What happens to the osteoporotic bone mesenchymal stem cells? Evidence from RNA sequencing.

Evidence presented that osteoporosis is closely related to the dysfunction of bone mesenchymal stem cells (BMSCs). But most studies are insufficient to reveal what actually happens to the osteoporotic BMSCs. In this study, BMSCs were harvested from ovariectomized and sham-operated rats. After checking the characteristics of rat models and stem cells, the BMSCs were carried out for RNA sequencing. Part of the findings were verified that seven mRNAs (Abi3bp, Aifm3, Ccl11, Cdkn1c, Chst10, Id2, Vcam1) were significantly up-regulated in osteoporotic BMSCs while seven mRNAs (Cep63, Fgfr3, Myc, Omd, Pou2f1, Smarcal1, Timm10b) were down-regulated. In addition, potential miRNA-mRNA and lncRNA-mRNA regulatory networks were illustrated. The changes in osteoporotic BMSCs covered a large set of biological processes, including cell viability, differentiation, immunoreaction, bone repairment and estrogen defect. This study enriched the pathophysiological mechanisms of BMSCs and osteporosis, as well as provided dozens of attractive RNA targets for further treatment.

Managing ecosystem services in oleaginous forests for bioenergy provision and climate change mitigation.

Oleaginous forests provide diverse ecosystem services, including timber, seed yield (a vital feedstock for biodiesel production), and substantial carbon savings. These carbon savings encompass carbon sequestration related to timber growth and carbon savings resulting from substituting fossil fuel with biodiesel. However, oleaginous forests are vulnerable to seed wasp attacks (disservice), which significantly threaten both seed yield and carbon savings. Using an integrated ecological-economic model that includes Faustmann's Land Expectation Value model and a pest damage control model, we aim to understand the intricate relationship among multiple ecosystem services and disservices of oleaginous forests. The results reveal four distinct phases contingent on varying pesticide application rates: the pesticide under-use phase, substitution phase, complementary phase, and over-use phase. Notably, a potential avenue to minimize pest damage is identified during the complementary phase by reducing the optimal rotation age at the expense of decreased carbon sequestration and bioenergy provision, posing a challenge to climate change mitigation. These findings have implications for formulating policies to manage conflicting ecosystem services of energy forests, offering valuable insights into the intersection of sustainable forest management and climate policy.

Autoantibodies against laminin-521 are pathogenic in anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disorder characterized by autoantibodies against GBM components. Evidence from human inherited kidney diseases and animal models suggests that the α, ß, and γ chains of laminin-521 are all essential for maintaining the glomerular filtration barrier. We previously demonstrated that laminin-521 is a novel autoantigen within the GBM and that autoantibodies to laminin-521 are present in about one-third of patients. In the present study, we investigated the pathogenicity of autoantibodies against laminin-521 with clinical and animal studies. Herein, a rare case of anti-GBM disease was reported with circulating autoantibodies binding to laminin-521 but not to the NC1 domains of α1-α5(IV) collagen. Immunoblot identified circulating IgG from this patient bound laminin α5 and γ1 chains. A decrease in antibody levels was associated with improved clinical presentation after plasmapheresis and immunosuppressive treatments. Furthermore, immunization with laminin-521 in female Wistar-Kyoto rats induced crescentic glomerulonephritis with linear IgG deposits along the GBM, complement activation along with infiltration of T cells and macrophages. Lung hemorrhage occurred in 75.0% of the rats and was identified by the presence of erythrocyte infiltrates and hemosiderin-laden macrophages in the lung tissue. Sera and kidney-eluted antibodies from rats immunized with laminin-521 demonstrated specific IgG binding to laminin-521 but not to human α3(IV)NC1, while the opposite was observed in human α3(IV)NC1-immunized rats. Thus, our patient data and animal studies imply a possible independent pathogenic role of autoantibodies against laminin-521 in the development of anti-GBM disease.

Development and validation of a prognostic nomogram model incorporating routine laboratory biomarkers for preoperative patients with endometrial cancer.

