Molecular Systematics and Taxonomic Analyses of Three New Wood-Inhabiting Fungi of Hyphoderma (Hyphodermataceae, Basidiomycota).

In this present study, three new wood-inhabiting fungal taxa, Hyphoderma niveomarginatum, H. sordidum and H. weishanense, are proposed. Hyphoderma niveomarginatum is characterized by the ceraceous basidiomata having a smooth, cracking hymenial surface and the presence of the moniliform cystidia and ellipsoid basidiospores (7-9 × 3.5-5 µm). Hyphoderma sordidum is characterized by its resupinate basidiomata with a smooth hymenial surface with the fimbriate margin, the presence of the tubular cystidia and ellipsoid basidiospores (3-4.5 × 2-3 µm). Hyphoderma weishanense differs in its membranous basidiomata with a slightly buff to buff hymenial surface and the presence of broadly ellipsoid basidiospores (4.5-8.5 × 4-7 µm). Sequences of ITS+nLSU+mt-SSU+RPB1+RPB2 genes were used for the phylogenetic analyses using three methods. The ITS+nLSU+mt-SSU+RPB1+RPB2 analysis of the genus Hyphoderma indicated that the 3 new species of Hyphoderma were nested into genus Hyphoderma, in which H. niveomarginatum formed a single group and then grouped with H. membranaceum and H. sinense; H. sordidum was a sister to H. nudicephalum; and H. weishanense closely grouped with H. crystallinum.

Cancer-associated fibroblast-secreted miR-421 promotes pancreatic cancer by regulating the SIRT3/H3K9Ac/HIF-1α axis.

This study was designed to explore the effects of exosomal miR-421 secreted by cancer-associated fibroblasts (CAFs) on pancreatic cancer (PC) progression and the mechanisms involved. CAFs and exosomes (exos) were isolated and identified. PC cells were treated with CAF-derived exos (CAF-exos). Western blotting and quantitative polymerase chain reaction (qPCR) were used to measure miR-421, sirtuin-3 (SIRT3), and hypoxia duciblefactors-1 alpha (HIF-1α) levels. Cell counting kit-8 (CCK-8), wound-healing, and transwell migration assays were used to measure proliferation, migration, and invasion abilities of the cells. Dual-luciferase assay and RNA immunoprecipitation (RIP) experiment analyzed the relationship between miR-421 and SIRT3. Chromatin immunoprecipitation (f)-verified H3K9Ac enrichment in the HIF-1α promoter region. In vivo tumorigenesis experiments were performed to further explore the effects of exosomal miR-421 from CAFs on PC. CAFs and exos were successfully isolated. CAF-exo-treated PC cells highly expressed miR-421 and had increased cell proliferation, migration, and invasion abilities. Knocking down miR-421 increased the expression of SIRT3. SIRT3 is a target of miR-421, and inhibiting the expression of SIRT3 reversed the negative effects of miR-421 knockdown on PC cell. Knocking down miR-421 in CAF-exo inhibited the expression of HIF-1α in PC cells. Moreover, SIRT3-mediated HIF-1α expression by regulating H3K9Ac. HIF-1α overexpression reversed the inhibiting effects of SIRT3 overexpression on PC progression and counteracted the inhibiting effects of miR-421 knockdown on glycolysis. Moreover, in vivo tumorigenesis experiments showed that knocking down miR-421 attenuated CAF-exo induced tumor growth. Exosomal miR-421 from CAFs promoted PC progression by regulating the SIRT3/H3K9Ac/HIF-1α axis. This study provided insights into the molecular mechanism of PC.

LINC00960 regulates cell proliferation and glycolysis in pancreatic cancer through the miR-326-3p/TUFT1/AKT-mTOR axis.

Pancreatic cancer (PC) is a common malignant cancer characterized by high mortality and poor prognosis. LINC00690 was involved in the occurrence and progression of PC, but the underlying mechanisms require further investigation. The goal of this study was to figure out how LINC00960 mediates glycolysis in PC. LINC00960, miR-326-3p, and Tuftelin 1 (TUFT1) expression levels were detected in PC cell lines. LINC00960 and TUFT1 expression levels were increased in PC cells when compared with normal pancreatic cells, whereas miR-326-3p expression levels were decreased. The expression levels of LINC00690 affected glycolysis in PC, and inhibition of LINC00960 inhibited tumor growth in vivo. LINC00690 targeted and suppressed the expression of miR-326-3p. MiR-326-3p bound to TUFT1, and miR-326-3p inhibited AKT-mTOR pathway activation via TUFT1. In conclusion, the depletion of LINC00960 repressed cell proliferation and glycolysis in PC by mediating the miR-326-3p/TUFT1/AKT-mTOR axis. Thus, we present a novel mechanism underlying the progression of PC that suggests LINC00960 is a potential therapeutic target for this cancer.

A better overall survival (OS) for total (ipsilateral) retroperitoneal lipectomy than standard complete resection in patients with retroperitoneal liposarcoma: a comparative multi-institutional study.

