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Background: Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among prostate cancer patients. Here, our aim was to ascertain the immune regulatory mechanisms involved in CRPC development and identify potential immunotherapies against CRPC. Methods: A CRPC model was established using Myc-CaP cells in immune-competent FVB mice following castration. The immune cell profile of the tumor microenvironment (TME) was analyzed during CRPC development. Different immunotherapies were screened in the CRPC tumor model, and their efficacies and underlying mechanisms were investigated in vitro and in vivo. Results: During CRPC development, the proportion of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the TME increased. Among the immunotherapies tested, IFNα was more effective than anti-PD-L1, anti-CTLA-4, anti-4-1BB, IL-2, and IL-9 in reducing Myc-CaP CRPC tumor growth. IFNα reduced the number of G-MDSCs both in vitro during differentiation and in vivo in CRPC mice. Furthermore, IFNα reduced the suppressive function of G-MDSCs on T cell proliferation and activation. Conclusion: G-MDSCs are crucial to effective immunotherapy against CRPC. Treatment with IFNα presents a promising therapeutic strategy against CRPC. Besides the direct inhibition of tumor growth and the promotion of T cell priming, IFNα reduces the number and the suppressive function of G-MDSCs and restores T cell activation.

To investigate the effect of crystallization treatment on the structure and magnetocaloric effect of Gd60Co40 amorphous alloy, the melt-spun ribbons were annealed at 513 K isothermally for 20, 40 and 60 min. The results indicate that, with increasing annealing time, the Gd4Co3 (space group P63/m) and Gd12Co7 (space group P21/c) phases precipitated from the amorphous precursor in sequence. In particular, in the samples annealed for 40 and 60 min, three successive magnetic transitions corresponding to the phases of Gd4Co3, Gd12Co7 and remaining amorphous matrix were detected, which induced an overlapped broadened profile of magnetic entropy change (|ΔSM|) versus temperature. Under magnetic field changing from 0 to 5 T, |ΔSM| values of 6.65 ± 0.1 kg−1·K−1 and 6.44 ± 0.1 J kg−1·K−1 in the temperature spans of 180–196 K and 177–196 K were obtained in ribbons annealed for 40 and 60 min, respectively. Compared with the fully amorphous alloy, the enhanced relative cooling power and flattened magnetocaloric effect of partially crystallized composites making them more suitable for the Ericsson thermodynamic cycle.

Abstract Background Circular RNA (circRNA) is one type of noncoding RNA that forms a covalently closed continuous loop. Similar to long noncoding RNA (lncRNA), circRNA can act as microRNA (miRNA) ‘sponges’ to regulate gene expression, and its abnormal expression is related to diseases such as atherosclerosis, nervous system disorders and cancer. So far, there have been no systematic studies on circRNA abundance and expression profiles in human adult and fetal tissues. Results We explored circRNA expression profiles using RNA-seq data for six adult and fetal normal tissues (colon, heart, kidney, liver, lung, and stomach) and four gland normal tissues (adrenal gland, mammary gland, pancreas, and thyroid gland). A total of 8120, 25,933 and 14,433 circRNAs were detected by at least two supporting junction reads in adult, fetal and gland tissues, respectively. Among them, 3092, 14,241 and 6879 circRNAs were novel when compared to the published results. In each adult tissue type, we found at least 1000 circRNAs, among which 36.97–50.04% were tissue-specific. We reported 33 circRNAs that were ubiquitously expressed in all the adult tissues we examined. To further explore the potential “housekeeping” function of these circRNAs, we constructed a circRNA-miRNA-mRNA regulatory network containing 17 circRNAs, 22 miRNAs and 90 mRNAs. Furthermore, we found that both the abundance and the relative expression level of circRNAs were higher in fetal tissue than adult tissue. The number of circRNAs in gland tissues, especially in mammary gland (9665 circRNA candidates), was higher than that of other adult tissues (1160–3777). Conclusions We systematically investigated circRNA expression in a variety of human adult and fetal tissues. Our observation of different expression level of circRNAs in adult and fetal tissues suggested that circRNAs might play their role in a tissue-specific and development-specific fashion. Analysis of circRNA-miRNA-mRNA network provided potential targets of circRNAs. High expression level of circRNAs in mammary gland might be attributed to the rich innervation.

