Group mating in Cretaceous water striders.

Fossilized mating insects are irreplaceable material for comprehending the evolution of the mating behaviours and life-history traits in the deep-time record of insects as well as the potential sexual conflict. However, cases of mating pairs are particularly rare in fossil insects, especially aquatic or semi-aquatic species. Here, we report the first fossil record of a group of water striders in copulation (including three pairs and a single adult male) based on fossils from the mid-Cretaceous of northern Myanmar. The new taxon, Burmogerris gen. nov., likely represents one of the oldest cases of insects related to the marine environment, such as billabongs formed by the tides. It exhibits conspicuous dimorphism associated with sexual conflict: the male is equipped with a specialized protibial comb as a grasping apparatus, likely representing an adaptation to overcome female resistance during struggles. The paired Burmogerris show smaller males riding on the backs of the females, seemingly recording a scene of copulatory struggles between the sexes. Our discovery reveals a mating system dominated by males and sheds light on the potential sexual conflicts of Burmogerris in the Cretaceous. It indicates the mating behaviour remained stable over long-term geological time in these water-walking insects.

[Spatial Prediction Modeling for Soil pH Based on Multiscale Geographical Weighted Regression(MGWR) and Its Influencing Factors].

Anhui, Henan, Jiangsu, and Shandong provinces were selected as the study area. A total of 599 soil samples and nine environmental factors of soil pH were collected. The spatial distribution of soil pH was modeled based on multi-scale geographically weighted regression(MGWR), mixed geographically weighted regression(Mixed GWR), geographically weighted regression(GWR), and multiple linear regression(MLR) models. Then, the spatial difference in the effect of environmental factors on soil pH was revealed using MGWR and quantile regression models. The results showed that:① soil pH showed significant global and local spatial autocorrelation at different spatial distances, and the clustering characteristics were obvious. ② The MGWR model was the best among the four models, and the Radj2 of MGWR, Mixed GWR, GWR, and MLR were 0.64, 0.62, 0.59, and 0.48, respectively. The residual of MGWR had the strongest independent distribution and the weakest spatial autocorrelation with a global Moran's I of 0.07. ③ Three types of GWR predictions showed that the spatial distribution of soil pH decreased gradually from north to south in the study area, with the highest in northern Henan and the lowest in southern Anhui. ④ MGWR modeling results showed that there was strong spatial heterogeneity of mean annual precipitation(MAP), multi-resolution valley bottom flatness(MRVBF), and elevation affecting soil pH. MAP had a stronger effect on soil pH in northern Jiangsu and most parts of Shandong. The positive effect of MRVBF on soil pH was stronger in northern Jiangsu and western Shandong. The negative effect of elevation on soil pH was stronger in northern and central Jiangsu. ⑤ The quantile regression analysis showed that the mean annual precipitation had a significant negative effect on soil pH at different quantile levels of soil pH, and influence intensity decreased with the increase in pH quantile level. MRVBF had a significant negative effect on soil pH at a low quantile level(θ=0.1 to 0.4) but had no significant effect on soil pH at a high quantile level(θ=0.5 to 0.9). These results can provide an important reference for mapping soil properties and analyzing its influence factors based on the MGWR model in large regions.

Idiopathic hypereosinophilic syndrome presenting as capsular warning syndrome: A case report and literature review.

RATIONALE: Few reports of idiopathic hypereosinophilic syndrome exist presenting as ischemic cerebrovascular disease, and the majority are watershed infarction. We report the first case of idiopathic hypereosinophilic syndrome that has clinical features of capsular warning syndrome lasting 6 weeks. PATIENT CONCERNS: A 26-year-old man complained of recurrent right limb weakness, accompanying slurred speech, and right facial paresthesia. DIAGNOSES: The patient was diagnosed with idiopathic hypereosinophilic syndrome (IHES). INTERVENTIONS: Adequate glucocorticoid and anticoagulant treatments were given. OUTCOMES: The patient's motor ability improved, and he was discharged 2 weeks later. Muscle strength in the right-side extremities had fully recovered at a 3-month follow-up after discharge. LESSONS: This case suggests that idiopathic hypereosinophilic syndrome should be considered as a cause of capsular warning syndrome, and the dose of glucocorticoid and the efficacy evaluation index needs to be reevaluated for the treatment of ischemic cerebrovascular disease associated with idiopathic hypereosinophilic syndrome.