BACKGROUND: Some biomarkers collected from routine laboratory tests have shown important value in cancer prognosis. The study aimed to evaluate the prognostic significance of routine laboratory biomarkers in patients with endometrial cancer (EC) and to develop credible prognostic nomogram models for clinical application. METHODS: A total of 727 patients were randomly divided into a training set and a validation set. Cox proportional hazards models were used to evaluate each biomarker's prognostic value, and independent prognostic factors were used to generate overall survival (OS) and progression-free survival (PFS) nomgrams. The efficacy of the nomograms were evaluated by Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, X-tile analysis and Kaplan‒Meier curves. RESULTS: Ten significant biomarkers in multivariate Cox analysis were integrated to develop OS and PFS nomograms. The C-indices of the OS- nomogram in the training and validation sets were 0.885 (95% confidence interval (CI), 0.810-0.960) and 0.850 (95% CI, 0.761-0.939), respectively; those of the PFS- nomogram in the training and validation sets were 0.903 (95% CI, 0.866-0.940) and 0.825 (95% CI, 0.711-0.939), respectively. ROC, DCA and calibration curves showed better clinical application value for the nomograms incorporating routine laboratory biomarkers. X-tile analysis and Kaplan‒Meier curves showed that the nomograms were stable and credible in evaluating patients at different risks. CONCLUSIONS: Nomogram models incorporating routine laboratory biomarkers, including NLR, MLR, fibrinogen, albumin and AB blood type, were demonstrated to be simple, reliable and favourable in predicting the outcomes of patients with EC.

Spatially modulated light harvesting with plasmonic crescent metasurface.

Harvesting light by metallic structures with sharp corners, or the so-called photonic singularities, has exhibit their potential in nanophotonics, sensing, and bio-medical applications. The high-quality light confinement of the light energy mainly relies on the precise preparation of nanoscale photonic singularities. However, the realization of massive photonic singularities still meets the challenges on integration and low-cost mask multiplexing. Here, we show an angle-dependent elevated nanosphere lithography to achieve massive photonic singularities for spatially modulated light harvesting at the near-infrared regime. The photonic geometrical singularity is constructed by the gold crescent array of plasmonic materials. The numerical simulation shows that the light can be localized at the spatially distributed singularities. This phenomenon is verified experimentally through the infrared spectral measurement. Our work provides the possibility to produce integrated light-harvesting devices for numerous optical applications in illumination, display, and enhanced nonlinear excitation.

Wafer-scale plasmonic metal-dielectric-metal structural color featuring high saturation and low angular dependence.

Structural color has been studied through various methods due to its distinguished features of stability, durability, high information storage density and high integration. However, the artificial structural color samples do not exhibit superior performance in color saturation and low angular dependence. Here, we present an approach to acquire additive reflective color based on a metal-dielectric-metal (MDM) stack. The upper layer composed of Ag particles is perforated in a hexagonal arrangement which profits from the dielectric anodic aluminium oxide (AAO) membrane. The size and shape of the Ag particles are getting inhomogeneous as the deposition thickness of the upper layer increasing, which expands the desired absorption range of surface plasmons. The residual non-anodized Al foil serves as a highly reflective substrate for efficient color presenting through the thin-film interference in this plasmonic MDM system. As a result, the color gamut area of this MDM stack is extended 8 times in CIE chromaticity coordinates. Finally, a wafer-scale (diameter of 83 mm) badge of Harbin Engineering University (HEU) with highly saturated colors and a pattern characterized with low angle-dependent property (up to 60°) are presented, which exhibit promising prospects in commercial coloring and imaging.

Gasless endoscopic transaxillary thyroid surgery: CUSUM analysis of a single surgeon's experience from 105 preliminary procedures.