Abstract Background Percutaneous nephrolithotomy (PCNL) remains the standard procedure for large (≥2 cm) renal calculi; however, laparoscopic pyelolithotomy (LPL) can be used as an alternative management procedure. The aim of present study was to compare LPL and PCNL in terms of efficacy and safety for the management of large renal pelvic stones. Methods A literature search was performed in Jan 2016 using electronic databases (Cochrane Central Register of Controlled Trials, Medline, and EMBASE) to identify relevant studies for the meta-analysis. Only comparative studies investigating LPL versus PCNL were included. Effect sizes were estimated by pooled odds ratio (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Results Five randomized and nine non-randomized studies were identified for analysis, involving a total of 901 patients. Compared with PCNL, LPL provided a significantly higher stone-free rate (OR 3.94, 95% CI 2.06–7.55, P

Abstract Fusion gene derived from genomic rearrangement plays a key role in cancer initiation. The discovery of novel gene fusions may be of significant importance in cancer diagnosis and treatment. Meanwhile, next generation sequencing technology provide a sensitive and efficient way to identify gene fusions in genomic levels. However, there are still many challenges and limitations remaining in the existing methods which only rely on unmapped reads or discordant alignment fragments. In this work we have developed GFusion, a novel method using RNA-Seq data, to identify the fusion genes. This pipeline performs multiple alignments and strict filtering algorithm to improve sensitivity and reduce the false positive rate. GFusion successfully detected 34 from 43 previously reported fusions in four cancer datasets. We also demonstrated the effectiveness of GFusion using 24 million 76 bp paired-end reads simulation data which contains 42 artificial fusion genes, among which GFusion successfully discovered 37 fusion genes. Compared with existing methods, GFusion presented higher sensitivity and lower false positive rate. The GFusion pipeline can be accessed freely for non-commercial purposes at: https://github.com/xiaofengsong/GFusion .

The histidine-rich calcium-binding protein (HRC) is a regulator of Ca2+ homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrates that HRC was upregulated in fibrotic liver and activated hepatic stellate cells (HSCs). TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagen expression, and inhibited HSC proliferation and migration. In addition, we found that the anti-fibrosis effect of HRC knockdown was associated with endoplasmic reticulum (ER) stress. Silencing of HRC decreased the expression of ER stress and autophagy markers. Moreover, ER stress agonist thapsigargin (TG) enhanced, whereas ER stress antagonist 4-phenylbutyric acid (4-PBA) alleviated HSCs activation and autophagy. In conclusion, these data indicate that depletion of HRC inhibited HSC activation through the ER stress pathway, and HRC may be a potential regulator of liver fibrosis.

Background & Objectives: The Previous studies of multidetector CT (MDCT) of the lower extremities for the detection of peripheral vascular disease showed high diagnostic accuracy but were performed with older generation systems. Our study aimed at assessing the diagnostic value of 128 MDCTA compared with that of digital subtraction angiography (DSA) in the grading of focal arterial disease of lower extremity arteries on the basis of anatomic regions.Materials & Methods: Forty-two patients with peripheral arterial occlusive diseases underwent both MDCTA and DSA. Lower extremity arteries depicted at MDCTA and DSA were graded separately for the degree of stenosis into 3 anatomic regions and 33 segments. Grading by MDCTA and DSA was done independently. Homogeneity analysis was used between MDCTA and DSA measurements in each patient. The sensitivity, specificity, positive predictive value and negative predictive value for detection of stenotic lesions were calculated for all anatomic regions, with findings at DSA used as the reference standard. Results: No statistically significant difference (P>.05) between DSA and MDCTA was present in Aorto-iliac and poplitiofemoral regions while there was statistically significant difference (PConclusion: MDCTA is excellent alternative in diagnosing lower extremity arterial occlusive diseases above the knee. DSA remains better on illustrating distal runoff vessels.

Abstract Chemokines are a group of low molecular weight peptides. Their major function is the recruitment of leukocytes to inflammation sites, but they also play a key role in tumor growth, angiogenesis, and metastasis. In the last few years, accumulated experimental evidence supports that monokine induced by interferon (IFN)‐gamma (CXCL9), a member of CXC chemokine family and known to attract CXCR3‐ (CXCR3‐A and CXCR3‐B) T lymphocytes, is involved in the pathogenesis of a variety of physiologic diseases during their initiation and their maintenance. This review for the first time presents the most comprehensive summary for the role of CXCL9 in different types of tumors, and demonstrates its contradictory role of CXCL9 in tumor progression. Altogether, this is a useful resource for researchers investigating therapeutic opportunities for cancer.

Somatic gene mutations play a critical role in immune evasion by tumors. However, there is limited information on genes that confer immunotherapy resistance in melanoma. To answer this question, we established a whole-genome knockout B16/ovalbumin cell line by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease technology, and determined by in vivo adoptive OT-I T-cell transfer and an in vitro OT-I T-cell-killing assay that Janus kinase (JAK)1 deficiency mediates T-cell resistance via a two-step mechanism. Loss of JAK1 reduced JAK-Signal transducer and activator of transcription signaling in tumor cells—resulting in tumor resistance to the T-cell effector molecule interferon—and suppressed T-cell activation by impairing antigen presentation. These findings provide a novel method for exploring immunotherapy resistance in cancer and identify JAK1 as potential therapeutic target for melanoma treatment.