Retroperitoneal Laparoscopic Hepatectomy for a Subcapsular Hepatocellular Carcinoma in Segment VI (Video).

INTRODUCTION: Hepatocellular carcinoma located in hepatic segment VI/VII or close to the adrenal gland were generally considered challenging for minimally invasive resection. For these individualized patients, this may be overcome by the novel use of a retroperitoneal laparoscopic hepatectomy; however, minimally invasive retroperitoneal liver resection is difficult to perform.1-3 This video article demonstrates a pure retroperitoneal laparoscopic hepatectomy for a subcapsular hepatocellular carcinoma. VIDEO: A 47-year-old male patient with Child-Pugh A liver cirrhosis presented with a small tumor located very close to the adrenal gland next to segment VI of the liver. An enhanced abdominal computed tomographic scan demonstrated a solitary 2.3 × 1.6 cm lesion. Considering the special location of the lesion, a pure retroperitoneal laparoscopic hepatectomy was performed after obtaining the patient's consent. The patient was positioned in the flank position. The procedure was carried out using the balloon technique for a retroperitoneoscopic approach, with the patient in the lateral kidney position. The retroperitoneal space was first accessed through a 12-mm skin incision above the anterior superior iliac spine in the mid-axillary line and was expanded by inflating a glove balloon to 900 mL. A 5 mm port below the 12th rib in the posterior axillary line and a 12 mm port below the 12th rib in the anterior axillary line were placed. Following incision of Gerota's fascia, the dissection plane between the perirenal fat and the anterior renal fascia located at the superomedial side of the kidney was explored. The retroperitoneum behind the liver was fully exposed after the upper pole of the kidney was isolated. After localization of the tumor by intraoperative ultrasonography through the retroperitoneum, the retroperitoneum was dissected directly above the tumor. We used an ultrasonic scalpel to divide the hepatic parenchyma, and a Biclamp for hemostasis. The blood vessel was clamped using titanic clips, and the specimen was extracted using a retrieval bag following resection. A drainage tube was placed after completing meticulous hemostasis. Closure of the retroperitoneum was performed using a conventional suture method. RESULTS: The total operation time was 249 min, with an estimated blood loss of 30 mL. The final histopathological diagnosis showed a 3.0 × 2.2 × 2.0 cm-sized hepatocellular carcinoma. The patient was discharged on postoperative day 6 without any complications. CONCLUSION: Lesions located in segment VI/VII or close to the adrenal gland were generally considered difficult for minimally invasive resection. Under these circumstances, a retroperitoneal laparoscopic hepatectomy might be a more suitable option as it is a safe, effective and complementary approach to standard minimally invasive technology for the resection of small hepatic tumors in these special locations of the liver.

piR-36249 and DHX36 together inhibit testicular cancer cells progression by upregulating OAS2.

Background: PIWI-interacting RNAs (piRNAs) are a class of noncoding RNAs originally reported in the reproductive system of mammals and later found to be aberrantly expressed in tumors. However, the function and mechanism of piRNAs in testicular cancer are not very clear. Methods: The expression level and distribution of piR-36249 were detected by RT-qPCR and immunofluorescence staining assay. Testicular cancer cell (NT2) progression was measured by CCK8 assay, colony formation assay and wound healing assay. Cell apoptosis was assessed by flow cytometry and western blot. RNA sequencing and dual-luciferase reporter assay were conducted to identify the potential targets of piR-36249. The relationship between piR-36249 and OAS2 or DHX36 was confirmed using overexpression assay, knockdown assay, pull-down assay and RIP assay. Results: piR-36249 is significantly downregulated in testicular cancer tissues compared to tumor-adjacent tissues. Functional studies demonstrate that piR-36249 inhibits testicular cancer cell proliferation, migration and activates the cell apoptosis pathway. Mechanically, we identify that piR-36249 binds to the 3'UTR of 2'-5'-oligoadenylate synthetase 2 (OAS2) mRNA. OAS2 has been shown in the literature to be a tumor suppressor modulating the occurrence and development of some tumors. Here, we show that OAS2 knockdown also promotes testicular cancer cell proliferation and migration. Furthermore, piR-36249 interacts with DHX36, which has been reported to promote translation. DHX36 can also bind to OAS2 mRNA, and knockdown of DHX36 increases OAS2 mRNA but downregulates its protein, indicating the enhancing effect of DHX36 on OAS2 protein expression. Conclusion: All these data suggest that piR-36249, together with DHX36, functions in inhibiting the malignant phenotype of testicular cancer cells by upregulating OAS2 protein and that piR-36249 may be used as a suppressor factor to regulate the development of testicular cancer.