BACKGROUND: We aimed to evaluate the feasibility and oncologic safety of gasless endoscopic transaxillary thyroidectomy (TAT) in patients with thyroid diseases. Improvements in surgical techniques were also reported, and the learning curves of gasless endoscopic TAT were further studied. METHODS: An exact 1:1 matching analysis was performed to compare the technical safety and oncologic outcomes between TAT and conventional open surgery. A questionnaire was designed to evaluate the quality of life of enrolled patients. A cumulative summation analysis was designed for the quantitative estimation of the learning curves. RESULTS: A total of 105 consecutive patients who successfully received endoscopic TAT were retrospectively enrolled in the current study. A standard three-step working space making procedure, an approach that does not free the superficial part of the sternal head of the sternocleidomastoid muscle (SCM, NFSSH) and a "point to line to surface" en bloc procedure utilized in lobectomy with ipsilateral central neck dissection (CND), were introduced in our surgical procedures. The mean operation time in the TAT group was significantly longer than that in the conventional open group (86.9 ± 31.3 vs 44.2 ± 8.3, p < 0.001). Significant differences in the complication rate were not found between the two groups. Discomfort in the anterior neck area and SCM was relieved over time in most cases (verbal response scores (VRSs) were gradually decreased over time). The learning curves for working space making, ipsilateral thyroidectomy and the total endoscopic TAT approach were 45 cases, 25 cases and 42 cases, respectively. The operation time in the proficient group was significantly shorter than that in the learning group (67.0 ± 8.4 vs 112.3 ± 35.7, p < 0.001). VRSs in the SCM were significantly lower in the proficient group (for 1 week: 1.25 ± 0.65 vs 2.40 ± 0.63, p < 0.001; for 1 month: 0.81 ± 0.69 vs 1.81 ± 0.40, p < 0.001). CONCLUSIONS: Gasless endoscopic TAT was safe in a cohort of patients with thyroid diseases, with satisfactory surgical outcomes and cosmetic appearance. The learning curve for endoscopic TAT was approximately 42 cases. The proficiency of the endoscopic TAT approach depended primarily on the proficiency of working space making.

Gasless, endoscopic trans-axillary thyroid surgery: our series of the first 51 human cases.

BACKGROUND: The safety of gasless endoscopic trans-axillary thyroid surgery is still undetermined. METHODS: Clinical findings and postoperative complications of patients who had undergone trans-axillary thyroid surgery due to thyroid cancer and thyroid nodules were retrospectively studied. The sensory change and paralysis results from this technique and patients' satisfaction with the cosmesis were also studied. RESULTS: Fifty-one patients (49 females and 2 males) received operations by gasless, endoscopic trans-axillary approaches with one patient whose operation was converted to open surgery because of internal jugular vein injury. Only two patients developed temporary vocal cord paralysis and no patients developed other severe complications. The alleviation of the discomfort in the anterior neck area and sternocleidomastoid, and the cosmetic effect of gasless endoscopic trans-axillary thyroid surgery were acceptable. No evidence of recurrence was found during the follow-up period. CONCLUSIONS: Gasless, endoscopic trans-axillary thyroid surgery is a feasible procedure with acceptable safety and better cosmetic results in strictly selected patients.

Identification of endocrine-disrupting chemicals targeting the genes and pathways of genital anomalies in males.

Hypospadias and cryptorchidism are the most common congenital malformations in male neonates, both of which are also the important clinical manifestations of testicular dysgenesis syndrome and share a same origin. Many studies have suggested that prenatal exposure to endocrine-disrupting chemicals (EDCs) is associated with hypospadias and cryptorchidism development. However, the consistent mechanisms remain unclear. To identify the key EDCs, genes and biological networks related to the development of hypospadias and cryptorchidism respectively and commonly, we conduct the present study and found a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals. Transcriptome profiles were obtained from the Comparative Toxicogenomics Database (CTD). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses and protein-protein interaction (PPI) network were applied for integrative analyses. The rat model and molecular docking were applied to furtherly verifying the findings of the integrative analyses. Besides the highly related genes, most enriched pathways and chemicals for hypospadias and cryptorchidism respectively, we found hypospadias and cryptorchidism share many same highly associated EDCs (e.g., dibutyl phthalate) and genes (e.g., androgen receptor and estrogen receptor 1) through comparing highly related chemicals or genes of hypospadias and cryptorchidism respectively. GO and KEGG analysis showed that these same interactive genes were mainly enriched in steroidogenesis, response to steroid hormone and nuclear receptor activity. PPI network analysis identified 15 biological hub genes. Furtherly, hypospadias and cryptorchidism were induced by prenatal dibutyl phthalate exposure. Decreased serum testosterone level, downregulation of nuclear androgen-dependent and upregulation of cytoplasmic estrogen-dependent pathways may lead to hypospadias and cryptorchidism. This study proposed a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals and found that hypospadias and cryptorchidism share many same highly associated EDCs and genes.

Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM Disease.

BACKGROUND: Antiglomerular basement membrane (anti-GBM) disease is characterized by GN and often pulmonary hemorrhage, mediated by autoantibodies that typically recognize cryptic epitopes within α345(IV) collagen-a major component of the glomerular and alveolar basement membranes. Laminin-521 is another major GBM component and a proven target of pathogenic antibodies mediating GN in animal models. Whether laminin-521 is a target of autoimmunity in human anti-GBM disease is not yet known. METHODS: A retrospective study of circulating autoantibodies from 101 patients with anti-GBM/Goodpasture's disease and 85 controls used a solid-phase immunoassay to measure IgG binding to human recombinant laminin-521 with native-like structure and activity. RESULTS: Circulating IgG autoantibodies binding to laminin-521 were found in about one third of patients with anti-GBM antibody GN, but were not detected in healthy controls or in patients with other glomerular diseases. Autoreactivity toward laminin-521 was significantly more common in patients with anti-GBM GN and lung hemorrhage, compared with those with kidney-limited disease (51.5% versus 23.5%, P=0.005). Antilaminin-521 autoantibodies were predominantly of IgG1 and IgG4 subclasses and significantly associated with lung hemorrhage (P=0.005), hemoptysis (P=0.008), and smoking (P=0.01), although not with proteinuria or serum creatinine at diagnosis. CONCLUSIONS: Besides α345(IV) collagen, laminin-521 is another major autoantigen targeted in anti-GBM disease. Autoantibodies to laminin-521 may have the potential to promote lung injury in anti-GBM disease by increasing the total amount of IgG bound to the alveolar basement membranes.

[Relationship between Asymptomatic Bacteriuria and Vaginal Colonization of Group B Streptococcus in the Third Trimester of Pregnancy].

Objective To reveal the relationship between asymptomatic bacteriuria (ASB) and vaginal colonization of group B Streptococcus in the third trimester of pregnancy.Methods A total of 4287 pregnant women who were followed up from January 2018 to June 2021 were enrolled in this study.The pregnant women with ASB were assigned as the observation group,and those without ASB were matched at a ratio of 1∶4 as the control group.Results Among the 4287 pregnant women,158 (3.69%) pregnant women had ASB,including 28 (17.72%) with group B Streptococcus colonization in the third trimester.Among the 632 pregnant women without ASB (control),44 cases (6.96%) had vaginal colonization of group B Streptococcus in the third trimester.The colonization rate of group B Streptococcus in the pregnant women with ASB was significantly higher than that in the pregnant women without ASB (χ2=17.666,P<0.001).Logistic regression showed that ASB was positively correlated with the vaginal colonization of group B Streptococcus in the third trimester of pregnancy (OR=2.577,95%CI=1.509-4.402,P=0.001).Conclusions ASB is positively correlated with the vaginal colonization of group B Streptococcus in the third trimester.The screening,prevention,and control of ASB in the early trimester is of great significance to reduce the vaginal colonization of group B Streptococcus in the third trimester.

GTPases Arf5 and Arl2 function partially distinctly during oocyte meiosis.