Purpose: To evaluate the potential added value of integrating anti-apoptotic molecules for improving the anti-tumor activity of CAR-T cells. Methods: Four small molecules inhibiting apoptosis were tested for their ability to prevent activated induced CAR-T cell death. Five CD20-targeting, CD137 (4-1BB) and CD3ζ integrated CAR-T cells (20BBZ) with constitutively expressed anti-apoptotic genes were established, and we screened out the strongest proliferation enhancer: Bcl-2. The memory subtype and the exhaustion markers of CAR-T cells were analyzed. The anti-tumor activities of Bcl-2 integrating CAR-T cells (20BBZ-Bcl-2) were evaluated in vitro and in a mouse xenograft lymphoma model. Conclusion: The 20BBZ-Bcl-2 CAR-T cells showed improved proliferation ability compared to 20BBZ CAR-T cells in vitro. In addition, activation-induced apoptosis was reduced in the 20BBZ-Bcl-2 CAR-T cells. Consistent with the enhanced proliferation in vitro, 20BBZ-Bcl-2 CAR-T cells exhibited improved anti-tumor activity in a mouse xenograft lymphoma model.

In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy (ADT) alone versus combined with radiation therapy (RT) or chemotherapy for locally advanced and metastatic prostate cancer (PCa). A literature search was performed using OvidSP. Randomized controlled trials (RCTs) that met the following criteria were included: including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT (n = 2344) and one compared ADT versus ADT plus docetaxel-estramustine (n = 413) in locally advanced PCa; two compared ADT versus ADT plus docetaxel (n = 1175) and two compared ADT versus ADT plus estramustine (n = 114) in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio (OR) of overall survival (OS) was 1.43 (95% confidence interval 1.20-1.71) when compared ADT plus RT with ADT alone (P < 0.0001). For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS: 1.29 [1.01-1.65]: P = 0.04). In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.

This paper was aimed to compare the clinical effectiveness and safety of adult male circumcision using the Shang Ring™ (SR) with the no-flip technique compared with Dorsal Slit (DS) surgical method. A single-centered, prospective study was conducted at the West China Hospital, where patients were circumcised using the no-flip SR (n = 408) or the DS (n = 94) procedure. The adverse events (AEs) and satisfaction were recorded for both groups, and ring-removal time and percentage of delayed removals were recorded for the SR group. Finally, complete follow-up data were collected for 76.1% of patients (SR: n = 306; DS: n = 76). The average ring-removal time for the SR group was 17.62 ± 6.30 days. The operation time (P < 0.001), pain scores during the procedure (P < 0.001) and at 24 h postoperatively (P < 0.001), bleeding (P = 0.001), infection (P = 0.034), and satisfaction with penile appearance (P < 0.001) in the SR group were superior to those in the DS group. After two postoperative weeks, the percentage of patients with edema in the SR group (P = 0.029) was higher but no differences were found at 4 weeks (P = 0.185) between the two groups. In conclusions, the no-flip SR method was found to be superior to the DS method for its short operation time (

The complementary metal oxide semiconductor (CMOS) microbolometer technology provides a low-cost approach for the long-wave infrared (LWIR) imaging applications. The fabrication of the CMOS-compatible microbolometer infrared focal plane arrays (IRFPAs) is based on the combination of the standard CMOS process and simple post-CMOS micro-electro-mechanical system (MEMS) process. With the technological development, the performance of the commercialized CMOS-compatible microbolometers shows only a small gap with that of the mainstream ones. This paper reviews the basics and recent advances of the CMOS-compatible microbolometer IRFPAs in the aspects of the pixel structure, the read-out integrated circuit (ROIC), the focal plane array, and the vacuum packaging.

This paper illustrates a simple yet effective spectroscopic technique for the prediction of soil organic matter (SOM) from moist soil through the synchronous 2D correlation spectroscopy (2D-COS) analysis. In the moist soil system, the strong overlap between the water absorption peaks and the SOM characteristic features in the visible-near infrared (Vis-NIR) spectral region have long been recognised as one of the main factors that causes significant errors in the prediction of the SOM content. The aim of the paper is to illustrate how the tangling effects due to the moisture and the SOM can be unveiled under 2D-COS through a sequential correlogram analysis of the two perturbation variables (i.e., the moisture and the SOM) independently. The main outcome from the 2D-COS analysis is the discovery of SOM-related bands at the 597 nm, 1646 nm and 2138 nm, together with the predominant water absorbance feature at the 1934 nm and the relatively less important ones at 1447 nm and 2210 nm. This information is then utilised to build partial least square regression (PLSR) models for the prediction of the SOM content. The experiment has shown that by discarding noisy bands adjacent to the SOM features, and the removal of the water absorption bands, the determination coefficient of prediction (Rp2) and the ratio of prediction to deviation (RPD) for the prediction of SOM from moist soil have achieved Rp2 = 0.92 and the RPD = 3.19, both of which are about 5% better than that of using all bands for building the PLSR model. The very high RPD (=3.19) obtained in this study may suggest that the 2D-COS technique is effective for the analysis of complex system like the prediction of SOM from moist soil.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In this paper, the chemical vapor deposition (CVD) processing for 4H-SiC epilayer is investigated with particular emphasis on the defects and the noise properties. It is experimentally found that the process parameters of C/Si ratio strongly affect the surface roughness of epilayers and the density of triangular defects (TDs), while no direct correlation between the C/Si ratio and the deep level defect Z1/2 could be confirmed. By adjusting the C/Si ratio, a decrease of several orders of magnitudes in the noise level for the 4H-SiC Schottky barrier diodes (SBDs) could be achieved attributing to the improved epilayer quality with low TD density and low surface roughness. The work should provide a helpful clue for further improving the device performance of both the 4H-SiC SBDs and the Schottky barrier ultraviolet photodetectors fabricated on commercial 4H-SiC wafers.