New material of Cretaceoushormiops Loureno from mid-Cretaceous Burmese amber (Arachnida: Scorpiones: Protoischnuridae).

Among the scarce Mesozoic fossils, protoischnurid scorpions (Arachnida: Scorpiones: Protoischnuridae) represent a Cretaceous extinct group. In this study, we present the description of a new protoischnurid fossil, assigned to the genus Cretaceoushormiops Loureno, from mid-Cretaceous Burmese amber. Distinguished by a median suture and a comparatively short anterior margin in its carapace, the new specimen differs from all other species within Cretaceoushormiops. Our discovery sheds further light on the high diversity of mid-Cretaceous scorpions.

LncRNA-MALAT1 Regulates Cancer Glucose Metabolism in Prostate Cancer via MYBL2/mTOR Axis.

It is known that the long noncoding RNAs (lncRNA) MALAT1 is associated with tumorigenesis and progression in various cancers; however, its functions and mechanisms in prostate cancer (PCa) initiation and progression are still unknown. In the present study, our findings revealed that MALAT1 plays a critical part in regulating PCa proliferation and glucose metabolism. Knockdown of MALAT1 affects the protein and mRNA levels of MYBL2. In addition, MALAT1 enhances the phosphorylation level of mTOR pathway by upregulating MYBL2. Knockdown of MALAT1 or MYBL2 in PCa cell lines significantly inhibits their proliferation capacity. Silencing MALAT1/MYBL2/mTOR axis in PCa cell lines affects their glycolysis and lactate levels, and we verified these findings in mice. Furthermore, we explored the underlying tumorigenesis functions of MYBL2 in PCa and found that high expression of MYBL2 was positively associated with TNM stage, Gleason score, PSA level, and poor survival rate in PCa patients. Taken together, our research suggests that MALAT1 controls cancer glucose metabolism and progression by upregulating MYBL2-mTOR axis.

LncRNA NEAT1-associated aerobic glycolysis blunts tumor immunosurveillance by T cells in prostate cancer.

Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is nuclear-located and transcribed from chromatin 11. To date, little is known about the cellular functions and regulatory mechanisms of NEAT1 in prostate cancer (PCa). In this study, whole-genome RNA sequencing data were downloaded from TCGA and GEO databases. Biological information was used to analyze the different expressions of NEAT1. In situ hybridization (ISH) was performed to detect the expression of NEAT1 in PCa and paracarcinoma clinical samples. Then, NEAT1 was knocked down in PC3 cells through lentiviral infection with a plasmid construct. Bioinformatics and integrative analytical approaches were utilized to identify the relationships of NEAT1 with specific cancer-related gene sets. Cell proliferation assay and colony formation assay were performed to evaluate the cell proliferative ability. Glycolysis stress test, metabolism assay, and infiltrating T-cell function analysis were implemented to assess the changes in metabolism and immune microenvironment of PCa. We found that the expression of NEAT1 was higher in PCa than in non-neoplastic tissues. The cell proliferative capability of PCa cells was significantly reduced in the NEAT1 knockdown group. PCR array and bioinformatics analysis revealed that the enrichment of acidic substance-related gene sets was associated with NEAT1 expression. NEAT1 depletion inhibited PCa cell aerobic glycolysis accompanied by the reduction of lactate levels in the medium. Further, we found that lactate dehydrogenase A (LDHA) expression was positively regulated by NEAT1. At last, co-culture systems indicated that NEAT1 or LDHA knockdown promoted the secretion of CD8+ T-lymphocyte factors, including TNF-α, IFN-γ, and Granzyme B, and enhanced the antitumor effects.

MicroRNA-140-5p exacerbates vascular cognitive impairment by inhibiting neurogenesis in the adult mouse hippocampus after global cerebral ischemia.

