Defect Engineering Simultaneously Regulating Exciton Dissociation in Carbon Nitride and Local Electron Density in Pt Single Atoms Toward Highly Efficient Photocatalytic Hydrogen Production.

The high exciton binding energy (Eb) and sluggish surface reaction kinetics have severely limited the photocatalytic hydrogen production activity of carbon nitride (CN). Herein, a hybrid system consisting of nitrogen defects and Pt single atoms is constructed through a facile self-assembly and photodeposition strategy. Due to the acceleration of exciton dissociation and regulation of local electron density of Pt single atoms along with the introduction of nitrogen defects, the optimized Pt-MCT-3 exhibits a hydrogen production rate of 172.0 µmol h-1 (λ ≥ 420 nm), ≈41 times higher than pristine CN. The apparent quantum yield for the hydrogen production is determined to be 27.1% at 420 nm. The experimental characterizations and theoretical calculations demonstrate that the nitrogen defects act as the electron traps for the exciton dissociation, resulting in a decrease of Eb from 86.92 to 43.20 meV. Simultaneously, the stronger interaction between neighboring nitrogen defects and Pt single atoms directionally drives free electrons to aggregate around Pt single atoms, and tailors the d-band electrons of Pt, forming a moderate binding strength between Pt atoms and H* intermediates.

Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers.

BACKGROUND: The development of endometrial cancer (EC) is closely related to the abnormal activation of the estrogen signaling pathway. Effective diagnostic markers are important for the early detection and treatment of EC. METHOD: We downloaded single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) data of EC from public databases. Enrichment scores were calculated for EC cell subpopulations using the "AddModuleScore" function and the AUCell package, respectively. Six predictive models were constructed, including logistic regression (LR), Gaussian naive Bayes (GaussianNB), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and neural network (NK). Subsequently, receiver-operating characteristics with areas under the curves (AUCs) were used to assess the robustness of the predictive model. RESULT: We classified EC cell coaggregation into six cell clusters, of which the epithelial, fibroblast and endothelial cell clusters had higher estrogen signaling pathway activity. We founded the epithelial cell subtype Epi cluster1, the fibroblast cell subtype Fib cluster3, and the endothelial cell subtype Endo cluster3 all showed early activation levels of estrogen response. Based on EC cell subtypes, estrogen-responsive early genes, and genes encoding Stage I and para-cancer differentially expressed proteins in EC patients, a total of 24 early diagnostic markers were identified. The AUCs values of all six classifiers were higher than 0.95, which indicates that the early diagnostic markers we screened have superior robustness across different classification algorithms. CONCLUSION: Our study elucidates the potential biological mechanism of EC response to estrogen at single-cell resolution, which provides a new direction for early diagnosis of EC.

Systematic Analysis of Tumor Microenvironment Patterns and Oxidative Stress Characteristics of Endometrial Carcinoma Mediated by 5-Methylcytosine Regulators.

As a widely distributed RNA methylation modification, m5C is involved in the regulation of tumorigenesis. Nevertheless, its fundamental process is not clear. This research sought to examine the genetic properties of the 5-methylcytosine (m5C) regulator in endometrial carcinoma, as well as the prognostic significance and impact of m5C regulators on oxidative stress. Therefore, the TCGA-UCEC data set was used to explore the characteristics of 17 RNAm5C-related genes in the transcriptome, genome, and regulatory network. The subtypes of RNAm5C in UCEC were identified based on the expression levels of 17 RNAm5C-related genes. The prognosis of RNAm5C-2 was significantly better than that of RNAm5C-1. Then, we examined the differences (variations) across various subtypes in terms of immune cell infiltration (ICI) as well as the expression of immune-related signal markers. The findings demonstrated that there were distinct variations in the infiltration level of immune cells in each subtype, which may be the reason for the differences in the prognosis of each subtype. In addition, the differentially expressed genes (DEGs) among RNAm5C subtypes of different UCEC tumors were identified, and the DEGs significant for survival were screened. After obtaining 34 prognostic genes, the dimensionality was reduced to construct an RNA methylation score (RS). As per the findings, RS is a more accurate marker for determining the prognosis for patients with endometrial cancer. The RS was used to categorize UCEC tumor samples, and these results led to the formation of high-score and low-score groups. The patients in the group with a high-RNA methylation score exhibited a survival time that was considerably longer in contrast with those in the group with a low-RNA methylation score. The capacity of RS to predict whether or not immunotherapy would be beneficial was explored further. In the group with a high-RNA methylation score, the objective response rate to the anti-PD-L1 therapy was substantially greater compared to that observed in the subgroup with a low-RNA methylation score. Additionally, there were variations across various RS groups in terms of clinical features, tumor mutation burden, and the infiltration level of immune cells. After binary tree analysis and PCR verification of 34 prognostic genes, it is finally found that the six genes of MAGOH3P, TRBJ2_3, YTHDF1P1, RP11_323D18.5, RP11_405M12.2, and ADAM30 are significantly overexpressed in cancer tissues. These genes can be used as potential biomarkers of endometrial cancer and provide data support for precise immunotherapy in UCEC tumors.