Background and Aims: Abnormalities in neural activity have been reported in cirrhosis with minimal hepatic encephalopathy (MHE). However, little is known about the neurophysiological mechanisms in this disorder. We aimed to investigate the altered patterns of regional synchronization and functional connections in hepatitis B virus-related cirrhosis (HBV-RC) patients with and without MHE using both regional homogeneity (ReHo) and region of interest (ROI)-based functional connectivity (FC) computational methods.Methods: Data of magnetic resonance imaging scans were collected from 30 HBV-RC patients with MHE, 32 HBV-RC patients without MHE (NMHE) and 64 well-matched controls. Several regions showing differences in ReHo after one-way analysis of variance (ANOVA) were defined as ROIs for FC analysis. Next, post hoc t-tests were applied to calculate the group differences in ReHo and FC (false discovery rate (FDR) correction, p < 0.05). Correlations between clinical variables and the altered ReHo and FC were then assessed in patient groups.Results: Across three groups, significant ReHo differences were found in nine ROI regions mainly within the visual network (VN), dorsal attention network (DAN), somatomotor network (SMN), fronto parietal control (FPC) network and thalamus. Compared with healthy controls (HC), the MHE group exhibited abnormal FC mainly between the right calcarine (CAL.R) and middle frontal gyrus (MFG.L)/right thalamus. The MHE patients showed increased FC between the MFG.L and CAL.R compared to NMHE patients. Disease duration of MHE patients was positively correlated with increased mean ReHo values in the right fusiform gyrus (FFG); psychometric hepatic encephalopathy score (PHES) test scores were negatively correlated with increased FC between MFG.L and CAL.R and positively correlated with reduced FC between the CAL.R and THA.R. For NMHE patients, the mean ReHo values in the right frontal pole were positively correlated with disease duration and positively correlated with the PHES scores.Conclusion: Our results exhibited that the functional brain modifications in patients with and without MHE are characterized by compound alterations in local coherence and functional connections in the VN, SMN, DAN, FPC networks and thalamus by using a combination of ReHo and ROI-based FC analysis. These functional imaging changes are correlated with disease duration/PHES. This study helped us gain a better understanding of the features of brain network modifications in cirrhosis.

PURPOSE:To evaluate the diagnostic performance of left coronary bifurcation angles and plaque characteristics for prediction of coronary stenosis by dual-source CT. METHODS:106 patients suspected of coronary artery disease undergoing both coronary computed tomography angiography (CCTA) and invasive coronary angiography (CAG) within three months were included. Left coronary bifurcation angles including the angles between the left anterior descending artery and left circumflex artery (LAD-LCx), left main coronary artery and left anterior descending artery (LM-LAD), left main coronary artery and left circumflex artery (LM-LCx) were measured on CT images. CCTA plaque parameters were calculated by plaque analysis software. Coronary stenosis ≥ 50% by CAG was defined as significant. RESULTS:106 patients with 318 left coronary bifurcation angles and 126 vessels were analyzed. The bifurcation angle of LAD-LCx was significantly larger in left coronary stenosis ≥ 50% than stenosis < 50%, and significantly wider in the non-calcified plaque group than calcified. Multivariable analyses showed the bifurcation angle of LAD-LCx was an independent predictor for significant left coronary stenosis (OR = 1.423, P = 0.002). In ROC curve analysis, LAD-LCx predicted significant left coronary stenosis with a sensitivity of 66.7%, specificity of 78.4%, positive predictive value of 85.2% and negative predictive value of 55.8%. The lipid plaque volume improved the diagnostic performance of CCTA diameter stenosis (AUC: 0.854 vs. 0.900, P = 0.045) in significant coronary stenosis. CONCLUSIONS:The bifurcation angle of LAD-LCx could predict significant left coronary stenosis. Wider LAD-LCx is related to non-calcified lesions. Lipid plaque volume could improve the diagnostic performance of CCTA for coronary stenosis prediction.