Vascular cognitive impairment (VCI) is the most common type of dementia after Alzheimer's disease (AD). Effective treatments for VCI are currently lacking. MicroRNA (miR)- 140-5p is associated with cerebral ischemia and poststroke depression, but its relationship with VCI remains unknown. A VCI model was established by bilateral common carotid artery occlusion (BCCAO) for 17 min in mice. Neurogenesis was evaluated by immunostaining for Nestin/bromodeoxyuridine (BrdU), NeuN/BrdU, and doublecortin (DCX)/BrdU. Neuroplasticity was assessed by quantifying synapsin-I and postsynaptic density protein 95 (PSD-95) protein levels. Predicted target genes were screened and verified using the dual luciferase reporter gene system. MiR-140-5p was upregulated in the hippocampus of the BCCAO mice 2 weeks following ischemia. Compared with control groups, the AAV-miR-140-5p group exhibited poorer cognitive performance alongside lower numbers of DCX/BrdU and NeuN/BrdU and less synapsin-I and PSD-95 in the dentate gyrus (P < 0.05). MiR-140-5p overexpression decreased the predicted target gene Prox1. Dual luciferase reporter system confirmed that Prox1 was a direct target site for miR-140-5p. In conclusion, our results suggest that miR-140-5p inhibits neurogenesis and neuroplasticity via downregulation of Prox1 and aggravates VCI. Our findings highlight that miR-140-5p is involved in the pathological process of VCI and provides information for the development of new treatments, which may need further inhibition tests to verify.

Periventricular White Matter Hyperintensity in Males is Associated with Post-Stroke Depression Onset at 3 Months.

OBJECTIVE: This study aimed to explore the correlation between white matter hyperintensity (WMH) and post-stroke depression (PSD) at 3 months, and to further investigate sex differences in the pathogenesis of PSD. METHODS: A total of 238 consecutive patients with acute cerebral infarction were recruited. PSD was assessed at 2 weeks and at 3 months after stroke onset. All stroke cases were divided into four subgroups according to the diagnosis of depression at two time nodes: continuous depression; depression remission; late-onset PSD; and continuous non-depression. The Fazekas and Scheltens visual rating scales were adopted to assess WMH. RESULTS: Logistic regression revealed that the presence of periventricular white matter hyperintensity (PVWMH) at baseline in male patients was an independent risk factor for PSD at 3 months. Further subgroup analysis revealed that PVWMH was associated with late-onset PSD in males, but not with continuous depression 3 months after stroke. Male acute stroke patients with PVWMH at baseline were more likely to develop PSD at 3 months, especially late-onset PSD. CONCLUSION: Our data suggest that sex differences may influence the pathogenesis of PSD.

Transfusion Strategies for Pediatric Cardiac Surgery: A Meta-Analysis and Trial Sequential Analysis.

This study aimed to compare the effects of restrictive and liberal red blood cell (RBC) transfusion strategies on pediatric patients undergoing cardiac surgery, including cyanotic and non-cyanotic children. A literature search of the MEDLINE, EMBASE, PubMed, and the Cochrane Library database was conducted. Meta-analyses were carried out comparing restrictive and liberal transfusion strategies. Subgroup analyses were performed based on the basis of cyanotic status. Five randomized controlled trials with a total of 497 children were included. There was no significant difference in the risk of in-hospital mortality between the two transfusion strategies (risk ratio 1.21; 95% confidence interval 0.49 to 2.99; P = 0.68). The trial sequential analysis suggested that the current meta-analysis had an absence of evidence for in-hospital mortality, and the data were insufficient. Moreover, no significant differences existed between groups in terms of risk of infection, blood loss, duration of mechanical ventilation, pediatric intensive care unit (PICU) stay duration, or hospital stay duration. Cyanotic children treated with a liberal transfusion strategy had a shorter ventilator duration, but the transfusion strategy did not affect in-hospital mortality, infection, hospital stay, or PICU stay duration. On the basis of the available data, our analysis indicates that a liberal transfusion strategy did not lead to a better outcomes, but the data are extremely sparse, which highlights the need for clearer transfusion guidelines specific to this specific population.Trial registration number CRD42018102283.