Mammalian female meiosis must be tightly regulated to produce high-quality mature oocytes for subsequent regular fertilization and healthy live birth of the next generation. GTPases control many important signal pathways involved in diverse cellular activities. ADP-ribosylation factor family members (Arfs) in mice possess GTPase activities, and some members have been found to function in meiosis. However, whether other Arfs play a role in meiosis is unknown. In this study, we found that Arl2 and Arf5 are the richest among Arfs in mouse oocytes, and they are more abundant in oocytes than in granular cells. Furthermore, Arl2 and Arf5 depletion both impeded meiotic progression, but by affecting spindles and microfilaments, respectively. Moreover, Arl2 and Arf5 depletion both significantly increased regular reactive oxygen species levels and decreased mitochondrial membrane potential and autophagy, indicating that oocyte quality was damaged by Arl2 and Arf5 depletion. These results suggest that Arl2 and Arf5 are two novel essential GTPases required for oocyte meiosis and quality control.

Potential of testis-derived circular RNAs in seminal plasma to predict the outcome of microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia.

STUDY QUESTION: Do testis-derived circular RNAs (circRNAs) in seminal plasma have potential as biomarkers to predict the outcome of microdissection testicular sperm extraction (micro-TESE) in patients with idiopathic non-obstructive azoospermia (NOA)? SUMMARY ANSWER: Testis-derived circRNAs in the seminal plasma can indeed be used for predicting the outcome of micro-TESE in patients with idiopathic NOA. WHAT IS KNOWN ALREADY: Micro-TESE is an effective method to obtain sperm samples from patients with idiopathic NOA. However, its success rate is only 40-50% in such patients. STUDY DESIGN, SIZE, DURATION: Six idiopathic NOA patients with different micro-TESE results were included as the discovery cohort. Their testicular tissues were used for extracting and sequencing circRNAs. Five circRNAs with the most significantly different expression levels were selected for further verification. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifty-two patients with idiopathic NOA were included as the validation cohort. Preoperative seminal plasma samples of 52 patients with idiopathic NOA and 25 intraoperative testicular tissues were collected and divided into 'success' and 'failure' groups according to the results of micro-TESE. Quantitative real-time polymerase chain reaction was performed to verify differences in the expression levels of the selected circRNAs between the two groups in the testicular tissues and seminal plasma. MAIN RESULTS AND THE ROLE OF CHANCE: Whether at the seminal plasma or testicular tissue level, the differences in the expression levels of the three circRNAs (hsa_circ_0000277, hsa_circ_0060394 and hsa_circ_0007773) between the success and failure groups were consistent with the sequencing results. A diagnostic receiver operating curve (ROC) analysis of the AUC indicated excellent diagnostic performance of these circRNAs in seminal plasma in predicting the outcome of micro-TESE (AUC values: 0.920, 0.928 and 0.891, respectively). On the basis of least absolute shrinkage and selection operator (LASSO) logistic regression, the three circRNAs were combined to construct a new prediction model. The diagnostic ROC curve analysis of the model showed an AUC value of 0.958. The expression levels of these circRNAs in seminal plasma using three normospermic volunteer samples remained stable after 48 h at room temperature. LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: This was a single-center retrospective study with relatively few cases. The functions of these circRNAs, as well as their relationship with spermatogenesis, have not yet been established. WIDER IMPLICATIONS OF THE FINDINGS: Testis-derived circRNAs in seminal plasma can reflect the microenvironment of the testis and can be used as reliable biomarkers to screen patients with idiopathic NOA who might be suitable for micro-TESE. STUDY FUNDING/COMPETING INTEREST(S): This article was funded by the National Natural Science Foundation of China (Grant no. 81871151). There were no competing interests.

Decreased expression of METTL14 predicts poor prognosis and construction of a prognostic signature for clear cell renal cell carcinoma.