Objectives. The aim of the present study was to analyze the association between pretreatment body mass index (BMI) and the aggressiveness of papillary thyroid carcinoma (PTC) along with its clinical outcomes in a Chinese population with BMI classification for Asians. Methods. A retrospective, observational study was conducted on patients from two teaching hospitals in China. 1622 classical PTC patients were categorized into four groups according to BMI. Results. We found that increased BMI was associated with extrathyroidal extension, multifocality, the presence of lymph node (LN) metastasis, and advancing TNM stage in PTC patients. Furthermore, compared to patients with normal weight, those in the overweight and obese group exhibited a significantly increased risk of extrathyroidal extension, multifocality, cervical LN metastasis, and advanced TNM stage. 40 and 37 patients experienced persistent and recurrent disease, respectively. No differences regarding persistent disease or recurrence were observed among the BMI groups. Conclusion. A higher pretreatment BMI has been strongly associated with aggressive features of PTC according to the BMI classification for Asians. Obesity was not found to be associated with a greater risk of recurrence.

[This corrects the article DOI: 10.1371/journal.pone.0172498.].

The incidence of melanoma, the most aggressive and life-threatening form of skin cancer, has significantly risen over recent decades. Therefore, it is essential to identify the mechanisms that underlie melanoma tumorigenesis and metastasis and to explore novel and effective melanoma treatment strategies. Accumulating evidence s uggests that aberrantly expressed long noncoding RNAs (lncRNAs) have vital functions in multiple cancers. However, lncRNA functions in melanoma tumorigenesis and metastasis remain unclear. In this study, we investigated lncRNA and messenger RNA (mRNA) expression profiles in primary melanomas, metastatic melanomas and normal skin samples from the Gene Expression Omnibus database. We used GSE15605 as the training set (n = 74) and GSE7553 as the validation set (n = 58). In three comparisons (primary melanoma versus normal skin, metastatic melanoma versus normal skin, and metastatic melanoma versus primary melanoma), 178, 295 and 48 lncRNAs and 847, 1758, and 295 mRNAs were aberrantly expressed, respectively. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to examine the differentially expressed mRNAs, and potential core lncRNAs were predicted by lncRNA-mRNA co-expression networks. Based on our results, 15 lncRNAs and 144 mRNAs were significantly associated with melanoma tumorigenesis and metastasis. A subsequent analysis suggested a critical role for a five-lncRNA signature during melanoma tumorigenesis and metastasis. Low expression of U47924.27 was significantly associated with decreased survival of patients with melanoma. To the best of our knowledge, this study is the first to explore the expression patterns of lncRNAs and mRNAs during melanoma tumorigenesis and metastasis by re-annotating microarray data from the Gene Expression Omnibus (GEO) microarray dataset. These findings reveal potential roles for lncRNAs during melanoma tumorigenesis and metastasis and provide a rich candidate reservoir for future studies.

A 44-year-old woman who underwent radical nephrectomy due to a left renal mass presented to our clinic. Results of the histopathological examination showed a mixed epithelial and stromal tumor of the kidney, a rare benign lesion of the kidney. The epidemiology, histopathological features, imaging features, possible pathogeneses, and treatment alternatives are discussed, and the relevant literature is reviewed. The postoperative course was uneventful, and the patient was free of local recurrence or metastasis until the last follow-up (12 months).

In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic rats P

Although acupuncture is widely used to manage pain, it remains highly controversial, largely due to the lack of a clear mechanism for its benefits. Here, we investigated the role of IL-33, a novel interleukin (IL)-1 family member, and its receptor ST2 in the analgesic effects of electroacupuncture (EA) on formalin-induced inflammatory pain. The results showed that 1) EA stimulation of ipsilateral Zusanli (ST 36) and Yanglingquan (GB 34) acupoints for 30 min remarkably suppressed the two phases of formalin-induced spontaneous pain; 2) subcutaneous or intrathecal administration of recombinant IL-33 (rIL-33) significantly inhibited the analgesic effect of EA, whereas the ST2 antibody potentiated EA analgesia in formalin mice; 3) EA treatment decreased the up-regulation of IL-33 and ST2 protein following formalin injection; and 4) the suppression of the formalin-induced expression of spinal phosphorylated ERK and JNK induced by EA treatment was significantly attenuated following subcutaneous rIL-33 delivery, and was further decreased by the ST2 antibody. These data suggest that EA alleviates formalin-induced inflammatory pain, at least partially, by inhibiting of spinal IL-33/ST2 signaling and the downstream ERK and JNK pathways.

In this study, we evaluated if male circumcision was associated with lower HIV acquisition for HIV (-) males and HIV (-) females during normal sexual behavior. We performed a systematic literature search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify studies that compared HIV acquisition for the circumcised and uncircumcised groups. The reference lists of the included and excluded studies were also screened. Fifteen studies (4 RCTs and 11 prospective cohort studies) were included, and the related data were extracted and analyzed in a meta-analysis. Our study revealed strong evidence that male circumcision was associated with reduced HIV acquisition for HIV(-) males during sexual intercourse with females [pooled adjusted risk ratio (RR): 0.30, 95% CI 0.24 0.38, P < 0.00001] and provided a 70% protective effect. In contrast, no difference was detected in HIV acquisition for HIV (-) females between the circumcised and uncircumcised groups (pooled adjusted RR after sensitivity analysis: 0.68, 95%CI 0.40-1.15, P = 0.15). In conclusion, male circumcision could significantly protect males but not females from HIV acquisition at the population level. Male circumcision may serve as an additional approach toward HIV control, in conjunction with other strategies such as HIV counseling and testing, condom promotion, and so on.