Clinical significance of apelin in the treatment of type 2 diabetic peripheral neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. As apelin is an adipocytokine closely associated with diabetes, this study explored the clinical significance of serum apelin levels in patients with type 2 DPN before and after treatment. METHODS: In total, 44 patients with T2DM without DPN (non-DPN group), 41 patients with DPN who received antihyperglycemic treatment (DPN-A group), 44 patients with DPN who received antihyperglycemic treatment combined with nutritional neurotherapy (DPN-B group), and 40 healthy control individuals (NC group) were selected continuously enrolled in the present study. Enzyme-linked immunosorbent assays (ELISA) were performed to determine serum levels of apelin and tumor necrosis factor-α (TNF-α). Related apelin, fasting blood glucose (FBG), glycosylated hemoglobin A1c, TNF-α, body mass index, fasting C peptide, and nerve conduction velocity (NCV) were recorded in each group before and after treatment. RESULTS: Serum levels of apelin and TNF-α were higher in patients with diabetes than those in the NC group, as well as in the DPN group as compared to the non-DPN group; furthermore, some NCV values were significantly reduced in the DPN group. After treatment, the serum levels of apelin, TNF-α, and FBG reduced in patients with diabetes; moreover, apelin levels were found significantly lower in the DPN-B group as compared to the DPN-A group, while some NCV values significantly increased in the DPN-B group. Apelin was negatively correlated with part of NCV values and positively correlated with TNF-α and FBG (P < .01). CONCLUSION: Our results show that the increase in serum apelin levels is an important clinical reference index for DPN, while a decrease indicates that the DPN treatment is effective.

Study on the Effect of Polymer Nano-Loaded Drug System on Bladder Cancer Perfusion.

Bladder tumor is a malignant tumor on bladder mucosa and the most common malignant tumor of urinary system. At present, bladder cancer is mainly treated by surgical resection and intravesical infusion of anticancer drugs. The high-molecular nano-drug-loading system has the advantages of direct focus of the drug in the treatment of cancer, reduced systemic toxicity and high local concentration. The purpose of this paper was to study the effect of polymer nano-drug loading system on bladder cancer perfusion. The synthesized polymer was applied to the establishedmouse bladder cancer model, the anticancer effect of polymer nano-drug loading system on mice in vivo was observed, and the health status of mice during administration was determined. It was found that a large number of drugs could adhere to the tumor tissue after perfusion of bladder cancer with polymer nano-drug loading system, and the effect of killing bladder cancer cells was better.

[Relationship of prostate volume and inflammatory cell infiltration with the positive rate of prostate biopsy].

OBJECTIVE: To investigate the factors influencing the positive rate of prostate biopsy and its relationship with the prostate volume and inflammatory cell infiltration (ICI). METHODS: We retrospectively analyzed the clinical data on 230 cases of double-plane transrectal ultrasound-guided prostate biopsy in our Department of Urology, including the patients' age, body mass index (BMI), serum total prostate-specific antigen (tPSA), PSA density (PSAD), prostate volume, and ICI in the prostate tissue. We also investigated the relationship of the above factors with the pathological results of prostate biopsy by binary logistic regression analysis. RESULTS: The positive rate of prostate biopsy was 38.7% (89/230) in the total number of cases, 28.57% (n = 56) in the 196 cases with tPSA < 100 µg/L, and 97.06% (n = 33) in the 34 cases with tPSA ≥ 100 µg/L. Binary logistic regression analysis showed that the positive rate of prostate biopsy in those with tPSA < 100 µg/L was correlated positively with age (P < 0.01, OR = 1.09), tPSA (P < 0.01, OR = 1.04) and PSAD (P < 0.01, OR = 10.04), negatively with the prostate volume (P < 0.01, OR = 0.98) and ICI (P < 0.01, OR = 0.22), but not with BMI (P > 0.05). As a predictor of positive prostate biopsy, tPSA > 10 µg/L exhibited a sensitivity of 82.14% and a specificity of 35.71%, while PSAD > 0.26 showed a sensitivity of 78.57% and a specificity of 71.43%. CONCLUSIONS: Non-specific elevation of the tPSA level induced by increased prostate volume and inflammatory cell infiltration may lead to unnecessary biopsies in some patients. As a predictor of positive prostate biopsy, PSAD > 0.26 has a higher clinical application value than tPSA > 10 µg/L.

MicroRNA-210-3p Targets RGMA to Enhance the Angiogenic Functions of Endothelial Progenitor Cells Under Hypoxic Conditions.