Background: Complete resection (CR) serves as the standard of surgical treatment for retroperitoneal liposarcoma (RPLS). Unfortunately, even at referral centers, recurrence rates are high, and CR may not address multifocal diseases, which are a common phenomenon in RPLS. We sought to retrospectively compare the clinical outcomes of RPLS patients treated with total (ipsilateral) retroperitoneal lipectomy (TRL) and CR. Because TRL remove potentially multifocal tumors in the fat, patients may have a better prognosis than CR. Methods: Patients with primary/first-recurrent RPLS who had been treated at 5 referral centers were recruited from December 2014 to June 2018. Multivariable Cox regression analyses were conducted to determine the effects of demographic, operative, and clinicopathological variables on the following primary endpoints: local recurrence (LR), local recurrence-free survival (LRFS), and overall survival (OS). Results: A total of 134 patients were enrolled in this retrospective study, 53 of whom underwent TRL, and 81 of whom underwent CR. The 2 groups were comparable in terms of age, gender, presentation (primary vs. first-recurrent RPLS), number of tumors (unifocal vs. multifocal) at presentation, and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade. The TRL group had higher levels of preoperative hemoglobin (Hb) (13 vs. 12.5 g/dL; P=0.008) and a lower amount of intraoperative blood loss (400 vs. 500 mL; P=0.034), but there were no significant differences in the length of hospital stay (23 vs. 22 d; P=0.47) or complications (32 vs. 30; P=0.82) between the 2 groups. In a subset of patients with multifocal tumors at initial presentation, OS was more prolonged in those treated with TRL than those treated with CR (P=0.0272). Based on the multivariable analysis, primary liposarcoma and a low FNCLCC grade were associated with decreased LR and improved OS. Conclusions: TRL is a safe procedure that positively affects the OS of patients with multifocal RPLS. This novel strategy deserves further investigation in prospective studies.

Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study.

BACKGROUND: Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods. METHODS: In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard. FINDINGS: For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886-0·936) in the internal dataset, 0·870 (95% CI 0·822-0·918) in external validation dataset 1, and 0·831 (95% CI 0·793-0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% [85·0-90·2] vs 78·3% [72·1-84·5], p<0·0001; 82·7% [78·5-86·9] vs 70·4% [59·1-81·7], p<0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p<0·05). INTERPRETATION: The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists' accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials. FUNDING: National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.

Down-regulation of lncRNA KCNQ1OT1 protects against myocardial ischemia/reperfusion injury following acute myocardial infarction.

This study aimed to investigate the protective effects of long non-coding RNA KCNQ1OT1 against myocardial ischemia/reperfusion (I/R) injury following acute myocardial infarction, as well as its regulatory mechanism. We used the cardiac muscle H9c2 cells under condition of oxygen glucose deprivation followed by reperfusion (OGD/R) to induce myocardial I/R injury. Then H9C2 cells were transfected with si-NC, si-KCNQ1OT1, pc-NC, pc-KCNQ1OT1, si-AdipoR1 and si-AdipoR2, respectively. The myocardial cell viability and apoptosis were respectively detected. In addition, the expression levels of inflammatory factors, apoptosis-related proteins and p38 MAPK/NF-κB pathway-related proteins were detected. Besides, an inhibitor of p38 MAPK/NF-κB pathway SB203580 was used to treat cells to verify the relationship between KCNQ1OT1 and p38 MAPK/NF-κB pathway. The expression of KCNQ1OT1 was significantly up-regulated in OGD/R-induced myocardial H9C2 cells. The OGD/R-induced decreased cell viability and AdipoR1 expression could be reversed after suppression of KCNQ1OT1. In addition, suppression of KCNQ1OT1 reduced OGD/R-induced increased expressions of TNF-α, IL-6 and IL-1ß and OGD/R-induced increased cell apoptosis, which were reversed after knockdown of AdipoR1. Besides, suppression of KCNQ1OT1 significantly down-regulated the OGD/R-induced increased expression of p-p38 and p-NF-κB, which were also reversed after knockdown of AdipoR1. Moreover, SB203580, an inhibitor of p38 MAPK/NF-κB signal pathway, could further enhance the inhibitory effects of KCNQ1OT1 suppression on the expression of p-p38, TNF-α, IL-6, IL-1ß and p-NF-κB in OGD/R-induced myocardial H9C2 cells. Suppression of KCNQ1OT1 may prevent myocardial I/R injury following acute myocardial infarction via regulating AdipoR1 and involving in p38 MAPK/NF-κB signal pathway.

Association of folate metabolism gene polymorphisms and haplotype combination with pulmonary embolism risk in Chinese Han population.