Extrauterine endometrial stromal sarcoma (ESS) arising in endometriosis is extremely rare, particularly in the colorectum. It should always be included in the differential diagnosis of primary tumors originating from gastrointestinal tract in females, given that preoperative endoscopical biopsy may reveal no specific changes. We reported a case of ESS arising in colorectal endometriosis and reviewed the previous 7 cases reported in the English literature. Our patient, who was unavailable for tumor resection and refused further adjuvant therapy, played a role in representing the natural history of low-grade extragenital ESS. This case was the only death from ESS arising in colorectal endometriosis.

We fabricate 2.6 μm InGaAs photodetectors by MBE technology and study its dark current mechanisms. Deep-level transient spectroscopy (DLTS) demonstrates a deep-level trap located at Ec - 0.25 eV in the absorption layer. Using the trap parameters, a dark current model is constructed and the device simulation generates the dark current characteristic which agrees well with the experimental data. The model suggests that the dark current at low reverse voltage is dominated by the Shockley-Read-Hall (SRH) and trap-assisted tunneling (TAT). Furthermore, it predicts some basic rules for suppressing the dark current in 2.6 μm InGaAs detectors.

Metastasis contributes to the poor prognosis of hepatocellular carcinoma (HCC). Anoikis resistance and orientation chemotaxis are two important and sequential events in tumor cell metastasis. The process of tumor metastasis is known to be regulated by AEG-1, an important oncogene that plays a critical role in tumor metastasis, though the effects of this oncogene on anoikis resistance and orientation chemotaxis in HCC cells are currently unknown. To directly assess the role of AEG-1 in these processes, we up-regulated AEG-1 expression via exogenous transfection in SMMC-7721 cells, which express low endogenous levels of AEG-1; and down-regulated AEG-1 expression via siRNA-mediated knockdown in MHCC-97H and HCC-LM3 cells, which express high endogenous levels of AEG-1. Our data directly demonstrate that AEG-1 promotes cell growth as assessed by cell proliferation/viability and cell cycle analysis. Furthermore, the prevention of anoikis by AEG-1 correlates with decreased activation of caspase-3. AEG-1-dependent anoikis resistance is activated via the PI3K/Akt pathway and is characterized by the regulation of Bcl-2 and Bad. The PI3K inhibitor LY294002 reverses the AEG-1 dependent effects on Akt phosphorylation, Bcl-2 expression and anoikis resistance. AEG-1 also promotes orientation chemotaxis of suspension-cultured cells towards supernatant from Human Pulmonary Microvascular Endothelial Cells (HPMECs). Our results show that AEG-1 activates the expression of the metastasis-associated chemokine receptor CXCR4, and that its ligand, CXCL12, is secreted by HPMECs. Furthermore, the CXCR4 antoagonist AMD3100 decreases AEG-1-induced orientation chemotaxis. These results define a pathway by which AEG-1 regulates anoikis resistance and orientation chemotaxis during HCC cell metastasis.

To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in "real-life" Chinese patients.A total of 38,464 "real-life" Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m) and M probe (for adults) were used. LSM failure defined as zero valid shots (unsuccessful LSM), or the ratio of the interquartile range to the median of 10 measurements (IQR/M) greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM).LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464), among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients (0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI) greater than 30 kg/m(2), female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P

Utilizing an inquiry-learning space (ILS) via the Go-Lab platform, we investigated students' technology acceptance, knowledge integration [KI] process, and learning outcomes of both the high-achiever KI student and low-achiever KI student. This study aimed to understand how students engage in knowledge integration tasks using an inquiry-learning space to learn Mendelian genetics and realize the relationship between student KI and domain knowledge. Using a quasi-experimental design, we examined 41 seventh-grade students in Taiwan completing Mendelian genetics KI tasks in ILS, pre/post-testing of domain knowledge tests, and a technology acceptance questionnaire. The analysis of students' interaction in the ILS and domain knowledge tests was conducted through descriptive statistics, t-tests, Pearson's correlation, and content analysis to indicate the direction and relationship between students' KI processes and learning outcomes. A technology acceptance questionnaire was analyzed through descriptive statistics and Pearson's correlation to reveal whether students accepted learning on the Go-Lab platform. The study showed that (i) students responded positively to the perceived usefulness of the Go-Lab platform, (ii) the high-achiever KI students could gradually construct links from simple to complex and diverse among genetic ideas, and the low-achiever almost built simple links, but (iii) the high-achiever and low-achiever KI students had similar learning outcomes. These findings have implications that the instruction design of knowledge integration tasks promotes students' Mendelian genetics conceptual understanding and KI progress.