Endothelial progenitor cells (EPCs) are multipotential stem cells considered to have immense clinical value for revascularization. However, the clinical application of EPCs has been hampered by their clinical potency in ischemic anoxic environments. This study aimed to explore the effect of microRNA-210 (miR-210) on EPCs under oxygen-glucose deprivation (OGD) conditions. We generated a model of EPCs cultured under OGD conditions to simulate ischemia and explore the expression of miR-210 in vitro. With longer exposure to hypoxia, we found that miR-210-3p expression was highly upregulated in OGD groups compared to that in controls from 4 to 24 h, but not miR-210-5p. We then transfected a miR-210-3p mimic and inhibitor into EPCs, and after 24 h, we exposed them to OGD conditions for 4 h to simulate ischemia. We detected miR-210 by real-time polymerase chain reaction (RT-PCR) and tested the proliferation, migration, and tube formation of normal EPCs and OGD-treated EPCs by CCK-8, transwell chamber, and Matrigel assays, respectively. The direct targets of miR-210-3p were predicted using miRWalk. Compared to that in normal EPCs, higher miR-210-3p expression was found in OGD-treated EPCs (p < 0.05). Moreover, upregulation of miR-210-3p was found to promote proliferation, migration, and tube formation in EPCs under normal and OGD conditions (p < 0.05), whereas down-regulation inhibited these abilities in OGD-treated EPCs (p < 0.05). Repulsive guidance molecule A (RGMA), a negative regulator of angiogenesis, was predicted to be a target of miR-210-3p. Accordingly, upregulation of miR-210-3p was found to inhibit its expression at the protein level in OGD-treated EPCs, whereas downregulation of miR-210-3p inhibited its expression (p < 0.05). A dual-luciferase reporter system confirmed that RGMA is a direct target of miR-210-3p. MicroRNA-210-3p overexpression enhances the angiogenic properties of OGD-treated EPCs by inhibiting RGMA.

MicroRNA-140-5p: A novel circulating biomarker for early warning of late-onset post-stroke depression.

We aimed to explore the circulating microRNAs biomarkers in the acute stage following cerebral ischemia to earlier warn late-onset post-stroke depression (PSD). A total of 251 consecutive patients with acute ischemic stroke were recruited. They were divided into three groups depending on whether PSD had occurred at 2 weeks or 3 months since stroke: early-onset PSD, late-onset PSD, and non-depressed group. Microarray assay was conducted to identify the different expression profiles of plasma miRNAs. Comprehensive bioinformatics analysis for their integrating putative target genes was performed. The key miRNA was validated in a larger cohort and its function was further studied in ischemic mice brain. We screened three differentially expressed miRNAs in the late-onset PSD individuals, miR-140-5p and miR-221-3p were significantly upregulated while miR-1246 was downregulated. The bioinformatics analysis demonstrated that their predicted target genes were mainly enriched in axon development and Ras signaling pathway. Logistic regression analysis revealed that miR-140-5p was an independent risk factor for late-onset PSD (P = 0.017, OR = 2.313, 95%CI 1.158 to 4.617). The miR-140-5p expression on admission was significantly positively correlated with HDRS scores assessed at 3 months after stroke (P = 0.0007). The predictive value of miR-140-5p for late-onset PSD is 83.3% sensitivity and 72.6% specificity (AUC = 0.8127, P < 0.0001). AAV-mediated overexpression of miR-140-5p decreased the protein level of IL1rap, IL1rapl1, VEGF, and MEGF10 in the ischemic mouse hippocampus and inhibited neurogenesis and capillary density. MiR-140-5p might be involved in the pathogenesis of late-onset PSD and used as a novel early warning biomarker.

Fenofibrate inhibits the growth of prostate cancer through regulating autophagy and endoplasmic reticulum stress.

Fenofibrate is a fibric acid derivative which exhibits a role of peroxisome proliferator-activated receptor-alpha agonist. It is widely utilized in therapy of hyperlipidemia and hypercholesterolemia. Its anticancer function is discovered in recent years. However, the role of fenofibrate in prostate cancer (PCa) is poorly understood. In this study, we investigated the function and mechanism of fenofibrate in PCa cells. Firstly, fenofibrate treated PCa cells showed more apoptosis compared with the control group. Further, we found that fenofibrate induced autophagy but finally blocked its complete flux in PCa cells through regulating AMPK-mTOR pathway. The intermediate metabolite from uncompleted autophagy induced endoplasmic reticulum stress (ER stress) via PERK and IRE1 signalings. In vivo mice model confirmed that fenofibrate inhibited the growth of PCa. This study suggests that fenofibrate is an effective inhibitor of PCa by regulating autophagy and ER stress.

Blood microRNA-15a Correlates with IL-6, IGF-1 and Acute Cerebral Ischemia.