BACKGROUND: METTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers. This study was aimed to investigate the prognostic value of METTL14 in clear cell renal cell carcinoma (ccRCC). METHODS: We collected ccRCC patients' clinicopathological parameters information and 13 m6A related genes expression from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to investigate whether METTL14 could serve as an independent factor correlated with overall survival (OS). Gene Set Enrichment Analysis (GSEA) was carried out to identify METTL14-related signaling pathways. Moreover, a risk score (RS) was calculated to predict the prognosis of ccRCC. Quantitative real-time PCR (qRT-PCR) was also utilized to verify the expression of METTL14 in clinical specimens. RESULTS: Differently expressed m6A related genes were identified between ccRCC tissues and normal tissues. Therein, METTL14 was lowly expressed in ccRCC tissues and verified by qRT-PCR (all p < 0.01). Survival analysis indicated that high expression of METTL14 was associated with better OS (p = 1e-05). GSEA results revealed that high METTL14 expression was enriched in ERBB pathway, MAPK pathway, mTOR pathway, TGF-ß pathway and Wnt pathway. Moreover, METTL14 was proved to be an independent prognostic factor by means of univariate and multivariate Cox regression analyses. Nomogram integrating both the METTL14 expression and clinicopathologic variables was also established to provide clinicians with a quantitative approach for predicting survival probabilities of ccRCC. Furthermore, a METTL14-based riskscore (RS) was developed with significant OS (p = 6.661e-16) and increased AUC of 0.856. Besides, significant correlated genes with METTL14 were also provided. CONCLUSIONS: Our results indicated that METTL14 could serve as a favorable prognostic factor for ccRCC. Moreover, this study also provided a prognostic signature to predict prognosis of ccRCC and identified METTL14-related signaling pathways.

A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration.

BACKGROUND: Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. METHODS: According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. RESULTS: Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. CONCLUSIONS: Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCA patients.

Naples prognostic score is an independent prognostic factor in patients with operable endometrial cancer: Results from a retrospective cohort study.

OBJECTIVE: Naples prognosis score (NPS) is a new immune and nutritional assessment method that can be used to predict tumor prognosis. This study aimed to identify whether NPS is an independent prognostic indicator of operable endometrial cancer (EC). MATERIALS AND METHODS: We retrospectively analyzed 1038 patients with endometrial cancer who underwent surgery. Patients were grouped according to NPS (NPS group 0, n = 362; NPS group 1, n = 589; and NPS group 2, n = 87), and differences in clinical characteristics were compared among the groups. Survival analysis was performed by the Kaplan-Meier method, P values were calculated by log-rank test, and prognostic factors were assessed by Cox proportional hazards regression models. RESULTS: Serum albumin levels, total cholesterol levels, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, total lymphocyte count, CA-125 levels, age, body mass index, FIGO stage, myometrial invasion depth, controlling nutritional status score, and systemic inflammation score were significantly different among the groups; significant differences in progression-free survival(PFS) and overall survival (OS) were also found. On multivariate analysis, NPS was identified as an independent prognostic factor for PFS (NPS group 0 vs. 1: aHR = 4.32, 95%CI = 1.133-16.47; NPS group 0 vs. 2: aHR = 21.336, 95%CI = 3.498-130.121) and OS (NPS group 0 vs. 1: aHR = 5.029, 95%CI = 1.638-15.441; NPS group 0 vs. 2: aHR = 20.789, 95%CI = 4.381-98.664). Moreover, NPS is an independent prognostic factor for PFS and OS in grade 2 or 3 EC (aHR = 7.768, 95%CI = 2.411-25.029 and aHR = 4.717, 95%CI = 1.794-12.407, respectively). CONCLUSION: High NPS is associated with poor PFS and OS and is a valuable independent prognostic factor in patients with EC.

CRISPR/Cas9-based generation of a recombinant double-reporter pseudorabies virus and its characterization in vitro and in vivo.

Pseudorabies, caused by pseudorabies virus (PRV) variants, has broken out among commercial PRV vaccine-immunized swine herds and resulted in major economic losses to the pig industry in China since late 2011. However, the mechanism of virulence enhancement of variant PRV is currently unclear. Here, a recombinant PRV (rPRV HN1201-EGFP-Luc) with stable expression of enhanced green fluorescent protein (EGFP) and firefly luciferase as a double reporter virus was constructed on the basis of the PRV variant HN1201 through CRISPR/Cas9 gene-editing technology coupled with two sgRNAs. The biological characteristics of the recombinant virus and its lethality to mice were similar to those of the parental strain and displayed a stable viral titre and luciferase activity through 20 passages. Moreover, bioluminescence signals were detected in mice at 12 h after rPRV HN1201-EGFP-Luc infection. Using the double reporter PRV, we also found that 25-hydroxycholesterol had a significant inhibitory effect on PRV both in vivo and in vitro. These results suggested that the double reporter PRV based on PRV variant HN1201 should be an excellent tool for basic virology studies and evaluating antiviral agents.

m6A RNA methylation regulators correlate with malignant progression and have potential predictive values in clear cell renal cell carcinoma.