In this study, we aimed to investigate the association of four single nucleotide polymorphisms (SNPs) (MTHFR 677 C > T, MTHFR 1298 A > C, MTR 2756 A > G and MTRR 66 A > G), gene-gene interaction and haplotype combination with pulmonary embolism (PE) risk based on Chinese Han population. Logistic regression was performed to investigate association between four SNPs within folate metabolism gene and PE risk, and GMDR model was used to investigate the additional gene-gene interactions among the four SNPs. Logistic analysis showed that rs1801133 and rs1801131 in MTHFR gene were associated with increased PE risk in both additive and dominant models. The carriers with homozygous mutant of rs1801133 polymorphism and homozygous of rs1801131 were associated with increased PE risk, and ORs (95% CI) were 1.71(1.24-2.21) and 1.58 (1.24-2.01), respectively. We also found a significant gene-gene interaction between rs1801133 and rs1801131 on PE. Overall, the cross-validation consistency of this two-locus model was 10/10, and the testing accuracy was 60.72%, after adjusting for covariates. Haplotype containing the rs1801133- T and rs1801131- C alleles were associated with a statistically increased PE risk, OR (95% CI) = 2.68 (1.28-4.13), P < 0.001. We found that rs1801133 and rs1801131 within MTHFR gene, their interaction, and haplotype containing the rs1801133- T and rs1801131- C alleles were all associated with PE risk.

Resveratrol lowers blood pressure in spontaneously hypertensive rats via calcium-dependent endothelial NO production.

OBJECTIVE: Resveratrol, a polyphenol of natural compounds, has beneficial cardiovascular effects, many of which are mediated by nitric oxide (NO). Resveratrol increases intracellular calcium and activates AMP-activated protein kinase (AMPK), all of which could increase NO production. We hypothesized that resveratrol via a calcium-dependent NO production lowers blood pressure (BP) in spontaneously hypertensive rats (SHR). METHODS: Acetylcholine (Ach)-induced endothelium-dependent relaxations in rat aortas were examined by organ chamber. Blood pressures were determined by radiotelemetry methods. RESULTS: Incubation of isolated aortas from SHR with resveratrol dramatically improved vasorelaxation induced by Ach. Preincubation of aortas with endothelial NO synthase (eNOS) inhibitor or calcium chelant blunted the effects of resveratrol on Ach-induced relaxation, as wells as NO production and eNOS phosphorylation. In animal studies, administration of resveratrol significantly lowered systemic BP in SHR. CONCLUSION: Resveratrol increases endothelial NO production to improve endothelial dysfunction and lowers BP in hypertensive rats, which depends on calcium-eNOS activation.

Prediction of long-term outcome after acute myocardial infarction using circulating miR-145.

BACKGROUND: Recent reports have shown that miR-145 concentration correlates with infarct size. In this paper, we attempt to predict heart failure and cardiovascular death after acute myocardial infarction using circulating miR-145 concentration. METHODS: We assessed 246 patients with first ST-segment-elevation myocardial infarction who underwent successful percutaneous coronary intervention. We measured circulating miR-145, N-terminal fragment of the precursor B-type natriuretic peptide, myocardial-band creatine kinase, and cardiac troponin-I concentrations on day 5 after primary percutaneous coronary intervention and assessed their correlations with long-term clinical outcome. RESULTS: During the one-year follow-up period, 72 patients experienced primary composite cardiac events (cardiac death or hospitalization for worsening heart failure). Multivariable Cox proportional hazards analysis indicated that circulating miR-145 (hazard ratio 7.174, 95% confidence interval 4.208-12.229); p < 0.0001) was a significant independent predictor of cardiac events after adjustment for multiple confounders. CONCLUSION: Circulating miR-145 may be a novel biomarker for predicting long-term outcome after acute myocardial infarction.

Effect of continuous positive airway pressure on blood pressure in hypertensive patients with coronary artery bypass grafting and obstructive sleep apnea.

BACKGROUND: Previous studies have documented that obstructive sleep apnea (OSA) increases the incidence of hypertension, respiratory failure and unexpected post-operative deaths during night in coronary artery bypass grafting (CABG) patients. We hypothesized that continuous positive airway pressure (CPAP) reduces blood pressure in these patients. METHODS: We conducted a prospective, controlled study in 51 patients. The subjects received CPAP treatment were defined as CPAP group, whereas those refused to use CPAP were served as controls. Blood pressure was measured by 24 h ambulatory blood pressure at baseline and at six months. RESULTS: Fifty-one patients completed the study. CPAP group and controls had similar characteristics. Compared with the control group, the 24-h SBP and 24-h DBP in the CPAP group had a tendency towards lower levels, but the differences were not statistically significant. But the change of SBP in CPAP treatment was significantly higher than controls (CPAP: 10.0 ± 13.5 mm Hg vs. CONTROL: 2.9 ± 10.5 mm Hg, P = 0.040). The rate of hypertension control was improved in the CPAP treatment, but had no statistical difference compared to the controls (CPAP, 76.0% vs. CONTROL, 61.5%; P = 0.260). Compared with controls, the proportion of non-dipping hypertension had a markedly improvement in the CPAP group (CONTROL, 46.2% vs. CPAP, 16.0%; P = 0.034). CONCLUSIONS: CPAP therapy decreased SBP and improved the status of non-dipping hypertension and alleviated daytime somnolence in hypertensive patients with CABG and OSA on standardized antihypertensive treatment. But DBP and hypertension control did not significantly change compared with the control group.