Construction of Molecular Subtype and Prognosis Prediction Model of Osteosarcoma Based on Aging-Related Genes.

Background: Osteosarcoma (OS) is a rare form of malignant bone cancer that is usually detected in young adults and adolescents. This disease shows a poor prognosis owing to its metastatic status and resistance to chemotherapy. Hence, it is necessary to design a risk model that can successfully forecast the OS prognosis in patients. Methods: The researchers retrieved the RNA sequencing data and follow-up clinical data related to OS patients from the TARGET and GEO databases, respectively. The coxph function in R software was used for carrying out the Univariate Cox regression analysis for deriving the aging-based genes related sto the OS prognosis. The researchers conducted consistency clustering using the ConcensusClusterPlus R package. The R software package ESTIMATE, MCPcounter, and GSVA packages were used for assessing the immune scores of various subtypes using the ssGSEA technique, respectively. The Univariate Cox and Lasso regression analyses were used for screening and developing a risk model. The ROC curves were constructed, using the pROC package. The performance of their developed risk model and designed survival curve was conducted, with the help of the Survminer package. Results: The OS patients were classified into 2 categories, as per the aging-related genes. The results revealed that the Cluster 1 patients showed a better prognosis than the Cluster 2 patients. Both clusters showed different immune microenvironments. Additional screening of the prognosis-associated genes revealed the presence of 5 genes, i.e., ERCC4, GPX4, EPS8, TERT, and STAT5A, and these data were used for developing the risk model. This risk model categorized the training set samples into the high- and low-risk groups. The patients classified into the high-risk group showed a poor OS prognosis compared to the low-risk patients. The researchers verified the reliability and robustness of the designed 5-gene signature using the internal and external datasets. This risk model was able to effectively predict the prognosis even in the samples having differing clinical features. Compared with other models, the 5- gene model performs better in predicting the risk of osteosarcoma. Conclusion: The 5-gene signature developed by the researchers in this study could be effectively used for forecasting the OS prognosis in patients.

Identification of an immune checkpoint gene signature that accurately predicts prognosis and immunotherapy response in endometrial carcinoma.

In this study, we performed a bioinformatics analysis to identify immune checkpoint genes (ICGs) associated with prognosis and the immunotherapeutic response in endometrial carcinoma (EC) patients. We classified 47 ICGs into high, medium, and low expression groups by performing RNA-sequencing data analysis of EC patient samples from The Cancer Genome Atlas (n = 521) and GSE77688 (n = 88) datasets. Univariate Cox regression analysis showed that seven ICGs (VTCN1, TNFRSF18, TNFRSF14, TNFRSF4, CD40LG, TMIGD2, and BTLA) were associated with prognosis in EC patients. Spearman correlation analysis showed that prognosis-related ICGs correlated positively with immunotherapy response factors, including tumor mutation burden (TMB), mismatch repair gene mutations, neoantigens, clinical stages, and adaptive immune resistance pathway genes. We identified a prognostic gene signature of four ICGs (IDO1, CD274, CTLA4, and TNFRSF14) that accurately predicted survival outcomes of EC patients. TIMER database and Kaplan-Meier survival analysis showed that OS among EC patients with low TNFRSF14 expression was significantly shorter than among those with high TNFRSF14 expression. In vitro experiments showed that TNFRSF14 silencing increased the migration and invasiveness of EC cells by promoting epithelial-mesenchymal transition (EMT). Collectively, these findings reveal an immune checkpoint gene signature that accurately predicts survival outcomes and immunotherapeutic responses in EC patients.

Efficacy of infection control pathway in reducing postoperative infections in patients undergoing neurosurgery.

INTRODUCTION: The environment of the operating room (OR) is closely related to the postoperative complications of patients, and it is necessary to study, to what extent, the stringent management of the OR can reduce postoperative complications. METHODOLOGY: 426 patients who underwent surgery between January 2016 and December 2017 were selected from two class-100 laminar flow ORs of equivalent area, and were divided into an experimental group and a control group. RESULTS: The experimental group had significantly lower total air-borne bacterial count in the OR than the control group 10 minutes before surgery (6.21 ± 4.14 vs. 11.58 ± 5.36 CFU/cm3), 10 minutes (15.67 ± 6.21 vs. 20.83 ± 5.78 CFU/cm3), 30 minutes (27.34 ± 8.18 vs. 39.56 ± 7.86 CFU/cm3) and 60 minutes (43.62 ± 7.66 vs. 51.63 ± 8.43 CFU/cm3) into surgery, and at the end of surgery (57.34 ± 7.67 vs. 69.33 ± 9.41 CFU/cm3) (all p < 0.05). The incidence rates of increased body temperature and leukocyte count 3 days post-surgery, and the duration of antibiotic therapy and hospital stay were significantly reduced in the experimental group compared to the control group (all p < 0.05). Furthermore, the total number of pathogens in the incision at 2 hours into surgery was also significantly lower in the experimental group than in the control group (p < 0.05). CONCLUSION: Stringent application of the infection control pathway is an efficacious measure for improving the air cleanliness of the neurosurgery OR, decreasing the incidence rates of postoperative complications and infection, as well as controlling pathogen transmission.