SPRY4-IT1 has been reported to have extremely high expression in normal placenta tissues. It is a Long noncoding RNA (lncRNA), which is associated with cell growth, migration, invasion, and apoptosis in melanoma. A 2.8-fold increase of SPRY4-IT1 expression was validated by Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in severe preeclamptic placenta as compared with that of the normal ones (n=25) in this study. Furthermore, the role of SPRY4-IT1 in proliferation, migration, apoptosis, and network formation ability of trophoblast cells HTR-8/SVneo was assessed. Suppression of SPRY4-IT1 using siRNA treatment and its overexpression using plasmid targeting SPRY4-IT1 were performed in order to explore the biological function of SPRY4-IT1 in the development and progression of trophoblast cells HTR-8/SVneo, in vitro. The results showed that SPRY4-IT1 knockdown enhanced the cell migration and proliferation, and reduced the response of cells to apoptosis. However, exogenous SPRY4-IT1 overexpression significantly decreased the cell migration and proliferation, while increased cell apoptosis. Our study showed for the first time that aberrant expression of lncRNA SPRY4-IT1 might contribute to the abnormal condition of trophoblast cells HTR-8/SVneo. Therefore, we proposed SPRY4-IT1 as a novel lncRNA molecule, which might be associated with the pathogenesis of preeclampsia and might provide a new target for its early diagnosis and treatment.

Auxin is one type of phytohormones that plays important roles in nearly all aspects of plant growth and developmental processes. The glycosylation of auxins is considered to be an essential mechanism to control the level of active auxins. Thus, the identification of auxin glycosyltransferases is of great significance for further understanding the auxin regulation. In this study, we biochemically screened the group L of Arabidopsis thaliana glycosyltransferase superfamily for enzymatic activity toward auxins. UGT74D1 was identified to be a novel auxin glycosyltransferase. Through HPLC and LC-MS analysis of reaction products in vitro by testing eight substrates including auxins and other compounds, we found that UGT74D1 had a strong glucosylating activity toward indole-3-butyric acid [IBA], indole-3-propionic acid [IPA], indole-3-acetic acid [IAA] and naphthaleneacetic acid [NAA], catalyzing them to form corresponding glucose esters. Biochemical characterization showed that this enzyme had a maximum activity in HEPES buffer at pH 6.0 and 37°C. In addition, the enzymatic activity analysis of crude protein and the IBA metabolite analysis from transgenic Arabidopsis plants overexpressing UGT74D1 gene were also carried out. Experimental results indicated that over-production of the UGT74D1 in plants indeed led to increased level of the glucose conjugate of IBA. Moreover, UGT74D1 overexpression lines displayed curling leaf phenotype, suggesting a physiological role of UGT74D1 in affecting the activity of auxins. Our current data provide a new target gene for further genetic studies to understand the auxin regulation by glycosylation in plants.

BACKGROUND: The goal of this study was to explore the feasibility of utilizing human umbilical mesenchymal stem cells (HUMSCs)-seeded Bladder acellular matrix graft (BAMG) for bladder reconstruction in a canine model. METHODOLOGY/PRINCIPAL FINDINGS: HUMSCs were isolated from newborn umbilical cords and identified by flow cytometry. Partial cystectomy was performed in the experimental and control group. Bladder defects were repaired with HUMSCs-BAMG in the experimental group and repaired with unseeded-BAMG in control group. The implanted grafts were harvested after surgery. H&E and immunohistochemistry staining were performed to evaluate the regeneration of the bladder defect. Primary cultured HUMSCs displayed typical fibroblast morphology with spindle-shaped. Flow cytometry indicated that these cells were positive for CD105 (97.3%) and CD44 (99%), but negative for CD34 (2.8%), CD31 (2.1%), and CD45 (1.7%). Immunohistochemistry staining showed that a multilayered urothelium and well-developed smooth muscle were observed at 12 weeks in experiment group. In contrast, multilayered urothelial tissues were also observed at 12 weeks in group B, but well-developed smooth muscle bundles were observed. CONCLUSIONS/SIGNIFICANCE: Our preliminary results demonstrate that UMSC-seeded BAMGs are superior to unseeded BAMGs to promote the regeneration of bladder defects. Our findings indicated that HUMSCs may be a potential cell source for bladder tissue engineering.

