact of various factors on the prognosis of such patients. In summary, this is the first pooled analysis including 149 cases of primary cervical melanoma. We found that patients who underwent radical hysterectomy-based surgery, those with non-metastatic lymph nodes and those who underwent lymphadenectomy had significantly higher survival rates. In patients who had RH-based surgery, survival rates at the 24m time point of those who did not add other treatments was higher than those who did, but for those who had total hysterectomy-based surgery, the addition of other treatments to prolong median survival may be considered. In the overall analysis, age and lymphadenectomy were associated with increased and reduced risk of death in these patients, respectively. Although there is no statistical difference, stage III&IV, TAH, lymphatic metastases increase the risk of death; whereas radical hysterectomy was associated with reduced risk of death. In the subgroup analysis, for patients who have undergone radical hysterectomy-based surgery, lymphadenectomy reduces the risk of death, while lymphatic metastases and complementary other treatments increase the risk of death. For patients who have undergone total hysterectomy-based surgery, complementary treatment reduces the risk of death. In conclusion, via summarizing previous reports, the recommended treatment procedure for PMMC are radical hysterectomy and lymphadenectomy. The addition of other treatment options for patients who undergoing RH-based surgery need further study.</p
Table2_Prognostic value of SOX9 in cervical cancer: Bioinformatics and experimental approaches.docx
No full textAmong gynecological cancers, cervical cancer is a common malignancy and remains the leading cause of cancer-related death for women. However, the exact molecular pathogenesis of cervical cancer is not known. Hence, understanding the molecular mechanisms underlying cervical cancer pathogenesis will aid in the development of effective treatment modalities. In this research, we attempted to discern candidate biomarkers for cervical cancer by using multiple bioinformatics approaches. First, we performed differential expression analysis based on cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas database, then used differentially expressed genes for weighted gene co-expression network construction to find the most relevant gene module for cervical cancer. Next, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the module genes, followed by using protein–protein interaction network analysis and Cytoscape to find the key gene. Finally, we validated the key gene by using multiple online sites and experimental methods. Through weighted gene co-expression network analysis, we found the turquoise module was the highest correlated module with cervical cancer diagnosis. The biological process of the module genes focused on cell proliferation, cell adhesion, and protein binding processes, while the Kyoto Encyclopedia of Genes and Genomes pathway of the module significantly enriched pathways related to cancer and cell circle. Among the module genes, SOX9 was identified as the hub gene, and its expression was associated with cervical cancer prognosis. We found the expression of SOX9 correlates with cancer-associated fibroblast immune infiltration in immune cells by Timer2.0. Furthermore, cancer-associated fibroblast infiltration is linked to cervical cancer patients’ prognosis. Compared to those in normal adjacent, immunohistochemical and real-time quantitative polymerase chain reaction (qPCR) showed that the protein and mRNA expression of SOX9 in cervical cancer were higher. Therefore, the SOX9 gene acts as an oncogene in cervical cancer, interactive with immune infiltration of cancer-associated fibroblasts, thereby affecting the prognosis of patients with cervical cancer.</p
Transition-metal-free arylation of benzoxazoles with aryl nitriles
No full textTransition-metal-free arylation of benzoxazoles with aryl nitriles has been developed to afford important 2-aryl benzoxazoles under simple reaction conditions.</p