Knockdown of Long Noncoding RNA NR_026689 Inhibits Proliferation and Invasion and Increases Apoptosis in Ovarian Carcinoma HO-8910PM Cells.

Ovarian cancer is one of the leading causes of gynecological cancer-related deaths worldwide. We investigated the role of a newly discovered long noncoding RNA, NR_026689, in cell proliferation, metastasis, and apoptosis in ovarian cancer cells. Our results showed that NR_026689 was overexpressed in both clinical ovarian cancer patients and cultured ovarian cancer cells. Knockdown of NR_026689 in HO-8910PM cells significantly decreased the cell proliferative rate and the ability to form colonies. Transwell assays revealed that depletion of NR_026689 suppressed cell migration ability by 68% and cell invasive capacity by 71% in HO-8910PM cells. Moreover, specific shRNAs against NR_026689 notably promoted cell apoptosis in HO-8910PM cells by upregulating the expression of proapoptotic proteins, including caspase 3, caspase 9, cytochrome C, and PARP. Our study suggests an oncogenic potential of NR_026689 in ovarian cancer and might provide novel clues for the diagnosis and treatment of ovarian cancer in the clinic.

The differential expression of OCT4 isoforms in cervical carcinoma.

OCT4 is a transcription factor involved in maintaining stem cell phenotype and pluripotential. However, it remains unclear the expression pattern and biological function of OCT4 isoforms in cervical cancer. Here, we reported that both nuclear OCT4A and cytoplasmic OCT4B were overexpressed in CC. OCT4A was responsible for self-renewal of cervical cancer stem-like cells (CCSCs). Furthermore, OCT4B overexpression in SiHa cervical cancer cell line significantly increased cell proliferation and tumorigenesis by inhibiting apoptosis. Moreover, OCT4B enhanced angiogenesis by the upregulation of CD34, VEGF, HIF-1α and IL-6, and promoted tumor cell mobility to the surrounding tissue by the upregulation of MMP2 and MMP9, and the induction of epithelial-mesenchymal transition (EMT). In conclusion, nuclear OCT4A may serve as a marker of CCSCs and the driving force for cervical cancer metastasis and recurrence, while cytoplasmic OCT4B may cooperate with OCT4A to regulate the progression of cervical cancer through inducing angiogenesis and EMT.

SPARC interacts with AMPK and regulates GLUT4 expression.

AMP-activated protein kinase (AMPK) is a critical regulator of glucose metabolism. To elucidate the biochemical mechanisms by which AMPK regulates glucose and fat metabolism, we conducted a yeast two-hybrid screen to identify its interacting partners. A yeast two-hybrid system was used to screen a mouse embryo cDNA library for proteins able to bind mouse AMPK alpha 1. We also demonstrated an endogenous interaction between AMPK alpha 1 and its interacting partner by co-immunoprecipitation of the endogenous proteins using specific antibodies in HepG2 cells, and in rat kidney, liver, skeletal muscle, and fat tissue. We show that secreted protein acidic and rich in cysteine (SPARC) is an AMPK-interacting protein, and the two proteins enhance each other. AMPK activation increases SPARC expression, and knockdown of AMPK to inhibit endogenous AMPK expression reduces SPARC protein levels. On the other hand, SPARC siRNA reduces AICAR-stimulated AMPK phosphorylation. SPARC affects AMPK-mediated glucose metabolism through regulation of Glut4 expression in L6 myocytes. Our findings suggest that SPARC may be involved in regulating glucose metabolism via AMPK activation. These results provide a starting point for efforts to clarify the relationship between AMPK and SPARC, and deepen our understanding of their roles in fat and glucose metabolism.

Effects of ipriflavone on postmenopausal syndrome and osteoporosis.

OBJECTIVE: To investigate the therapeutic effects of ipriflavone on postmenopausal syndrome and osteoporosis in women. METHODS: A randomized and double-blind study was conducted. Sixty postmenopausal women with osteoporosis were chosen and they were randomly divided into three groups: Treatment group I was given oral compound calcium acid chelate and Vitamin AD guttate; treatment group II was given oral compound calcium acid chelate, Vitamin AD guttate and ipriflavone; Control group was given placebo and compound calcium acid chelate. The postmenopausal syndrome, bone mineral density (BMD), and bone biochemical markers were assessed 6 and 12 months after the treatment. RESULTS: In treatment group II, hot flush and ostalgia syndromes were dramatically relieved, BMD and serum calcium level increased markedly and alkaline phosphatase, parathyroid hormone and tartrate-resistant acid phosphatase decreased markedly, comparing with treatment group I and control group (p < 0.05). CONCLUSION: Ipriflavone could inhibit bone resorption and promote bone formation. It is an effective drug for the prevention and treatment to menopausal syndrome and osteoporosis. Ipriflavone could be used as a supplement to estrogen replacement treatment.