OBJECTIVES: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the therapeutic outcome of fluorescence cystoscopy (FC) guided transurethral resection (TUR) in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Relevant RCTs were identified from electronic database (MEDLINE, Embase and the Cochrane Library). The proceedings of relevant congress were also searched. The primary parameters were recurrence rate, the time to fist recurrence, recurrence free survival rate (RFS) and progression rate. RESULTS: 12 RCTs including 2258 patients, which were identified for analysis in our study. Our study showed that the FC group have lower recurrence rate than the white light cystoscopy (WLC) group with statistically significant difference (OR: 0.5; p

BACKGROUND: To investigate the expression and role of special AT-rich sequence-binding protein-2 (SATB2) in laryngeal squamous cell carcinoma (LSCC) tissue and cell line (HEp2), and to evaluate the clinical and prognostic significance of SATB2 protein in patients with LSCC. METHODS: The expression of SATB2 was examined in LSCC tissue and HEp2 cells by Western-blotting, Real-time PCR and immunohistochemical staining. Cell growth curve assay and colony formation assay were used to verify the effect of SATB2 on the proliferation and tumor progression ability of HEp2 cells. Tumor formation assay in nude mice was used to analyze the effect of SATB2 on the tumorigenicity of HEp2 cells. RESULTS: The status of SATB2 protein in carcinoma tissues is much lower than that in paracarcinoma tissues. The overall survival of the patients with high SATB2 expression was significantly higher than the low SATB2 expression group. Lower or negative SATB2 expression was significantly correlated with advanced clinical staging, histological grade and tumor recurrence. In vitro experiments demonstrated that over-expression of SATB2 in HEp2 cells inhibited cell proliferation and tumor progression ability, and down-regulation of SATB2 showed the opposite effects. Over-expression of SATB2 repressed the tumorigenicity of HEp2 cells by in vivo experiments. Moreover, multivariate analysis suggested that SATB2 expression might be an independent prognostic indicator for the survival of LSCC patients after curative surgery. CONCLUSIONS: SATB2 might involve in the development and progression of LSCC as a tumor suppressor, and thereby may be a valuable prognostic marker for LSCC patients.

Protein turnover metabolism plays important roles in cell cycle progression, signal transduction, and differentiation. Those proteins with short half-lives are involved in various regulatory processes. To better understand the regulation of cell process, it is important to study the key sequence-derived factors affecting short-lived protein degradation. Until now, most of protein half-lives are still unknown due to the difficulties of traditional experimental methods in measuring protein half-lives in human cells. To investigate the molecular determinants that affect short-lived proteins, a computational method was proposed in this work to recognize short-lived proteins based on sequence-derived features in human cells. In this study, we have systematically analyzed many features that perhaps correlated with short-lived protein degradation. It is found that a large fraction of proteins with signal peptides and transmembrane regions in human cells are of short half-lives. We have constructed an SVM-based classifier to recognize short-lived proteins, due to the fact that short-lived proteins play pivotal roles in the control of various cellular processes. By employing the SVM model on human dataset, we achieved 80.8% average sensitivity and 79.8% average specificity, respectively, on ten testing dataset (TE1-TE10). We also obtained 89.9%, 99% and 83.9% of average accuracy on an independent validation datasets iTE1, iTE2 and iTE3 respectively. The approach proposed in this paper provides a valuable alternative for recognizing the short-lived proteins in human cells, and is more accurate than the traditional N-end rule. Furthermore, the web server SProtP (http://reprod.njmu.edu.cn/sprotp) has been developed and is freely available for users.

Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family of ligand-inducible transcription factors, which have three different isoforms: PPARα, δ and γ. It has been demonstrated that PPARα and γ agonists have renoprotective effects in proteinuric kidney diseases; however, the role of PPARδ agonists in kidney diseases remains unclear. Thus, we examined the renoprotective effect of GW501516, a PPARδ agonist, in a protein-overload mouse nephropathy model and identified its molecular mechanism. Mice fed with a control diet or GW501516-containing diet were intraperitoneally injected with free fatty acid (FFA)-bound albumin or PBS(-). In the control group, protein overload caused tubular damages, macrophage infiltration and increased mRNA expression of MCP-1 and TNFα. These effects were prevented by GW501516 treatment. In proteinuric kidney diseases, excess exposure of proximal tubular cells to albumin, FFA bound to albumin or cytokines such as TNFα is detrimental. In vitro studies using cultured proximal tubular cells showed that GW501516 attenuated both TNFα- and FFA (palmitate)-induced, but not albumin-induced, MCP-1 expression via direct inhibition of the TGF-β activated kinase 1 (TAK1)-NFκB pathway, a common downstream signaling pathway to TNFα receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases.

Scientific modeling (SM) is a core practice of science and an important component of scientific literacy. Supporting students in developing the competence to construct, use, evaluate, and revise models is hence of particular relevance. While research has shown that spatial visualization (SV), a core component of spatial ability, is correlated with students' SM performance, it is unclear which role SV plays in students performing the four elements of SM: the construction, the use, the evaluation, and the revision of models. This study analyzes the role of SV in the performance of a series of SM tasks by 279 students in Grades 4 and 7. The findings indicate that SV affects students' performance in SM but that the effect is more significant in Grade 4 than in Grade 7. More specifically, SV is significantly predictive for model revision in Grade 4, but significant for model evaluation in Grade 7. However, there was no gender difference in the effect of SV on SM. The implications are that science teaching and learning must better attend to supporting younger students through visual aids when engaging them in SM. The study also suggests that further studies are needed to understand the different cognitive processes involved in students' SM and their complex interplay.