N6-methyladenosine (m6A) has been reported to be involved in several biological processes in tumors. In this study, we found that most of the m6A RNA methylation regulators were not only differentially expressed between clear cell renal cell carcinoma (ccRCC) and normal but also among ccRCC stratified by different clinicopathologic characters. Two ccRCC subgroups, cluster 1 and 2, were identified using consensus clustering based on the expression of m6A methylation regulators. Although no obvious differences were observed between two subgroups regarding clinicopathologic characters, except gender, patients in cluster 1 had a relatively more favorable survival rate than cluster 2. Moreover, we established a risk signature with two m6A methylation regulators, METTL3 and METTL14, which was not only of great value for prognosis prediction but also closely associated with clinicopathological features. In conclusion, m6A RNA methylation regulators play an important role in ccRCC progression and are potentially favorable for prognostic stratification.

Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats.

Di-n-butyl phthalate (DBP) is a widely used plasticizer and an environmental endocrine-disrupting compound. However, whether prenatal exposure to DBP can impair erectile function remains unknown. We conducted this study to investigate the potential effects of prenatal exposure to DBP on erectile function and the underlying mechanisms. A rat model of prenatal DBP exposure (12.5, 100 or 800 mg/kg/day by gavage during gestational days 13-21) was established. Prenatal DBP exposure significantly decreased penis/body weight ratio, myelin sheath thickness of cavernosum nerves and serum testosterone level in male rats at the age of 10 weeks. Furthermore, erectile dysfunction was detected in all DBP exposure groups, which exhibited substantial increases in transforming growth factor-ß1 (TGF-ß1) expression and decreases in the expression of alpha smooth muscle actin (α-SMA), neuronal and endothelial nitric oxide synthase (nNOS and eNOS). Additionally, the phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratio and caspase-3 were higher in DBP exposure groups than in the control group. Notably, prenatal exposure to DBP increase the risk of ED in male adult rats, even taking low dose of DBP (12.5 mg/kg/day). DBP exposure causing penile fibrosis, decreased testosterone level, and endothelial dysfunction may be responsible for ED by activating Akt/Bad/Bax/caspase-3 pathway and suppressing NOS/cGMP pathway in penis.

Cognitive emotion regulation strategies and depressive symptoms among nurses exposed to workplace violence: a person-centered approach.

BACKGROUND: Cognitive strategies are preferred among nurses who have limited opportunities in the workplace to use behavioral strategies to cope with negative life events. AIMS: To explore whether different cognitive emotion regulation profiles could be distinguished in nurses exposed to workplace violence, and to investigate whether such profiles had differential associations with depressive symptoms. METHOD: An online survey was conducted among nurses exposed to workplace violence (N = 399). Latent profile analysis was performed to identify discrete profiles based on the use of cognitive emotion regulation strategies. The Bolck, Croon, and Hagenaars method was applied to compare the latent profiles on the depressive symptoms. RESULTS: Seven latent profiles were identified: Low Regulators, Medium Regulators, High Regulators, Intensely Adaptive Regulators, Moderately Adaptive Regulators, Intensely Maladaptive Regulators, and Moderately Maladaptive Regulators. High Regulators had the highest level of depressive symptoms. Although using less adaptive strategies, Low Regulators did not report significantly more depressive symptoms than Medium Regulators, Intensely Maladaptive and Moderately Maladaptive Regulators. CONCLUSIONS: The adaptability of cognitive emotion regulation strategies depends on the conjunction of different strategies one person has at his disposal. Cognitive emotion regulation skill training should focus on flexible implementation of strategies and decreasing use of maladaptive strategies.