OBJECTIVE: This study aims to explore the function of blood microRNA-15a (miR-15a) in the pathogenesis of acute cerebral ischemia (AIS). METHODS: Blood samples were collected from healthy control and AIS patients within 72 h after onset. A model of ischemia in human umbilical vein endothelial cells (HUVECs) was established through oxygen and glucose deprivation (OGD). MiR-15a in patients and in cells was measured using real-time quantitative polymerase chain reaction (qPCR). The predicted target of miR-15a such as interleukin-6 (IL-6) and insulin-like growth factors-1 (IGF-1) in plasma was detected by enzyme-linked immunosorbent assay (ELISA). The relations between blood miR-15a and stroke severity, stroke etiology, infarct location, stroke prognosis, predicted targets were analyzed by Statistical Product and Service Solutions (SPSS) software respectively. RESULTS: Higher miR-15a levels were found in AIS patients and ischemic cells within 72 h, compared to control (p < 0.05). Receiver Operating Characteristic (ROC) analysis showed that blood miR-15a predicted stroke onset with 98.67% specificity. Blood miR-15a had a negative correlation with National Institutes of Health Stroke Scale (NIHSS) scores (r = -0.3695, p < 0.01). The AIS patients with increased miR-15a levels had a better prognosis. MiR-15a was up-regulated in anterior circulation infarction and small-artery atherosclerosis stroke. Plasma levels of IL-6 and IGF-1 were associated with blood miR-15a (r = -0.6051, 0.3231, p < 0.05, respectively). CONCLUSION: Blood miR-15a associates with IL-6, IGF-1 and acute cerebral ischemia. It could serve as a potential diagnostic biomarker and therapeutic target for stroke.

Age-Related Frontal Periventricular White Matter Hyperintensities and miR-92a-3p Are Associated with Early-Onset Post-Stroke Depression.

Objective: To explore the correlationship among white matter hyperintensities (WMHs), miR-92a-3p and early-onset post-stroke depression (PSD). Methods: We recruited consecutively 238 patients with acute cerebral infarction and MRI examination in the Department of neurology, Ruijin hospital, Shanghai Jiaotong University School of Medicine. The diagnosis of early-onset PSD was made in accordance with DSM-IV criteria for depression in 2 weeks after stroke. Clinical information and assessments of stroke severity were recorded on admission. The analysis of plasma miR-92a-3p was performed using quantitative PCR at the same time. WMHs were evaluated by the Fazekas and Scheltens visual rating scales. The relationship among WMHs, miR-92a-3p and PSD were analyzed by SPSS 22.0 software. Results: Logistic regression demonstrated that periventricular WMHs (PVWMHs) in frontal caps was an independent risk factor with early-onset PSD (OR = 1.579, 95% CI: 1.040-2.397, p = 0.032). The age and numbers of lacunes were related to frontal PVWMHs. Plasma miR-92a-3p in the PSD group was higher compared with the non-depressed group. Receiver operating curve analysis revealed that miR-92a-3p could predict early-onset PSD with 90% sensitivity and 90% specificity. The higher miR-92a-3p trended toward association with greater frontal PVWMHs. Conclusion: Acute ischemic stroke patients with frontal PVWMHs or a high plasma miR-92a-3p at baseline were more likely to develop early-onset PSD. MiR-92a-3p might be involved in the white matter impairment and post-stroke depression.

CtBP2 is associated with angiogenesis and regulates the apoptosis of prostate cancer cells.

Angiogenesis is associated with prostate cancer (PCa) development and progression. Aberrant expression of C-terminal binding protein (CtBP)2 has been observed in PCa, but whether its change in expression plays a significant role in angiogenesis has not been completely characterized. we attempted to integrate and analyze the genome-wide association study (GWAS) of follicle stimulating hormone receptor (FSHR) and CtBP2, the Cancer Genome Atlas (TCGA) data and CtBP2 binding data in CistromeMap (18) to explore the mechanism of CtBP2 in PCa, and performed pathway enrichment analysis. We revealed that the top 6 pathways were closely related with angiogenesis. We used siRNA and overexpression plasmids to silence and overexpress CtBP2 expression. Altered expression of CtBP2 affected the expression of VEGFA, FSHR, FHL2 and SMAD3 which are closely related with angiogenesis. In addition, silencing of CtBP2 markedly increased the apoptosis of PCa cells in vitro, and decreased the expression of IL-8, AT2R, CCND1 and MMP9 which are associated with cancer progression. These results highlight the association between CtBP2 and angiogenesis in PCa and indicate that CtBP2 may be a potential therapeutic target for PCa.